Aflatoxin and liver cancer in Karachi, a preliminary survey. A cause and effect relationship of Aflatoxin and liver cancer is well established. The incidence of liver cancer is 3.6% in Karachi (Zuberi et al., 1976) and Aflatoxins have been detected in 43% of 28 samples of food analysed in this study. The long term ingestion of aflatoxin with food may have some effect on the existing pattern of liver cancer in Karachi.


Patients with acute poisoning seen in the department of intensive care-Jinnah Postgraduate Medical Centre, Karachi. A review of 157 cases of acute poisoning admitted to the intensive care unit shows that poisoning was responsible for 40 15% of the cases treated at this unit between 15th January to 31st December, 1976. Inspite of limited facilities the over all mortality from acute poisoning was 9.5% while that due to organo-phosphorus insecticides alone was 7%. A considerable infrequency of organophosphorus insecticides poisoning was observed in developed countries when their data was compared with the present series.


Organo-phosphorus insecticide poisoning-review of 53 cases. A review of 53 cases of organo-phosphorus insecticide poisoning admitted to the department of intensive care at the Jinnah Postgraduate Medical Centre between 15th January to 31st December, 1976 has shown that these insecticides form a majority of the causes of acute poisoning and are associated with a comparatively high mortality rate. Out of a total of 157 cases of acute poisoning admitted to the department, 34% were cases of organo-phosphorus insecticide poisoning forming 13 5% of the total admissions. These insecticides being easily accessible, are frequently used as suicidal agents specially by uneducated housewives. They are highly toxic and their management is very complicated. Of a total of 15 deaths from poisoning, 11 (73%) were due to this cause. This being such a common mode of poisoning in our country, we have presented here our experience of the clinical features and management of these cases.


Trace element analysis: a diagnostic tool. Human body continuously assimilates a variety of elements from the environment and the concentration of these elements in blood is regulated by means of various homeostatic mechanisms. Some of the elements, though present in very small amounts perform highly specialized functions in initiating many biochemical reactions. These elements, known as essential trace elements, are closely related to human diseases as their deficiency or excess induces physiological changes. Many diseases such as hypertension, atherosclerosis, diabetes etc are related to trace element imbalance. Therefore the measurement of trace elements in body fluids and tissues can be effectively employed for diagnostic tests.


Restoration of the infectivity of Rickettsia tsutsugamushi to susceptible animals by passage in athymic nude mice. Restoration of the infectivity of three prototypes of Rickettsia tsutsugamushi (i.e., Gillium, Karp and Kato strains) was examined to obtain each antiserum for the diagnosis of rickettsiosis and to prepare target antigens. When successively passed in embryonated yolk sac, rickettsiae gradually lost their infectivity to susceptible animals; after several passages in mice only Kato strain retained infectivity and others became completely avirulent. When these strains were passaged in athymic nude mice only once, they restored even stronger infectivity than original ones to other animals. The infectivity was retained in further passages in BALB/c, DDD mice or in guinea pigs. Thus excellent strain specific antisera were produced in guinea pigs, enabling defined diagnosis of rickettsial infection. Furthermore, successful restoration of the infectivity is expected to contribute to the studies on pathogenesis of rickettsiosis.


Infection protective property of the common antigen (OEP) of Pseudomonas aeruginosa and its chemical composition. The protein moiety (OEP) of the endotoxin of Pseudomonas aeruginosa is a proteinaceous compound composed of possessing 77% protein and a small amount of lipid and sugar. The antigen has been proved to possess a common protective property against P. aeruginosa infections regardless of serotype and also to possess an antigen common to all the serotype strains of P. aeruginosa. When OEP was subjected to protease digestion, (protease-treated OEP) the protein content was reduced to 17% without a change in the lipid and sugar composition. The protease-treated OEP was no longer found to possess a serologically common antigen and was also found to have lost the common protective property against infections due to all the serotypes of P. aeruginosa. In conclusion, a serologically common antigen (OEP) as well as a common infection protective property was found to reside in a protein portion of the antigen.


Encephalomyelitis induced by canine distemper virus in non-human primates. A strain of canine distemper virus was shown to be highly neuro-virulent in non-human primates. Intracerebral inoculation induced in monkeys histological lesions of encephalomyelitis, i.e., degenerative changes consisting mainly of neuronal damage and inflammatory changes such as perivascular cuffings and glial proliferation, in wide areas in the brain and spinal cord. In one monkey observed for 70 days, lesions with a tendency of subacute sclerosing were also noticed. Immunosuppression with cyclophosphamide or antithymocyte serum was found to aggravate the clinical course and to modify the histological lesions in the central nervous system as well as the level of antibody response to the virus in cerebrospinal fluid. Possible application of distemper encephalomyelitis in monkeys as a primate model for analysis of the immune mechanism involved in paramyxovirus-induced encephalomyelitis was discussed.


Chloride-induced contraction in a skinned fiber of toad striated muscle. Cl- -induced contraction was studied in a skinned fiber dissected from toad sartorius muscle. When K-methanesulphonate in a relaxing solution was replaced isotonically with KCl, the skinned fiber contracted due to 'depolarization'-induced Ca++ release on the SR. Contraction was induced by superfusing the fiber with solutions containing different concentrations of Cl-. In the presence of 2 mM EGTA, the Cl- -induced contraction developed when the relaxing solution was replaced by a Cl- solution which contained up to 20 mM Cl-, while contraction started at 15 mM-Cl- in the presence of 0.5 mM EGTA. The peak tension of the Cl- -induced contraction depended on Cl- concentration without obeying the all-or-none law. When the fiber was treated with 1.5 mM caffeine, the threshold for the Cl- -induced contraction was significantly lowered. In spite of previous application of Cl- at different concentrations below 80 mM, the skinned fiber contracted by sudden increase in Cl- concentration, and the tension versus Cl- concentration curve revealed almost the same shape as that in a fiber equilibrated with Cl- -free solution. This suggests that the SR membrane is repolarized after transient depolarization caused by elevation of Cl- concentration.


Time- and Na-dependent effects of Ca depletion on potassium contracture in frog twitch muscle fiber. The effect of the extracellular Ca depletion on potassium contracture was investigated in single fibers isolated from frog semitendinosus muscle mainly in relation to its time and Na dependency. The shortening of plateau duration and the increase in the rate of relaxation of the potassium contracture appeared within 3--5 sec and 15 sec, respectively, after the fiber was immersed in Ca-free Na Ringer solution containing 1 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA) (EGTA-Na Ringer solution) or Ca-free choline Ringer solution containing 1 mM (EGTA (EGTA-choline Ringer solution). These effects were independent of the presence or absence of extracellular Na. In EGTA-Na Ringer solution, the potassium contracture tension was inhibited only by about 20% after 20--90 min and was abolished after 120 min. The inhibition of the peak tension was accelerated by the depletion of extracellular Na; in EGTA-choline Ringer solution, the tension was gradually inhibited by about 20% during the first 7 min and abolished after 10--12 min. When the peak tension of potassium contracture was abolished in EGTA-choline Ringer solution, the depolarization by Ca depletion was about 10 mV and the caffeine contracture was sufficiently produced. The results suggest that the inhibition of the potassium contracture tension in EGTA-choline Ringer solution is due to the dissociation of excitation-contraction coupling. On the basis of these results, an aspect of the inactivation of the potassium contracture was proposed.


[Case report on a retinal complication in long-term-therapy with oral hormonal contraceptives (author's transl)]. An exudative retinal process was noticed in a 38-year-old woman who had taken oral hormonal contraceptives for about 8 years. An incidental finding was a fundus albipunctatus in combination with an euryblepharon. There was further a strange shading in the colour of fundus, perhaps identical with the well known Mizuophenomenon. It seems that the macula is starting point of this phenomenon (Fig. 3). Possibly exudative processes in the plexus chorioidei of brain, also are due to complications in the ZNS from contraceptives.


[The oculo-oto-vertebral syndrome (author's transl)]. A new case of a combined malformation of the ear (anotia), eye (anophthalmia) and vertebral colum is presented. The distinction from the Goldenhar Syndrome and possible embryologic causes are discussed.


[Central nervous manifestations of neurofibromatosis in children (author's transl)]. Serious central nervous manifestation of neurofibromatosis have been reported in 11 children aged 1,5-12 years. According to the present literature we conclude: 1. Central nervous lesions of neurofibromatosis are common even in childhood. 2. About two thirds of these patients suffer from brain tumors. 3. The tumors involve the suprasellar region in many cases. 4. By this localisation endocrine manifestations, especially precocious puberty, are frequent.


[Phenyketonuria associated with Rubinstein-Taybi syndrome, spondylic dysplasia, left vascular shrinking of adrenal gland (author's transl)]. Report of a 10 year old girl, who demonstrated the following diseases independent from each other: Phenylketonuria, Rubinstein-Taybi syndrome, dysplasias of the skeleton, especially dysplasia of the vertebra and finally, left-sided shrinkes adrenal gland, which caused presumably an increased production of androgens with a premature pubarche.


Thoracic duct cannulation of the rhesus monkey (Macaca mulatta) for lymphocyte collection: thoracic approach. The thoracic duct of the rhesus monkey (Macaca mulatta) was cannulated with medical grade tubing through a thoracatomy at right interspace 9-10. In 42 monkeys successfully cannulated, a mean of 1.194 x 10(9) lymphocytes was collected in the 70-hour period after surgery. A second collection, 1-3 weeks later, was possible for a shorter period (up to 60 hours) in a portion of these monkeys (15) with a smaller mean yield of lymphocytes (1.076 x 10(9). A third, but still shorter, collection period of up to 48 hours was possible in only five monkeys from which a mean yield of 0.698 x 10(9) lymphocytes was collected. A temporary postoperative weight loss in the monkeys was followed by a return to normal weight several months later.


Baseline pulmonary physiologic values for the squirrel monkey (Saimiri sciureus). Baseline pulmonary physiologic values were determined on 43 (421-910 g) male and 47 (425-604 g) female squirrel monkeys (Saimiri sciureus). Respiratory rate was found to be 55 +/- 1.9 (SE) breaths per minute for males and 58 +/- 1.7 breaths per minute for females. Tidal volume was 8.9 +/- 0.37 ml for males and 7.5 +/- 0.28 ml for females. Airway resistance for the male was 0.052 +/- 0.006 cm H2O/ml/second; while for the female it was 0.086 +/- 0.011 cm H2O/ml/second. Dynamic compliance was found to be 1.78 +/- 0.15 ml/cm H2O for males and 1.48 +/- 0.124 ml/cm H2O for females. An index of distribution of ventilation was 48 +/- 2.5 breaths for males and 42 +/- 1.7 breaths for females.


Identification of hemoglobins within individual rhesus monkey (Macaca mulatta) erythrocytes. Rabbit and goat antibodies to monkey adult and fetal hemoglobin were prepared and purified to apparent monospecificity. After conjugation with fluorescein isothiocyanate, the antibodies were employed to identify the hemoglobin types within individual cells in peripheral erythrocyte smears. The percentage of neonatal monkey erythrocytes containing fetal hemoglobin was found to decrease with time. The existence of adult or fetal hemoglobin in the erythrocytes appeared to be mutually exclusive.


Measurement of hemolytic complement and the third component of complement in nonhuman primates. Complement, determined by hemolytic assay, and the third component of complement (C3), determined by radial immunodiffusion assay, were measured in nine nonhuman primate species. The species studied were the titi (Callicebus mollach). The sooty mangabey (Cercocebus atys), the thick-tailed galago or bushbaby (Galago crassicaudatus panganiensis), the crab-eating monkey (Macaca fascicularis), the rhesus monkey (Macaca mulatta), the bonnet monkey (Macaca radiata), the stumptailed macaque (Macaca speciosa), the yellow baboon (Papio cynocephalus), and the black-and-red tamarin (Saguinus nigricollis). Both sheep and bovine erythrocytes were used in the hemolytic complement assays. With the sheep erythrocyte system, sera from four species (yellow baboon, sooty mangabey, bonnet monkey, black-and-red tamarin) had similar titers with both antibody sensitized and non-sensitized erythrocytes. In contrast, the titers obtained using sensitized bovine erythrocytes was always higher than the values obtained using non-sensitized bovine erythrocytes. In all species, the titers for non-sensitized sheep erythrocytes was higher than the titer for non-sensitized bovine erythrocytes. When the species were compared for cross reactivity using the radial immunodiffusion assay for human C3, the rhesus monkey showed the strongest cross reaction; the thick-tailed galago, a prosimian, showed no detectable cross reactivity; and the other species examined showed intermediate degrees of reactivity.


Total parenteral nutrition in inflammatory bowel disease. Nutritional depletion is a common feature of inflammatory bowel disease. The advent of total parenteral nutrition (TPN) has allowed nutritional repletion or maintenance while total bowel rest is achieved. The experience with total parenteral nutrition in inflammatory bowel disease is varied; our recommendations for use of total parenteral nutrition in specific situations are presented with a description of the techniques for administration in patients with inflammatory bowel disease.


Gallstones. The present and future of medical dissolution. Adequate concentrations of bile acids and phospholipids are necessary to keep cholesterol in solution in bile. When the amount of cholesterol exceeds the capacity of bile acids and phospholipids to keep the cholesterol in micellar solution, bile becomes supersaturated; then, under appropriate conditions, cholesterol crystals form and gallstones may develop. Current dissolution therapy is aimed at desaturating the bile, thereby shifting the equilibrium of cholesterol from a crystalline phase back toward a micellar state, thus permitting gallstones to dissolve. Chenodeoxycholic acid is the drug being most extensively tested for efficacy in dissolution; at present, it is successful in about 60 per cent of cases. The primary mechanism of action appears to be suppression of biliary secretion of cholesterol. Further experience is needed to confirm the safety of chenodeoxycholic acid, to gain more precision in patient selection, and to determine ideal dose. The role of chenodeoxycholic acid in prophylaxis and in prevention of recurrence needs further study. Other potential agents for dissolution also deserve investigation.


[The intramural duodenal diverticulum, a topical variation of the intraluminal duodenal diverticulum (author's transl)]. The intramural duodenal diverticulum is a topical variation of the intraluminal duodenal diverticulum. It is manifested not before adult age by noncharacteristic upper abdominal symptoms. Diagnosis is made by radiologic examinations, the therapy is excision of the diverticulum. Structure and topography of the diverticulum are explained by its embryological development.


Parameters of thyroid function in patients with active acromegaly. In order to determine if acromegaly per se may be associated with abnormalities in thyroidal economy, serum thyroxine-binding globulin (TBG), resin T3 uptake, total and free T4, T3, and reverse T3 concentrations were measured in 21 patients with active acromegaly. Mean (+/- SE) total T4, T3, and reverse T3 levels were 7.1 +/- 0.2 microgram/dl, 111 +/- 4 ng/dl, and 45 +/- 2 ng/dl, respectively, and the mean TBG concentration was 3.6 +/- 0.2 mg/dl. Similarly, mean free T4, T3, and reverse T3 concentrations were 2.4 +/- 0.09 ng/dl, 383 +/- 22 pg/dl, and 118 +/- 7 pg/dl, respectively. None of these values is significantly different from normal and the thyrotropin response to thyrotropin-releasing hormone was also normal. In contrast to several earlier reports, these data suggest that parameters of thyroid function are generally normal in patients with active acromegaly.


[Glucose transport system and regulation of gene expression in Escherichia coli]. The object of this work was to study the effect of mutations damaging protein components of the phosphoenolpyruvate-dependent phosphotransferase system (PTS) of E. coli on the regulation of the activity of catabolite-sensitive operons. Mutations ptsI and ptsH affecting the activity of the enzyme I and HPr protein made the synthesis of catabolite-sensitive enzymes resistant to the action of glucose, and at the same time decreased the rate of transport of this compound. Mutation tgl affecting the activity of the glucose enzyme II lead to the same effect on the enzyme syntheses, though utilization was not altered in this case. The disturbance of beta-galactosidase synthesis in ptsI and ptsH mutants is due to interference of pts mutations into transcription of the lac operon at the lac promoter level. It is concluded that the proteins of the Escherichia coli PTS take part not only in glucose transport, but are also involved in the regulation of transcription of the catabolite sensitive operons.


[Bacteria-cortical symbionts of Thichonympha turkestanica, a protozoan from the gut tract of the termite Hodotermes margabicus]. Intracellular symbiotic bacteria of the flagellate Trichonympha turkestanica located in the surface cortical part of the animal cell are described. The cell structure of the symbionts is typical of gramnegative bacteria, but contains also an additional outer membrane. The membrane is an element of the electron-dense structures which have contacts, at many points, with the kinetosomes or membranes surrounding flagella. A possible functional significance of symbiotic bacteria for the operation of flagella is discussed.


[Alkane-induced protein biosynthesis in Pseudomonas aeruginosa]. Protein disc-electrophoregrams of cell-free homogenates have been compared in the "non-adapted" and "preliminarily-adapted" to n-hexane strains of Pseudomonas aeruginosa. A statistically reliable increase in the content of protein by 60 per cent was found in fractions a (M. W. 70,000) and b (M. W. 130,000) when the cells of both strains were gorwn on hexane as compared to the cells cultivated on glucose. The content of protein in each a and b band was about 4 per cent of the total cell protein before the induction by hexane. No differences were found when the cells of the two strains were grown on identical substrates. The induced proteins are supposed to belong to the system of primary oxidation of n-alkanes with short chains and to be localized in the cytoplasm of Ps. aeruginosa.


Significance of red-cell irregular antibodies in the obstetric patient. Irregular antibodies were identified in 1.3% of obstetric patients who were delivered at the Royal women's Hospital, Melbourne. The most common antibodies found were anti-P1 and anti-Lewis, but, although these antibodies may cause difficulty in obtaining compatible blood if transfusion is required, they were not associated with haemolytic disease of the newborn. Immunization with other irregular antibodies, especially Rhesus subtype and Kell, may occur due to pregnancy alone or follow the combination of pregnancy and incompatible blood transfusion. Irrespective of the initial cause of immunization, these antibodies are often associated with haemolytic disease of the newborn which may be severe enough to result in perinatal death. As most irregular antibodies are found in patients with Rh-positive blood, the need for screening of all antenatal patients in each pregnancy must be recognized.


[Lysis from without of a culture of Actinomyces griseus--producer of the antibiotic kormogrizein]. A polylysogenic culture of Actinomyces griseus 15 producing the antibiotic cormogrisin is sensitive to actinophages, denoted as types 15 I, 15 II and 15 III, which are the virulent mutants of its temperate phages. In certain cases, the variants of Act. griseus 15, obtained by selection and resistant to the phages types 15 I and 15 II, can undergo lysis-from-without by these phages. A study of the mechanisms involved in this phenomenon has shown that the lytic activity is entirely eliminated if the phages have been a titre of 10(9) and higher. The lytic activity is entirely eliminated if the phages have been treated with a specific serum or inactivated by UV. The variants resistant to phage 15 I can adsorb this phage and undergo lysis-from-without at a high multiplicity of infection if only the age of the variant does not exceed 13 hours. The variants resistant to phages 15 I and 15 II can undergo lysis-from-within under the action of phage 15 III. The variants resistant to this phage have acquired this resistance as a result of lysogenization. They have entirely retained the ability to adsorb phage 15 I, but their ability to absorb phage 15 III is much lower. Therefore, the rate of mycelium growth is only slightly inhibited, but the lysis of the culture is not observed, under the action of phage 15 III having titres of 10(9) and 10(10).


[Metabolism of carotenoids during dark and photooxidative degradation in Anabaena variabilis]. Changes of carotenoids were studied in the cells of the blue-green alga Anabaena variabilis incubated in dark for a long period of time in a phosphate buffer, and also upon photooxidative degradation of the "dark" culture, i. e. a culture that had been grown for 8 days and incubated in the darkness for a certain period of time. Incubation in the dark resulted in the formation and accumulation in the cells of two new pigments, xanthophyll-450 and beta,beta-carotene-4,4'-dione, whose content decreased only with lysis of the culture. The second pigment is presumed to be formed from less oxidized epiphase carotenoids. Dark and photooxidative degradation of the cells is accompanied with an increase in the level of epiphase xanthophylls (particularly, ketoxanthophylls) and a decrease in the level of carotenes and glycoside xanthophylls, whereas the total content of carotenoids decreases.


[Metabolic products of hydrocarbon-oxidizing strains of Mycococcus lactis and Pseudomonas fluorescens and their influence on culture growth]. The effect of concentrations of organic acids in the cultural broth on growth was studied with the strains of Mycococcus lactis and Pseudomonas fluorescens oxidizing hydrocarbons. The ratio between the acid and neutral fractions in the cultural broth of Mycococcus lactis was also investigated as well as their action on the bacterial growth. Mycococcus lactis growing on paraffin was found to produce acid and neutral products at a ratio of 1:2. The acid and neutral products of metabolism produced different action on the growth of the carbohydrate oxidizing bacteria. The acid products inhibited the growth at a concentration of organic acids in the medium above 500 mg/litre. The neutral products were partily assimilated by Mycococcus lactis.


Synthetic multifunctional proteins: isolation of covalently linked tryptophan synthetase alpha-subunit-lac-repressor-beta-galactosidase chimeras. Several E. coli mutants were isolated which produce triple chimeras between one of the trp enzymes lac, repressor and beta-galactosidase. The mutants were isolated as TonB- Lac+ derivatives of a phenotypically Lac- TrpR- strain carrying a lac I+ -Z+ fusion on a phi80dlac phage. The phage is integrated into the chromosome in such a way that the lac and the trp genes are transcribed in the same direction. Of a total of 58 candidates 2 TrpA- and 3 Trp- strains produce triple chimeras. The chimeras from the two TrpA- strians were further examined. They consist of tryptophan synthetase alpha-subunit, lac repressor and beta-galactosidase. In crude extracts of these strains the tryptophan synthetase alpha-subunit part can be identified by its ability to aggregate with the beta-subunit since some of the beta-subunit activity can be precipitated with antiserum against beta-galactosidase. Furthermore beta-galactosidase precipitates with antiserum against tryptophan synthetase alpha-subunit. The lac repressor part is able to bind IPTG, but not lac operator DNA in vitro. The beta-galactosidase part is as unaffected as in the original lac repressor-beta-galactosidase chimera. The molecular weights of both chimeras are 175,000 when determined by SDS gel electrophoresis. The chimeras are partially degraded giving rise to fragments of distinct molecular weights.


Macromolecular synthesis in chromosome initiation mutants of Bacillus subtilis. Inactivation of the dna B or dna D gene product in Bacillus subtilis stimulates RNA and protein synthesis. Strains containing ts dna B and D mutations have been constructed by introducing the mutations by transformation into a thymine requiring strain which does not lyse during thymine starvation. The consequences of inactivation of these gene products have been assessed by comparing RNA and protein synthesis during thymine starvation at the restrictive temperature with the recipient strain. In the ts+ strain, there is a doubling in rate of RNA synthesis during thymine starvation. In the ts dna B and D mutations at the restrictive temperature the rate of RNA synthesis increases four fold. By preincubating the mutants in the absence of thymine for one generation at the permissive temperature the two fold increase in rate of RNA synthesis associated with inactivation of the initiation complex can be demonstrated under conditions where the ts+ strain shows a decrease in rate of RNA synthesis. The rate of protein synthesis observed largely reflects the rate of RNA synthesis in all strains. Completion of the chromosome at the restrictive temperature has no significant effect on the rate of RNA synthesis. It is suggested that inactivation of the initiation complex after chromosome initiation could play an important role in control of RNA synthesis in relation to the cell cycle.


Transformation in Bacillus subtilis: biological and physical evidence for a novel DNA-intermediate in synchronously transforming cells. Competent B. subtilis cells exposed to transforming DNA in the presence of EDTA bind, but do not take up DNA. Rapid and almost synchronous uptake of the bound DNA is achieved by the addition of Mg2+ ions in excess of the EDTA. At 30 degrees and at 17 degrees comparable numbers of transformants are produced from cells pre-loaded with DNA at 30 degrees (after termination of uptake by the addition of DNA ase the samples were incubated at 37 degrees). However, almost no transformants are produced when cells are exposed to DNA at 17 degrees, although binding does take place then. Because DNA is taken up at 17 degrees after having loaded the cells at 30 degrees, whereas no uptake occurs after binding at 17 degrees, it is suggested that binding of DNA to the cellular surface involves at least two steps. In DNA re-extracted from cells at 17 degrees, pre-loaded with DNA at 30 degrees, little recombinant type activity is present, indicating that integration is blocked at 17 degrees. However, physico-chemical analysis of the re-extracted DNA indicates that a complex between single-stranded donor DNA and the recipient chromosome is formed at 17 degrees. This complex has a higher buoyant density than donor-recipient complexes formed at 30 degrees.


On the dose response in B. subtilis transfection: involvement of aggregates in phi 29 transfection. Transfection with phi 29 DNA is predominantly caused by multimolecular, protease-sensitive aggregates of DNA. A minority of transfecting DNA molecules having properties of unit-length phi 29 genome molecules show a quadratic dose response in transfection.


The phenoloxidases of the ascomycete Podospora anserina. XIII. Action and interaction of genes controlling the formation of laccase. 1. Eight mutants were isolated following mutagen treatment which are deficient in laccase formation. Seven of these had a pleiotropic effect and exhibited defects in growth rate and in mycelial and sexual morphology. 2. By means of tetrad analysis the mutations were assigned to 6 loci. Three mutations were in the incolora locus, the others were non-allelic. Only two of these loci were closely linked. 3. All genes exhibit numerous interactions. These concern the morphological expression of the laccase genes and also the laccase spectra. 4. The mutants could be separated into four classes on the basis of the amount and type of laccase produced. 5. Five of the loci studied appear to be structural genes because mutations alters the physical properties of the laccase protein. The sixth gene has a regulatory role.


An adaptive response of E. coli to low levels of alkylating agent: comparison with previously characterised DNA repair pathways. We have described previously an inducible response in Escherichia coli which occurs during growth on low levels of the methylating agent, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and which enables cells both to survive better and to be less mutated by a subsequent challenge dose of MNNG than control cultures (Samson and Cairns, 1977). We show here that this response is distinct from previously characterised pathways of DNA repair, and particularly from the SOS response, which is another inducible effect resulting from DNA damage. An examination of the cross-reactivity of this response with other mutagens has shown that it is a generalised mechanism affecting alkylation damage to DNA. It cannot, however, be induced by UV or the UV-mimetic mutagen, 4-nitroquinoline 1-oxide, nor act on lesions put into DNA by those mutagens.


Molecular cloning and in vitro transcription of Bacillus subtilis plasmid in Escherichia coli. A composite plasmid (pAT2010) has been constructed in vitro from RSF2124 and Bacillus subtilis IFO3022 plasmid (pAT1060) by covalent joining of the two DNA molecules by means of Escherichia coli DNA ligase through the cohesive ends generated by restriction endonuclease RI (EcoRI) cleavage. The composite plasmid was selected by transformation of E. coliC600r-m- with the ligated mixture after enrichment for composite plasmid by preparative agarose gel electrophoresis, and plating of the transformants on a medium containing ampicillin and colicin E1. Treatment of the composite plasmid with EcoRI yielded two fragments corresponding to the linear forms of the parental plasmids. The composite plasmids replicated as biologically functionally units in E. coli, and expressed genetic information carried by RSF2124. In the presence of chloramphenicol, the composite plasmids continued to replicate and the copy number gradually increased. Such nature of replication in the presence of chloramphenicol is characteristic to RSF2124 derived from colicin E1 factor, and so it is suggested that the replicator of RSF2124 is functional in the composite plasmid. The composite plasmid was found to synthesize mRNA of B. subtilis plasmid in cell-free extracts of E. Coli, by hybridization of the mRNA to the original plasmid DNA of pAT1060.


Streptomycin-resistant, asporogenous mutant of Bacillus subtilis. A streptomycin-resistant mutantant of Bacillus subtilis that is also asporogenous, was isolated and partially characterized. This strain, SRB15, sporulated at a frequency of about 1% compared to the wild type frequency of greater than 70%. The two phenotypes were inseparable by transformation, suggesting that this strain carries a single mutation that causes it to be both streptomycin-resistant and spore-minus. The mutation cotransduces with cysA, the closest auxotrophic marker to the "ribosomal region" of the B. subtilis chromosome, with a frequency of 68%. SRB15 showed no cross resistence to other antiobiotics tested, including the aminoglycosides kanamycin, neomycin and spectinomycin. Ribosomes obtained from the mutant were at least 200-fold more resistant in vitro to streptomycin than were wild type ribosomes in the translation of phage SPO1 RNA. The kinetics of in vitro translation of this natural message were indistinguishable for mutant and wild type ribosomes. The level of misreading, as measured by poly(U)-directed isoleucine incorporation, by mutant ribosomes was less than that by wild type ribosomes.


[Quantitative plasma protein determination as an aid to diagnosis (author's transl)]. The lack of internationally comparable reference standards for plasma proteins causes problems. For this reason, it is only possible to evaluate the "accuracy" of measurements by comparison of methods. Differences in results which may sometimes be based on technical procedure, physical chemistry or biology are gone into with reference to diagnostically important examples such as albumin, transferrin, ceruloplasmin, fibrinogen and complement 3. It is shown which plasma protein constellations may frequently be expected in certain reactions and what protein patterns have principal importance in clinical practice, e.g. in acute and chronic inflammatory diseases, protein depletion diseases and in liver diseases.


[Immunohistological investigations and complement analysis in immunological diseases (author's transl)]. Immunohistological techniques and complement analysis are essential methods of investigation in the diagnosis of immunologically induced disease processes today. Immunopathogenesis or participation of immunological reactions in inflammatory processes such as glomerulonephritis, dermatitis, arthritis for example, can be detected through immunohistological demonstration of deposits of immunoglobulin and complement in biopsy material. Numerous antibodies against tissue and infection pathogens can be demonstrated in the serum by indirect immunofluorescence techniques.


[Inflammatory diseases of the vessels. Clinical aspects, immunopathology, characteristic features of therapy (author's transl)]. Arterial obstructive diseases become manifest principally in the great peripheral vessels, visceral symptoms are rare. In the overwhelming majority of inflammatory vascular processes changes in the small arteries are impressive, visceral symptoms are common, in many cases the rule, peripheral occlusive syndromes are exceptions, although possible, and then prognostically especially serious in the individual case. The diagnosis of such vascular processes can be extraordinarily difficult if there is systemic spread because of the great variety of symptoms, and in the individual case may be almost impossible. Principles of classification should contribute to the facilitation of necessary clinical differentiation and lead to the proper therapeutic indication of the fundamental process. But they should also serve for the understanding of those inflammatory vascular diseases whose special position is based on the new scientific knowledge of immunopathology.


[Problems of cancer immunotherapy (author's transl)]. Active immunization has received a new impulse most recently through the treatment of tumor cells with the enzyme neuraminidase from Vibrio cholerae. There is no passive specific immunotherapy in humans. In the field of unspecific active immunotherapy there are very many, partly contradictory, findings, especially with BCG, Corynebacterium parvum and preparations from these and other organisms. A cellularly transmitted immunity has been attempted, but so far without very encouraging results. It must be emphasized that all these statements refer to humans.


[Hypothesis for the use of levamisole in rheumatic diseases (author's transl)]. For years the treatment of rheumatoid arthritis has been based on the assumption that the autoimmune processes and bone lesions occuring in rheumatic patients are due to inflammatory and immune reactions. Treatment was aimed at restricting these reactions. But various investigators have come to the conviction that the primary factor is not an immunological hyperreactivity but an immunodeficiency in autoimmune diseases. The immunotherapeutic use of transfer factor, BCG and levamisole in patients with rheumatoid arthritis is based on this hypothesis. From the fact that a therapeutic effect is demonstrable in such patients treated with levamisole, the theory that rheumatoid arthritis is an immunodeficiency disease should be accorded greater importance.


[Immunostimulation in the treatment of chronic joint rheumatism (author's transl)]. Results of a Double Blind Study: In a randomized double blind study, 22 patients were treated with levamisole. The intention was to find out whether immunostimulation would have a favorable influence on rheumatic complaints in patients with rheumatoid arthritis and whether an objectifiable improvement of the synovial reaction can be obtained. The course was monitored with an extensive laboratory diagnostic program in 13 patients treated with levamisole and 9 patients with placebo. The medicament did not cause a pseudo-LE syndrome. In the overall result, 84.6% of the patients were significantly improved compared to 33.3% of the placebo group. Gastric complaints were occasionally seen as side effects. In one patient, the treatment had to be interrupted several times because of recurrent leukopenia and was prematurely ended in the 21st week.


[Development and trial of a civic disaster plan (author's transl)]. Because of the changing complexities of the world the potential for disaster changes from day to day. It is, therefore, the responsibility of every community to plan for possible disasters and to alter their plans as the disaster potential for their community changes. "Exercise London" showed that a workable community plan can be prepared, and illustrated the errors that can occur in handling a large number of casualties. These errors are now being corrected and, when it seems feasible, another exercise will be carried out.


[First aid measures in emergency pediatric surgery (author's transl)]. The type of first aid given to patients requiring emergency pediatric surgery is decisive for the prognosis in many cases. With this aspect in mind, individual disease pictures from the group of connatal deformities (esophageal atresia, intestinal atresia, gastroschisis, diaphragmatic hernia and defect, myelomeningocele), from emergency surgical situations beyond the neonatal stage (acute abdomen and ileus, esophageal varices, pneumothorax), and accident injuries (blunt abdominal trauma, cranio-cerebral trauma, burns) are selected and the most important first aid measures described. But for all diseases, the general rule for the treatment of all seriously ill children applies: provision of a safe venous access, readiness to intubate, adequate oxygenation and control of the acid-base, water and electrolyte balances.


[Spa treatment of adiposity. Experiences about more than 1000 patients (author's transl)]. The value of spa treatment granted by insurance institutions is often called in question. We treated 1070 inpatients at a spa because of extreme overweight. An average weight loss of 5.8 kg was achieved in 4 weeks by 545 men on a weighed 1000 calorie diet. A decrease of 3.7 kg was achieved by 299 women over 45 years of age. With complete fasting for 4 weeks followed by convalescent diet, 88 men lost an average of 16.4 kg while the weight loss in women depended greatly on age. Favorable results can only be obtained by consistent treatment and guidance of the patients. The therapeutic procedure is described in detail and the results are discussed particularly from the point of view of the longterm fitness for work.


[Pregnancy in adolescence (author's transl)]. Pregnant women and maternity patients up to 20 years of age not only have a lower level of education but also neurotic personality traits three times more frequently than pregnant women over the age of 21. This affects the attitude to pregnancy which, in women up to 20 years was a surprise and unwanted twice as often as in women aged from 21 to 30. After the birth women up to 20 years of age wanted to leave the hospital particularly early. Almost half of them wanted to begin work again.


[Incidence of different types of urinary incontinence (author's transl)]. The incidence of different forms of incontinence is reported as a short survey. Particular attention is given to the various opinions on the effect of pregnancy, birth and diminishing ovarian function on the occurrence of closure insufficiency. Also the frequency of urinary incontinence arising from bladder conditions is variously assessed. The proportion is certainly high in "operation failure" or recurrent incontinence. Organic causes are only found in a bare fifth of patients with stress incontinence, Iatrogenic urinary incontinence is rare, but imposes particular demands on the attending doctor. Involuntary loss of urine is very widespread among women, but it is relatively seldom found to be troublesome and to require treatment.


[Ovulation induction by cyclofenil (author's transl)]. The ovulation-inducing action of cyclofenil was investigated in 135 sexually mature women aged 20--35 years. The patients were only included in the trial if no ovulation in 2 consecutive cycles with the following criteria: basal temperature, cervix score, ascorbic acid retention, basophil count, serum hormone levels, e. g. LH and progesterone and the estrogens in the 24-hour urine could be determined. Ovulation was only considered to have occurred when all the parameters named indicated it. The lack of ovulation was accompanied by amenorrhea in 21 of the 135 patients. The ovulation rate in the 241 cycles observed was 101, corresponding to 42%. In the 114 patients with anovulatory cycles, the ovulation rate in the 184 cycles observed was 95, corresponding to 50%. In the 21 amenorrheic patients, ovulation occurred 6 times in the 57 cycles observed. Nausea or vomiting occurred as side effects in only 2 cases.


[The importance of risk factors in cerebrovascular processes while taking oral contraceptives (author's transl)]. 21 young female and 15 young male patients with cerebrovascular insults were examined for risk factors. 14 of the 15 male patients showed clear cut risk factors: obesity, diabetes, hyperlipidemia, arterial hypertension, smoking, thromboses, vitium cordis. 20 of the 21 female patients took oral contraceptives. 60% of the female patients with angiographically confirmed stenoses and occlusion did not show any other risk factor. These results support the hypothesis that oral contraceptives are in themselves a risk factor.


[Guy's Hospital home dialysis program (author's transl)]. The first home dialysis was carried out from Guy's Hospital in London in 1968. Since then, 141 patients have been treated in this manner. The age of the patients ranged from 4 to 64 years. 24 patients have died (cerebrovascular accidents, myocardial infarction, pulmonary edema, sepsis, peritonitis, hyperkalemia etc.). Some of the deaths were due to a slackening of discipline on the part of the patients and nursing staff during the years of constant dialysis. Of 60 adults 52 were able to start work again; full rehabilitation still seems possible in 6 cases. Nevertheless, many patients cannot lead a normal life because their social and sexual activity is greatly restricted. The present economic crisis led to financial limitations in the National Health Service. In future, home dialysis may have to be reduced and more transplantations performed.


[Home dialysis (author's transl)].

[Home dialysis (author's transl)]. 100 patients requiring dialysis were trained between 1970 and 1975. Up to 31. 12. 1975, 56 patients were on home dialysis, 10 on the self-care program and 6 were freshly trained. Training usually lasts 8 weeks. The training course is briefly presented and the supervision of home dialysis patients after discharge from training is described. The possibility of vacation plays an important role in social rehabilitation. Since the spring of 1976, the hospital has operated a camping dialysis bus, the use of which is reported.


[Supervision of patients with artificial heart valves (author's transl)]. Valvulotomy mortality is 2--5% depending on the age and the condition of the myocardium. Ball valves, disk valves and biological prostheses are most commonly used. The most important complications of valve prostheses include bacterial endocarditis, loosening of the artificial valve, hemolytic anemias and thromboembolism. Presently, the Hancock prosthesis gives the best results. Thrombus formation, the most frequent complication of ball and disk valves--sometimes in spite of anticoagulation--does not occur with the biological prosthesis. Strict anticoagulant therapy and supervision is therefore not necessary. Should the Hancock prosthesis continue to prove satisfactory, it is to be hoped that resistance to early operation will be overcome and that the most important cause of failure, valvulotomy in an irreversible damaged heart, will thus be eliminated.


[Practical diagnosis of arterial occlusive diseases of the lower extremities (author's transl)]. A peripheral arterial occlusive disease can be diagnosed by a clinical examination. Technical methods serve for documentation, definition of localization and differentiation of doubtful findings and special therapeutic measures. A definite sequence of diagnostic procedures simplifies diagnosis. History (risk factors), individual clinical or biochemical findings, intermittent claudication, pain at rest are important for the assessment of peripheral arterial circulation when considered with the appropriate differential diagnosis of various internal disease conditions, inspection, palpation and especially auscultation at rest and on effort. Ratschow's circulation test provides information on the degree of compensation. Mechanical or electronic oscillography and Doppler echography have proved valuable as technical methods for measuring post-stenotic pressure.


[Controlling the course of arterial occlusive diseases in practice and prognostic aspects (author's transl)]. The earlier an arterial occlusive disease is recognized and intensively treated the more favorable the longterm prognosis. Such therapy includes to an equal extent the elimination or treatment of "risk factors" and intensive collateral training. Assessment of the course of this, per se chronic, disease requires longterm observation. Contrary to general opinion, however, neither clinical angiological findings nor most of the customary angiological methods can give a satisfactorily reliable judgment as a rule: only venous obstruction plethysmography and the Doppler ultrasonic flow measurements provide objective figures. The latter are suitable for general practice with regard to both expenditure of time and money and to the accuracy of their measurements.


[Pathophysiological prerequisites in the diagnosis and treatment of arterial occlusive diseases (author's transl)]. The pathophysiological consequences of an arterial occlusive disease are mainly governed by a) the location, degree, and temporal course of the vascular obstruction, b) the installation of a sufficient arterio-arterial bypass of the site of obstruction, and c) the behaviour of the postocclusive arterial vascular region. The acute total blockage of a larger artery usually can be diagnosed without major difficulties (the problems of comparative indirect blood pressure measurements for the localization of the occlusion are discussed). A partial obstruction, on the contrast, may be secret in the beginning. A stenosis of longer duration can be followed by the poststenotic bulging of the vessel wall; in this area platelet microemboli can take their origin. Compared with a limitation of O2-supply by the occlusion of a larger vessel the direct obstruction of the microvasculature will result in a more severe disturbance of organ function.


[Coronary heart disease risk factors in white-collar and manual workers at a large Munich industrial firm (author's transl)]. 1477 employees of a large industrial firm in Munich (868 males and 609 females, aged 40-59) were examined for coronary heart diseases risk factors. Among males, hypercholesterolemia predominates with a distribution of over 40%. Every fifth male has high blood pressure or is a heavy cigarette smoker. The females under 50 years of age clearly show fewer risk factors, but toward 60 years they exceed the males in frequency of some factors. Among women, too, the top risk factor is cholesterol, followed by overweight and high blood pressure. On the average, about 8% of the men and women have a preclinical or manifest diabetes. About every fifth male examined and every seventh female can be considered as especially endangered by the presence of 3 or more risk factors.


[Medical counselling of the hypertensive patient (author's transl)]. The diagnosis of arterial hypertension cannot be in doubt with repeated high blood pressure readings (140/90 under 40 years and over 40 years 160/95). In particular it will be easier to reconcile a patient who has no symptoms and who is not motivited by complaints to the understanding of a usually lifelong therapy by an exhaustive discussion. The patient must know that the risk of secondary cardiac diseases increases continuously with the level of the average arterial pressure (both systolic and diastolic) and that this average pressure includes all values of the excessive range of fluctuation of the blood pressure in hypertensive disease (stress peaks, resting values). The diagnostic program leads to a causal (surgical) therapy only in isolated cases (1 to 2%). For symptomatic therapy the general measures "adjustment of the way of living" and "diet" are the decisive basis for effective treatment.


[Sports and breathing (author's transl)]. The effect of physical training on pulmonary function and the changes in pulmonary parameters during physical exertion is described. Respiratory mechanics, vital capacity, forced expiratory volume and related variables are of less importance in judging the state of physical fitness and training condition. On the other hand, ventilation, respiratory gas exchange and regulation of breathing are important. Continuous analysis of alveolar and arterial partial pressures of gas and measurement of diffusion capacity may improve the assessment of the exercise test and physical fitness. Regular physical training may be of increasing significance for the rehabilitation of patients with chronic lung diseases.


[Quantitative changes in peripheral T-lymphocytes during hyperthermia (author's transl)]. A uniform, highly significant fall in T-lymphocytes in the peripheral blood, without any change in the absolute lymphocyte count occurred in 6 healthy test subjects in a standardized hyperthermal bath with a mean rise in the rectal body temperature of 1.35 degrees C. A redistribution from the blood into the tissue structures of the rapidly recirculating T-lymphocytes in the body is assumed. The clinical significance of this redistribution cannot yet be stated. With increased recirculation of immunoreactive T-lymphocytes an increased contact with antigenic material in the tissues traversed would be possible. This could be the basis of the "immunostimulation" during hyperthermia assumed by some authors.


[Grass pollen in Munich air. Preparations for a forecast (author's transl)]. To forecast pollen concentrations of the air of a particular place the following data of the area in question should be known: The basic grass pollen content of the air from volumetric measurements made during several years and its mean seasonal changes; the mean daily grass pollen content of 1 m3 of air and its changes, especially at the beginning of the main grass pollen season; the influence of temperature, humidity, precipitation and wind speed on the grass pollen content; weather forecast of the day for which the pollen forecast is to be made and the grass pollen content of the previous day; the composition of the grass flora in the surroundings and the state of flowering of the main components of the grass flora. These data for the city of Munich are presented and discussed. In addition the grass pollen content in the air during the summers of 1975 and 1976 is compared with allergic complaints of 96 and 45 persons respectively.


[Treatment of hypertension with propranolol in internal medicine and general practice. A field trial with a simplified twice daily administration of Dociton 80 (author's transl)]. More recent investigations on the duration of effect and plasma half-life of propranolol suggest a simplification of dosage for the beta-blocker in the treatment of hypertension. A field trial with Dociton 80 twice daily as initial therapy was carried out in over 2000 patients with essential hypertension with relatively few side effects and confirmed the distinctly longer-persisting effect of the beta-blocker on longterm application. Including the marginal values, the response rate in this collective was relatively high at 73%.


[Paradoxes in the clinical aspects of depression (author's transl)]. An attempt is made to present the contradictions in the clinical picture of depression as "paradoxes". 12 of these are briefly reported. In the author's opinion, they are, on the one hand, the sequel to a sudden lowering of bio-energetic potential of the patient and on the other, caused by the maintained formal logic of his consciousness. Some of these paradoxes, although again rooted in the behavior of the patient, are chiefly seen as such in the consciousness of the doctor because the doctor is accustomed to having a different image of the depressed patient. The opinion is expressed that pathophysiological phase symptoms in the activity of the cerebral cortex (in the Pavlovian sense) are responsible for the nature of these paradoxes which are, to a certain extent, understandable psychologically.


[Intuition and imagination in Psychiatric diagnosis (author's transl)]. Intuition in the medical diagnostic sphere is a subconscious cognitive act, the result of which appears consciously as a flash of imagination. Scientific intuition presumes expert knowledge and works consciously with the mnemic reservoir and the associative forces from the subconscious. Low degrees of a hysterical and paranoic nature facilitate access to the subconscious and projection. Intuitive knowledge is corrected by rational thinking.


[Apoplexy (author's transl)].

[Apoplexy (author's transl)]. Apoplexy is a common clinical picture. The clinical diagnosis is unsatisfactory. The procedure hitherto, in which angiographic clarification of the intracranial space-occupying lesions and of the extracranial vascular changes is almost always performed, will change with the introduction of computer tomography in favor of the bloodless method (Doppler echography). Angiography will then only be carried out in proven hemodynamically active stenosis after the neurological symptoms have receded. The treatment of ischemic cerebral disease is a task for the hospital. Transient ischemic attacks also require hospital supervision, preferably under conditions of intensive care. In addition to support from infusions and digitalization, Actovegin infusions are standard therapy.


[Histotopography of chronic gastritis in localized processes of the gastric wall and in resected stomach (author's transl)]. The topography of gastritis was investigated by selective endoscopic biopsies from the antrum and body of the stomach in 231 patients with duodenal or gastric ulcers, 165 patients with gastric carcinoma, 83 patients with polyps of the gastric epithelium and 122 patients after gastric resection (Billroth II). The results of this study show that gastritis, even with localized gastric processes or lesions is not a general inflammation involving the whole of the gastric mucosa. Gastric epithelial polyps and gastric carcinoma are associated with a chronic atrophic gastritis in the affected gastric mucosal areas in less than or in about 50% of cases. A diffuse uniform gastritis was found in little more than 65% of gastric resections.


[Application of plate thermography in the diagnosis of scrotal diseases (author's transl)]. Plate thermography for the diagnostic differentiation of scrotal diseases is an easy, quick method for the doctor without any great expenditure for apparatus; for the patient it is painless and without danger. After application in 58 patients with various changes in the scrotal contents the characteristic findings of acute epididymitis, varicocele and scrotal tumor were obtained. As an additional investigational procedure, plate thermography permits improvement of preoperative diagnosis of scrotal tumors and epididymitis, control of postoperative treatment of varicocele, early recognition of torsion of the testis and confirmation of discrete varicoceles.


[Active therapeutic exercises in combination with vasoactive drug in intermittent claudication (author's transl)]. Earlier investigations have shown that the success of physiotherapeutic exercises in peripheral arterial circulatory disturbances in stage II (Fontaine) can be increased by additional administration of "vasoactive" substances. In the present double-blind study, therefore, 102 outpatients were treated with magnesium nicotinate-magnesium dehydrocholate or a placebo in addition to basic physical therapy. The drug collective (n = 50) showed an increase in walking distance of 24.1% compared with the placebo group (n = 52). Also, in respect to the success rate, the drug collective did better, which, however, may have been due to the unequal distribution of the prognosis factors. Yet it may be concluded that the physiotherapeutic exercises can be effectively supported by the drug tested.


The formation and recovery of two-break chromosome rearrangements from irradiated spermatozoa of Drosophila melanogaster. Chromosomes and chromatid-type rearrangements can be induced by exposure of spermatozoa of Drosophila to ionising radiation. A model, proposed to explain the formation and recovery of compound autosomes, has been extended to account for the induction of centric fragments capped by a duplication of paternal chromosome material. Three basic assumptions have been used; (1) that the sperm nucleus contains a haploid set of unreplicated chromosomes, (2) that the broken chromosome ends can be joined together before or after replication, and (3) that one of the first two cleavage nuclei may be lost and an adult organism derived from the other. The present paper reports a theoretical application of this combination of assumptions to the general case of the formation and recovery of two-break rearrangements. This has led to an elucidation of the relation between repeats, compounds, fragments, and deficiencies on the one hand and inversions and translocations on the other hand. Dicentric chromosomes and segmental aneuploidy can be simply explained. A selective screen is formed by the segregation of chromatid rearrangements and the aneuploidy tolerance levels of the early cleavage nuclei. Thus there is an alternative way of explaining observations which might indicate preferential breakage or joining.


Clinical laboratories. Profit center, production industry or patient-care resource? The clinical laboratory is an essential component of the medical-care system. Rapidly increasing expenditures for laboratory services, fraudulent practices and reports of laboratory error are precipitating legislative and regulatory actions that will affect clinical laboratories and how they are used by physicians in caring for their patients. Many problems related to clinical laboratories are due to the rapid introduction of new technologies, to methods of educating medical students and house officers, to the rapidly expanding scientific base of medicine and to economic factors that have subordinated medical and scientific objectives in the laboratory to economic ones. Implementation of existing legislation would settle many of the economic issues, but more effective integration of the clinical laboratory into the patient-care process and better methods for educating medical students in the use of laboratory information are critical tasks for the medical profession.


Immunopathology of follicular lymphomas. A model of B-lymphocyte homing. To investigate whether follicular lymphoma has a monoclonal origin, we stained frozen tissue sections from 22 afflicted patients for kappa and lambda light chains with an immunofluorescence technic. F(ab')2 antibody fragments were used to avoid binding by Fc receptors. In 20 cases the lymphoma nodules comprised a monoclonal population of immunoglobulin-producing cells. The nodules were usually surrounded by a normal, polyclonal population of B lymphocytes. Reactive lymphoid follicles were easily differentiated from lymphoma nodules on the basis of clonality. Eight cases contained multiple immunoglobulin heavy chains. All the lymphoma nodules in the same tissue or in multiple tissues in the same patient showed identical light-chain and heavy-chain staining even if different histologic subtypes were identified. Follicular lymphoma is the outgrowth of a single clone of immunoglobulin-bearing cells that retain the tissue-homing characteristics of B lymphocytes.


Examination of fungal growth and aflatoxin production on marihuana. Under favorable growth conditions, Aspergillus flavus and A. parasiticus produced aflatoxins on marihuana. Cultures of A. flavus ATCC 15548 produced both aflatoxin B1 (AFB1) and G1 (AFG1). The production of AFG1 was substantially greater than that of AFB1. Cultures of A. flavus NRRL 3251 and A. parasiticus NRRL 2999 produced only AFB1. All natural flora cultures tested negative for aflatoxins. No Aspergilli sporulations were observed in these cultures. In the cultures inoculated with known toxigenic fungi, the highest mean level for total aflatoxins was 8.7 microgram/g of medium. Marihuana appears not to yield large quantities of these mycotoxins but sufficient levels are present to be a potential health hazard for both the user and the forensic analyst who is in daily contact with such plant material. Careful processing, storage, and sanitation procedures should be maintained with marihuana. If these conditions are disregarded due to the illicit status of marihuana, the potential for mycotoxin contamination must be considered.


The formation of germtubes by Candida albicans, when grown with Staphylococcus pyogene, Escherichia coli, Klebsiella pneumoniae, Lactobacilius acidophilus and Proteus vulgaris. The formation of germtubes by twelve clinical isolates of C. albicans was studied in human serum containing per millilitre 10(3) to 10(9) organisms as: Staphylococcus pyegene, Escherichia coli, Klebsiella pneumoniae, Lactobacillus acidophilus and Proteus vulgaris. All the five bacteria inhibited formation of germtubes by C. albicans at all concentrations and the percent germtube formed diminished with increasing concentration of the bacteria. Lactobacillus acidophilus inhibited the formation of germtubes maximally followed by Staphylococcus pyogene, Escherichia coli and Klebsiella pneumoniae. Proteus vulgaris in the concentrations of 10(3) to 10(7) bacteria per millilitre produced only insignificant inhibition of formation of germtubes by C. albicans. Since germtubes of C. albicans are invasive, it is suggested that inhibition of "blastospore-germtube transformation" may be significantly responsible for prevention of infection by C. albicans by coexisting bacterial flora.


Sodium valproate in the treatment of intractable seizure disorders: a clinical and electroencephalographic study. A 12-week study of clinical response, EEG changes and serum antiepileptic drug (AED) levels using sodium valproate (VAL) was undertaken. The study showed that VAL is a powerful adjunct in the treatment of intractable epilepsy. It was most effective in patients with generalized seizures, but no seizure type was totally resistant. No serious adverse effects were encountered; nausea was easily overcome by readjusting the drug dosage. In most cases the only EEG change was decrease of epileptiform activity, and this correlated well with decreased frequency of clinical seizures. These two features in turn were most often seen with a serum VAL level of 40 microgram per milliliter or greater. Intoxication with VAL was accompanied by marked slowing of the background rhythms, but no increase in beta activity. Other modifications of the EEG were probably due to changes in the plasma levels of other drugs. Interactions between VAL and conventional antiepileptic drugs occur, so that serum concentrations of all drugs must be monitored in patients receiving VAL.


[Diagnostic difficulties in facial hemispasm in a child]. The authors report a case of facial hemispasm in a 7 years old child observed for several years. Spasms appeared at the age of 13 months. Based on the observations and results of clinical investigations the authors come to conclusion that facial hemispasm in this case was probably due to irritation of the facial nerve coexisting with epileptic seizures. They assume that a diffuse central nervous system damage is present in the patient, probably due to meningoencephalitis at the age of 3 months.


Internal and external carotid vascular responses to vasoactive agents in the monkey. Internal and external carotid blood flows in anesthetized monkeys were measured simultaneously using electromagnetic flowmeters. Complete dose-response relationships were established for the effects of intracarotid infusion of several humoral agents implicated in migraine. Both the internal and external carotid vasculatures were constricted by serotonin and prostaglandin F2alpha and dilated by bradykinin, histamine, and acetylcholine. Noradrenalin and adrenaline constricted the external carotid vasculature but had little direct effect in the internal carotid territory. Prostaglandin E1 dilated the external carotid vasculature. Low doses of prostaglandin E1 produced dilation in the internal carotid circulation, but with higher doses there was a paradoxical abolition of this effect.


[Analysis of benefits and costs in the eradication of transmissible diseases of endemic character with special reference to poliomyelitis]. Cost-benefit analysis is an important in the rational direction of health policy. The results with respect to poliomyelitis are examined in the light of the money spent and the advantages obtained. It is shown that the cost-benefit ratio has been 1 : 12.98, i.e. every lira spent on vaccination has resulted in a direct saving of 12.98 lire with respect to cases prevented and the cost of their treatment and patient rehabilitation. The ratio is, of course, higher if indirect benefits of a social, moral and occupational kind are included. Some observations are offered on the areas to which cost-benefit analysis can be applied and the ground that it covers.


Home parenteral nutrition.

Home parenteral nutrition. Home parenteral nutrition on a permanent basis can be done by patients who are reasonably intelligent and well motivated. The various aspects of such a scheme are described with reference to three patients in the Waikato area who have had extensive bowel resections. Use of A-V loop vein grafts avoids the necessity for indwelling plastic shunts or catheters.


[Theoretical and applied aspects of experimental teratology]. The dependence of teratogenic effect from the agent specific properties, dose and exposition and the genotype of embryo and maternal organism is considered. The stage specificity of teratogens and the concepts of critical developmental periods are analyzed. The data on general mechanisms of embryonic defects related to the mutations and their phenocopies induced by teratogens are evaluated. The applied aspects of experimental teratology and, in particular, the testing of drugs' teratogenicity and the development of mathodical bases for the establishment of teratogens among the chemical pollutions are intimately connected with and depend on more profound studies of the theoretical bases of teratology. A new method of testing the chemical substances is proposed: search for embryotoxic and teratogenic factors in the blood of animals which were in contact with teratogens. With this aim the cleaving postimplantation mouse and rat embryos are cultivated in the medium with the blood serum from the animals treated with teratogens. This allows to detect in the blood not only the substance in question, but also the toxic products of its metabolism and the toxic substances formed in the maternal organism under the effect of this teratogen. The approaches to the express methods of estimation of teratogenicity are evaluated and the grounds of many steps testing the chemical polutions for teratogenicity are provided.


[Trial of immunodiffusion on cellulose acetate. Application to the estimation of immunoglobulins A and serum transferrin. Results in alcoholism and cirrhosis (author's transl)]. The authors propose electro-immunodiffusion on cellulose acetate instead of agar gel. This simple, rapid and economical method was applied to the estimation of serum immunoglobulins A and transferrin. The following results were obtained for the IgA/transferrin ratio in 108 cases: Normal: 0.87 +/- 0.29; alcoholics without proved cirrhosis: 1.61 +/- 0.95; alcoholic cirrhosis: 3.36 +/- 2.30. The interest of this determination in detection is increased by this simple test.


Relationship of serum theophylline concentration to inhibition of exercise-induced bronchospasm and comparison with cromolyn. Exercise-induced bronchospasm was induced by treadmill running in 12 children on two days preceding either inhaled cromolyn sodium (Intal) or oral theophylline (Slo-Phyllin tablets), 7.5 mg/kg, administered in a double-blind manner. A second exercise period identical to the first followed two hours later; the medication administration had been timed so that the second exercise stress followed two hours after theophylline administration and 15 minutes following cromolyn administration. The patients subsequently were exercised twice more at two-hour intervals on both days. Blood was drawn from serum theophylline measurement immediately after each of the exercise periods. There was little demonstrable exercise-induced bronchospasm resulting from the first postmedication exercise period following theophylline administration. The two subsequent exercise periods were associated with some return of postexercise bronchospasm. The degree of inhibition of exercise-induced bronchospasm correlated with serum theophylline levels that averaged 16, 13, and 10 microgram/ml at two, four and six hours after the theophylline dose (mean Spearman rank correlation coefficient = .71, P less than .01). The effect of cromolyn in suppression exercise-induced bronchospasm that matched or excelled that seen with theophylline.


Conspecific images as elements of compound stimuli controlling operant responding in female rhesus monkeys. Six adult female rhesus monkeys (Macaca mulatta) performed food-reinforced button presses in a compound stimulus discrimination paradigm. Three subjects were trained on a compound stimulus consisting of a color motion picture of an adult male rhesus superimposed over a homogeneous blue field of color. A second group of three subjects was trained on a compound consisting of a color slide depicting an adult male rhesus and the blue field. Subsequent testing of relative stimulus control exerted by either compounds, conspecific stimuli (movie-slide) or blue field alone was carried out. Results indicated that for the movie group, stimulus control was attenuated when  either the conspecific stimulus or blue field was presented as a single S+ stimulus compared to tests using the compound stimulus as S+. Subjects in the movie group shared attention to both constituent elements of the compound. Statistically significant differences in stimulus control between compound, conspecific stimulus, and blue field were not found for the slide group. Superior control by the compound movie-blue field was explained as the result of increased visual salience of an altered (blue) conspecific image.


Electrodermal response in the squirrel monkey. An effort to find evidence of electrodermal response in the squirrel monkey (Saimiri sciureus), as found in man, some infra-human genera of Simiae, and some lower mammals and amphibians, failed to locate an example. Given anatomical considerations, the availability of this response in Saimiri was suspected. In this study, using the skin conductance (constant voltage) method, monophasic electrodermal response as a result of novel or startle stimuli presentation was detected and a range of skin conductance level for test cases was determined.


PCB's in fish from selected waters of New York State. PCB residues in fish from 41 stations throughout New York State were monitored in 1975. Nearly all fish contained PCB's in detectable amounts although the levels of contamination and specific Aroclor varied. The Hudson River contained the highest known PCB concentrations within the United States; levels often exceeded 100 ppm. Other waters and fish which were significantly contaminated include Lake Ontario salmonids and Cayuga Lake lake trout. Onondaga Lake, previously closed to fishing because of mercury contamination, also appears to have abnormally high levels of PCB's approaching in some instances the action level of the Food and Drug Administration, U.S. Department of Health, Education, and Welfare. Samples from marine waters generally have contaminant levels substantially below 5.0 ppm.


The effects of hypotension and hypovolaemia on the liberation of vasopressin during haemorrhage in the unanaesthetized monkey (Macaca mulatta). Using unanaesthetized monkeys, experiments were performed to examine the effects of haemorrhage on the liberation of arginine vasopressin (AVP). Haemorrhages of 10%, 15% or 20% total blood volume were performed via a catheter with its tip in the abdominal vena cava. A catheter in the left internal jugular vein was used for blood sampling. Arterial blood pressure was monitored via a catheter whose tip resected in an iliac artery. The monkeys showed no signs of discomfort from this catheterisation. Blood samples for AVP assay were taken at different times from 0-90 min after the end of the haemorrhage. At the end of the experiment, blood removed was reinfused. Results show that haemorrhage resulted in liberation of AVP, but only if there was a fall in arterial blood pressure. AVP release occurred more readily as the total volume of blood withdrawn increased, but the absolute rise in hormone concentration was not related to the total volume of blood withdrawn. However, comparing the area under the curve of mean arterial blood pressure with that for AVP concentration showed the two to have a significant exponential relationship. It is concluded that, as in other species, haemorrhage is a potent stimulus for AVP liberation in the monkey. However, in contrast to some other species, the fall in arterial pressure seems to be the prime stimulus rather than hypovolemia per se.


[The rapid detection and specific identification of bacterial antigens by electro-immunodiffusion in 80 cases of purulent meningitis (author's transl)]. The cerebrospinal fluid of 120 subjects, 80 of whom were suffering from a purulent meningitis, were examined comparatively by classical bacteriological techniques (direct examination and culture) and by electro-immunodiffusion. This procedure makes it possible to detect not only viable bacteria, but also capsular polysaccharide antigens. It revealed the diagnosis in 96.9% of cases of meningococcal, pneumococcal and Haemophilus meningitis, as against 80.3% positive results using classical bacteriological techniques, for the same organisms. Electro-immunodiffusion provides a rapid answer (20 minutes) and, amongst other things, makes it possible: - to confirm the serotype or capsular type within the species, - to determine the aetiological diagnosis in certain types of meningitis where diagnosis is rendered difficult by blind antibiotic therapy, - to quantify and follow over a period of time the levels of polysaccharide antigens in the cerebrospinal fluid and serum of the patients. The sensitivity and specificity of electro-immunodiffusion render it a technique of the future in the diagnosis of purulent meningitis. By virtue of its simplicity, it should become a routine examination.


[Intrahepatic organic cystals in artificial feeding of children (author's transl)]. Crystals have been observed in the liver of 4 children, submitted to a parenteral nutrition and or, continuous enteral nutrition. Those crystals appear to be birefringent with polarized light extra and intracellular in electron microscopy, they contain a large amount of calcium, phosphore and sulfur. They are thought to represent organic crystals precipitating within the bile ductules of the portal areas. The occurence of those organic crystals seems to be related to a lack of bile secretion due to the exclusion of kinetic and secretory activity of the stomach and the duodenum.


[The treatment of recent myocardial infarction by prolonged infusion of trinitrin (author's transl)]. Seventy four clinically comparable cases of myocardial infarction, admitted on average at the 10th hour were divided at random in two groups: thirty nine were treated with a prolonged intravenous infusion of trinitrin lasting for 24 hours in 12 cases and during 5 at 7 days in 27 cases: 35 served as controls. The results showed the following: a) the good tolerance of the drug used in this way; b) on the basis of precordial cartography, a reduction of 56.2 +/- 14.5% to 30 +/- 7.3% in the index of secondary extension of necrosis; c) clinical signs of left ventricular failure developed in 60% of the controls as compared with 45.8% of the treated group; d) the prevalence of rhythm disturbances was also lower in those treated; e) overall mortality during the first 4 weeks was 8 amongst the 35 controls and 2 of the treated patients (p less than 0.05).


The nucleotide sequence of a major glycine transfer RNA from the posterior silk gland of Bombyx mori L. The nucleotide sequence of tRNA1Gly isolated from the posterior silk gland of Bombyx mori has been determined. This transfer RNA is present in high amounts in the posterior silk gland during the fifth larval instar. It has a GCC anticodon, capable of decoding a major glycine codon in the fibroin messenger RNA, GGU. Structural features of Bombyx tRNA1Gly and its homology to other eukaryotic glycine tRNAs are discussed.


Influenza virus messenger RNAs are incomplete transcripts of the genome RNAs. The results of ribonuclease T1 oligonucleotide fingerprint analyses indicate that influenza virus messenger RNAs are incomplete transcripts of the corresponding genome RNAs and that in this respect they differ from the unpolyadenylated virus specific complementary RNAs obtained from infected cells. From the position of the untranscribed oligonucleotide in the virus RNA sequence and the ability or inability of the different transcripts to protect the 5' terminal nucleotide of virus RNAs against nuclease S1 digestion, it is concluded that whereas the unpolyadenylated cRNAs are complete transcripts, the polyadenylated messenger RNAs lack sequences complementary to the 5' end of the genome molecules.


Nucleotide sequence of a lysine tRNA from Bacillus subtilis. A lysine tRNA (tRNA1Lys) was purified from Bacillus subtilis W168 by a consecutive use of several column chromatographic systems. The nucleotide sequence was determined to be pG-A-G-C-C-A-U-U-A-G-C-U-C-A-G-U-D-G-G-D-A-G-A-G-C-A-U-C-U-G-A-C-U-U(U*)-U-U-K-A-psi-C-A-G-A-G-G-m7G(G)-U-C-G-A-A-G-G-T-psi-C-G-A-G-U-C-C-U-U-C-A-U-G-G-C-U-C-A-C-C-AOH, where K and U* are unidentified nucleosides. The nucleosides of U34 and m7G46 were partially substituted with U* and G, respectively. The binding ability of lysyl-tRNA1Lys to Escherichia coli ribosomes was stimulated with ApApA as well as ApApG.


Studies on the primary structure of the ribosomal 23S RNA of Escherichia coli: II. A characterisation and an alignment of 24 sections spanning the entire molecule and its application to the localisation of specific fragments. We have employed new methodology to obtain 23S RNA fragments which includes a) the digestion of the RNA within 50S subunits and b) the limited hydrolysis of the 13S and 18S fragments. By comparing all 23S RNA fragments, obtained heretofore, we have characterised and aligned 24 sections of this RNA spanning nearly the entire molecule. These results allow the localisation of any new 23S RNA fragment by comparison of the fingerprint of its T1 ribonuclease digest to the characteristic ones of the different sections. In this way we obtained a more definite localisation of the binding sites of the 50S proteins L1, L5, L9, L18, L20, L23 and L25. We also specified a ribonuclease sensitive region of 23S RNA in native 50S subunits, extending from the 1100th nucleotide from the 5' end to the 1000th nucleotide from the 3' end; this region contains a cluster of 5 modified nucleotides and may be at the subunit interface.


Thyroid disorders and the distribution of orally administered radioiodine. 128 control, thyrotoxic, hypothyroid and goitrous euthyroid children were administered 1-2 muCi Na131I orally and studied in a shadow-shield whole-body counter. 48-hr whole-body counts permitted the differentiation of the first 3 groups (p less than 0.005). Ratio of extrathyroid:excreted 131I was 3 times greater in thyrotoxics than in goitrous euthyroids, but the thyroid:extrathyroid ratio was 3 times greater in the latter group. The whole-body profile scan obtained at 48 hr on an attached strip chart recorder, revealed activity not only in the thyroid but even lower down in the vicinity of the knees and feet.


Regulation of appetite during total parenteral nutrition. To study effects of total parenteral nutrition (TPN) on appetite, in an effort to obtain an objective assessment of hunger separated from underlying pathology, caloric intake and levels of TPN were measured in two male rhesus monkeys. TPN was found to affect appetite by reducing voluntary food intake. One monkey showed precise regulation of daily oral caloric intake and maintained stable body weight during this period. The other monkey did not show such precise regulation. When TPN was stopped, both continued suppression of oral intake for a time. Implications are discussed.


Method for detection of specific RNAs in agarose gels by transfer to diazobenzyloxymethyl-paper and hybridization with DNA probes. We describe a technique for transferring electrophoretically separated bands of RNA from an agarose gel to paper strips. The RNA is coupled covalently to diazobenzyloxymethyl groups on the paper. After transfer and appropriate treatment of the paper to destroy remaining diazo groups, specific RNA bands can be detected by hybridization with 32P-labeled DNA probes followed by autoradiography. This procedure allows detection of specific RNA bands with high sensitivity and low background.


Use of gene fusions to study outer membrane protein localization in Escherichia coli. Escherichia coli strains have been isolated that produce hybrid proteins comprised of an NH2-terminal sequence from the lamB gene product (an outer membrane protein) and a major portion of the COOH-terminal sequence of beta-galactosidase (beta-D-galactoside galactohydrolase, EC 3.2.1.23; a cytoplasmic protein). These proteins exhibit beta-galactosidase activity. One such strain, pop 3105, produces a hybrid protein containing very little of the lamB gene protein; the protein is found in the cytoplasm. The protein found in a second strain, pop 3186, contains much more of the lamB gene protein; a substantial fraction of the beta-galactosidase activity is found in the outer membrane, probably facing outward. These results indicate that information necessary to direct the lamB gene product to its outer membrane location is located within the lamB gene itself. The properties of such fusion strains open up the prospect of a precise genetic analysis of the genetic components involved in protein transport.


[Serum immunoglobulins in children with diabetes mellitus]. The authors present the results of studying immunoglobulins of classes A, M, and G in 40 children with diabetes mellitus; immunoglobulin level was analyzed depending on a number of clinical diabetes mellitus indices and insulin antibody titres. The III type of dysgammaglobulinemia was found to be characteristic of patients with microangiopathies; changes in the immunoglobulin content were directly opposite to the changes revealed in patients with microangiopathies. With increasing the duration of diabetes there was an aggravation of dysgammaglobulinemia characteristic of these two groups of patients. The level of immunoglobulins under study was greater in the patients with lipoatrophies and in those without any hereditary predisposition to diabetes than in patients without lipoatrophies and without any hereditary predisposition to diabetes, respectively. A regular reduction of all the immunoglobulins level was observed only in patients with glucosuria of not less than 100 g/24 hours. Immunoglobulin content showed no significant association with the patients' sex, age, the insulin antibody titre, and the age at which diabetes developed, or with hyper cholesterolemia and enlargement of the liver.


In vitro degradation of guanosine 5'-diphosphate, 3'-diphosphate. The degradation of guanosine 5'-diphosphate,3'-diphosphate (ppGpp) by the "crude" ribosomal fraction of Escherichia coli CP78 (rel+, spoT+) was demonstrated and characterized. When the 3'-pyrophosphoryl group of ppGpp was hydrolyzed, the primary degradation product was 5'-GDP. Phosphorylation of ppGpp to guanosine 5'-triphosphate,3'-diphosphate (pppGpp) prior to degradation was not necessary. The degradation process required Mn2+ and was inhibited by EDTA. Levallorphan, an inhibitor of in vivo ppGpp degradation, also inhibited ppGpp degradation by the crude ribosome. Thiostrepton and tetracycline did not have any inhibitory effect, indicating that the reaction is not a reversal of pyrophosphorylation catalyzed by the stringent factor/ribosome complex. Crude ribosome fractions from E. coli NF161 and NF162, both spoT-, contained little degrading activity, but similar fractions of E. coli CP79, a relA- and spoT+ strain, contained ppGpp degrading activity.


Variable and constant parts of the immunoglobulin light chain gene of a mouse myeloma cell are 1250 nontranslated bases apart. A DNA fragment carrying an immunoglobulin gene coding for both variable (V) and constant (C) regions of a mouse lambda light chain was enriched about 15-fold from a total endonuclease EcoRI digest of a plasmacytoma (HOPC 2020) DNA by preparative agarose gel electrophoresis. The DNA fraction was used for cloning of a lambda chain gene in the phage lambdagtWES vector. After screening [Benton, W. D. & Davis, R. W. (1977) Science 196, 180-182] of about 70,000 plaques, each arising from an independent transfection event, we isolated one clone (Ig 303) that contained both a Vlambda and a Clambda DNA sequence. Electron microscopy of R-loops formed between the cloned DNA and purified lambda chain mRNA (HOPC 2020) revealed that the Vlambda and Clambda DNA sequences are separated by a 1250-base DNA fragment.


Physiological regulation of antigen binding to T cells: role of a soluble macrophage factor and of interferon. A soluble product of macrophages (MF) and mouse viral interferon (IF) increase both major histocompatibility antigenic determinants and the number of antigen-binding cells in nonstimulated T cell-enriched mouse lymphocyte cultures. MF increases Ia and not H-2 antigens; IF increases H-2 but not Ia antigens. The increased antigen binding due to MF can be inhibited by anti-Ia but not by anti-H-2 sera, whereas IF-induced binding is sensitive to anti-H-2 but not to anti-Ia sera. The specificity of IF- or MF-induced binding of branched synthetic polypeptides by T cells is different from that of B cells and similar to the specificity of the Ir gene regulation. MF increases antigen binding only in Ir high-responder animals. The IF-induced antigen binding is not dependent on the Ir genotype. MF-reactive cells express the Ly-1 marker, and the IF-reactive antigen binders express the Ly-2 phenotype. It is suggested that MF and IF are physiological mediators of antigen binding by T cells.


Amino acid sequence of the precursor region of MOPC-315 mouse immunoglobulin heavy chain. Partially purified mRNA coding for the MOPC-315 heavy immunoglobulin alpha chain was translated in a reticulocyte lysate containing 20 labeled amino acids. Radiolabeled MOPC-315 heavy chain precursor protein, purified by preparative gel electrophoresis and immunoprecipitation, was sequenced by Edman degradation. The labeled phenylthiohydantoin amino acid obtained in each cycle was identified and quantitated by high-pressure liquid chromatography. The precursor sequence of 18 amino acids, Met-Lys-Val-Leu-Ser-Leu-Leu-Tyr-Leu-Leu-Thr-Ala-Ile-Pro-His-Ile-Met-Ser, preceded the sequence corresponding to the NH2 terminus of the mature secreted heavy chain.


Unusual pulmonary vasodilator activity of 13,14-dehydroprostacyclin methyl ester: comparison with endoperoxides and other prostanoids. Microsomes from stomach fundus and blood vessels transform the endoperoxide, PGH2, into a newly discovered unstable substance, PGI2, that relaxes arterial strips and inhibits platelet aggregation. 13,14-Dehydro-PGI2 methyl ester, a newly synthesized, stable PGI2 analog, was found to have potent vasodilator activity in the feline and simian pulmonary vascular bed. The PGI2 analog decreased lobar arterial perfusion pressure in the intact cat and monkey. Because pulmonary blood flow was held constant and left atrial pressure was unchanged, the decrease in perfusion pressure reflects a decrease in pulmonary vascular resistance. The dilator response was unusual in that it persisted for 10-12 min, whereas the response to PGE1, the only other vasodilator prostaglandin in the mature animal, persisted for only 1-2 min. The dilator response to the PGI2 analog was enhanced when pulmonary vascular resistance was increased. This substance had less effect on cardiac output and aortic pressure than PGE1, whereas it was a more potent pulmonary vasodilator. These data demonstrate that prostacyclin-like substances possess novel vasodilator activity in the pulmonary circulation and suggest a therapeutic use in the treatment of pulmonary hypertensive diseases.


The effect of delta 9-tetrahydrocannabinol, cannabidiol, and cannabinol on the anaesthesia induced by various anaesthetic agents in mice. delta 9-Tetrahydrocannabinol (2.5-80.0 mg/kg) significantly prolonged the anaesthesia induced by ketamine, pentobarbitone, thiopentone, propanidid, and Alfathesin in a dose-dependent manner. Cannabinol and cannabidiol (both 5.0-80.0 mg/kg) were essentially inactive, except that cannabidiol prolonged pentobarbitone-induced anaesthesia. The interaction of delta 9-tetrahydrocannabinol with the anaesthetic agents was postulated to be due to a centrally mediated action, whereas the effect of cannabidiol on pentobarbitone-induced anaesthesia probably depended on a metabolic interaction. The interaction between the cannabinoids in influencing anaesthesia induced by the above agents was examined, and the interactions were found to be complex.


Responses of the flexor reflex to LSD, tryptamine, 5-hydroxytryptophan, methoxamine, and d-amphetamine in acute and chronic spinal rats. The flexor reflex of acute (40-48 h after mid-thoracic spinal transection) and chronic (at least 2 months after transection) spinal rats was evoked by tetanic electrical stimulation of both hindfeet and recorded on a polygraph using a transducer connected to the left hindfoot. The flexor reflex in the chronic spinal rat was more responsive to electrical stimulation and to the actions of drugs studied than was the flexor reflex in the acute spinal rat. In chronic spinal rats, d-amphetamine, methoxamine, LSD, tryptamine, and 5-hydroxytryptophan (5-HTP) facilitated the flexor reflex and induced spontaneous movements. These facilitative effects were seen in acute spinal rats only when much larger i.p. doses of amphetamine, methoxamine, and LSD were used. Small i.v. doses of tryptamine also produced the facilitation. The facilitation caused by LSD and tryptamine, but not 5-HTP, in chronic spinal rats was antagonized by cyproheptadine. These observations suggest that chronic spinal rats were more sensitive to the drugs than acute spinal rats and support the hypothesis that the mode of action of LSD is similar to that of tryptamine but different from that of 5-HTP since cyproheptadine antagonized the facilitative effects of LSD and tryptamine but not those of 5-HTP.


Anorexigenic and ancillary actions of MK-212 (6-chloro-2-(1-piperazinyl)-pyrazine; CPP). In rats allowed to eat for 2 h/day and injected i.p. 30 min before feeding, MK-212, ED50 = 1.5 mg/kg, was two times more potent as an anorexigen than fenfluramine. However, the compounds were equiactive in the rat following p.o. administration 1.5 or 3 h before the test, while fenfluramine was more potent if the interval was extended to 6 h. In cats permitted to eat for 3 h/day, the ED50 dose (mg/kg p.o.) for MK-212 determined at 0.5, 1 and 3 h after feeding was, respectively, 15, 10, and 3 times less than that of fenfluramine. Emesis and diarrhea were frequently observed ancillary effects in cats treated with fenfluramine, whereas apparent sedation and salivation were commonly detected in animals after MK-212. In rats or cats pretreated with methergoline, the decrease in food consumption elicited by MK-212 was markedly inhibited, suggesting that the mechanism of action involves a serotoninlike effect. Compared with the marked stimulant action of amphetamine, MK-212 had only a minor and inconsistent effect on motor activity in rats and mice. Similar results were obtained with fenfluramine. MK-212 was not self-administered by rats, while the self-administration of amphetamine and morphine were demonstrated using the same experimental protocol.


Mesolimbic dopamine neurons: effects of 6-hydroxydopamine-induced destruction and receptor blockade on drug-induced rotation of rats. Bilateral injections of 6-hydroxydopamine (6-OHDA) into the nucleus accumbens greatly reduced the dopamine content of this nucleus and the olfactory tubercle and blocked the ipsilateral rotation induced by amphetamine and methamphetamine in rats with unilateral 6-OHDA lesions of the caudate nucleus. In contrast, apomorphine-induced contralateral rotation was enhanced. Similar results were obtained when the destruction of forebrain noradrenergic neurons, normally produced by the nucleus accumbens 6-OHDA lesion, was prevented by desipramine (DMI) pretreatment. Microinjections of the dopamine receptor antagonist heloperidol into the nucleus accumbens did not spread to the olfactory tubercle, as assessed by the distribution of 3H-haloperidol, and blocked circling induced by amphetamine and apomorphine. Amphetamine-induced circling was less effectively blocked by haloperidol injected into the olfactory tubercle. These results suggest that activity at nucleus accumbens dopamine receptors can greatly affect circling behavior, perhaps by amplifying asymmetries of nigrostriatal activity.


Circadian susceptibility rhythm to neuroleptics: tetrabenazine. In order to clarify the influences of situational factors on the effects of psychotropic drugs, the sedative effects of tetrabenazine after injection at various times of the day were studied. When 50 mg/kg body weight of tetrabenazine was injected into rats at eight different times of the day (07:30-19:30 dark, 19:30-07:30 light), a circadian rhythm of sedative effect was observed with a peak sedative time of 1490 min at 10:30 and a nadir of 736 min at 07:30. With 10 mg/kg body weight of tetrabenazine a similar circadian rhythm of sedative effect was observed. This rhythm did not appear to be due to differences of metabolism of tetrabenazine in the tissues, but rather to be closely related to daily fluctuation of serotonin synthesis and release in the brain.


The effects of psychotropic drugs on exploratory and stereotyped behaviour of rats studied on a hole-board. Exploratory and stereotyped behaviour of Male Wistar rats was studied on a hole-board. The two forms of behaviour were differentiated according to the pattern of hole-dipping activity. Increasing doses of dl-amphetamine stimulated both forms of behaviour with stereotyped behaviour becoming predominant particularly at the higher dose levels. At the highest dose of amphetamine used (16 mg/kg) a gradual transition from exploratory to stereotyped behaviour was observed with time. As the drug wore off this transition was reversed. Haloperitol at a dosage of 0.1 and 0.05 mg/kg blocked the response to a high dose of amphetamine whereas a lower dose (0.02 mg/kg) blocked the stereotyped response to amphetamine while some exploratory behaviour still took place. Apomorphine inhibited hole-dipping but at lower doses another form of exploratory behaviour was induced, this behaviour becoming stereotyped as the dose was increased. It is concluded that there is a close relationship between exploratory and stereotyped behaviours. Monoamine systems appear to play a significant role in the regulation of both forms of behaviour.