Decrease of concanavalin-A activated and short lived suppressor T cell function in thyrotoxicosis. Function of short lived and concanavalin-A activated suppressor T cells of peripheral blood was studied in patients with thyrotoxicosis and normal individuals. It was found that the activity of short lived and concanavalin-A activated suppressort T cells decreased in untreated patients. Function of concanavalin-A activated suppressor cells relatively increased in euthyroid stage induced by methimazole treatment but failed to reach the normal level. Both the short lived and Concanavalin-A activated suppressor cell activity proved to be in inverse relationships with titres of anti-thyroglobulin antibodies and transformation indices to human thyroglobulin. These findings suggest a possible role of suppressor T cell function in the pathogenesis of Graves' disease.


Immunosuppressive activity of a purified spleen extract (lymphocytic chalone?) is not due to polyamines spermine and spermidine. Spermine, spermidine and a purified spleen extract (PSE) have been compared in vivo in these three tests: hemolytic plaque forming capacity in sensitized mice, delayed hypersensitivity reaction and 3H-thymidine incorporation into various tissue cells. The results obtained demonstrated that the immunosuppressive activity of PSE cannot be attributed to those polyamines. Ion exchange analysis of PSE before and after acid hydrolysis confirmed the absence of free and/or bound polyamines in the studied extract.


[Immune response dynamics during malignant tumor development]. Several mathematical models for the development of immune reaction during cancer diseases were plotted. The models describe both stimulation of the immune system by the tumor and its suppression. Non-specific inhibition was considered which resulted from glucose deficiency accompanying the development of a malignant tumor. The inhibiting effect of antitumour antibodies on toxic influence of limphocytes-killers was taken into account. The qualitative and quantitative study of the models showed the limits for the description of real interactions between tumour and organism by the mechanisms stated.


Levamisole treatment of inflammatory acne. Restoration of impaired T-cell function accompanied by clearing of the lesions. Serum hemolytic complement activity and its components C3, C4 and C1q, serum immunoglobulins A, M and G and peripheral E-rosette forming cells were determined in 11 patients with inflammatory acne. IgG levels were increased and the E-rosette formation was markedly impaired. Levamisole treatment restored the E-rosette formation and improved or cured the inflammatory lesions in 10 out of 11 patients.


Muscle and serum adenosine triphosphatase in patients suffering from tetanus. Serial estimation of muscle and serum adenosine triphosphatase (ATPase) activity was performed in 16 healthy control patients and 32 cases with tetanus. There was no significant difference due to age and sex in muscle and serum ATPase activity between the normal and tetanus cases. Tetanus patients showed a marked increase in muscle and serum ATPase activity as compared to normal. The ATPase activity increased with the severity of convulsion and disease. There was increased mortality in tetanus patients having higher values of muscle and serum ATPase.


The younger disabled unit at Fazakerley Hospital. The activities of a new younger disabled unit reflect the changing pattern of care now being provided for severely physically disabled young people. A co-ordinated team approach to their rehabilitation has enabled all but a few of the severely disabled to continue living at home. This represents a considerable saving on the cost of hospital-based care and has afforded them the best opportunity for developing their lives to the full and enjoying a satisfactory life in the community.


Effects of inflammatory disease on plasma oxprenolol concentrations. When single oral doses of oxprenolol were given to three healthy subjects on three separate occasions under standardised conditions the plasma concentration-time curves for each subject were closely similar. In two of the subjects, however, a mild illness led to a dramatic, temporary increase in the peak plasma concentration and area under the plasma concentration-time curve (AUC). This effect of inflammatory disease was confirmed by comparing a group of patients with an erythrocyte sedimentation rate (ESR) of over 20 mm in the first hour with a group whose ESR was below this value. The mean peak plasma concentration and AUC were significantly higher in the group with a raised ESR. This may be related to altered concentrations of one of the acute-phase proteins. Thus it is concluded that plasma oxprenolol concentrations are raised in inflammatory disease, but further work is needed to determine the mechanism of this increase.


[Cardiac anti-arrhythmic effect of various N-substituted piperazine derivatives with respect to aconitine in the rat]. Anti-arrhythmic activity of some piperazine derivatives has been investigated upon cardiac arrythmia induced by aconitine in albinos rat. Among mono-substituted derivatives trimetazidine is active. Among di-substituted derivatives cinepazide and hydroxyzine are active but medibazine have a doubtful activity and piribedil and cinnarizine are devoid of activity.


[Effect of adenosine on phosphofructokinase and phosphoglycerate kinase of rat liver]. Effects of adenosine on purified rat liver phosphofructokinase and phosphoglycerate kinase activity were investigated in vitro. Stimulation by adenosine of the phosphofructokinase has been observed at low concentrations, but the activity was markedly inhibited at high concentrations. Adenosine was an inhibitor of the phosphoglycerate kinase : Lineweaver-Burk analysis indicated that adenosine inhibition was competitive with ATP and non competitive with 3-phosphoglycerate. An interpretation of these results is proposed.


[Alterations in concanavalin A binding during retinal development in Xenopus laevis]. Changes in concanavalin A binding were observed in the retina of Xenopus laevis throughout development. Prior to stage 37, the optic cup and nervous sysetm displayed a light, diffuse staining. Abruptly at stage 37, however, intense staining reaction occurred in the ganglionic fibers, both plexiform layers and photoreceptor inner segments, remaining thus throughout larval and adult life. Our results suggest that important structural modifications occur in retinal cells at the time of establishment of connections with the tectum, preceedings, and possibility related to, electrical functioning of the visual system.


[New data on serotoninergic mechanisms in ovulation in the cyclic female rat]. Injection of parachlorophenylalanine on dioestrus II at 18:00 was shown to decrease ovulation frequency in 4-day cyclic female rats. This effect was overcome by either HTP, or oestradiol benzoate, when administered on dioestrus II, at 18:00 and 10:00 - 11:00 respectively. No antiovulatory action of PCPA was observed on prooestrus at 13:00. These results provide support to the specificity of action of serotonin in the control of ovulation in the cyclic rat. They also suggest an interaction of serotonin and oestrogens in this control.


[Effect of testosterone or progesterone implants on the intensity of experimental infestation with Schistosoma mansoni in the female golden hamster]. When administered in pellet form of 20 mg to castrated Golden female hamsters, testosterone leads to a decrease of the intensity of experimental infestation with Schistosoma mansoni. The same result is obtained when estradiol is used in place of testosterone under the same conditions. On the contrary, no statiscally significant decrease has been observed with progesterone.


[Combination of chemotherapy and radiotherapy. I. Differential effect on the intestinal syndrome of irradiation combined with the drug administered in fractional doses and at various times]. We have studied the different effects on the intestinal syndrome between the administration of fractional doses of 5-Fu before and after irradiation. There is no difference between the diverse modalities and we obtain the same result when the 5-Fu is administered, fractionated or not, before or after the irradiation.


[Combination of chemotherapy and radiotherapy. II. Differential effect on the medullary syndrome of irradiation combined with the drug administered in fractional doses and at various times]. We have studied the effect of 5-Fu in fractional doses on the medullar syndrome after a single whole body cobalt irradiation in mice. The bone marrow is not sensitive to the fractionation of 5-Fu and it is the single dose of 5-Fu injected 72 hours after the irradiation which is the most effective.


[Interstitial transudation with postural changes in man]. Starling-Landis concepts of formation of interstitial fluids are in agreement with measurements of calf volume in normal young women, in horizontal recumbency or after horizontal immersion. The volume of the calf is reduced when the hydrostatic pressure of the blood column is diminished under the phlebostatic level and when the external pressure is increased by the hydrostatic pressure of the water bath.


[Various aspects of lipid metabolism in the rat testicle after sulpiride treatment]. Testicular lipids were extracted from 20 rats which had received 40 mg sulpiride per kg per day for 20 days as well as from 20 controls. The extracts were weighed and chromatographed on thin layer in order to analyse them for the main fatty constituants : phospholipids and neutral fats. In addition total cholesterol, triglycerides and lipid phosphorus were determined. The total testicular lipid content and the phospholipids were unaltered. The distribution of phospholipids wasn't influenced either. Among the neutral fats the precursors of steroid hormones such as cholesterol and its esters didn't show any modification. The triglycerides on the other hand suffered a significant decrease which was partly compensated in situ by the increase of free fatty acids. Since plasma electrophoresis didn't reveal a parallel increase of the complex albumin--free fatty acids, the hypothesis of an in situ lipolysis is proposed. But it is not possible yet to attribute to sulpiride the role of a direct activation on a testicular triglyceride lipase nor that of an indirect activator by way of prolactine for example.


[Effects of the virus-inhibiting factor or interferon on the in vitro multiplication of mouse tumor cells]. 1) The in vitro effect of virus-inhibiting factor (IF) or interferon on Ehrlich ascites tumor and sarcoma 180 was found to be cytostatic, but not cytocidal. 2) Mouse peritoneal macrophages or splenic lymphoid cells, in the presence of IF, did not affect multiplication of the tumor cells examined.


[Comparative ultrastructural study of the inhibiting effect of deoxyguanosine and of caffeine on Allium sativum L. cytokinetics]. These two inhibitors of cytokinesis have two different modes of action, the first one acting during G2 and the second during M. This study underlines the action of caffeine on the fusion of cytokinesis vesicles. On the other hand, the cell vacuolization induced by deoxyguanosine is not directly relevant to the stathmodieretic action.


[Activities evoked in different strain structures by stimulation of the contralateral tectum in the chick]. In the chick, as soon as hatching, the responses recorded in various areas in the "accessorius hyperstriatum" (Wulst) seem to be very localized in relation with the stimulated region of the contralateral tectum. Very similar results are obtained within the other striate structures. These observations suggest in first part, that the tectal efferents project very diffusely to various striate structures and, in other part, that it exists in these a rather precise tectotopy and a columnar organisation. These results appear very constant during the first month of the hatching.


[Uptake and esterification of (4-14C) cholesterol after injection into the cerebral ventricles of conscious cats]. The brain tissue had appreciable capacity to take up and to esterify (4-14C) cholesterol from the cats cerebral ventricles. The highest values of radioactive material in the brain tissue were found 30 minutes after intraventricular injection of (4-14C) cholesterol. Thereafter, within a few hours most of the labelled cholesterol disappeared and by the end of 48 h the brain tissue retained only small amounts of it. at the same time, radioactive material was found in the peripheral venous blood, but in very small amounts. The analysis for cholesterol esters showed that about 50 % of (4-14C) cholesterol taken up by the brain tissue had undergone esterification. The rate of esterification of cholesterol within 48 h remained more or less constant, although a significant peak was noted by the end of 24 h.


[Cytotoxic action of Pseudomonas aeruginosa hemolysin]. The cytopathic action of haemolysin of Pseudomonas aeruginosa has been studied in mouse and human leucocytes. The morphological changes suggest that haemolysin affects the molecular architecture of the cell membrane, whose permeability is increased. It does not induce non-specific stimulation of peripheral lymphocytes. Normal sera and albumin neutralize the hemolytic activity of haemolysin; this inhibition is also observed, to a les extent, on the lytic action on leucocytes. This raises the possibility that the two activities are probably associated with the same molecule.


[Ultrastructural study of the different zones of the rat liver acinus after portacaval anastomosis]. Liver atrophy is a main feature in rats with a porto caval shunt. Histological studies revealed small size hepatocytes. Ultrastructural differences between periportal and centrolobular zones were noticed, in particular, the dilatation of the nuclear envelope and of the rough endoplasmic reticulum which appeared dilated, desorganized and sometimes without ribosomes, was more pronounced in the periportal zone. Hepatocytes of this zone might be more sensitive to the decrease of O2 and/or hepatotrophic factors.


[Chemical study on acetabular cartilage adjoining a prosthetic implant: experimental study in the rabbit]. The authors present an experimental study of the rabbit femoral prosthesis compatibility : macroscopical aspect, proteoglycan content and metabolism of the acetabular cartilage.


[Vasomotor innervation of the maxillary canines of the dog]. Maxillary canine pulpar pressure was recorded on anesthetized dogs by means of a small bore cannula threaded into a hole drilled through the lateral surface of the tooth. Vasoconstriction was brought by the electrical stimulation of the cranial cervical ganglion. Vasodilation was induced by stilmulation of the pterygo-palatine ganglion. This vasodilation was inhibited by atropine. Most often, constrictor fibres follow the course of the pterygo-palatine nerve, when dilator fibres follow the infraorbital nerve. However, both sorts of fibres may be found in the infraorbital nerve.


[Effect of anti-inflammatory agent administration on Balb/c mouse peritoneal macrophage activity]. A study of the mouse Balb/c peritoneal macrophages has been made after oral antiinflammatory drugs administration on animals which previously had an inflammation with carrageenan. The results show an enhancement of the number of the macrophages, of their enzymatic activities and of their proteins' content. These three parameters fall down more or less rapidly according to the considered antiinflammatory drug.


[Nidation in the Triton W.R. 1339 treated mouse: effect of progesterone and estradiol]. In the mouse injection of 800 mg/kg of Triton W.R. 1339 during the first four days of gestation prevents nidation. Examination of the uterine horns between days 6-12 reveals that a daily injection of 5 mg progesterone up from day 1 of gestation assures the survival of the blastocysts in Triton W.R. 1339 treated females and determines a delayed nidation. Nidations occur only after injection of 0.1 microgram of oestradiol benzoate at the beginning of the 5th day.


Separation of odontoblast Ca2+-ATPase and alkaline phosphatase. Ca2+-ATPase activity was solubilized, partly purified, and separated from nonspecific alkaline phosphatase activity (APase1) of dentinogenically active rat incisor odontoblasts. Attempts were made to extract the enzymes by various agents, such as Triton X-100, deoxycholate, butanol, EDTA, and buffers of decreasing ionic strength. Solubilization by butanol followed by extraction with low concentrations of EDTA proved to be most effective. Purification and separation were done by molecular sieve chromatography. Ca2+-ATPase showed no activity against p-nitrophenyl phosphate (p-NPP) or inorganic pyrophosphate (PPi) and was unaffected by R 8231 [+/-)-6(m-bromophenyl)-5,6-dihydroimidazo(2,1-b)thiazole oxalate]. It was activated by Ca2+ and Mg2+ ions in equimolar concentrations with the substrate. The enzyme was rapidly inactivated in the solubilized state. An apparent molecular weight of about 18,000 was obtained from molecular sieve data. APase, showing activity against ATP, PPi, and p-NPP, was virtually totally inhibited by R 8231. It was activated by Mg2+ ions but slightly reduced in activity by Ca2+ ions. It had an apparent mol. wt. of 79,000. The results provide direct evidence for earlier suggestions of the existence in hard tissue forming cells of two phosphatases active at alkaline pH.


Transduction of penicillinase production in Staphylococcus epidermidis and nature of the genetic determinant. Four strains of Staphylococcus epidermidis from clinical sources were capable of serving as donors for the transduction of either penicillinase production, ethidium bromide resistance, or tetracycline resistance. Three typing phages served as transducing phages and, depending upon the combination of transducing phage, donor strain, and recipient strain, the rates of transduction ranged between 10(-5) and 10(-9). In one strain, cotransduction of penicillinase production and ethidium bromide resistance was observed. Although ultraviolet irradiation kinetics indicated that both the tetracycline resistance and the penicillin resistance determinants were located on plasmids, only resistance to tetracycline could be eliminated by growth in the presence of curing agents or at elevated temperature. However, evidence was obtained by agarose gel electrophoretic studies that both the tetracycline resistance and the penicillin resistance determinants are located on separate plasmids in this organism.


Isolation of the chicken beta-globin gene and a linked embryonic beta-like globin gene from a chicken DNA recombinant library. A library of random chicken DNA fragments, 15-22 kb long, has been prepared in the vector lambda Charon 4A. This library was screened with combined adult and embryonic globin cDNA, and several independent globin gene-containing recombinants were isolated. One of these recombinants, lambda Chicken beta-globin 1 (lambda C beta G1), contains the adult chicken beta-globin gene and a closely linked embryonic beta-like globin gene. Both genes are transcribed in the same direction with the adult gene located 5' to the embryonic gene. Electron microscopic visualization of R loop structures generated by hybridization of globin RNA to lambda C beta G1 demonstrates that both globin genes contain major intervening sequences about 800 bp long, similar to those present in mammalian beta-globin genes. The adult beta-globin gene also contains a minor (approximately 100 bp long) intervening sequence analogous to the one observed in mammalian beta-globin genes. Restriction enzyme analysis of the adult beta-globin gene on lambda C beta G1 is consistent with the hypothesis that its two intervening sequences occur in the same positions with respect to the beta-globin amino acid sequence as do the corresponding mammalian intervening sequences.


[Cloning of the hepatitis B virus genome in Escherichia coli]. The whole genome of the hepatitis B virus (Dane particles) was inserted in vitro in the genome of the bacteriophage lambda gtWES . LAMBDA B. The recombinant DNA molecule was cloned in E. coli. Amplification of the hybrid bacteriophage enables the preparation of large amounts of hepatitis B virus DNA. The possibilities offered by the utilization of this recombinant bacteriophage are discussed.


Interventricular septal thickness and left ventricular hypertrophy. An echocardiographic study. Septal and left ventricular posterior wall (LVPW) thicknesses and their ratios were studied at the left ventricular outflow tract and left ventricular cavity in 66 patients with echocardiographically diagnosed left ventricular concentric hypertrophy, 20 with idiopathic hypertrophic subaortic stenosis (IHSS), and 34 normal subjects. Concentric hypertrophy was due to hypertension in 41 subjects and to valvular disease in 15 subjects. Septal thickness in normal subjects was related to body surface area (p less than 0.02). In 12% of normal subjects, 39% of patients with concentric hypertrophy and 95% with IHSS, the septal/LVPW ratio was greater than or equal to 1.3. Thirty-two percent of patients with hypertension, 78% with aortic stenosis, and 60% with aortic insufficiency had septal/LVPW ratios greater than or equal to 1.3 at left ventricular midcavity level. In conclusion, a septal/LVPW thickness ratio of greater than or equal to 1.3 is common in patients with concentric left ventricular hypertrophy and may also occur in normal subjects. A ratio greater than or equal to 1.5 may be more specific for genetically determined asymmetric septal hypertrophy.


Adenylate cyclase and ATPase activities in red cell membranes of patients and genetic carriers of Duchenne muscular dystrophy. Basal adenylate cyclase activity was increased in red cell ghosts from both patients with Duchenne muscular dystrophy and their mothers when the activities were compared to proper age-matched controls. The activity of ATPase measured in the presence of Na+, K+, and Mg2+ was not found to be different in erythrocyte ghosts from Duchenne dystrophic patients, age-matched controls, or the mothers of Duchenne patients, and ouabain inhibited ATPase in ghosts to the same extent in all membrane preparations.


Psychological factors in feeding disorders occurring in mentally or multiply handicapped children. This is a discussion of the psychological aspects of non-organic feeding problems occurring in infancy and early childhood. There are particular difficulties caused by parental responses to a handicapped child and these increase the likelihood of feeding problems. The temperament and personality of the child can pose additional problems. Early counselling for families of handicapped babies can facilitate normal mourning and the mobilization of practical help, and reduce the incidence of non-organic feeding problems.


A chromosome survey of a hospital for the mentally subnormal. A cytogenetic survey of 756 resident, but otherwise unselected, mentally retarded patients in a Scottish hospital is reported. The karyotypes of all patients were examined using orcein-stained cells, and those found to be abnormal, other than those with standard trisomy 21, were further investigated using a banding technique. A total of 103 patients were found to have an abnormal chromosome complement, of whom 91 had Down's syndrome (including six with translocations), six had some other autosomal abnormality, and six had an abnormality of the sex chromosome complement, including two with an XXYY complement. Details of the clinical and cytogenetic features are presented.


Immunological and purine enzyme studies on hyperuricaemic and normouricaemic patients with Down's syndrome. Hyperuricaemia in Down's syndrome is unreleated to the activity of phosphoribosylamidotransfrease, which catalyses the activity of the first specific step on the purine biosynthetic pathway, and to the activity of hypoxanthine phosphoribosyltransferase and phosphoribosylpyrophosphate synthetase, abnormalities of which are known to be associated with hyperuricaemia. Immunological studies involving serum immunoglobulins, natural E. coli antibodies, test immunization with pneumococcal polysaccharide type III (PnPS), in vitro lymphocyte transformation to mitogens, and pokeweed mitogen (PWM) induced immunoglobulin production showed no difference between hyperuricaemic or normouricaemic Down's patients and institutionalized controls. The Down's patients had higher serum IgA, IgG and IgE, and some also produced more immunoglobulin in PWM-stimulated lymphocyte cultures when compared to normal healthy controls. However, both patients with Down's syndrome and the institutionalized controls had significantly lower responses to PnPs than normal healthy controls. The only deficiency confined to the Down's patients was a signficant depression in delayed hypersensitivity to dinitrochlorobenzene. These findings indicate that the in vivo abnormality of depressed cellular and humoral immunity in Down's patients is not paralleled by in vitro function as measured by PHA lymphocyte transformation and immunoglobulin production by PWM-stimulated lymphocytes. There is also no apparent link between a putative defect in purine metabolism in Down's patients and any immunological abnormalities.


Relationship of donor-specific mixed lymphocyte culture reactivity to graft function in recipients of cadaveric renal allografts. The response of twelve cadaveric renal allograft recipients was serially studied in one-way MLC using the specific donor spleen lymphocytes as stimulating cells. The stimulation index (SI) progressively decreased between the second and the eighteenth post-transplantation week in the presence of normal plasma. The appearance of MLC non-reactivity (SI of less than 2.3) correlated well with the achievement of excellent graft function. In nine recipients allograft rejections have not occurred once the non-reactive state in cultures with normal plasma was established. In two of the recipients reactivity reappeared after an interval of non-reactive phase. In both instances rejection followed such reactivity and non-reactivity followed successful management of rejection. In one patient severe irreversible allograft rejection occurred in spite of the appearance of an early MLC non-reactive phase. This patient developed donor-specific lymphocytotoxic antibodies and his rejection was perhaps of antibody mediated type. Donor-specific MLC reactivity may represent cellular immune response of host to an allograft and predict cellular allograft rejection.


Selective defects in T cell function in ataxia-telangiectasia. We have studied three patients with ataxia-telangiectasia (AT) and found two of them to have a normal mixed leucocyte culture stimulating and responding ability. However, all three patients and one parent had defective cell-mediated lympholysis (CML), even in the face of a potent proliferative response to allogeneic leucocytes. None of these patients showed significant proliferative responses to common microbial antigens (tetanus toxoid, Candida albicans, purified protein derivative (PPD), diphtheria toxoid, influenza). Our studies indicate tha the T cell defect in AT preferentially affects certain T cell functions associated with antigen recognition and the generation of allogeneic CML, while sparing the allogeneic proliferative response. The selective deficiency of specific lymphocyte functions in a thymic immunodeficiency with a known defect in DNA repair is consistent with the concept that DNA modulating enzymes are important for T cell function.


Translocation and other recombination events involving the tetracycline-resistance element Tn10. Insertions of Tn10 are characterized by the presence of a direct repetition of a 9-bp target gene sequence on either side the insertion. The occurrence of these repetitions undoubtedly reflects an important feature of the way in which DNA molecules are broken and joined during translocation. Our experiments further suggest, however, that these 9-bp sequences are probably not responsible for Tn10-insertion specificity and that their presence is not required for normal Tn10 translocation elsewhere. We therefore suggest that the genetic information which controls the quality and quantity of Tn10 translocation actually resides somewhere other than these 9-bp sequences. We presume that much of this information lies within the ends of Tn10 itself and that signals on the target DNA which guide Tn10 to preferred positions must occur near, but not actually at, the eventual physical site of the integration event. Consideration of  Tn10-promoted deletions and inversions reemphasizes the role of these ends in Tn10-promoted recombination events. Since Tn10-promoted events almost always consist in joining the physical end of one of the putative IS sequences of Tn10 to some other DNA segment, one comes again to the conclusion that these ends must contain important genetic information governing recombination events.


Fibrogenesis and biosynthesis of elastin in cartilage. This study presents direct evidence that dissociated chondroblasts from rabbit ear cartilage grown in vitro are capable of synthesizing insoluble elastin. Ultrastructural examination indicated that at an early stage of tissue development, elastogenesis is initiated producing a form of primary fibrils which later condense into an electron dense amorphous material which, unlike other elastin-containing tissues, is heavily stained by metal cations and lacks peripheral microfibrils. Native elastic fibrils and the mature elastic fiber bundles are both susceptible to elastase digestion. Transmission electronmicroscopy demonstrated the presence of many intracellular filaments all showing a substructural organization and localized in close proximity to the nucleus. Their possible contractile nature is discussed. Amino acid analysis of cartilage elastin and of the elastin synthesized in vitro revealed a close chemical similarity between the two molecules. Ultrastructural analysis of the in vitro elastin demonstrated a substructural organization quite similar to that of the elastin observed in an in vivo system.


Chondroitin sulfates and proteoglycans from normal and arthrosic human cartilage. The structure of chondroitin sulfates and proteoglycans extracted from human normal young and adult cartilages and also from human arthrosic cartilages are reported. The adult articular cartilage contains almost exclusively chondroitin 6-sulfate, whereas the normal young and the arthrosic cartilage chondroitin sulfates are hybrid polymers, containing 4-sulfated and 6-sulfated disaccharide units, distributed in a quite random way along the molecules. The young cartilage proteoglycans also differ from the adult cartilage proteoglycans by their contents of keratan sulfate, the relative proportion of nonaggregating proteoglycans and electrophoretic migration in agarose gel slabs. The proteoglycans from arthrosic cartilages are very similar to those from young normal cartilages. Such changes in composition could lead to alterations in the proportion and size of the aggregates they form in the cartilages, furnishing the conditions for the processes of growth and calcification to occur.


Circadian rhythms and the urinary excretion of acid glycosaminoglycans in normal human adults. Urine from normal human adults (11 males, 4 females) was collected for 24 hours in four-hour samples, commencing at 08.00 hours. The urine volume, and concentrations of chondroitin sulfate, heparan sulfate, cetylpyridinium turbidity, and creatinine were measured on every sample. Concentrations and total output of glycosaminoglycans were significantly higher in male urine than in female urine. Chondroitin sulfate total output/four hours showed a significant negative correlation with creatinine concentration in males, but not in females. A testicular hyaluronidase is implicated. No such correlation was observed for heparan sulfate. Glycosaminoglycans are filtered into the urine. Plasma clearances are very low. Heparan sulfate is excreted with a circadian rhythm, as is glycosaminoglycan assayed by cetyl pyridinium turbidity. Peak excretions are at 06.00 and 10.00 hours respectively. Chondroitin sulfate excretion is not rhythmic in the male, perhaps because hyaluronidase activity in the urine complicates the assay. A rhythm may be present in the female.


The relationship between interventricular septum thickness and its function. An echocardiographic study. By means of a single beam echocardiography the authors investigated the relationship between interventricular septum diastolic thickness and its function, evaulated as percentage of systolic thickening. 55 persons were examined, partly healthy subjects and partly those with various cardiac diseases, excluding the cases with reversed septum motion or local septum dyskinesis. The found correlation between septum thickness and its function was exponential and statistically significant (p less than 0.001; r = --0.805). Thus, the hypothesis concerning the quantitatively dependent deterioration of the septum function on the degree of its hypertrophy was confirmed.


Inhibition of ADP-induced aggregation of human platelets by beta, gamma-methylene-ATP. Like ATP the analogue beta, gamma-methylene-ATP (AMP-PCP) is shown to be an inhibitor of both ADP-induced shape change and aggregation of human platelets. The effect of AMP-PCP on aggregation is not dependent on its conversion to adenosine, though in the presence of plasma adenosine is produced and the inhibitory effect is enhanced. Since AMP-PCP cannot be enzymatically cleaved at the beta, gamma-position the inhibitory effect cannot be attributed to utilisation of the analogue by a surface-located ATPase as has been suggested for ATP. Alternative explanations for the effect are considered with respect to some current theories of ADP-induced platelet aggregation.


ECG alterations with progressive left ventricular hypertrophy in spontaneous hypertension. Although many ECG criteria exist for diagnosis of left ventricular hypertrophy (LVH) in hypertensive man, little is known of which specific ECG changes accompany progression of LVH with duration of hypertension. The spontaneously hypertensive rat (SHR) provides the best animal model thus far developed for studying this process since these animals demonstrate a progressive increase in left ventricular/body weight ratio with age. Electrocardiograms were performed under light ether anesthesia in four age groups of SHR and two normotensive Wistar strains (NR and WKY). Analysis of variance for two factors (rat strain and age) revealed progressively increased QRS and P-wave duration and delay in intrinsicoid deflection in SHR (p less than 0.001). Bipeak P-wave notching was also noted in SHR similar to left atrial abnormality in hypertensive man. Thus, specific ECG indices can be identified in association with the known progressive increase in left ventricular mass in SHR and should provide a better means to understand evolving ECG changes in LVH.


Gut mucosal lymphocytes in inflammatory bowel disease: isolation and preliminary functional characterization. We have developed an enzymatic technique for isolating human intestinal mucosal lymphoid cells. This method was found to be superior to mechanical methods in regard to cell yield and survival. It is based on treating mucosa with serum-free solutions containing collagenase and deoxyribonuclease, followed by isolating the lymphoid cells through centrifugation steps involving fetal calf serum and ficoll-hypaque. Exposure of peripheral blood lymphocytes to the components of the enzymatic solution did not appreciably alter their uptake of tritiated thymidine in the presence or absence of mitogens. Application of the method to derive lymphoid cells from Crohn's disease, ulcerative colitis, and normal intestinal mucosa has shown that gut mucosal lymphocytes from inflammatory bowel disease (1) exceed the number of those from normal mucosa by a factor of 3 to 5; (2) show different degrees of tritiated thymidine uptake, spontaneously and in response to mitogens, depending upon the time they are harvested during the dissociation process; (3) are better stimulators than responders in the allogeneic mixed lymphocyte reaction; (4) generate suppressor cell activity comparable to that of peripheral blood lymphocytes; (5) cannot, in contrast to peripheral blood lymphocytes, generate antibody-dependent cell mediated cytotoxicity; and (6) produce an average of 5 times more IgM than equal numbers of peripheral blood lymphocytes.


[Cement ulcers].

[Cement ulcers]. It is told of a toxic contact dermatitis of a mason with hitherto intact skin. One is searching for the reason of this rarely appearing skin damage by taking into consideration the chemical process during the cement preparation as well as in the following working process. The low number of cases known so far in relation to the millions of tons of processed cement on the one hand and the serious professional consequences for the persons concerned on the other have caused us to discuss once again the causal correlations in this essay.


[Persistance of epidermal sensitizations in occupational allergic contact eczemas (author's transl)]. Allergic contact eczemas occur in the region of Halle (DDR) in the chemical industry, in health services, in architecture, in the metal industry and in local logistics. In 732 cases of occupational eczemas, "para"-substances, chromates, plastic materials and adhesives, technical oils and fats, turpentine oil, dyestuffs and disinfectants were the principal noxious substances. Phenothiazine, synthetic resins and adhesives, nickel, turpentine oil, chromates, iodine, p-phenylendiamine, mercury compounds, etc. cause epidermal sensitizations that persist up to 10-12 years. Sensitized persons must strictly avoid these noxious substances, even in their para-professional shere; repeated tests should be abandoned because the epidermal sensitization might be "boosted".


[Lyell' syndrome: a review with special regard to the form caused by drugs (author's transl)]. The clinical evolution of Lyell' syndrome (LS), its complications, the histological findings, the nosological position and the differentiation from erythema exsudativum multiforme are dealt with. There are at least two etiological forms of LS: the LS caused by staphylococci, and the LS caused by drugs. The former mainly occurs in children, and is caused by staphylococci of the phagous group II, while the latter is mainly caused by sulfonamides, pyrazolones, penicillines, barbiturates and salicylates. The causative responsibility of a certain drug can be proved by three criteria: 1. Relapse of LS after exposure to the same drug. 2. Allergy to the drug taken before the onset of LS. 3. Positive allergy tests. The hypothesis concerning the pathogenesis of LS caused by drugs, the differential diagnosis and therapeutical guidelines are dealt with.


[New German legislation on occupational dermatoses (author's transl)]. According to the new German legislation on occupational dermatoses of January 1, 1977, a person suffering from an occupational dermatosis can be idemnified only in case that occupational disease "has compelled him to abstain from all activities that have caused or might be responsible of, the appearance, the aggravation or the recurrence of that disease".


[Polyvalent contact allergy in a florist]. A female florist, who ran a flowershop from 1954 to 1966 had to quit her job because of her known contact allergy due to chrysanthemums and primrose. Though in the meantime 12 years had passed she suffered occasionally from redness of the pharynx and stomachache after ingestion of tea prepared from yarrow and camomile. Cleaning off her garden from weeds and frequently followed by swelling of her face and pruritus. After epicutaneous testing she developed positive reactions to chrysanthemum as well as cross reactions to sunflower, arnica, camomile, yarrow, tansy, mugwort and frullania (this lichen does not occur in the Northern part of Germany). Patch test with primin revealed the persistence of the highgrade hypersensitivity to Primula.


[Allergen specificity in protein dermatitis (Hjorth)]. Combination of animal specific antigen reactions and tissue specific factors were found in a female patient with protein dermatitis (Jorth). Positive reactions to muscle-tissue of pigs but no reaction to renal tissue of pigs, tested intracutaneously were obtained. These observations suggest, that muscle specific aminoacids 3-methyl-histidine, monomethyl lysin and tri-methyl-lysin cause antigen reactions.


[Pilonidal sinus in a hairdresser].

[Pilonidal sinus in a hairdresser]. The patient is a 28-year-old hairdresser who began his apprenticeship after school and has worked in this profession since then. Within the last two years fistulas formed on both hands between the second and third fingers in which hairs accumulated during his daily work of cutting hair. So an infection with lymphadenitis occurred. The excision lead to the histological result of an interdigital pilonidal-sinus.


[Recognition of a skin disease as an occupational disease according to the current legislation]. Admission of the insurance qualifying occupational skin disease (No. 5101 of Schedule 1 of the Occupational Disease Regulations = BeKV) has as its pre-requisite the availability of the medical evidence. The beginning of the period qualifying for insurance benefit shall be determined retrospectively. A hazardous activity appertains even if only a minor portion of the field of activity is the cause of the disease. Qualifying for insurance benefits requires that this activity shall have been finally given up and that the same or other hazardous activities are avoided in the future. This prognosis must have a good measure of probability. Otherwise, if the insured acts in bad faith, a pension may be withheld; if the insured acted in good faith a worsening of a syndrome by the hazardous activity (whether carried on as occupation or on one's own behalf) is not compensated for. The insurance qualifying date, furthermore, is dependent on the necessity for first-time medical treatment, medicines or therapeutic agents, or the incapacity for work, or the arising of a pension-qualifying reduction in earning power.


[Occupational dermatoses in workers of a prefabricated houses' factory]. Dermatological examinations in workers of the Dwelling Houses Factory were performed 1-5 years apart. On the whole 1011 subjects have been examined. The most frequent professional disease was oil acne brought about by the contact with anti-adhesive oils. The effects of the kind of anti-adhesive oils, the post at work (degree of exposure to the contact with oil) as well as the work period on the acne changes have been analyzed. It was found that the most acnogenic preparation was formol, then ceramic oil while isoform proved to be much less active. It was shown that the longer the work period the more decreased the oil acne morbidity. A low percentage of allergic contact eruption (1.8%) is probably related to the highly mechanized production cycle.


[Gonococcal pharyngitis in a woman with genital gonorrhea]. Gonococci were isolated from pharyngeal swabs in a woman suffering from genital gonorrhoea. She admitted orogenital contact at her most recent intercourse. A single dose treatment with spectinomycin cured the genital and pharyngeal infections.


Contact sensitivity to phenylglycidyl ether. From among 40 workers with dermatitis who did not have contact with phenylglycidyl ether but worked with epoxy resins, 5 were positive to Epidian 5 and phenylglycidyl ether. Cross reactions between these contactants were noted in 3 of the 17 guinea pigs with primary sensitization to epoxy resin or the tested diluent. For 58 persons coming into contact with phenylglycidyl ether the frequency of sensitization to the contactant was determined and the mean period between starting work and the occurrence of dermatitis was calculated.


[The allergenic nature of p-tert-butylphenolformaldehyde resin]. Until now allergic contact dermatitis to polychloroprene glues was thought to be caused by uncondensed p-tert.-butylphenol (monomer) or by the p-tert. burylphenol formaldehyde resin molecule (polycondensate) as allergens. This opinion could not be verified. We found the following two contact allergens: 2-hydroxy-5-tert.-butylbenzyl alcohol and a four nuclear-condensate from four p-tert-butylphenol molecules linear combined by methylene bridges.


[Allergic skin reactions in metallurgic industries (author's transl)]. The sensitizing properties of additives to cooling emulsions are reviewed. Presently the majority oft skin disorders due to cooling emulsions is of toxic and not of allergic origin. However, the introduction of new chemical substances either as substitutes of nitrites or for a more effective preservation may reverse this ratio especially if potent allergens are used unitentionally. In evaluating the advantage of a new additive its possible sensitizing properties has to be considered.


Genetic screening of compounds used in drug abuse treatment. I. Naltrexone hydrochloride. Several compounds used clinically in drug abuse therapy were evaluated for genetic activity in a series of in vitro assays. This initial report describes the results for one of these compounds, Naltrexone. Nalrexone is a relatively nontoxic drug antagonist related to Naloxone which appears to be effective in diminishing the euphoria and dependence upon heroin in clinical studies. With the exception of weak nonspecific DNA damage observed in an E. coli DNA repair test and possibly with WI-38 cells as well, Naltrexone did not demonstrate significant potential for the induction of gene mutations or chromosomal aberrations under the conditions of this evaluation.


Serotonin as a differentiation signal in early neurogenesis. The hypothesis that serotonin (5-HT) influences the onset of differentiation (cessation of division) of prospective 5-HT target neurons during embryogenesis was tested by administering the 5-HT depleting drug p-chlorophenylalanine (pCPA) to pregnant rats and dating the time of last cell division for fetal neurons using long survival 3H-thymidine autoradiography. PCPA specifically retarded the onset of neuronal differentiation in brain regions known to contain 5-HT terminals or to have a high 5-HT content in the adult (5-HT target cells). Conversely, the 'stress' of daily vehicle injections accelerated onset of differentiation in these regions, possibly due to stimulation of 5-HT synthesis by glucocorticoids. These data support the model of 5-HT as a humoral signal for the differentiation of cells later recognized by 5-HT neurons as appropriate targets for synaptogenesis.


Endoscopic therapy of a congenital oesophageal stricture. A sixteen months old girl with Down's-Syndrome suffered from congenital oesophageal membrane and segmental oesophageal stricture. In the neonatal period, two other associated malformations of the gastrointestinal tract (malrotation of gut and duodenal web) had been operated successfully. The first endoscopic examination of the eosophagus was performed at the age of sixteen months because of increasing dysphagia. A solid membrane in the lower part of the oesophagus was incised by diathermy. The associated segmental stenosis necessitated repeated bougienages. After this treatment the child developed well without clinical signs of dysphagia.


Adenosine triphosphatase of Aspergillus nidulans: existence of isoenzymes of Ca2+-ATPase. Ca2+-ATPase activity increased five- to six fold when the cells were subjected to growth at 37 degrees C in protein hydrolysate-supplemented media as compared to that of the cells grown in minimal media. One major isoenzyme and one minor isoenzyme were present in minimal-medium-grown cells while two major isoenzymes were present in the cells grown in protein-supplemented media. When the cells were subjected to heat stress (43 degrees C), they exhibited significantly decreased activity as compared to 37 degrees C grown cells. However, all the cultures subjected to growth at 43 degrees C showed two isoenzymes independent of growth medium.


Kinetics of the reactions between streptokinase, plasmin and alpha 2-antiplasmin. Streptokinase reacts very rapidly with human plasmin (rate constant 5.4 S 10(7) M-1 s-1) forming a 1:1 stoichiometric complex which has a dissociation constant of 5 X 10(-11) M. This plasmin-streptokinase complex is 10(5) times less reactive towards alpha 2-antiplasmin than plasmin, the inhibition rate constant being 1.4 X 10(2) M-1 s-1. The loss of reactivity of the streptokinase-plasmin complex towards alpha 2-antiplasmin is independent of the lysine binding sites in plasmin since low-Mr plasmin, which lacks these sites, and plasmin in which the sites have been blocked by 6-aminohexanoic acid, are both equally unreactive towards alpha 2-antiplasmin on reaction with streptokinase. The plasmin-streptokinase complex binds to Sepharose-lysine and Sepharose-fibrin monomer in the same fashion as free plasmin, showing that the lysine binding sites are fully exposed in the complex. Bovine plasmin is rapidly inhibited by human alpha 2-antiplasmin (k1 = 1.6 X 10(6) M-1 s-1) and similarly loses reactivity towards the inhibitor on complex formation with streptokinase (50% binding at 0.4 microM streptokinase).


Primary structure of human fibrinogen and fibrin. Structural studies on NH2-terminal part of B beta chain. The cyanogen bromide fragment, N-DSK, containing the NH2-terminal portions of the three chains of fibrinogen, was found to exist in dimeric and polymeric forms. These different forms gave rise to identical chain fragments on reduction and alkylation. The B beta chain of N-DSK from fibrinogen and the beta chain of N-DSK from fibrin were isolated and characterized. The B beta chain fragment has a blocked NH2-terminal residue, and fibrinopeptide B is released on digestion with thrombin. The beta chain fragment has glycine as NH2-terminal residue. The molecular weight of the B beta chain fragment is 12200 as determined by ultracentrifugal analysis. Gel electrophoresis in sodium dodecyl sulphate gave the molecular weights of 14000 and 13000 for the B beta chain and beta chain fragments, respectively. The NH2-terminal B beta chain fragment consists of 118 amino acid residues and the beta chain fragment of 104 residues. The amino acid sequence of beta chain fragment is identical to B beta chain fragment except for the fibrinopeptide B portion. The isolation of a B beta-related fragment (B beta +), with a molecular weight of 30000, is also reported. The presence of B beta + was explained on the basis of incomplete cleavage at the Met-118 residue during treatment with cyanogen bromide. Some functional aspects of the B beta chain fragment are discussed.


Investigation of soluble mitochondrial ATPase by the reacting enzyme sedimentation method. Soluble mitochondrial ATPase from bovine heart (factor F1) loses its activity during ATP hydrolyses. The inactivation is accelerated by moderate pressure, which is generated in an ultracentrifuge cell. The rate of inactivation slows down if the concentration of the substrate (MgATP) is diminished. ATP hydrolysis proceeds at an almost constant rate if the substrate concentration is as low as 0.05 mM. One intersubunit cross-link formed by dimethylsuberimidate per molecule of factor F1, prevents its inactivation during the ATPase reaction both without pressure and in an ultracentrifuge. Sedimentation coefficients measured by the reacting enzyme centrifugation method of both unmodified factor F1 at a low (about 0.05 mM MgATP) substrate concentration and of its dimethylsuberimidate cross-linked form in the presence of 10 mM MgATP, were determined to be s20, w = 12.4 +/- 0.4 S. The value is the same as that obtained by the conventional boundary sedimentation method in the absence of the substrate. This result testifies to the fact that the conformation of reacting factor F1 in solution is similar to that of the enzyme in the absence of the substrate.


Level and turnover of polyadenylate-containing ribonucleic acid in Neurospora crassa in different steady states of growth. Mycelia of Neurospora crassa in a steady state of growth in different media have a ribosomal content proportional to the rate of growth. Moreover, both the percentage of polysomes and the average ribosomal activity are about the same at all different growth rates. The content of polyadenylated RNA was determined in three different conditions of exponential growth, which allowed growth rates that ranged from 0.26 to 0.51 duplications/h, and was found to constitute about the same fraction of total RNA (4.5--5.2%). Using a kinetic approach, an equation was derived which allowed determination of the average half-lives of polyadenylated RNA: in each medium the cultures were labeled from the moment of the inoculation with [32P]orthophosphate and were then given a 10-min pulse with [5-3H]uridine when they were in the exponential phase. It was found that the determined half-lives of polyadenylated RNA vary, depending on the growth medium, between 30 and 60 min, but with no direct correlation with the growth rate. Moreover, the rate of synthesis of polyadenylated RNA relative to that of stable RNA decreased with the growth rate. On the basis of previous data on the rates of synthesis of stable RNA, it was possible to make an evaluation of the absolute rate of synthesis of polyadenylated RNA. Whereas the rate of synthesis of stable ribosomal RNA increases as a function of the square of the number of duplications per hour, the increase in the rate of synthesis of polyadenylated RNA with the growth rate is much less consistent. It is concluded that in Neurospora the growth rate does not depend on the rate of synthesis of mRNA but rather on the rate of synthesis of rRNA, which sets both the ribosomal level and the steady-state level of mRNA.


A DNA-dependent ATPase of calf-thymus.

A DNA-dependent ATPase of calf-thymus. A DNA-dependent ATPase has been purified from calf thymus. The enzyme hydrolyses ATP and dATP in the presence of heat-denatured DNA. It does not hydrolyse the corresponding nucleoside triphosphates of guanine, uridine and cytosine. The Km values for ATP and dATP are both 0.62 mM. The enzyme requires magnesium or manganese ions. Its sedimentation coefficient is about 4.4 S. The catalytic activity is inhibited by N-ethylmaleimide but is not sensitive to novobiocin and nalidixic acid which are potent inhibitors of bacterial DNA gyrase. In some cases, during purification, chromatographically distinct additional DNA-dependent ATPase activities were detected. Limited proteolysis or covalent modification of the enzyme in the tissues, or during the first steps of its extraction, are probably responsible for the appearance of these chromatographically distinct forms.


Calcium uptake by sarcoplasmic reticulum of rat muscle: inhibition by DDT. Sarcoplasmic reticulum fragments capable of accumulating calcium were isolated from rat skeletal muscle by differential and sucrose gradient centrifugation. The ability of these fragments to accumulate calcium was impaired by adding 2,2-bis-(p-chlorophenyl)-1,1,1-trichloroethane (DDT) to the assay medium at concentrations of 0.06 to 6 muM. DDT (6 muM) caused a sharp lag in calcium uptake, with an 82% reduction in reaction rate 30 sec after calcium was added and a 62% reduction after one min. Basal ATPase activity of the microsomal fraction was inhibited by DDT but the calcium-stimulated increment of ATP hydrolysis was not. The findings show that DDT hinders calcium uptake by sarcoplasmic reticulum, but by some means other than inhibition of the calcium-stimulated ATPase. An apparent antagonism between DDT and ouabain or oligomycin was indicated. We propose that the presence of the lipid-soluble DDT molecule within the membrane of the sarcoplasmic reticulum interferes with the normal rapid uptake of calcium ions required for muscle relaxation, and that this interference may contribute to loss of muscle control in organisms poisoned by DDT.


Expression of Ly-6 alloantigen during differentiation of cytotoxic T cells. We have prepared anti-Ly-6.2 by immunization of (CBA/Ca X A-Thy-1a)F1 with AKR/Crc lymphocytes and used the antiserum to study heterogencity of peripheral T lymphocytes. The Ly-6 alloantigen is found on all activated cytotoxic T cells studied, directed to a variety of different target antigens. The antiserum reveals heterogeneity among the precursors of T killer cells, i.e. allogeneic precursors are Ly-6-, whereas the generation of cytotoxic cells to hapten-modified syngeneic cells and xenogeneic cells is partially abrogated by serum pretreatment. Precursors of some in vivo primed responses are also Ly-6+. These findings indicate that the expression of Ly-6 antigen is, at least, partially related to the stage of T cell activation. The in vitro proliferative response of T cells to allogeneic Ia antigens is substantially reduced by pretreatment with anti-Ly-6.2 serum suggesting that this antiserum may be a useful tool for the study of heterogeneity in the Ly-1+ pool of T cells.


Close association between particular I region-determined cell surface antigens and Ir gene-controlled immune responsiveness to synthetic polypeptides in wild rats. The relationship between major histocompatibility complex (MHC) and genetic control of immune responsiveness to the synthetic polypeptides (T,G)-A--L [poly-(LTyr,LGlu)-poly(DLAla)--poly(LLys)] and (H,G)-A--L [poly(LHis,L-Glu)-poly-(DLAla)--poly(LLys)] has been studied in 26 wild rats. The major histocompatibility complex (MHC) genotype frequencies observed were not different from those expected according to the Hardy-Weinberg formula. More than half of the wild rats carried MHC-linked responder Ir-TGAL and Ir-HGAL genes. High or intermediate responsiveness to (T,G)-A--L and high responsiveness to (H,G)-A--L were always found to be associated with particular I region-determined cell surface antigens. These antigens could be identified serologically and by primary and secondary mixed lymphocyte reactions, and were similar or identical to I region products of (T,G)-A--L high responder or (H,G)-A--L intermediate responder inbred rat strains. The strong association between cell surface antigens and immune responsiveness could be due to linkage disequilibrium or to pleiotropy. Since the same I region-determined cell surface structure could be associated either with high or intermediate anti-(T,G)-A--L antibody titers, the presence of the Ia antigen(s) identified did not seem to guarantee high antibody responsiveness to the test antigen.


Spontaneous activity and responses of reticular neurones in monoamine-depleted rats. Depletion of rat brain serotonin by p-chlorophenylalanine (PCPA) pretreatment, or of monoamines by reserpine pretreatment, was associated with reduced spontaneous firing rates of bulbar reticular neurones. Administration of 5-hydroxytryptophan to PCPA-treated rats reversed the reduction of neuronal activity. It is suggested that the results indicate a tonic excitatory serotoninergic input to a significant proportion of these neurones, which is abolished by serotonin depletion. Responses to serotonin and noradrenaline were greater in PCPA-treated and reserpire-treated rats respectively, indicating the development of supersensitivity.


Pimozide and p-chlorophenylalanine blockade in DL-amphetamine and pargyline-treated rats held at two environmental temperatures. In rats, treated with DL-amphetamine + monoamine oxidase inhibitor, and held at an ambient temperature of 28.5 degrees C, hyperthermia was completely eliminated by treatment with pimozide + p-chlorophenyl-alanine. The same drugs markedly reduced the hypothermic effects in rats treated similarly at 4 degrees C. Results implied that serotoninergic and dopaminergic neurones were involved in the thermoregulatory effects of amphetamine.


An uptake of fluorescein isothiocyanate labeled neocarzinostatin into the cancer and normal cells. An uptake of fluorescein isothiocyanate labeled neocarzinostatin into normal and cancerous epithelial cells from bladder was investigated. Results showed that neocarzinostatin traversed the cell membrane into cytosol and nuclei, and it appeared to have a preferential cytotoxicity for the cancer cell.


Circadian variation of the streptozotocin-diabetogenic effect in mice. Streptozotocin was injected in normal mice every 4 h, during the day. Greatest number of diabetic animals were obtained at 16.00 h (95%) and lowest at 08.00 h (50%). Magnitude of hyperglycemia also showed similar distribution. This effect might be considered when planning its use for both experimental and clinical purposes.


Treatment of female infertility due to tubal obstruction by operative laparoscopy. The advent in recent years of safe endocoagulation (thermocoagulation within the abdomen) has permitted operative laparoscopic treatment of the tubal factor in infertility in selected cases. This paper reviews the results of operative laparoscopy in 223 cases treated for infertility between 1971 and 1976. Tubal occlusion was present in 133 patients before surgical intervention. Following operative laparoscopy, tubal patency was demonstrated in 67% on testing at the time of operation and in 12% at the first postoperative hydrotubation. In only 21% of cases was tubal patency not achieved by these methods. Those cases requiring isthmic salpingostomy, ampullary or isthmic-tubal implantation, or end-to-end anastomosis were further treated by laparotomy and microsurgery. Ninety cases of pelvic endometriosis were treated by a combination treatment of thermocoagulation, ovarian cyst resection, and the antigonadotropin agent, danazol. Ovariolysis, salpingolysis, fimbrioplasty, and salpingostomy can easily be performed using operative laparoscopy as the method of choice with a minimum of complications, shortened hospitalization time (2 days), and the potential for a repeat procedure or a follow-up laparotomy should this be necessary. The pregnancy rate following laparoscopic treatment for the correction of distal tubal occlusion was 30.5% and for endometriosis genitalis externa, 40%. These rates compare favorably with the rates following procedures involving laparotomy and microsurgery for correction of similar lesions.


[Onychomycoses caused by moulds].

[Onychomycoses caused by moulds]. The authors studied in vitro and in vivo the invasion of the nail keratin by saprophytes. This invasion takes palce in the same way in both cases: mycelian filaments and spores penetrate in the hyponychium, filaments penetrate in the upper part of the tablet, filaments and, as far as some saprophytes are concerned, 'boring hyphae' penetrate in the lower part of the tablet. Those ways of invasion are responsible for the clinical pictures (onychomycosis, pachyonychia, leuconychomycosis). Electron microscopically the mycelian filaments appear to be both intercellular and intracellular. The authors insist in the importance of the criteria of evaluation which allow us to establish the saprophytic origin of onychomycosis.


[Opportunistic fungi. Demonstration of some cases]. Demonstration of some cases of mycoses caused by opportunistic fungi.


[New transducing phage with RNA polymerase beta- and beta'-subunit genes derived from a hybrid phage lambda att80: isolation, genetic analysis and physical mapping]. A hybrid lambda att 80 phage with the genetic structure lambda (A-J) phi 80 (att-int-xis) imm lambda..cI857s7 is shown to be a convenient vector for creating transducing phages. On the one hand, the restriction analysis indicates that it has 3 restriction sites for EcoRI in comparison with 5 and 9 sites for parental phages lambda and phi 80 respectively. On the other hand, its buoyant density is less than that of phage lambda and under centrifugation it is easier separated from the phage transducing particles. When lambda att 80 prophage was excluded from the bfe locus of Escherichia coli, transducing phages with genes of two RNA polymerase beta-subunits (rpoB and rpoC) were isolated. To identify the latter, a convenient genetic test was worked out. A physical map of lambda att 80 drifd 35 transducing phage, carrying rpoB and rpoC genes has been constructed using endonucleases EcoRI and HindIII. A comparison of this map and the corresponding maps of transducing phages lambda drifd 18 and lambda drifd 47, studied earlier, led to the discovery of two integration sites of phage lambda within the locus bfe spaced apart by about 1800 nucleotide pairs. At all the sites both phages (lambda and lambda att 80) have integrated in the locus bfe in the counter clockwise order.


Cancer and environment.

Cancer and environment. The attention of scientists has been directed mostly to analyze the influence of the environment on tumor induction. However, the external environment can also enhance the reactivity of the host organism towards tumors, by activating several immune mechanisms. Moreover, the host organism is the first "foreign" environment with which tumor cells come into contact in a dynamic way, characterized by a continuous evolution.


Enzyme histochemistry of Wallerian degeneration in the immature optic nerve of rabbits. A histochemical study was performed on the activity of several phosphatases, esterases and oxidoreductases in the immature optic nerve of rabbits undergoing Wallerian degeneration. Unilateral enucleations of the eye bulb were performed on 7 days old animals and the degenerated optic nerves were examined in rabbits, 5, 23, 63 and 173 days afterwards. The following results were obtained: 1. The reactive cells appearing in the immature optic nerve undergoing Wallerian degeneration exhibit distinctly increased activities of many hydrolytic and oxidoreductive enzymes. 2. The histoenzymic pattern of changes displayed by the reactive cells occurring in the immature, degenerating optic nerve is distinct from and bears no relation to that seen in the normally developing optic nerve. 3. The genetic formation contained in the oligodendroglial cells is not the sole factor safeguarding the transformation of immature and mature oligodendroglia into myelinating cells.


Suppressor T-cells in BCG-infected mice. Specific pathogen-free B6D2 hybrid mice were infected with high (10(8) cells, intravenous), moderate (10(6) cells, intravenous), and low 10(3) cells, aerogenic) doses of viable BCG Pasteur. The growth of the BCG in the lungs and spleens of the three groups was followed over a 90-day period and correlated with the level of tuberculin hypersensitivity. Spleen cells were harvested from the three groups of mice at increasing time intervals and filtered through nylon wool to remove adherent cells, and the level of blast transformation after exposure to phytohemagglutinin and purified protein derivative was determined. Early in the BCG infection both the high- and the intermediate-dose groups showed enhanced thymidine incorporation by the spleen cell cultures, followed by a profound depression late in the infection. At this time, both groups of mice were anergic to purified protein derivative injected into footpads. Cell mixing studies demonstrated the presence of a population of suppressor cells in the spleens of the anergic animals. The suppressive abilities of these cells would be ablated by treatment with anti-Thy-1 antiserum and complement. The aerogenically infected mice were unresponsive to purified protein derivative but showed no evidence of suppressor T-cells. The lack of tuberculin sensitivity in these mice seemed to be due to a lack of sensitized T-cells in the spleen rather than to active immunosuppression.


Development of suppressor T-cells in Mycobacterium habana-infected mice. Mice were infected intravenously with increasing numbers of Mycobacterium habana (simiae serotype II), and the levels of delayed-type hypersensitivity to purified protein derivative and M. habana cytoplasmic protein antigen were determined after 14, 30, and 90 days. A footpad delayed-type hypersensitivity response was seen in 14-day-infected mice and was followed by a persisting anergy. T-cell-enriched suspensions collected 30 and 90 days into the infection (anergic donors) showed depressed transformation indexes after phytohemagglutinin and M. habana cytoplasmic protein antigen treatment in vitro. The corresponding B-cell mitogen (lipopolysaccharide) responses were not affected. Mixing experiments with T-cell-enriched suspensions from day-90 M. habana-infected donors adoptively suppressed lymphocyte transformation by normal and day-14 spleen cells. This effect could be ablated by anti-theta serum and complement treatment of the day-90 cells, indicating that the lack of in vitro responsiveness to cytoplasmic protein antigen was mediated by a population of suppressor T-cells present in the heavily infected spleens. There was no evidence that similar cells were present in the spleens of the 14-day-infected animals. Suppressor T-cells could be induced in vitro by exposure of day-14 spleen cells to concanavalin A or M. habana cytoplasmic protein antigen before they were mixed with normal or day-14 indicator splenic lymphocytes. The timing of the appearance of suppressor T-cells in the infected spleens corresponded to a loss of footpad hypersensitivity by the M. habana-infected animals.


A lipophilic derivative of neocarzinostatin. A polymer conjugation of an antitumor protein antibiotic. A lipophilic derivative of neocarzinostatin (NCS), an antitumor antibiotic, was prepared by reaction with a synthetic water-soluble polymer, [(styrene)1 approximately 3-(maleic acid 4 approximately 7/anhydride 1)]. The reaction was carried out at pH 8.6 for 3 h and aimed at modifying the two nonessential amino groups (alpha-amino of Ala-1, epsilon-amino of Lys-20). The NCS-polystyrene (SMANCS) was purified on a column of Sephadex G-100 in 0.05 M ammonium bicarbonate and the main product was obtained as a single peak. The elemental analysis showed an increased C and a decreased N content. U.v. and i.r. absorption spectra for SMANCS showed the presence of styrene. SDS-acrylamide gel electrophoresis at pH 8.5 and the decreased N content suggested a molecular weight of about 25 000, indicating the numbers of polymers conjugated to be about six units, two of which were found attached to the two amino groups. SMANCS was soluble in organic solvents, in contrast to NCS, and in water. SMANCS exhibited increased chemical and biological stability and appeared to possess similar in vitro biological activity.


Serotonergic mediation of reward within the medial raphe nucleus: some persistent problems in interpretation. Adult male Sprague Dawley rats were implanted with unipolar stimulating electrodes aimed at the medial forebrain bundle (MFB) or the medial raphe nucleus (MR). All MFB implanted subjects self-stimulated at high stable rates for at least three weeks. Only a minority (1/3) of MR rats self-stimulated at all. Rates for the MR group were considerably more variable, and could not be maintained for more than two weeks. Treatment with methysergide increased MFB self-stimulation but decreased MR self-stimulation. While this result suggests serotonergic mediation of self-stimulation this conclusion must be interpreted cautiously since parachlorophenylalanine (PCPA) reinstated self-stimulation in raphe animals which had spontaneously ceased responding.


Benzoyl peroxide gel therapy in acne in Singapore. The results of an open clinical trial of 200 patients in Singapore show that benzoyl peroxide, in a stable gel formulation, both in 2.5% and 5% strengths, was highly efficacious in the topical treatment of acne vulgaris without concomitant systemic therapy. The series included a small number of Caucasians (13 patients) who were also treated effectively. Side effects noted were generally mild and transient.


The combined use of topical benzoyl peroxide and tretinoin in the treatment of acne vulgaris. A clinical trial using tretinoin lotion 0.05%, benzoyl peroxide 5% and 10% as topical application was performed on 250 ambulatory patients suffering from various degrees of acne vulgaris. The results indicate that tretinoin applied in the morning and benzoyl peroxide applied at night is the most efficacious regimen to be used, with minimal side effects.


Providing a less restrictive environment for profoundly retarded persons by teaching independent walking skills. A basic right of all handicapped persons is to live in the least restrictive environment possible. In this investigation, procedures were evaluated for teaching four institutionalized males with profound retardation necessary skills to increase their individual freedom of movement. Following baseline, a travel training program with a backward chaining format was implemented to teach each person to walk independently from his living area to school. Travel training included instructions, practice, praise, feedback, verbal reprimands, prompts, and edible reinforcers. Each resident began walking the entire distance to school independently during training and also began walking back to the living area, although the latter set of skills was not specifically trained. Following termination of the formal investigation, follow-up measures of 1 to 8 weeks showed the residents continued going to school independently. A survey of residential facilities in 43 states provided social validation for the seriousness of the problems associated with transporting seriously retarded persons to school. Also, time efficiency measures indicated that training independent travel resulted in reductions of staff time required in school transportation. Results were discussed in light of the potential contributions of behavior analysis in providing less restrictive environments for seriously handicapped persons.


The application of pattern recognition techniques in the analysis of metacarpophalangeal lengths. Pattern recognition techniques have been applied to the analysis of metacarpophalangeal lengths obtained from hand radiographs. A data base consisting of healthy subjects, and subjects exhibiting achondroplasia, Down's syndrome, and Turner's syndrome was studied. A classification technique was found which effectively separates these conditions. The technique is suitable for computer automation.


A conformational model of the action of general anesthetics at the membrane level. III. Anesthetics and the properties of membrane-bound enzymes: mitochondrial ATPase. We have studied the effect of general anesthetics on the kinetic properties of the mitochondrial Mg2+-dependent ATPase. The enzyme is inhibited by anesthetics (alcohols, halotane, pentrane, ketamine) at concentrations of the order of those found to affect lipid-protein interactions. The inhibition appears usually uncompetitive with respect to the substrate, ATP, with a decrease of both Vmax and KM, indicating a possible stabilization of the enzyme-substrate complex. Arrhenius plots of ATPase activity show a striking increase in activation energy below 17-20 degrees C. Anesthetics affect the temperature dependence by increasing the activation energy above the break or abolishing the break whatsoever. An exception is diethyl ether, that induces a decrease in activation energy and a shift of the break to lower temperatures. Anesthetics make the ATPase insensitive to energy transfer inhibitor, oligomycin and dicyclohexyl carbodiimide. At low anesthetic concentration the oligomycin inhibition curve is changed from sigmoidal to hyperbolic, showing a loss of cooperativity in the inhibition.


Role of polymeric forms of the bacteriophage phi X174 coded gene A protein in phi XRFI DNA cleavage. Gene A of the phi X174 genome codes for two proteins, A and A* (Linney, E.A., and Hayashi, M.N. (1973) Nature New Biol. 245, 6-8) of molecular weights 60,000 and 35,000, respectively. The phi X A* protein is formed from a natural internal initiator site within the A gene cistron while the phi X A protein is the product of the entire A gene. These two proteins have been purified to homogeneity as judged by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Previous studies have shown that the phi X A protein is an endonuclease which specifically introduces a discontinuity in the A cistron of the viral strand of supertwisted phi XRFI DNA. In addition to this activity, the phi X A protein also causes relaxation of supertwisted phi XRFI DNA and formation of a phi XRFH DNA . phi X A protein complex which has a discontinuity in the A cistron of the viral strand. This isolatable complex supports DNA synthesis when supplemented with extracts of uninfected Escherichia coli which lack phi X A protein and phi XRFI DNA. The phi XRFII DNA . phi X A protein complex can be attacked by exonuclease III but is not susceptible to attack by E. coli DNA polymerase I, indicating that the 5'-end of the complex is blocked. Attempts to seal the RFII structure generated from the phi XRFII DNA . phi X A protein complex with T4 DNA ligase in the presence or absence of DNA polymerase were unsuccessful. The phi X A protein does not act catalytically in the cleavage of phi XRFI DNA. Under conditions leading to the quantitative cleavage of phi XRFI DNA, the molar ratio of phi XRFI DNA to added phi X A protein was approximately 1:10. At this molar ratio, cross-linking experiments with dimethyl suberimidate yielded 10 distinct protein bands which were multiples of the monomeric phi X A protein. In the absence of DNA or in the presence of inactive DNA (phi XRFII DNA) no distinct protein bands above a trimer were detected. We found it possible in vitro to form a phi XRFII DNA . phi X A protein complex with wild-type phi XRFI DNA (phi X A gene+) and with phi XRFI DNA isolated from E. coli (su+) infected with phage phi X H90 (an am mutant in the phi X A gene). Thus, in vitro, in contrast to in vivo studies, phi X A protein is not a cis acting protein. The purified phi X A* protein does not substitute for the phi X A protein in in vitro replication of phi XRFI DNA nor does it interfere with the action of the phi X A protein which binds only to supertwisted phi XRFI DNA. In contrast, the phi X A* protein binds to all duplex DNA preparations tested. This property prevents nucleases of E. coli from hydrolyzing duplex DNAs to small molecular weight products.


Substrate regulation of the sarcoplasmic reticulum ATPase. Transient kinetic studies. The rate of phosphorylation of the Ca2+-dependent ATPase of sarcoplasmic reticulum vesicles by ITP and ATP was studied using a millisecond mixing and quenching device. The rate of phosphorylation was slower when the vesicles were preincubated in a Ca2+-free medium than when preincubated with Ca2+, regardless of the substrate used and of the pH of the medium. When the vesicles were preincubated with Ca2+ at pH 7.4 an overshoot of phosphorylation was observed in the presence of ITP. The overshoot was abolished when the pH of the medium was decreased to 6.0 or when the vesicles were preincubated in a Ca2+-free medium. Using vesicles preincubated with Ca2+ the apparent Km for ITP found was 2.5 mM at pH 6.0 and 1.0 mM at pH 7.4. The Vmax observed (77 mumol g-1 s-1) did not change with the pH of the medium. Both at pH 6.0 and 7.4 the apparent Km for ATP was 3 microM when preincubated in a Ca2+-free medium. At pH 6.0 the Vmax for ATP varied from 96 to 33 mumol g-1 s-1 depending on whether the vesicles were preincubated in the presence or absence of Ca2+. At pH 7.4 the Vmax for ATP was 90 mumol g-1 s-1 in both conditions. The rate of phosphorylation of the vesicles was dependent on the relative Ca2+ and Mg2+ concentrations of the reaction medium regardless of the substrate used.


Purification of the (Ca2+-Mg2+)-ATPase from human erythrocyte membranes using a calmodulin affinity column. The (Ca2+-Mg2+)-ATPase from human erythrocyte membranes has been solubilized in Triton X-100 and purified on a calmodulin affinity chromatography column in the presence of phosphatidylserine, to limit the inactivation of the enzyme. The enzyme was purified at least 150 times when compared with the original ghosts and showed a specific activity of 3.8 mumol.mg-1.min-1. In sodium dodecyl sulfate-polyacrylamide gels, a single major band was visible at a position corresponding to a molecular weight of about 125,000; a minor band (11% of the total protein) was present at a position corresponding to Mr = 205,000. Upon incubation of the purified preparation with [32P]ATP, both bands were phosphorylated in proportion to their mass, suggesting that both were active forms of purified ATPase.


Subunit interaction during catalysis. Alternating site cooperativity of mitochondrial adenosine triphosphatase. ATP concentration modulates oxygen exchange catalyzed by purified, soluble mitochondrial ATPase during ATP hydrolysis so that water oxygen incorporation into each Pi formed increases markedly as ATP concentration is lowered. This behavior is readily explained by catalytic cooperativity between subunits of the ATPase. However, other reasonable explanations also need consideration. A new approach for assessing these various explanations is used, based on measurement of the [18O]Pi species formed by hydrolysis of ATP highly labeled with 18O in the gamma-phosphoryl group. The results and other supporting data give what appears to be the most compelling evidence yet attained for alternating site catalytic cooperativity in an enzymic catalysis.


The impact of musculoskeletal disorders on the population of the United States. Musculoskeletal disorders constitute such a large component of impairments of individuals in the working and geriatric population that good statistical data on them are essential for planning health care. We have collected the pertinent data, with references to recent source material, to determine the incidence, effect on the quality of life, and associated costs of these disorders in the United States.


Phage heterogeneity of coagulase-negative staphylococci isolated in the United States and Sweden from bovine milk. A Swedish bovine and a Dutch human phage set for coagulase-negative staphylococci were used to phage type coagulase-negative staphylococci isolated from bovine milk from Minnesota dairy herds. A comparison was also made of the deoxyribonuclease activity of coagulase-negative staphylococci isolated from bovine milk in Sweden and Minnesota. Of 133 Minnesota isolates, only one could be typed with the Swedish set and one by the Dutch set, whereas of 218 Swedish strains, 49 could be typed with the Swedish set and 7 by the Dutch set. A larger number of coagulase-negative isolates from Sweden were deoxyribonuclease positive (35%) than were the similar isolates from Minnesota (12%). These findings substantiate the marked heterogeneity of coagulase-negative staphylococci isolated from bovine udders. Results presented point to the usefulness of establishing regional phage sets for epidemiological investigations of coagulase-negative staphylococci in cattle. It is anticipated that at a later stage the regional phage sets will be coordinated internationally.


The impact of chronic pain on the self-concept. Compared self-concepts of three groups, medical patients, chronic low back pain patients and chronic head pain patients (N = 60) to determine (1) whether chronic pain patients have self-perceptions that differ from other medical patients; (2) whether changes in self-perception are limited to physical attributes and capacities; and finally (3) whether persons who suffer different types of chronic pain would have differing self-concepts. Significantly lower self-concepts were obtained from groups of head pain and low back pain patients. Self-concept patterns for the two pain groups were quite similar with the exception of two self-concept components that were significantly lower for the head pain group. Differences were explained in terms of loss of many normal functions and disruption of normal life-styles. Implications for treatment of pain patients and for training of health professionals were discussed.


Bacteriophage typing of coagulase-negative staphylococci. Cultures comprising the 10 species of coagulase-negative staphylococci proposed by Kloos and Schleifer (J. Clin. Microbiol. 1:82--88, 1975) were typed with bacteriophages isolated from Staphylococcus epidermidis. Although only 10.5% were typable, 50% of those identified as S. epidermidis were typed. Cultures from patients with middle ear infections were also classified by this system and phage typed.


[The interstitial pregnancy. Report of three observations (author's transl)]. The recent occurrence at the Port-Royal obstetrics and gynaecology center of three cases of interstitial pregnancy out of a total number of 208 ectopic pregnancies give us the opportunity to discuss the diagnosis and present management of the rarest form of tubal pregnancies. The diagnosis is always difficult. Nowadays, thanks to the use of echography and especially of laparoscopy, interstitial pregnancies can be detected earlier. Thus the precocity of the diagnosis should permit a conservative surgical treatment. Hysterectomy should not be considered but in very special cases.


Adrenal and gonadal steroids and pituitary response to LHRH in girls. I. Delayed puberty. Plasma levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), dehydroepiandrosterone (DHA), dehydroepiandrosterone-sulphate (DHA-S), 17-hydroxyprogesterone (17P), androstenedione (A), testosterone (T), dihydrotestosterone (DHT) and estradiol (E2) were measured in basal conditions in eleven young women from 16 to 25 years of age characterized by delayed puberty. The gonadotropin response to LHRH (50 microgram iv) was also tested in these cases. The results, as far as gonadotropins and E2 are concerned, indicate that delayed pubertyin girls is a heterogeneous disorder: an impairment in the negative feedback between E2 and FSH coexists with a reduced ovarian response to endogenous gonadotropins. All cases showed evidence of a more or less pronounced delayed adrenarche, which was demonstrated by the markedly reduced levels of DHA-S and DHA (with the exception of this latter steroid in two cases with idiopathic hirsutism). Furthermore, the very low plasma progesterone (P) levels in all cases suggest the existence of impaired delta 5 - delta 4 isomerase activity in the adrenal cells. Despite the low levels of A and T, DHT is within the upper limits of the normal range in all cases.


Rehabilitating the severely disabled: the foreign experience. This paper sets forth a model for examining the relationships between fourteen policy and politicoeconomic variables, and the social benefits and costs of rehabilitation. Based on discussions in early 1977 with scholars, ministry officials, trade unionists, and politicians in several northwestern European countries, as well as on documentation relating to the rapid growth of disability expenditures and the factors thought to influence it, some "lessons" are presented for policymakers in the United States and other countries. In general, current trends are seen as depressing the post-service earnings of individual rehabilitants, limiting the stabilizing effects of rehabilitation on labor market turnover, and increasing available time for unpaid work in the home and elsewhere. Unequal intergovernmental cost sharing in the provision of benefits and services, it is argued, seems likely to promote inefficient allocation of scarce rehabilitation resources with negative consequences for goal attainment. The high rates of inflation which prevail in the United States and in many northwestern European countries are causing the immediate costs of providing rehabilitation services to rise and simultaneously increasing the opportunity costs of spending for rehabilitation. The net effect of these cost increases is a reduction in the overall benefit/cost ratio that results from investments in rehabilitation. A number of predictions are made about how the United States will shape its disability and rehabilitation policies in the course of the next twenty years.


Studies on the effects of ionization on bacterial aerosols in a burns and plastic surgery unit. The effect of the ionization of the air on the decay of bacterial aerosols was studied in a Burns and Plastic Surgery Unit. Ions were generated by free corona needles. The air content of bacteria measured by settle plates was found to be smaller during the ionization period than during the controls period. The number of individual phage typed Staph. aureus strains was especially found to be lower during ionization. The opposite potential increased the disappearance of bacteria from the air. The size of skin particles carrying bacteria is not optimum, but the results obtained show that the ionization may have applications in controlling airborne infection.


Genetically restricted immune responses in guinea pigs primed in vivo with antigen-bearing macrophages. Guinea pigs injected intradermally with antigen pulsed macrophages generate a population of immune T cells that proliferate in vitro on second exposure to antigen. T cells from F1 (2 X 13) guinea pigs immunized with DNP-OVA on one parental macrophage respond in vitro only to DNP-OVA on macrophages identical to those used for immunization and not to DNP-OVA associated with the other parental macrophages. These results demonstrate that the immunogenicity of antigen is dependent upon the macrophages used for priming in that, with this approach, strain 2 or 13 guinea pigs immunized with allogeneic macrophages pulsed with antigen do not respond to either allogeneic or syngeneic antigen-bearing macrophages. However, lysates of antigen-pulsed macrophages can still immunize either allogeneic or syngeneic recipient via their own macrophages. F1 (2 X 13) guinea pigs are immunized by insulin B chain pulsed strain 13 macrophages (responder) but not by strain 2 macrophages (nonresponder) suggesting that whether a F1 (nonresponder X responder) guinea pig recognizes antigen bound to a parental macrophage is genetically restricted before immunization to the same extent as the donor parental macrophages used for immunization.


Human placental delta 5-3 beta-hydroxysteroid dehydrogenase, delta 4,5 isomerase: in vitro effect of dehydroepiandrosterone and allyestrenol. The in vitro effects of dehydroepiandrosterone (DHA) and allylestrenol on human placental delta 5- 3 beta-hydroxysteroid dehydrogenase, delta 4,5 isomerase activity (delta 5-3 beta-HSDH) was investigated by incubation of subcellular fractions with [4-14C] pregnenolone. It has been found that DHA inhibits the delta 5-3 beta-HSDH activity up to -81% at 5 X 10-5 M concentration while allylestrenol seems to be able to lightly stimulate the delt a 5-3 beta-HSDH activity with a maximum effect (+15-26%) at 5 X 10-7 M concentration. The data concerning allylestrenol, seem of particular interest as this compound is used as a progestative drug during pregnancy, if one consider the inhibitory effect exerted by several natural and synthetic steroids on the delta 5-3 beta-HSDH activity.


Production of chemotactic activity in mixed leukocyte cultures: maximum effect caused by H-2I region disparity. Primary mixed mouse leukocyte culture supernatants contain an activity chemotactic for mouse peritoneal exudate cells and it can be detected within 72 h after initiation of the culture. Disparity for H-21 region leads to maximum production of chemotactic activity whereas H-2K or H-2D region differences result in the production of significantly less activity. The rate of production of chemotactic activity follows closely the rate of incorporation of 3H-thymidine, and both attain the peak on day 4 after initiation of the culture. But whereas proliferation is sensitive to gamma-irradiation, chemotactic activity production is not. It is our hypothesis that proliferating cells are primarily responsible for the production of chemotactic activity. The possible relevance of chemotactic activity production to graft rejection is discussed.


Competitive nephelometric immunoassay method for antiepileptic drugs in patient blood. We established a competitive nephelometric immunoassay method for the determination of the widely used antiepileptic drugs, phenobarbital and diphenylhydantoin, in human blood plasma. The anti-drug antiserum was collected from the immunized rabbit. The human serum albumin possessing numerous drug moieties was easily prepared for the assay reagent. A laser nephelometer was used to measure the scattered light from the immunoprecipitate. The assay was rapid (incubation time 10 min), required as little as 6 microliters of plasma, required neither troublesome pretreatment nor separation procedure. The patients' plasma specimens were analyzed, and the values correlated well to those determined by the high-performance liquid chromatography (correlation coefficient: 0.983 for phenobarbital, 0.987 for diphenylhydantoin).


Improved methods for the assay and activation of 3-hydroxy-3-methylglutaryl coenzyme A reductase. A simple and rapid mixed-phase method for the quantitative assay of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase and a procedure for the efficient reactivation of Mg-ATP-inactivated microsomal HMG-CoA reductase by potato acid phosphatase are described. The mixed-phase assay entails the direct addition of the acidified, deproteinized incubation mixture to a toluene-based scintillation fluor. The enzymatic reaction product [3H]-mevalonolactone partitions into the toluene while unreacted 3H-labeled HMG-CoA substrate remains in the aqueous phase and is not detected on scintillation counting. The accuracy and reproducibility of this method are compared to a thin-layer chromatographic assay for HMG-CoA reductase. Microsomal and solubilized HMG-CoA reductase inactivated by incubation with Mg-ATP is reactivated by purified potato acid phosphatase. Under appropriate conditions quantitative reactivation of HMG-CoA reductase is achieved, indicating that endogenous inhibitory and activating proteins regulate HMG-CoA reductase via a kinase-phosphatase system.


Mechanism of action of fibrinolytic enzymes in vivo. Plasminogen-rich and plasminogen-poor radiolabeled human fibrin clots were inserted into large veins of baboons and stump-tailed monkeys. The thrombolytic effects of plasminogen activators (urokinase, streptokinase), and plasmin preparations with activator activity (streptokinase-activated human plasmin) and without activator activity (trypsin-activated porcine plasmin, Lysofibrin) were studied. Plasminogen-free and plasminogen-rich clots lysed at equal rates. Preparations with and without activator activity were equally effective as thrombolytic agents. Endogenous activation of plasminogen in the clot thus appears not to be the essential mechanism of thrombolysis. The exogenous pathway of enzyme adsorption to fibrin fibers seems to represent an important thrombolytic mechanism. Clot lysis was achieved with doses of fibrinolytic enzymes which produced little or no significant hematologic changes including hypofibrinogenemia and decreases of other blood coagulation factor levels.


Interaction of glucocorticoid and insulin in the responses of rats to starvation-refeeding. Experiments designed to determine whether the role of glucocorticoid (GC) in the induction of the enzyme overshoot response to starvation-refeeding was direct or permissive through insulin were conducted. Intact, adrenalectomized (ADX), and streptozotocin (STREP) treated rats with or without insulin and/or GC replacements were starved for 48 hours and refed a 65% glucose diet for 48 hours. The typical enzyme overshoot response to starvation-refeeding was observed in the intact rats, ADX rats given GC, STREP rats given insulin and ADX-STREP rats given glucocorticoid plus insulin. No overshoot was observed if glucocorticoid was absent whereas a modest increase in enzyme activity could be observed in insulin deficient rats treated with GC.


Hypertensive pulmonary vascular disease in Down syndrome. Clinical studies have suggested that patients with Down syndrome have precocious development of pulmonary hypertension, even in the absence of congenital heart disease. To examine the pathologic basis of this impression, we studied 82 patients with Down syndrome autopsied at The Johns Hopkins Hospital from 1913 to present. The patients ranged in age from 26 hours to 25 years; 41 (50%) were female. Atrioventricular canal defect was present in 40 patients, nine of whom also had pulmonary stenosis. Eight had isolated ventricular septal defect and seven had other malformations. Histologic sections of the lung from each patient were studied and the degree of hypertensive pulmonary vascular disease graded. Age and sex-matched controls without cardiovascular manifestations, all other autopsied patients with atrioventricular canal defect not associated with Down syndrome, and age-matched patients with ventricular septal defect or other malformations were similarly studied for pulmonary vascular changes. Comparison of the 27 patients with Down syndrome and no cardiovascular malformations with normal controls showed no differences, with one notable exception: an 8-month-old child with Down syndrome had severe HPVD secondary to idiopathic pulmonary hypertension. HPVD in patients with the various cardiovascular malformations was similar for those groups with Down syndrome and those without, when HPVD was considered as a function of the patients' age and the type of malformation. We conclude that, in general, patients with Down syndrome have no predisposition to develop severe or precocious hypertensive pulmonary vascular disease.


Intrauterine supraventricular tachycardia. Six examples of intrauterine supraventricular tachycardia together with 31 previously reported cases are described and analyzed. Among the 37 infants, structural heart disease was present in only four (11%), three of whom died. Males comprised 68% of the group without identifiable heart disease or pre-excitation. Congestive heart failure was evident in 62% of the infants at birth or shortly thereafter; ascites was the predominant finding in three (8%). Neither the duration of SVT nor heart rate was predictive of the clinical status at birth. Infants without underlying heart disease or conduction abnormalities had a benign course after the neonatal period. Thirty-eight percent of the babies converted to sinus rhythm during or shortly after delivery without medication, and most of the others converted after digitalization. The failure of maternal digitalization to convert SVT to sinus rhythm in two of our infants was perhaps related to subtherapeutic maternal and fetal digoxin levels. Newborn infants presenting with unexplained ascites or congestive heart failure should have an ECG to determine whether pre-excitation is present, and their cardiac rhythm should be monitored for several days.