Blood polymorphonuclear dysfunction in patients with alcoholic cirrhosis. Polymorphonuclear leucocyte function was investigated in twenty patients with alcoholic cirrhosis and three patients with cryptogenic cirrhosis. Bacterial ingestion, oxygen-dependent bactericidal capacity, and chemotactic response were measured. Serum dependent abnormalities were common; they included deficiencies of ingestion and of all subsequent oxygen-dependent metabolic events (three patients), all oxygen-dependent metabolic events (one patient), cytochrome c reduction and iodination deficiencies (six patients), isolated cytochrome c reduction deficiency (ten patients), and chemotactic deficiencies (fourteen out of eighteen patients). Serum-independent abnormalities were much less common; they included increased ingestion rate (four patients), decreased stimulated reduction of nitroblue tetrazolium (three patients), and decreased myeloperoxidase content (eight patients). Polymorphonuclear leucocyte abnormalities are frequent in cirrhosis and may account in part for increased susceptibility to infection in that disease.


The effects of administrations of HCl, NH4Cl and NH4HCO3 on the excretion of urea and ammonium in man. In man, HCl acidosis reduces blood and urinary urea with a concomitant rise in ammonium (NH4+) excretion. Significantly less urea is excreted following NH4Cl administration than following equimolar ingestion of NH4 HCO3. The results of these alterations in nitrogen excretion are interpreted in terms of bicarbonate utilization and production.


Cholesterol and DNA content in arterial tissue in severe obesity: their relation to some risk factors for ischaemic heart disease. Arterial tissue was obtained from twelve severely obese patients during jejuno-ileal by-pass surgery. The arterial DNA content was inversely correlated with the sum of venous glucose values during an oral glucose tolerance test (rs = -0.72). This observation may have implications on the known relationship between decreased glucose tolerance and early manifestations of atherosclerosis.


Human fat cell adenylate cyclase: regional differences in adrenaline responsiveness. The effect of adrenaline on adenylate cyclase activity in membranes prepared from human abdominal and gluteal adipose tissue was examined. Basal enzyme activity averaged 1.0 mmol cAMP/mg protein/15 min in abdominal tissue and 0.68 nmol cAMP/mg protein/15 min in ghosts from the buttock. Maximally effective concentrations of sodium fluoride (20 mmol/1) induced an eight-fold increase in both membrane preparations. The maximal response to adrenaline (1.0 mmol/1) averaged 170% in ghosts of abdominal tissue compared with 60% in gluteal membranes. The concentrations of adrenaline required to produce half-maximal stimulation were similar in membrane preparations of both regions (about 5 X 10(-5) mol/1).


Surface immunolglobulin on rabbit lymphoid cells. VI. Failure to detect d and e group immunoglobulin allotypes on lymphocytes by immunoelectron microscopic labeling. Surface immunoglobulin allotypes on rabbit peripheral blood lymphocytes (PBL) and spleen lymphocytes are detected by an immunoferritin labeling technique for electron microscopy. Human red blood cells, chemically coated with purified rabbit IgG of specific allotypes, served as test cells to assess the labeling specificity and efficiency. Immunoelectron microscopic labeling reveals that groups a, b, d and e allotypic specificities are readily detectable on passively coated test cells. However, only a and b group markers are detectable on lymphocytes. On rabbit PBL both a (VH of Fd region) and b (kappa chain constant region) group allotypes are detectable (73-78% and 68-77%, respectively); on spleen cells, 46% and 52-55% are positive for a and b locus allotypes, respectively. The d and e allotypes (i. e. gamma chain-specific) are undetectable on PBL or on spleen lymphocytes using this method. We conclude that the d and e group allotypes are either not present on the lymphocyte surface or are buried in the surface membrane and unacessible to the antisera used in this immunoferritin labeling technique.


Presence of common idiotypes on antibodies induced by glutamic acid-lysine-containing terpolymers in responder and nonresponder mice with the Ig-1b heavy chain allotype. A B10.A (5R) responder mouse to the random linear terpolymer, poly--(Glu, Lys, Phe), GLphi, can produce immunoglobulins which bind poly-L (Glu, Lys), GL, that share idiotypic determinants with GL-binding antibodies produced by other members of the same strain. Expression of these common idiotypic determinants, termed BGL, is independent of the H-2 halotype and closely linked to the Ig-lb heavy chain allotype. Moreover, nonresponder mice with the Ig-lb heavy chain allotype, when immunized with GLphi that has been chemically coupled to an immunogenic carrier, chicken IgG, can produce GL-binding antibodies that share BGL idiotypic specificities with anti-GLphi antibodies produced by responder animals. Also, the responses to other GL-containing polymers, such as poly-L (Glu, Lys, Ala) and poly-L (Glu, Lys, Pro), which are under the control of distinct Ir genes, can stimulate the production of GL-binding antibodies that share common BGL idiotypic determinants with antibodies induced with GLphi. These findings are discussed with respect to their implications concerning the mechanism(s) of Ir gene control.


Regulation of allotype expression in heterozygous rabbits. III. Concomitant modulation and concomitant suppression oa a2 and a3 allotypes on individual peripheral blood lymphocytes. Sensitization of peripheral blood lymphocytes from heterozygous a2/a3 rabbits with purified, monospecific anti-a3 antibodies, raised in a1/a1 rabbits, resulted in the disappearance of surface a2 and a3 allotypes (concomitant modulation) after subsequent incubation at 37 degrees C, as determined by the mixed antiglobulin (rosette) test. Similar results were obtained when anti-a2 antibodies were used. The dose dependence of modulation and comodulation were also studied. Testing of mixtures of homozygous a2/a2 plus a3/a3 cells never led to comodulation. Blocking studies, performed to determine the surface contiguity of a2 and a3 determinants, indicated that both allotypes are situated close together in the membrane on cells exhibiting allotype inclusion. Overnight culture in serum-free medium revealed that cells which underwent extensive modulation and comodulation were often suppressed for both homologous and alternate allotypes (concomitant suppression). These and other data suggest that a single modulation event, in which extensive removal of cell membrane Ig occurred, could serve to inhibit the re-expression of Ig. This may, in part, reflect interactions with membrane receptors involved in the regulation of expression of VH gene products. Implications of VH allotype inclusion are discussed.


Enhancement of acetylcholine secretion by two sulfhydryl reagents. Two sulfhydryl reagents (N-ethyl maleimide and p-chloromercuribenzoate), used in a concentration of 0.1 mmol/l, increased both spontaneous and evoked acetylcholine secretion at the toad neuromuscular junction, the former in the absence of extracellular calcium ions.


Intensity coding in primate visual system. The pupil reflex and the discharge of LGN cells of the awake macaque were measured under stimulus conditions that yielded evidence for wide-range intensity coding in human psychophysical experiments. Ganzfeld flashes of white light were delivered under dark-adapted conditions to the surgically immobilized eye of the monkey while the other eye was observed in the infrared. Three-sec flashes elicited a consensual pupil reflex that was graded from -8 to 0 log Lamberts (L), indicating that the optic nerve fibers are capable of coding at least an 8 log-unit range of light intensity. In the physiological experiments, shorter flashes (0.1-0.5 sec) but otherwise identical conditions elicited monotonically graded responses from one type of LGN cell over the photopic range of -5 to 0 log L. Responses from other types of LGN cells were also graded over wide ranges but had different thresholds and, in some cases, nonmonotonic intensity-response functions. Latency of the excitatory LGN responses decreased with increasing intensity according to a power function with slope of-0.08. The pupil reflex and the LGN cell excitatory responses approximate power functions of light intensity with exponents of 0.22 and 0.14-0.29 respectively. The range of intensity coding found for single LGN cells is the widest yet reported for diffuse stimuli.


Evaluation of a surgical method for immobilizing the eye of an alert monkey. One eye of a macaque monkey was immobilized by severing the third, fourth, and sixth cranial nerves. The residual movements of the operated eye were measured by repeatedly mapping the position of a visual receptive field. Movements of several degrees were caused by contraction of the orbital musculature during the closure blink. The amount of movement was dramatically reduced by paralysis of the superficial orbital muscles with a local anesthetic. Side effects of surgical immobilization include increased risk of corneal clouding and eye infection. In one monkey intraocular pressure was lowered for several weeks. Regeneration of the severed nerves causes return of some voluntary movement of the eye, which is not coordinated with movements of the unoperated eye even after nine months postoperative survival. The suitability of this approach for studies on the visual nervous system is discussed.


Lipofuscin accumulation in squirrel monkey spinal cord consequent to protein malnutrition during gestation. The formation of lipofuscin pigment in the anterior horn cells of the cervical spinal cord has shown in the fetuses and neonates under the extrinsic influence of maternal protein deprivation during the gestation period in the squirrel monkeys.


Intravenous thyrotropin releasing hormone (TRH) enhances the excitatory actions of acetylcholine (ACh) on rat cortical neurons. I.v. administered TRH (1.25--10 mg/kg) enhanced the excitatory actions of iontophoretically applied ACh on spontaneously active cerebral cortical neurons of pentobarbital-anaesthetized rats. These observations are consistent with the hypothesis of a cholinergic-link in the anti-anaesthetic actions of exogenously administered TRH.


Scanning-autoradiography--a new method for the demonstration of membrane-surface-associated structures. A method for the demonstration of membrane-localized markers and receptors is described which results from the combination of autoradiography and scanning electronmicroscopy.


A controlled trial of adenine arabinoside and trifluorothymidine in herpetic keratitis. The effectiveness of two anti-viral agents, adenine arabinoside and trifluorothymidine, were studied in cases of human superficial herpetic keratitis (dendritic ulceration). A highly satisfactory response to each drug was demonstrated in most cases.


Antibacterial activity of sisomicin.

Antibacterial activity of sisomicin. A study of the in vitro antibacterial activity of a new aminoglycoside, sisomicin, is reported. The results show no significant differences between the activity of sisomicin and gentamicin.


Effect of BCG and C. parvum on in vivo Listeria clearance and tumor growth. Comparative studies in normal and congenitally athymic (nude) mice. Clinically, it is important to know whether agents used for immunostimulation require the presence of functional thymus-derived (T) cells. Previous studies showed that both BCG and C. parvum induced a macrophage-dependent enhanced in vivo listeria clearance and in vivo inhibition of a fibrosarcoma induced by 20-methylcholanthrene. These two models were re-evaluated in congenitally thymusless (nude or nu/nu) B10LP mice lacking functional T cells. In nu/nu mice, (1) BCG failed to enhance listeria clearance, and when given simultaneously with tumor cells, had no effect on tumor growth; (2) C. parvum enhanced listeria clearance and simultaneous administration of C. parvum and tumor cells exerted an inhibitory effect on tumor growth. The general conclusion was that under the experimental conditions chosen functional T cells are required for an effect of BCG, but not for that of C. parvum. It is not clear whether these observations have any clinical significance.


Studies on the immunostimulating and anti-tumour activity of a fraction isolated from Corynebacterium granulosum. The immunostimulating activity of the anaerobic corynebacteriae is well documented. Fractions isolated from while cells have not been much investigated. We have reported that the immunostimulating activity is present in fractions isolated from Corynebacterium granulosum. A few fractions have shown anti-tumour activity in grafted tumours in mice. One of these fractions (P 40) has been investigated in more detail, since it proved to be inhibitory when administered after grafting of the non-syngenic P 815 tumour in mice.


Comparative studies of different strains of BCG vaccine in mice: T-cell dependent immune responses. Three tests have been selected to demonstrate the close relationship between the innate immunogenicity and immunopotentiating capacity of different strains of BCG vaccines grown under the same conditions. The five strains of BCG which have been most extensively studied were PASTEUR, PHIPPS, TICE, CONNAUGHT and GLAXO. The first four are alike, they have similar growth characteristics and closely resemble each other, in immunological properties-lymphoproliferative response in vivo and T-cell potentiating effect-PASTEUR BCG being the strongest. GLAXO strain is different in these respects and is shown to have atypical properties.


Conditions favouring the selection of either specific or non specific C. parvum-mediated, systemic antitumour immunity in mice. Accumulated data suggest that one of two antitumour mechanisms of C. parvum may predominate depending on the route of injection of C. parvum and its distribution in relation to the tumour. After systemic C. parvum the mechanism is considered to be immunologically non specific (i.e. not requiring tumour specific antigens) and mediated by C. parvum activated macrophages. After local injection of C. parvum the interaction (direct or lymph node mediated) between C. parvum and tumour specific antigens has resulted in the generation of immunologically specific T-lymphocytes with antitumour activity.


The effect of Corynebacterium parvum on the proliferation of monocyte precursors in the bone marrow of mice. The anti-tumour activity of C. parvum is thought to be mediated via the monocyte/macrophage system (Scott, 1974). These cells originate from rapidly dividing precursors in the bone marrow and it might be at this level that C. parvum exerts its action. To test this hypothesis bone marrow T0 Swiss mice has been cultured according to the method of Bradley and Metcalf (1966), which gives an index of the number of proliferating macrophage precursor cells at the time of sacrifice. Experiments were set up at various times following a single i.p. injection of 700 microgram of an anti-tumour strain of C. parvum (CN 6134-Wellcome Research Laboratories). Controls received 700 microgram of either C. diphtheriae CN 2000 or C. parvum CN 5888, a strain with no anti-tumour activity. Macrophage colony counts in those mice receiving "active" C. parvum were significantly higher than those in controls at intervals from 2 h to 3 weeks post-treatment. This time course parallels certain immunological properties of C. parvum and suggests a possible mode of action.


Amino acid degrading enzymes for cancer therapy. The development of microbial enzymes for cancer therapy presents difficulties not commonly experienced with biological drugs. The development of the enzyme asparaginase from Escherichia coli in the USA and of the serologically different asparaginase from the plant pathogen Erwinia carotovora in this Establishment, has not only added to the choice of antileukaemia drugs but also provided a valuable guide to the selection and development of new therapeutic enzymes. Our own programme has led to the study of enzymes that degrade other amino acids (glutamine, arginine, phenylalanine and tyrosine) that appear to be important to certain leukaemia cells. Microbes with only remote associations with man were considered as a source of these to minimize initial immunological sensitivity. In the case of erwinia asparaginase the benefits of this have probably included a lower incidence of anaphylaxis compared with the escherichia enzyme. The selection of a stable, high-affinity enzyme that operates efficiently under physiological conditions ensures effective depletion of a circulating amino acid but the choice is very limited. It is also difficult to assess from laboratory tests the likely persistence, toxicity and efficacy of the enzyme in clinical use and to arrive at meaningful biological tests for the quality control of the finished product. Some of the difficulties will be described and proposals made for criteria of acceptance for this type of drug in experimental use.


Proposals for quality control methods of bacterial vaccines for immunostimulation. III. Effect of BCG and C. parvum on in vivo Listeria clearance and tumor growth. Two quality control methods for BCG and C. parvum are described. First, in vivo macrophage dependent-spleen clearance of Listeria monocytogenes in inbred B10LP mice. BCG and C. parvum were administered intravenously prior to listeria inoculation (a prophylactic model). Conditions for enhanced listeria clearance including dose, route and time interval were described for each vaccine. Next, a tumor model was developed: i.e. a fibrosarcoma, chemically induced by 20-methylcholanthrene in inbred Balb/c mice. Increase in footpad thickness was used as a criterion for tumor growth. Optimal dose, route and time interval were established both in prophylactic and therapeutic situations, including intratumoral application. Depending on the conditions chosen, both inhibition and enhancement of tumor growth were observed. General conclusions of these studies are: (a) both models yield information on the effect of bacterial vaccines for immunostimulation; (b) statements on the effectiveness of any product should be based on careful studies including all variables.


Effect of oral pancreatic enzymes on the course of cholera in protein-deficient vervet monkeys. The effect of pancreatic extract on the course of cholera infection in protein-deficient vervet monkeys (Cercopithecus aethiops) was studied. Eleven animals were made protein deficient by diet. Thier intestinal pancreatic enzyme concentration decreased as they became protein depleted. These animals were then challenged with Vibrio cholerae. Four control animals given a standard diet were similarly challenged. Immediately after challenge, 6 of the protein-deficient monkeys were given a highly purified pancreatic extract at a dose of 500 mg per day, and the other 5 protein-deficient animals received heat-inactivated pancreatic extract. Pancreatic extract significantly reduced the severity and duration of diarrhea in the treated animals so that they resembled the controls. The period of fecal excretion of vibrios was prolonged in the group of monkeys which received inactivated pancreatic extract. In addition, the response of intestinal antibody titers to cholera toxin was also significantly lower in this latter group. These observations suggest that exocrine pancreatic secretion is involved in the local defense mechanism against cholera during prtein deficiency.


Percutaneous transhepatic drainage of the biliary tract: technique and results in 104 cases. A two-step procedure for percutaneous transhepatic drainage (PTD) of the biliary tract is described. This technique was applied on a total of 105 cases of obstructive jaundice, 84 with malignant and 21 with benign lesions, and was successful in 104. Decompression effect was adequate and reduction in serum bilirubin level was quick. Operative mortality, which used to be high in jaundiced patients with serum bilirubin levels above 10 mg per dl, has been significantly reduced with this procedure employed as the first step in a two-stage operation for malignant biliary obstruction. PTD proved to be very useful in the management of acute obstructive suppurative cholangitis and ensuing liver abscesses. Continuous drainage was also achieved by PTD in inoperable cases, and 1 patient with a hilar carcinoma was kept alive for 2 years and 1 month by PTD alone. With the improvement in the diagnosis of biliary tract disease this procedure will assume an important position in the management of obstructive jaundice.


Plasma amino acid abnormalities in the alcoholic: respective role of alcohol, nutrition, and liver injury. Plasma amino acid abnormalities are common in alcoholics, but the respective role of alcoholism, nutrition, and liver injury in producing these abnormalities is unknown. To elucidate this question, amino acids were measured in 56 alcoholics and 32 nonalcoholics with liver disease, and in an experimental model of alcoholic liver injury in the baboon. Dietary protein deficiency depressed branched-chain amino acids with a tendency to decreased alpha-amino-n-butyric acid. By contrast, chronic alcoholic consumption selectively increased these amino acids both in short term (2 to 4 weeks) studies in human beings and in 1 to 4-year studies in baboons. Moderate liver injury had no significant effects on these amino acids whereas advanced cirrhosis depressed branched-chain amino acids. Thus, plasma branched-chain amino acids and alpha-amino-n-butyric acid in the alcoholic are affected by at least three variables: dietary protein deficiency and advanced cirrhosis which tend to decrease these amino acids, and chronic alcohol consumption which tends to increase them.


Secretory immunoglobulin deficiency in a family with inflammatory bowel disease. A family with 4 of 10 first-degree relatives affected with inflammatory bowel disease (IBD) was studied to determine whether any distinct immunological abnormalities occur in the affected members, as compared with unaffected members of the family, normal controls, and other unrelated patients with IBD. Red cell blood type and HL-A phenotypes did not distinguish between healthy and affected members, although HL-A2, 32, B27, and B12 were the predominant haplotypes in members with IBD. There was no significant difference between the two groups in the lymphocyte subpopulation counts of T cells, B cells, and cells carrying Fc or complement receptors. The in vitro mitogen response, however, to phytohemagglutinin and pokeweed mitogen were depressed in the affected members. Serum IgA and C3 levels were significantly elevated in members with IBD compared to healthy subjects with values of 232 +/- 69 (mean +/- SD) versus 148 +/- 29 mg per dl for IgA (P less than 0.05) and 173 +/- 32 versus 115 +/- 22 mg per dl for C3 (P less than 0.025), respectively. Plasma and, to a lesser extent, peripheral lymphocytes from 2 affected members who were tested were cytotoxic to allogeneic colonic epithelial cells. Salivary IgA was normal in the affected family members and unrelated patients with IBD. However, the free secretory component of salivary IgA was absent or markedly depressed in family members, as well as in unrelated patients with ulcerative colitis. This deficiency of the secretory immune system appears to characterize more frequently ulcerative colitis than Crohn's disease and may compromise mucosal host defenses in IBD.


[Comparative and functional morphology of musculus canalis ani in tetrapod mammals and primates]. Comparative anatomy of structure and function of the M. canalis ani in tetrapode mammals and primates is described for the first time. The muscle itself lies on the sphincter ani internus in the area between the anorectal ("pectinate") and anocutaneal ("white") lines and its circumference is intact around the entire anal canal. The canalis ani muscle orginates from the superior part of the sphincter ani internus and concomitantly receives additional fibers from the longitudinal muscle. Caudally the muscle dips back into the sphincter ani internus and, at the same time, a small portion of the fibers go to the longitudinal muscle and, likewise, a portion also sets itself on the perinaal skin. On the basis of its morphological relationship to the convoluted vessels of the rectal venous plexus, the canalis ani muscle appears to be able to complete the closing of the anus in the continence phase to such an extent that a complete closing of the anal lumen is guaranted.


The anatomical relations of the ductus vomeronasalis and the occurrence of taste buds in the papilla palatina of Nycticebus coucang (primates, prosimiae) with remarks on strepsirrhinism. Nycticebus coucang is typically strepsirrhine. This condition is basically the same in all prosimians except Tarsius. The rhinarium shows a labial part; the marked furrow in its median plane clefts the margin of the upper lip. The latter is attached to the gum between the median incisors by means of paired folds (not corresponding to a frenulum labii superioris). The labial cleft is continued in the sulcus papillae palatinae. The ductus vomeronasalis opens into the ductus nasoplatinus which, in turn, enters the aboral part of the sulcus palatinus. Thus strepsirrhinism provides, occasionally, an open communication of the olfactory systems (nose, vomeronasal organ) with the environment in front of the rhinarium. Strepsirrhine primates possess an internarium very similar to the one of platyrrhine monkeys. The shape of the nostrils is not characteristics for strepsirrhinism. A split-lip condition is likely ancestral to the complete lip condition, since it is found in several stems of mammals, especially in archaic forms. Strepsirrhinism, such as in lemuroid prosimians, is probably just one case of the primitive split-lip condition. Therefore, a median furrow in the external hairy skin of the upper lip, found in some platyrrhine monkeys, could be a rudiment of a cleft, indicating that a kind of a split lip condition was ancestral to the undivided lips of platyrrhine monkeys. Taste buds occur in the epithelium of the lateral surface of the papilla palatina of Nycticebus. Other lorisid prosimians have not been studied in this respect. The taste buds test water soluble substances entering the sulcus either way. These substances may come from the environment entering the sulcus through the labial cleft.


Variance component analysis of allozyme frequency data from eastern populations of Drosophila melanogaster. Gene frequency variation at eight polymorphic allozyme loci in Drosophila melanogaster populations in North Carollina and the east coast of the United States were analyzed utilizing the variance component estimation procedures suggested by Cockerham (1969, 1973). These variance components were used to estimate correlations of genes within small geographic regions. The average (over loci) correlation between genes in the same individual within subpopulations was estimated to be 0.033. That between genes in the same subpopulation in different individuals was estimated to be very small, although significantly different from zero. The macrogeographic variation measured by the correlation of genes sampled from the same local region was large for some loci and smaller for others. this variation was also analyzed by correlation with latitude and longitude. Several previously recognized clines were identified as were several new clines.--These results were interpreted as indicating either some degree of nonrandom mating and local breeding unit isolation or a low frequency of null alleles. The geographic and temporal variation has no simple interpretation.


A genetic locus having trans and contiguous cis functions that control the disproportionate replication of ribosomal RNA genes in Drosophila melanogaster. The results of deficiency mapping experiments reveal the presence of a compensatory response (cr+) locus that is located distal to the cluster of ribosomal RNA (rRNA) genes and is responsible for disproportionately replicating these genes when cr+ locus is present in a single dose, as in X/O males or X/sc4-sc8 females. The cr+ locus is novel in that it exhibits both trans and contiguous cis acting properties in somatic cells. It acts in trans to detect the presence of its partner locus in the opposite homolog, and if that partner locus is absent, it acts in cis to drive the disproportionate replication of those rRNA genes (rDNA) that are contiguous with it. The ability of cr+ to function is independent of the number of ribosomal RNA genes present. Furthermore, it can be shown that the cr+ locus is not required for the magnification or reduction of germ line rDNA. Finally, the implication of cr+ for position-effect variegation and the apparent reversion of the abnormal oocyte (abo) phenotype are discussed.


Electron microscope analysis of mouse and rabbit globin and immunoglobulin gene sequences. Mouse and rabbit globin and immunoglobulin gene sequences, which had been synthesized in vitro from eukaryotic mRNAs and inserted into plasmids, have been examined in the electron microscope. The size of the inserted beta rabbit and alpha and beta mouse globin DNA sequences has been estimated as 620 base pairs while the size of the inserted alpha rabbit globin DNA sequences was found to be about 490 base pairs. Heteroduplex analysis has revealed no structural abnormalities at the insertion sites of the chimeric plasmids except in the case of a plasmid containing an immunoglobulin light chain gene sequence of about 830 bases, in which 3 kb deletion adjacent to the insertion site was observed.


[Behavior of blood amino acids and fatty acids during complete parenteral hyperalimentation with carbohydrates, amino acids and fats]. Over a period of 12 hours a total amount of 190 g fructose, 190 g glucose, 145 g xylitol, 96 g fat and 99 g amino acids were infused. The utilization of carbohydrate was not diminished despite the high fat load. In addition, the antiketogenic action of carbohydrate was still provable. The nitrogen balance was positive as an indicator of good utilization of amino acids. Therefore, simultaneous administration of a carbohydrate mixture and a fat emulsion as energy sources during application of amino acids is recommended.


[Costs and benefits of measles vaccination]. Former calculations of the medical benefit of measles immunization, concerning frequency of measles complications, effectiveness and risk of vaccination, showed that measles vaccination is a very useful measure. As the decision to introduce vaccination on a broad scale depends on financial deliberations, too, a cost-benefit analysis for Austria has been performed and the cost-benefit ratio as well as the cost-benefit difference calculated. The costs of measles vaccination which is performed mainly by private pediatricians at the present time, include costs of vaccine, physician and additional antipyretic and is 257.90 AS. The average costs of therapy per child consist of home treatment (287.20 AS), hospital treatment (162.50 AS) and care of residual cerebral damage (88.50 AS). Together with the costs of one week vacation which is warranted in Austria for the nursing of a sick child once a year, this makes a total sum of 1081.--AS. From these data the cost-benefit ratio was calculated by 2.95, the cost-benefit difference by 715.--AS per child. 5 years after the start of general measles vaccination of 1 year old children the accumulated costs of vaccination are equalled by the profit gained by prevention of the disease. The annual cost-benefit difference is positive after 3 years. 10 years after introduction of general vaccination the accumulated cost-benefit difference in Austria would be approximately 167 Mill. AS.


[The etiology of epilepsies in children by considering the case histories in comparison with a control group (author's transl)]. To clarify the etiology of epileptic illnesses in children a detailed questionnaire was prepared, with questions on both genetic factors and the possibility of pre-, peri- and postnatal injury. The questionnaire was filled out by the parents of 422 epileptic children and those of 150 healthy control children of the same age. The differences were statistically calculated by means of the x2 test, small values being corrected according to Yates. Hereditary factors were found in 10.2% of all patients, ranging from 5.6% to 13.5% for the various seizure types (control group:0.6%). A high rate of hereditary afflictions was found even in those types of seizure which are considered predominantly symptomatic (salaam [West] or myoclonic-astatic convulsions: 13.5%, focal attacks: 11.2%). The significance of some exogenic factors, e.g. illnesses during pregnancy, prematurity, birth complications, was statistically confirmed in some instances for all types, in other instances only for certain types of seizure. As regards other factors, however, whose causative role has hitherto been considered proven or at least very probable, no differences were found between patients and controls (e.g. protracted labor, uterine inertia, coiling of the umbilical cord). Confirmation was found for the generally accepted rule that exogenic injuries are most often demonstrable in children with salaam or myoclonic-astatic convulsions and least often in those with absences. In conclusion, it is emphasized that an absolute dividing line can no longer be drawn between genetic and symptomatic epilepsies; in many cases the exogenic influence merely serves as a touching-off factor for a gentic epilepsy.


Effect of CO2 on carbonic anhydrase activity and isozyme levels in respiratory failure. The activity and the isozyme B and C levels of red cell carbonic anhydrase was examined before and during CO2 inhalation in 18 patients with chronic respiratory failure. Carbonic anhydrase B and C levels did not change during 5 min breathing of high (8-9%) and low (3-5%) CO2 mixture. Carbonic anhydrase activity decreased in patients with combined hypercarbia (Paco2 greater than or equal to 45 mmHg) and hypoxemia (Pao2 less than or equal to 60 mmHg). This was accompanied by an increase in red cell K+ content, 2, 3-DPG and Hct/Hb. The activity did not change in patients with only hypoxemia. Carbonic anhydrase activity and plasma HCO-3 concentration were positively correlated (r = 0.4, P less than 0.05). A significant inverse correlation was also found between changes in red cell K+ content and those in carbonic anhydrase activity (r = - 0.42, P less than 0.05). These results indicate that 1), there is a dissociation between activity and isozyme levels in red cell carbonic anhydrase during the initial 5 min of CO2 breathing in patients with combined hypercarbia and hypoxemia, and 2), there seems a linkage exists between K+ movement across the red cell membrane and carbonic anhydrase activity.


Thyroxine-binding globulin, triiodothyronine, thyroxine and thyrotropin in newborn infants and children. Thyroxine-binding globulin (TBG), triiodothyronine (T3), thyroxine (T4) and thyrotropin (TSH) have been determined by radioimmunoassay in plasma of newborn infants and throughout childhood until puberty. Mean maternal TBG concentration was 1.65 +/- 0.09 mg/100 ml (SEM) and significantly higher (p less than 0.01) than cord blood levels of TBG (1.16 +/- 0.08 mg/100 ml (SEM). Throughout infancy and childhood TBG remained significantly elevated (p less than 0.01) compared to a middle age control group of healthy blood donors. T3, T4 and TSH concentrations behaved postnatally as known from previous studies. The T3 and T4 increase observed immediately after birth was not a secondary phenomenon due to changes in TBG concentration since this globulin did not change significantly during this period.


Hospitals in Utah reduce costs, improve use of facilities. A serious problem in rural areas is low occupancy for acute care hospital beds and a desperate need for additional long-term care beds. In Utah, this problem has been solved through the "swing bed" concept. Under this program, underutilized acute care beds can be used for long-term care patients. As a result, all beds are more fully utilized, and long-term care patients in rural areas do not have to be moved to cities.


The histiocytic origin of the multinucleated giant cells in myeloma kidney. A recent case of myeloma kidney disease was studied to determine the cellular origin of the syncytial multinucleated giant cell. Light, immunofluorescence, and electron microscopy of the giant cells revealed features characteristic of histiocytes. This finding contradicts the generally accepted conclusion that the giant cell represents a syncytial mass of degenerating or reactive tubular epithelial cells. We conclude that the giant cells arise in the interstitial tissues, migrate through breaks in the tubular basement membrane, and engulf and surround intratubular protein casts.


Genetic control of the immune response to ferritin in F1 hybrid mice. The immune response to the antigen horse spleen ferritin, has been investigated in ten inbred parental strains and seven different F1 hybrid strains of mice, using an antigen excess technique. The degree of dominance in an F1 hybrid system can be estimated by using the Fisher dominance index. The responses in F1 hybrid animals, obtained from crosses of high and low responder parents, varied from dominant to recessive but the overall mean dominance index for the ferritin immunogenetic system was found to be -0.0467 +/- 0.0083 (mean +/- s.e.), a value close to zero, which suggests a codominant mode of inheritance of IR-genes to ferritin and this is consistent with most published data in other F1 IR-gene systems.


Some effects on leukaemic B lymphocytes of antibodies to defined regions of their surface immunoglobulin. During the growth of the L2C leukaemia in strain 2 guinea-pigs there is excreted in the urine a monoclonal light chain of lambda class. This is believed to arise from synthesis by the leukaemic cells of a small molar excess of the light chains incorporated into their surface IgM. Antibodies to this light chain have been raised in rabbits and separated by immunosorption into those directed against idiotypic determinants (anti-Id), and those against determinants also present on other lambda chains (anti-lambda). Both antibodies react with L2C cells via the surface immunoglobulin. In accord with prediction anti-Id is specific for L2C cells while anti-lambda also reacts with 7 per cent of normal nodal lymphocytes. L2C cells are agglutinated strongly by anti-Id, weakly by anti-lambda. Both antisera inhibit migration of the cells, and both can kill them by invoking complement or K-cell cytotoxic mechanisms. The results emphasize the potential of anti-idiotype sera for identifying and specifically attacking neoplastic B lymphocytes.


Allograft cytotoxicity. Two populations of effector cell detectable by cytolytic and cytostatic assays in vitro. Using both the 51Cr-release assay to measure cytolysis and the [125I]UdR incorporation assay to detect cytostasis of target cells, two different effector populations have been identified in C57BL10 mice primed to P815Y cells. As expected, the cytolytic cells were T cells possessing a specific surface receptor. After elimination of T cells with specific antisera and complement the cytostatic effector was found to be an adherent cell which lacked an immunologically specific receptor, and exerted significant activity against the C57BL lymphoma, EL4.


The incomplete anti-Rh antibody agglutination mechanism of trypsinized ORh+ red cells. The capacity for binding to trypsinized and non-trypsinized ORh+ red cells, of the IgG incomplete anti-Rh antibody and its F(ab')2 and Fc fragments has been investigated. An analysis has also been made of the capacity of non-specific human IgG, aggregated non-specific human IgG, human IgM (19S) and IgM (7S), and of fragments Fcgamma, Fcmu and Fc5mu to inhibit the agglutination of trypsinized ORh+ red cells by the IgG incomplete anti-Rh antibody. The results obtained indicate that these antibodies behave in a similar manner to that of nonprecipitating antibodies, and that the agglutination of trypsinized red cells seems to be a mixed reaction due to the interaction of an Fab fragment with its Rh antigenic determinant present in the surface of a red cell and the Fc of the same molecule with a receptor for Fc present in adjacent red cells. The trypsin treatment apparently results in the liberation of occult Fc receptors. It has also been demonstrated that in the agglutination of ORh+ red cells by IgG incomplete anti-Rh antibody in the presence of albumin, interaction must occur in some manner between the albumin and the Fc fragment since the F(ab')2 fragment does not give rise to agglutination under such conditions.


Opsonic requirements for staphylococcal phagocytosis. Heterogeneity among strains. Efficient phagocytosis of staphylococci by human neutrophilis is dependent on bacterial opsonization by serum factors. These factors include specific antibodies as well as components of the classical and alternative complement systems. In this study the opsonic requirements of three strains of S. aureus and three strains of S. epidermidis were investigated by incubating [3H]thymidine-labelled bacteria in sera with different opsonic activities and measuring rates of phagocytosis by human neutrophils. Opsonization of S. aureus Cowan I and 502 A depended primarily on activation of the classical complement pathway. Effective opsonization occurred in the absence of immunoglobulin but not in the absence of complement. A protein A deficient mutant of S. aureus Cowan I was poorly opsonized in the absence of IgG, however. S. aureus Wood 46 and two strains of S. epidermidis were opsonized primarily through the alternative complement pathway and depended on the presence of serum IgG. A third S. epidermidis strain was efficiently opsonized in heat-inactivated serum without complement activity. Thus, a heterogeneity of opsonic requirements was found among staphylococcal strains. It is proposed that cell wall protein A may be an important determinant of this heterogeneity.


[Nitrogen balance and plasma amino acids in premature and newborn infants with partial parenteral feeding during the first 3 days of life]. Eight pre-terms, five with postnatal asphyxia, two hypotrophic newborns and one term infant with severe postnatal asphyxia (mean birth weight 2317 g) were fed in addition to oral nutrition partialy parenterally with glucose solution and a mother-milk adapted amino-acid solution during their first three days of life. At increasing protein supplies with a parenteral share of more than 50% during the three days, the N balances resulted positive on all days although the calories supplied were far below the postulated optimum. On days two and three N retention was about 60% of the supply. Every four hours after discontinuation of the total 16 hours' amino-acid infusion the amino acid levels in plasma were controlled by means of column chromatography. The resulting mean values did not show any imbalances of the amino-acid homeostasis. The maximum mean loss in weight of the present group was 4% of their birth weight during the first ten days of life and thus equalled the loss in weight of normal, healthy pre-terms. Clinical and chemical paramters did not reveal any disadvantageous side effects of parenteral nutrition.


[The serum level of substances to be excreted in the urine and the acid-base equilibrium after parenteral feeding]. By the present study it was demonstrated that the administration of an amino acid solution containing 20 essential and non-essential amino acids (Aminoplasmal L) together with a fat emulsion (Lipofundin S) and a full electrolyte solution with 10% dextrose (Sterofundin G-10) do not give rise to an increase in creatinine, uric acid, urea and bilirubin in the serum during an observation time of 11 hours.


Immunological response to infection with human reovirus-like agent: measurement of anti-human reovirus-like agent immunoglobulin G and M levels by the method of enzyme-linked immunosorbent assay. The report describes the development of an enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies against the human reovirus-like agent of infantile gastroenteritis (HRVLA). This ELISA system proved to be four times as sensitive as the standard anti-HRVLA fluorescent-antibody assay and ten times as sensitive as the standard anti-HRVLA complement fixation assay. In addition, the ELISA was capable of determining immunoglobulin G (IgG) and IgM subclasses of anti-HRVLA antibody using a single dilution os serum. With this assay, it was discovered that 11 of 21 infected children had anti-HRVLA IgM in their acute sera before the appearance of anti-HRVLA IgG. ELISA is a useful tool in the evaluation of immunological response to HRVLA infection.


Impaired chemotactic responsiveness of macrophages from gnotobiotic rats. Peptone-induced macrophages obtained from gnotobiotic (GB) rats responded poorly to chemotactic stimuli that have a powerful, attractive influence upon the cells of conventional donors. Monocyte recruitment from the circulation into peptone-induced exudates also was impaired in GB subjects. Although relatively more resident cells are present in exudates borne by GB donors, their number cannot in itself account for the sluggish response of peptone-induced cells from GB rats. Neutrophil accumulation in the inflamed peritoneal cavities and their responsiveness in vitro were similar in GB and conventional rats. The levels of serum-derived chemotactic factors were similar in such animals. Furthermore, germ-free rats exhibited no obvious defects in their capacity to generate lymphocyte-dependent monocyte chemotactic activity in situ upon specific stimulation with Listeria monocytogenes. It is suggested that the diminished chemotactic responsiveness of exudate macrophages is related in some way to the level of cell activation. This state of affairs might account for the impairment of delayed-type hypersensitivity in GB animals and their inability to resist intracellular bacterial infections.


Host defenses in experimental scrub typhus: genetics of natural resistance to infection. Genetic resistance to lethal infection with Rickettsia tsutsugamushi was studied in over 30 inbred strains, inbred hybrids, and outbred stocks of mice. Inbred mice infected intraperitoneally with the Gilliam strain of R. tsutsugamushi showed three patterns of response: susceptible (A/HeJ, C3H/HeDub, C3H/HeJ, C3H/HeN, C3H/St, CBA/J, DBA/1J, DBA/2J, and SJL/J), resistant (AKR/J, BALB/cDub, BALB/cJ, C57BL/6J, C57L/J, and SWR/J), and selectively resistant (A/J). The selectively resistant pattern was characterized by random deaths occurring throughout the titration range and was also observed in three of the six outbred mouse stocks surveyed. No correlation was evident between the H-2 haplotype of inbred mice and their response to Gilliam infection. The progeny from five different Gilliam-resistant by Gilliam-susceptible inbred parental crosses were all resistant. Study of F(1), F(2), and parental backcross generations of BALB/cDub (resistant) and C3H/HeDub (susceptible) hybrids indicated resistance was dominant and was controlled by a single gene or a closely linked cluster of genes that were autosomal and not linked to coat color. The resistance of BALB/cDub mice was not due to an inability of host cells to support rickettsial growth, since C3H/HeDub and BALB/cDub embryo cell cultures supported similar growth of Gilliam organisms. C3H/HeDub mice, although susceptible to intraperitoneal Gilliam infection, were capable of mounting an immune response to Gilliam antigens, since subcutaneous infection was not lethal and did protect animals against subsequent intraperitoneal challenge with either the Gilliam or Karp strains of R. tsutsugamushi.


Purification of Pseudomonas aeruginosa proteases and microscopic characterization of pseudomonal protease-induced rabbit corneal damage. Extracellular proteases of three cornea-virulent strains of Pseudomonas aeruginosa were isolated by sequential ammonium sulfate precipitation, Ultrogel AcA 54 gel filtration, and flat-bed isoelectric focusing. The purity of the preparations was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis , thin-layer isoelectric focusing in polyacrylamide gel, immunodiffusion and immunoelectrophoretic procedures, and tests for the presence of other known pseudomonal products. Light and electron microscopic examination of rabbit corneal lesions observed 4 to 6 h after the intracorneal injection of submicrogram amounts of the proteases revealed: (i) degeneration and necrosis of epithelium, endothelium, and keratocytes, (ii) infiltration, degeneration, and necrosis of polymorphonuclear leukocytes, (iii) loss of the characteristic weblike pattern, colloidal iron staining, and ruthenium red staining of the stromal proteoglycan ground substance, (iv) dispersal of strucutrally normal appearing collagen fibrils, ground substance, (iv) dispersal of structurally normal appearing collagen fibrils, and (v) accumulation of plasma proteins and fibrin in the necrotic corneas. These structural alterations are very similar to those observed previously during experimental P. aeruginosa keratitis, and this similarity supports the idea that pseudomonal proteases are responsible, at least in part, for the rapid and extensive liquefaction necrosis characteristic of pseudomonal-induced keratitis. In addition, the results support the idea that pseudomonal proteases elicit severe corneal damage by causing the loss of the corneal proteoglycan ground substance, thus resulting in dispersal of undamaged collagen fibrils, weakening of the corneal stroma, and subsequent descemetocele formation and corneal perforation by the anterior chamber pressure.


Biochemical characteristics of typhus group rickettsiae with special attention to the Rickettsia prowazekii strains isolated from flying squirrels. Six strains of Rickettsia prowazekii, two derived from human infections and four isolated from flying squirrels, two strains of R. typhi, and the single available strain of R. canada, were characterized by several biochemical procedures. The electrophoretic patterns on polyacrylamide gels of rickettsial proteins solubilized by sodium dodecyl sulfate revealed several species differences, but strains of the same species appeared to have identical patterns. Cytoplasmic fractions of the rickettsiae were examined for enzymatic activities and for polyacrylamide gel isoelectric focusing patterns. Some species differences were encountered in the activities or ratios of activities of glutamate-oxaloacetate transaminase, glutamate dehydrogenase, and malate dehydrogenase. When polyacrylamide gels were stained for malate dehydrogenase after electrophoresis, a single band became apparent with single extracts or mixtures of two strains of R. prowazekii, but two bands were seen with mixtures of a strain of R. prowazekii and one of R. typhi. The isoelectric focusing patterns of the soluble proteins revealed numerous species differences, especially between R. canada and the other two species, and a few differences among the strains of R. prowazekii. The patterns of the two human strains, Breinl and E(R), differed in at least one location, and both differed from the flying squirrel strains in the displacement of one band. One of the flying squirrel strains, GvF-16, contained a protein band not seen in the other five strains. Despite these minor differences, a striking similarity was revealed by all the biochemical tests performed between the R. prowazekii strains of human and flying squirrel origin.


Inhibition of Neisseria gonorrhoeae by aerobic and facultatively anaerobic components of the endocervical flora: evidence for a protective effect against infection. The ability of aerobic and facultatively anaerobic endocervical flora to inhibit the growth of Neisseria gonorrhoeae in vitro was assayed. Factors influencing the occurrence of inhibitory components of the flora in vivo were evaluated. Endocervical swabs were obtained from 229 women at a local venereal disease clinic. Endocervical flora and N. gonorrhoeae were isolated and identified, and the ability of the flora to inhibit the growth of N. gonorrhoeae was determined by an agar overlay assay. Results revealed the most active inhibitors to be streptococci, staphylococci, and lactobacilli, in that order. Among only those women harboring inhibitory endocervical flora, inhibitory lactobacilli were recovered from fewer women infected with N. gonorrhoeae than uninfected women (P less than 0.05). Among women having contact with an infected partner, those who subsequently developed gonorrhea were less likely to have inhibitory lactobacilli than those who did not become infected (P less than 0.05). No other significant differences in the composition of the inhibitory flora were noted between infected and uninfected women. During the 2 weeks following menses, recovery of inhibitory lactobacilli on culture was highest, whereas recovery of N. gonorrhoeae was lowest. These observations suggest that the presence of certain lactobacilli may reduce risk of acquisition of N. gonorrhoeae following exposure to infected partners and that the potential protective effect may be greatest during the 2 weeks after menses.


A primate model of allergic bronchopulmonary aspergillosis. Allergic bronchopulmonary aspergillosis (ABA) in man is featured by the presence of IgE skin sensitizing and IgG precipitating antibodies against Aspergillus fumigatus (AF). An animal model of this disease was created. 2 monkeys immunized with AF produced IgG-precipitating antibody. Normal human serum was infused into both immunized and unimmunized monkeys and allergic human serum containing a high titer of IgE against AF was infused into another pair of immunized and unimmunized monkeys. All monkeys then received an aerosol of AF. Lung biopsies were obtained and light microscopic, immunofluorescent and electron microscopic studies were performed. Only the monkey with precipitating antibody to AF who received human allergic serum showed changes which included an interstitial cellular infiltrate containing large numbers of eosinophils, edema of the intra-alveolar spaces, thickening of the alveolar septa, intracellular and interstitial deposits of IgG and IgM and proliferation of collagen fibrils. No evidence of vasculitis was observed. This primate model of ABA should enhance our understanding of the inflammatory response and the immunologic processes in this disease.


Investigation of the reputed inhibition of the Prausnitz-Küstner reaction by the pentapeptide Asp-Ser-Asp-Pro-Arg. An investigation has been made of the inhibitory activity of the so-called Hamburger pentapeptide, Asp-Ser-Asp-Pro-Arg, in both the human Prausnitz-Küstner and baboon passive cutaneous anaphylaxis systems. With a dose of 6 microgram peptide, administered intradermally 24 h prior to diluted allergic serum from a horse-dandruff-sensitive individual, partial inhibition of wealing was observed in three different normal recipients following the pricking in of specific allergen. In one of the recipients, inhibition of flaring was observed at test sites subsequently challenged with timothy grass pollen allergen. A similar dose of pentapeptide, again injected intradermally 24 h prior to passive sensitisation, was shown to inhibit extravasation in a normal baboon on subsequent challenge with horse dandruff (but not grass pollen) allergen by subcutaneous injection into the upper arm. In vivo tests performed in the forearms of grass-pollen-sensitive individuals failed to provide convincing evidence of displacement of mast-cell-bound IgE antibody by the pentapeptide.


Inhibition of allergic reactions by cromoglycate and by a new antiallergy drug U-42,585E. II. Activity in primates against aerosolized Ascaris suum antigen. Immediate type hypersensitivity to Ascaris antigen in Rhesus reactor monkeys was used to assess the pharmacologic profile of cromolyn Na (DSCG) and a new inhibitor of IgE-mediated lung function changes (U-42,585E). Two parameters used to measure lung function, respiratory rate increase and tidal volume decrease, were significantly altered in a dose-related fashion by U-42,585E when the latter was administered either by the intravenous, intrabronchial, or the oral route. Oral activity of U-42,585E was demonstrated with doses as low as 5 mg/kg in Ascaris reactor primates.


Peritoneal anaphylaxis in the rat after sensitization with mouse antiserum. Passive peritoneal anaphylaxis in rats, sensitized with mouse antiserum, had characteristics of an IgE-mediated reaction, in that the serum was heat-labile and pretreatment of the rats with disodium cromoglycate (DSCG), or sodium nivimedone, inhibited the release of both histamine and slow-reacting substance of anaphylaxis (SRS-A). Sodium nivimedone was more potent than DSCG as an inhibitor of histamine release. Peak concentrations of histamine and SRS-A in the peritoneal fluids of the rats, were reached within 2 min of antigen challenge and fell to control levels after 20-30 min.


Activation of complement by radiographic contrast media: generation of chemotactic and anaphylatoxin activities. Iodinated radiographic contrast media such as methylglucamine diatrizoate and sodium ioglycamate activate serum complement in vitro. This was shown by a dose-, time-, and temperature-dependent decrease of total hemolytic complement activity in normal human serum, consumption of C4 and C6 activity, conversion of C3 to C3b, and generation of C5-derived chemotactic and smooth muscle contracting activity. Complement activation was achieved even in sera depleted of immunoglobulin and properdin, which may indicate that contrast media induce complement activation by mechanisms different from the classical or alternative pathway.


Profits in medicine: a context and an accounting. The U.S. health care industry is composed of a dynamic mixture of profit and non-profit entities. These sectors sometimes compete in the same activities and may have virtual monopolies over other activities. Estimates of the relative and absolute sizes and growth trends of the profit and non-profit sectors are developed in this article. These estimates show that approximately 39 percent of total health care expenditures in the U.S. in 1975 went to for-profit institutions, generating $3.3 billion in profit. This represented 7 percent of for-profit and 2.8 percent of total expenditures. Some for-profit subsectors grew more rapidly and others less rapidly than total health care expenditures. As a whole, the for-profit sector grew faster than the non-profit sector before and after Medicare and Medicaid were introduced as well as during the period when price controls were in effect. The relative growth of the for-profit sector was greatest right after the introduction of Medicare and Medicaid. The true significance of profit lies not in numbers, but in the effects that the drive for profit have on the nature and quality of health and health care. This is discussed in the final section.


The political economy of federal health programs in the United States: an historical review. In the 1960s the federal government of the United States added a wide range of new health programs--Medicare, Medicaid, health manpower training, occupational safety, and others--to its long-established support for biomedical research and hospital construction. Total federal health outlays rose from $5 billion in 1965 to almost $37 billion in 1975. This paper describes the legislative history of federal health programs and reports the recent trends in expenditures by functional category. The expenditures of major programs are related to the populations they serve and data are presented to document the enormous inflow of resources to medical care during the last 10 years. This inflow has been induced by the structural changes in the medical care market first set in motion by private health insurance, and accelerated by the new federal programs. Designing some way to control it is a major problem in health policy for the late 1970s.


Biochemical studies on polychlorinated biphenyl toxicity in rats: manipulation by vitamin C. The effects of chronic polychlorinated biphenyl (PCB) compound toxicity on L-ascorbic acid metabolism in rats have been studied. PCB treatment brought about a depression in the activities of the enzymes L-gluonolactone oxidase and dehydroascorbatase along with an increased tissue levels and urinary excretion of L-ascorbic acid. PCB toxicity drastically disturbed the normal histological pattern of the liver cells and also significantly changed the hepatic lipid composition. L-ascorbic acid supplementation to the toxicated group of animals, although could not prevent the growth retardative effect of PCB, could afford a definite protection against the enzyme activity alterations and histological changes as caused by PCB toxicity.


Jejunal diverticulosis.

Jejunal diverticulosis. Diverticulosis of the jejunum is an uncommon condition. We found four patients with such diverticula among 40,341 hospital admissions. All four patients presented with acute volvulus of the small bowel. It is suggested that the diverticula bearing segment becomes heavier due to the diverticula and the semisolid jejunal contents consisting of roughage, millet and cereals in the staple diet of our patients. Both factors contribute to small bowel volvulus. Jejunal diverticula may be missed because they are buried between the leaves of mesentery or adherent loops of jejunum. With a patient has vague abdominal symptoms, the possibility of jejunal diverticula should be considered.


Evaluation of absorbable suture materials in biliary tract surgery. A comparative study of absorbable suture materials in the presence of digestive fluids has been made. At day 7, plain and chromic catgut had lost 81% and 64% respectively of their initial tensile strengths in bile at a temperature of 37 degrees C, whereas Dexon and Vicryl preserved 82+ and 49% respectively of theirs. Plain and chromic catgut are completely dissolved in gastric juice within two days and had lost about 90% of their initial tensile strength in pancreatic juice on day 4. They produce significant tissue reaction. Dexon and Vicryl appear to be similar in their tissue reaction which is minimal. However, the former is stronger than the latter in the presence of bile. We believe the surgeon who undertakes any type of biliary tract surgery may wish to review his choice of absorbable suture material used in view of the information presented herein.


Enzyme activity during the metabolism of glycogen. II. Cytochemical study of glycogen synthetase in the sensory cells of the tuberous organ of Gnathonemus petersii (Mormyridae). Glycogen synthetase (2.4.1.11) forms I (independent or active) and D (dependent or passive) as well as the enzymes active in the transformation of the pathways, protein kinase and phosphatase transferase, were studied in the sensory cells and glycogen rich epidermal cells of the weakly electric fish Gnathonemus petersii (Mormyridae). For light microscopy an indirect cytochemical method which differentiated between glycogen originally present and that produced during incubation in the presence of UDPG was used. This differentiation was obtained by iodine, PAS and alpha and beta amylases. Glycogen synthetase is present in the sensory cells in the I and D forms. The epidermal cells only contain the D form. Protein kinase (active I yields D) has only been found in the sensory cells but phosphatase transferase (active D yields I) has been found in both the epidermal cells and the sensory cells, but only within certain organs. Electron microscopy studies of glycogen synthetase I and D and protein kinase were restricted to the sensory cells only. As with the light microscope it was possible to differentiate between native glycogen and newly formed glycogen. This was done using ultrathin sections and staining with uranyl acetate, lead citrate or by the PATAg reaction. It was possible from these observations to locate precisely the positions of these enzymes. In fact, glycogen synthetase I and D are found both in the sensory cytoplasm and in the sensory cavity with the polysaccharide filaments. Protein kinase is also abundant in the sensory cytoplasm especially in the periphery of the cell near the microvillary border.


Uptake of (methyl-14C)-sisomicin and (methyl-14C)-gentamicin into bacterial cells. Eight sensitive strains (two Staphylococcus aureus, two Escherichia coli, two Pseudomonas aeruginosa and two Klebsiella pneumoniae) and four resistant Pseudomonas aeruginosa strains were used to study uptake of sisomicin and gentamicin by the bacterial cells. In eleven out of the twelve organisms studied employing (methyl-14C)-sisomicin and (methyl-14C)-gentamicin, uptake of the former was found higher that that of the latter. In one organism, the uptake of the two antibiotics was similar. This higher uptake of sisomicin may help explain the superior potency of the antibiotic in relation to gentamicin.


Mode of action of pyocin R1.

Mode of action of pyocin R1. The effects of pyocin Rl on transport systems and syntheses of macromolecules in Pseudomonas aeruginosa strain P14 were studied under two conditions, 0.4 mM and 40 mM Magnesium ions. In the presence of 0.4 mM magnesium ions, the incorporation of [14C]leucine into protein and the uptake of [14C]leucine into the leucine pool were completely inhibited by pyocin. Furthermore, [14C]leucine which had been taken up into the leucine pool was depleted by pyocin. Comparing the concentration of amino acid within cells with that in the medium, it was concluded that the active transport in P14 cells was inhibited completely by pyocin. Such an effect of pyocin Rl on transport systems was not specific to leucine but common to many amino acids and uridine. On the other hand, under the condition of 40 mM magnesium ions, [14C]-leucine once accumulated was not depleted by pyocin, but uptake of [14C]leucine into the leucine pool stopped immediately while incorporation of [14C]leucine into protein continued at a considerably reduced rate; therefore the machinery for protein synthesis was not directly inhibited by pyocin. It is suggested that the loss from the amino acid pool in cells brings about the rapid cessation of protein synthesis under the condition of 0.4 mM magnesium.


Role of the 21,000 molecular weight polypeptide of Bacillus subtilis RNA polymerase in RNA synthesis. DNA-dependent RNA polymerase from Bacillus subtilis contains a 21,000 molecular weight (21K) peptide subunit. This subunit was purified and added to 21K-depleted polymerase isolated from both uninfected and SP85-infected B. subtilis. The effect of the subunit on total RNA synthesis, on enzyme-DNA binding, on RNA chain initiation and elongation, and on enzymatic specificity were examined. A comparison was made of the effects of the 21K peptide and NaCl on polymerase activity, RNA chain elongation, and symmetry of transcription of SP82 DNA. The addition of the 21K peptide to enzyme preparations lacking this subunit stimulated total polymerase activity 20 to 40%. In contrast, addition of NaCl at concentrations greater than 0.1 M significantly reduced polymerase activity. The 21K peptide appeared to alter the general affinity of the polymerase for DNA. The rate of RNA chain initiation was not affected by the 21K peptide, but RNA chain elongation was stimulated. Both the 21K peptide and NaCl increased the asymmetry of transcription of SP82 DNA by phage-modified polymerase. The 21K effect was related to the stimulation of elongation while high concentrations of NCl appeared to act at RNA chain initiation. RNAs synthesized in vitro by polymerase lacking and supplemented with the 21K peptide were translated by a Escherichia coli cell-free system. The 21K peptide had little direct effect on the selection of promoters in vitro as measured by this technique, but it dramatically increased the translatability of the product.


Anti-glycosyl antibodies. Two sets of isoantibodies with specificity for different carbohydrate moieties of the same glycosyl antigen. Two sets of anti-glycosyl antibodies have been isolated by affinity chromatography methods from the antisera of rabbits immunized with a vaccine of nonviable cells of Streptococcus faecalis, strain N. Both types of antibodies are directed against a dineteroglycan of glucose and galactose present in the cell wall of this organism. The members of one set, anti-galactose antibodies, combine with the terminal lactose residues of the glycan and the member of the other set, anti-lactose antibodies, combine with terminal lactose residues of the same glycan. Each set of antibodies is composed of multiprotein components. The electrofocusing method had been used to isolate the individual antibody proteins in homogeneous states as shown by both electrophoresis and ultracentrifugation techniques. Since the components of each set combine with the same structural unit of the antigen, they have been designated as isoantibodies. The sedimentation constants, electrophoretic properties, carbohydrate constituents, and amino acid compositions of the two sets of antibodies are recorded.


Properties of the thioesterase component obtained by limited trypsinization of the fatty acid synthetase multienzyme complex. The fatty acid synthetase from lactating rat mammary gland is shown to consist of two polyfunctional polypeptides of similar molecular weight (about 220,000); a 4'-phosphopantetheine residue is covalently bound to one, or both subunits. Limited trypsinization of the fatty acid synthetase releases on enzymatically active thioesterase component which has been purified and its properties studied. The thioesterase sediments in the ultracentrifuge as a single component of molecular weight 32,000; its sedimentation coefficient is 2.9 x 10-(13) s its diffusion coefficient 5.0 x 10-(7) cm2 s-(1). The thioesterase also elutes from a column of Sephadex G-75 as a single, symmetrical peak of constant specific activity. However, electrophoresis of the denatured thioesterase in the presence of sodium dodecyl sulfate reveals that the enzyme has been partially nicked during isolation. The kinetic data of the enzyme reaction were studied using palmityl-CoA as a model substrate. Solvent pH was found to affect both Vmax and Km (Km = 0.5 micron at pH 6.6, 2.5 micron at pH 8.0) wereas solvent ionic strength affected Vmax but no Km. The thioesterases from the fatty acid synthetases of rat liver and lactating mammary gland have identical physical properties, identical amino acid compositions, and are immunologically indistinguishable. Both thioesterases hydrolyze long chain, in preference to short chain, thioesters of CoA, an observation consistent with their role in regulation of the chain-terminating step in fatty acid synthesis by the parent multienzyme complexes.


Keratin filaments of cultured human epidermal cells. Formation of intermolecular disulfide bonds during terminal differentiation. Human epidermal cells grown in culture synthesize abundant keratins. These keratins are similar to those of stratum corneum of human epidermal callus in their insolubility in dilute aqueous buffers, their molecular weight range of 40,000 to 60,000, their immunolgical reactivity, and their ability to assemble into 80 A tonofilaments in vitro; but there are differences in the molecular weights of some of the proteins, the number of components, and their charge heterogeneity, related at least in part to phosphorylation. About 30% of all the proteins of living cultured keratinocytes consists of keratins, compared with over 85% of stratum corneum. All the keratins of human stratum corneum were found to be cross-linked by intermolecular disulfide bonds while most keratins of the living cells were not. As the cells mature in Methocel-stabilized suspension culture, their keratins become increasingly disulfide cross-linked. When uncross-linked tonofilaments of living keratinocytes are dissolved in 8 M urea and the filaments reconstituted in vitro their keratins become disulfide cross-linked under aerobic conditions and consequently insoluble in solutions of 8 M urea or sodium dodecyl sulfate. The results indicate that the uncross-linked state of the keratins in living cells is due to the reducing intracellular environment and not to a precursor state related to the primary structure of the proteins. The disulfide cross-links stabilizing the keratin filaments must be distinguished from the epsilon-(gamma-glutamyl)lysine cross-links stabilizing the cornified cell envelope.


Purification and properties of the bacteriophage T4 gene 31 protein required for prehead assembly. A low molecular weight (approximately 16,000), early protein is characterized as the product of the essential T4 head assembly gene 31. This gene is known to be required to allow formation of any ordered head structure from the major T4 capsid protein, P23 (Laemmli, U.K., Beguin, F., and Gujer-Kellenberger, G. (1970) J. Mol. Biol. 47, 69-85). In wild type infection P31 synthesis ceases at late times; in contrast, P31 is overproduced in certain early or regulatory T4 mutant infections, particularly gene 55 mutant infections. P31 was purified preparatively from Escherichia coli infected with the latter mutant, but could only be obtained for the most part in modified form, possibly due to unusual sensitivity to a proteolytic activity. P31 is not cleaved in vivo during normal head assembly, nor does it become a part of the mature head or any ordered prehead structure as determined by an immunological assay using antiserum prepared against the purified protein. However P31 does appear to become a part of the unordered P23 aggregates (lumps) which accumulate when ordered P23 assembly is prevented. We cound find no evidence for P31 association with T4 DNA or the host membrane. Our experiments favor the hypothesis that P31 directly affects the aggregation state and solubility properties of P23.


Isolation of 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine from a riboflavin-adenine-deficient mutant of Bacillus subtilis. Studies were carried out to determine possible intermediates involved in the biosynthetic pathway of riboflavin, using resting cells of a riboflavin-adenine-deficient mutant, Bacillus subtilis AJ1988. The cells excreted 6,7-dimethyl-8-ribityllumazine, the end product in the biosynthetic pathway, into the incubation medium in large amounts. The addition of glyoxal caused a large accumulation of a green fluorescent compound; an inverse relation was observed between the formation of the lumazine and the concentration of glyoxal. Furthermore, added [2-14C]guanine effectively incorporated into the lumazine and the fluorescent compound in the same specific activity during incubation. The fluorescent compound was isolated, purified, and identified by paper chromatographic, fluorometric, and spectrophotometric analyses. It was proved to be 8-(1'-D-ribityl)lumazine, which appeared to have been formed by a reaction between glyoxal and a possible intermediate in the cells. Accordingly, 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine was concluded to be an immediate precursor of 6,7-dimethyl-8-ribityllumazine.


Glycoproteins from human colonic adenocarcinoma. Isolation and characterization of cell surface carcinoembryonic antigen from a cultured tumor cell line. Alterations in cell surface glycoproteins have been implicated in malignancy. We examined surface membrane proteins of a cultured cell line, SKCO-1, which had been derived from a human colonic adenocarcinoma. Cell surface labeling of SKCO-1 cells with galactose oxidase, followed by reduction with sodium borotritide, revealed five major labeled glycoproteins upon sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. At least three additional labeled glycoproteins could be detected if galactose oxidase treatment was preceded by neuraminidase treatment. Some, but not all, of the glycoproteins could be iodinated by lactoperoxidase. The predominantly labeled glycoprotein (GPI) had a molecular weight of 200,000 and co-migrated in SDS gel with carcinoembryonic antigen (CEA). GPI was not removed from the cell surface by EDTA, hypertonic saline, or sonication but was released from the membrane by detergents. This glycoprotein was subsequently purified using lectin-agarose columns and gel filtration. GPI was judged homogenous by protein- and carbohydrate-stained SDS-polyacrylamide gels and had an amino acid composition similar to that of CEA. The carbohydrate composition of GPI was qualitatively similar to CEA but quantitatively distinct. GPI had a greater proportion of sialic acid and galactosamine and less fucose and glucosamine than CEA. Immunological studies, however, demonstrated identity between GPI and CEA. A study of the turnover rate of GPI showed it to have a half-life of 5 days.


Kinetics of interaction of heavy and light chains in immunoglobulins. Use of a sulfhydryl-specific light chain fluorescent probe. The fluorescent probe N-(iodoacetylaminoethyl)-8-naphthylamine-1-sulfonic acid (1,8-I-AEDANS) reacts stoichiometrically with the COOH-terminal cysteine residue of a human immunoglobulin light (L) chain. The absorption and fluorescence spectral properties of the L-AEDANS product and the environmental sensitivity of the fluorescence suggest the utility of L-AEDANS in the study of the subtle conformational changes accompanying interactions between light chain and other proteins or ligands. Its applicability to the problem of immunoglobulin assembly is illustrated by the association of L-AEDANS with heavy chain dimers, which results in an enhancement of fluorescence. The data indicate that L-AEDANS binds to kinetically equivalent, noninteracting sites with an apparent second order rate constant of 6 X 10(6) liters mol(-1) s(-1) at 20 degrees, pH 7.5.


Histologic response to porous PMMA implant materials. Poly(methyl methacrylate) as used in polymer replica tooth implants was fabricated into 6 X 6 mm cylindrical specimens and cured in either an air oven, pressure pot, autoclave, or microwave oven. Polymer porosity was achieved by means of either 1) intrinsic foaming agents, or 2) compacting different sizes of large beads with a minimum of monomer, with dense PMMA used as a control. Specimens were then implanted in the long bones of baboons. Histology of thin-sectioned and ground specimens from the sacrificed animals revealed complete tissue ingrowth into implanted material made of medium and large PMMA beads, very superficial ingrowth into material containing foaming agents and anorganic bone chips, and no ingrowth into dense PMMA implants. None of the implants were rejected or caused chronic inflammation. The effect on histologic response of the different curing methods could not be distinguished.


Rat liver nuclear skeleton and ribonucleoprotein complexes containing HnRNA. Rat liver nuclei deprived of chromatin and nucleoplasm show a spongelike network which preserves its connection with nucleoli, the inner membrane of the nuclear envelope, and nuclear pore complexes. It contains all of the HnRNA, provided the endogenous proteolytic activity is inhibited by a proteolytic inhibitor such as phenylmethyl sulfonyl chloride (PMSC) or the fluoride form (PMSF). In the absence of these proteolytic inhibitors, HnRNA is dissociated from the spongelike network and sediments in a sucrose gradient as polydispersed ribonucleoprotein complexes. Furthermore, purified HnRNA as well as rRNA do not bind to the spongelike network when added to these nuclei. These observations demonstrate that the association of HnRNA to the nuclear skeleton is not an artifact. RNase treatment of the spongelike network digests the majority of the rapidly labeled RNA but does not alter the morphological aspect nor the architecture of this network. EDTA and heparin treatments affect neither the attachment of HnRNA nor the structural organization of this network. Electron microscope studies of the network reveal a characteristic flexuous configuration. Its relationship with diffused and condensed chromatin is discussed.


Modified culture technique for Corynebacterium diphtheriae isolation from desiccated swabs. Corynebacterium diphtheriae was isolated from pyoderma and ulcerative skin lesions with a modified delayed culture procedure as late as 9 weeks after field collection of silica gel-desiccated swabs. Biotypes gravis and mitis were identified. Most isolates were nontoxigenic. Todd-Hewitt broth enrichment enhanced recovery of C. diphtheriae by 70%.


Survey for positive Limulus amoebocyte lysate test in plasma from humans and common research animals. A survey for positive Limulus amoebocyte lysate tests was conducted on apparently healthy humans, mongrel dogs, rats, mice, rabbits, and squirrel monkeys. Only mongrel dog (45.8%) and human (32.8%) plasma samples gave positive tests. In dogs, a significant correlation between positive Limulus amoebocyte lysate tests and the presence of intestinal parasites was found. Positives found in human plasma samples were thought to be due to the presence of background levels of endotoxin or some possible mimicker substance found in the plasma after chloroform extraction. It was concluded that there was a need to distinguish between these positive Limulus tests and those which represent significant endotoxemia.


Relationships between mean velocity of circumferential fiber shortening (VCF) and heart rate - the diagnostic value of a normalization of VCF to heart rate. Previous studies relating mean velocity of circumferential fiber shortening (VCF) to heart rate suggested a linear correlation. Since there is considerable variability in the heart rate of normal subjects and in patients with myocardial disease, a normalization of VCF to heart rate could possibly increase the reliability of this echocardiographic parameter of myocardial function. In 106 normal subjects, a linear correlation between VCF and heart rate was confirmed (r=0.87). Values normalized to an arbitrary heart rate of 60/min by the calculated regression were called "relative velocity of contraction" (RVC). Because of the independence of RVC from heart rate, the RVC shows an obviously smaller physiological variation than VCF. Two hundred seventy-six patients were grouped and classified according to hemodynamic and angiographic parameters. These parameters correlated closer to RVC than to VCF. In addition, RVC gave definitely superior diagnostic information in separating patients with cardiac abnormality from normal individuals than did VCF.


Television synchronization of a real time ultrasonic sector scanner. The interaction of the scan rates of ultrasonic scanning and television recording systems often causes portions of the resultant television image to be either over- or under-scanned. This results in objectionable bright and dark sectors within the ultrasonic image on a television monitor during single-frame playback. The usual method for dealing with this problem is to exchange time resolution for image quality when preparing pictures for analysis or presentation. Time resolution can be preserved by operating the ultrasonic scanner at a scan rate one-half of the television frame rate and phase locking the ultrasonic scanner to the television system so that each angular scan of the ultrasonic system is initiated coincident with the beginning of each television frame.


The dynamic uterus revealed by time-lapse echography. The dynamic aspects of the uterus have hitherto gone unrecognized by ultrasonographers. The inherent contractility of the uterus produces dynamic artifacts on static echograms that may lead to serious misdiagnoses. Four cases are presented which illustrated these dynamic changes. Time-lapse echography is proposed as a method of assessing uterine dynamics and improving diagnostic accuracy.


Ultrasonography in the management of unexplained renal failure. A series of seven cases of acute renal failure is presented in which sonographic study of the kidneys provided diagnostic information not otherwise obtainable. Ultrasonic imaging should be among the first diagnostic procedures applied in cases of acute unexplained renal failure because it provides rapid answers to the most urgent management problems--whether there is an obstructive component, and what is the potential for recovery.


Water enema: a new ultrasound technique in defining pelvic anatomy. A new technique is described for delineating pelvic structures by using a distended bladder in combination with a water enema. The distended urinary bladder, which acts as a sonic window to the pelvis, fully defines only the portion of structures that abut against the surface. With fluid in both the bladder and rectosigmoid colon, and occasionally the cecum, a 'sandwich effect' can be obtained, resulting in a more complete definition of interposed structures. Questionable masses that might be feces in the bowel can be easily distinguished from significant pathology. This new technique has the potential for increasing accuracy of diagnosis of pelvic masses and delineating tumor extension of masses arising in such pelvic organs as the bladder, prostate, and uterus.


Cross sectional visualization of the normal heart by the UI Octoson. The UI Octoson can provide accurate compound and simple scan cross sectional views of the heart. Sections taken in the transverse, sagittal, and other planes normal and parallel to the long axis of the heart are useful for providing full information that may be obtained by the examination. The views allow the visualization and measurement of most major structures of the heart, giving a more complete description of the geometry of the heart.


A comparison of the "phrygian cap" deformity with bistable and gray scale ultrasound. Sixteen patients with a "phrygian cap" deformity of the gall bladder seen with oral cholecystography were further evaluated with both bistable and gray scale ultrasound. The bistable technique produced internal echoes that were suspicious of gall stones. When this same area was reevaluated with the more accurate gray scale technique, the folded-fundus deformity was clearly visualized.


Ultrasonic examination of orbital vasculature. Patients with orbital varices form a diagnostically important group of those referred for ultrasonic study of orbital proptosis. Two cases are presented in which diagnosis of dilated orbital blood vessels was established by B scan ultrasonography. The echographic appearance of normal and dilated orbital vessels is discussed.


False placenta previa: a clinical observation. A misleading appearance of placenta previa was observed in three sonographic examinations of pregnant women. In these women the fetuses were in a transverse lie and the placentas were implanted on the anterior uterine wall. In these circumstances it appears possible for the lower anterior portion of the uterine wall and the attached portion of the placenta to falsely simulate placenta previa.


Antenatal diagnosis of congenital chylothorax by gray scale sonography. In a patient with hydramnios, fetal hydrops was diagnosed by B mode ultrasound. Gray scale sonography visualized fluid in the fetal pleural cavity. The diagnosis (congenital chylothorax) was confirmed at autopsy.


Echocardiographic assessment of a Blalock-Taussig shunt. A case of echocardiographic confirmation of the patency of a Blalock-Taussig anastomosis is presented. Using the left atrium-to-aortic ratio (LA/Ao), we could document an increase in left atrial size representing an increase in pulmonary blood flow. This is the first report using echocardiography to prove the patency of a systemic-to-pulmonary artery anastomosis.


Sporicidal activity of mixtures of alcohol and hypochlorite. In an investigation of the activity against Bacillus subtilis spores of various mixtures of alcohol and sodium hypochlorite 50% methanol with enough hypochlorite to provide 2000 parts per million available chlorine water was the most sporicidal. This mixture, both when freshly prepared and for at least eight hours after mixing, achieved a five-log reduction in spore count in 10 minutes. The sporicidal activity of mixtures containing the same initial level of available chlorine was found to vary with the alcohol, initial alcohol concentration, and age of the mixture. Such mixtures may be useful for disinfecting heat-sensitive instruments.


Identification of clinical isolates of Neisseria gonorrhoeae by a coagglutination test. Ninety-eight per cent of laboratory isolates of Neisseria gonorrhoeae from a veneral disease clinic gave positive reactions with a gonococcal coagglutination test. The prototype reagent, however, was poor at distinguishing between different species of the genus Neisseria: 75% of strains of Neisseria meningitidis and 40% of other Neisseria species tested gave positive reactions. None of the origanisms other than Neisseria growing on the diagnostic cultures from the clinic gave positive reactions. We therefore suggest that the present reagent is unsuitable for testing isolates from the upper respiratory tract. The technique is simple, rapid, and convenient and with a more specific antibody could be useful. Results of coagglutination reactions of 126 strains of Neisseria grown on serum-containing and serum-free media were very similar and there is no need to use special serum-free media.


The qualitative evaluation of airway responses to immunologic and pharmacologic stimuli in rhesus monkeys. This report describes the current status of a colony of rhesus monkeys composed of a group of animals with consistent asthmatic responses to Ascaris antigen challenge, a variable group and a negative group. The cumulative experience with the consistent group of 5 animals totals 144 months of observation with 86 positive respiratory responses to 86 aerosol challenges. Further studies compare rhesus airway responses to Ascaris antigen, anti-IgE, histamine, prostaglandin (PG)F2alpha, carbocholine, and physostigmine. We report that two abnormalities of pulmonary function which occur as a result of aerosol challenge, an increase in breathing frequency (f) and pulmonary resistance (PR), differ in degree of abnormality and time of onset following challenge with different agonists. These results indicate that the f and PR changes in response to these agonists are controlled by different physiologic mechanisms in rhesus monkeys. We suggest that the f changes may occur as a result of reflex afferent vagal stimulation and PR changes as a result of direct effect on smooth muscle receptors. The effect of histamine and PGF2alpha on the airway of rhesus monkeys more closely simulates the airway response to immunologic stimuli than does the effect of cholinergic type agonists.


Medical direction in long-term care.

Medical direction in long-term care. This report presents the views of over 1000 administrators, nurses and physicians with respect to the responsibilities, authority and impact of the medical director in a long-term care facility (LTCF), as well as the nature and future of long-term care and geriatric medicine in the USA. Nurses, administrators and physicians were more able to agree on the bureaucratic functions of the medical director than on the functions which might be considered more clinical or activist in terms of the total needs of the LTCF. There was no consensus about the external factors which might determine the future of LTC, i.e. alternatives to institutionalization, public attitudes or community hospital relations. Instead, concern seemed to focus upon the "low level" of funding for LTC. With respect to the nature of LTC itself, most respondents felt that the area was clinically challenging. However, only 40 percent of the physicians believed that clinical skills were more important than a sympathetic regard for patients. As a corollary, physicians were the least supportive of geriatrics as a new specialty in medicine.


Mortality of the aged with chronic brain syndrome: further observations in a five-year study. In order to pursue the question of excess mortality due to chronic brain syndrome (CBS), 330 residents of a home for the aged were independently evaluated prior to admission by psychiatrists and by general physicians. Five years later, their medical records were searched to determine: 1) age on admission, 2) diagnosis of CBS on admission, 3) physical status on admission, and 4) if death had occurred, the age at death and the cause of death. Women outnumbered men by 3:1. Subjects with CBS outnumbered those without CBS by 2:1. A previous mortality study on 145 aged subjects at the same institution provided an excellent frame of reference for this investigation. Among the men there was no difference between the mortality rates for those with CBS and those without. Among the women a statistically significant difference in mortality was found between those with CBS and those without. Women with CBS and a "poor" physical status had the highest mortality rate. Those who initially had CBS died significantly sooner even if their admission physical status had been "good." Their mortality rate exceeded that for women with a "poor" physical status who did not have CBS. Bronchopneumonia caused death twice as often in subjects with CBS as in those without CBS, both among men and women. It is concluded that CBS per se is a significant factor in increasing mortality in the aged.


The effect of devascularization on the regeneration of lacerated peripheral nerves: an experimental study. The functional, biochemical, and histological changes in a severed median nerve, 9 months after epineurial repair, were studied in 14 monkeys. In seven the mesoneurium had been stripped 5 cm proximal and 5 cm distal to the site of repair, and in seven the nerve had been stripped only over a 0.5 cm area, just enough to allow repair. In the first group the mean muscular strength in the abductor pollicis brevis was 197 gm, as compared to 257 gm in the second group. The amount of collagen in the perineurium was 57 microgram/mg, as compared to 43 microgram/mg, and the incidence of the h-l-h-nl cross-link was 16% to 21%, as compared to 9% to 11%. If the regeneration of the lacerated nerve was compromised by the deposition of collagen resulting from mobilization of the distal segment, as suggested by the decrease in the strength of the abductor pollicis brevis muscle, then any mobilization of a nerve necessary to obtain a sutured junction with minimum tension should be limited to the proximal segment.


Prevalence of Bacillus cereus in the faeces of healthy adults. In a survey designed to determine the prevalence of Bacillus cereus in the faeces of healthy persons, the organism was found in low numbers in 100 (14%) of single faecal specimens from 711 adults in the general population. In addition, in an attempt at assessing the changes in the B. cereus distribution within the faecal flora of the individual, weekly faecal specimens were submitted over a seven-week period by 18 members of staff of two laboratories. The total isolation rate was again 14%, with 15 serotypes represented. In four individuals B. cereus was isolated in two consecutive weeks and in all cases the isolates were of different serotypes. Excretion was never recorded for more than two consecutive weeks. These findings probably reflect the intake of B. cereus in the individual's diet.


Leukocyte complement: assembly of the membrane attack complex of complement by human peripheral blood leukocytes in the presence and absence of serum. The specific neoantigenic determinants (neoAg) that are indicative of the assembled C5b-9 C complex are generated on the surface of peripheral blood leukocytes (PBL) during collection and processing of blood. Formation of neoAg on PBL could be prevented by collecting blood directly into 20 mM EDTA and, could be induced in vitro by adding autologous serum to isolated PBL that lacked neoAg. When neoAg was induced by the addition of serum containing 125I-labeled C8, the C8 was incorporated into a 23S complex which could be eluted from PBL. A mechanism for neoAg formation on PBL independent of exogenous serum factors was detected when PBL were placed into culture in serum-free medium. Results with metabolic inhibitors and 14C-leucine suggest that PBL can synthesize C5 and assemble the C5b-9 complex. The possible relevance of these findings to the understanding of mechanisms of cell-mediated cytotoxicity is discussed.


The chromosome complement of an Aotus hybrid. Two divergent haploid chromosome sets were encountered in the chromosome complement of laboratory-born Aotus. Comparison of G-banded chromosomes of this individual with seven other established G-banded Aotus karyotypes revealed that this monkey is a hybrid offspring of two allopatric chromosome races (Brazilian Aotus X Colombian Aotus).


Immunoquantitation of free light chain immunoglobulins: applications in multiple myeloma. A single radial immunodiffusion (RID) assay for the free lambda (lambda) and kappa (kappa) light chain (LC) immunoglobulins was developed for study of clinical samples of serum, urine, and bone marrow of patients with multiple myeloma. Using highly specific rabbit anti-LC sera, we were able to quantitate: (a) free serum LC after fractionating the serum sample using an Amicon ultrafiltration chamber equipped with an XM100A diaflow membrane and an 125I-LC standard for calculating filtration efficiencies, (b) directly, Bence Jones (BJ) proteins in the urine, and (c) the in vitro LC synthesis by myeloma plasma cells obtained from bone marrow aspirates. The median values of free LC levels in sera (n = 12), urines (n = 25), and marrow culture synthetic rates (n = 17) were 116.2 mg/dl, 0.775 g/day and 15.3 pg/plasma cell/day, respectively. These data were useful in initial evaluation of patients and serial follow-up studies. The assays have also been of use in our research on the determination of total body tumor mass in patients with BJ multiple myeloma.


Effect of pemphigus antibodies on desmosomal structure in vitro. Changes in desmosomes were noted in nonacantholytic regions of skin explants cultured in the presence of intercellular antibodies. These changes included dissociation of desmosomes, as well as a "selective loss" of desmosomal components in one or both of neighboring cells.