Interdisciplinary health care: part I.

Interdisciplinary health care: part I. The development of the Health Care delivery system has been unorganized and fragmented. A need to integrate the various health care components is essential and a discussion of interdisciplinary health teams is presented as one model to alleviate these problems. Part I will discuss the historical parameters and the philosophical components of health care. Part II will present the problems and inherent possibilities of health teams. Part III will include a review of the Interdisciplinary Health Teams course at the University of Houston, College of Optometry.


The contact lens--part 3.

The contact lens--part 3. The patient adapting to contacts, the overwearing syndrome, the lens surface and edges, the foreign body, the traumatized eye, the ocular/lid infection, and the allergy can all exhibit many similar symptoms. The innocent contact lens is often held accountable for problems that have their etiology in diametrically opposed areas.


Complications of the Austin-type bunionectomy. The California College of Podiatric Medicine has evaluated the complications encountered in the Austin-type bunionectomy and compiled the following list of possible causes: 1) improper preoperative criteria, 2) incorrect angle between arms of the V-osteotomy, 3) incorrect direction of the osteotomy on the transverse plane, 4) removal of too little or too much bone medially in a bi-correctional procedure, 5) transposition of capital fragment too far laterally, 6) failure to remove medial wedge at least 80% through the head, 7) placement of V-osteotomy in cystic or osteoporotic bone, and 8) improper instrumentation. Dr. Gerbert believes that the use of templates preoperatively will minimize the number of complications.


Liposarcoma of the foot: a case report.

Liposarcoma of the foot: a case report. A 56-year-old black, apparently healthy female presented with a rapidly growing mass on the medial aspect of her left hallux. The mass was seen on x-ray examination, and did not appear locally invasive. Excision revealed the mass to be a well differentiated liposarcoma, and after further consultation, the left hallux was amputated. Although the incidence of differentiated liposarcoma in the foot is rare, the preceding case should reiterate to all the need for closer investigation of soft tissue masses which may appear in the foot. Prompt excision of malignant tumors results in a good prognosis for the patients, whereas misdiagnosis based on the apparently benign appearance may lead to unnecessary delay and a less fortuitous prognosis for the patient.


Hypoglycemia: clinical significance and management during foot surgery. Hypoglycemia, an abnormally low level of glucose in the circulating blood, is discussed in this paper. Dr. Kaner describes the clinical significance, signs, symptoms, and etiology, as well as the evaluation and management during pre- and postoperative foot surgery. Although there is no direct relationship between hypoglycemia and foot pathology and it is not generally a contraindication to elective foot surgery, the disease must be correctly evaluated preoperatively and properly managed before, during, and after the surgical procedure.


Policy, politics, and child health: four decades of federal initiative and state response. This paper analyzes the continuity and change in the relationship between federal and state governments in the formation and implementation of child-health programs. After reviewing developments in federal child-health policy since the Sheppard-Towner Act of 1923, methods of implementation and changes in state laws and administrative organization in Vermont and Connecticut are compared with a focus on the major programs authorized by Title V of the Social Security Act. Four broad interactive areas of comparison--governmental relations, program delivery systems, expenditure patterns, and private interests--serve as vantage points for exploring, understanding and explaining the process of policy implementation. Specific conclusions are drawn regarding each area and the overall conclusion is that federal efforts under Title V have not lessened the general neglect of child health in state legislation; nor have they greatly expanded the volume of direct services for child care. They have been sufficiently ambiguous and diffuse to leave the providers dominant, treating diseases and existing conditions rather than focusing energy on preventive measures. Federal resources have been absorbed by expanding administrative overhead, state bureaucracies have been inflated rather than motivated.


A model for the coordination of international donor activities with national government health services. This study is a descriptive analysis of an attempt to coordinate donor agency and government activities in the national leprosy control program of the Philippine Islands. A twofold strategy is employed to realize this purpose: (1) the evolution of the present coordinated program as recorded in both published and unpublished documents is described, and (2) an opinion survey of Philippine personnel active in the present leprosy control program is reported. The most significant finding, in terms of relating the Philippine experience to other areas of donor-recipient exchange, is the emergence of a model of coordinated effort where a donor agency's assistance to a foreign national government is transmitted through a third indigenous and intermediary organization. By advancing the interests of both donor and recipient organizations, this approach has the potential of promoting a successful coordination of activities which might not otherwise be attained.


Chromium concentration by proximal renal tubule cells: an ultrastructural, microanalytical and cytochemical study. After treating rats with potassium bichromate, x-ray microanalysis of the proximal renal tubule cells demonstrated the presence of chromium in intracellular vacuoles. The lysosomal nature of these vacuoles is shown by the visualization of acid phosphatase activity. Chromium is concentrated both in the autolytic vacuoles and in their residual forms. The metal is eliminated quite late, concomitant with cellular necrosis.


An improved acriflavine-Feulgen reagent for quantitative DNA cytofluorometry. We have modified the acriflavine-Feulgen histochemical method for the quantitative determination of DNA by performing the staining of hydrolyzed cells affixed to cover slips with acriflavine dissolved in 90% ethanol. Compared to conventional techniques, in which the acriflavine is dissolved in aqueous HCl plus potassium metabisulfite, this method not only decreased non-Feulgen (background) staining in both the nucleus and the cytoplasm, but also increased the fluorescent intensity of Feulgen stained nuclei more than four-fold. Cells stained by our modified method exhibited a fluorescence maximum of 507 nm, which is similar to the 500 nm fluorescence maximum obtained with acriflavine bound to apurinic acid solution by a modification of the acriflavine-Feulgen method. These fluorescence maxima are in contrast to the 510 nm to 625 nm fluorescence maxima which are obtained when cells are stained according to conventional protocols. The fluorescence intensities of nuclei of synchronized cells stained by the modified method were proportional to DNA content. Thus, by the criteria of staining specificity, in situ and in solution fluorescence spectra agreement and quantitative staining, we conclude that our modified acriflavine-Feulgen method is more satisfactory for quantitatively measuring DNA in situ by cytofluorometry than the usual acriflavine-Feulgen method.


The use of polyethyleneimine for demonstration of anionic sites in basement membranes and collagen fibrils. Strong cationic polyethyleneimine (PEI) is used to trace anionic sites in lung, choroid plexus, glomeruli, blood vessels and also on collagen fibrils. In the mentioned tissues, PEI is found in the basement membranes with a spacing identical to that found on collagen fibrils. It is assumed that the acid endgroups of tropocollagen molecules are responsible for the binding of PEI.


[Fluorescence histochemistry and neurohistologic studies of the adrenergic innervation of the pyriform cortex in the rat]. The pyriform region of normal adult rats was investigated by fluorescence histochemistry and Golgi-rapid-impregnation technique. Fluorescence microscopically noradrenaline and dopamine fibers could be described in typical arrangement and distribution. It is suggested that various Golgi-"beaded" -axons in the cortex pyriformis may be equivalent to the fluorescence histochemically demonstrated varicose  catecholamine axons. This would raise the possibility of interpreting, in the Golgi impregnation technique, kinds of axons in a functional manner.


The tectum opticum of Pantodactylus schreiberii Wiegmann (Teiidae, Lacertilia, Reptilia). We study the histology of the optic lobe of Pantodactylus schreiberii Wiegmann. It has 14 layers with characteristic cells in each of them. We study with emphasis the elements of the superficial layers, discussing some physiologic implications. We described four strata of optic terminals. To the strata 1 and 3 reach fibres from layer 14. To the stratum 4, from the layer 12 and to the stratum 2, fibres from both layers 14 and 12. Some optic fibres from layer 12 send collaterals which reach the stratum 4 of optic terminals.


The distribution of axon terminals with flattened vesicles in the nuclei of the amygdaloid body of the cat. The morphology of synapses in the amygdaloid nuclei was studied in 10 cats. On the basis of the percentage of axon terminals with flattened vesicles (F-type) nuclei were distinguished, in which these terminals are as sparsely distributed as in most areas of the central nervous system, from other nuclei in which they are abundant (about one-third to one-half of all synaptic boutons). The lateral, basal dorsal and basal ventral nuclei belong to the first, the medial and central nucleus and the anterior amygdaloid area--to the second group. The cortical nucleus, which generally has a small number of boutons of F-type has some parts seemingly belonging to the first, and others to the second group. In all amygdaloid nuclei axon terminals of F-type form symmetrical synaptic contacts. In nuclei with a low percentage of F-type terminals these boutons are predominantly small and synapse either with perikarya or with large dendrites. The amygdaloid nuclei having numerous F-type terminals contain not only small but also larger terminals with flattened vesicles. Both, the larger and smaller axon terminals form in these nuclei synaptic contacts with various parts of dendrites even with very small ones and with dendritic spines. The subdivision of amygdala into two parts, one with a low and another with a high number of F-type boutons would seem to support the hypothesis that amygdala may be subdivided physiologically into a dorsomedial--"excitatory" and basolateral--"inhibitory" portion.


Quantitative histological studies on the lateral geniculate nucleus in the cat. I. Measurements on Golgi material. Numerical data of neuron and fiber elements were observed and measured on Golgi preparations. The aim of the quantitative Golgi analysis was to obtain data on the spatial arrangement of arely neurons, their relations to the interneurons, on the spatial architecture of the arborizations of optic fibers and their relations to the main neuron types. The quantitative data on arely neurons include numbers of dendrites, of their chief points of ramification as the main targets of the optic afferents, geometric data on the "specific active sphere" of the dendritic tree; on the arborization of initial collaterals. The data on interneurons refer both to numeric and geometric parameters of their axonal arborizations, and to those of various characteristics of their dendritic processes. The data on optic fibers include the size of their arborization space, the numbers of bouton clusters and preterminal bouquets per arborization.


Quantitative histological studies on the lateral geniculate nucleus in the cat. II. Cell numbers and densities in the several layers. In the cat lateral geniculate nucleus all cells of all types were counted: their absolute numbers, their densities and their relative distribution. The nuclear volume and the volume of each layer was measured. The data of volume was applied on living material. The average densities of cells were calculated from the volume of LGN. The density of the cells was combined with the "specific active dendritic sphere" of relay neurons and it could be estimated that there may be a large number of spatially overlaping of ramification points around the cell body of relay neurons.


Organization and projections of the neurons in the dorsal tegmental area of the rat. The organization and projection of the neurons in the dorsal tegmental area at the locus coeruleus level of the rat have been investigated by means of the horseradish peroxidase (HRP) method, combined with monoamine oxidase staining to identify the noradrenaline (NA) neurons. Judging from the anatomical aspects elucidated in this study, this area is composed of various different cell groups. Although the functional role of these neuronal groups remains to be determined, the present study strongly suggests that the dorsal tegmental area participates in important regulation of several brain functions.


Phylogenetical changes and functional specializations in the dorsal lateral geniculate nucleus (dLGN) of mammals. Depending on their visual specialization and their place in the zoological system the mammalian species show some peculiarities in the morphology of the dorsal lateral geniculate nucleus (dLGN). The lamination of dLGN can be find in mammals with a highly developed visual system and a proportionally big part of ipsilaterally projecting retinogeniculate fibres. Number and sequence of ipsi- and contralaterally innervated laminae varies between species of different taxonomical categories. Hence these features depend on phylogenetical trends which could traced back to the beginning of the "mammalian radiation" in the cretaceous period and the earliest tertiary. Ancestral conditions may be found in mammals with an unlaminated dLGN and a medially located ipsilaterally innervated part. It may be registrated that a cytoarchitectonical separation of laminae (concerning the ipsi- and contralateral innervation) is the secondary step after fibre anatomical separation. The most primitive status may be realized in mammals having a zone of mixed ipsi- and contralateral fibre input. Some conclusions are made with regard to the suitability of lab mammals for generalization of results in the dLGN morphology.


Chronic, intractable, benign pain: a syndrome and its treatment with intensive short-term group psychotherapy. There is sufficient reason to classify some ongoing pain problems as syndromes. Patients who suffer with chronic, intractable, benign pain syndromes (CIBPS) have truly functional biopsychosocial disorders. There is no longer any current pathophysiology operative, and the pain syndrome persists with its psychosocially perpetuating and disrupting features. An intense group psychotherapy approach in the therapeutic milieu of a medical-surgical setting fosters and evokes affect expression and understanding. This encourages the formation of cognitive patterns that are therapeutically useful in that they extend coping abilities and, hence, diminish the pain and suffering experience and life problems attendant to it.


Studies on the activity of the sympathetic nervous system in essential hypertension. Plasma catecholamine and norepinephrine concentrations have been measured in carefully characterized ambulatory patients with essential hypertension under basal conditions and following experimental procedures known to enhance sympathetic activity. The studies have demonstrated increased levels of plasma catecholamines in patients with mild hypertension as compared with matched controls following 70 degree upright tilt or cold pressor testing. Considerable heterogeneity was apparent in the population of patients with essential hypertension with respect to their plasma norepinephrine concentrations. Significantly greater levels of plasma norepinephrine were present in patients with high plasma renin activity and lesser levels in patients with low renin activity than in normal renin or labile hypertensives. Blood pressure correlated significantly with plasma norepinephrine in male patients with normal renin essential hypertension but not in females. Administration of the diuretic furosemide produced an increase in plasma norepinephrine in almost all hypertensive subjects studied. These studies suggest that peripheral sympathetic activity is abnormal in certain patients with essential hypertension. The results underscore the need to differentiate between subgroups of essential hypertension in studies relating to the role of the adrenergic system in the hypertension. The findings also suggest that the recently developed sensitive techniques for measuring plasma catecholamines of plasma norepinephrine are of value in assessing changes in peripheral sympathetic activity but that enzymatic assays of serum dopamine-beta-hydroxylase activity are probably not useful for this purpose.


Stress, the sympathetic nervous system and hypertension. Stress may be an important contributor to the pathogenesis of idiopathic (essential) hypertension. The probable pathway involves activation of the sympathetic nervous system and thereby an increase in peripheral resistance. This paper reviews the hemodynamics of early hypertension and attempts to relate them to stress-mediated overactivity of the sympathetic nervous system. Attention is also given the relations between obesity, race, sex and geography to hypertension.


A strategy for research on psychological and social factors in hypertension. Stress-related research has thus far failed to provide an adequate understanding of hypertension and other psychosomatic ailments for three main reasons: First, there has been a continual failure to view stress as a relational phenomenon, that is, as a particular kind of transaction between person and environment. Second, there has been much confusion about the social, psychological and physiological levels of stress analysis; each is to some extent independent of the other, so that what happens at one level cannot stand for what happens at another. Third, the predominant research model has been structural and static. That is, the researcher looks at some environmental or personality characteristic, treating it as a stable property, and attempts to relate it to the risk of hypertension across persons or groups. Such an approach overlooks the key social, psychological and physiological mediating processes (e.g., social supports, cognitive appraisals, and coping) that are concurrent with and have causal significance in blood pressure elevation or change. Structural research models need to be supplemented with process-oriented ones in which the same persons are observed across various adaptational encounters and over time.


Antibiotic resistant staphylococci acquired during the first year of life. Nasal swabs were taken from 492 babies born consecutively to residents of two South Wales towns soon after their discharge from maternity hospitals. Staphylococcus aureus was isolated from 352 babies (72%) and in 79 (22%) of these it was resistant to at least one antibiotic. By the time these babies were a year old the prevalence of both sensitive and resistant strains had fallen, so that only 12% still carried nasal staphylococci, but 64% of these organisms were then resistant to penicillin. Administration of penicillin to the baby seemed to be a more important factor in selecting resistant organisms than other antibiotics given to the baby, any antibiotic treatment to other members of the household, or discharge from hospital.


Enumeration of micro-organisms in food: a comparative study of five methods. Five methods for the enumeration of micro-organisms in food (pour plate, surface spread plate, surface drop, agar droplet, and microdilution) were used in parallel to examine 100 samples selected from a wide range of food products. Statistical analyses of the results showed that the regression and correlation coefficients between the methods were highly significant; the lowest correlation coefficient derived for any pair of methods was 0.979. A variation in count between the methods of less than 0.5 log10 cycles was given by 98% of the samples. Analysis of the operation times and material requirements of each method showed that substantial savings in cost, time, space and support labour were achieved with the microdilution and agar droplet techniques as compared with the conventional pour plate and spread plate methods.


The serology of experimental Salmonella dublin infections of cattle. Agglutinating antibodies to somatic "O" and flagellar "H" antigens of S. dublin were measured in the serum of 43 pregnant heifers before intravenous or oral infection with S. dublin and in the serum of 21 uninfected control animals. The data from these animals were analysed statistically and a titre of 1/80, to both antigens, has been interpreted as of doubtful significance and a titre of 1/160 to both antigens, has been interpreted as significantly raised. Animals in which fetal infection occurred after challenge by either the intravenous or oral route developed significant increases in "H" and "O" titres indicating the value of measure "H" titres in the diagnosis of S. dublin abortion. In animals which were infected orally and in which infection appeared to be confined to the alimentary tract the "H" titre did not become significantly raised. Lack of correlation between antibody titres and faecal excretion of S. dublin and persistence of infection in carcasses confirms that the serum agglutination test is of no value in detecting latent carriers.


Salmonellosis in wild birds feeding at sewage treatment works. Between June 1976 and August 1977 faeces were collected from 599 wild British birds caught during ringing operations at two sewage treatment works in south-east England. Samples were incubated with selenite-F broth to detect the presence of Salmonella. Salm. anatum was isolated from one bird, a Dunnock Prunella modularis an incidence of 0.17% of the total birds examined and 3.23% of the Dunnocks. Comparisons are drawn with previously reported studies and it is suggested that sewage treatment works play little part in the transmission of Salmonella infections to wild birds feeding there.


A study of acute respiratory disease in the community of Port Chalmers. II. Influenza A/Port Chalmers/1/73: intrafamilial spread and the effect of antibodies to the surface antigens. During the first year of a study of respiratory disease in the semi-isolated community of Port Chalmers, New Zealand, an epidemic of clinical influenza occurred from which the variant influenza A/Port Chalmers/1/73 (H3N2) was isolated. Within a selected group of 26 families, 59 (46%) members had clinical or laboratory evidence of infection. During intrafamilial spread the infection frequency was highest for school-aged children (77%),  followed by female adults (67%), infants (64%) and male adults (41%). The index infection in each family was a school-age child on 10 occasions, suggesting the role of this age group in the transmission of influenza A in this community. The secondary attack rate (SAR) of 58.3% was higher than expected. In sera taken before the 1973 epidemic, 59% of family members had detectable HI antibody and 25% NI antibody to A/England/42/72 while 38% had detectable HI antibody and 8% NI antibody to A/Port Chalmers/1/73. The relation between pre-existing antibody and infection frequency is discussed.


The distribution of Bacteroides fragilis serotypes amongst clinical strains. Three hundred and twenty-two strains of Bacteroides fragilis isolated from infected patients at three different hospitals were tested against 20 type specific B. fragilis antisera using the tube agglutination technique. Of these strains 41.3% were assigned to a single O-serotype, a further 20.5% were agglutinated by several antisera and could not be classified and the remainder showed no reactions. Three different serotypes were prevalent in the three hospitals and minor geographical variation was observed. No correlation was found between serotypes and the origin of infection, but those from the blood were the most readily typable strains. No correlation was found between serotypes and biotypes of B. fragilis.


Shedding of bacteria and skin squames after handwashing. Particles released into the air by wringing the hands together were collected in a slit sampler before and after washing with bar soap, with three surgical scrubs, and after rubbing them with a spirit-based lotion. The particles were identified, their number estimated, those that bore bacteria counted, and the bacteria themselves classified. It was found that there was a significant increase, averaging 17-fold, in the number of particles carrying viable bacteria released after washing with soap. The increase in bacterial dissemination was suppressed if a surgical scrub was used in place of soap, or when the lotion was used without washing. The number of skin squames released increased by 18-fold or more after washing with soap or a surgical scrub, but not after using the lotion. This suggests that a surgical scrub should be used more widely in clinical practice, and that a spirit-based hand lotion might with advantage become a partial substitute for handwashing, particularly in areas where handwashing is frequent and iatrogenic coagulase-negative staphylococcal infection common.


Structural studies on protein products of murine chromosome 17. III. Partial amino acid sequence of an H-2Kq molecule. Twenty-one of the amino terminal twenty-seven amino acid residues have been assigned in the murine H-2Kq molecule and several additional assignments and corrections have been made in both the H-2Kk and H-2Kb molecules. The study shows that 1) H-2Kk and H-Kq, which are serologically related, have an identical amino acid sequence for all twenty positions that can be compared, 2) the H-2Kk and H-2Kq molecules differ from H-2Kb at only two positions--9 and 22, and 3) the additional sequence data on the H-2Kk, -Kb, and -Kq molecules increases the already striking homology between murine and human transplantation antigens.


Quantitative analysis of spleen cell and immunoglobulin allotype composition of (CBAxCBA/H-T6) in equilibrium C57BL/6 allophenic mice. Fifteen (CBAxCBA/H-T6) in equilibrium C57BL/6 allophenic mice were analyzed for the parental composition of their spleen white blood cells and serum immunoglobulin allotypes. The spleen compositions, assessed by a microcytotoxicity test, showed that the animals covered a range of parental cell mixtures. The allotype compositions of the IgG2a and IgG2b subclasses were determined by a solid phase radioimmunoassay. Although the absolute amount of IgG2a and IgG2b varied markedly from animal to animal, the percentage of the two allotypes in each subclass was remarkably constant. This suggests that the synthesis of IgG2a and IgG2b may be under a coordinate control system. Also, the spleen cell compositons were in excellent agreement with both the IgG2a and IgG2b subclass compositions. The quantitative analysis of the immune systems of allophenic mice may be first step toward the understanding of the mechanisms of tolerance of histoincompatible cells in allophenic mice.


Idiotypic analysis of anti-GAT antibodies. I. Presence of common idiotypic specificities in both responder and nonresponder mice. The synthetic terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) induced anti-GAT antibodies in D1.LP mice. Some of these antibodies shared common idiotypic specificities. The interaction between idiotypic antibody and anti-idiotypic antiserum was specifically inhibited by GAT and the closely related polymer of L-glutamic acid and L-tyrosine (GT) but not by the copolymer of L-glutamic acid and L-alanine (GA). The binding of labeled GAT by the anti-GAT antibodies was also specifically inhibited by the anti-idiotypic antiserum. These results indicated a close association of idiotypic determinants with the antibody-combining sites. Furthermore, such active site-related common idiotypic specificities were found in individual sera of both responder mice (D1.LP) and nonresponder mice (DBA/1) immunized with GAT and GAT-MBSA, respectively, indicating that both responder and nonresponder mice carry B cells with common clonotypes.


The primary structure of a human immunoglobulin G2 (IgG2) pFc' fragment. Amino acid sequence analysis of the pFc' fragment obtained by pepsin digestion of a human IgG2 myeloma protein PIG Gm (n or 23) negative shows it to consist of 112 residues. It starts at position 334 (gamma1 numbering) and contains eight residues from the Cgamma2 region, and the whole Cgamma3 domain. Comparison with the sequence of gamma1 shows two differences at positions 339 and 397. Each of them can be explained by a single base substitution. This high degree of homology among gamma-chain subclasses suggests a recent diversification.


Cytotoxic activities of gut mucosal lymphoid cells in guinea pigs. Populations of lymphoid cells were obtained from the gastrointestinal tract of guinea pigs and compared with splenic cells for effector cell activity in assays of spontaneous cell-mediated cytotoxicity (SCMC), mitogen-induced cellular cytotoxicity (MICC), and antibody-dependent cellular cytotoxicity (ADCC). Lymphoid cells were isolated from mesenteric lymph nodes (MLN), Peyer's patches (PP), and the small intestinal mucosa. Mucosal lymphoid cells were separated into a population of cells containing intraepithelial lymphocytes (IEL), and a second population of cells containing intraepithelial lymphocytes (IEL), and a second population of cells containing lamina propria (LP) lymphocytes by a combination of physical and enzymatic methods. All populations of lymphoid cells from the gastrointestinal tract were capable of mediating MICC. Relative to spleen cells, IEL possessed more MICC effector cell activity whereas cells from MLN, PP, and LP possessed less activity. In contrast, SCMC and ADCC effector cell activities were present only in the IEL population and these cytotoxic activities were comparable to that of splenic cells. These results demonstrate that mucosal lymphoid cells possess cytotoxic effector cell activities that may contribute to local mucosal immunologic reactivity.


Structural studies of the H-2D products of the mouse mutant BALB/c-H-2Ddb and the parental strain BALB/cKh-H-2Dd. The tryptic peptide profile characteristics of the H-2D glycoprotein, isolated by immunoprecipitation from the MHC mutant mouse strain BALB/c-H-2Ddb, were compared with those of the H-2D molecule from the parent strain BALB/cKh-H-2Dd. At each stage of purification these molecules exhibited identical biochemical properties and on peptide mapping we observed that the Ddb molecule showed no detectable peptide differences from the Dd molecule of the nonmutant parent. These data thus support the concept that the site of mutation in this mutant strain, although located in the D region of the MHC, is distinct from the gene coding for molecules bearing the H-2.4 private specificity.


Amplification of the activity of human leukocyte inhibitory factor (LIF) by the generation of a low molecular weight inhibitor of PMN leukocyte chemotaxis. Leukocyte inhibitory factor (LIF), which was derived from human peripheral blood lymphocytes by stimulation with concanavalin A ad partially purified by Sephadex G-100 gel filtration, inhibited the in vitro spontaneous migration and chemotaxis of human PMN leukocytes as assessed in a Boyden chamber micropore filter assay. The inhibitory activity was attributed to LIF, a principle defined in terms of its inhibition of PMN leukocyte migration from glass capillary tubes since it was preferentially directed to PMN leukocytes as compared to mononuclear leukocytes, exhibited a size comparable to LIF by gel filtration, and was inactivated by diisopropyl fluorophosphate in parallel with LIF. Incubation of PMN leukocytes with LIF released additional inhibitory activity, distinct from LIF, which resembled the neutrophil-immobilizing factor (NIF) by virtue of its approximate m.w. of 4000 by filtration on Sephadex G-25, inactivation by trypsin digestion, and preferential noncytotoxic inhibition of spontaneous migration and chemotaxis of PMN leukocytes as compared to mononuclear leukocytes. Thus LIF inhibits PMN leukocyte migration both by a direct action on the cells and by an amplification pathway that is mediated by low m.w. chemotactic inhibitors similar to NIF.


Concanavalin A increases glyoxalase enzyme activities in polymorphonuclear leukocytes and lymphocytes. Glyoxalase I converts methylglyoxal and glutathione to S-lactoylglutathione and glyoxalase II converts this compound to D-lactic acid, regenerating glutathione in the process. A recent study from my laboratory has provided evidence that S-lactoylglutathione modulates microtubule assembly in vitro whereas concanavalin A (Con A) has been shown to increase microtubule occurrence in polymorphonuclear leukocytes (PMN). The present report describes the dose-dependent activation by Con A of both glyoxalase I and II in PMN and lymphocytes. In nine experiments with PMN, Con A (100 microgram/ml) increased glyoxalase I and II activities by 19 +/- 8% and 12 +/- 10% (mean +/- S.D.). In 17 experiments with lymphocytes, activation of the two enzymes by 10 microgram/ml Con A was 30 +/- 14% and 28 +/- 8%. Changes occurred after a 1-min incubation with Con A and persisted for at least 60 min. Since both enzyme activities are increased it is not clear if S-lactoylglutathione levels are increased or decreased but presumably they change. The present findings are compatible with the hypothesis that Con A increases microtubule occurrence in PMN by affecting the glyoxalase enzymes. They also represent a newly described early biochemical change caused by Con A in lymphocytes.


Immunologic block against antigen absorption from isolated perfused rabbit lungs. In previous studies with isolated perfused rabbit lungs, we observed that inhaled human serum albumin (HSA) or ovalbumin (OA) entered the pulmonary circulation antigenically intact. The inhaled proteins were also metabolized in the lung. Immunization reduced the amount of intact protein and increased the amount of metabolites absorbed. In the present study, we have begun to characterize the immune mechanisms responsible for reduced antigen absorption. A humoral immune mechanism appeared to be involved because the phenomenon could be passively transferred to normal animals by administering immune serum either 18 hr or immediately before antigen inhalation. The reduction was also observed when lungs from immunized rabbits were perfused with normal rabbit blood, indicating that antibodies in both lung and blood may be involved. Experiments, in which lungs from immunized rabbits were simultaneously insufflated with the immunizing antigen and with a nonspecific protein, demonstrated that the block against antigen absorption was specific for the immunizing antigen and was not due to some antigen-induced nonspecific changes in lung physiology.


Lung injury produced by immune complexes of varying composition. Immune complexes consisting of rabbit antibody to bovine serum albumin (BSA) have been made up at 1X, 3X, 6X, 8X, and 20X antigen equivalence. The complement fixing activity of these complexes is inversely proportional to the amount of antigen present in the complexes, and, as expected, solubility of the complexes progressively increases with increasing amounts of antigen. The ability of these complexes to induce acute pulmonary injury and inflammatory responses has been quantitatively assessed. Complexes preformed at antigen equivalence are the most damaging to lung, correlating with their complement fixing activity. When the antigen concentration in the complexes is increased 3 to 6 times beyond the point of equivalence, the phlogistic activity of the complexes drops off rapidly, as demonstrated by a sharp decline in the changes in vascular permeability, hemorrhage, and morphologic evidence of inflammation. These studies provide the first evidence that changing the physicochemical parameters of preformed immune complexes by simply altering the ratio of antigen to antibody can dramatically alter the phlogistic properties of immune complexes for pulmonary tissue.


H-2 linked Ir gene control of antibody responses to porcine insulin. I. Development of insulin-specific antibodies in some but not all nonresponder strains injected with proinsulin. Cell-mediated and humoral immune responses to heterologous insulins in mice are controlled by H-2 linked, dominant, immune response (Ir) genes. For example, mice bearing the H-2d haplotype develop T cell proliferative responses and produce antibody after injection with porcine insulin, whereas mice bearing other H-2 haplotypes do not. Data presented in this communication demonstrate that homozygous and heterozygous H-2d mice produce insulin-binding antibodies when immunized with porcine insulin or proinsulin. Some (H-2b,k,s) insulin-nonresponder mice produce insulin-binding antibodies after injection of proinsulin, whereas other insulin-nonresponder strains (H-2q) do not. All strains, except homozygous H-2q mice, produce antibodies specific for proinsulin, suggesting that the response to porcine proinsulin is also controlled by H-2-linked Ir genes. More importantly, F1 hybrids between insulin-nonresponder C57BL/10 (H-2b) and DBA/1 (H-2q) produce no insulin-binding antibodies when injected with proinsulin, despite the fact that proinsulin-binding antibodies are produced by these mice.


Effect of tunicamycin on IgM, IgA, and IgG secretion by mouse plasmacytoma cells. Tunicamycin, an antibiotic that prevents glycosylation of glycoproteins by blocking the formation of N-acetylglucosamine-lipid intermediates, was used to study the importance of glycosylation for the secretion of immunoglobulins by mouse plasmacytoma lines that produce immunoglobulins of different classes. Biosynthetically labeled secreted and intracellular immunoglobulins were measured by immunoprecipitation assays. Tunicamycin, at a concentration of 0.5 mug/ml produced an 81% inhibition of IgM secretion by MOPC 104E plasma cells without significantly affecting the initial rate of synthesis of intracellular IgM. No increase in the intracellular degradation of nonglycosylated IgM could be demonstrated. Tunicamycin also produced a 64% average inhibition of IgA secretion by several mouse IgA-secreting plasmacytoma lines. In contrast, despite inhibiting the incorporation of D-[14C] glucosamine into newly synthesized IgG, tunicamycin only produced a 28% average inhibition of IgG secretion, which was only slightly more than the nonspecific inhibition of secretion of the normally nonglycosylated lambda2 light chains by variant MOPC 315 plasmacytomas. These data indicate that the extent of inhibition of immunoglobulin secretion produced by tunicamycin depends on the immunoglobulin class produced by the plasma cell.


Relationship between trinitrophenol and H-2 antigens on trinitrophenyl-modified spleen cells. III. Quantitative aspects of trinitrophenol binding on cells treated with trinitrobenzene sulfonic acid. Splenic lymphoblasts or normal spleen cells were treated with varying concentrations of TNBS in order to assess whether cell membrane H-2 molecules were derivatized with TNP. Cells treated with high concentrations of TNBS had their cell membrane H-2 molecules derivatized and functioned antigenically as inhibitors in a cold target TNP-CML competition assay. In contrast, cells derivatized with lower concentrations of TNBS had a significant proportion of their membrane proteins derivatized with TNP but did not have their H-2 molecules derivatized. These latter cells were unable to block anti-TNP cytotoxic effector cells in the competition assay. When cells were treated with 3H-TNBS, it was observed that TNP couples to cell membrane H-2, Ia and Ig molecules, and an estimate of the number of TNP molecules bound per cell at varying concentrations of TNBS was determined. The data obtained are consistent with there being a requirement for TNP to directly derivatize H-2 molecules on the cell membrane in order to create antigenic determinants that can be recognized by cytotoxic anti-TNP effector cells. As an alternative, there may be a requirement for the presence of a high density of TNP molecules per cell rather than direct H-2 derivatization by TNP in order to account for activity.


Immunoglobulin allotypes in African populations. I. Gm--Am haplotypes in a Nigerian population. The study of immunoglobulin allotypes in various Negro populations has shown that their polymorphism is different from that in other populations. This particularly true for the alleles of the gamma3 and alpha2 locus. Numerous investigations have been made in which a limited number of markers were determined. It seems to be of importance to compare the results of the determination of all markers known at present in different tribes from various African countries. Such information may ultimately lead to additional support for theories on the origin and migration of early African inhabitants. In this paper we resent the results of the study of the first of a series of studies on African populations.


X chromosome complement and serum levels of IgM in man and mouse. The levels of IgM were measured in sera from mice with different chromosome complements, including 39,XO mice and phenotypically male mice bearing the sex-reversed gene (Sxr) (XX,Sxr/+ and XY,Sxr/+). The mean values of IgM were found to be higher in normal female mice than in the males belonging to two different strains. This is in agreement with the higher mean serum levels of IgM observed in two groups of sera from normal human females and males. However, while we could confirm that the mean level of IgM was lower in 45,XO women than in normal females and comparable to the mean value of normal males, the same effect was not seen in 39,XO mice. In fact, the mean concentration of serum IgM in 39,XO mice was similar to that in normal females. Furthermore, it was observed that the mean values of serum IgM in the two groups of sex-reversed male mice (XX,Sxr/+ and XY,Sxr/+) were also not statistically different from those in normal males. Thus the role that the number of X chromosomes plays in the control of the serum levels of IgM is different in man and the mouse, in agreement with the observed different phenotypic manifestations, and in particular with the hormonal situations existing in X chromosome abnormalities in these two species.


Inherited structural variation and linkage relationships of C7. Three structural forms of C7 have been distinguished by isoelectric focusing. They are the products of three co-dominantly expressed alleles at an autosomal locus. The C7 locus is close to that for C6, but is not close to the HLA complex.


HLA antigens as possible markers of heterogeneity in schizophrenia. The distribution of HLA-A-, B- -and -C-locus antigens was tested in 200 male patients with final diagnosis of schizophrenia. A significant increase of HLA-A28 and HLA-Cw4 antigens and haplotype A10--B18 was found. Indications were obtained for the increase of HLA-A1 in hebephrenic patients. It was presumed that the increase of CW4 represents the common denominator of the diverse findings on paranoid schizophrenia. The increase of CW4 indicates that the paranoid schizophrenia disease susceptibility locus is either the C locus itself or another closely linked locus (or loci). This would stress the importance of the HLA 'central' regions for HLA and disease associations. A hypothesis is presented which points to the possibility that HLA antigens could be genetic markers of three ethiopathogenetic subgroups of schizophrenia. The possible tests of this hypothesis are also suggested.


Temperature stress and immunity in mice: effects of environmental temperature on the antibody response to human immunoglobulin of mice, differing in age and strain. Physiological responses at different ambient temperatures and temperature-dependent changes in immune responsiveness are polymorphic. At 4 degrees C, the antigen elimination from the bodies of SJL and C57Bl/6 mice is accelerated. In SJL, but not in C57Bl/mice, the half-life of antigen elimination decreased between the ages of 3 and 11 weeks. Parental mice and their F1 hybrids showed a fall in rectal temperature, which was greatest in young animals. Hypothermia was greater in C57Bl/6 than in SJL and F1 hybrids; in 3 week old C57Bl/6 it resulted in high mortality. The response to aggregated human immunoglobulin (HGG) was evaluated by (a) the number of animals with detectable antibody, (b) the minimal dose of antigen eliciting detectable antibody, and (c) the mean titre of haemagglutinating antibody. SJL mice were more responsive than C57Bl/6 mice. Low antibody formation in the secondary response was dominant, i.e. the amount of antibody produced by (SJL X C57Bl/6)F1 mice was the same as that produced by the parental C57Bl/6 strain. In a primary response, the quantity of antibody varied with the age of the immunized animal; 18 week old mice responded to lower minimal doses of antigen and produced more haemagglutinating antibody than 3 week old animals. After a second injection with HGG, SJL but not C57Bl/6 mice produced more antibody when kept at 14 degrees C rather than at 22 degrees C or 30 degrees C, and produced the lowest antibody titres when kept at 4 degrees C. The relation between ambient temperature and the response of the SJL mice was dominant over that of the C57Bl/6strain. Primary differed from secondary responsiveness in that neither strain produced significantly lower titres when ambient temperature fell to 4 degrees C; only 18 week old SJL mice responded with a marginal decrease in peak antibody production. The described polymorphism may affect both the individual capacity to cope with low temperatures and the evolutionary adaptation of a species to climatic extremes.


Inhibition of connective tissue proliferation by dermal extract. Following the subcutaneous injection of a water soluble dermal extract (DE) of neonatal rat skin into young adult male rats, depression of nuclear labeling (DNA synthesis) was observed in proliferating connective tissue in several wound sites. At 16--20 hr following DE injection, DNA synthesis was depressed most in back wounds (57--87%) and maxillary palatal wounds (45--68%), and least in ear wounds (24--29%). Epithelium in the wound margins of back, ear and palate did not show a similar depression in DE-injected animals. This study suggests that a chalone-like negative feedback mechanism may be partially responsible for in vivo control of fibroblastic proliferation in wound healing.


Inflammatory and immune cell function in psoriasis--a subtle disorder I. In vivo and in vitro survey. Intradermal skin testing of normal and psoriatic subjects with common antigens, SKSD, Derm-O and PPD, reveals psoriatic subjects to have a decrease in both the amount (not incidence) of erythema (p less than 0.005) and in-duration (p less 0.005) to SKSD. Among all subjects having more than 10 mm erythema to Derm-O and SKSD, 49% of psoriatic and 77% of normal subjects have more than 10 mm induration (p less than 0.001). After sensitization, the response to 30 microgram challenge dose of dinitrochlorobenzene is positive in 50% of psoriatic and 88% of normal subjects (p less than 0.02). Uptake of (3)H thymidine by mitogen stimulated lymphocytes from psoriatic subjects is suppressed at each point of the linear component of a dose response curve. The mitogen dose to produce peak responses in psoriatics was 125% greater than that for normal subjects. In one-way mixed lymphocyte responses to pooled allogeneic stimulator lymphocytes, peripheral blood mononuclear cells from psoriatic subjects show suppression, the mean stimulation index was 55% of that of normal (p less than 0.01). Finally, in vitro polymorphonuclear leukocyte functions (chemotaxis, phagocytosis, and NBT reduction) appear to be within normal limits. When the foregoing parameters were compared with disease activity, there was no correlation.


Inflammatory and immune cell function in psoriasis: II. Monocyte function, lymphokine production. We have previously confirmed that subjects with psoriasis have an alteration of cell-mediated immune responses. We now report a possible in vitro corollary; the amount of lymphokine (lymphocyte-derived chemotactic factor) released by both antigen-stimulated and control lymphocytes is decreased in psoriatic subjects; 61% of similar values for normal subjects. Monocyte migration to complement-derived chemotactic factors is reported to directly correlate to skin tests; however, in psoriasis the relation is inverse, i.e., a 200% increase in complement factors and 136% increase to lymphocyte-derived chemotactic factor in monocyte migration is noted in psoriatic subjects when compared with normal subjects. This increased migration does not correlate with amount of disease and is still present in "disease-free" subjects. Culturing monocytes from psoriatic subjects in media alone demonstrates they reduce more (205%) nitroblue tetrazolium than do monocytes of normal subjects. These data demonstrate that monocytes from subjects with psoriasis are altered and suggest an apparent inherent metabolic disorder.


In vitro responses of the epidermis to triiodothyronine. The effect of exogenous triiodothyronine on replication and anabolic activity in human epidermis has been studied in vitro. Measurements of epidermal replication, as estimated by a labeling index technique and by thymidine incorporation into skin sheets, were increased (p less than 0.005) from the control value by exogenous triiodothyronine at twice its physiological unbound concentration. Higher concentrations of triiodothyronine did not alter these elevated values significantly. Epidermal anabolism, measured by the rates of incorporation of tritiated proline and histidine, and by histidine uptake assessed autoradiographically, responded similarly with increased values (p less than 0.005) compared to controls in specimens incubated with twice physiological concentrations of the hormone. Further increases in the hormone concentration failed to change these measurements significantly. These observations indicate that the epidermis does respond to exogenous triiodothyronine in vitro, and support the concept that there are receptors for triiodothyronine associated with epidermal cells.


Physical forces in blister formation. The role of colloid osmotic pressure and of total osmolality in fluid migration into the rising blister. The physical forces operative in the fluid migration from the interstitial spaces into the blister cleft have not been directly measured until now. The colloid osmotic pressure and the total osmolality were determined in suction blister fluid after mild suction blister production by a modified "Dermovac" and in blister fluid of patients with dermatitis herpetiformis, bullous allergic contact dermatitis and pemphigus vulgaris and in the sera of healthy persons. The colloid osmotic pressure was measured by means of a recently developed osmometer with a semipermeable membrane between 2 chambers, one of them filled with Ringer solution, the other with the blister fluid or serum sample. The negative pressure in the first chamber was determined. The colloid osmotic pressure of suction blister fluid averages approximately 7 cm H2O, the values reach about 20 cm H2O in bullous diseases and about 38 cm H2O in the normal sera. The blister fluid colloid osmotic pressure has to rise to about 15 cm H2O or more to cause the fluid transport from the interstitial spaces of the surrounding tissue into the blister because of the negative interstitial fluid pressure and the colloid osmotic pressure of the interstitial fluid. Otherwise the blister fluid is reabsorbed back into the interstitial spaces. The total osmolality does not differ in the serum and in the blister fluid. It does not seem to be etiologically connected with the fluid transport into the rising blister.


Serum immunoglobulin E in pemphigus.

Serum immunoglobulin E in pemphigus. Immunoglobulin E levels in the sera of patients with pemphigus (12 with Brazilian pemphigus foliaceus (BPF) and 11 with pemphigus vulgaris (PV)) were determined by means of a solid phase radioimmunoassay. A significant increase in IgE level was observed in BPF patients compared to the level of IgE in PV patients and healthy adults. The implications of an elevated level of IgE with respect to other aberrations of immunologic responsiveness and the suggested infectious etiology of BPF are considered.


Metabolism of cholesterol-enriched chylomicrons. Catabolism of triglyceride by lipoprotein lipase of perfused heart and adipose tissues. The chemical and biochemical properties of cholesterol-enriched and cholesterol-poor chylomicrons from rat lymph have been compared. The enriched particles, prepared from cholesterol-containing lipid dispersions, passed into the duodenum, had four to ten times the cholesteryl ester content of the control chylomicrons but had the same content of total "core" (cholesteryl ester + triglyceride) lipid. Both chylomicron species had the same protein composition, the same phospholipid composition, and the same composition of triglyceride fatty acids. The rate of hydrolysis of chylomicron triglyceride for enriched and control particles was determined using both soluble and membrane-supported lipoprotein lipase (LPL) species from heart and adipose tissues. The lipase that was functional in the isolated perfused heart showed no significant difference in initial catabolic rate with cholesterol-enriched and control chylomicrons. The same result was obtained with this isolated LPL species in vitro. The lipase that was functional in isolated perfused epididymal adipose tissue showed a slightly lower catabolic rate with cholesterol-enriched particles (84% of that obtained with control chylomicrons). The same result was obtained with isolated adipose tissue LPL. It is concluded that cholesteryl ester content of chylomicrons under these conditions neither affects their protein composition nor has a major effect on their rate of reaction with lipoprotein lipase.


Composition of proteins of mesenteric lymph chylomicrons in the rat and alterations produced upon exposure of chylomicrons to blood serum and serum proteins. Protein composition was determined in mesenteric lymph chylomicrons from fat-fed rats. Among the proteins of intermediate molecular weight, apoproteins A-I and the arginine-rich apoprotein accounted for 31% and 4% of the total protein mass, respectively. Apoprotein B and apoprotein A-IV each accounted for about 10% and proteins of low molecular weight (C apoproteins and apoprotein A-II) accounted for most of the remainder. Apoprotein A-I also accounted for more than 30% of the protein mass of mesenteric lymph lipoproteins of density less than 1.006 g/ml ("small chylomicrons") obtained from rats fed glucose. Aproprotein A-I was partially dissociated from chylomicrons during brief ultracentrifugation. Both the arginine-rich apoprotein and the C apoproteins in rat blood serum were transferred to lymph chylomicrons from fat-fed rats during incubation in vitro. Content of arginine-rich apoprotein, determined immunochemically, increased six-fold when chylomicrons were diluted to a final concentration of 500 mg/dl in blood serum. Upon incubation of chylomicrons in equivalent volumes of ultracentrifugal fractions of serum, the increase of the arginine-rich apoprotein was: very low density lipoproteins, 1.5-fold; high density lipoproteins, 1.8-fold; density fraction greater than 1.006 g/ml, 5.0-fold; density fraction greater than 1.21 g/ml, 11-fold. Content of apoprotein A-I, also determined immunochemically, was not altered appreciably by exposure to serum or its ultracentrifugal fractions, whereas content of C apoproteins, estimated from intensity of staining of the low molecular weight protein component in polyacrylamide gel electropherograms, increased in all cases except for the density fraction greater than 1.21 g/ml. The fractional content of apoprotein A-I in the protein of chylomicrons fell after incubation, whereas that of the arginine-rich apoprotein remained constant or rose substantially. The fractional content of apoprotein A-IV in chylomicron-protein tended to follow that of apoprotein A-I, as judged from polyacrylamide gel electropherograms. Transfer of the arginine-rich and C apoproteins to chylomicrons from blood serum was directly related to the volume of serum in which the chylomicrons were diluted and occurred rapidly at room temperature or at 4 degrees C.


Changes in biliary lipid and biliary bile acid composition in patients after administration of ursodeoxycholic acid. Twenty-three patients with gallstones were treated with two dosage levels of ursodeoxycholic acid, 600 mg/day and 150 mg/day. Two to three months after the treatment, the molar percentage of cholesterol in bile significantly decreased (from 7.4 to 4.5 mole % in the 600 mg group and from 7.6 to 4.0 mole % in the 150 mg group), so that bile became unsaturated in most patients in both treatment groups. However, there was no significant difference between the two groups. Biliary ursodeoxycholate increased in proportion to dose, and the sum of ursodeoxycholic acid plus chenodeoxycholic acid in biliary bile acids was over 70%. The was no significant increase in the proportion of lithocholate in bile. The major fecal bile acid of patients receiving ursodeoxycholic acid was lithocholic acid. Serum bile acid concentration rose slightly after 3 months of ursodeoxycholic acid treatment, and the major circulating bile acid became ursodeoxycholic acid. Ursodeoxycholic acid is well absorbed from intestine, undergoes little biotransformation during hepatic passage, and is 7-dehydroxylated by colonic bacteria. The litholytic activity of ursodeoxycholic acid was demonstrated in two patients receiving 450 mg and 150 mg, respectively, of the bile acid per day.


Effects of acetate, acetaldehyde, and ethanol on lipolysis in isolated rat adipocytes. The effects of different concentrations of acetate, acetaldehyde, and ethanol, alone or in combination, on the lipolysis rate, measured as glycerol release, were studied in isolated adipocytes from fed or fasted rats, in the basal state and at various levels of norepinephrine stimulation. Acetate inhibited the glycerol release in a dose-dependent manner (congruent to 10% inhibition at 2 mM, 25--70% at 10 mM) with the most marked effects at low to moderate norepinephrine concentratione and at maximal (100 ng/ml) hormone stimulation. Ethanol, up to 100 mM concentration, had no effect on the lipolysis rate. Acetaldehyde, up to 1 mM concentration, had no reproducible effect. Ethanol, acetaldehyde, and acetate in combination inhibited glycerol release to an extent similar to that of acetate alone.


Resolution of desmosterol, cholesterol, and other sterol intermediates by reverse-phase high-pressure liquid chromatography. A highly efficient technique has been developed for the resolution of several sterols that are intermediates in the biosynthesis of cholesterol and that differ only by one carbon-carbon double bond or by one methyl group. The technique described utilizes reverse-phase high-pressue liquid chromatography on a micronBondapak-C18 column with acetonitrile as eluting solvent. This procedure is capable of measuring the enzymatic conversion of desmosterol to cholesterol. This chromatographic separation can be conducted by reverse-phase high-pressure liquid chromatography in approximately 10 min, whereas other procedures can require several days.


Effects of small amounts of pentadecan-2-one on the growth of Clostridium butyricum. Primary alcohols occur as trace lipids and are the only long-chain alcohol species present in Clostridium butyricum. Secondary alcohols do not occur physiologically in this microorganism. Exposure of these cells to the methyl ketone, pentadecan-2-one, results in a marked decrease in the primary alcohol content with the secondary alcohol, pentadadecan-2-ol, becoming the major alcohol present. This change in lipid composition is associated with a significant decrease in growth rate that is proportional to the log of the pentadecan 2-one concentration of the incubation medium. When these cells are incubated with pentadecan-2-ol alone, growth is unaffected. Simultaneous exposure of the bacteria to pentadecan-2-one and a mixture of primary alcohols results in a partial relief of the growth inhibition observed with the ketone alone. These observations indicate that pentadecan-2-one inhibits the formation of primary alcohols that are important for normal growth of this bacterium.


Analysis of bile acids in serum and bile by capillary gas-liquid chromatography. Various liquid phases for glass capillary columns have been evaluated for gas-liquid chromatographic analysis of methyl ester trimethylsilylether derivatives of bile acids from serum and bile. Bile acid analysis is rapid and exhibits high separation efficiency with a 20 X 0.3 mm glass capillary column whose internal surface is covered with a crystal layer of barium carbonate and coated with polyethyleneglycol 20000 as liquid phase according to Grob et al.


Quantification of adipocyte free and esterified cholesterol using liquid gel chromatography. A reliable method for the separation of free and esterified cholesterol in adipocyte extracts is described. The procedure uses Sephadex LH-20, a lipophilic dextran gel, with a solvent system of chloroform-hexane 55:45 (v/v). Interference by excess triglyceride, such as that encountered in adipocyte total lipid extracts, was not observed, and overall recovery of both sterols exceeded 98%.


A rapid biosynthetic method for the preparation of radioactive phosphatidyl-CMP(CDP-diacylglycerol) of high specific activity. A procedrue is described for the preparation of [32P]phosphatidyl-CMP(CDP-diacylglycerol) from rat pineal glands incubated with [32P]orthophosphate and DL-propranolol. The product is 95% radiopure and a high specific acitivity. The yield of liponucleotide is 0.4--0.9 micron Ci/mCi of [32P]orthophosphate in the medium. The same method can also be used for the biosynthesis and purification of [3H]phosphatidyl-CMP when [3H]cytidine is the precursor.


Bile acids. OV. 2,2-Dimethoxypropane: an esterifying agent preferred to diazomethane for chenodeoxycholic acid. Artifacts formed by methylation of chenodeoxycholic acid with diazomethane are identical to the synthetic 3alpha- and 7 alpha-monomethyl ethers of methyl chenodeoxycholate. The extent of formation of these artifacts with time has been studied. No detectable artifacts were found with 2,2-dimethoxypropane as the methylating agent.


Alternation of atrial cycle length in supraventricular tachycardia. Nine cases of alternation of the atrial cycles during supraventricular tachycardia are presented, three of which were manifestly due to digitalis toxicity. They presented the following features: absence of 1/1 conduction, upright P waves in Lead II, atrial rates of 156-218. When alternation disappeared, the atrium adopted the longest of the previously inscribed cycles. A ventriculophasic cause was excluded. The possible mechanisms are discussed in terms of the known functional anatomy of the various forms of SVT.


A paucity of chronic electrocardiographic changes with adriamycin therapy. Serial electrocardiograms (ECGs) of 49 patients receiving adriamycin were analyzed for the development of persistent changes. The ECG changes were compared with those of a control group of 20 patients receiving other chemotherapeutic drugs, which were comparable to the additional chemotherapy received by the adriamycin patients. The only chronic ECG changes noted with adriamycin over control were the loss of P wave amplitude in the greater than 500 mg/m2 dose subgroup and the clockwise rotation of the precordial QRS in the 250-500 mg/m2 dose subgroup. In contrast, systolic time intervals demonstrated a gradual diminution in left ventricular function at increasing doses of adriamycin. The electrocardiogram itself appears to be of limited value in the assessment of cardiac toxicity with adriamycin therapy.


A quantitative technical quality assay method for electrocardiograms. A method is presented for quantitative assessment of ECG technical quality to permit sensitive detection of performance trends of individual technicians or entire ECG laboratories. The common flaws in ECG recording technic are those which introduce ultra-low frequency artifact or baseline shift, powerline artifact, myographic and intermediate frequency artifact, clipping of waveforms, disconnection or reversal of electrodes and general faults of protocol adherence. Procedures for quantitating these attributes are presented and explained in order to arrive at a mean figure of merit for each ECG recording. Use of such a method can aid ECG technicians' understanding of the important features of tracing quality and provide an objective basis for the recognition of outstanding performance, on one hand, or the need for remedial training, on the other.


A controlled study of a new ECG electrode system. A newly marketed resting ECG electrode system was compared with conventional metal suction and plate electrodes, electrode cream and patient cable. Two experienced technicians were given special training in the use of the new electrode, electrolyte and patient cable system and alternated daily in using new and conventional equipment. Nearly equal numbers of perfect-scoring ECGs were recorded with each system, attesting to the impartiality of the technicians. A total of 1,062 ECGs were evaluated, 554 with the new system and 508 with the conventional one. ECG tracings were evaluated by electrocardiographers unaware of which system was used for each. A quantitative scoring system was used to measure the technical quality of each tracing in terms of baseline drift, powerline artifact and myographic plus miscellaneous artifacts. The new system received mean scores of 2.33, 3.08, and 2.72, respectively, while the conventional electrodes received scores of 2.56, 3.03 and 2.79. We concluded that the two types of electrodes produced ECGs of essentially equal quality.


Metastatic atrial tumor: case report with electrocardiographic-pathologic correlation. This report describes a case in which the pre-mortem diagnosis of a right atrial metastasis from a bronchogenic carcinoma was made on the basis of distinctive PR segment (atrial repolarization) changes and atrial arrhythmias. The differential diagnosis of such PR segment deviations also includes functional changes, pericarditis, atrial infarction, and other types of atrial injury.


Concealed atrial electrical activity.

Concealed atrial electrical activity. In the following paragraphs we describe a case diagnosed clinically and haemodynamically as a cardiomyopathy. Atrial flutter which was not in evidence in the standard ECG was diagnosed by the use of a new technique of amplification and filtering of special surface leads (T.A.F.). The diagnosis was later confirmed by means of special internal techniques (intra-atrial ECG and His bundle recording). The existence of a subpraventricular rhythm, probably sinusal, and also unapparent in the standard ECG, was observed by using the same method after electrical defibrillation. We comment on the extreme rareness of discovering concealed atrial rhythms and their possible explanation, and we emphasize the usefulness of the T.A.F. technique in their diagnosis.


[Influence of specimen withdrawal on the results of chemical analyses of blood, plasma and serum in patients with stable or centralized circulation (author's transl)]. The influence of circulatory conditions, point of blood withdrawal (arterial, central or peripheral venous) and the plasma-serum relation on 29 clinical chemical and hematological parameters were studied with 22 polytraumatized patients. The conditions studied significantly affect the results, and must be taken into consideration in evaluating the results and their comparison to reference values. This is especially important for the determination of the catalytic activities of creatine kinase, aspartate and alanine aminotransferases, and alkaline phosphatase in centralized-circulatory patients, for the total protein the electrophoretic fractions and analyses of blood gas as a function of the point of blood withdrawal, and for the total protein, gamma-globulins and potassium when plasma is analysed instead of serum.


Development of a radioimmunoassay for pig pancreatic kallikrein. A radioimmunoassay for the determination of pig pancreatic kallikrein was developed. The chloramine-T method was employed for the labelling of the antigen with 125I. The assay allows the determination of kallikrein in concentrations as low as 0.4 microgram/l. Pig urinary and pig submandibular kallikreins are indistinguishable from pig pancreatic kallikrein by the assay. No cross reactivity was observed for bovine trypsin and chymotrypsin, porcine trypsin and kallikreins of guinea pig submandibular glands and guinea pig coagulation glands. Because of the high specificity of the assay, which is not attainable with conventional assays based on the enzymatic activity, the radioimmunoassay is highly suited for investigations into the physiological role and the pharmacological mechanism of action of pig glandular kallikreins.


[Determination of the serum protein concentration based on the measurement of density by the mechanical oscillator technique (author's transl)]. A linear relation is well established between the density and protein concentration of the serum. The measurement of protein concentration by a new technique for the determination of the absolute density, the mechanical oscillator technique, was investigated. The method is based on the determination of the resonant frequency of a mechanical bending-type, U-shaped glass tube oscillator filled with the sample. The shift in the resonant frequency of the oscillator caused by the mass of the defined volume of the sample taking part in the vibration can be used to calculate the density or protein concentration of the sample. In spite of the low specificity of the method, the interference of substances like glucose, urea or triglycerides is small. Simplicity and rapid results of high accuracy recommend the mechanical oscillator technique for the routine laboratory.


[Quantitative determination of serum proteins using a new laser nephelometer (author's transl)]. Methodological aspects of quantitative serum protein determinations, using a newly developed laser nephelometer (PDQTM laser nephelometer, Hyland), are reported. For within-day precision, determination of the four serum proteins IgG, IgA, IgM and C'3, showed coefficients of variation between 2.5% and 4.6%. For precision from day to day, the average variation coefficient was 8%, the lowest value being 5%. Provisional normal values for the four proteins were ascertained from a small group of 60 healthy individuals. These results, as well as those obtained in states of disease, correlate with values obtained by radial immunodiffusion. It is concluded that the method is reliable, and has a number of important advantages compared to radial immunodiffusion; namely, the much higher precision, better sensitivity, particularly in lower concentration ranges, and availability of results within two hours.


Evaluation of a micromethod for the determination of glucose in skin-puncture blood for the DuPont aca. A micromethod is described for the determination of glucose in 20 microliter of skin-puncture blood for the DuPont aca. For the determination of glucose we prefer whole blood which is deproteinised with uranyl acetate. Some modification of test conditions are programmed into the computer II. The emergency analysis of supernatant on the aca then gives the same values as the Technicon Autoanalyzer II, using glucose dehydrogenase for routine analyses. The aca readout is linearly related to glucose concentrations up to 60 mmol/l.


[Investigation of the interaction of carbamazepine or promazine with bovine serum albumin, using a new dialysis device (author's transl)]. The construction and operation of a new dialysis device are described. The unbound fraction of a drug in a buffered solution of albumin can be determined after 10-15 minutes. The usefullness of this device was demonstrated by the determination of the unbound fraction of Carbamazepine or Promazine in buffered solutions of bovine serum albumin. The results agreed with those obtained by control methods (equilibrium dialysis and gel filtration). Furthermore, the binding of Carbamazepine to bovine serum albumin was characterised by determining the overall binding constant (K1), the apparent binding constant (k+), the number of binding sites per molecule of albumin (n), the free reaction energy deltaFdegrees, and the unbound fraction of the drug.


Limulus psychophysics: temporal summation in the ventral eye. Physiological experiments on the properties of temporal summation in single cells of the peripheral visual system of Limulus have shown that the type of temporal summation and the value of the critical duration depend on the way in which the investigator arbitrarily chooses to analyze the same physiological response. The behavioral expression of temporal summation should therefore depend upon the way in which the central nervous system actually analyzes responses transmitted by peripheral structures as well as upon the nature of these peripheral responses. Accordingly, the present two behavioral experiments investigated the analysis of temporal summation carried out by the central nervous system of Limulus by investigating the psychophysics of temporal summation mediated by the ventral eye. Supersummation occurred in both psychophysical experiments up to critical durations near 4.5 sec, which was approximately the same as the reaction times or latencies of the behavioral responses at threshold. The degree of supersummation was extreme; a fourfold change in stimulus duration required an almost 40,000-fold change in stimulus intensity to remain at threshold. Even though some features of physiologically recorded receptor potentials have critical durations less than 10 msec, these findings suggest that the central nervous system of Limulus can integrate peripheral signals over intervals of many seconds. Since the source of the supersummation is the nonlinearity of the receptor transfer function at high levels, these results also indicate that a behavior at threshold can be mediated by a strong neural response.


Recognition failure of recallable words and recognizable words. Three experiments are reported introducing variations in testing mode and cuing context into the general procedures used to demonstrate recognition failure of recallable words. Recognition failure of recognizable words can be demonstrated when a cued recognition test replaces the cued recall test in these general procedures. Also, recall failure of recallable words can be demonstrated if an uncued recall test replaces the initial uncued recognition test. If the initial recognition test involves cued recognition, then both the recognition failure of recallable words and the recognition failure of recognizable words are attenuated. Recognition failure of recognizable words was also present when distractors were not used in recognition testing. It was concluded that recognition-failure phenomena represent a special class of context effects; that is, they simply result from removing original study cues from one testing context and restoring them in a second testing context. It was suggested that theories of memory that recognize that memory performance may be sensitive to testing context are not contraindicated by the demonstration of recognition failure of recallable words.


Chronic granulomatous disease in the adult. Chronic granulomatous disease is a rare, inherited disease occasionally found in adults. It is characterized by repeated infections of the skin, lymph nodes, and viscera. The underlying cause is a metabolic inability of the leukocyte to destroy certain ingested bacteria and fungi that normally are saprophytes. The diagnois should be suspected in children and adults who present with repeated episodes of infection without an apparent underlying cause. The diagnosis can be established by the nitroblue tetrazolium test. Treatment is nonspecific and directed towards the underlying bacterial or mycotic infection rather than the genetically related deficiency of the leukocyte.


Polio immunization: benefits and risks.

Polio immunization: benefits and risks. There are epidemiological as well as legal risks to polio immunization. The physician should compare the risks of vaccination with the risks which attend nonvaccination. Another view of the incidence of paralysis following oral poliovaccine (OPV) shows that the risk is about 1.6 cases per 10(6) nonimmune children given OPV and that this rises to about ten cases per 10(6) nonimmune adults exposed to OPV. There is little evidence of reversion to virulence of the virus and it is proposed that susceptibility of vaccinees and contacts to OPV is genetic. The risk of contracting poliomyelitis from either vaccine or wild virus rises about tenfold from the age of about three years to about ten years and thereafter remains constant. The risk of vaccinating children must be balanced against a tenfold risk of vaccinating when older and against a very much higher risk of paralysis or death from a wild virus. Present vaccination policies have virtually eliminated wild virus from the United States but have left many nonimmunes. The consequences of reintroduction of wild virus are examined, and the legal implications of genetic susceptibility are briefly discussed.


Quality of life and factors affecting the response to hysterectomy . Hysterectomy is the most commonly performed major surgery in the United States. A hysterectomy does not produce significant psychopathology in a psychologically mature woman. Yet a mourning process occurs as a woman reintegrates her gender identity. Organic pathology, age, socioeconomic class, types of significant relationships, meaning given menses, coitus, childbearing, children, and vocational and avocational involvements are variables affecting every woman's attitudes toward, decision to have, and reactions to a hysterectomy. Each woman's characteristic coping pattern in a personally threatening situation is apparent during her hospitalization. In the process of reorganizing her gender identity, other interests (vocational and avocational) and intimate interpersonal relationships will assume new significance. The most frequent psychopathological reaction is depression. A woman's potential for depression is increased with malignancy, predisposing personality features, a history of depressive responses to stress, and concurrent marital disruption. Data support a higher incidence of depression in posthysterectomy than in other postsurgical female patients.


Group therapy in family medicine: part 4: a case report. This paper is the last of a four-part series and presents a case report of a patient who attended a 20-week course of group therapy in a family practice. She was a patient who identified herself as medically, but not psychiatrically, sick. She was appropriately investigated and referred within the practice for assessment of her suitability for group therapy. Her course of treatment is described and explained. The satisfactory outcome of this case suggests that there may be a place in a busy family practice for referral of this type of patient.


Recognition of depression by family medicine residents: the impact of screening. Psychiatric problems are often encountered in general medical settings, yet physicians frequently fail to identify such problems. Validated questionnaires assessing psychiatric symptoms have been shown to be more sensitive than physicians in detecting cases of psychiatric morbidity. This study deals with depression, the psychiatric problem most frequently seen in primary care settings. A self-administered depression questionnaire was used to alert residents to possible cases of depression. Relay of information from the questionnaire significantly increased resident recognition of depression.


Experience of family practice residents as athletic team physicians. Providing exposure for family practice residence to all aspects of community medicine is a common goal of training programs. The Antelope Valley Hospital Medical Center Family Practice Program has initiated an innovative project which involves residents serving as team physicians for local college athletic teams. This provides a valuable opportunity for residents to learn skills they can be expected to need in their future practice. The team physician's role offers educational potential for family practice residents through experience with acute orthopedic problems as well as the preventive and psychological aspects of sports medicine. This role also serves as an example of physician responsibility for health-related activities in the acommunity.


Family medicine in the undergraduate medical curriculum. Family medicine has become an integral part of the under-graduate medical curriculum in many schools. The process of developing this important segment of the curriculum has encountered many difficulties which have centered around the particular phase in which family medicine is introduced in the student's development. The student must recognize family medicine as an academic discipline comparable to, and as important as, other traditional specialties. Through the use of the model practice unit, the development of cognitive behavioral objectives, and the provision of continuity of care experiences during the undergraduate medical curriculum, the student can grow to understand that family medicine is, in fact, as academically strong as other more traditional specialties. This article describes the experience, problems, and the development of these components in one medical school.


Pilot experience of a family practice-based combined clerkship. In order to explore alternatives in clinical undergraduate medical education, an experimental Combined Clerkship was developed and implemented on the Grand Rapids campus of Michigan State University. Two third-year medical students spent three half-days per week for 36 weeks seeing patients in the family practice office, of a facluty member. Hospitalized patients from this practice were worked-up and used as the source of inpatient specialty learning. The students attended lectures and took oral and written examinations of all required clerkships, but had no specific hospital assignment during this  time. Two hundred nineteen patients were followed by these students, compared to 174 required by the clerkships. All written and oral examinations were passed. In addition to meeting all clerkship objectives, the students cared for 680 outpatients presenting 1,035 ICHPPC-coded problems. The top ten diagnoses were identified collectively and individually, and were compared to other published studies for corroboration of representative patient problems. This project demonstrates that the objectives of required clerkships can be met in an alternative setting that allows the addition of other important experiences.


Hospital problems cared for by one family physician. Most family physicians provide regular care in the community hospital setting. The North American literature is quite deficient in documenting this aspect of family practice. The purpose of this paper is to present the content of problems cared for in a small community hospital. The study population consisted of all inpatients care for principally by the author during the first year in practice. The hospital is a 100-bed facility in a representative midwestern community of 15,000. Data analyzed included age, sex, discharge diagnoses, and outcome. Diagnoses were coded and organized according to the ICHPPC code. During the one-year study period, 509 hospital problems were cared for. Primary responsibility for 235 hospitalizations was assumed, for an average of 19.6 patients hospitalized per month. The age/sex profile, when corrected for newborns and obstetric patients, showed peaks in the 75+ age category for both sexes. By major ICHPPC category, circulatory system diseases ranked first and respiratory diseases ranked second. Most frequent specific diagnoses were: (1) newborn care, (2) vaginal delivery, (3) congestive heart failure, (4) diabetes, and (5) chronic lung disease. There were eight deaths of 3.4 percent of the hospitalizations.


Process and outcome: lack of correlation in a primary care model. Records of 87 hypertensive patients in a group family practice were reviewed to assess the validity of the process audit in determining medical care quality. Although a significant reduction in mean diastolic blood pressures was found at two follow-up intervals, physician performance scores showed no significant correlation with this outcome. Nor could an association between medical process and outcome be demonstrated when control of blood pressure to less than 95 mmHg was used as an outcome measure. The reliability between two chart auditors was poor, with complete agreement being achieved in only 29 percent of cases. Accurate quality assessment will require more practical methods of review which relate directly to patient outcomes.


Cervical cytology: use and follow-up.

Cervical cytology: use and follow-up. The Pat smear was introduced to clinical medicine 35 years ago. It is the most practical means of screening for precancerous lesions of the cervix. Endocervical and ectocervical samples improve detection. Colposcopy and colposcopically directed biopsy will document the most advanced lesion in almost all cases. The need for conization has been greatly reduced. Treatment of intraepithelial neoplasia will prevent the development of invasive cancer of the cervix.


Incidence of asymptomatic gonorrhea in women. Sixty-six of 70 consecutive cases of gonorrhea in women were reviewed retrospectively for presenting symptoms. Forty-four (44) percent were asymptomatic while an additional 48 percent mentioned only a vaginal discharge. The importance of taking routine gonorrhea cultures on all sexually active women is stressed. In medical settings where experience has shown a low yield of positive cultures, the Pennsylvania Health Department's priorities can be used to select the patients at highest risk of disease.


The response of the Limulus retina to moving stimuli: a prediction by Fourier synthesis. The Limulus retina responds as a linear system to light stimuli which vary moderately about a mean level. The dynamics of such a system may conveniently be summarized by means of a spatiotemporal transfer function, which describes the response of the system to moving sinusoidal gratings. The response of the system to an arbitrary stimulus may then be calculated by adding together the system's responses to suitably weighted sinusoidal stimuli. We have measured such a spatiotemporal transfer function for the Limulus eye. We have then accurately predicted, in a parameter-free calculation, the eye's response to various stimulus patterns which move across it at several different velocities.


Potassium transference in Nitella.

Potassium transference in Nitella. Transmembrane movements of K+ and Cl- were studied under a variety of experimental conditions. Potassium was found to carry more than 50% of an externally applied inward positive current. The increase in K+ influx was much greater than that predicted by the purely passive model. The increase in Cl- efflux accounted for less than 10% of the applied current, in agreement with the value predicted for passive movement. 2,4-Dinitrophenol (DNP) caused an 80% reduction in K+ transference and a corresponding increase in the measured electrical resistance of the membrane. DNP also reduced the isotopically measured resting K+ influx and caused a substantial increase in both Cl- influx and efflux. Lowering of the pH from 5.7 to 4.7 also reduced the net K+ influx but without drastically altering the membrane resistance. It appears the major portion of an externally applied current does not travel through passive channels, but rather is shunted through a different membrane component. In conjunction with evidence previously establishing the H+ pump as the primary ion pump in Nitella, the data presented here are consistent with a K+/H+ exchange mechanism which can account for the observed net K+ accumulation and maintenance of the membrane potential above the electrochemical equilibrium potential of the major ions. This mechanism appears to be a likely candidate for the current shunt.


Alteration of sensitivity and time scale in invertebrate photoreceptors exposed to anoxia, dinitrophenol, and carbon dioxide. The effects of anoxia, 2,4-dinitrophenol (DNP), and carbon dioxide (CO2) on the late receptor potential of Balanus lateral ocelli, Limulus ventral eyes, and the retinular cells of Linulus lateral eyes have been studied. Either anoxia, DNP, or exposure to 100% CO2 causes a depolarization of 5-30 mV and a gradual reduction and eventually abolition of the late receptor potential and an increase in the latency and time to peak of the response. This lengthening of the time scale is in contrast to the response obtained in photoreceptors that have been light-adapted or injected with calcium. In that case a loss in sensitivity is associated with a decrease in latency and time to peak. Because of these observed differences, the effects of metabolic inhibition cannot be attributed merely to a loss in regulation of intracellular free calcium. Rather, because alteration of intracellular pH (pHi) by using either (NH4)2SO4 or CO2 produced changes in the photoresponse similar to those caused by metabolic inhibition, it is suggested that changes in pHi during metabolic inhibition can account in part for the lengthening of the time scale. In addition to the changes in pHi and internal Ca++ concentration due to metabolic inhibition, the possible role of other consequences of metabolism in the transduction mechanism is also discussed.


Lithium transport pathways in human red blood cells. In human red cells, Li is extruded against its own concentration gradient if the external medium contains Na as a dominant cation. This uphill net Li extrusion occurs in the presence of external Na but not K, Rb, Cs, choline, Mg, or Ca, is ouabain-insensitive, inhibited by phloretin, and does not require the presence of cellular ATP. Li influx into human red cells has a ouabain-sensitive and a ouabain-insensitive but phloretin-sensitive component. Ouabain-sensitive Li influx is competitively inhibited by external K and Na and probably involves the site on which the Na-K pump normally transports K into red cells. Ouabain does not inhibit Li efflux from red cells containing Li concentrations below 10 mM in the presence of high internal Na or K, whereas a ouabain-sensitive Li efflux can be measured in cells loaded to contain 140 mM Li in the presence of little or no internal Na or K. Ouabain-insensitive Li efflux is stimulated by external Na and not by K, Rb, Cs, choline, Mg, or Ca ions. Na-dependent Li efflux does not require the presence of cellular ATP and is inhibited by phloretin, furosemide, quinine, and quinidine. Experiments carried out in cells loaded in the presence of nystatin to contain either only K or only Na show that the ouabain-insensitive, phloretin-inhibited Li movements into or out of human red cells are stimulated by Na on the trans side and inhibited by Na on the cis side of the red cell membrane. The characteristics of the Na-dependent unidirectional Li fluxes and uphill Li extrusion are similar, suggesting that they are mediated by the same Na-Li countertransport system.


Kinetics and stoichiometry of Na-dependent Li transport in human red blood cells. This paper describes the kinetics and stoichiometry of a tightly coupled Na-Li exchange transport system in human red cells. The system is inhibited by phloretin and furosemide but not by ouabain. Li influx by this system increases and saturates with increasing concentrations of external Li and internal Na and is inhibited competitively by external Na. Comparable functions relate Li efflux and Na efflux to internal and external Li and Na concentrations. Analysis of these relations yields the following values for the ion concentrations required to half-maximally activate the transport system: internal Na and Li 9.0 and 0.5 mM, respectively, external Na and Li 25 and 1.5 mM, respectively. The system performs a 1:1 exchange of Na and Li moving in opposite directions across the red cell membrane. We found no evidence for a simultaneous transport of more than one Na and Li by the system. The maximum transport rate of Na-dependent Li transport varied between 0.1 and 0.37 mmol/(liter of cells X h) in the red cells of the five normal male subjects studied. No significant variations between individual subjects were observed for bicarbonate-stimulated Li transport and for the residual Li fluxes which occur in the absence of bicarbonate and in the presence of ouabain plus phloretin.


The chemotactic response of plasmodia of the myxomycete Physarum polycephalum to sugars and related compounds. A new technique, the double strip method, for studying the chemotaxis of myxomycete plasmodia is described. Physarum polycephalum was attracted by the aldohexoses D-glucose, D-galactose and D-mannose and their derivatives 2-deoxy-D-glucose and maltose, thresholds ranging from 0.25 mM (D-glucose) to 5 mM (D-mannose). These sugars competed with each other, a uniform background of one of them inhibiting taxis to the others. Other attractants were N-acetyl-D-glucosamine and mannitol, with thresholds at 1 mM, and fucose (6-deoxy-D-galactose). Although in general only those carbohydrates which could support growth were attractants, there were exceptions such as 2-deoxy-D-glucose; hence metabolism of a compound was not necessary for attraction. In addition, some compounds, such as fructose, could be metabolized but did not attract. At high concentrations (about 100 mM) all the compounds tested, including attractants, could under appropriate conditions cause repulsion, probably through osmotic effects.


Kinetics of net RNA degradation during development in Dictyostelium discoideum. Based on dry weight, first-order kinetics adequately describe the net decrease of RNA in Dictyostelium discoideum NC-4 until culmination, when a cessation of RNA degradation occurs. Between aggregation and sorocarp formation, the cells lose 40% of their RNA, or 19 mM-glucose equivalents expressed in terms of cell volume at aggregation. In sorocarps the spores contain a disproportionately large amount of RNA. Net RNA contents in sorocarps and in spores are unaffected by the availability of exogenous glucose. The relationship of dry weight, cell number and packed cell volume during differentiation is given.


Growth and migration of plasmodia of the myxomycete Physarum polycephalum: the effect of carbohydrates, including agar. A method for studying the growth and migration of myxomycete plasmodia on the surface of agar and other gels was devised. The migration rate of plasmodia of Physarum polycephalum was greatly reduced when nutrients that permit rapid growth were present, and slightly reduced by most sugars tested at 56 mM, including some that were not utilized. The carbohydrate requirement of the myxomycete could be satisfied by a range of sugars and derivatives, including mannitol and agar, utilization of the latter being slight but definite. Fructose could be utilized as long as it was not the sole carbohydrate present.


Morphological conversion of 'immature' Rauscher leukaemia virus cores to a 'mature' form after addition of the P65-70 (gag gene product) proteolytic factor. When the partially purified P65-70 proteolytic factor was added at increasing concentrations to 'immature' core sub-particles of Rauscher leukaemia virus (RLV), we observed an increased cleavage of P65-70 (the gag gene product) and P40 (an intermediate cleavage product containing p30) to p30, the major group specific antigen. When examined by electron microscopy the immature cores exhibited a linear decrease in number, with a concomitant increase in the number of mature cores after treatment. Various intermediate structures retaining elements of both immature and mature forms were also observed, suggesting that the in vitro conversion from immature cores to mature cores can occur on a I:I basis.


Synthesis of transfer ribonucleic acid in KB cells infected with adenovirus type 2. The synthesis of low mol. wt. RNA has been studied in KB cells infected with adenovirus type 2 after labelling with 3H-uridine or 32P. An increasing amount of virus-coded VA RNA is detected from 8 h after infection onward. The rate of synthesis of tRNA is unchanged up to 16 h after infection and thereafter decreases; from 24 to 48 h after infection, the specific activity of tRNA is about 60% of the control value. The specific activity of cellular 5S RNA increases from 12 h after infection. When the tRNA is analysed by a two-dimensional gel electrophoresis system resolving the tRNA into 42 to 47 spots, changes in synthesis of tRNA in individual spots are seen. From 8 to 12 h after infection, an increase in the relative rate of incorporation into RNA is observed in 7 spots, while a significant decrease is detected in 8 spots. From 12 to 16 h after infection, incorporation into RNA is increased in 6 spots, but is most marked (sevenfold) in 1 spot. A decrease of incorporation into RNA in 6 spots is observed at the same time. From 24 to 34 h after infection, an increase in synthesis of RNA in 8 spots is observed and a decrease also in 8 spots. Incorporation into RNA in 2 spots is virtually shut off.


Effect of temperature on the order of electrophoretic migration of influenza virus neuraminidase and nucleoprotein genes in acrylamide gels lacking denaturing agents. When subjected to electrophoresis at 33 degrees C in 3% polyacrylamide gels with no urea added, the nucleoprotein and neuraminidase genes of an H2N2 and H3N2 virus migrate as RNA bands 5 and 6 respectively. If the temperature of electrophoresis is increased to 46 degrees C, however, this order of migration is reversed.