[Quantitative model of human erythrocyte glycolysis. Region of cell viability determined by ATP concentration].

The boundaries of the cell vitality domain in the enzyme activity space are calculated on the basis of a mathematical model of erythrocyte glycolysis. The boundaries are determined by key metabolite concentrations. The results obtained are compared with experimental data related to erythrocytic enzymopathies. It is shown that theoretical boundary enzyme activities coincide with the activities of hexokinase and in some cases phosphofruktokinase in enzyme deficient erythrocytes.


[Two forms of Ca2+-dependent ATPase from sarcoplasmic reticulum].

Two highly purified sarcoplasmic reticulum membrane fractiones differing in their sensitivities to the uncoupling action of caffeine were isolated from white skeletal muscles of the rabbit. The main protein component of both fractions is a catalytical polypeptide of Ca2+-dependent ATPase. Treatment of the caffeine-sensitive reticular fraction by trypsin or DTNB completely removes the effect of caffeine. It was found that similar effects on the caffeine-sensitive reticular fraction are exerted by bemegride, camphor, ethymizole and cordiamine. Isolation of Ca2+-dependent ATPase from both reticular fractions and reconstruction of Ca2+-transporting vesicles were carried out. Ca2+ transport by the vesicles enriched by ATPase from the caffeine-sensitive reticular fraction is uncoupled under the effect of caffeine; however, caffeine has no effect on the vesicles enriched by caffeine-insensitive reticular ATPase. The molecular weight of caffeine-sensitive and caffeine-insensitive ATPases determined in the presence of sedium dodecyl sulfate are found to be identical. Electrophoresis in the presence of digitonin revealed different electrophoretic behaviour of the two forms of ATPase.


[Interaction of platinum and palladium 5-sulfo-8-mercaptoquinoline complexes with sarcoplasmic reticulum Ca2+-dependent ATPase].

5-Sulfo-8-mercaptoquinoline complexes of platinum and palladium (complexes I and II) effectively inhibit Ca2+-dependent ATPase from sarcoplasmic reticulum. However, in contrast to K2PtCl4, K2PdCl4 and other previously investigated platinum and palladium complexes, they do not interact with the thiol groups of the enzyme. The inhibiting effects of complexes I and II are reversible and competitive with respect to ATP. In aqueous solutions complexes I and II decrease the fluorescence of tryptophane with a simultaneous shift in fluorescence towards the long-wave region. The same effect is exerted by the complexes on the fluorescence of tryptophane residues in Ca2+-dependent ATPase preparations. An addition of tryptophane to the enzyme preparations preincubated with complexes I and II partly restores the enzyme activity. It is assumed that the inhibiting effect of complexes I and II is due to their non-covalent interactions with the trytophane residues vicinal to the ATPase center.


Effects of rate of repetitive stimulus presentation on the visual evoked brain potentials of young adults with Down's syndrome.

Visual evoked brain potentials (VEP) to repeated stimuli of several interstimulus intervals (ISI) were recorded from young adults with Down's syndrome (DS). The following results were obtained: (i) An ISI effect previously observed in normals: VEP amplitudes increased with increase in ISI; some ISI effect on latency was also observed; (ii) VEP amplitudes of DS subjects were larger than VEP amplitudes of normals; (iii) VEP peak latencies of DS subjects were longer than VEP peak latencies obtained from normals; (iv) ISI had a more pronounced effect on VEP amplitudes of DS than normal subjects. These results are discussed with respect to CNS differences and issues of attention and information processing.


Totally implantable directional Doppler flowmeters.

Two totally implantable Doppler blood flowmeters have been developed for the chronic measurement of deep-body flows; made possibly by two custom-integrated circuits. The CW and pulsed Doppler instruments are small (less than 2.5 cm3), use little power (less than 30 mW), and have excellent baseline stability. The pulsed Doppler flowmeter is applied principally when velocity-profile information or a nonencircling transducer assembly is required but where minimal restraint of the animal for inductive telemetry is permissible. Using a circumferential cuff, the CW Doppler flowmeter monitors Doppler data over a at least a 3-meter range by means of RF telemetry and produces a single velocity estimate. These instruments compliment each other and other telemetry systems by proving the researcher with alternatives for the long-term measurement of deep-body flow without percutaneous leads.


Totally implantable dimension telemetry.

A totally implantable dimension telemetry system has been developed to instrument animals for chronic physiological research. Implantable signal processing electronics allow free-roaming animals with no percutaneous leads while retaining the long-term redproducibility of fixed implanted transducers. Two low-powered, custom-integrated circuits have been developed and assembled into an implantable package capable of measuring one dimension channel. The system has been operated in the amplitude modes of through-transmission and reflection as well as in a new Doppler-power configuration and aimed at determining interfaces between blood and surrounding structures. In a addition to single channel systems, these ICs are key elements in multimode, multidimensional implants capable of more accurate characterization of deep body structures.


An integrated circuit approach to totally implantable telemetry systems.

A series of totally implantable telemetry systems has been developed to determine such key physiological parameters as blood flow, pressure, dimensions, temperature, and bioelectrical activity in chronic research animals. Custom integrated circuits provide the signal-processing complexity and performance required to sufficiently instrument the animals for an accurate prediction of human responses. Additional implant and transducer technologies are necessary to complete the instrument package. Although the costs of these technologies are high, they are more than offset by the unique information obtained and overall reduction in the expenses of medical research because fewer animals can be studied over longer periods. A number of the IC-based implants are in use in several physiology and experimental drug studies where adequate reliability and performance could not be achieved by alternate approaches.


The exceptional responsiveness of certain human myeloid leukemia cells to colony-stimulating activity.

We have studied the marrow cells from a patient with acute myeloid leukemia (AML) for their responsiveness to colony-stimulating activity (CSA) in vitro. The AML cells were stimulated by CSA to rapid and extended growth in liquid culture. In the absence of CSA, the majority of cells died. CSA also stimulated the clonal growth of AML cells, and the minimum requirement for CSA was one-tenth to one-fiftieth that required to stimulate the growth of normal marrow CFU-C. CSA for AML cells was eluted from Sephacryl S-200 columns in fractions that represented an apparent molecular weight of 45,000 daltons. This fraction also produced optimal stimulation of normal human marrow. During remission, the patient's marrow cells did not grow in liquid culture and produced normal numbers of granulocytic and erythroid colonies in response to CSA and erythropoietin. Extended culture of the AML cells resulted in cell differentiation evidenced by decreasing proliferative capacity and by morphological and histochemical changes. These studies indicate that certain AML cells are extraordinarily responsive to CSA, an in vitro mediator of normal granulopoiesis.


Sensitivity of Neisseria gonorrhoeae to antibiotics in London (1976-78).

Three surveys of the sensitivity of pretreatment isolates of gonococci to penicillin, ampicillin, tetracycline, spectinomycin, streptomycin, and co-trimoxazole were carried out during the period 1976-78. Compared with the results of previous surveys in the London area the decline in the proportion of strains of gonococci which are insensitive to penicillin appears to have halted. No changes were found in the levels of resistance to ampicillin, tetracycline, or spectinomycin during the period surveyed, although there was a slight increase in the proportion of strains requiring concentrations of 20 microgram spectinomycin per ml for inhibition. Streptomycin resistance has decreased considerably and 91% of strains are now sensitive to 10 microgram streptomycin per ml.


[Left ventricular function in chronic obstructive lung disease (author's transl)].

Left ventricular function was studied at rest and during post-extrasystolic potentiation in 18 patients with chronic obstructive lung disease. The contractility indices used were obtained from pressures recorded in the isovolumetric period (left ventricular end-diastolic pressure, Vmax., VECmax., dP/dtmax.) and from volume variations during ejection (end-diastolic volume, ejection fraction, VCF). Left ventricular diastolic compliance was also evaluated. All patients were hypoxic (PaO2 = 58 +/- 7 torr); six of them had cor pulmonale (group B); the remaining 12 patients constituted group A. Left ventricular function of groups A and B was similar; we conclude that right cardiac failure, in cor pulmonale, is not secondary to left ventricular failure. However, left ventricular dysfunction exists; the left ventricle is hypertrophied (probably resulting from chronic hypoxia). Pump function is altered (abnormal ventricular function points are found), but left ventricular kinetics is normal or exaggerated (ejection fraction and VCF are increased). Isovolumetric phase contractility indices are diminished; however, they may increase normally during post-extrasystolic potentiation. Left ventricular compliance is abnormal due to left and right ventricular hypertrophy and to paradoxical movement of the interventricular septum which impedes diastolic expansion of the left ventricle. These changes are responsible for decreased left ventricular output. There seems to exist an impairment of left ventricular function related to both intrinsic (secondary to hypoxia, hypercapnia, left ventricular hypertrophy) and extrinsic factors (right ventricula hypertrophy deviating interventricular septum, lowering of left ventricular preload).


[Increase of non-specific resistance to infection by synthetic adjuvants].

MDP and some other synthetic glycopeptides which are endowed with adjuvant properties are also able to increase non-specific resistance of mice to bacterial infections. They are effective by various routes including the oral route, and this protective activity can be demonstrated in animals having a poor immune status.


[Mechanism of action of T cell factors regulating antibody formation].

While the induction of antibody synthesis depends on antigen specific T cell factors, its magnitude is under control of non antigen specific T cell factors. In this respect, TRF ("T cell Replacing Factor") amplifies antibody responses while IBF ("Immunoglobulin Binding Factor") acts as a suppressor factor. Using cultures of spleen cells from nude mice, we show that both factors act sequentially, influencing the final differenciation of B cells to antibody producing cells. We have no evidence of direct interaction between TRF and IBF.


[Macrophage receptors].

Macrophages are involved in many immunological functions such as phagocytosis, cytotoxicity, antigen binding and cooperation with lymphocytes. The triggering of those functions involves membrane receptors. Several receptors species are well characterized, but some phenomena can be accounted for only if macrophages are endowed with nonspecific adhesive structures. A study of the effect of various physical or chemical factors on the binding of several particle species by rat peritoneal macrophages allowed us to classify nonspecific receptors and discuss the mechanisms involved in some types of cellular interaction.


[Pharmacologic study of inflammatory processes. Modification of polynuclear neutrophil chemotaxis].

A study of rat polymorphonuclear chemotaxis has been made by a direct microscopic method and the effect of inflammatory reactions induced by carrageenan, calcium pyrophosphate and complete Freund's adjuvant has been studied. In addition the action of various drugs such as cholera toxin, colchicine, prostaglandins and certain immunomodulators, was investigated. The results have been analysed with special regard to the role of chemotaxis in inflammatory responses.


[Cell mediated cytolysis: identification, enumeration and characterization of killer cells].

Killer cells responsible of the cell mediated cytolysis are identified by a microtechnique: effector cells are individually associated to target cells and incubated at 37 degrees C; killers are identified by their associated target lysis. Thus killer cells are enumerated in the effector cell suspensions. Furthermore, isolated killer can be characterized and their lethal action studied.


[Contribution of two-dimensional immunoelectrophoresis technics to the study of the structure and the morphogenesis of human adenovirus].

The two-dimensional immunoelectrophoresis has been applied to human adenovirus type-2 structural analysis. This method is both qualitative and quantitative and was used in the following studies. 1) Detection of major and minor capsid antigens. 2) Identification of viral antigenic components in the infected cell material. 3) Quantification of antigens and serological characterization of ts mutants. 4) Identification of polymeric forms of structural proteins. 5) Assembly analysis of capsid subunits. 6) Stoichiometric analysis of proteins within the virion. 7) Obtaining of monospecific sera.


[Sickle cell anemia and the affinity of the blood for oxygen].

Blood affinity for oxygen is reduced in patients with homozygous HbS disease. The mechanisms were related to polymerisation and sickling process. In the HbS blood, P50 values were related to the percentage of sickling, the effect of prior deoxygenation on P50 measurement was established. This work underlines the influences of experimental conditions on the determination of sickle cell blood affinity and the difficulties inherent in the evaluation of in vivo oxygen transport in sickle cell disease.


[Localization of binding sites in the hemoglobin-haptoglobin complex].

The binding and specific elution of Hb peptides from Hp was studied. Our results were confirmed by the study of inhibition of binding of alpha chains to Hp. In conclusion, a model of contact areas of Hp-Hb complex is proposed.


[Non-enzymatic hemoglobin glycosylation in the normal and diabetic patient].

The criteria to be satisfied for a valid quantitation and the physiopathological significance of results: nature, site-specificity and kinetics of glycosylation, finally theoretical consideration of glycosylation of other proteins are the problems discussed.


[Methods of tissue characterization with ultrasonic spectroscopy, analysis of the results obtained, prospects for clinical application in a short time].

So far, to account for ultrasonic attenuation in soft tissues molecular scale relaxation theory is retained. In addition to these mechanisms, the authors have obtained experimental evidence proving the role also plaid by cellular scale resonance mechanisms. Moreover, in addition to incoherent diffusion, it has been found that some tissues exhibit some coherent diffusion. All these experimental findings allows us to establish the feasability of non invasive ultrasonic biopsies.


[Clinical and biological forms of cytochrome b5 reductase deficiency].

Twenty-four personal cases of recessive congenital methemoglobinemia (RCM) due to cytochrome b5 reductase deficiency are analysed. They can be divided into two categories: 1) RCM type I, in which cyanosis is the single clinical symptom; 2) RCM type II in which cyanosis is associated with severe mental retardation and bilateral athetosis. The enzyme deficiency is restricted to the red cell soluble cytochrome b5 reductase in RCM type I, whereas in the type II form the enzyme defect is generalized to all tissues, involving both the soluble and the microsomal forms of cytochrome b5 reductase. Different mutations occurring at the same locus might account for this heterogeneity. However the mechanism of brain damage in case of generalized deficiency of cytochrome b5 reductase is still unknown.


[Medical aspects of superoxide dismutases].

The role of superoxide radicals and of superoxide dismutases in inflammation is described. Encapsulation of the enzyme in liposomes leads to an increased organ specificity on injection into animals. Preliminary results of medical application are presented.


[Ultrastructural study of cardiotoxicity and skin alterations in the golden hamster after treatment with 8 different anthracyclines].

Golden hamsters were submitted to i.p. administration during 4 weeks of 8 anthracyclines, adriamycin (ADM), detorubicin (DTR), daunorubicin (DNR), 4'-epi-adriamycin (eADM), adriamycin hydrochloride (ADMh), rubidazon (RBZ), aclacinomycin (ACM) and AD32, at doses equivalent to 3/4 of those which are optimally oncostatic on murine L1210 leukemia. The comparative study of the mortality, the electron microscopic (EM) alterations of the myocardium, and the light microscopic (EM) alterations of the myocardium, and the light microscopic (LM) lesions of the skin, show that ACM and AD32 are the least toxic drugs. EM detected almost no early lesions of myocardium in ACM treated animals, but, after 4 week's treatment, severe cardiac alterations appeared which, like those after AD32 treatment, are non lethal and reversible. Similarly. LM revealed no histologic changes in the skin following ACM and AD32 administrations, but pathologic alterations, atrophy and alopecia, were observed in animals receiving all other drugs.


[Recent results in the field of vinblastine group antitumour alkaloids. Biochemical studies].

Studies on the interaction between vinblastine-like alkaloids and their receptor, i.e. tubulin, are reported. They shed some light on the structure-activity relationships in this medicinally important series: the configuration at C14' and C16', as well as the presence of the methoxycarbonyl group on C16' seem to play an essential role in the determination of biological activity. A new analogue, detected by its specific behaviour with tubulin, was found, in vivo, to be as active and less toxic than vinblastine.


[Recent data on the kidney tubule behavior of phosphorus, calcium and magnesium ions].

Information recently obtained about tubular renal handling of phosphorus calcium and magnesium ions deals with: 1. Localization of transport processes along the nephron; 2. Effects of several hormones on those transports, particularly parathyroid hormone and calcitonin, and localization of their receptor sites along the nephron; 3. Adaptation of phosphate tubular handling to its content in the diet; 4. Mechanisms of cellular transports.


[Regulation of calcium metabolism ; its rhythmic variations].

In rats fed a calcium-deficient diet, the amplitude of daily variation of plasma ionized and total calcium increased markedly whereas plasma 45Ca daily fluctuation remained essentially unchanged. Normal daily fluctuations in plasma 45Ca, lost after thyroparathyroidectomy, were restored by feeding rats a high-calcium diet. A suggestion is that circadian rhythmicity originates as a result of dynamic properties involving nonlinear processes of calcium metabolism.


[Experimental study of left ventricular assistance].

An experimental study, on normal dog and a model of cardiogenic shock, using an extracorporeal circuit including 2 cannulae and a centrifugal pump, has shown the superiority of the ventriculo-aortic bypass on the atrio-aortic bypass, for a complete left ventricular mechanical assistance.


[Reactive metabolites of xenobiotics : their role in the hepatotoxicity of drugs].

Certain drugs are transformed into reactive metabolites by cytochrome P-450, a hepatic microsomal enzyme. The reactive metabolites covalently bind to hepatocyte macromolecules, thus determining liver lesions. Induction of microsomial enzymes increases the formation of reactive metabolites and exaggerates hepatotoxicity of these drugs.


[Hepatic tissue enzymes: study in cultures of rat liver epithelial cells. Control and analysis of cells by cytogenetic and mass spectrometric methods. Pharmacological applications].

Extensive studies of parameters conditioning selection and high plating efficiency of epithelial liver cells at primary seeding allowed us to set up a technique for the routine culture of liver cells from rats of various ages (18 day-old pc to 7 month-old) in Ham F10 medium supplemented with 10 p. cent fetal calf serum and 10 p. cent human serum. Cultures, after several passages, or sometimes at primary seeding were free of fibroblasts. The quality of water for culture medium preparation was found to be a very important parameter. G-banding caryotype showed that cells in culture were diploid until 15-20 passages. Various metabolic pathways have been studied in primary culture and in cell lines: enzymes of the anaerobic metabolism of hexoses and metabolism of steroid hormones and xenobiotics. Activity of glucose-6-phosphatase was nearly lost in all cultures. Activity of glucose-6-phosphatase was nearly lost in all cultures. Aldolase showed a specific liver activity with a cleavage ratio of phosphofructoses (F-1,6-diP/F-1-P) equal to 1 or about 1 in several primary cultures and cell lines. Many metabolites arising from incubation of cell lines with 14C-labelled corticosterone, corticosterone-21-sulfate, testosterone and progesterone have been isolated and quantitated by gas liquid chromatography (GC) and mass fragmentography coupled to GC, using 14C/12C isotope ratio measurements. These metabolites indicate the presence in cultured cells of 3 alpha/beta-steroid-reductases, 4-ene steroid reductases and hydroxylases at various positions: 2 alpha, 2 beta, 6 alpha, 6 beta, 7 alpha, 17 beta and 16 alpha. These cell lines were able to activate carcinogens through the epoxide-diol pathway and are suitable for drug metabolism study.


[Hypothalamic control of TSH secretion. Current methods of exploration and perspectives for the future].

The progress about the control by the pituitary gland of TSH secretion involves the clinical use of TRH test. However some TSH deficiencies are due to an hypothalamic disorder. A better knowledge about the aminergic regulation of the TRH secretion is necessary to design a new test exploring the hypothalamic structures which control TSH secretion.


[Value of 17-hydroxyprogesterone determination in exploration of adrenal cortex enzyme deficiencies].

17-hydroxyprogesterone (17-OH-P) was measured in various populations by radioimmunoassay, using a highly specific antibody produce in the rabbit. Dynamic tests were performed with ACTH, dexamethasone and estroprogestative drugs  and the role played by the adrenals and the ovaries in 17-OH-P production could be assessed. 17-OH-P determination is of interest in that, it allows the diagnosis of 21-hydroxylase deficiency, where values above 10 ng/ml are often found. Associated with the measure of testosterone and delta 4-androstenedione, it is also useful in the management of the disease. In the mild form of congenital adrenal hyperplasia with late revelation of the symptoms, determination of 17-OH-P following ACTH stimulation allows of relative diagnosis.


Chronic pain syndromes and their treatment. III. The piriformis syndrome.

The piriformis is a deep-seated muscle, most of its muscular portion being part of the dorsal wall of the pelvis. The lateral portion and its insertion is extra-pelvic and lies deep to the glutei. Like more superficially located and therefore more easily accessible skeletal muscles, the piriformis too can be the seat of trigger points, giving rise to symptoms indistinguishable from those of other causes of low backache, unless a deliberate search is made for the signs specific to the piriformis syndrome. Having made a presumptive diagnosis, confirmation is gained by palpating the muscle itself via rectum or vagina and reproducing the pain by digital pressure. If this test also is positive, the muscle is injected, the approach being either through the sciatic notch, from the perineum, or through the vagina. Immediate relief of pain is experienced after the solution of local anaesthetic and steroid has been deposited deep within the fleshy portion of the muscle.


Effect of a vegetarian diet and dexamethasone on plasma prolactin, testosterone and dehydroepiandrosterone in men and women.

This study reports the effect of a vegetarian diet and dexamethasone administration on the hormone status of healthy Caucasian men and premenopausal women. A lower nocturnal release of prolactin and testosterone occurred in men fed a vegetarian diet, while in women, dexamethasone administration decreased the nocturnal release of prolactin and caused a greater decrease of plasma dehydroepiandrosterone (DHEA). These results show that diet modification can induce hormonal changes, If similar changes occur in patients with breast and/or prostatic cancer, diet modification may be of benefit in these patients with tumors known to be hormonally dependent.


Cell proliferation kinetics of epidermis and sebaceous glands in relation to chalone action.

Median S-phase lengths of pinna epidermis and sebaceous glands, and of epithelia from the oesophagus and under surface of the tongue of Albino Swiss S mice were estimated by the percentage labelled mitoses method (PLM). The 18.4 and 18,8 hr for the median length of S-phase for pinna epidermis and sebaceous glands respectively made it possible for these two tissues to be used experimentally for testing tissue specificity in chalone assay experiments. The 10.0 and 11.5 hr for oesophagus ang tongue epithelium respectively made experimental design for chalone assay difficult when pinna epidermis was the target tissue. The results of the Labelling Index measured each hour throughout a 24-hr period showed no distinct single peaked diurnal rhythm for pinna epidermis and sebaceous glands. Instead a circadian rhythm with several small peaks occurred which would be expected if an S-phase of approximately 18 hr was imposed on the diurnal rhythm. This indicates that there may be very little change in the rate of DNA synthesis. The results are given for the assay in vivo of purified epidermal G1 and G2 chalones, and the 72--81% ethanol precipitate of pig skin from which they could be isolated. These experiments were performed over a time period which took into account the diurnal rhythm of activity of the mice as well as the S-phase lengths. Extrapolating the results with time of action of the chalone shows that the G1 chalone acts at the point of entry into DNA synthesis and that the S-phase length was approximately 17 hr for both the pinna epidermis and sebaceous glands. This may be a more correct value since the PLM method overestimates the median S-phase length as it is known that in pinna skin the [3H]TdR is available to the tissues for 2 hr and true flash labelling does not take place. The previous reports that epidermal G1 chalone acts some hours prior to entry into S-phase resulted from experiments on back skin where the S-phase is shorter and there is a pronounced diurnal rhythm which could mask the chalone effect. The epidermal G2 chalone had no effect on DNA synthesis even at different times in the circadian rhythm. Thus the circadian rhythms and S-phase lengths of the test tissues need to be considered when experiments are performed with chalones. Ideally, the target tissues selected for cell line specificity tests should have the same cell kinetics for the easier and more accurate assessment and interpretation of results. When the tissues have markedly different cell kinetics, experimental procedures and results need to be evaluated accordingly. The point of action of G1 chalone can only be assessed if the effect is measured over the peak of incorporation of [3H]TdR into DNA. The results of the effects of skin extracts are analysed in relation to changes in the availability of [3H]TdR for the incorporation into DNA and to the possibility of there being two distinct populations of proliferating cells.


Ultrastructural and biochemical study of extracellular matrix vesicles in normal alveolar bone of rats.

The occurrence of vesicles in the extracellular matrix of alveolar bone of normal young rats was demonstrated by both ultrastructural and enzymatic studies. Transmission electron microscopy revealed abundant vesicles in the matrix. The presence of hydroxyapatite crystals, both within the vesicles and in the matrix, was affiliated with rupture of the vesicular membrane. Calcifying nodules were scarce. High levels of both specific and total activities of alkaline- and pyrophosphatases were found in the fraction of isolated vesicles. This fraction also showed activities of different ATPases and acid phosphatase.


The abdominal muscle receptor organ in Astacus leptodactylus (Crustacea).

The structure of both the slow- and the fast-adapting abdominal muscle receptor organ of Astacus leptodactylus is described with particular reference to differences between the two systems. The receptors are composed of a thin muscle that extends from the front edge of one segment to the front edge of the following and a sensory cell connected with this muscle. In the zone where the sensory cells enter their respective muscle, muscle fibers are reduced (zone of relative muscle exclusion = ZRME) and partly replaced by connective tissue. The occurrence of dendritic processes of both the slow and the fast neurons is confined to this zone. The following differences between the two receptor types are established: (1) The fast receptor muscle reveals a smaller sarcomere length than the slow receptor muscle and a higher myosin/actin filament ratio. (2) Muscle fibers that pass the ZRME are always found at its periphery in the fast system, separated from dendritic processes by layers of connective tissue, while in the slow system muscle fibers frequently are intermingled with the sensory elements. (3) The ZRME of the slow receptor is 20-30% longer than that of the fast receptor. (4) The dendritic varicosities of the slow neuron, on an average, contain many more mitochondria than those of the fast neuron. (5) Dendritic processes (fine twigs as well as varicosities) are juxtaposed to the sarcolemma of the muscle fibers only in the slow system; in the fast system dendrites and muscle are spatially separated by connective tissue. It is assumed that these differences between the two receptor types are at least in part responsible for the different thresholds observed in physiological experiments.


Capillary distribution and metabolic histochemistry of the lateral propulsive musculature of pelagic teleost fish.

Metabolic and vascular adaptation of teleost lateral propulsive musculature to an active mode of life was investigated in four pelagic teleosts (mackerel, yellowtail scad, pilchard and Australian salmon). Histochemical profiles and capillarisation data of the red and white muscle were compared to those of less active demersal species. Pelagic white muscle stained positively for the aerobic enzymes succinate dehydrogenase and NADH diaphorase, and had both subsarcolemmal and intermyofibrillar mitochondria which corresponded to the loci of the histochemical stain. Subsarcolemmal mitochondria tended to be localised close to capillaries. In contrast, white muscle from demersal species was unstained for the same enzymes and was devoid of mitochondria. Red muscle of all species had abundant mitochondria and stained intensely for aerobic enzymes. Capillarisation was quantified by determining the percentage of fibres surrounded by a given number of peripheral capillaries, mean fibre diameter, mean number of peripheral capillaries, capillary: fibre ratio and sharing factor where appropriate. Red muscle of mackerel, Australian salmon, pilchard and scad are better vascularised than red muscle of the flathead having 153, 200, 242, 291 and 309 microns 2 of cross-sectional fibre area per peripheral capillary, respectively. White muscle of mackerel, pilchard and scad are better vascularised than white muscle of the Australian salmon and flathead having 2040, 3367, 4992, 9893 and 10,469 microns 2 of cross-sectional fibre area per peripheral capillary, respectively. Red muscle of Australian salmon had distinct regional variation. Deep red muscle was found to be more highly vascularised (4.2 peripheral capillaries per muscle fibre) than lateral red muscle (1.9 peripheral capillaries per muscle fibre). Red muscle of the other species was less heterogeneous. White muscle capillarisation was slightly variable in all species. It is concluded that the white muscle of the pelagic species studied is functionally and structurally adapted for sustained aerobic activity with relatively abundant mitochondria being preferentially situated close to the source of gas and metabolite exchange.


The cytoplasmic origin of variability in the timing of S phase in mammalian cells.

The time at which S phase begins in mammalian cells is highly variable with respect to cell age. Evidence is presented that this variability does not arise because the initiation of DNA synthesis depends on the stochastic interaction of an initiator substance with a rare initiation site. Instead, the signal responsible for starting S phase must appear at random in the cytoplasm and may be transient.


Immune depression in trypanosome-infected mice. IV. Kinetics of suppression and alleviation by the trypanocidal drug Berenil.

Mice infected with T. congolense were monitored for numbers of parasites in peripheral blood, changes in spleen cell populations, immune depression and suppressor cell activity. Depression of B and T lymphocyte responses and the appearance of suppressor cell activity in spleens of infected mice paralleled the appearance of parasites in the peripheral blood. The immune depression was manifest before any visible changes in spleen cell populations occurred. Treatment of infected mice with the trypanocidal drug Berenil resulted in a rapid clearance of parasites from the peripheral blood, a parallel loss of immune depression and suppressor cell activity and a gradual return towards normal spleen cell composition. The splenic white pulp showed severe depletion following longstanding infection with T. congolense. However, following treatment with Berenil there was rapid repopulation of the white pulp and widespread active germinal centre formation.


The clinical spectrum of Reiter's syndrome and similar postenteric arthropathies.

Certain infections of the genitourinary and gastrointestinal tracts, such as nongonococcal urethritis, dysentery and yersiniosis, precipitate characteristic arthritic syndromes in genetically susceptible individuals. Eye and skin lesions in the form of conjunctivitis, iritis, keratodermia blenorrhagica and erythema nodosum occurring in association with particular distributions of arthritis make recognizable clinical entities. Reiter's syndrome may be diagnosed with certainty from the presence of tender heels, low back pain, a predominance of knee and foot arthritis and pyuria, when the more obvious clinical markers of the syndrome are absent; a flagrant case represents one of the easiest clinical diagnoses in medicine. Diagnosis is important for a good prognosis, optimal treatment and sometimes prophylactic measures. Sacroiliitis often progressing to spinal ankylosis is a prominant feature in the B27-positive patient. Erythema nodosum occurs in B27-negative subjects as a response to yersiniosis and ulcerative colitis.


Penetration of protective gloves by epoxy resin.

A gas jointer developed dermatitis from epoxy resin of Bisphenol A type. This substance penetrates plastic and rubber gloves. The man was compelled to change his job. There is a need for new types of gloves which are impermeable. The wearing of the existing types of glove by those not sensitised may be worthwhile because it probably lessens the dose of allergen absorbed and hence lessens the incidence of sensitisation.


Captafol dermatitis in the timber industry.

Captafol is a common cause of dermatitis amongst workers in the timber industry. In a survey of 14 timber treatment plants 23% of 133 workers exposed to captafol gave a history suggestive of occupationally induced dermatitis. Although allergic dermatitis can occur, irritant dermatitis is far more common. Attention to plant and personal hygiene will reduce the prevalence of captafol dermatitis significantly. Recommendations on how to achieve this are made. "The ultimate end...is not knowledge, but action. To be half right on time may be more important than to obtain the whole truth too late."


Oil of turpentine--a disappearing allergen.

Oil of turpentine has become an infrequent allergen because of its replacement by the petroleum product white spirit, its deliberate exclusion from industrial products, and because the balsam oils used nowadays do not contain the sensitiser delta 3-carene. On the basis of the generally low incidence of sensitisation being currently recorded, the International Contact Dermatitis Group recommend that oil of turpentine be removed from standard patch test series.


Acne vulgaris associated with antigonadotropic (Danazol) therapy.

A case of a young woman in whom nodulocystic acne developed while being treated for endometriosis with danazol, an antigonadotropic drug, is described herein. Although this agent, a derivative of 17 alpha-ethinyl testosterone, has been noted to possess weak androgenic properties, it has not been widely appreciated that danazol's androgenic side effects, particularly acne and seborrhea, occur frequently and may require prompt treatment.


Hypertrophic obstructive cardiomyopathy and coronary artery spasm.

Three patients had hypertrophic obstructive cardiomyopathy and coronary artery spasm. The clinical diagnosis of hypertrophic obstructive cardiomyopathy, in all patients, was confirmed by echocardiography and angiography. Significant spasm of the right coronary artery was demonstrated in each patient by selective coronary arteriography. One patient had atherosclerotic obstructive three vessel disease, while the other two showed no evidence of any fixed organic narrowing of the coronary arteries. ST segment elevation in the inferior ECG leads was documented in two of the patients in association with coronary spasm.


Formation and properties of reactive aldehydes.

4-Hydroxyalkenals react easily with SH groups in enzymes and structural proteins to give stable adducts in which the aldehyde is bound through a thioether linkage to the protein. This reaction represents the mechanism by which these compounds block certain metabolic processes (DNA, RNA and protein synthesis, respiration, glycolysis) and exert their antitumour activity. A highly significant inverse correlation exists between the number of hydroxypentenal-sensitive SH groups in the soluble proteins and the doubling time of 12 transplantable animal tumours. Hydroxyalkenals applied peritumourally completely prevent or significantly delay growth of the solid forms of four animal tumours. The almost non-toxic adducts of 4-hydroxypentenal-cysteine 1:1 and crotonal-cysteine 1:2 applied intraperitoneally prevent or inhibit growth of Ehrlich ascites tumour in mice. The possible formation of unsaturated aldehydes in vivo from lipids, carbohydrates and diamines is discussed.


Carcinostatic activity of methylglyoxal and related substances in tumour-bearing mice.

Methylglyoxal treatment of tumour cells in vitro primarily depresses protein synthesis, in contrast to trans-4-hydroxypent-2-enal (HPE) which preferentially inhibits DNA synthesis. Methylglyoxal and hpe are potent carcinostatic agents in vitro but relatively ineffective in vivo. Both aldehydes have a short half-life in vivo which may explain their poor carcinostatic properties when administered other than peritumorally. Several possibilities of increasing the effective half-life were investigated including (i) multiple intraperitoneal injections, (ii) concomitant administration of an inhibitor of glyoxalase I, (iii) administration of aldehyde-cysteine adducts, and (iv continuous intravenous infusion. Methylglyoxal (36 mg/kg i.p., twice daily) was slightly less effective in inhibiting the growth of the solid form of Ehrlich carcinoma than a dose of 72 mg/kg (inj. 1); 36 mg/kg (inj. 2) 46.2% compared to 51%. The aldehyde was more effective aginst the ascitic form of the tumour, with 99.76% inhibition of growth after giving 72 mg/kg twice daily for five days followed by 36 mg/kg for five days. The glyoxalase I inhibitor S-(p-bromobenzyl)-glutathione didnot significantly enhance the activity of methylglyoxal against the solid form of the tumour. Nicotinamide (1% w/v in the drink) was similarily inactive. Methylglyoxal in combination with nicotinamide was significantly more effect (P less than 0.05) than methylglyoxal alone (36 mg/kg, twice daily) in inhibiting the growth of the ascitic tumour. Methylglyoxal-N-acetyl-L-cysteine was four times less toxic than methylglyoxalalone but was marginally less effective against the ascitic form of the tumour. Doses of these adducts equivalent to 144 mg/kg per day of methylglyoxal were more effective P less than 0.05) than the optimal regime of methylglyoxal in inhibiting the solid tumour (67.5% inhibition compared to 51%). Treatment of mice bearing the ascitic form of Sarcoma 180 with five daily doses (i.p.) of an HPE-cysteine adduct equivalent to a dose of HPE alone of 32-256 mg/kg per day significantly increased survival time by comparison with controls. The adduct was 2-3 times more effective, dose-for-dose, than HPE alone in inhibiting tumour growth. Purified buffered methylglyoxal has an LD50 on continuous infusion into the right lateral tail vein in mice of more than 3.0 mg/g per day (seven days at 2.8 ml/day). Local oedema followed by tail necrosis occurs at doses in excess of 0.25-0.5 mg/g per day in mice bearing the solid forms of the syngeneic tumours: squamous carcinoma D; lymphosarcoma 1 (WH/Ht mice); and spontaneous mammary D5056 (CBA/CA mice). A maximum tumour volume growth delay of 3.4 days at Day 17 (P less than 0.001) after transplantation was observed after infusion of 0.5 mg/g per day methylglyoxal on Days 11-17 in the CBA/CA D40 syngeneic mammary tumour. Tumour regrowth after termination of therapy eliminated the significant difference between control and methylglyoxal-treated tumours by Day 27. Methylglyoxal infusion (0...


Regulation of mitotic activity in rat vaginal epithelium: relationships between the level of its inhibitor (G2-chalone) and estrogens.

The level of a tissue-specific inhibitor of mitotic activity (G2-chalone) and mitotic activity in the vaginal mucosa of cycling rats of varying age and castrated rats were studied. A direct correlation between the level of the inhibitor and mitotic index is found in cycling animals. Both parameters are maximal during estrus and minimal in proestrus, when estrogen level in blood circulation is the highest. The undulating variations in G2 inhibitor level during estrous cycle are less pronounced and the concentrations of the inhibitor in relevant phases are significantly lower in aged females than in adult rats. Administration of estradiol benzoate (1 microgram/100 g) to castrated female rats was followed by a significant decrease in mitotic inhibitor level in vaginal mucosa within 12 hrs. This, in turn, was followed by a rise in mitotic activity 18 hr after estrogen administration. Therefore, the estrogen exerts its effect on mitotic activity in target tissue after it has induced a decrease in the level of the antimitotic factor (G2-chalone).


Active transport of calcium in membrane vesicles from Mycobacterium phlei.

Active transport of calcium ions has been demonstrated in inside-out membrane vesicles from Mycobacterium phlei mediated by respiratory linked substrates as well as by ATP hydrolysis. The uptake of calcium exhibited an apparent Km of 80 microM and V of 16.6 nmol calcium uptake x min-1 x mg protein-1. A fortyfold concentration gradient for calcium ions was calculated for both the ATP-induced and the respiration-induced transport of calcium. Removal of coupling-factor-latent ATPase resulted in the complete loss of ATP-driven Ca2+ transport whereas the respiration-driven uptake was reduced by 40-50%. The uptake of calcium was inhibited by the proton conducting ionophores carbonylcyanide m-chlorophenylhydrazone and Gramicidin-D. The accumulated calcium was freely exchangeable with external calcium and was rapidly released by the addition of inhibitors of energy transduction, proton-translocating uncouplers or the ionophore A23187. The uptake of the weak base, methylamine, upon the oxidation of respiratory-linked substrates or the hydrolysis of ATP showed the generation of a protein gradient (inside acidic) which was partially collapsed on the addition of calcium ions. These results suggest that a Ca2+/H+ antiport mechanism may be responsible for the transport of calcium.


Urinary acid mucopolysaccharides in multiple sulfatase deficiency (mucosulfatidosis).

Urinary acid mucopolysaccharides (AMPS) excretion was investigated in a Japanese case with Multiple Sulfatase Deficiency (MSD) (Mucosulfatidosis). The patient excreted AMPS 4 to 5 times more (as carbazoluronic acid) than controls. The cellulose acetate gel electrophoresis clearly indicated two major AMPS which co-migrated with heparan sulfate and chondroitin sulfate A/C. Enzymic digestion with chondroitinase AC and ABC, and by testicular hyaluronidase plus amino sugar analysis also confirmed that our case excreted heparan sulfate and chondroitin sulfate A/C. These findings suggest that there are heterogeneities of urinary AMPS excretion among cases with MSD.


Changes in antiplasmin and plasmin activities during extreme hemodilution and open heart surgery in dogs.

The effects of extreme hemodilution and open heart surgery on antiplasmin and plasmin activities were investigated in dogs. Assays for plasmin and antiplasmin activities were performed with a chromogenic peptide substrate for plasmin. After hemodilution and during cardiopulmonary bypass (CPB), plasmin activity on the substrate was observed and levels of both "fast-reacting" and "total" antiplasmins fell. The plasmin activity was shown to be due to the formation of alpha2-macroglobulin-plasmin complex which exhibited amidolytic activity on the chromogenic substrate. The falls in antiplasmin activity together with the appearance of the alpha2-macroglobulin-plasmin complex revealed that activation of the fibrinolytic system had occurred. After the operation and following reinfusion of autologous blood, decreased plasmin and increased antiplasmin activities were observed. On the first and sixth days following the operation plasmin activities were still slightly higher than pre-operation values, whilst antiplasmin activities were normal.


The in vitro cellular response of human lymphocytes to trinitrophenylated autologous cells: HLA-D restriction of proliferation but apparent absence of HLA restriction of cytolysis.

Primary as well as secondary proliferative and cytotoxic responses to 2,4,6-trinitrophenyl (TNP)-modified autologous human cells have been studied. Proliferative responses have been obtained both by primary (peak on day 6) and secondary (peak on day 2--3) stimulation. Both responders and nonresponders were found among the panel of unrelated individuals tested. All responders in a secondary reaction also gave significant primary responses. Intrafamilial studies showed that the ability to restimulate a proliferative response followed the major histocompatibility complex haplotype of the responder; in some cases, the two haplotypes differed in their ability to restimulate. Using unrelated individuals typed for HLA-A, B and C, as well as HLA-D and DR, proliferation was shown to occur only when the unrelated stimulator shared HLA-D region products with the responder. In contrast, no HLA restriction was found in cell-mediated lympholysis (CML) (neither in primary nor in secondary responses) in most cases. The data suggest that the observed killing is independent of sensitization. Both responders and nonresponders in proliferation yielded high levels of lysis; no increase of lysis was found in kinetic studies; most allogeneic CML combinations were highly lytic for the TNP-modified responder cells at a time when the lysis of the specific allogeneic target is negligible. These preliminary data suggest that the killing observed might be different from classical T cell-mediated lympholysis.


PPD-induced blastogenesis is auto-regulated by suppressor cells generated in vitro.

Suppressor cell induction can be demonstrated during antigen specific blastogenesis by using the same methods which have shown induction of suppressor cells by Con A. Since suppressor cells are rapidly generated during antigen specific blastogenesis, they must regulate the final level of blastogenesis induced during the seven day in vitro incubation.


A rationale for the therapeutic action of aprotinin.

Aprotinin, a protease inhibitor, has been used in a wide variety of pathophysiological states thought to be associated with an increase in protease activity. Opinion differ with respect to the success of the therapy. This paper proposes a rationale for the therapeutic action of aprotinin based on biochemical and physiological evidence. In the kallikrein-kinin system, in addition to kallikrein, other serine-esterases such as trypsin, plasmin, etc. can generate kinin production. In certain disease states such as pancreatitis there is not only an increase in serine-protease activity but frequently these enzymes reach parts of the organism where they are not found in health. Thus in such circumstances increased production of kinins can result. The consequences of increased kinin generation are discussed in light of work indicating their role in metabolic and circulatory homeostasis. Aprotinin is specifically a serine-esterase inhibitor. It is suggested that perhaps the most important action of this compound is as an inhibitor of the kallikrein-kinin system. On this basis a therapeutic regime in various disease states for the use of aprotinin, which allows for control of kinin generation, is suggested.


Effects of levamisole in Sézary syndrome. Apparent acceleration of disease.

2 patients with Sézary syndrome were treated with levamisole. Both patients had clinical and hematological evidence of acceleration of their disease and ultimately died, although 1 patient had improvement in skin test reactivity. We suggest that levamisole be used with caution, if at all, in patients with T-lymphocyte malignancies.


The retinoic acid derivative Ro 11-1430 (Tasmaderm) in patients with acne vulgaris not tolerating retinoic acid. A controlled multicenter trial against placebo.

In a double-blind randomized comparative multicenter trial, consisting of 29 patients with acne vulgaris who were unable to tolerate daily applications of retinoic acid, the retinoic acid derivative Ro 11--1430 (0.1% vanishing cream) was compared in a 6--8 weeks topical treatment with vanishing cream alone (placebo). Regarding efficacy, for most criteria measured the response was always better with Ro 11--1430 than with placebo, although the differences were not always statistically significant for several reasons, one probably being the small number of patients in the trial. Regarding tolerance, both treatments were satisfactory. Ro 11---1430 and placebo did not differ significantly regarding frequency and severity of erythema, desquamation and burning. These results suggest that treatment with Ro 11--1430 should be considered in acne patients who are unable to use retinoic acid due to severe local reactions.


Gamma-aminobutyric acid in peripheral tissue, with emphasis on the endocrine pancreas: presence in two species and reduction by streptozotocin.

A screen of selected periphral organs of the rat found that gamma-aminobutyric acid (GABA) is generally present outside the central nervous system, and, of those organs examined, GABA was present at the highest concentration in the pancreas (approximately 40 pmol/mg wet wt). Furthermore, this putative inhibitory neurotransmitter was found to be present at even higher levels in islets of Langerhans tissue isolated from rat pancreas (190 pmol/mg). Administration of streptozotocin, a selective beta-cell toxin, decreased pancreatic GABA levels significantly, but had no or only small effects on the GABA content of other organs. Normal teleost (catfish) Brockmann body contains about the same level of GABA as normal rat islet tissue.


A longitudinal study of very low-birthweight infants. II: Results of controlled trial of intensive care and incidence of handicaps.

Between 1966 and 1970, infants with birthweights between 1000 and 1500g entered a randomized controlled trial to determine the short-term and long-term results of neonatal intensive care. Of 158 long-term survivors, five were lost to follow-up, but the multidisciplinary research team prospectively followed 143 children up to the age of eight years. Useful data were available for the other 10 children. Of the long-term survivors 74 had received routine, and 84 had received intensive nursery care. At eight years of age there were no statistically significant differences in the frequencies of a variety of individual abnormalities; fewer of the intensively managed children had cerebral palsy, but sensorineural deafness and ocular abnormalities occurred more frequently. Individual children were graded into four carefully defined groups: (a) profound handicap (4.4 per cent of entire study group); (b) severe handicap (10.1 per cent); (c) significant handicap (37.3 per cent); and (d) trivial or no handicap (41.8 per cent). Inadequate data were available for 6.3 per cent of the children. It was apparent that the improved survival attributed to intensive neonatal care was achieved at the expense of additional severely handicapped children, and this feature is discussed.


Effect of neocarzinostatin on microtubules.

Effect of Neocarzinostatin (NCS) on microtubules was examined both in vitro and in vivo. Although NCS had no effect on microtubule assembly in vitro nor dissociated cytoplasmic microtubular network in vivo, microtubular network appeared to be changed to coarse form in NCS-treated 3T3 and HeLa cells. Effect of NCS on microtubules was discussed in comparison with colchicine.


[Proline-dependent wild strains and proline-dependent mutants of the plague microbe].

It is found that the growth of Yersinia pestis wild strains, isolated from Citellus musicus Menetrié in the Central Caucasus, depends on the presence of proline in the medium. Proline can not be substituted by glutamic acid, other amino acids or vitamins. 28 proline-requiring mutants were selected from Y. pestis marmot strain 20b. Three groups of proline-requiring Y. pestis mutants are established, similar to those of Escherichia coli. The requirement of proline does not affect the virulency, pigment formation and calcium dependence.


Construction and properties of hybrid plasmids carrying the E. coli gal operon.

A family of hybrid plasmids carrying the entire gal operon of E. coli and designated pgal was constructed in vitro. In the case of pgal 1 (mol. wt. 16.4 Md), a fragment cut by Bam HI endonuclease from lambda gal phage DNA (lambda D-J-gal-att-int) was joined to pMB9 and cloned in the gal-strain of E. coli, which was grown on selective media with galactose as a sole source of carbon. Plasmid pgal2 was derived from pgal 1 by elimination of the 1.1 Md fragment located between the two EcoRI sites and carrying the lambda att-int region and part of pMB9. To obtain pgal3, the 10.7 Md fragment of lambda DNA located between the two SmaI sites (lambda D-J and part of pMB9) in pgal2 was cut out and the resulting flush-end fragments were sealed by the T4DNA ligase. The mol. wt. of pgal3 containing one SmaI site amounted to 4.6 Md, while several pgal3 variants that had lost their SmaI site were still smaller. Plasmid pgal1 inhibited the growth of the gal- host cells, which effect could be overcome by the accompanying helper pMB9. The presence of pgal2 and pgal3 supported the growth and multiplication of gal- cells on selective media even without the helper plasmid. The total amount of pgal plasmid DNA per cell was constant and equalled 60--70 Md (4 copies of pgal1 or 15--16 copies of pgal3, ColE1 or pMB9). This might explain why the co-presence of pMB9 helper does alleviate the "harmful" effects of the plasmid pgal1 (which carries att-int genes), by reducing the copy number of the latter from four to one.


Characterization of mouse ribosomal gene fragments purified by molecular cloning.

Four mouse ribosomal gene fragments cloned in lambda gtWES were studied by restriction enzyme mapping and Southern transfer experiments. These fragments were found to contain 18S DNA and transcribed as well as non-transcribed spacer DNA. Variation in the structure of these mouse DNA inserts was limited to one region of spacer DNA. This variation may reflect real structural differences found in mouse ribosomal genes or possibly deletion events which occurred during cloning. The transcribed regions of the inserts appear identical to one antoher and restriction enzyme fragments from this region correspond to fragments observed in digests of total mouse DNA. These clones will be useful in studying the structure of transcribed spacer DNA including the ribosomal gene promoter.


A study of the relationship between ex vivo and in vivo effects of sulphinpyrazone in the guinea pig.

In guinea pigs, sodium arachidonate-induced platelet aggregation ex vivo proved a more sensitive method for detecting drug-related effects after the administration of sulphinpyrazone than collagen-induced platelet aggregation. It was possible to detect inhibition of platelet aggregation after giving sulphinpyrazone orally in a single dose of 3 mg/kg. Excellent correlation was achieved between ex vivo and in vivo inhabition of platelet function with sulphinpyrozone using the Arthus reaction. The results are consistent with the formation, in the guinea pig of metabolites more potent than the parent molecule.


[The prognosis for high-risk newborns].

By good perinatal care the perinatal mortality rate can be brought down to 10 promille. A great number of high risk newborns will survive. The developmental prognosis of these at risk babies has strikingly improved. Among these babies the rate of neuromotor defects has been reduced by about 50%. Babies with birth weights of less than 1501 g will develop spastic diplegia in less than 5% and more than 80% of the babies with birth weights of less than 1001 g and the babies after artificial ventilation will develop normally.


[The concept of social pediatric assistance in the development of handicapped children. Possibilities, problems and future measures].

Principles and possibilities of the social pediatric concept (Hellbrügge) in treatment and aids for handicapped children are demonstrated. Beside positive experiences there are still some unsolved problems: control of therapeutic efficiency, increasing amount of psychic and social handicaps, lack of psychotherapeutic possibilities, problems of the organization and the public rôle of social pediatric work.


Down's syndrome in brother and sister without evident trisomy 21.

In the present report two siblings with the typical Down's phenotype but without evident full or partial 21 trisomy are described. The finding of a regular 21 trisomy in a minority of the cells in the elder patient favors the hypothesis that both present a hardly demonstrable normal/trisomy 21 mosaicism and may be examples of a constitutional familial tendency to nondisjunction in man.


Pseudocholinesterase activity and E1 phenotypes in Down's syndrome and mental retardation.

Pseudocholinesterase activity and the phenotypes controlled by the E1 locus have been determined in a sample of 307 Down's syndrome patients and 206 patients suffering from nonspecific mental retardation and compared to those in the healthy population. Both groups of patients have an elevated frequency of phenotypes possessing the rate E1f allele. The mentally retarded patients have a higher mean pseudocholinesterase activity than those with Down's syndrome who, in turn, have activity than the healthy controls.


The cellular control of delayed hypersensitivity to Staphylococcus aureus in mice.

The cells which suppressed delayed hypersensitivity (DH) to Staphylococcus aureus in the mice were non-phagocytic, adhered to nylon wool and possessed surface immunoglobulin but no detectable Thy 1. antigen. They were probably B lymphocytes and the suppression which they mediated appeared to be specific. The mature suppressor cells were radiosensitive. Their precursors were sensitive to large doses of cyclophosphamide. Suppressor-cell activity in the spleen reached a peak after two subcutaneous S. aureus infections and declined thereafter. This decline might be related to the appearance of DH to S. aureus in mice after four or more staphylococcal infections.


Human myeloma cells and their strong stimulating capacity in 'one-way' mixed lymphocyte reaction: a comparative study with leukaemic B lymphoid cells.

Cultured human myeloma cells (ARH-77, RPMI-8226 and U-266), like leukaemic B lymphoid cells, consistently exerted a strong stimulating capacity on allogeneic lymphocytes in the 'one-way' mixed lymphocyte reaction. An optimal stimulation was seen when a 1:1 ratio or 1:2 ratio of responding cell:stimulating cells of each cell line was utilized. The stimulating capacity of ARH-77 or RPMI-8226 cells was significantly diminished when a 1:4 ratio of responding cells:stimulating cells was utilized. Fresh bone marrow cells containing more than 80% plasma cells from a patient with multiple myeloma, on the other hand, failed to exert the stimulating capacity on two occasions. The striking difference between cultured myeloma cells and fresh plasma cells is that the Ia-like antigen is present on cultured myeloma cells, and this antigen is absent on fresh plasma cells. The relationship between the Ia-like antigen and the stimulating capacity in 'one-way' mixed lymphocyte reaction is discussed.


Restoration of impaired immune functions of aged animals by chronic bestatin treatment.

An attempt to correct the state of immunodeficiency in old age was made by repeatedly injecting a chemically defined immunostimulating agent, bestatin, to 16 month old (C57Bl/6 x BALB/c) F1 mice. Aged mice were found to have depressed T-cell and B-cell responses but increased ADCC activity. Weekly injections of bestatin over a period of 6 months resulted in varying effects depending on the dose administered. Small doses (10 microgram per injection) were more effective in restoring humoral responses to SRBC rather than delayed-type hypersensitivity reactions, whereas large doses (100 microgram per injection) acted in the opposite way. Macrophage activation was only obtained after the administration of the high doses of bestatin. Continuous treatment with bestatin did not prevent the appearance of suppressor cells induced by ageing. It led to a significant reduction of ADCC activity in aged animals near to the base line value of young animals. Animals were examined for the presence of spontaneous tumours from the end of the treatment until the age of 28 months. A significant reduction of spontaneous tumour incidence was observed in mice given repeated injections of 100 microgram bestatin when compared to untreated aged mice and to mice given the low doses of bestatin.


Rabbit anti-EL4 serum. A reagent with specificity for a population of murine suppressor cells.

Antisera against the C57B1 (H-2b) mouse lymphoma, EL4 were prepared in rabbits. After absorption with mouse liver, red cells and thymocytes the antisera appeared to be cytotoxic for a subpopulation of peripheral T cells. The absorbed antisera blocked the immunosuppressor function of Con A-stimulated splenic lymphocytes, but was unreactive against Con A-stimulated and allogeneically primed cytotoxic cells, or helper T cells. Consequently, heteroantiserum against EL4 may provide a useful reagent for the differentiation of cytotoxic from suppressor T-cell subsets.


[Paralytic abdominal hernia in zoster].

In a 56 year old patient with zoster in the thoracic segments 10 and 11 an abdominal hernia developed. The hernia was caused by peripheral motorial paresis.


[Acne fulminans].

Acne fulminans is a rare disorder of male teenage patients. The disease is characterized by the sudden appearance of highly inflammatory, tender, ulcerative and crusted lesions on back, chest and face. At the onset of the disease all patients show febrile temperature, leucocytosis, increased sedimentation rate and frequently polyarthralgia. The reported case showed typical lesions and distribution, fever, leucocytosis, elevated sedimentation rate, anemia, a decrease in albumin and an increase in alpha 2-globulin. Intradermal skin tests (delayed reactivity) showed marked decrease responses. Systemic treatment with antibiotics (ampicilline, tetracycline) with concomitant topical therapy was effective.


On the heterogeneity of capillaries of pigeon pectoralis muscle: a histoenzymatic and ultrastructural study.

Earlier studies had failed to show the presence of capillaries between the white fibres of pigeon pectoralis muscle. In this paper, data are reported for the first time documenting that these capillaries occur in both intra- and inter-fasicular areas of the muscle. Fresh frozen sections of pigeon pectoralis major muscle were incubated for alkaline ATPase reaction following pretreatment with different EDTA solutions (4.3 mM, pH 4.3). The results showed the existence of an inherent heterogeneity of capillaries. The capillaries of white fibres stained intensely for K+/Mg2+-EDTA or Mg2+-EDTA pre-incubated ATPase; the capillaries of red fibres stained poorly. Both white fibre and red fibre capillaries were examined ultrastructurally in the non-perfused pigeon pectoralis muscle. It is suggested that a possible correlation exists between the distinctive metabolic and mechanical characteristics of the Type II white, glycolytic, fast-twitch fast-fatigue muscle fibres and the high ATPase activity of their capillaries.


The ultrastructural localization of membrane ATPase in rat thin limbs of the loop of Henle.

The cytochemical distribution of nonspecific membrane ATPase activity in the epithelial membranes of the thin limbs of the loops of Henle of rat nephrons was studied at the ultrastructural level. Membrane ATPase activity was localized in the luminal, lateral, and (to a lesser extent) basal membranes of only the outer medullary segment of the thin descending limbs of long nephrons (Type II epithelium). The reaction product was lacking in the thin limb of short nephrons (Type I epithelium) as well as in the inner medullary descending (Type III epithelium) and ascending (Type IV epithelium) segments of the thin limbs of long nephrons. These data reinforce the concept of thin limb heterogeneity and may indicate a specialized role for the outer medullary segment of thin descending limbs of long nephrons in the concentrating mechanism.


Histochemical characteristics of a tonic smooth muscle.

It is suggested that ABRM, smooth muscle of Mytilus edulis L. and Mytilus galloprovincialis Lmk. (Mollusca Pelecypoda), is composed of one histochemical fibre type. The fibres are characterized by a low myofibrillar ATPase activity. Succinic and nicotinamide adenine dinucleotide oxidoreductase activities are distributed in a reverse pattern than that of the ATPase activity. Glycogen phosphorylase is richly represented in ABRM fibres and this detection is in opposition with the negative detection of alkaline phosphatase activity. These preliminary histochemical observations are similar to those found in some vertebrate smooth muscles. Mitochondrial glycerol-3-phosphate, 6-phosphogluconate, lactate and octopine dehydrogenases are not detected in muscle fibres whereas glio-interstitial tissues show weak but distinct reactivity. These last results especially characterize Mytilus catch fibres and are briefly discussed in relationship with previous physiological, biochemical and morphological observations.


Volume-displacement body plethysmograph using a large flowmeter without pressure compensation.

A modification of the conventional volume-displacement whole-body plethysmograph was done using a low-resistance flow element and integrating the plethysmographic pressure signal. A flow element with a resistance of 0.036 cmH2O/(l/s), linear to 75 l/s was fitted to a 440-liter plethysmograph, resulting in an instrument with a volume-amplitude-frequency response flat to 15 Hz and in phase with mouth flow and esophageal catheter-balloon to at least 15 Hz without pressure compensation.


Evaluation of a hot-wire respiratory flowmeter for clinical applicability.

A hot-wire flowmeter was evaluated for clinical applicability. 1) Calibration with a syringe could be done if emptying duration was 1-15 s. 2) Outputs linearly decreased with decreasing concentration of N2 in O2. Outputs with CO2 in O2 and N2O in O2 represented nonlinear convex relationships with varying concentrations of CO2 and N2O. Correction for each gas mixture to be measured is required. 3) Outputs linearly decreased with decreasing barometric pressure. 4) Stability assessed with a piston respirator was excellent (within +/- 2% of syringe volume) after 15 min warmup time. However, daily calibrations are recommended in clinical situations. 5) Nebulization, if not excessive, was acceptable if the expired gas was measured at the mouth. 6) Hot-wire burning, which occurred when it was partially in contact with materials whose specific heat differed with air, was successfully protected with a simple shutoff circuit. 7) The possibility of producing nitrogen oxides by the catalytic action of the platinum hot-wire was denied by colorimetric determination. Interchangeability and sterilizability of transducers and improved mechanical strength with platinum-rhodium alloy are also discussed.


Effect of Sindbis birus infection on survival of mice in the cold.

Mice infected with 10(9) plaque-forming units (PFU) of Sindbis virus 9 h prior to exposure to cold (5 degrees C) died more rapidly after entering the new environment than saline-injected control mice. The early deaths occurred in animals singly housed without bedding and only when food was withheld. Because deaths could be prevented by providing the infected animals with food, it was concluded that metabolic alteractions resulting from the virus infection were responsible for the deaths. As evidence, corticosteroid-inducible hepatic enzymes did not respond to hydrocortisone administration in virus-infected mice housed at 5 degrees C. Phosphoenolpyruvate carboxykinase (PEPCK) (EC 4.1.1.32) was induced significantly in control mice held at 5 degrees C for 5 h, but failed to induce in infected mice in the cold. Tryptophan oxygenase (TO) (EC 1.13.11.11) activity was also induced in control mice at 5 degrees C, but was too low to be measured in livers of all infected mice including those exposed to cold. The conclusion that Sindbis virus-infected mice were unable to make the metabolic adjustments required for survival at 5 degrees C was further indicated by severe hypoglycemia and rapid drop in rectal temperature that occurred in infected mice after 5 h in the cold.


Myosin from striated adductor muscle of Chlamys nipponensis akazara.

Myosin was isolated from striated adductor muscle of Akazara shell-fish, and purified on DEAE-Sephadex A50. The sedimentation constant (s 20,2 0 W) and the intrinsic viscosity, [eta] of Akazara myosin thus purified were estimated to be 6.6 S and 2.10 dl/g, respectively. In many respects, Akazara myosin was similar to scallop myosin. (1) Only one size of light-chain component (17,000 daltons) was detectable in SDS-gel electrophoresis of Akazara myosin, but two types of light-chain component were seen in urea-gel electrophoresis; these were equivalent to EDTA-light chain and SH-light chain of scallop myosin. The molar ratio of heavy chain (206,000 daltons), EDTA-light chain, and SH-light chain in Akazara myosin was estimated, from the staining densities of gel-electrophoretic bands, to be approximately 1 : 1 : 1. (2) EDTA-washing procedure removed EDTA-light chain only, causing desensitization of Akazara myosin. EDTA-light chain isolated from Akazara myofibrils was able to resensitize EDTA-washed Akazara myosin. Akazara myosin, however, was found to be different from scallop myosin in two important properties: (1) complete removal of EDTA-light chains was required to achieve a complete loss of calcium sensitivity, and full resensitization was attained on recombination of EDTA-light chains with desensitized myosin prepared essentially free from EDTA-light chains. (2) EDTA-light chains isolated from Akazara myofibrils show a calcium-induced UV absorption difference spectrum.


Reversible effects of fatty acids on respiration, oxidative phosphorylation, and heat production of rat liver mitochondria.

1. Oleic acid at low concentrations (0--70 nmol/mg protein) stimulated mitochondrial state 4 respiration 4-fold, increased the apparent enthalpy change of the respiration per gram atom of oxygen consumed from -112 to -208 kJ/O and completely inhibited ATP synthesis without significant effect on the Mg-ATPase activity of mitochondria. 2. Similar effects on mitochondrial respiratory activities were observed with other fatty acids. 3. Bovine serum albumin (BSA) protected mitochondria from the effects of oleic acid irrespective of the order of addition of oleic acid and BSA to mitochondria. The capacity of BSA to bind oleic acid was calculated to be 3.6--7.1 (mean, 4.9) mol of oleic acid/mol of BSA. 4. The response time of mitochondrial respiration to added oleic acid or BSA was 20--25 s.


Modification of cardiac and smooth muscle myosins with 2,4,6-trinitrobenzenesulfonate. Evidence for differences in structure around the active sites of cardiac, smooth, and skeletal muscle myosin ATPase.

Myosins purified from cardiac (porcine heart) and smooth (chicken gizzard) muscles were modified with 2,4,6-trinitrobenzenesulfonate (TNBS) and the effects on the kinetic properties of myosin ATPase [EC 3.6.1.3] were studied. The following results were obtained. 1. About 0.5 mol of TNBS per mol of myosin head was incorporated rapidly, irrespective of the presence of PP1 (2mM), into both types of myosin studied. 2. The size of the initial burst of P1 liberation for both myosins was found to be 0.5--0.6 mol/mol head. 3. The rapid incorporation of TNBS into cardiac muscle myosin was accompanied by a rapid decrease in the size of the initial P1 burst, and it was completely lost after modification for 20 min. However, smooth muscle myosin retained its P1 burst. 4. The EDTA (K+)-ATPase activity of both myosins modified in the presence or absence of PP1 decreased sharply with incorporation of TNBS. 5. Superprecipitation and ATPase activity of reconstituted actomyosin from cardiac myosin and skeletal F-actin decreased only after 10 min of modification with TNBS in the absence of PP1. 6. The spectra of TNP bound to myosins from cardiac and smooth muscles were unchanged by the addition of PP1. The above findings are compared with those previously obtained for skeletal muscle myosin [Miyanishi, T., Inoue, A., & Tonomura, Y. (1979) J. Biochem. 85, 747--753], and the structural and functional differences among the myosins derived from skeletal, cardiac, and smooth muscles are discussed.


In vitro and in vivo evaluations of dacron velour and knit prostheses.

Dacron velour and knit prostheses were compared with respect to long-term patency when used as canine aortic implants. These grafts were rated, according to the average numerical value of six equally weighted criteria, in decreasing order of performance: velour I, velour II, circular knit III, velour IV, circular knit V, warp-knit VI, warp-knit VII and VIII, warp-knit IX and warp-knit X. In general, compacting and crimping methods using halogenated hydrocarbons produced the least successful grafts. Grafts of identical brand but compacted and crimped by different methods exhibited different patencies. No true healing of the grafts was observed. Layered deposits of inner fibrous capsule were formed at rates and thicknesses characteristic for each type of graft employed. A functioning Dacron femoral-popliteal bypass removed from a human after 9 months exhibited inner and outer fibrous capsules similar to those from canine implants.


Requirement of Zn to demonstrate HCO3-stimulated ATPase activity of rat small intestinal brush border.

The existence of a membrane-bound HCO3-stimulated ATPase in intestinal mucosa is controversial. A crude brush border fraction of rat small intestinal homogenates contained HCO3-ATPase activity which was inhibited by preincubation with 3 mM EDTA. Alkaline phosphatase activity of this preparation was also inhibited in a parallel, time-dependent fashion by preincubation with EDTA. When 5 mM ZnSO4 accompanied 3 mM EDTA in the preincubation mix, preservation of both enzyme activities occurred, demonstrating a requirement of Zn for the activity of both these phosphatases. These studies support the earlier contention that HCO3-ATPase and alkaline phosphatase activities may be different properties of the same enzyme, and raise the possibility that the ATPase could play a role in intestinal ion transport. The failure to identify a membrane-bound HCO3-ATPase by other workers could be due to the exposure of EDTA which occurred in their tissue preparation.


alpha-Amanitin and 5-fluorouridine inhibition of serum-stimulated DNA synthesis in quiescent AKR-2B mouse embryo cells.

AKR-2B mouse embryo cells undergoing the serum-stimulated transition from a quiescent to a proliferating state exhibit an increase in the rate of hnRNA synthesis which appears to be mediated through an increase in the actual number of RNA polymerase II molecules. alpha-Amanitin, administered early in the prereplication interval following stimulation, effectively inhibits hnRNA synthesis, polysomal mRNA accumulation, polyribosome formation, and subsequent DNA synthesis, and cell division. Unexpectedly, alpha-amanitin treatment also produces almost complete inhibition of the synthesis of 45S rRNA precursor and the increase in accumulation of cytoplasmic rRNA following serum stimulation. In order to determine whether the inhibition of new ribosomal synthesis might in itself be sufficient to prevent serum-stimulated DNA synthesis, the effects of 5-fluorouridine (5-FU), a specific inhibitor of 45S rRNA processing, were investigated. If added within eight hours following serum stimulation, 5-FU was found to completely inhibit subsequent DNA synthesis. These results suggest that quiescent AKR-2B cells do not contain a sufficient excess of ribosomes to support the synthesis of proteins which are required for DNA synthesis in response to serum growth factors. Furthermore, an early polymerase II mediated synthesis of mRNA(s) coding for some factor(s) necessary for ribosomal gene transcription may be an essential step in the serum-stimulated synthesis of new ribosomes.


Predicting pain treatment results by personality variables in organic and functional patients.

Recent literature has suggested that the traditional dichotomy of organic vs. functional classification for pain patients is unimportant in determining the role of personality variables in predicting treatment outcome. The present study examined the role of MMPI variables in predicting treatment outcome in pain patients with definitive physical disorders (N = 58) (organic) and in patients without definitive physical findings (N = 46) (functional). In the organic group, the presence of high Hs was associated with poor outcome, while in the functional group K scores were associated with poor outcome. Results suggested that although personality variables played an equal role in both groups, the nature of that contribution may vary in the functional and organic groups.


Circulating and deposited immune complexes in renal disease and their clinical correlation.

In 48 patients undergoing renal biopsy there was a strong correlation (chi 2 11.45 (P less than 0.01)) between the demonstration of circulating and deposited immune complexes. Serial studies of circulating immune complex levels have shown fluctuations which only sometimes appear to coincide with clinical changes in individual patients.


The allopurinol hypersensitivity syndrome.

Hypersensitivity reactions to allopurinol, a drug commonly used in the treatment of hyperuricemia, are being reported with increasing frequency. Of thirty-eight patients reviewed herein (including seven from our hospital and thirty-one from a review of the literature), ten deaths (26%) were related to complications of allopurinol hypersensitivity. Preexisting renal disease was present in 97% of patients, and, in the majority of these, the dosage of allopurinol was not reduced despite instructions contained in the package insert for this drug. At least 78% of patients were taking a thiazide diuretic prior to starting allopurinol therapy. Over 60% of patients had received allopurinol for asymptomatic hyperuricemia. Hallmarks of this hypersensitivity syndrome include a prolonged illness initially manifested by fever, a prominent cutaneous reaction, eosinophilia, hepatic abnormalities, and acute renal failure. Other involvement such as gastrointestinal bleeding is common. The mechanism of the hypersensitivity reaction is not clear, but it may represent an immune complex disease prolonged by the persistence of a currently undefined antigen. Treatment with systemic corticosteroids, often for several months, is usually necessary for the gradual resolution of this potentially fatal syndrome.


Statistical relationship of morsal to bucco-lingual, approximal and sulcal caries in rats.

The correlation of morsal with sulcal, bucco-lingual and approximal caries scores of rats was compared. The morsal with bucco-lingual plus approximal correlation was significantly better than the morsal with sulcal correlation. When reporting rat caries, sulcal scores should be reported alone; morsal scores should be grouped with bucco-lingual and approximal to demonstrate total smooth surface lesions.


Undergraduate clinical pedodontic education: an overview of two teaching systems.

This paper compares and contrasts two clinical teaching systems in undergraduate pedodontics: the block system and the total patient care system (TPC). Descriptions and rationales are given for specific block and TPC systems at two universities. Theoretical advantages and disadvantages are reviewed. Clinical data are presented that represent experiences of the graduating classes of 1978 at The University of Iowa (block) and the University of North Carolina (TPC). From this limited sample there appears to be little quantitative evidence that one system is better than the other when examining clinical experiences in the two schools studied.


Encoding voice fundamental frequency into vibrotactile frequency.

Measured in this study was the ability of eight hearing and five deaf subjects to identify the stress pattern in a short sentence from the variation in voice fundamental frequency (F0), when presented aurally (for hearing subjects) and when transformed into vibrotactile pulse frequency. Various transformations from F0 to pulse frequency were tested in an attempt to determine an optimum transformation, the amount of F0 information that could be transmitted, and what the limitations in the tactile channel might be. The results indicated that a one- or two-octave reduction of F0 vibrotactile frequency (transmitting every second or third glottal pulse) might result in a significant ability to discriminate the intonation patterns associated with moderate-to-strong patterns of sentence stress in English. However, accurate reception of the details of the intonation pattern may require a slower than normal pronounciation because of an apparent temporal indeterminacy of about 200 ms in the perception of variations in vibrotactile frequency. A performance deficit noted for the two prelingually, profoundly deaf subjects with marginally discriminable encodings offers some support for our previous hypothesis that there is a natural association between auditory pitch and perceived vibrotactile frequency.


Nonspecific suppressor cell function in atopic subjects.

The status of concanavalin A (Con A)--nonspecific suppressor cell function and histamine-receptor--carrying mononuclear cells in 19 allergic and 27 nonallergic individuals was investigated. No differences were detected between the two groups with respect to suppression by Con A--activated suppressor cells of polyvalent Ig biosynthesis, IgG secretion, or mitogen-induced proliferative responses. Histamine-receptor--carrying cells of the allergic subjects were numerically equal to those of the nonallergic subjects. Mononuclear cells from the allergic group, however, required a higher dose of histamine than did those for the nonallergic group to induce suppression in vitro (p less than 0.02 for 10(-4) M histamine and p less than 0.05 for 10(-3) M histamine). Plasma from the allergic group  contained higher levels of histamine activity (p less than 0.05). Plasma from either allergic or normal groups did not affect histamine activity in vitro. There are no apparent functional abnormalities of antigen-nonspecific mononuclear cells in the allergic patients with respect to non--IgE-mediated in vitro parameters. The demonstrated dysfunction of histamine-receptor--carrying cells could be attributed to high levels of circulating histamine that could result in receptor modulation in vivo. More work is needed to clarify the status of antigen-nonspecific and antigen-specific suppressor cells that regulate IgE biosynthesis in allergic states.


Topical fluorouracil therapy for precancers and cancers of the skin.

Topical fluorouracil (FU) is an extremely effective agent for treating multiple actinic keratoses. It is also of value in the treatment of Bowen's disease, actinic cheilitis, arsenical keratoses, radiodermatitis, X-ray-induced keratoses, leukoplakia, and the erythroplasia of Queyrat. Topical FU may be successful in the treatment of superficial basal-cell carcinomas, but should not be used for nodular carcinomas of the face or neck except under unusual circumstances and with mandatory histologic follow-up evaluation. The usual method of treatment is twice daily application of a 1 percent FU solution in propylene glycol. Several modifications of various types of commonly employed preparations and the manner in which each is used are described, along with the respective indications. The considerable discomfort associated with the use of topical FU can be lessened by the stepwise approach outlined--a method extraordinarily valuable for older patients. Occasional complications are primary irritant dermatitis and allergic contact dermatitis; these must be recognized promptly and treated, as must other less frequent side effects. Topical FU appears to be of great value in the destruction of existing precancerous skin lesions. When used repeatedly, it may postpone indefinitely the development of significant precancerous and cancerous skin lesions.


The effects of estrogen treatment of carcinoma of the prostate on regional adipocyte size.

Fat cell size was determined in the gluteal, femoral and hypogastric regions of subcutaneous adipose tissue in men with carcinoma of the prostate before and after 5--6 months of estrogen treatment. Body weight and several metabolic variables did not change. Gluteal fat cell size increased. It was suggested that increase of the gluteal fat cell size is a characteristic effect of estrogens on adipose tissue because a similar increase has been previously found in young women in comparison with young men.


Biomechanical evaluation of metacarpophalangeal joint prosthesis designs.

A laboratory biomechanical analysis of metacarpophalangeal joint prosthesis designs was done with fresh cadaver finger rays. The center of rotation, range of motion, tendon excursion, and fingertip force were determined on the specimens before and after implanting Swanson, Niebauer, Steffee II, St. Georg-Buchholz, Schultz, and modified Strickland prostheses. Their biomechanical behavior varied considerably and none duplicated the normal metacarpophalangeal (MP) joint. Each has design characteristics that may be clinically advantageous as well as disadvantageous. Irrespective of the design, the studies done cannot be divorced from the following factors: (1) implant material properties--silicone rubber implants buckled with tendon loading; this deformity created a significant flexor mechanical advantage and an extensor mechanical disadvantage; (2) implant fixation--freely movable implant stems dampened part of the applied load; braided suture provided inadequate immediate fixation; (3) implantation technique--the articulated prostheses can be technically unforgiving; errors in technique resulted in alteration of their biomechanical behavior.


Staphylococcal sepsis in a burns unit.

An outbreak of staphylococcal sepsis in a burns unit occurred between January 1976 and May 1978. Many patients and members of staff had boils, and a number of patients also developed septicaemia. Most of the boils in the early period of the trial and a large proportion of boils in patients during the later period yielded Staphylococcus aureus resistant to penicillin, tetracycline and erythromycin only (PTE), and were shown to be of phage type 95 in the early period while strains were phage typed. From blood cultures, most strains in the early period were of resistance pattern PTE and phage type 95, but in the later period other resistance patterns were predominant. Strains from burns were usually multiresistant (PTEKNML) and of the phage pattern 29/77, which had been endemic in the Unit, but during the early period of the outbreak there was an increased proportion of strains in burns with the resistance pattern PTE and of phage type 95. Staphylococcal sepsis has for many years been very infrequent in the burns unit. This outbreak seems to have been initiated by a strain of phage type 95 and resistance pattern PTE, but during the course of the outbreak the endemic strain of type 29/77 and some other staphylococci seem to have developed enhanced ability to cause clinical infections, conceivably by transduction from the epidemic strain of phage type 95.


Comparison of Staphylococcus aureus carriage and skin infection rates in hospital and office employees.

The incidence of Staphylococcus aureus in the nose, throat and superficial wound infections of 99 office staff, 129 psychiatry staff and 115 surgical staff was studied over a 4-week period with the purpose of assessing the potential risk to hospital personnel of staphylococcal infection. Incidence rates, both average and cumulative, were essentially similar in the three groups but certain differences in the ecology of the staphylococcal phage groups were observed. Surgical staff appeared to have a more labile pattern of carriage. As in other Scandinavian studies throat carriage rates were high. Staphylococcal carriage seems largely to depend on individual characteristics rather than environmental factors.


A microculture technique for rat lymphocyte transformation.

We report the development of an economical microculture technique suitable for measuring rat lymphocyte response to mitogens and in mixed lymphocyte reactions. The effects of varying culture conditions, i.e. source of serum, addition and concentration of 2-mercaptoethanol, mitogen concentrations, culture incubation times, absorption of serum, lymphocyte numbers and microtitre plate well shape are described.


A newly designed whole microplate automatic harvester for lymphocyte stimulation assays.

A unique automated sampling manifold designed to recover cells grown in standard 96 well microplates from their culture medium is described. Cells are recovered and washed on fiber glass filter discs. Incorporation of radioisotopes into cells, can then be measured by appropriate counting of the filter discs. Typical applications include termination of mixed lymphocyte cultures, assays of mitogen stimulation of lymphocytes and antigen-specific lymphocyte transformation and assays of interferon activity. The harvester can also be used in other biological systems where collection and washing of precipitates is desired.


Mitogen-induced suppressor T cell activity in the in vitro cellular immune response.

A 24 h preincubation of human peripheral lymphocytes (PBL) in the presence of phytohemagglutinin (PHA) or concanavalin A (Con. A) renders them suppressive for the response of untreated cells to PHA, Con. A, candidin and allogeneic cells. However, cells stimulated with lipopolysaccharide (LPS) show no suppression.


Immune responses during pregnancy. Evidence of suppressor cells for splenic antibody response.

The primary IgM antibody response to sheep erythrocytes in vivo as well as in vitro is markedly decreased in the spleen cells of pregnant mice, compared to age-matched female controls. Decreased antibody synthesis appears to be mediated by nonspecific suppressor cells, because the addition of pregnant spleen cells to the normal spleen cell cultures causes a significant suppression of plaque-forming-cell responses of the normal spleen cells. Suppressor cell activity was not observed in lymph nodes of pregnant mice. At least two populations of pregnant spleen cells were shown to exert a suppressor cell activity; one is T lymphocytes and the other a nylon-adherent cell present in the B-cell-enriched macrophage-depleted fraction. Pregnant spleen cells cultured in vitro were shown to secrete a soluble suppressive factor(s) into the supernatant medium.


Manual materials handling: the cause of over-exertion injury and illness in industry.

It is reported from various sources that overexertion due to lifting, pushing, pulling, and carrying objects accounts for about 27 percent of all compensable industrial injury and illness in the United States. Resulting strain/sprain injuries account for over 50 percent of workmen's compensation clams in many industries. Almont two-thirds of these involve back pain, with reported compensation and medical payments totaling well over one billion dollars annually in the U.S. An estimated 300,000 plus workers will be affected each year, 5 to 10 percent of whom will have a permanent disability and often will be unemployable. This paper attempts to describe four basic approaches used to study this occupational health problem. In so doing, a concerted effort is made to identifiy the gaps in knowledge which need to be more fully researched. The approaches utilized to understand and control the hazards of manual materials handling are: 1) epidemiological studies of job and worker attributes to identify those that individually and in combination cause musculoskeletal incidents, 2) psychophysical studies to ascertain the volitional tolerance of workers to the stress mitigated by manual materials-handling activities, 3) biomechanical studies of the musculoskeletal system during common exertions required in manual materials-handling activities, and 4) physiological studies of the strain imposed on the cardiovascular system during repeated load-handling activities. The state of knowledge from each of these approaches is summarized briefly, and a case is made that much research is still needed to substantiate the necessary controls to lessen the economic burden and human suffering associated with manual materials-handling acts in industry.


Suppression of idiotype and generation of suppressor T cells with idiotype-conjugated thymocytes.

Inoculation of A/J mice with syngeneic thymocytes conjugated with specifically purified A/J anti-phenylarsonate (anti-Ar) antibodies, selectively suppressed the subsequent synthesis of those anti-Ar antibodies which carry the major cross-reactive idiotype. High titers of anti-Ar antibodies were produced upon subsequent immunization but in most mice the idiotype was undetectable. Suppression similarly occurred in F1(A/J X BALB/c) and in C.AL-20 mice. Although some mice were suppressed when unconjugated antibody was injected, the suppressive effect was much more pronounced, particularly in the F1 and C.AL-20 recipients, when the antibody was coupled to thymocytes. The state of suppression could be adoptively transferred with T cells to mildly irradiated syngeneic recipients. A population enriched for B cells had little if any suppressive effect. There was no requirement for antigen in the generation of suppressors. Thymocytes conjugated with antibody did not induce idiotype-specific suppression in mice that had been recently challenged with antigen. Thymocytes from BALB/c and C57BL/10 mice were effective carriers for the anti-Ar antibodies, i.e., there was no evidence for H-2 restriction. The experiments demonstrate the feasibility of suppressing idiotype production and generating idiotype-specific suppressor T cells without the use of anti-idiotypic antibody or antigen.