Studies on endoparasites of the black bear (Ursus americanus) in the southeastern United States. Examination of 53 black bears (Ursus americanus) from six states in the southeastern United States revealed at least 17 species of endoparasites, including Sarcocystis sp., Spirometra mansonoides (spargana), Macracanthorhynchus ingens, Ancylostoma caninum, Arthrocephalus lotoris, Baylisascaris transfuga, Capillaria aerophila, Capillaria putorii, Crenosoma sp., Cyathospirura sp., Dirofilaria immitis, Gnathostoma sp., Gongylonema pulchrum, microfilariae, Molineus barbatus, Physaloptera sp. and Strongyloides sp. Twelve of these represent new host records for black bear, and two are considered to be new species. Data are presented on prevalence, intensity and geographic distribution of each species. Pathologic effects were associated with infections of spargana of S. mansonoides and adults of C. aerophilia.


Parasites of the coyote (Canis latrans) in central Utah. Seventeen coyotes, Canis latrans, from central Utah were surveyed for parasites. Five species of parasites not reported previously from coyotes in Utah were detected: Filaroides osleri, Physaloptera sp., Spirocerca sp., Ancylostoma caninum, and Cediopsylla simplex. In all, 11 genera of parasites were observed.


Caryospora cheloniae sp. n.: a coccidial pathogen of mariculture-reared green sea turtles (Chelonia mydas mydas). Caryospora cheloniae sp. n. is described from mariculture-reared green sea turtles (Chelonia m. mydas). The sporulated oocyst has a thin, transparent, single-layered wall which often ruptures, leaving a naked sporulated sporocyst. Oocysts measured 33.8 to 40.1 micrometer by 11.0 to 14.6 micrometer (mean 37.4 by 12.8 micrometer). Greatest concentrations of developmental stages of C. cheloniae were found in the hindgut. Transverse binary fission was observed in dividing tissue stages. Pathologic alterations were most pronounced in the posterior third of the intestines (hindgut). The hindgut lumen was greatly dilated and filled with blood, oocysts and tissue debris. The hindgut wall was thinner than normal and the mucosal folds had sloughed into the intestinal lumen. Free blood escaped from the blood vessels of the tunica propria into the intestinal lumen. Epithelial hyperplasia was pronounced at the margins of denuded mucosal areas. Numerous inflammatory cells infiltrated the infected mucosal surface.


Rocky mountain spotted fever caused by blood transfusion. Transfusion of 500 ml of blood, contributed by a donor three days before the onset of Rocky Mountain spotted fever and refrigerated for nine days, caused this disease in the recipient. The blood donor died of Rocky Mountain spotted fever after six days; rickettsia were identified in various tissues by immunofluorescence techniques. The recipient of the blood became mildly ill and recovered fully; specific antibiotic treatment was initiated on the fourth day of illness. Diagnosis of Rocky Mountain spotted fever was confirmed in the recipient by positive serologic reactions and isolation of Rickettsia rickettsii from blood after inoculation in animals and tissue culture.


Preliminary screening of amino acids excretion in the urine of newly born babies. The paper attempts to characterize the qualitative as well as quantitative estimations of aminoacids in the urines of new born babies using two dimensional paper chromatography. The objective of this investigation was to know the extent of amino acid defects in these samples and to correlate such defects with the physical abnormalities in infants. Based on the overall results, it is inferred that phenylalanine excreted in the urine gave a positive response with PKU test and some particular amino acids are identified and estimated in the urine of new born babies to confirm the diagnosis of phenylketonuric patients.


Composition of gall stones-microchemical analysis. The composition of gall stones removed surgically from 31 patients was determined by microchemical analysis. Twenty six had mixed infective, 2 cholesterol and 3 pigment stones. All the stones consisted of combination of various constituents in varying amount. Bilirubin was detected in the centre and peripheral layers of all, protein was found in the centre of 84.6% and cholesterol in the centre of 54% and the peripheral layers of all the gall stones. The findings in this study suggest that infection is the most likely cause of biliary lithogenesis.


[The effects of a new type of laser on fixed tissue of the angle of the anterior chamber in the monkey eye (author's transl)]. Segments of fixed tissue of the chamber angle of the monkey eye are irradiated with a neodymium (YAG-) q-spoiled laser at a pulse duration of 50 ns, a pulse energy of 200 mJ and an optic distance of 15 mm. Perforating injuries are observed between the anterior chamber and Schlemm's canal. When an acute angle of the laser beam relative to the cornea is chosen, the application point must be at the anterior part of the trabecular meshwork, close to the cornea, to open the canal of Schlemm. An impact further back toward the iris would create cyclodialysis.


[Diabetic cataract and flavonoids (first results) (author's transl)]. The possible effects of Quercetine, a potent inhibitor of aldose-reductase, on cataract formation and vascular permeability were investigated in streptozotocine-diabetic rats. Preliminary results after peroral administration of Quercetine did not allow to demonstrate a clear inhibitory effect on cataract formation.


Output value analysis of an alcoholism treatment program. A form of cost--benefit analysis is used to measure the efficiency and effectiveness of an alcoholism treatment program in caring for patients grouped by year of admission, sex and level of impairment.


Age-dependent alpha-glycerophosphate dehydrogenase activity changes in mutant and wild type Drosophila melanogaster. The age-related changes in the activity of the extramitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPDH) were compared in two mutants of Drosophila melanogaster, a vestigial-winged and an alpha-glycerophosphate dehydrogenase deficient mutant with that of the wild type. The age-dependent patterns of activity change in both mutants were shown to be identical to that of the wild type. This is in spite of the lack of flight ability in both mutants, the reduced enzyme activity levels in the alpha-glycerophosphate mutant, and in the case of the vestigial flies, of reduced life-span. The results suggest that those mechanisms responsible for the observed aged-related activity changes in alpha-GPDH are intrinsically regulated, independent of functional flight, genetic alteration of specific activity, and life-span.


Patient outcomes in alternative long-term care settings. The purpose of this study was to compare health status outcomes in three alternative long-term care settings in the Veterans Administration : 1) home care; 2) community-based nursing home care; and 3) hospital-based nursing home care. Patients were measured on a behavioral index of health status, at two points in time: when transferred from the acute care hospital to one of the three treatment programs (pretest and three months later (posttest). Since patients could not be randomly distributed to programs, two methods were employed to control for potential sample selection bias: the choice of a nonequivalent control group design, and multivariate analytic techniques. First, within each program type, patients were randomly selected from both a hospital that offered only that program as a long-term care alternative and from a hospital that provided all three treatment settings. Second, multiple regression analysis was used to control for pretest differences among patients. Patients placed in the home care program displayed the greatest mean improvement in functional health status, holding all other variables constant. This treatment effect was not uniform, however; patients showed differential rates of improvement across the three programs, based upon both initial health status and prognosis.


Assessing the impact of tonsillectomies. This paper explores outcomes associated with the tonsillectomy operation using multiple control groups and a large claims-based data bank from the Canadian province of Manitoba. Given the difficulty of conducting large-scale clinical trials of common surgical procedures, the use of multiple methods for evaluating such interventions is both advocated and implemented in this study. When the data are restricted to respiratory diagnoses, the findings suggest that, on the average, tonsil surgery saves between one half and one and a half episodes of illness per patient over the two years after surgery. Such savings are much more pronounced among individuals having several tonsillitis episodes in the preoperative year. However, when all medical claims are considered, the estimated savings from the tonsillectomy operation are somewhat reduced. Individual variation in predisposition to "see the doctor" appears to account for such results; visits about conditions other than respiratory take up much of the "savings" produced by tonsil surgery. The findings are discussed in terms of the costs and benefits of the tonsillectomy operation, and future research needs are outlined.


Failure of 3,3'-diiodothyronine administration to alter TSH and prolactin responses to TRH stimulation. In order to determine whether elevations in serum 3,3'-diiodothyronine (3,3'T2) concentrations influence the hypothalamic-pituitary--thyroid axis, thyrotropin (TSH) and prolactin responses to thyrotropin-releasing hormone (TRH) were assessed in five patients both prior to and during 3,3'T2 administration. Mean (+/- SE) peak TSH responses to TRH were 168 +/- 64 microU/ml during 3,3'T2 administration and 168 +/- 65 muU/ml during 3,3'T2 administration. Mean basal and peak prolactin concentrations after TRH were 6 +/- 3 ng/ml and 54 +/- 26 ng/ml, whereas during 3,3'T2 administration the basal and peak prolactin levels were 6 +/- 2 ng/ml and 55 +/- 28 ng/ml, respectively. Hypothyroid rats administered triiodothyronine (10 migrogram b.i.d.) for 5 days had a mean TSH response to TRH stimulation of 0.051 +/- 0.003 mU/ml, whereas rats to whom saline or 3,3'T2 (50 microgram b.i.d.) had been given for the same time interval had mean TRH-induced TSH responses of 1.127 +/- 0.179 mU/ml and 1.324 +/- 0.286 mU/ml, respectively. None of the TSH or prolactin responses to TRH, in either human or rat studies, were apparently altered by 3,3'T2. These observations suggest that elevation of serum 3,3'T2 levels are not associated with alterations in the hypothalamic--pituitary--thyroid axis in the experimental systems employed.


[Refinement of the diagnosis of the genera and species of methane-using bacteria]. The diagnoses of taxons have been corrected for methane assimilating bacteria of the family Methylomonadaceae Leadbetter 1974, of the genera Methylomonas Leadbetter 1974. Methylococcus Foster a. Davis 1966, Methylosinus Whittenbury. Phillips a. Wilkinson 1970, Methylocytis Whittenbury, Phillips a. Wilkinson 1970, and of 16 species. The diagnosis of the species Methylomonas rubra Whittenbury, Phillips a. Wilkinson 1970 has been completed, and the new species Methylomonas gracilis sp. nov. and Methylococcus luteus sp. nov. have been described. Since information about the properties of certain strains is not complete, they should be transferred to the category incertae sedis. Diagnostic keys for identification of methane assimilating bacteria are presented in the paper.


[Possibility of culturing hydrogen bacteria in the presence of CO]. The growth of Hydrogenomonas eutropha Z-1 was studied in the presence of CO in the gaseous phase. The culture was found to be resistant to the action of carbon monoxide at concentrations of 5 per cent (periodic cultivation) and 7 per cent (continuous cultivation). The hydrogen bacteria can assimilate CO as a source of carbon.


Widespread distribution of variant forms of carbonic anhydrase in Australian aboriginals. Three distinctive genes which control variants of carbonic anhydrase (CA) have been detected in tests on nearly 3000 Aboriginals from various parts of Australia. Two of these genes affect the products of the CA1 locus, the other affects the products of the CA2 locus. In some populations of Aboriginals, more than 10% of persons have a variant carbonic anhydrase. It is suggested that such an unusual frequency of CA variants may be an evolutionary response to metabolic stress connected either with low zinc concentrations in the diet or with the altered needs of ion regulation in an arid environment.


[Changes in the intracellular desoxyribonuclease activity in the process of Bacillus subtilis cell growth and division]. DNA synthesis and cell division were studied in Bacillus subtilis in relation to their intracellular DNAase activity. The specific activity of DNAases was found to increase prior to the beginning of DNA synthesis and cell division. Active DNA synthesis and cell division were accompanied with a decrease in the specific activity of intracellular DNAases.


[Optimization of the conditions for beta-galactosidase biosynthesis in eukaryotes]. Liquid whey can be subsituted by dry whey in the growth medium for Saccharomyces fragilis producing endocellular beta-galactosidase. The total biosynthesis of beta-galactosidase by the yeast on the medium containing dry whey can be increased by 40-50 percent as a result of additional stepwise introduction of lactose into the medium or optimization of the medium by mathematical planning of the experiment. Constructive metabolism of the yeast is not correlated with the rate of biosynthesis of beta-galactosidase. Damages in constructive metabolism of facultative anaerobes - yeast cultures - caused by the limitation of aeration result in an increase of the rate of beta-galactosidase biosynthesis. Such a correlation between the rate of the enzyme biosynthesis and the degree of aeration of the culture is not found in strict aerobes - fungi Alternaria tenuis and Curvularia inaequalis.


[Physiology of xerophytic microorganisms that grow under very dry conditions]. The biology of xerophytic microorganisms surviving and growing under conditions imitating Martian ones was studied, as well as the zone of tolerance of several microorganisms towards the activity of water. The xerophytic nature of microorganisms is suggested to be evaluated by means of quantitative determination, using gas chromatography, of carbon dioxide which is evolved when microorganisms are cultivated on media with different values of aw.


A clinical look at Stuart's transport medium. The development of Stuart's Transport Medium is described, followed by an inquiry into the rationale of its composition. Suggestions are made for the optimal use of the medium.


The initial attachment of transforming DNA to competent Bacillus subtilis. The initial attachment of transforming DNA to competent Bacillus subtilis is temperature independent between 25 degrees and 45 degrees. However, below 15 degrees there is a significant reduction in the amount of DNA attached to compentent cells. The DNA that is attached at 4 degrees can lead to transformation or interfere effectively with the subsequent attachment of a distinctive DNA when the cells are shifted to a permissive temperature (37 degrees). These data suggest that the attachment of DNA at 4 degrees is to sites normally involved in the transformation process. The amount of DNA that is initially attached to the bacteria at 4 degrees or 37 degrees after perturbation of the cells by ionic strength changes, repetitive washings, or periodate oxidation varies with the temperature at which the treatment occurs. These results are consistent with a reorientation of the DNA attachment sites upon lowering the temperature to 4 degrees, such that their affinity for DNA and susceptibility inhibitory treatments are reduced.


[Intermediate states formed during discharge separation in the reaction centers of Rhodospirillum rubrum in the presence of a low-redox potential]. The intermediate short-lived states arising in reaction centre preparations (RC) of purple bacterium Rhodospirillum rubrum are investigated under the conditions of low redox potential. Excitation by 353 and 530 nm laser pulses produced two states characterized by optical absorption changes in the range of 350--650 nm and lifetimes: 10--30 ns for the first state and 2.5 +/- 0.5 microseconds for the second one. The first state is similar to the state PF, described previously by Parson et al. for RC from Rps. sphaeroides. Carotenoid extraction with isooctane resulted in changing the spectrum with tau = 2.5 microseconds and in the appearance of new absorption changes similar to those for the R state observed before in carotenoidless bacterial strains within microsecond time range. The comparison of the microsecond spectra with difference spectra (continuous light minus dark) of RC from R. rubrum in the range of 350--650 nm made it possible to identify the states with tau = 2.5 microseconds as carotenoid triplet states. The ratio of quantum yields of PR and carotenoid triplet states production was determined as being 1 : 1. The conclusion was made that triplet-triplet energy transfer from state PR to carotenoid is responsible for the production of carotenoid triplet states.


[Effect of flunarizine (sibelium) on the arterial blood flow (author's transl)]. 31 patients with intermittent claudication were treated with 10 mg Flunarizine (Sibelium) daily for 6 months. Before the beginning of the trial and after a period of 6 months, a plethysmographic examination was undertaken to determine the reactive hyperemia elicited by a temporary arterial occlusion. 25 patients showed an improvement in at least one of the parameters measured during the reactive hyperemia. Lengthening of the walking distance was also seen at the same time in 24 of these patients. In a further analysis of our results it was shown that in each of the 25 patients those parameters of the reactive hyperemia improved which had deviated furthest from the normal.


Doctors, damages and deterrence. An economic view of medical malpractice. Damages awarded in a malpractice suit must be viewed not only as compensating the victim but also as deterring health-care providers from negligent behavior. Economic analysis of the malpractice system indicates that awards can send a signal to providers that informs them how much to invest in avoiding mishaps. The malpractice system is beset by difficulties, but not the ones commonly incriminated. The signal to the physician, as determined by the number of claims and size of awards ("expected damages"), appears to be insufficient for ideal deterrence. Moreover, the deterrence signal is attenuated because malpractice premiums are set for groups of physicians, not for individuals according to their record of previous malpractice incidents. Replacing the present tort system with a no-fault insurance scheme would not necessarily be cheaper, and might well abolish the deterrent signal or distort clinical decision making.


How do health-maintenance organizations achieve their "savings"? Health-maintenance organizations have been suggested as a way to stop spiraling medical costs. Although many of the arguments have been largely rhetorical, theoretical considerations suggest that the shift from fee for service to a fixed budget for the providers (physicians and hospitals) will result in substantial savings. Total costs (premium and out-of-pocket) for enrollees are 10 to 40 per cent lower than those for comparable people with health insurance. Enrollees in health-maintenance organizations have about as many ambulatory visits as comparison groups. Most of the cost differences are attributable to hospitalization rates about 30 per cent lower than those of conventionally insured populations. These lower hospitalization rates, in turn, are due almost entirely to lower admission rates; the average lenth of stay shows little difference. There is no evidence that health-maintenance organizations reduce admissions in discretionary or "unnecessary" categories; instead, the data suggest lower admission rates across the board.


Pathology of radiation damage to the normal brain of the monkey. Model I: A portion of the monkey brain, the right occipital lobe, was exposed to 3,500 rads of orthovoltage radiation in a single dose. This demonstrated a) the delayed, 4 to 5 months, massive break in blood-brain barrier with extravasation of plasmatic fluid throughout the right hemisphere causing gross brain distortion, and b) after a protracted course, a remaining impairment in function extending beyond the irradiation lesion. Model II: The whole brain was exposed to supervoltage radiation in single doses of 1,000, 1,500, and 2,000 rads, respectively. This demonstrated a) the lack of effect from 1,000 rads; b) the wide scatter of necrotic lesions in the forebrain white matter from 1,500 rads at 6 months, followed by confluent necrosis in the cerebral hemispheres at 12 months; and c) the numerous focal lesions throughout the brain from 2,000 rads, with the lesions in the brain stem precluding survival beyond 6 months. Model III: The whole brain was exposed to fractionated doses of 4,000, 6,000 and 8,000 rads in 4, 6, and 8 weeks, respectively. This demonstrated a) the lack of effect from 4,000 rads; b) the wide scatter of small focal lesions at different stages of breakdown and repair accompanied by focal edema from 6,000 rads at 6 months, followed by more of the reparative processes including mineralization of focal lesions, and widespread telangiectasia, at 12 months; and c) with 8,000 rads, at 6 months, focal lesions similar to those from 6,000 rads, but at 12 months, gross brain loss from coalescing necrosis.


Neuropathology of tissues from patients treated by the Brain Tumor Study Group. The histopathologic diagnoses in 718 brain tumor patients entered in the Brain Tumor Study Group were reviewed, as well as those for 53 of these patients who were reviewed, as well as those for 53 of these patients who were autopsied later. This review documented instances of progression of histologic analplasia. Of particular interest in the autopsied cases were several instances of extensive necrosis in white matter distant from persisting glioma following chemotherapy and radiotherapy. This observation suggested the presence of a structural and/or metabolic alteration in the diseased hemisphere that perhaps makes it more susceptible to further alterations secondary to the adjunctive therapy.


Pavlovian conditioning analysis of morphine tolerance. It has been demonstrated that many conditional responses to a variety of drugs are opposite in direction to the unconditional effects of the drug, and the conditioning analysis of morphine tolerance emphasizes the fact that subjects with a history of morphine administration display morphine-compensatory conditional responses when confronted with the usual administration procedure but without the drug. Thus, when the drug is presented in the context of the usual administration cues, these conditional morphine-compensatory responses would be expected to attenuate the drug-induced unconditional responses, thereby decreasing the observed response to the drug. Research has been summarized which supports this compensatory conditioning model of tolerance by demonstrating that the display of tolerance is specific to the environment in which the drug has been previously administered. Further evidence supporting this theory of tolerance has been provided by studies establishing that extinction, partial reinforcement, and latent inhibition--non-pharmacological manipulations known to be effective in generally affecting the display of conditional responses--similarly affect the display of morphine tolerance. Additional research has suggested many parallels between learning and morphine tolerance: Both processes exhibit great retention, both are disrupted by electroconvulsive shock and frontal cortical stimulation, both are retarded by inhibitors of protein synthesis, and both are facilitated by antagonists of these metabolic inhibitors.


Narcotic tolerance and operant behavior. Narcotic tolerance was measured as a shift to the right in dose-effect relations on operant behavior following repeated administration of drug. Tolerance has been observed with operant responding in both pigeons and rhesus monkeys. The amount of tolerance observed with food-reinforced responding is related both to the amount of morphine administered and to the nature of the drug-induced change in operant responding. Pharmacological specificity of the narcotic tolerance has been confirmed by equivalent loss of sensitivity to other narcotics without concomitant changes in sensitivity to nonnarcotic stereoisomers. Tolerant birds do not show disturbed operant behavior when narcotic administration is terminated abruptly. Tolerance has been induced by narcotic self-injection and its effects measured on rates and patterns of food- and narcotic-reinforced responding. Tolerance does not necessarily confer changes in narcotic-reinforced responding. Moreover, narcotic-reinforced responding may be initiated and maintained for periods of over one month without conferring tolerance.


Use of melatonin and synthetic TRH to determine site of pineal inhibition of TSH secretion. An experiment was performed on 21-day-old male rats to determine the combined effects of pinealectomy, constant light and darkness, and intraperitoneal (i.p.) thyrotropin-releasing hormone (TRH) on pituitary and plasma radioimmunoassayable thyrotropin (TSH), serum thyroxine (T4), and pituitary, thyroid and body weights at the age of 25 days. In saline-treated rats, pinealectomy or constant illumination decreased pituitary TSH and increased plasma TSH and serum T4. Constant darkness with an intact pineal, however, decreased all 3 of these parameters. When i.p. TRH was injected all rats showed an increase in plasma TSH as compared to saline-treated controls. Another study was performed on 25-day-old male rats to determine the effects of intraventricular administration of melatonin (MEL) alone, and intraventricular MEL plus i.p. TRH on pituitary and plasma TSH. MEL decreased plasma TSH levels as compared to non-treated and saline-treated controls, whereas the concurrent administration of TRH obviated the effect of MEL and increased plasma TSH levels above those of the control animals. The results are interpreted as indicating that the inhibitory effect of the pineal in dark-reared, sham-operated prepuberal male rats is exerted at the level of hypothalamic secretion of TRH.


Meningiomas in five members of a family over two generations, in one member simultaneously with acoustic neurinomas. Despite four reports of familial occurrence of meningiomas, the inheritance of this tumor remains an open question. We describe a family in which four members in two generations had meningiomas without evidence of neurofibromatosis. Another member of the family, however, had multiple meningiomas and bilateral acoustic neurinomas, while yet another had multiple café-au-lait spots. We suspect that a highly unusual presentation of neurofibromatosis explains this otherwise very unlikely occurrence.


The day hospital: efficacy and cost effectiveness. Analysis of the operation of the Roberts day hospital has demonstrated that this is economically a sound alternative to other methods of care of the disabled with not only good maintenance of independence of the patients going through the centre but also an increased social involvement in the community. Lessons with regard to the operation of a day hospital team are discussed with particular attention being drawn to the controversial area of team leadership.


Subtotal thyroidectomy for thyrotoxicosis: a reassessment, including TRH responsiveness. Thyroid function was assessed in patients treated surgically for thyrotoxicosis in Christchurch between 1965 and 1972. Seventy-eight of the 89 thyrotoxic patients were available for reassessment. Seventy-one were clinically and biochemically euthyroid. Seven patients had received radioiodine therapy for post-operative relapse and 10 patients were receiving thyroxine replacement therapy. At the time of the survey five patients were clinically thyrotoxic and two patients were hypothyroid and an additional nine patients had grossly elevated TSH levels. TRH tests performed on 31 clinically euthyroid patients with normal baseline thyroid parameters demonstrated that more than a third had excessive TSH responses consistent with reduced thyroid reserve and only one patient showed a lack of response consistent with persistent thyroid autonomy.


Paraproteinemia in normal family members of eight cases with primary intestinal lymphomas in Iraq. Normal family members of eight patients with paraproteinemia of the primary intestinal lymphoma, had been investigated by immunoelectrophoresis, for IgA heavy chain pattern. IgA heavy chain pattern was demonstrated in four families only, of different members, but all are of the first degree relationship. Detailed clinical, laboratory, radiological and histopathological findings of those eight cases were suggestive of malaborption. Out of the 129 normal family members of the 8 cases, 23 cases (17.8%) had abnormal immunoglobulin in their sera. These results may explain a hereditary factor which is responsible for production of alpha-chain diseases. Supports for this hypothesis need further research.


Plasma prolactin levels and ovarian responsiveness to exogenous gonadotropins. Standard gonadotropin stimulation tests of ovarian function and basal plasma prolactin measurements have been carried out in 151 patients with amenorrhea or severe oligomenorrhea. In 90 of these a standardized multiple pituitary stimulation test, including the prolactin response to thyrotropin releasing hormone, was also performed. There was a tendency for the basal estrogen excretion and the ovarian response to gonadotropin to be lower in patients with hyperprolactinemia. These correlations were weak and did not reach the levels of statistical significance except when compareing the ovariance response in patients with mild hyperprolactinemia to those with moderate or severe hyperprolactinemia. It is concluded that, in women, elevated plasma prolactin levels have little, if any, direct inhibitory influence on the ovariance response to gonadotropins in vivo.


Neurofibromatosis and congenital glaucoma. A case report. Congenital glaucoma may be associated with other developmental disorders and particularly with neurofibromatosis. A baby girl, with unilateral buphthalmus, thickening of the upper eye lid on the same side and café  au lait spots on her body lost this eye in spite of repeated interventions. Histological examination revealed the presence of neurofibromatic and congenital glaucoma changes in the eye. There was no neurofibroma in the angle area which could have caused glaucoma. Glaucoma was due to failure of normal development of the angle.


[Virginiamycin resistance in staphylococci (author's transl)]. Virginiamycin M factor transformation into an o-acetyl derivative has been observed in a particular Staphylococcus strain, naturally resistant to virginiamycin (Vr). It could not be detected in induced strains nor in sensitive ones. Turbidimetric studies with the naturally resistant strain showed that increasing concentration of the antibiotic had a progressive prolongation effect on the lag phase, without change in the growth rate. The prolonged lag phase could be reduced or eliminated by using an inoculum of cells previously "adapted" to M factor or virginiamycin. Preadapted cells had an increased acetylating power. Acridine dye treated cells showed a decreased o-acetyl derivative formation. This all suggested that virginiamycin resistance in the particular Vr strain was effectively connected with o-acetylation of the M factor.


Immunological studies with aortic and venous tissue antigens. III. Examination of cell-mediated and humoral immune response induced by human vascular antigens. The effects of human vascular antigens on the cell-mediated and the humoral immune response were studied in guinea pigs. In animals immunized with buffer extracts of aortic and venous wall a well measurable cell-mediated and humoral immune response were developed. Between the two kinds of vascular extracts in the skin tests, migration inhibition tests and antibody-production tests a cross-reactivity was observed, whereas the induction of desoxyribonucleic acid-synthesis proved to be specific. No cellular or humoral immune response to vascular extracts was detectable in the control animals. Analysing the time-kinetics of the cell-mediated and humoral immune response it was found, that with the increased production of antibodies the cellular immune reactions did not cease until the ninth week.


Studies on the primary and secondary structure of potato spindle tuber viroid: products of digestion with ribonuclease A and ribonuclease T1, and modification with bisulfite. Potato spindle tuber viroid (PSTV), a small infectios RNA, has been completely digested with RNase T1 and RNase A, and the resulting oligonucleotides have been sequenced using 5'-terminal 32p-labelling with gamma-32p ATP and T4 polynucleotide kinase, fingerprinting and controlled nuclease P1 digestion. Modified nucleotides have not been detected in 5'-positions of these oligonucleotides. PSTV consists of about 359 nucleotides and contains a remarkable stretch of 18 purines, mainly adenosines; there is no AUG initiation triplet present. The established oligonucleotide sequences preclude a perfect intramolecular base complementarity within the covalently closed viroid circle. Therefore, the rigid, rod-like native secondary structure of PSTV, as seen in the electron microscope, must be based on a defective rather than on a homogeneous RNA helix. The detailed analysis of the bisulfite-catalized modification of cytidine to uridine in PSTV revealed a higher reactivity for the majority of the cytidines than would be expected for a perfect helix. Since only cytidines in single-stranded regions are knonw to be fully reactive, this finding provides additional evidence for defects in the helical secondary structure of PSTV.


On the biosynthesis of 5-methoxyuridine and uridine-5-oxyacetic acid in specific procaryotic transfer RNAs. The uridine-5-0-derivatives, 5-methoxyuridine (mo5U) and uridine-5-oxyacetic acid (cmo5U) occupy the first position of anticondons in certain tRNA species of B. subtilis and E. coli, respectively. Here we present experimental evidence showing that both modifications are derived from a common precursor, 5-hydroxyuridine. Incompletely modified tRNASer and tRNAVal from E. coli met- rel-. All five tRNAs accepted methyl groups from S-adenosylmethionine with B. subtilis extracts in vitro and mo5U was formed. In B. subtilis tRNAs the mo5U was proved to be at the specific site; in E. coli tRNAVal the mo5U was demonstrated to be present in the oligonucleotide that comprises the anticodon. In submethylated E. coli tRNAVal,5-hydroxyuridine was detected whereas considerable amounts of cmo5U were lacking.


[Puncture of central veins venesection in childhood (author's transl)]. Due to advances in parenteral feeding the indications for creating access to the central veins in infants and young children have become less strict. The technique of establishing such access by puncture of the internal jugular or subclavian vein is reviewed. Venesection is now indicated only in exceptional cases. The technique of placing a catheter into the umbilical artery or vein is described.


Multiple receptors for brain dopamine.

Multiple receptors for brain dopamine. This study was done to obtain direct in vitro evidence for the possible existence of more than one type of dopaminergic binding site in homogenates of the caudate nucleus from calf brain. Five radioligands for dopaminergic sites were tested. The inhibitions of two agonist radioligands ([3H]dopamine, [3H]apomorphine) by haloperidol, chlorpromazine, or piflutixol were biphasic. The inhibitions of [3H]haloperidol, [3H]spiroperidol, and [3H]dihydroergocryptine binding by dopamine and (-)-norepinephrine were also biphasic. Thus, both 3H-labeled agonists and 3H-labeled antagonists were possibly binding to two high-affinity sites.


Promoter recognition by phage SP01-modified RNA polymerase. A modified form of Bacillus subtilis RNA polymerase containing a phage SP01-coded regulatory protein (the gene 28 product) selectively transcribes "middle" genes of the phage genome in vitro. In this paper, we identify a subset of restriction endonuclease fragments of SP01 DNA that promote specific transcription by the phage-modified polymerase. In the absence of nucleoside triphosphates, RNA polymerase containing the gene 28 protein selectively binds to these DNA fragments thereby forming stable binary complexes that can be isolated on nitrocellulose filters. In contrast, unmodified RNA polymerase containing sigma factor selectively binds to and transcribes a subset of phage DNA fragments that contain "early" sequences and that are in large part distinct from the fragments recognized by the phage-modified transcriptase. Our results strongly suggest that phage "early" and "middle" genes are transcribed from distinct promoters and that the RNA polymerase containing the gene 28 protein binds to sites that are located at or near promoters for SP01 "middle" genes.


Two thymidylate synthetases in Bacillus subtilis. Bacillus subtilis grown at temperatures below 37 degrees contains two thymidylate synthetases, TSaseA and TSaseB. Their presence is dependent on functional thyA and thyB genes, respectively. When cells are grown at 46 degrees they only contain TSaseA activity. This allous an easy positive selection for thyA and thyA, THYB mutants. The two TSases have been physically separated, and they show similar overall requirements for activity. However, they differ significantly in both their kinetic and their physicochemical properties.


Regulation of prolactin and somatotropin mRNAs by thyroliberin. The tripeptide thyroliberin (thyrotropin-releasing hormone, TRH) regulates the levels of cytoplasmic prolactin and growth hormone (somatotropin) mRNAs in a line of functional rat pituitary tumor cells. Intracellular mRNA levels were determined with specific complementary DNA probes in RNA-excess hybridization reactions and independently by two-dimensional gel electrophoretic analysis of the products of mRNA-directed cell-free translation. Prolactin mRNA sequences increased from 1.1 to 4.5% of the cytoplasmic poly(A)containing mRNA within 48 hr after addition of TRH to the medium; in parallel, growth hormone mRNA sequences were decreased. Similar effects on prolactin mRNA levels were observed in cells grown in serum-containing medium or when the cells were maintained in a serum-free medium for 72 hr prior to addition of TRH, suggesting that TRH is responsible for the stimulation of prolactin mRNA levels rather than for exerting a permissive effect for another factor present in serum.


Membrane lateral phase separations and chlortetracycline transport by Bacillus megaterium. Chlortetracycline, a fluorescent probe of its own active transport, has been used to study lateral phase separations of membrane lipid in Bacillus megaterium cells. Arrhenius plots of initial accumulation rates are triphasic, with transitions or characteristic temperatures of 20 degrees and 9.5 degrees . At the higher temperature, the mobility of the chloretracycline, as measured by fluorescence polarization, is markedly altered. Chlortetracycline transport exhibits saturation kinetics, and fluorescence energy transfer from protein to bound antibiotic can be observed. N-Phenyl-1-naphthylamine, a lipophilic fluorescent probe, responds to changes in the hydrophobic regions of the membrane that are distinct from membrane protein. The fluorescent properties of N-phenylnaphthylamine in partitioning and polarization experiments are altered most significantly at the lower characteristic temperature. No fluorescence energy transfer between N-phenylnaphthylamine and membrane protein or bound tetracycline can be detected. In correlative electron spin resonance experiments on the partitioning of a lipid-soluble spin label, the same characteristic temperatures detected in the fluorescence studies were measured. These data suggest that different probes may respond to either or both of the characteristic temperatures describing the lateral phase separation. Between these characteristic temperatures the chlortetracycline transport system is most intimately associated with relatively immobile lipids that are surrounded by a more mobile lipid phase.


Neoplastic transformation of human diploid fibroblast cells by chemical carcinogens. Cultured fibroblast cells derived from a skin biopsy sample taken from normal human adult were exposed to a potent carcinogen, 4-nitroquinoline 1-oxide. Alterations of cell growth pattern such as higher density and piling up of cells were noticed in some fractions of cultures that were successively subcultured after nitroquinoline oxide treatment. Morphologically altered cells retained this growth pattern and became established lines of transformed cells without showing the limited life-span characteristic of normal cells in culture. The transformed cells showed a higher saturation density and the ability to grow in soft agar, properties that are usually correlated with neoplastic transformation of cells in culture. Selection of preexisting transformed human cells as a mechanism of this observed transformation seemed unlikely because clones of these normal cells could also be used to assess the transforming effect of nitroquinoline oxide. Preliminary results suggest that numerous cell divisions were required for the development of the transformation after nitroquinoline oxide treatment of these human cells. When the transformed cell lines were injected subcutaneously into nude (athymic) mice, solid tumors were produced at the site of inoculation. Treatment with N-methyl-N'-nitro-N-nitrosoguanidine also induced cell transformation, in a manner similar to treatment with nitroquinoline oxide. However, transformation was not induced with (i) 4-aminoquinoline 1-oxide (a noncarcinogenic derivative of 4-nitroquinoline 1-oxide), (ii) 3-methylcholanthrene (a carcinogen that cannot be metabolically activated by the target cells employed), or (iii) the solvent dimethyl sulfoxide.


Molecular cloning of genetically active fragments of Bacillus DNA in Bacillus subtilis and properties of the vector plasmid pUB110. Plasmid pUB110 (approximately 2.8 x 10(6) daltons), originally detected in Staphylococcus aureus, specifies resistance to neomycin and has been transformed into Bacillus subtilis 168, In B. subtilis, pUB110 is stably maintained at about 50 copies per chromosome and renders the host resistant to neomycin sulfate at 5 microgram/ml. pUB110 isolated from B. subtilis transforms Rec+ and recE4-containing strains of B. subtilis at frequencies greater than or equal to 10(3) transformants per microgram of plasmid. pUB110 was transferred by PBS1 or SP10 transduction from B. subtilis to strains of B. pumilus and B. licheniformis. pUB110 is compatible with each of four previously described Bacillus plasmids, including pPL576, pPL10, pPL7065, and pPL2. pUB110 contains a single EcoR1-sensitive site and was used as vector to clone DNA fragments that complement the trpC2 mutation in B. subtilis 168 from EcoR1 digests of the chromosome DNA isolated from B. pumilus strains NRRL B-3275 and NRS576, B. licheniformis strains 9945A and 749C, and B. subtilis 168. Genetic and physical properties of each of the constructed Trp derivatives of pUB110 are described.


Construction and properties of chimeric plasmids in Bacillus subtilis. Antibiotic resistance chimeric plasmids have been constructed by in vitro enzymatic manipulation and introduced into Bacillus subtilis by transformation. The parental plasmids used had been introduced into B. subtilis from Staphylococcus aureus by transformation. Of the seven recombinant plasmids constructed using restriction endonucleases, one was made using EcoRI, another using Hpa II, and five with Xba I (from Xanthomonas badrii), demonstrating the utility of the latter enzyme for molecular cloning experiments. Although all of the recombinant plasmids we have made replicate and express their antibiotic resistance characters, three of them have suffered a loss of DNA, either in vitro or, more likely, in vivo. The deletion event in all cases involved one of the two termini used to join the parental plasmids. The plasmid chimeras reported in this paper should prove useful for the study of plasmid replication, incompatibility, and recombination. In addition, the utility of the B. subtilis system for molecular cloning has been clearly illustrated.


DNA cloning in Bacillus subtilis.

DNA cloning in Bacillus subtilis. A plasmid pC194, encoding resistance to chloramphenicol, can serve as a cloning vector in Bacillus subtilis 168 for other HindIII-cleaved DNA segments. Replicons constructed by linking pC194 to several Escherichia coli plasmids can be used to introduce and compare the expression of the same genes in these two bacterial hosts.


Sequence of a mouse germ-line gene for a variable region of an immunoglobulin light chain. We have determined the sequence of the DNA of a germ-line gene for the variable region of a mouse immunoglobulin light chain, the VlambdaII gene. The sequence confirms that the variable region gene lies on the DNA separated from the constant region. Hypervariable region codons appear in the germ-line sequence. A sequence for the hydrophobic leader, 19 amino acids that are cleaved from the amino terminus of the protein, appears near, but not continuous with, the light chain structural sequence: most of the leader sequence is separated from the rest of the gene by 93 bases of untranslated DNA.


Lambda2 light chains in normal mouse immunoglobulins. Light (L) chains of the lambda type are rare in mouse immunoglobulins. One lambda chain, the L chain of myeloma protein 315 (L315), differs in amino acid sequence at many positions in the COOH-terminal domain from all other lambda chains whose sequences have been determined (called lambda1 chains). To determine whether chains of the L315 type (called lambda2) occur in normal mouse immunoglobulins, we synthesized the COOH-terminal peptides expected in tryptic digests of K, lambda1, and L315 and developed procedures to separate the S-carboxymethyl derivatives of these peptides. Peptide maps of tryptic digests of [14C]carboxymethyl-labeled L chains from normal serum immunoglobulins showed that about 1% of mouse 7S immunoglobulins have L chains of the L315 or lambda2 type.


Opposing effects of calcium and barium in vertebrate rod photoreceptors. Intracellular recording in outer segments of red rods of the toad retina showed that increasing Ca(2+) concentration in the perfusate mimicked certain aspects of light adaptation. Light sensitivity was reduced, the amplitude of light responses was reduced, the time course of light responses was altered by shortening the delay to the peak and increasing the decay rate, and the resting membrane potential was generally increased. These results provide further support for the hypothesis that Ca(2+) acts as an internal transmitter that is subject to light-induced release from the rod saccules. The addition of Ba(2+) to the perfusate mimicked dark adaptation by having effects opposite to all those described for Ca(2+). The Ba(2+) effects were specific, Mg(2+) and Sr(2+) being ineffective in similar or greater concentration. Also, Ba (2+) gave clear effects at concentrations as low as 0.1 mM. It is proposed that Ba(2+) enters the cell and reduces the uptake of Ca(2+) into the rod saccules, because the various effects of Ba(2+) upon light responses all seem explicable from this hypothesis. Ba(2+) also reduced the resting membrane potential, probably by reducing the membrane conductance for K(+). The demonstrated effects of Ba(2+) indicate an important role for Ba(2+) in analyzing the ionic aspects of transduction in vertebrate photoreceptors. They also suggest a critical physiological role for Ba(2+) in controlling both the resting properties and light-induced responses of vertebrate rods, because barium has been reported to be concentrated in outer and inner segments of cat photoreceptors.


Protein deficiency and energy restriction in young cebus monkeys. Infant cebus monkeys (Cebus albifrons) were fed liquid formulas that were limited in protein, energy, or a combination of the two restrictions. Weight gain, food intake, hematological development, and plasma protein and cholesterol levels were monitored over a 20-week period. The animals restricted in protein developed the classical signs of protein deficiency--reductions in plasma albumin, a mild anemia, accumulation of fat in the liver, and, in a few cases, facial edema. These animals maintained a relatively high energy intake, and apparently wasted energy when compared to similarly non-growing energy-restricted animals. Energy-restricted animals did not exhibit these symptoms, even when their daily protein intake was reduced to match that of protein-restricted monkeys. It is concluded that an energy restriction superimposed upon a limited protein intake did not increase protein requirements or precipitate protein deficiency.


Metrazol-induced petit mal: the role played by monoaminergic mechanisms and striatum. Gradually accumulating subconvulsive doses of metrazol give rise to behavioral and electrographic effects close to petit mal epilepsy: slow negative waves and spike-wave complexes on EEG, frozen and myoclonic jerks. Intensification of monoaminergic transmission with apomorphine, DOPA or 5-hydroxytryptophan attenuates, but inhibition (chlorpromazine, haloperidol and p-chlorphenylalanine), on the contrary, increases the subconvulsive effect of the metrazol. Low frequency stimulation of the striatum potentiates, and lesion limits expressiveness of metrazol-induced petit mal. Bilateral electrolytic lesion of the striatum eliminates apomorphine, DOPA and haloperidol action, but slight changes the effects of chlorpromazine, 5-hydroxytryptophan and p-chlorphenylalanine.


Effects of d-amphetamine and prefrontal cortical cooling on delayed matching-to-sample behavior. The interaction was examined between d-amphetamine (s-A) and dysfunction induced by localized cooling of the dorsolateral prefrontal cortex. Saline or d-A(0.1,0.2 or 0.4 mg/kg) was administered to monkeys in two conditions; normal cortical temperature (no cooling -NC) and frontal cooling (FC). Errors, reaction time (RT), eye movements, and motor activity were recorded during performance of a delayed matching-to-sample task with intratrial delays of 1-32 sec. Although d-A and FC had little effect on percentage of correct responses at the shortest delay, each of the two treatments significantly decreased correct responses, at longer delays; drug and FC combined produced a significantly greater decrease than either treatment alone. Motor activity and eye movements were increased by either d-A or FC; the two treatments combined had an even greater effect. In the NC condition, two-choice RT was decreased by the drug; it was increased by drug-FC combinations. These findings indicate that d-A and FC potentiate each other in their behavioral effects.


The social outcome of patients in a trial of long-term continuation therapy in schizophrenia: pimozide vs. fluphenazine. A blind social assessment at home carried out twice during a year's follow-up of 41 patients on continuation therapy, 21 randomly allocated to pimozide tablets and 20 to fluphenazine decanoate injections. Patients on pimozide were significantly more favourably rated on aspects of sociability, use of leisure, warmth of personal relationships, household tasks and child-rearing. The mode of production of this result is discussed.


Disappearance of chlorpromazine from plasma following drug withdrawal. Plasma chlorpromazine measured by a gas chromatographic procedure was found to disappear rapidly during the first week after withdrawal of chlorpromazine treatment in a group of 17 chronically hospitalized patients. The drug or its metabolites were no longer measurable in plasma after 8 days.


PRL-8-53: enhanced learning and subsequent retention in humans as a result of low oral doses of new psychotropic agent. The effect of 3-(2-benzylmethylaminoethyl) benzoic acid methyl ester hydrochloride (PRL-8-53) on learning and on retention of verbal information in human subjects was investigated. Using the serial anticipation method under double-blind conditions it was found that PRL-8-53 causes slight improvement of acquisition. Retinetion of verbal information was found improved to a statistically significant degree (most P values better than 0.01, some better than 0.001). No significant changes were found for either visual reaction time or motor control after drug when compared with placebo values.


Morphine-induced regional and dose-response differences on unit impulse activity in decerebrate rats. Previous studies have indicated that morphine alters nerve impulse activity differently in various brain areas of intact animals. Because morphine has profound effects on visceral organs and on the spinal cord, cervically transected preparations, in which hypothermia was prevented, were used for recording spontaneous impulse activity before and for 30 min after morphine simultaneously from six regions of the brain: caudate (Cau), midbrain reticular formation (MBRF), central grey (CG), cingulate cortex (CC), hippocampus (Hip), and substantia nigra (SN). Morphine (5 and 15 mg/kg, i.p.) caused a naloxone-preventable depression of impulse activity in most brain areas. The depression was, however, especially pronounced in the CG, more so with the lower than the higher dose; naloxone completely blocked the low-dose effect. The MBRF responded with increased impulse activity after 5 mg/kg, but with depression after 15 mg/kg; naloxone blocked both responses. Activity in both the Hip and CC was depressed by the low dose of morphine, but not by the high dose; naloxone blocked the depression. Both doses of morphine generally depressed the variance in impulse activity, with a clear preferential depression of CG variance; naloxone blocked the CG variance effect, but not that of other brain areas.


Relationship between body temperature and brain monoamines during the development of tolerance to delat9-tetrahydrocannabinol in the rat. The development of tolerance to delat9-tetrahydrocannabinol (delta9-THC) was examined. Rats with permanently indwelling intravenous catheters were injected daily with delta9-THC, 2 mg/kg, for up to 10 days and on each day subjective behaviour and body weight of each rat were noted. Tolerance appeared to develop to both the excitatory and depressant behavioural effects of delta9-THC, whereas the rate of gain in body weight of delta9-THC treated rats was retarded and tolerance to this phenomenon did not develop over the experimental period. On days 1, 2, 3, 5, 6, and 10 body temperature was recorded continuously for at least 2 h after delta9-THC and in other groups of rats the brain levels of noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were measured spectrophotofluorimetrically 1 h after delta9-THC. Tolerance developed to the delta9-THC-induced hypothermia by day 3, and on days 6 and 10 hyperthermia was observed. delta9-THC did not markedly affect the brain levels of NA or DA over the experimental period. The brain levels of 5-HT were unchanged on days 1--5 but there was a decrease on days 6 and 10. On days 1, 2, and 3 brain levels of 5-HIAA were raised, whereas on day 6 there was a decrease. These results show that delta9-THC induces tolerance to the hypothermia and elevation of brain 5-HIAA levels in a linear manner. An inverse relationship appears to exist between these two parameters.


Ethanol dependence in the rat: temporal changes in neuroexcitability following withdrawal. Electrodes were chronically implanted in the dorsal hippocampus of rats. Pretreatment levels of neural excitability were assessed by determining the duration of direct hippocampal electrical stimulation sufficient to induce forelimb clonus in each rat. Following baseline measurements the rats were administered an alcohol or sucrose-containing liquid diet and 19--22 days later were withdrawan. Two postwithdrawal stimulation sessions were conducted on each animal. Separate groups of ethanol-dependent and control rats were given primary stimulation sessions at 8 h, 24 h, 72 h, or 1 week postwithdrawal. Secondary stimulation sessions were conducted 1 week or 2 weeks postwithdrawal. The results from the primary stimulations indicated that ethanol-dependent animals exhibited significant neural hyperexcitability for at least 72 h, but not 1 week, postwithdrawal. Results from the secondary stimulations demonstrated the presence of a relative neural hypoexcitability in ethanol-dependent groups as compared to controls. The pattern of results suggests, however, that the observed relative neural hypoexcitability was not the direct result of ethanol withdrawal.


Stages of constant amphetamine intoxication: delayed appearance of abnormal social behaviors in rat colonies. Rats in colonies were observed for 7 days after half of them were implanted with slow-release silicone pellets containing d-amphetamine base. The drug-implanted animals were initially hyperactive and exploratory, but this gradually evolved over the next 24 h into motor stereotypies of an increasingly more circumscribed nature. On the 4th day after amphetamine implantation they transiently withdrew to the burrows area; thereafter they were characterized by heightened startle responses and increased social behaviors such as fighting and fleeing. During the last phase some of the drug-implanted animals tended to focus their fighting behaviors on one other drug-implanted animal. This late phase of constant amphetamine intoxication in rats has a number of similarities to amphetamine psychosis in humans, and can serve as a useful animal model for the study of its biochemical correlates.


The effects of scopolamine on extinction and spontaneous recovery. The effects of scopolamine hydrobromide on baseline extinction levels and spontaneous recovery were assessed. Rats were trained on one of four reinforcement schedules (CRF, FR 10, FR 20, FR 40) with either food or water reinforcement. Scopolamine increased response rates in extinction and spontaneous recovery following training on all four schedules when the reinforcer was water, but had no effect on responding previously maintained by food. The results are discussed in terms of the limitations of a general theory of a cholinergic system mediating all suppressed behavior and the effects of anticholinergic drugs on central thirst mechanisms and consummatory behavior.


Methylxanthine-facilitated shock-induced aggression in the rat. The methylxanthines caffeine and aminophylline, in daily doses of 100 mg/kg, facilitated shock-induced aggression in the rat. Under the limited parameters of this study, there was no induction of mouse-killing behavior or alteration of jump thresholds. Additional studies showed the optimal dose and time course for the facilitation of shock-induced aggression by caffeine to be 50 mg/kg administered i.p. 4 h prior to testing. Facilitation of a central adrenergic system may be the mechanism of action.


Studies on the interactions of copper and cannabis. The action of copper (CuSO4, 5 mg/kg, oral) on selected neuropharmacological actions of cannabis resin (CI, oral) was studied on albino rats and mice. Copper potentiated the barbiturate hypnosis-potentiating activity of CI in albino rats and mice and had no effect on hypothermic activity in albino rats. Single doses of copper partially inhibited tolerance to barbiturate hypnosis-potentiation activity and markedly delayed the development of tolerance to hypothermic activity of CI. Oral as well as i.c.v. copper (CuSO4, 0.1 microgram) in single dose antagonised the tolerance to hypothermic activity of cannabis or THC for one to two weeks. Copper-CI interaction could be antagonised by penicillamine. Zinc (ZnSO4, 5 mg/kg, oral) had an action similar to that of copper in antagonising the development of tolerance to the hypothermic activity of CI, but magnesium (MgSO4, 5 mg/kg, i.p.) was devoid of any such action. Studies indicate that, although copper has no significant neuropharmacological action, it interacts with CI activity, especially in tolerant rats, in effects on hypothermia. The site of action of copper is possibly the hypothalamus, where it inhibits the processes of tolerance development to CI on the noradrenergic neurone.


Opiates, catecholamines, behavior, and mood. Indirect evidence has linked opioid reinforcement with changes in noradrenergic metabolism secondary to drug administration. Methodological precedents for biobehavioral correlations in depressive illness have suggested an important association between changes in mood and biogenic amine excretion patterns in the urines of patients during depression and recovery. This paper presents preliminary data on the possible relationship between changes in catecholamine excretion that were observed and the changes in behavior, mood, psychiatric status, and cardiorespiratory physiology secondary to heroin administration and methadone-assisted withdrawal. This study focuses on the urinary excretion of MHPG, since an appreciable fraction of this metabolite is probably derived from norepinephrine originating in the brain. The subjective changes in mood associated with heroin use, the decrease in respiratory rate, and the behavioral and mental status effects associated with opiate intoxication were observed only in the individuals whose MHPG excretion increased during the period of opiate administration.


Decrease in brain NE turnover after chronic DMI treatment; no effect with iprindole. Previous studies have suggested that chronic treatment with tricyclic antidepressants alters brain NE turnover. This action is more likely a biochemical correlate of their clinical effect than is the blockade of amine reuptake, because the latter occurs with acute administration, whereas tricyclics must be given chronically for clinical improvement. In this paper the effects of chronic treatment with the tricyclics desmethylimipramine (DMI) and iprindole (a clinically effective tricyclic that does not potently block amine reuptake) on rat brain NE turnover, as measured by the Conversion Index, was studied. Chronic DMI, but not iprindole, decreased NE turnover. These results are discussed regarding the proposed mechanism of action of tricyclics and the 'catecholamine hypothesis of affective disorders'. Chronic DMI also tended to decrease endogenous brain NE, and chronic treatment with either DMI or iprindole tended to decrease brain and plasma tyrosine.


Tolerance to the increased locomotor activity produced by L-5-hydroxytryptophan following peripheral decarboxylase inhibition in mice. The development of tolerance to hyperactivity produced by L-5-hydroxytryptophan (5-HTP) was studied in mice pretreated with the peripheral decarboxylase inhibitor MK-486. The results of Experiment I indicated that partial tolerance developed to 5-HTP given twice daily (i.p.) at a dose of 400 mg/kg, but not at a dose of 800 mg/kg. Sustained hyperactivity at the greater dose (800 mg/kg) apparently resulted from the induction of seizures and stereotypy rather than increased locomotor activity. When 5-HTP (400 mg/kg) or saline was administered three times daily (Experiments II and III), the locomotor activity of saline control groups did not differ significantly from chronic 5-HTP-treated groups, but both differed significantly from that of acute 5-HTP-treated animals. Cessation of treatments resulted in a recovery of 5-HTP-induced hyperactivity for experimental animals when later retested. These findings suggest that mice develop tolerance to the effects of 5-HTP on locomotor activity and agree with the hypothesis that behavior change is more closely correlated with the rate of change in concentration of neurotransmitters than the absolute concentrations.


Ethanol drinking by rhesus monkeys as a function of concentration. Ethanol deliveries maintained fixed-ratio (FR) responding of three rhesus monkeys during daily 3-h sessions. At FR values of 8 or 16, ethanol concentration was varied in the sequence 0 (water), 8, 11.3, 16, 22.6 32, 8, and 0% (w/v). As the ethanol concentration increased, number of liquid deliveries decreased somewhat. Blood ethanol levels were usually greater than 200 mg% and occasionally greater than 300 mg%.


Experimental barbiturate dependence. I. Barbiturate dependence development in rats by drug-admixed food (DAF) method. A method for testing a rat's physical-dependence liability to sedaditive-hypnotic agents and for evaluating that dependence was studied by using the method. Rats received phenobarbital- or barbital-admixed food on a graded-increase dosage schedule over 30-40 days. Manifestations of CNS-suppressing action of either drug (e.g., systemic muscle relaxation, motor incoordination, staggering gait, and ptosis) persisted day and night during the drug medication. Twenty-four to 48 h after withdrawal of either drug, abstinence symptoms (e.g., muscle fasciculation, nuchal twitching, vocalization, increased irritability, ataxia, hyperthermia, and clonic-tonic and grand mal-type convulsions) were evidenced in all animals (N = 6), some of which died after convulsions. These withdrawal signs in rats were classified and found to be closely correlated with the magnitude of weight loss during the withdrawal. The calssification provides a basis for quantitatively assessing physical-dependence liability. The data obtained in the present study suggest that rats, like dogs and monkeys, are suitable experimental animals for tests in early stages of dependence liability, and that the administration of drug-admixed food is a useful method of developing dependence on both barbiturate and morphine-type drugs.


Movement induced in cataleptic rats: differential effects produced by electrical stimulation of the lateral hypothalamus, substantia nigra, and reticular formation. Haloperidol catalepsy can be countered by electrical stimulation of the lateral hypothalamus (LH) and, to a lesser extent, the reticular formation (RH). Substantia nigra (SN) stimulation proved to be least effective in this regard. Dissociation between behavioral arousal and cortical EEG during stimulation of the RF in cataleptic rats was observed.


Influence of the new 5-HT-uptake inhibitor paroxetine on hypermotility in rats produced by p-chloroamphetamine (PCA) and 4,alpha-dimethyl-7-tyramine (H 77/77). Two different forms of hypermotility produced by the amphetamine derivatives PCA and H 77/77, 5 mg/kg of each, was studied in rats treated s.c. with the new 5-HT uptake inhibitor paroxetine. The substance inhibited the effect of PCA but did not influence that of H 77/77. The 5-HT-uptake inhibitors paroxetine, imipramine, and chlorimipramine were also administered p.o. at various times before PCA. The three substances inhibited PCA-induced hypermotility. Paroxetine 0.5-2 mg/kg, was active at intervals of 1-4 h and 4 mg/kg was active at 18-h interval. Imipramine and chlorimipramine 25-30 mg/kg showed PCA inhibition at treatment intervals of 1-2h, but 80-100 mg/kg or more was required to inhibit PCA at intervals of 4 and 18 h. Previous results have shown that PCA-induced hypermotility is antagonized by substances inhibiting 5-HT synthesis and uptake, whereas H 77/77-induced hypermotility is inhibited by substances blocking NA synthesis, uptake, and receptors. The previous and present results indicate that paroxetine is a selective 5-HT-uptake inhibitor. After oral administration paroxetine presumably produces a more potent and long-lasting 5-HT-uptake inhibition than imipramine and chlorimipramine.


Changes in the behavioral response to a novel environment following lesioning of the central dopaminergic system in rat pups. During the third week of life, a hyperactive period for laboratory rat, the occurrence of 8 behavioral categories was recorded in individual littermates transferred to a novel environment. Neonatal destruction of the catecholaminergic system by intraventricular injection of 6-OH-DA resulted in increased motor activity during the third week of life. Selective lesioning of the dopaminergic system by the combined treatment of 6-OH-DA + desmethylimipramine also induced a significant increase in some active behavioral categories. It appeared that in contrasts to the gross behavioral sequence, as seen in controls, which compromised locomotion and rearing leads to grooming leads to sitting and lying down, the lesioned animals showed a prolonged phse of restless locomotion. These data are interpreted as a disability to habituate adequately to a novel environment after neonatal lesioning of the dopaminergic system.


Studies on the effect of lesions of the ventral noradrenergic tract on the antinociceptive action of morphine. In rats, lesions were placed in the ventral tegmental noradrenergic tract (VT). In some animals lesions also involved the dorsal tegmental noradrenergic tract (DT). Morphine (Mf) analgesia was examined by the tail compression method 8-9 days after lesions. VT lesions produced no changes in Mf activity, while lesions involving VT + DT produced a partial attenuation of the antinoceptive action of Mf. These results suggest that the ascending NA fibres forming the VT are not essential for the antinoceptive effect of Mf.


Effects of chronic ingestion and withdrawal of sodium barbitone on learning in rats. Rats were submitted to three different manipulations: chronic ingestion of sodium barbitone, which was added to the drinking water; chronic administration of barbitone and subsequent withdrawal of the drug; and drinking water only. Both groups of experimental animals showed deficient acquisition in both shuttle-box avoidance and passive-avoidance response when compared to the control animals. Nevertheless, no impairment was observed in passive avoidance when the period of withdrawal was 15 days. Neither was impairment observed when the animals were tested in a T-maze or in another appetitive task. These results cannot be explained by differences in weight or fluid consumption.


Attenuation of stereotyped behaviour by sex steroids. Effects of sex steroids, testosterone, progesterone, and estradiol on PEA-induced stereotyped behaviour (SB) has been studied in normal, castrated, and ovariectomised mice. Effects of sex steroids on amphetamine-induced sterotypy and hyperactivity are also described. In castrated and ovariectomised mice B-phenylethylamine (PEA) increased SB. Pretreatment with sex steroids attenuated PEA-induced stereotypy in normal, castrated, and ovarietomised mice. Sex steroid pretreatment significantly inhibited PEA- and amphetamine-induced SB, but failed to alter increased motor activity due to amphetamine or PEA. The possible effect of sec steroids on SB through changes in central neurotransmitters are discussed.


The effects of divalent ions on morphine analgesia and abstinence syndrome in morphine-tolerant and -dependent mice. Intracerebral administration of copper sulfate potentiated morphine analgesia in morphine-tolerant and -dependent mice, but copper failed to affect other abstinence signs. When abstinence was precipitated with a partial antagonist, nalorphine, stereotyped jumping was not inhibited by either calcium or copper. These modifications of narcotic effects by copper were produced without alterations in the brain disposition of morphine. Total radioactivity in the brain following radioactive naloxone administration was also not altered.


The effects of intravenous phosphate loading on salivary phosphate secretion and plasma parathyroid hormone levels in the sheep. Adult sheep were given intravenous infusions of a solution of Na2HPO4 and the effects on parotid salivary composition and on plasma parathyroid hormone levels were studied. Infusion of the phosphate solution resulted in increases in the concentration of inorganic phosphate in the plasma and to proportional increases in the concentration and amount of phosphate secreted in the saliva. There was, however, no evidence that the salivary response was dependent upon a change in endogenous parathyroid hormone release. In other studies infusion of bovine parathyroid hormone or stimulation of endogenous hormone release through infusion of EDTA both led to a fall in the concentration of inorganic phosphate in the plasma and to a fall in the concentration and amount of phosphate secreted in the saliva. Taken together these results suggest that the major factor affecting salivary phosphate secretion in these studies was the concentration of inorganic phosphate in the plasma. Parathyroid hormone does not appear to have any direct effect on salivary phosphate secretion in the sheep though it may indirectly influence phosphate secretion through its effects on plasma inorganic phosphate level.


[Early immunological aspects in rats infected by Trypanosoma cruzi. I. Agglutination and immunofluorescence tests with antigen of trypomastigotes recovered in successive days of the infection (author's transl)]. From rats infected with the Y strain of T. cruzi trypomastigotes were recovered in successive days to be used in agglutination tests (AT) and in direct immunofluorescence tests (DIT). Titres obtained in AT reached 1/640 with trypomastigotes in the fourth and fifth days, decreased to 1/160 in the sixth day and were negative in the seventh day; in the tenth day the titers were again up to 1/40 and reached 1/320 in the eleventh day. The DIT were negative with trypomastigotes in the fourth and fifth days, a few were positive in the sixth day and numerous were positive in the seventh day; again a few were positive in the tenth day and all were negative in the eleventh day. These results seems to indicate that the trypomastigotes are blocked by circulating antibodies when they are not agglutinated by immune sera in vitro.


Dibenz[a,c]anthracene: a potent inhibitor of skin-tumor initiation by 7,12-dimethylbenz[a]anthracene. The mechanism by which the weak tumor initiator dibenz[a,c]anthracene (DB[a,c]A) inhibits the skin-tumor-initiating activity of 7,12-dimethylbenz[a]anthracene (DMBA) was investigated. DB[a,c]A was found to be a potent inhibitor of DMBA initiation when given either 5 min, or 1, 12, or 36 hours before DMBA. Pretreatment of mice with unlabeled DB[a,c]A at either 1, 12, or 36 hours before killing increased the in vitro epidermally mediated covalent binding of [3H]DMBA to DNA more than pretreatment with unlabeled DMBA at comparable times. Only when the tumor experiments were mimicked did a decrease in DMBA covalent binding to DNA in vitro occur. The results suggests that some competition at the level of polycyclic hydrocarbon metabolism or at the genome level may exist between metabolites of the weak carcinogen and those of the strong carcinogen.


Erythrocytic forms of Theileria velifera. The enigmatic veil associated with the cattle parasite Haematoxenus veliferus has been shown to be crystallike in ultrastructure and to stain with benzidine like haemoglobin. The ultrastructure of the organism is similar to that of other theilerial parasites. As less distinct veil-like structures are known to occur with some other Theileria species, and in one case, have also been shown to be crystalline in structure, it is proposed to sink the genus Haematoxenus as a synonym of Theileria.


[Primary chemoresistance to tuberculostatics in the district of Dolj between the years 1971 and 1975]. Primary resistance to tuberculostatics between 1971 and 1975 was studied in a lot of 676 adults with pulmonary tuberculosis, as well as the incidence and overall prevalence of primary and secondary resistance within the district covered by the tb. dispensary of Craiova. The incidence of primary resistance was of 13,61% of the entire lot, falling from 20.41% in 1971--1972, to 14.28% in 1973--1974 and to 7.25% in 1975. The incidence fell from 6.66 per 100 000 in 1971 to 2.3 per 100 000 in 1975, and the total prevalence of resistance from 27.7 per 100 000 in 1971 to 6.67 per 100 000 in 1975. Monoresistance was predominant (8.14% of the total), followed by biresistance (5.18%); primary triresistance was seldom recorded (0.29%). Biresistance rapidly decreased with years down to 1.55% in 1975 and triresistance disappeared in 1975. Although the frequency of primary resistance varies in terms of environment, sex and age of the patients, the differences are not statistically significant. Primary resistance to isoniazide and streptomycin occured in 7.99% of cases each, to ethambutol in 0.15% and to rifampicin in 0.51%. In order to reduce the cases of tuberculosis with primary resistance, endeavours should be directed towards the detection of all M. tuberculosis eliminators, applying a surveyed chemotherapy and following up the bacteriologic evolution of patients under specific treatment.


Interrelationships between Vitamin B12 and folic acid in myelomatosis: cobalamin coenzyme and tetrahydrofolic acid function. Cobalamin and folate metabolism was investigated in 43 patients with myelomatosis, in 8 control subjects of similar age and 22 younger controls. Plasma total cobalamin was lower in myeloma patients than in either of the control groups and methylcobalamin (Me-Cbl) was disproportionately reduced. Erythrocyte levels of total cobalamin were very similar in patients and elderly controls but were half the levels in younger controls. Erythrocyte levels of Me-Cbl were slightly higher in patients than in the dlderly controls. FIGLU excretion after L-histidine was elevated in 53% of the patients but values did not correlate with serum or erythrocyte folate or with plasma total cobalamin. FIGLU excretion decreased after DL-methionine or Me-Cbl only in patients whose FIGLU excretion was initially high. The results are discussed in the light of the 'methylfolate trap hypothesis' and suggest that some patients with myelomatosis have insufficient activity of methionine synthetase to meet the additional metabolic demand for one carbon compounds.


Acute renal failure associated with a malignant lymphoproliferative disorder with monoclonal light chain immunoglobulin production. Report of a case. A case of a 32-year-old male negro is reported in whom acute renal failure was the first manifestation of a diffuse lymphocplasmocytic infiltrative disorder. The malignant cells only produced immunoglobulin light chain (lambda-type). A description of the pathological findings is given. The case presented can be considered an intermediate form between macroglobulinaemia and multiple myeloma.


Natural killer cells may be the only cells in normal mouse lymphoid cell populations endowed with cytolytic ability for antibody-coated tumour target cells. Mouse normal lymphoid cells were analysed as to their ability to perform in three cytolytic systems: Ability to act as 'natural killer', NK, cells against a NK sensitive tumour target, YAC; as effector cells against IgG-coated 815 cells, or to function as effector cells against IgG-coated CRBC. NK activity and ADCC against the IgG-coated P815 cells were found to vary in parallel as affected by age, organ distribution and genotype of the effector cells. On the other hand, ADCC against CRBC was largely carried out by effector cells distinct from those functioning as NK cells or in ADCC against P815. Temperature pretreatment schedules at 37 degrees C showed both NK cells and ADCC ability against P815 to be highly sensitive on contrast to ADCC against CRBC. Likewise, inoculation of Corynebacterium parvum intraperitoneally will lead to reduction in ADCC ability against CRBC but increase in ADCC against P815 and NK activity. Blocking experiments using 'cold' inhibitor cells in the cytolytic assays indicated that NK cells and effector cells against IgG-coated P815 cells are the very same cells. We thus conclude that NK cells in the mouse also have the ability to express K cell activity against IgG-coated tumour target cells. In fact, our data suggest that the NK cells may be the only cell type in the mouse equipped with cytolytic potential for antibody-coated murine nucleated cells


Isolation and partial characterization of rat lymphoid cell surface histocompatibility antigens and immunoglobulins. Cell surface molecules of rat normal lymphoid cells were selectively labelled by lactoperoxidase catalysed iodination or by a galactose oxidase tritiated sodium borohydride technique, subsequently detergent solubilized, isolated by indirect immunoprecipitation and analysed on SDS-polyacrylamide gel electrophoresis. Four polypeptide chains were isolated by using the alloantiserum DA anti-Lewis. The molecular weights of the antigens were calculated as 41,000, 33,000, 27,000 and 12,000. Based on functional in vitro characteristics of the antiserum used and on the physiochemical properties as well as genetics of inheritance and tissue distribution, the polypeptide chains were identified as being subunits of Ag-B and Ia antigens. Two types of immunoglobulin heavy chains exhibiting the molecular weight 70,000 and 64,000 were isolated from unfractionated normal spleen cells by use of a polyvalent rabbit anti-rat immunoglobulin serum and tentatively identified as mu and delta chain. Using the same anti-immunoglobulin serum, no molecules could be precipitated from the lysated of Lewis thymocytes or peripheral T cells.


[The question of use of glucose or fructose for parenteral feeding. Results of a comparative study]. Glucose and fluctose (400 g/24 h) were compared as sources of carbohydrate in parenteral nutrition in patients following major abdominal operations or following multiple injuries. Group A (n = 8) received glucose during the first 2 days and fructose for another 2 days thereafter. In group B (n = 8) the sequence of carbohydrate infusion was reversed (2 days' fructose follwed by 2 days' glucose). The additional infusion to amino acids and a fat emulsion remained constant (total calories: 2,700 kcal/24 h). The following results were obtained: 1. Mean blood glucose concentrations were elevated in both infusion periods. During infusion of glucose the values were about 10% higher than those obtained during fructose infusion. Insulin administration was not necessary any of the patients studied. 2. Urinary excretion of both monosaccharides was negligible. 3. Blood lactate concentrations were higher during the infusion of fructose when compared to the glucose infusion period. The concentration of ketone bodies in the blood was not significantly influenced by either regimen. No major changes in base-acid equilibrium were observed. 4. The serum concentration of uric acid and several other metabolites did not differ significantly during the two infusion periods. 5. Mean urinary urea excretion exhibited a 30% increase during fructose infusion when compared to the glucose infusion period (p less than 0.012). From the results of t;is study and earlier findings it is concluded that fructose in a dose up to 400 g/day has no proven advantages over glucose in postoperative parenteral nutrition.


[Long-term animal experimental studies of a new dentin and pulp protective varnish (Bayer D-520)]. A new polyurethan varnish (Bayer D-520) was tested on 4 monkeys with a total of 96 cavities after the norms of "Recommended standard practices for biological evaluation of dental materials" of the ADA 1975. After the successful short-term experiment of two weeks, a long-term examination of dentin and pulp protective properties followed. 6 combinations were used: - 16 silicate cement fillings with varnish, 16 with Dycal base (negative control), 16 without protection (positive control) - 16 composite fillings with varnish, 16 with Dycal and 16 without protection After an observation time of 3 months, with marks of 0-3 for each criterion of the histological sample a significant difference (p less than or equal to 0.01) in favour of the varnish- and Dycal-protected cavities resulted. A difference between the varnish and the Dycal base could not be statistically established.


Potent antidopaminergic activity of estradiol at the pituitary level on prolactin release. Prior incubation of rat anterior pituitary cells with 17beta-estradiol led to an almost complete reversal of the inhibitory effect of two dopamine agonists, dihydroergocornine and RU 24213, on both basal prolactin release and thyrotropin releasing hormone-induced prolactin release. These experiments thus demonstrate a direct interference of dopamine action by a peripheral hormone. Prolactin secretion by pituitary cells in primary culture could possibly serve as an easily accessible model of a system under dopaminergic control.


Opportunistic infections in certain non-malignant diseases. In this paper infections associated with immunological and white blood cell deficiencies are discussed, together with certain aspects of infection in patients suffering from chronic renal failure and other non-malignant disease states. Reference is made to experience of opportunistic infections at East Birmingham Hospital, and certain aspects of the prevention and management of these conditions are outlined.


Drug kinetics in protein energy malnutrition. Potential problems of drug metabolism in human protein energy malnutrition (PEM) are reviewed in the light of the pathophysiological changes seen in PEM. Data derived from human studies and animal experiments are discussed, and a plea is made for further research in this area.


[Possible methods of control of virus disease in swine today and in the future (author's transl)]. To begin with, possible approaches to the control of virus disease in swine are discussed in general. The choice of a method of control will be decided by various factors such as the ecological and geographical environment of the animal population, the epizootiological behaviour of the causative virus itself as well as economic and political considerations. These consist in definitely freeing the swine population and/or keeping it free from a particular virus, maintaining a particular virus in an enzootic state, promoting this enzootic state within the herd, vaccinating and, finally, combining the above procedures. In conjunction with the trend towards increasingly large piggeries, the equilibrium between natural or specific immunity of the animal population and various viruses is often upset to the advantage of the virus. The pressure of infection will increase unduly and the epizootiological behaviour of the virus in question will not infrequently undergo alterations. Therefore, it is believed that the need for artificially increasing immunity or maintaining it at its current level will constantly increase in the long run. This can only be achieved by frequent vaccination. It is not unlikely that vaccination will remain as the sole and last possibility of effectively controlling various forms of virus disease in pigs.


A new heterophile antigen: man distinguished from higher apes and other mammals. Human cell membranes acquired an antigenic substance from the bovine serum in culture medium. The antigen was named the heterologous membrane antigen (HM Ag). Cross-reactive antigen was found in sera of all mammals tested, except for man. The distribution of the HM Ag serologically distinguished man from other mammals.


Neurophysiological correlates of acupuncture: limbic and thalamic responses to analgesic studies in non-human primates. Single unit activity from chronically implanted squirrel monkeys was analyzed to evaluate the effect of acupuncture stimulation on limbic and thalamic structures associated with pain. Extracellular recordings and computer-generated interspike interval histograms (ISIH) were obtained from n. parafasicularis and n. ventralis posteromedialis of the thalamus and the laternal septum, basal amygdala and anterior cigulate cortex. Thalamic activity remained unchanged while limibc units demonstrated statistically significant alterations in both cell firing rate and the ISIH in response to acupuncture stimulation. Although pain thresholds in response to tooth pulp stimulation were increased by morphine (37-51% +/- 2.1), acupuncture proved totally ineffective. This may be interpreted as a selective response to acupuncture in CNS structures primarily concerned with the affective component of pain.


Neurotoxic response of infant monkeys to methylmercury. Four infant monkeys were dosed orally with 500 microgram Hg/kg body wt./day /as methylmercury (MeHg) chloride dissolved sodium carbonate) beginning at 1 day of age. Neurological and behavioral signs of MeHg toxicity and blood Hg levels were monitored weekly. At first sign of MeHg intoxication, dosing with MeHg was terminated and the infants were monitored to assess reversal of the signs of MeHg toxicity. The first signs of MeHg toxicity, exhibited as a loss in dexterity and locomotor ability, were observed after 28--29 days of treatment; the blood Hg levels were 8.0--9.4 microgram Hg/g blood. Dosing was terminated at 28--29 days of treatment but the signs of MeHg toxicity continued to develop. The infants became ataxic, blind, comatose and were necropsied at 35--43 days after initiating treatment with MgHg. The mercury concentrations in tissues analyzed after necropsy were highest in liver (55.8 +/- 3.2 microgram Hg/g) followed by occipital cortex (35.6 +/- 4.8 microgram Hg/g) renal cortex (32.8 +/- 1.6 microgram Hg/g). The frontal and temporal cortices had 27.0 +/- 3.4 and 29.6 +/- 4.9 microgram Hg/g respectively while the cerebellar Hg concentration averaged 13.0 +/- 1.5 microgram Hg/g. The mean blood/brain ratio was 0.21 +/- 0.4. Histopathologic lesions were marked in the cerebrum with less severe lesions in the cerebellar nuclei. The Purkinje and granular cells of the cerebellar vermis appeared histologically normal. Lesions were not observed in the peripheral nervous system. The signs of MeHg intoxication, the tissue distribution of MeHg and histopathologic lesions observed in the infant monkeys were similar to those reported for adult monkeys.


The toxicity of 1-amino-3-chloro-2-propanol hydrochloride (CL88,236) in the rhesus monkey. The toxicity of 1-amino-3-chloro-2-propanol is associated with acute histopathological change in the medulla oblongata, characterised lesions of focal oedema. Continued administration results in neurological scars. Lesions can be induced at dose levels of 50 mg . kg-1 day-1. Clinical manifestations of neurological involvement are periods of slight incoordination and loss of balance in a few animals only.


[Haptoglobins in gynecologic tumors (author's transl)]. Serum concentrations of haptoglobins were checked in 100 women with benign or malign gynecologic tumors. Typification of haptoglobins was determined by starch gel electrophoresis, quantification by single radial immunodiffusion. Cases with malignancies showed significant increased levels in comparison to healthy women. In cases with cervical carcinoma, a significant increase of the haptoglobin level was evaluated according to advanced carcinoma.


Ebola haemorrhagic fever: experimental infection of monkeys. Experimental infection of rhesus and vervet monkeys with Ebola virus produced a uniformly fatal illness. The course of the disease resembled that found in man with weight loss, anorexia, fever, haemorrhages and skin rash being frequently seen. Viraemia was obvious within two days of infection and persisted until death which occurred between days five and eight. Virus was found in high concentrations in several organs but particularly in the liver, spleen, and lungs.


Rhodopsin and blindness.

Rhodopsin and blindness. Systemic immunization with purified homologous rhodopsin from retinal outer segments induced blindness in primates (Macaca mulatta). Inflammation and characteristic retinal changes were the earliest clinical signs of the disease. Perivasculitis, subretinal exudations and bullous detachments of the retina were progressive and unrelenting pathological processes leading to rapid and irreversible visual deterioration. Electroretinographic responses (ERG) at this stage of the disorder became abolished. Antibodies and delayed hypersensitivity to rhodopsin were demonstrated only in the experimental diseased animals. Homologous visual purple appears to be organ and immunopathologically specific. Histological confirmation of these findings showed a pathological spectrum of destructive alterations confirmed specifically to the outer segments of the entire retina. The pathologic reaction was supported by a distinct and pronounced granulomatous inflammatory response.


Double controlled comparison of IDU and trifluorothymidine in thirty-three patients with superficial herpetic keratitis. Thirty-three patients were followed in a double controlled study to test the efficacy of IDU and TFT on superficial epithelial herpes simplex virus infection. Sixteen received TFT and 17, IDU. There were four failures in patients on IDU therapy and no failures in the 16 patients using TFT. These results indicate a trend for greater efficacy of TFT than IDU. In those patients who healed with IDU and with TFT, there was no difference in the number of days to heal in each group.


Chromosomal abnormalities associated with cyclopia and synophthalmia. At the present time, essentially all known facts concerning cyclopia are consistent with some chromosomal disease, including clinical features of the pregnancy (fetal wastage, prematurity, intrauterine growth retardation, maternal age factor, complications of pregnancy), the generalized developmental abnormalities, specific ocular dysgenesis, by the high incidence of chromosomal abnormality already demonstrated, and the possibility of error in those cases of cyclopia with normal chromosomes. Even if chromosomal aberrations represent only one group of several different etiologic factors leading to cyclopia, at the present time chromosomal errors would seem to be the most common cause of cyclopia now recognized. Further studies will establish or disprove a chromosomal error in those instances which are now considered to be the result of an environmental factor alone or those with apparent familial patterns of inheritance. This apparent diverse origin of cyclopia can be clarified if future cyclopic specimens are carefully investigated. The evaluation should include a careful gross and microscopic examination of all organs, including the eye, and chromosome banding studies of all organs, including the eye, and chromosome banding studies of at least two cyclopic tissues. Then the presence or absence of multiple causative factors can be better evaluated.


Massive periretinal proliferation: a logical approach to therapy. Massive periretinal proliferation (MPP), a serious complication of retinal surgery is caused by proliferation and fibrous metaplasia of cells mostly deriving from retinal pigment epithelium and retinal glial cells. Contracting fibrous membranes in the vitreous and on and also under the retina cause the intraocular changes of MPP. Early signs such as increased "tobacco dust," pigmented clumps in the vitreous, subtle preretinal and even retroretinal membranes are usually overlooked. The late signs such as starfolds, irregular retinal folds and funnel-shaped detachments are well known. The pathogenesis of the clinically visible signs is described and a four stage classification of the disease is given. Based on the improved understanding of this disease, a new therapeutic approach is presented, with the technique of pars plana vitreous surgery. Not only vitreous membranes but also preretinal membranes are removed. Forty-seven consecutive patients who suffered from severe massive periretinal proliferation were  operated on with this technique and followed for six months or more. Seventeen patients (36%) had an attached retina. Twelve patients had a major visual improvement. The major postoperative complication is phthisis bulbi (10 eyes, 21%).


Production of anterior segment ischemia. Anterior segment ischemic changes can occur without detachment of any muscles. The most common cause of such ischemic changes of the anterior segment is the removal of too many rectus muscles in one operation. Twenty dog eyes and eight monkey eyes were subjected to the disinsertion and detachment of various combinations of extraocular muscles. The dogs were sacrificed at intervals from 30 to 90 days. During the observation period, they were observed for gross and slit-lamp changes. The enucleated eyes were studied microscopically for signs of ischemic and necrotic changes. Two patients who were studied, observed, and treated for anterior segment ischemia following muscle surgery are described. The changes which occur after extraocular muscle surgery are extensive and include corneal edema, cataract, chemosis, corneal changes, decreases in intraocular pressure, decreases in outflow or glaucoma, and frank necrosis. The variables which lead to this reaction are described in detail. Also, some unanswered queries, such as the duration of the reaction and the time interval of the reaction after multiple muscle operations are discussed.


[Comparative evaluation of different nitrogen sources in parenteral feeding]. The problem dealing with the effect of various nitrogen sources upon the protein metabolism indices and also with the effect of the main pathological process and volume of surgical intervention upon these indices in the closest postoperative period following gastrointestinal surgery, are discussed in this paper. According to the authors' findings there is no statistically significant difference in using such nitrogen sources in parenteral feeding as moriamine, aminozol and hydrolyzine solution. Some findings prove a higher albumin and beta-albumin contents and a high albumin-globulin coefficient in recovered patients within the first days after the operation. The authors came to the conclusion on the necessity of elaborating individual parenteral feeding programs.