Deaths from coronary artery disease and coalworkers' pneumoconiosis. When pneumoconiosis makes a material contribution to a miner's death benefit is paid to his widow. Doctors from the Department of Health and Social Security have argued that extensive pneumoconiosis not only does not increase the risks of death if coronary thrombosis develops but also that it may exert a beneficial effect. This view has been put to the National Insurance Commissioners on at least three occasions recently. There are however, several reasons for coming to the opposite conclusion. THERE IS NO EVIDENCE THAT PROGRESSIVE MASSIVE FIBROSIS Reduces mortality or the development of atheroma, and until such evidence is produced it is unwise to believe that the presence of any severe disease improves anyone's changes of surviving coronary thrombosis. Rather, it should be recongised that any disease which produces a high mortality is inevitably associated with a lower  mortality from other conditions. As doctors from the Department will continue to argue that severe pneumoconiosis does not increase the risk of death from coronary thrombosis informed readers are asked to adjudicate between the conflicting views.


Separation of functional Schwann cells and neurons from normal peripheral nerve tissue. A method has been devised for obtaining viable cultures of normal sensory neurons and normal Schwann cells from rat dorsal root ganglia, using cytosine arabinoside and fluorodeoxyuridine for control of non-neuronal cell proliferation. These cultures were used to demonstrate (a) that Schwann cells could be generated and maintained in culture free of fibroblast contamination, (b) that Schwann cells could exist in either a quiescent or proliferative state, depending on the absence of neurons, (c) that sensory ganglia could be obtained that would provide an outgrowth of axons entirely free of non-neuronal cells even in the absence of antimitotic agents, and (d) that quiescent Schwann cells, induced to proliferate by 'bare' axons, could ensheath and, in time, myelinate some of these axons.


Differential effects of para-chlorophenylalanine on amphetamine-induced locomotion and stereotypy. Amphetamine-induced locomotion and stereotypy were concurrently evaluated in order to determine if pretreatment with para-chlorophenylalanine (PCPA) (which is reported to facilitate some of the effects of amphetamine) results in a behavioral pattern similar to the augmentation previously reported to occur with repeated amphetamine administration. In the present study the behavioral response of rats was characterized after administration of saline or various doses of D-amphetamine (0.5, 2.5 and 4.0 mg/kg) for 48 h following PCPA (300 mg/kg) or vehicle injection. The predominant effects produced by the low dose of D-amphetamine (0.5 mg/kg), i.e., enhanced crossovers and rearings, were found to be significantly elevated after PCPA administration. This effect persisted (relative to PCPA controls) when the response of non-PCPA pretreated animals returned to corresponding control levels, thus indicating that the two drugs acted synergistically. However, while the locomotor component of the amphetamine response was potentiated by PCPA pretreatment, the more focused stereotypies produced by higher doses of amphetamine (2.5 and 4.0 mg/kg) were significantly displaced by enhanced crossovers and rearings. These differential effects of PCPA on amphetamine-induced locomotion and stereotypy are in contrast to the uniform pattern of behavioral augmentation resulting from repeated amphetamine administration. The relationship between the various behavioral components of the amphetamine response and the possible neurochemical mechanisms subserving their interaction are discussed.


[Cytophotometric assays of ribonucleic acids in Ehrlich tumor cells]. The RNA content was measured in individual mouse Ehrlich ascites tumour cells by absorption cytophotometry after gallocyanin chrome alum staining. The cellular RNA content doubles during the preparation for mitosis and is twice as high as in an hyperdiploid line in an hypertetraploid cell lines.


[Implantation defect in the mouse treated by WR 1339 triton: study after transplantation of ova]. Doses of 600 to 800 mg/kg of Triton W.R. 1339 from day 1 to 4 is very noxious in the mouse. In only 12 to 20% of animals the gestation is not interrupted. The morphology of the morulas examined on day 4 and the results of transplantation experiments on pseudopregnant mice gives evidence that Triton W.R. 1339 has no a direct toxic effect on the fertilized egg but acts probably on the maternal organism.


Diphenylhydantoin facilitation of labile, protein-independent memory. Diphenylhydantoin (DPH 10(-4)M) administered subcutaneously to chicks 5 min after a one-trial passive avoidance learning task successfully counteracted amnesia induced by pretreatment 5 min before learning with ouabain or cycloheximide (CXM). Biochemical assays confirmed that in chick forebrain homogenate DPH at concentrations of 1 and 5 X 10(-4)M enhanced Na+/K+ ATP'ase activity. Since both DPH and ouabain inhibit post-tetanic potentiation, the results support the hypothesis of an initial labile phase of memory based on sodium pump (Na+/K+ ATP'ase) activity. DPH was less effective in counteracting ouabain-induced amnesia if administered later than 10 min after learning and CXM-induced amnesia if administered later than 30 min after learning. This suggests that the effect of DPH on CXM-induced amnesia is through enhancement of Na+/K+ ATP'ase activity. It was suggested that the possible hyperpolarization of membrane potential associated with sodium pump activity may serve to mark the labile memory trace, enabling formation of a more permanent trace through protein synthesis.


[Determination of the action of WR 1339 triton on the 1st stages of gestation in the mouse: action of progesterone]. Injection of 600 to 800 mg/kg of Triton W.R. 1339 from day 1 to day 4 of pregnancy is highly noxious in the mouse. Only 12 to 20% of females continue their pregnancy. The causes of this action could be determined. Triton W.R. 1339 has not a direct toxic action on the fertilized ovum, but impairs the hormonal balance of the pregnant mouse, inducing a progesterone deficiency. Daily injection of 5 mg progesterone per animal from day 1-17 or from day 4 to 17 improve pregnancy performance or suppresses completely the noxious action of Triton W.R. 1339.


Selective blockage of the sensory terminal activites by micro-application of tetrodotoxin in the frog muscle spindle. Micro-application of tetrodotoxin to the sensory nerve terminal of the frog muscle spindle made a semi-blocked condition, in which propagated spikes were blocked selectively but reversibly, while abortive spikes survived. In the semi-blocked condition an antidromic spike was often followed by an abortive spike without a significant pause, in contrast with the normal condition in which the antidromic spike was always followed by an abortive spike or a propagated spike with a pause more than 50-100 msec. An analysis of the spike train as a stochastic point process suggests that the abortive spikes originate at the places which the antidromic spike can scarcely invade in the semi-blocked condition.


[Action of prostaglandin F2 alpha on pregnancy in mice. Prevention of its abortive property by progesterone]. Prostaglandin F2alpha determines a high proportion of abortions in the mouse when administered before implantation at a dose level of 2 mg/kg. After implantation between days 6-8 or 7-9, doses 20 times higher are necessary to produce the effect. Daily progesterone administration, 5 mg per animal, from day 1 to day 17 allow the evolution of pregnancy in 60% of the mice even when 120 mg/kg prostaglandin is given. This dose determines usually 100% abortions. No teratogenic effect has been observed.


[Analysis of the abortive action induced by prostaglandin F2 alpha in the mouse. Study of ova and their transplantation]. In mice PGF2 alpha injections (120 mg/kg from first to the 4th day) determines a high proportion of early abortions. The mechanism of this action has been investigated by transplantation of blastocysts removed from PGF2 alpha treated mice to pseudopregnant mice. The results of transplantation experiments indicate that the percentage of implantation is the same whether the eggs are taken from PFG2alpha treated or control mice. The number of eggs present in the uterine horns 84 hours after fertilization is 40 % lower than in control animals. At an earlier stage, 60 hours after fertilization, the uterus of PGF2 alpha treated females contains 85 % of eggs as compared to 20 % in controls. This proportion is reversed in the fallopian tubes. It can therefore be concluded that the high abortion rate of PGF 2 alpha treated mice is not due to an embryotoxic effect but to a faster transport of the fertilized eggs which reach therefore the uterus before implantation can take place.


[Influence of anti-lactate dehydrogenase M antibodies on the proliferation of KB tumor cells]. The IgG antilactate-dehydrogenase M inhibits the corresponding isozyme in the KB tumoral cells cultivated in vitro. It has an inhibitory action on the prliferation of these cells. These data corroborate those obtained previously with chemical inhibitors of LDH-M.


[Epistatic disequilibrium in an experimental population of Japanese quail (Coturnix coturnix japonica)]. In an experimental population of the japanese quail Coturnix coturnix japonica, two polymorphic ovoglobulin loci, two polymorphic esterase loci, and PGD versus G-6-PD loci are in epistatic disequilibrium. Epistatic interactions occur between structurally and physiologically very closely related proteins and enzymes.


[Electrical activity of cultured cells of the guinea pig heart. Comparison with the rat]. For the first time, action potentials were recorded with the use of microelectrodes from myocardial cells beating spontaneously which were obtained by trypsination of guinea-pig embryonic hearts. 4-5 weeks old embryos have been found most suitable for such experiments. The development of cultures and the recordings obtained were compared to those observed in rat hearts under the same experimental conditions. These results showed that inspite of the known physiological differences between adult rat hearts and adult guinea-pig hearts, the cardiomyoblasts cultured under the same conditions possess common features relating to the repolarization phase of action potential, specially a lack of the plateau.


[Excito-motor action of succinyldicholine and other cholinic esters on the spinal cord of the mouse]. We have realized on mice the spinal animal experiment, cutting the spinal chord below the bulb during artificial respiration. We have observed that the cholin esters and particularly the succinyldicholin injected into a caudal vein produce muscular contractions, of which we give a graphic. After having discussed these experimental results, we conclude that every cholin ester has an excitatory effect on the spinal chord. It must now be determined which of these esters is the normal medullary transmitter.


[Development of tectum-striatum and striatum-tectum connections in the chick]. In the chick, polyphasic evoked responses displaying a first negative component have been registered in the superficial part of the "Wulst" after stimulation in the depth of the contra or ipsilateral optic tectum, as early as the first hours following hatching. Moreover, responses on the surface of the tectum have been elicited by contra or ipsilateral stimulation of the Wulst. Latencies of both responses decrease markedly with increasing age but, in the whole, ipsilateral responses remain more latent than contralateral responses.


[Variations in the loudness of a brief sound compared to another brief sound as a function of the duration of both sounds]. Loudness equalizations between two short 2500 Hz tones (15 to 120 ms, about 50 dB SPL) were made. One tone, either the first or the second one, was twice as long as the other. The intensity level differences between tones of the same loudness were calculated. Results show that the relations between duration and loudness of the tones differ for different subjects. Nevertheless the calculated differences diminished with subject experience. Subject evaluations in accordance with the intensity levels of tones, i.e. independently of the duration, were quite often obtained even for the pairs 15 ms-30 ms.


[Action of L-azetidine in in vitro culture on the formation of uropygial invaginations and the branching of glandular buds in the duck embryo]. Azetidine-2-carboxylic acid, a proline analogue which depresses collagen deposition in extracellular spaces, stops uropygial invaginations morphogenesis and epithelial buds branching in vitro. The results show that uninterrupted collagen synthesis is necessary for preen gland morphogenesis.


[Relationship between evaluation of the duration and loudness of short sounds]. The relation between loudness and duration judgments of short tones was investigated. Sounds (15 to 120 ms, 2500 Hz, about dB SPL), were exposed in pairs; one tone of the pair, the first or the second one, was twice as long as the other. Subjects had to compare the loudness of the tones, or the duration, or the loudness and the duration at the same time. Results show that the loudness judgments are independent of experiences with duration judgments and of immediate duration judgments, but duration judgments were less precise when loudness judged at the same time.


[Anticomplement actions of heparin-like and protamine-like substances]. A reciprocal inhibition exist in vitro between the anticomplementary activity of protamine and heparin like substances. The concentration required for inhibition is approximately of the same order for the both groups of substances.


[Cyto-immunological study of the somatostatin hypothalamic peptidergic system in the fox (Vulpes vulpes)]. Immunocytological investigations on the hypothalamus of the red fox with rabbit anti-SRIF showed large or small perikarya in the supra-optical and paraventricular nuclei. In the median eminence SRIF-positive nerve fibres and their endings have a characteristic distribution in areas different from those of LH-RH containing nerve fibres.


[Effects of atropine sulfate on the hypothalamic LH-RH cells of the guinea-pig]. A single 30 mg/kg., s.c. injection of atropine sulfate into male guinea pigs produces a storage of LH-RH immunoreactive material in hypothalamic neurons. In diestrus female there is no increase of immunoreactive LH-RH substance in neuron and in eminential terminals; the rate of LH-RH synthesis may be still slight. The LH-RH immunoreactive neuronal increase, in male may be related to an atropine blockade of LH-RH portal cession, perhaps via infundibular dopaminergic neurons.


[Muscle synergy in isometric flexion of the elbow]. A technique was developed for calculating the torque generated by two individual muscles (biceps brachii and brachioradialis) that contribute to the isometric flexion of the elbow. The external torque is the sum of individual torques which are unknown. Each individual torque (CB or CBR) can be related to the corresponding integrated surface EMG (QB or QBR) by means of coefficients (pB or PBR). A block of several equations C = pB QB + pBR QBR is obtained by exploring several experimental conditions. In these conditions, isometric flexion efforts of the elbow were associated to isometric efforts of supination or pronation so as to vary integrated EMG by reciprocal inhibition. By means of a least square method it was possible to know the coefficients PB and PBR. With these coefficients, it was possible to calculate the individual torques generated by the biceps brachii and brachioradialis muscles in each experimental condition.


[Conditioning of the avoidance to the contact call in the red face lovebird (Agapornis roseicollis, Aves, Psittacidae)]. Two experiments were run on 10 lovebirds to test the reinforcing effect of the social call in an operant conditioning task. In the first experiment, the reinforced behavior (perching) which provoked the occurence of the call decreased. In the second experiment, where the same behavior stopped the continuous emission of the call, the behavior increased. This behavior may results from an avoidance to the call recorded from a lovebird which do not belong to the group of our experimental birds.


[Effect of noncontingent electric shocks on subsequent avoidance learning in the rat, in a maze situation]. Rats were put in a Y maze and then pretreated with 0, 1, 3, or 10 noncontingent electric shocks. One day later, they were given an avoidance conditioning in the same apparatus. The 1-preshock group performed as well as the o-preshock group (control group). As compared to the control group, we found a facilitation of the avoidance response in the 3-preshock group and an impairment of the escape response in the 10-preshock groups. The impairment was still shown by the subjects when 3 weeks elapsed between the 10-preshock session and the learning session.


[The curve of the intraventricular pressure-volume relationships is not mono-exponential]. The graphic and statistic investigations have let us to assert that the right ventricular P/V relationship's curve is characterized by two successive segments: linear and exponential respectively. We have proposed an interpretation based on Roach's and Burton's works. Interest of information about this curve is double: 1) it is a function of the ventricular cavity volume; 2) it gives a general idea about the mode of ventricular filling.


[Characterization of various digestive enzyme activities of Palaemon serratus Pennant (Crustacea, Decapoda) after polyacrylamide gradient gel electrophoresis]. Soluble proteins of hepatopancreatic, extracts of Palaemon serratus (Crustacea, Deapoda) are separated by polyacrylamide gradient gel electoresis. The characterisation of the enzymatic activities is carried out directly on the polyacrylamide gel. The zymogram includes the following activities: acid and alcalin phosphatses, phosphamidase, alpha-glucosidase, beta-glucosaminidase, beta-glucuronidase and twenty bands with esterasic activities. The molecular weights are indicated.


[Experimental role of the unicellular algae Prototheca and Chlorella (Chlorellaceae) in anti-cancer immunogenesis (murine BP8 sarcoma)]. Bacteria and Yeasts are able to induce, when inoculated into laboratory rodents, a general stimulation of defences by an immune process. We could estimate that unicellular algae would induce the same phenomenon because the chemical compounds of their walls are related to those of the precedings microorganisms specially to bacteria. Indeed, two Chlorellaceae, Prototheca segbwema and Chlorella pyrenoidosa are respectively protecting 78% and 82% CH3 mice against the sarcoma BP8 grafting.


[Mixed lymphocyte culture and HLA typing in a family with a recombination between loci of the major HLA histocompatibility system]. A new case of recombination at the HLA region has been established by mixte lymphocyte culture in the family of potential kidney recipient. Serological family study, MLC and HLA typing were performed to localize the recombination. This corroborates the primordial interest of MLC in family pretransplant matching.


[Action of difluorodichloromethane (FC 12) and of adrenaline on the isolated rabbit heart]. Does difluorodichloromethane (FC 12) sensitize the cardiac muscle in vitro to epinephrine-induced arrhythmia ? We have tried to answer this question by comparing : the action of epinephrine alone on the isolated rabbit heart perfused by an ordinary nutritive solution  and the action of epinephrine on the heart perfused by a nutritive solution containing various concentrations of FC 12. The results are: 1) the general action of epinephrine (inotropic and chronotropic positive effects, increase of coronary flow) is not significantly modified by the action of FC 12. 2) FC 12 does not sensitize the rabbit heart in vitro to the arrhythmogenic action of epinephrine. The few cases of arrthymia recorded under the action of adrenalin do not necessarily occur in the presence of FC 12, but rather depend on the weakened state of the preparation.


[Attempt to obtain in vitro pre-erythrocyte forms of Plasmodium vivax in human liver cell cultures inoculated with sporozoites]. Using sporozoites of a strain of Plasmodium vivax of North Korean origin maintained in human subjects and in Anopheles atroparvus, the authors inoculated human liver cell cultures (primary cultures and Ist subcultures). The appearance of some rare intracytoplasmic forms is described, which are thought to be very likely connected with the pre-erythrocytic cycle of P. vivax. Further attempts are nevertheless necessary to confirm, or invalidate, the obtained results.


[Annual cycle of oxygen consumption (QO 2) in a hibernating animalthe garden dormouse: reduction of the QO 2 and hypothermia following fasting]. A circannual cycle of oxygen consumption (QO2) was observed in active garden dormice maintained during 19 months under external conditions for temperature and lighting. QO2 was minimum in october and maximum in may. In the same animals deprivation of food induced hypothermia and a 23% decrease in QO2 which always preceeded hypothermia. No circannual rhythm was noted in the amplitude of this reduction.


[The hypotensive action of bradykinin in the guinea pig and cat]. In the guinea-pig as in the cat, the duration of the bradykinin general arterial hypotension is reduced by indometacine. This decrease is due to the inhibition of the synthesis of endogenous vasodilatator prostaglandins. The guinea-pig and the cat present the same type of reactivity for bradykinin as the rabbit, the dog and the rat.


[Influence of thymectomy on the lymphoid regeneration of hematopoietic bone marrow after sublethal irradiation]. In C57BL mice, bone marrow lymphoid regeneration after a sublethal irradiation is modified by a graft of normal marrow cells. This effect is suppressed in thymectomized mice since a lymphoid peak is observed after a 350 R irradiation; its composition is heterogeneous: small lymphocytes, lymphoblasts and peculier cells named "X cells". The same phenomenon is observed in mice where all the thymocytes and thymus derived and peripheral lymphocytes are destroyed. These results exclude that bone marrow lymphoid regeneration after irradiation is due to a migration of lymphoid cells of thymic origin to the marrow. They could be explained by the effect of a humoral thymic factor on marrow lymphopoiesis.


[Influence of body position on the urinary output of adrenaline and noradrenaline]. In normal subjects in basal conditions, urinary excretion of noradrenaline is directly related to the hydrostatic pressure changes induced by the body posture in the dependant parts of the venous system. Adrenaline elimination is no influenced by these factors.


[Presence in the heart of Protopterus annectens (Fishes, Dipneuste) of nodal and conducting cells histologically distinct from common myocardial cells]. Contrary to Francis and Davies's assumption according to which the impulse-conducting system of the Homoiothermal Vertebrates is a neomorphic structure, we have been able to identify in the heart of a Poikilothermal (Protopterus) impulse-conducting cells which possess distinctive histological characters.


[Annual lipid cycle of the grassland Varanian lizard]. The circannual chronobiology of Varanus exanthematicus exanthematicus Bosc, lacertilian reptile of Senegal, is characterized by a period of rest from January to June (dry season) and a period of activity from July to December (wet season). The study of the lipids metabolism shows a two month deplacement period: as a matter of fact from November to April the lipogenesis prevails, while from May to October it is the lipolysis. These two phases correspond to the periodicity of the development of the gonads, which are at rest from November to April and in activity from May to October. The synchronism of the phases of lipolysis and of gonads muturation argues in favour of the lipids utilization for the growth of the gonads.


[Unusual traumatic rupture of the thoracic aorta with avulsion of the left subclavian artery]. Of the many cases of traumatic rupture of the aorta diagnosed each year at l"Hôpital du Sacré-Coeur, Montreal, most patients are already in irreversible shock when seen. However, during the period Oct. 1, 1974 to Sept. 30, 1975, prompt surgical treatment saved six patients. One of these six patients had a complete trans-section of the aortic arch between the left carotid and left subclavian arteries with avulsion and slight retraction of the left subclavian artery. Repair of the aortic arch and left subclavian artery was accomplished without extracorporeal circulation. A sutureless temporary bypass shunt was created by (a) cannulating the ascending and descending aorta, the cannulas being secured with purse-string sutures and joined by a 3/8-inch (94-mm) polyvinyl chloride (PVC) tube connected to a "double T" adapter, and (b) joining two small PVC tubes from the adapter with two straight cannulas, a no. 14 being inserted into the innominate artery and a no. 12 being inserted into the left carotid artery. With this temporary bypass created, the ascending and descending aorta and aortic arch vessels were all clamped. Aortic continuity was re-established with a tubular Dacron graft (diameter, 19 mm) to which was anastomosed a side-arm of knitted Dacron (diameter, 10 mm) to repair the left subclavian artery. Throughout the temporary perfusion the brain, spinal cord and all abdominal viscera were well protected. No sign of ventricular distension was detected. This report is the first in which complete transsection of the aortic arch has been managed by a sutureless bypass shunt allowing perfusion of all aortic arch vessels without extracorporeal circulation.


Reactivity of lymphocytes from primary neoplasms of lymphoid tissues. Proliferative responses by blood and tumor lymphocytes to plant mitogens and allogeneic leukocyte antigens were tested concomitantly on 12 patients with Hodgkin's disease, 10 with chronic lymphocytic leukemia, and seven with non-Hodgkin's lymphomas. In 13 control studies, 3H-thymidine incorporation by blood and lymph node lymphocytes was brisk and, overall, comparable. With Hodgkin's disease, where extent of disease involvement and lymphocyte-depleted tumor histology were factors in the degree of responsiveness, incorporation was higher or at least comparable by tumor lymphocytes when compared with incorporation by autologous blood lymphocytes. Lymph node lymphocytes, especially with clinically stable disease, were more responsive than blood lymphocytes with chronic lymphocytic leukemia. Conversely, tumor lymphocytes were hyporesponsive compared with autologous blood lymphocytes with non-Hodgkin's lymphomas, where prognosis is usually less favorable than with chronic lymphocytic leukemia. Plasma from four out of 33 patients, although not lymphocytotoxic, inhibited lymphoproliferative responses.


Cytogenetic studies and clinical implications in patients with Sézary syndrome. Chromosome studies were carried out on 11 National Institutes of Health (N.I.H.) patients who had the diagnosis of Sézary syndrome. Heteroploidy, multiple markers including minute and ring chromosomes, and a lack of modality and clone formation, were the common chromosomal findings in this syndrome. Abundant spontaneous division of heteroploid cells in unstimulated peripheral blood cultures, a high percentage of heteroploid cells in stimulated culture, and finally, clone formation, are signs of a fulminant process and lead to the terminal phase of this disease. Early chemotherapeutic eradication of these heteroploid neoplastic cells would, therefore, be the treatment of choice in this disease.


Identification and characterization of the insulin receptor in the R3230AC mammary adenocarcinoma of the rat. The binding of labeled insulin to dissociated R3230AC mammary adenocarcinoma cells from diabetic and intact rats was investigated in vitro. At 20 degrees, specific binding (total binding minus binding in the presence of 1000-fold excess or 10(-6) M unlabeled insulin) reached a plateau at 45 to 60 min and was directly related to the number of cells used. Degradation of labeled insulin, as measured by trichloroacetic acid precipitation, was related to the number of cells used, was not prevented by trasylol or phenylmethylsulfonyl fluoride (general proteolytic enzyme inhibitors), but was prevented by addition of 1 to 2% bovine serum albumin to the incubation medium. Specificity of insulisulin, and desoctapeptide insulin were capable of competing for insulin binding in an order of potency related to their relative biological activity; prolactin and glucagon were unable to compete for insulin binding. Scatchard analysis of the binding data demonstrated a curvilinear-plot; specific binding (over the concentration range of 10(-11) to 10(-10) M insulin) showed a high affinity (Kd approximately 1 to 3 X 10(-10) M), and the estimated number of sites was greater in tumors from diabetic animals than in tumors from intact animals or intact animals given insulin prior to sacrifice. Reversibility of insulin binding was studied by dissociation experiments; dissociation was enhanced in the presence of added unlabeled insulin compared to dissociation examined under conditions of "infinite" dilutions only. Maximum dissociation of bound insulin was observed in the presence of 10(-7) M unlabeled insulin, with less of an effect at lower or higher concentrations of added insulin (no effect seen at 10(-10) M insulin). Two techniques were investigated for separating cells from unbound labeled insulin; the procedure using centrifugation was found to be more efficient. Thus, in the R3230AC mammary adenocarcinoma, data obtained on saturability, reversibility, and specificity of insulin binding indicate the existence of an insulin receptor with properties similar to those found in normal cells.


Inhibition of membrane transport of 5-fluoro[6-3H]deoxyuridine into L5178Y mouse leukemia cells. The influx of 1.0 muM 5-fluoro[6-3H]deoxyuridine (5F[6-3H]dUrd) into L5178Y mouse leukemia cells followed a linear function with time from 2 to 10 min. Ammonium 5-bromodeoxyuridine 5'-methylphosphonate (BrdUrd-OPO2Me) inhibited the membrane transport of 5F[6-3H]dUrd into L5178Y cells. Influx of 5F[6-3H]dUrd into inhibited cells was observed from zero to 3 min; after 3 min the net rate of 5F[6-3H]dUrd uptake into the cells treated with 18 muM BrdUrd-OPO2Me was almost zero. The cellular uptake of 2'-deoxy[6-3H]uridine or 5-bromo[6-3H]deoxyuridine was inhibited by BrdUrd-OPO2Me. The L5178Y cells were grown for 96 hr in a medium that contained tritium-labeled BruDur-OPO2Me. An analysis of the labeled products in the growth medium showed that the ester linkage is not cleaved to separate the [3H]methylphosphonate group and the nucleoside moiety of BrdUrd-OPO2[3H]Me. The activity of thymidine kinase in a cell-free preparation from L5178Y cells was demonstrated. Although 37 muM 5-bromo-2'deoxyuridine produced an inhibition of approximately 45% in kinase activity, BrdUrd-OPO2Me had no effect on enzyme activity. The results indicate that BrdUrd-OPO2Me is an inhibitor of the cell membrane transport of the 5-fluoro and 5-bromo derivatives of 2'-deoxy[6-3H]uridine.


Protein synthesis in dextran sulfate-treated ascites tumor cells. Treatment of ascites tumor cells with dextran sulfate resulted in a marked inhibition of the incorporation of [14C]valine into protein in the presence of a high Na+ medium. Amino acid incorporation was restored after i.p. injection of these cells into mice or by exposure of the cells to ascites fluid in vitro. In a medium high in K+ and low in Na+, [14C]valine incorporation into protein took place in dextran treated cells. Rotenone inhibited the reaction, which could be restored by addition of both inorganic phosphate and either glucose or glucose 6-phosphate. Quercetin, an inhibitor of the Na+-K+-ATPase, markedly depressed the incorporation of [14C]valine into protein in intact sdviyrd tumor cells in a high Na+ medium. There was little or no inhibition of protein synthesis in dextran sulfate treated cells when tested in a high K+-low Na+ medium. These experiments suggest a relationship between protein synthesis and the operation of the membranous Na+-K+-ATPase.


Dihydroergotamine: an effective treatment for postural hypotension due to antihypertensive drugs (ganglion-blocking agents excepted). In this study the effect of DHE on postural hypotension induced by major antihypertensive drugs was evaluated in 40 patients. 30 patients were treated with methyldopa, five with guanoxan sulphate and five with bethanidine sulphate. To obtain a more accurate picture of the effectiveness of DHE and to test the reproducibility of its effect, each patient was observed during five separate, successive periods: in the first period the antihypertensive agent was given alone; in the second period it was given along with placebo; in the third period it was given with DHE; in the fourth period the antihypertensive agent was given alone again; and in the fifth period it was again given with DHE. In the third and in the fifth period, DHE was administered at the same time as the antihypertensive agent in a dose of 9-15 mg/24 h (3-5 mg three times daily). The first dose was given 1 h before rising, and the daily dosage was progressively increased. The beneficial effect of DHE on postural hypotension was evaluated by assessing the clinical symptoms in a semiquantitative manner and by measuring the arterial blood pressure and heart rate in a recumbent and standing position. The results were classified as follows: excellent, good, moderate and no response. In most cases, DHE was found to be an effective drug for the treatment of postural hypotension, an improvement in clinical symptoms being noted in 57.5% of patients tested (excellent and good results). In these patients the standing arterial blood pressure showed a significant response (p less than 0.01). DHE did not interfere with the therapeutic effect of the antihypertensive agents. Furthermore, DHE did not affect the heart rate, nor did it give rise to any adverse reactions.


Effect of mechanical stimulation on cell proliferation in mouse epidermis and on growth regulation by endogenous factors (chalones). Mechanical stimulation of dorsal mouse skin by skin massage or removal of the horny layer results in a mutually comparable increase in DNA-labelling and mitotic activity. However, only after injury such as removal of the horny layer hyperplasia develops. This phenomenon, called "hyperplastic transformation" is characterized by a transient abolition of the epidermal G1 chalone responsiveness. There is some indication that the susceptibility to a heat labile factor, probably the epidermal G2 chalone, is not affected. Skin massage neither interferes with the responsiveness to epidermal G1 chalone nor induces "hyperplastic transformation". Mouse tail epidermis shows a "functional hyperplasia" and responds to the G1 chalone. To explain these observations, it is assumed that the epidermal stem cell population is heterogeneous consisting of G1 chalone-sensitive and G1 chalone-insensitive cells.


Differentiation of the plasma membrane of hepatic cells in monolayer cultures. Hepatocytes from rats were isolated by treatment with trypsin and cultured. Plasma membranes at different culture stages were observed by electron microscopy. The activities of 5' nucleotidase and adenosinetriphosphatase on the plasma membranes were examined. The cell coat was also studied by use of the concanavalin A-peroxidase technique. The surfaces of single cells, covered with microvilli, are the site of adenosinetriphosphatase activity only and are devoid of 5'-nucleotidase activity. After a few h of culture, the cells are grouped together in tight clusters or long trails and are separated by an intercellular space of 250 A, partially permeable to lanthanum nitrate. The juxtaposed plasma membranes on which 5'-nucleotidase and adenosinetriphosphatase activities occur also delimit spaces similar to bile canaliculi. The formation of junction complexes and their permeability to lanthanum nitrate was also studied. No enzymatic activity is observed at the junctions. The numerous tight junctions, impervious to the tracer, are always accompanied by a profusion of microfilaments. Mature desmosomes are rare, and are present only in the form of "maculae adhaerentes diminutae." The gap junctions, nearly always permeable to the tracer, form rapidly and assume a variety of shapes (trail, bulge and ring-like), the significance of which is open to discussion. The use of concanavalin A permits localization of the free sugar sites on the surface of the cells, in the pinocytotic vesicles and in the internal space of the gap junctions.


Developmental aspects of the innervation of skeletal muscle fibers in the chick embryo. The M. complexus in the chick, commonly called the hatching muscle, undergoes conspicuous growth during the latter stages of embryonic development. Myogenesis of this muscle was compared to that of M. biceps femoris with regard to development of types of muscle fiber and their innervation. In both muscles beta fibers are of relatively uniform size and show little growth in diameter between 12 days of development and hatching; alpha fibers develop continuously and display a wide range of diameters at all stages. Initial thickenings on the sarcolemma of beta fibers where axons are closely approximate were first observed at 10 days of development in both muscles. In both muscles beta fibers are innervated prior to alpha fibers. Terminal axon networks bridge intercellular spaces and contact beta fibers in different myogenic clusters. alpha fibers that develop on the surface membrane of beta fibers exhibit focal thickenings of the membrane and some cell projections  that are directed toward axon-beta fiber contacts. These changes occurred only in alpha fibers of M. complexus. At 14 days of embryogenesis, the processes of synaptogenesis and of myelin formation are less advanced in M. biceps femoris than in M. complexus. At this stage alpha fibers were observed to be innervated in M. complexus, but not yet in M. biceps femoris. Each beta fiber was observed to be encircled by several preterminal axons. It is concluded that the earlier development of M. complexus is correlated with an equally early development of nerve-muscle interactions.


Myocardial contractile function and myofibrillar adenosine triphosphatase activity in chemically sympathectomized rats. The contractile properties and contractile protein enzymatic activity of skeletal muscle can be altered by neural influences. To determine whether similar influences apply to cardiac muscle, adult rats were chemically sympathectomized by intravenous injection of 6-hydroxydopamine (6-OHDA). After 2 weeks of treatment, rats were anesthetized and an index of myocardial contractility (max dP/dt) was measured in situ. Max dP/dt was depressed in 6-OHDA-treated rats [4560 +/- 420 (mean +/- SE) mm Hg/sec] when compared to controls (6710 +/- 580 mm Hg/sec). Sympathectomy was verified by reduced hemodynamic responsiveness to tyramine injections. After functional measurements had been completed, the heart was excised. Myofibrils were prepared from left ventricular tissue and analyzed for ATPase activity. Myofibrillar protein yield averaged 38 +/- 2 mg/g in controls and was not significantly different in 6-OHDA rats. Myofibrillar ATPase activity was 0.314 +/- 0.014 mumol P1/mg per min in controls. Enzyme activity was significantly reduced to 0.230 +/- 0.020 mumol P1/mg per min in 6-OHDA rats. The results demonstrate that a chronic reduction in sympathetic stimulation to the heart results in a depression of an index of myocardial contractile function which is accompanied by reduced myofibrillar ATPase activity. Acute (16-18 hours) chemical sympathectomy depressed the contractile function index without altering ATPase activity. Bilateral adrenalectomy produced no further decrement in myofibrillar ATPase activity in chronically (2 weeks) sympathectomized rats. Therefore, it appears that the changes in contractile protein enzymatic properties are mediated by sympathetic neural influences and may involve the synthesis of new contractile protein(s) with altered enzymatic properties.


Report of the Inter-Society Commission for Heart Disease Resources. Medical instrumentation in peripheral vascular disease. Resource and planning guidelines for the hospital and physician. This is a resource and planning guideline for hospitals and physicians. The status of medical instrumentation in peripheral vascular disease diagnosis is reviewed and the application of examination methods to categories of vascular disease discussed. Resour


Sarcolemmal membrane changes related to enzyme release in the imipramine/serotonin experimental animal model. We report specific findings in the imipramine/serotonin animal model that are consistent with sarcolemmal membrane alterations. Among these findings are cytoplasmic enzyme release, diminished uptake of alpha-aminoisobutyrate (an amino acid analog), decreased oxygen consumption in isolated rat diaphragm, and ribosuria. Furthermore, we describe for the first time the release of the MB isoenzyme of creatine kinase from a source other than cardiac tissue; that is, isolated diaphragms from imipramine/serotonin-treated animals release increased amounts of MB isoenzyme as compared to diaphragms from control animals. We believe the similarities between this animal model and the human disease (Duchenne muscular dystrophy) support a genetically determined generalized membrane abnormality in the pathogenesis of this form of muscular dystrophy.


Metabolic response of humans to ingestion of nicotinic acid and nicotinamide. The identification of nicotinamide-N1-oxide as a metabolite in the urine of a schizophrenic patient prompted a study of the relative metabolism of nicotinic acid and nicotinamide in mental patients and healthy volunteers. Metabolites quantified included N1-methyl-2-pyridone-5-carboxamide, N1-methyl-4-pyridone-3-carboxamide, N1-methylnicotinamide, nicotinuric acid, and nicotinamide-N1-oxide. More of most of these metabolites evidently was excreted after nicotinamide ingestion than after nicotinic acid. At the highest doses (3000 mg/day), the relative proportions of these metabolites in the urine were changed. There were only slight difference between healthy individuals and mental patients in the quantities of metabolites excreted, and no statistically significant trends were noted.


[Diphenoloxidases: presence in the membrane of human erythrocyte (author's transl)]. Diphenoloxidases, enzymes which accelerate the auto-oxidation of epinephrine and Dopa, have been described by one of us in blood platelets. Earlier we identified these enzymes in different animal species and particularly in human red blood cells. With the object of localising these enzymes and of understanding their function in vivo, we separated the ghosts of red blood cells according to the method described by Fairbanks G., Steck, T.L. and Wallach, D.F.H. (1971) (Biochemistry 1, 2606) and using the protease inhibitors diisopropylfuorophosphate (DFP) (10(-3) M) and 6-aminocaproic acid 10(-2) M in sodium phosphate buffer, 5 X 10(-3) M (pH 8). These ghosts, totally free of haemoglobin, were first of all pulverised in liquid nitrogen then treated ultrasonically. The supernant shows the presence of a band of diphenoloxidase activity on starch gel electrophoresis and two bands on isoelectrofocusing in polyacrylamide gel pH 5 to pH 8 after incubation with 0.02 M Dopa, 0.076 M Tris, 0.005 M citric acid, 0.004 M magnesium, pH 8.7 for 2 h at 37 degrees C. These enzymes differ from (Na, K)-ATPase in that they are neither inhibited by DFP (10(-1) M) nor by EDTA (10(-2) M) but are inhibited by lead acetate 10(-2) M. Like (Na, K)-ATPase diphenoloxidases are present at membranes level. The role in vivo of these diphenoloxidases in ATPase activity of red blood cells is discussed.


Alpha-1-antitrypsin (Pi) types in Down's syndrome. Alpha-1-antitrypsin (Pi) phenotypes have been determined in 40 patients suffering from Down's syndrome. Thirty-six of the patients were found to have a normal M phenotype, whereas two deficient phenotypes of the MS variety were observed. In addition, two M variants were noted. The significance of an M variant phenotype in some patients with Down's syndrome is not completely understood and is currently under investigation. Since the majority of the patients had a normal alpha-1-antitrypsin phenotype, the results of this study indicate that a deficiency in alpha-1-antitrypsin plays no role in the respiratory fragility of individuals with Down's syndrome.


Association of overt glomerulonephritis and liver disease: a study of 34 patients. Thirty-four patients with overt glomerulonephritis and chronic liver disease were studied. Kidney specimens were examined by light, electron and immunofluorescence microscopy. Plasma C3 levels were measured and a search for cryoglobulinemia was carried out in all patients. Twenty-six out of the thirty-four patients had an immune complex type glomerulonephritis (membrano-proliferative glomerulonephritis or glomerulosclerosis with mesangial deposits) suggestive of hepatic glomerulonephritis. The glomerular deposits almost always contained IgA and very frequently other immunoglobulins as well as C3. The membrano-proliferative glomerulonephritis was characterized by severe renal symptoms, mixed cryoglobulinemia and the frequent finding of low C3 levels. These data suggest that there is a linkage between liver disease and glomerulonephritis. The immunomorphological type of glomerulonephritis and the cryoglobulinemia are both suggestive of an immune complex disease. The lowering of the C3 levels could be due to activation of complement components by immune complexes, to hepatic hyposynthesis, or to a combination of the two.


Persistent intravascular C3 activation after bilateral nephrectomy in patients with thrombotic microangiopathy. Four patients with thrombotic microangiopathy had evidence of intravascular C3 activation on presentation which persisted after bilateral nephrectomy. In several serum samples, C3-splitting activity was not associated with the presence of circulating immune complexes, which were detected in all four patients before nephrectomy and in three after nephrectomy.


Combination chemotherapy with adriamycin and streptozotocin. I. Clinical results in patients with advanced sarcoma. In a prospectively randomized study, 17 evaluable patients treated with adriamycin alone, 60 mg/m2 intravenously every 3 wk, were compared with 14 patients treated with adriamycin in the same dose and schedule plus streptozotocin. 500 mg/m2/day intravenously for 5 days every 3 wk. All patients had advanced sarcomas, but none had previously received either adriamycin or streptozotocin. Objective responses were seen in 9 patients on the single drug arm (4 with more than 50% tumor shrinkage and 5 with stabilization of disease), and in 8 patients given the combination drug arm (2 with more than 50% tumor shrinkage and 6 with stabilization of disease). Duration of response and survival from treatment for both treatment groups were similar. Transient hepatic dysfunction, renal function abnormalities, and nausea with vomiting were additive in the combination drug arm, the last two limiting therapy most. Leukopenia, thrombocytopenia, and mucositis appeared to be synergistically increased in patients receiving both adriamycin and streptozotocin. Patients with abnormal pretreatment renal function were able to tolerate the combination therapy without undue incidence of severity of renal toxicity. Patients who developed transient streptozotocin-related renal dysfunction were able to tolerate further doses of streptozotocin after their renal parameters normalized. Adriamycin in combination with streptozotocin did not offer any therapeutic advantage over adriamycin alone.


Combination chemotherapy with adriamycin and streptozotocin. II. Clincopharmacologic correlation of augmented adriamycin toxicity caused by streptozotocin. Plasma pharmacokinetics were compared in patients with advanced sarcomas receiving adriamycin, 60 mg/m2 intravenously (iv) on day 1 every 3 wk in combination with streptozotocin, 500 mg/m2/day iv on days 1 to 5 every 3 wk, and patients receiving adriamycin alone in the same dose and schedule. The combination-treated group had greater adriamycin drug exposure (concentration X time) when serial plasma levels were analyzed by fluorescence assay and by radioimmunoassay (RIA). The plasma t 1/2 of adriamycin equivalents measured by fluorescence assay was also significantly prolonged in the combination-treated group. These changes correlated well with an increase in adriamycin-related toxicity--mucositis and myelosuppression-seen in the patients who received the combination drug therapy. Plasma streptozotocin kinetics and the incidence of streptozotocin-related side effects--hepatic and renal function abnormalities--were those published for streptozotocin alone. Evidence is presented to support the hypothesis that the increased incidence of adriamycin side effects is due to streptozotocin-related hepatic dysfunction, affecting both the detoxification and excretion of adriamycin. Combination of other drugs with adriamycin should take into account their potential for inducing hepatic dysfunction which may affect the therapeutic index of adriamycin.


Variations in size of the bony lumbar canal in patients with prolapse of lumbar intervertebral discs. Prolapse of the lumbar intervertebral disc is one of the commonly accepted causes of low back pain. Most patients respond well to conservative treatment, but some may not respond at all. Though the reason for this variation is not clearly understood, it is felt that a developmentally narrow spinal canal might have some relation to the persistence of backache and sciatica. The canal was therefore measured at each of the lumbar vertebral level by a method described by Jones and Thomson (1969) in 100 consecutive patients operated upon for prolapsed lumbar intervertebral discs, in 100 normal patients for comparison. This method does not give direct measurements of the bony spinal canal but provides a ratio of the size of the canal to the adjacent vertebral body. We found a trend towards the presence of a narrower than normal lumbar canal in patients with prolapsed lumbar intervertebral discs. It is concluded that in patients with prolapsed lumbar intervertebral discs necessitating operation, the canal tends to be narrower than normal, and such narrowing enhances the effect of any disc protrusion leading to severe symptoms of backache and sciatica.


Total anomalous pulmonary venous return with associated patent ductus arteriosus. Two cases with successful correction. A large patent ductus arteriosus associated with total anomalous pulmonary venous return results in a unique hemodynamic pattern, and long-term survival has been rare. Two patients, aged five and 18 years, underwent successful surgical repair of supracardiac total anomalous pulmonary venous return and an associated large patent ductus arteriosus. The association of the Noonan syndrome in the 18-year-old woman is of additional interest.


Increased reactivity of responding cells in the mixed lymphocyte reaction by a thymic humoral factor. A thymic humoral factor (THF) induces competence in a certain sector of the lymphoid cell population. The target cell for THF activity was studied using the one-way mixed lymphocyte culture (MLC). Cells from various lymphoid tissues (responding cells) were preincubated in THF for 1 hour and then mixed with mitomycin-C-treated cells (stimulating cells). The results obtained indicate that THF increases MLC competence of lymphocytes from spleen and thymus origin of intact mice and that of spleen of thymus-deprived mice. In contrast, no enhancing effect in the MLC response by THF could be observed when bone marrow-derived spleen cells, cortisone-resistant thymocytes or lymph node cells were used as responding cells. These results confirm our hypothesis that THF leads to differentiation of young thymus-derived (T) cells, promoting them to maturation and thus to the acquisition of full immune competence.


Lymphocyte membrane receptors in human lymphoid leukemias. Membrane-bound immunoglobulins, receptors for the Fc fragment of IgG and receptors for the third component of human or murine complement were used as B cell membrane markers to study peripheral blood lymphocytes from twenty-two patients with chronic lymphatic leukemia (CLL), five patients with acute lymphoblastic leukemia (ALL) and one patient with Sézary syndrome. The capacity of human T cells of forming "spontaneous rosettes" with sheep erythrocytes was employed as T cell membrane marker. In nineteen out of twenty-seven CLL or ALL cases tested a larger percentage of cells than that found in normal individuals expressed at least one of the three B cell membrane markers studied. In the patient with Sézary syndrome the percentage of cells forming "spontaneous rosettes" with sheep erythrocytes was larger than the normal, while cells bearing B cells markers were below the normal values.


Effect of delayed addition of 2-mercaptoethanol on the generation of mouse cytotoxic T lymphocytes in mixed leukocyte cultures. The generation of mouse cytolytic T lymphocytes (CTL) in primary or secondary mixed leukocyte cultures (MLC) is greatly enhanced by the addition of 2-mercaptoethanol (2-ME) to the culture medium. This enhancement can be equally demonstrated with either reduced or oxidized 2-ME. Addition of 2-ME to MLC as late as 3 days after the initiation of the culture results in a peak CTL response which is nearly as high as the one in cultures containing 2-ME throughout the 4 day-incubation period. Quantitative analysis of the CTL response in MLC supplemented with 2-ME on day 3 shows a 50-fold increase in lytic activity within 24 h, suggesting that cell differentiation, in addition to proliferation may be affected by this agent.


Mixed lymphocyte reactivity of human lymphocytes primed in vitro. I. Secondary response to allogenic lymphocytes. In order to study the mixed lymphocyte culture reactivity of human lymphocytes primed in vitro, a nucleopore culture chamber technique allowing human lymphocytes to be cultured for a period of at least two weeks has been developed. During the primary culture period in nucleopore chambers, human lymphocytes were sensitized against mitomycin-treated allogenic stimulating cells. It was shown that the stimulated lymphocytes underwent a blastogenic reaction and the results suggest a reversion to the state of small, resting, primed lymphocytes. In vitro primed lymphocytes displayed allogenic memory. This was characteristic of a secondary response, which is shown by the following: 1) acceleration, the peak of thymidine incorporation occurring on day 4,2) specificity, the accelerated response was observed only when the primed lymphocytes were confronted with the cell used for priming. Contact with a third party cell did not produce this kind of activation. 3) Amplitude; the peak DNA synthesis response was greater than that of unprimed lymphocytes cultivated for the same length of time.


Isolation on discontinuous gradients of bovine albumin of a subpopulation of human lymphocytes exhibiting precursor characteristics. Purified subpopulations of lymphocytes were obtained from discontinuous bovine serum albumin (BSA) gradients and by rosetting sheep erythrocytes (E) or EAC1-3. Cells from layers 1 to 3 of the BSA gradient which failed to rosette with E were highly reactive with EAC1-3 and with anti-human IgM. Demonstrating a high spontaneous rate of DNA synthesis and primitive morphology, these cells responded to pokeweed mitogen, concanavalin A and alloantigens, but not to phytohemagglutinin or soluble antigens. Constituting from 0.5% to 3.0% of all lymphocytes from each of the tissues studied, these lymphocytes appear to represent an earlier stage in human lymphocyte development distinct from both T and B cells.


Cell-free media of mixed lymphocyte cultures augmenting sensitization in vitro of mouse T lymphocytes against allogeneic fibroblasts. Using an in vitro mouse lymphocyte anti-fibroblast reaction (AFR), we recently reported that the addition of allogeneic stimulator lymphocytes to the sensitization phase of the AFR enhanced sensitization to fibroblast antigens as evidenced by a marked increase in the cytolytic activity of the sensitized lymphocyte population. In the present report we studied the mechanism of this helper effect by testing the capacity of cell-free media derived from 48-h mixed spleen cultures to enhance anti-fibroblast sensitization. We found that such cell-free media could produce a marked helper effect when applied to the sensitization phase of the AFR, but not when added to the cytolytic effector phase. The stimulator cells in the mixed lymphocyte culture (MLC) did not have to be syngeneic with the sensitizing fibroblasts in the AFR in order for the helper effect to be demonstrated. Lymphocytes sensitized to fibroblast antigens in the presence of MLC medium retained their specificity of the effector phase. Our data suggest that the MLC medium acts by enhancing differentiation processes of antigen-triggered lymphocytes. Generation of helper activity by the MLC was abolished by 1000 r irradiation of the responder cells. By using nu/nu and normal spleens, both from two different strains, as cell sources for the MLC, we found that the generation of helper activity depended on T cells capable of proliferation. Furthermore, stimulator lymphocytes differing from responder lymphocytes by non-H-2 alloantigens as well as by point mutation with the H-2 complex were capable of eliciting helper factor(s). Thus, soluble factor(s) produced in a MLC, which are dependent on T lymphocyte proliferation, have the capacity to enhance the sensitization of mouse lymphocytes against antigens present on allogeneic fibroblasts.


Micromethods for induction and assay of mouse mixed lymphocyte reactions and cytotoxicity. A new method in which induction of mixed lymphocyte responses and cytotoxicity can be performed under identical conditions is described. This enables the investigation of the relationship between MLR and cytotoxicity. A micro method for the 51Cr release assay for cytotoxicity is described using both mitogen-induced blasts and tumors as target cells. Under the conditions used data obtained is suitable for linear regression analysis, enabling quantitative comparisons to be made.


Stimulation of mixed lymphocyte cultures and cytotoxic responses: evidence that T cells express SD but not LD antigens, whereas B cells express both. By separating T and B cells from stimulator spleens it has been found that mixed lymphocyte response (MLR) and cytotoxic cells are generated in responder T cell populations by B but not by T stimulator cells in a wide variety of strain combinations. It is suggested that MLR-stimulating or LD antigens are expressed on B but not T cells, and that their presence is necessary in order to generate cototoxic responses to H-2K and/or H-2D (or SD) antigens which are present on both T and B cells. The finding that B cells and macrophages stimulate MLR is consistent with the hypothesis that Ia antigens, expressed on both these cell types but not on nylon column purified peripheral T cells, are the MLR-stimulating or LD determinants.


T cell proliferation in the mixed lymphocyte culture does not necessarily result in the generation of cytotoxic T effector cells. It was tested whether T lymphocytes, when stimulated in vitro by M locus-coded lymphocyte activating determinants (LAD), are able to mediate cytotoxic effector functions. The assay for cytotoxicity included both the use of purified appropriate target cells (i.e. purified lipopolysaccharide blasts) as well as the use of phytohemagglutinin dependent cytolysis as a model for detecting cytotoxic T lymphocytes (CTL). Although strong proliferative responses were obtained in the mixed lymphocyte culture, the T cell blast generated did not display any detectable cytotoxic effector function. Thus, it is concluded that LAD, at least in the M locus-dependent system, do have the capacity to induce T cell proliferation but do not induce CTL.


Effect of tryptaminergic drugs on electroshock fighting behaviour in rats. The effect of some tryptaminergic drugs on electroshock fighting behaviour in rats was determined. Reserpine and tetrabenazine reduced the fighting responses while 5-hydroxytryptophan increased the fighting responses in normal as well as reserpine-treated animals. p-Chlorophenylalanine, a specific depletor of brain serotonin, also reduced the fighting responses. The results suggest that an increase of brain serotonin may have a facilitatory effect on electroshock fighting behaviour and a decrease of brain serotonin may impair fighting behaviour.


Effect of substrate pretreatment on renal organic ion transport in the adult rat. The ability of renal cortical slices to accumulate PAH and NMN was not significantly affected by pretreatment of adult rats with large doses of PAH. Pretreatment of adult rats with THAM significantly increased PAH accumulation but had no effect on NMN. Inulin and PAH clearance and filtration fraction were significantly decreased by PAH pretreatment but unaffected by THAM pretreatment. The effects of pretreatment on transport are probably due to non-specific toxicity.


Hyperinsulinemia and hyperglucagonemia following pancreatic islet transplantation in diabetic rats. Fasting blood glucose (FBG), serum immunoreactive insulin (IRI), plasma immunoreactive glucagon (IRG), body weight, and caloric intake were measured in long-term islet-isografted rats eight to 10 months following intraperitoneal islet transplantation in in age-matched, sham-operated, concurrently followed normal and diabetic controls. Islet recipients had normal body weights, but they were significantly polyphagic, hyperinsulinemic, and hyperglucagonemic when compared with normals. Fasting blood glucose levels were reduced by 10 per cent. Several factors may be related to the occurrence of these abnormalities in long-term islet-isografted rats, including (1) the mass of islets transplanted, (2) the age of donor tissue, (3) the heterotopic location of islet grafts, and (4) the lack of normal innervation of transplanted islet cells.


Effects of streptozotocin in vitro on proinsulin biosynthesis, insulin release and ATP content of isolated rat islets of Langerhans. Proinsulin synthesis, insulin release and intracellular ATP concentrations were measured in isolated rat islets of Langerhans under control conditions in vitro incubation and after treatment with several concentrations of streptozotocin for different periods of time. It was found that streptozotocin inhibited proinsulin synthesis, as well as insulin release, in a time and concentration dependent manner. The characteristics of the inhibition of these two processes were similar in general terms, but one dissimilarity was noted, i.e. after 60 min exposure to a high concentration of streptozotocin, proinsulin synthesis was inhibited more than insulin release. ATP content was reduced by high concentrations of streptozotocin, but it was found that proinsulin synthesis and insulin release could be inhibited without any effect on ATP content by a low (6.22 mM) concentration of streptozotocin. The effect of streptozotocin on proinsulin synthesis was judged to be the result of a target specificity for the B-cell rather than a specific effect on proinsulin relative to total protein synthesis.


Streptozotocin: its excretion and metabolism in the rat. The excretion of radioisotope following the administration of three specifically 14C-labelled forms of streptozotocin was investigated in the rat using ureter and bile duct cannulation techniques. The urine collected during the first hour following the administration of the drug contained the highest proportion of injected radioactivity (approximately 34% with (3'-methyl-14C)-streptozotocin and approximately 40% each with (1-14C)-and (2'-14C)-streptozotocin. Over the entire experimental period (6 hours), approximately 70% of the injected radioactivity of (1-14C)- and (2'-14C)-streptozotocin appeared in the urine. With (3'-methyl-14C)-streptozotocin, only 53% of the injected radioactivity appeared in the urine over the same period. In contrast to the high urinary excretion, less than 3% of the injected radioactivity from all three radiolabelled streptozotocin samples appeared in the bile. The in vivo and in vitro metabolism of streptozotocin was also investigated. In addition to substantial amounts of unchanged drug, three radiolabelled metabolites (two major and one minor) were detected in the urine during the 6 hour collection period following the administration of (1-14C)- and (2'-14C)-streptozotocin. In contrast, only unchanged (3'-methyl-14C)-streptozotocin was detected in the urine collected over the same period following the administration of the methyl labelled drug. The two major metabolites were also produced when (1-14C)-and (2'-14C)-streptozotocin were incubated with a rat liver supernatant fraction (100,000 X g). The liver was further demonstrated to be the major site of metabolism in isolated liver perfusion studies in which both (1-14C)- and (2'-14C)-streptozotocin were quantitatively converted to the two major metabolites. The two major metabolites of (1-14C)-streptozotocin, whether produced in vivo or in vitro, were chromatographically homogenous with the two major metabolites formed from (2'-14C)-streptozotocin. Nicotinamide pretreatment had no apparent effect on the urinary excretion of streptozotocin and its metabolites.


[The VCG in ventricular septal defect in the first two years of life. Qualitative and quantitative analyses (author's transl)]. A group of 37 patients, less than 2 years old, with a ventricular septal defect of variable degree, and a left to right shunt, were studied by vectorcardiography. The duration, the direction and the aspect of the QRS loop on the three orthogonal planes, the voltage of the 0.01; 0.02; 0.04 vectors, the right and the left maximum spatial vectors and their projection on the H and F planes were analyzed and correlated to the right ventricular systolic pressure and Qp/Qs. A clockwise or an eight-type loop on the frontal plane, regardless of RVSP, was observed; on the H plane the loop is, usually, counterclockwise when the pressure is low or medium, and can be of the eight-type but never clockwise when the pressure is systemic. Very interestingly, the quantitative analysis showed a consistent increase of the LMSV. A progressive relationship between the spatial vectors and the right ventricular pressure was noted. The diagnosis of combined ventricular hypertrophy depend upon the following findings: the majority of cases showed a large, counterclockwise and anterior QRS loop on the H with the maximum vector to the left and anteriorly; in all cases the 0.01; 0.02; 0.04 vectors were enlarged, thus warranting the diagnosis of combined ventricular hypertrophy in the first few months of life. 4 cases with low RVSP presented increased initial forces to the right and anteriorly directed, while the major portion of the loop was in the left posterior quadrant on the H plane, with a counterclockwise direction. In our view, the differential diagnosis between this type of aspect and that of diastolic overload of the left ventricle can rest only on the increased voltage of the 0,02 vector which means both systolic and diastolic overload of the right ventricle when accompanied by an increased 0.01 vector which indicates volume overload of left ventricle. Likewise only a quantitative analysis can help in differentiating a combined ventricular hypertrophy from a normal tracing in children under 6 months who show an eight-type loop on the H plane with initial and medium vectors directed anteriorly to the left and counterclockwise, and terminal vectors to the right, posteriorly and clockwise, or in those cases with an anterior clockwise loop on the H plane. Moreover, in the first month of life, the VCG of large VSD with increased pulmonary flux and pressure, can be differentiated from the normal by the QRS loop on the H plane which is clockwise, with initial vectors directed to the left and anteriorly with increased LMSV.


[Influence of left anterior hemiblock on electrocardiographic indices of left ventricular hypertrophy (author's transl)]. The influence of left anterior hemiblock (LAH) on some electrocardiographic criteria of left ventricular hypertrophy (LVH) was investigated. 131 subjects were studied: 34 of them were normal (control group); 30 were carriers of isolated LAH; 38 were carriers of isolated LVH; 29 showed a pattern of combined LVH and LAH. The maximal voltages of QRS waves in leads usually analyzed for LVH, the QRS duration and the time of onset of the intrinsicoid deflection were compared among the groups. The specificity, the sensitivity and the performance of some LVH criteria were examined as well. LAH has been shown to conceal LVH on precordial leads, while it tends to make LVH more manifest on limb leads. The Romhilt and Estes' point score system proved to be the least affected by LAH. On the grounds of theoretical considerations and of empirical trials, we suggest modifying the Romhilt and Estes' point score system; furthermore we suggest modifying Sokolow's and Grant's criteria only when LAH is present. Such modified criteria have improved the accuracy of LVH prevision.


[Frequency of genes and blood groups of the ABO, MN, Rh and P systems among Belorussians and Poles in the Grodno region]. A distribution of the gene frequencies and blood groups of the ABO, Rh, NM and P system in the poles and the byelorussians in the Grodno region is investigated. The following frequencies of genes in the byelorussians were revealed: r(0)-0,6210; p(A)--0.2451; q(B)--0,1339; D--0,6093; d--0,3907; M--0,6063; N--0,3937; P(+)-- 0,4971; P(--)--0,5029; and in the poles: r(0)--0,6284; p(A)--0,2353; q(B)--0,1363; D--0,6065; d - 0,3935; M - 0,6093; N - 0,0397; P(+) - 0,4966; P(-) - 0,5034. No statistically reliable differences were revealed in frequencies of the alleles and phenotypes of the investigated systems in the poles and byelorussians. By comparison of the same isoantigen systems of the byelorussians in the Grodno region with the common population of the byelorussians in the BSSR it was found that statistically significant differences do not exist. The comparison of the poles in the Grodno region with the poles in the Polish People's Republic showed a statistically reliable difference of their genofunds in terms of the gene frequencies: r(0), p(A), D, d, P(+), P(-). This confirms the hypothesis about an indigenous origin of the poles in the Grodno region.


[Inbreeding, endogamy and exogamy among relatives of schizophrenia patients]. An increased frequency of consanguineous marriages among the parents of schizophrenic patients in comparison with the control group of exogenous-somatic patients (infections, trauma) was found. Endogamy among the parents of schizophrenic patients and the control group was practically the same. The data obtained indicate a certain, but not the leading, role of inbreeding in the etiology of schizophrenia.


[Characteristics of inbreeding of the population and distribution of schizophrenia in one of the rural regions of Azerbaijan]. The investigation was carried out in Pushkin region of Azerbaijan SSR. The coefficient of inbreeding was found to be 0,01306 and 0,01142 in 2 typical villages; the frequency of consanguineous marriage in both villages was 30%. The occurrence of consanguineous marriage is explained by a little migration of the population, large families and a stability of marriage traditions. An increased frequency of parental consanguinities of sporadic schizophrenic patients in comparison with the average one was found. This indicates the determination of somes cases by rare recessive genes.


[Medico-genetic study of isolates in Uzbekistan. IV. Clinico-biochemical diagnosis of hereditary diseases]. An exhaustive clinico-biochemical examination of the population of two kishlaks of the Samarkand Region, viz. Karakent (210 persons) and Ishan (248 persons) was carried out. The program of this examination permitted to exclude over 160 forms of hereditary pathology. A total of 45 persons affected with diseases belonging to 12 nosological forms were revealed in the course of the examination. Among the diseases observed only 5 are hereditary sensu stricto, viz. myoclonus-epilepsy, Bonevi-Ulrich's syndrome, imperfect osteogenesis, pigment choreoretinite and Down's syndrome, others belong to diseases with a pronounced hereditary predisposition. The main part of this group comprises neuro-psychic diseases, such as non-differentiated olygophreny (5.0%), epilepsy (1.3%), schizophreny; many of these cases have a familial character, particularly in Karakent. Besides the persons suffering from diseases, 20 heterozygous carriers of beta-thalassemia and 17 heterozygous carriers of G6PD-deficiency were discovered in the kishlaks examined. On the whole the frequency of the diseases revealed did not exceed the level in the general population. Despite the different degree of isolation of the kishlaks examined (Karakent is isolated on a religious basis, F = 0.0064; while Ishan is a desintagrated isolate, F = = 0.0014), no substantial differences between them in the distribution of pathological phenomena were observed. On the basis of the experience of this expedition recomendations are proposed concerning the origination and accomplishment of medico-genetic expeditions. A scheme is proposed for the performance of medico-genetic examination through several stages. The first stage in the composition of tentative maps of the distribution of hereditary diseases within a region on the basis of the information obtained from the medical personnel and from the examination of the documents of district and regional hospitals. Subsequently the primary information is specified, the regions to be examined are determined, as well as concrete tasks and the staff of the expedition. The conclusive stage is the medico-genetic examination proper, including clinical, biochemical, immunological and cytogenetic diagnoses of hereditary pathological phenomena. The place of the disposition is a village or a district hospital. More complicated laboratory studies should be performed on the basis of the institution by which the expedition is formed. The results obtained by such expeditions would be important for the investigation of the problems of genogeography, for the discovery of new forms of mutant alleles, for the investigation of the causes and the conditions of the formation of the definite populational structure, of clinical polymorphism of human hereditary diseases.


The left ventricle in emphysema and chronic bronchitis. There's no doubt that chronic obstructive lung disease can have a disastrous impact on the heart's right ventricle--often producing hypertrophy or even failure--but its effects on the left ventricle are less clear. Some researchers speculate that disease of the right ventricle leads to disease of the left, while others consider the lung disease itself to be the more likely mechanism. Ordinarily, the left ventricle holds up well, even in far-advanced emphysema and chronic bronchitis. Recognizing the cases that do occur is important, however, since only minimal left ventricular failure can seriously compromise respiratory function. Treatment is the same as for left ventricular failure of any cause, but special precautions should be observed, particularly in prescribing diuretics. If frank pulmonary edema supervenes, mechanical ventilation and supplemental oxygen are necessary.


The study of variability and strain selection in Streptomyces atroolivaceus. III. Isolation and preliminary characteristics of mutants impaired in the biosynthesis of mithramycin. Mutants of Streptomyces atroolivaceus blocked in the biosynthesis of mithramycin were isolated both by natural selection and after treatment with mutagenic factors (UV and gamma rays, nitrous acid). Both physical factors were more effective than nitrous acid. The selection was complicated by a high instability of isolates, out of which 20-80% (depending on their origin) reversed spontaneously to the parent type. The primary screening (selection of morphological variants and determination of their activity using the method of agar blocks) made it possible to detect only potentially non-productive strains; however, the final selection had to be performed always under submerged conditions. Fifty-four stable non-productive mutants were divided, according to results of the chromatographic analysis, in five groups differing in production of six biologically inactive metabolites (compounds A-H). The mutants did not accumulate chromomycinone, chromocyclomycin and chromocyclin. On mixed cultivation none of the pairs of mutants was capable of cosynthesis of mithramycin or new compounds differing from standard metabolites. Possible causes of the above results are discussed.


Dehydroepiandrosterone concentration in adipose tissue of normal and overweight subjects. Unconjugated dehydroepiandrosterone has been isolated from human abdominal adipose tissue and identified by double isotope derivatization and recrystallization to constant isotope ratio. Gas chromatography with electron capture detection revealed an actual dehydroepiandrosterone concentration between 0.32 to 2.82 mug/g in adipose tissue of normal and overweight subjects. The approximate dehydroepiandrosterone content of the total adipose tissue mass varied between 30 and 173 mg in subjects with severe obesity.


The influence of streptozotocin diabetes on adrenal function in male rats. Male Wistar rats were treated with an i.v. dose of 100 mg/kg of Streptozotocin (STZ). Either 5 days or 1, 2 or 3 months after induction of diabetes, the adrenal function of these animals was studied. Short course diabetes (5 days) was accompanied by adrenal hypertrophy and high plasma corticosterone levels; during later periods the diabetic rats consistenly showed signs of adrenal hyperactivity, yet both adrenal weight and plasma corticosterone tended to be lower than in the 5 day-treated animals. Adrenal incubations with 14C-progesterone showed that 5 days and one month diabetic animals synthesized more deoxycorticosterone than controls; production of corticosterone and 18-hydroxydeoxycorticosterone was normal at all time periods studied. Synthesis of 18-hydroxycorticosterone, a compound which affects sodium metabolism, was increased in 5 day-treated rats; thereafter, the function of the zona glomerulosa seemed to be impaired in diabetic rats. These results suggest that early after induction of diabetes there is adrenal hyperfunction of the mixed type (i.e. gluco and mineralcorticoid), and that in the later periods (2-3 months), the deranged metabolism of the diabetic rat acts as a chronic stress.


Decay of succinate dehydrogenase activity in rat skeletal muscle following streptozotocin injection. Succinate dehydrogenase activities of 4 skeletal muscles with widely divergent fiber compositions were determined in rats that recieved either 70 or 80 mg streptozotocin per kg body wt at various time intervals following injection. Enzyme activities in all muscles declined to a lower final level and exhibited a more rapid decay in animals receiving the larger dosage. White gastrocnemius muscle, which contains no slow-twitch fibers, experienced the greatest relative loss of activity, and soleus muscle, possessing the highest proportion of slow-twitch fibers, the smallest loss. The findings indicate that extrapancreatic effects of the drug may have been partially responsible for the differential effects of the 2 dosages on the muscles.


A parent-implemented early intervention program for preschool children. The Regional Intervention Program is a data-based, parent-implemented early intervention program providing comprehensive services to parents and their handicapped preschool children in a 26-county area of middle Tennessee. The program's service modules teach parents how to manage their child's behavior and how to teach their child essential prelanguage, language, and self-help skills. The preschool component develops the child's motor, language, and peer-interaction skills in order to prepare him for placement in a preschool in the community. A liaison module conducts follow-up on each family every six months. Several evaluation components ensure that the program is accountable to both the funding source and the families served.


The specificity of anti-actin serum.

The specificity of anti-actin serum. The immunogenicity of smooth muscle actin is increased by ageing at 4 degrees for at least a week. Rabbits lacking natural smooth muscle antibodies were injected with 1 mg of aged purified actin in adjuvant. Fourteen out of thirty-six rabbits produced serum antibodies which precipitated with actin solution, but not with smooth muscle tropomyosin, myosin, light or heavy meromyosin or with other unidentified non-actin proteins in crude extracts. Analysis of crude actin extract before and after precipitation by antiserum (i) by Sephadex G-200 chromatography and (ii) for its stimulating effect on myosin ATPase activity showed that actin was selectively removed. The precipitate itself, analysed on SDS-polyacrylamide gel, showed one band in the actin position, and otherwise only bands representing immunoglobulins. The antiserum also inhibited the ability of actin to stimulate myosin ATPase activity, and prevented polymerization of G-actin to F-actin, as shown by viscosity and EM studies. On immunoflouresence with cryostat tissue sections or cell cultures, anti-actin serum stained smooth muscle fibres and many non-muscle cells, in the latter staining the microfilaments. The staining was prevented by absorbing the antiserum with actin (16 mug per 5 mul serum), and was abolished by pretreatment of the cells with cytochalasin B. No species specificity was demonstrated for these anti-actin antibodies.


Human thymus cells: blastogenic response to mitogens, antigens and allogeneic cells. Over 90 per cent of the thymus cells from each of twenty-six donors were T lymphocytes, identified by E-rosetting and less than 3 per cent of the cells were B lymphocytes identified by EAC-rosetting. With advancing age, the proportion of T lymphocytes decreased while that of B lymphocytes increased. The degree of (3H)thymidine incorporation of thymus cells was inversely proportional to the age of the thymus-cell donor. The PHA or PWM- induced blastogenic response of thymus cells gradually increased with advancing age when the response was expressed as the stimulation index. However, the actual rate of (3H)thymidine incorporation in all three groups was rather similar when cells were cultured with mitogens. The difference in stimulation index was due to the variation in incorporation rate in cultures without stimulants. The PHA response was approximately four-fold higher than that of PWM response. Thymus cell response to allogeneic lyphocytes, on the other hand, had no correlation with the age of thymus donor. The most surprising result in the present study was that the thymus cells from each of ten donors, aged 1-14 years, were incapable of responding to all four different recall antigens. Peripheral blood lymphocytes from nine to ten randomly selected age-matched children responded very well to one or more antigens.


T and B lymphocytes. Exclusive role as responders and stimulators in human one-way mixed lymphocyte reaction. Four different combinations of one-way mixed lymphocyte reactions between human peripheral blood T and B lymphocytes (at a ratio of 1:1), purified by the E-rosetting technique, were carried our. A significant mixed lymphocyte reaction was observed only in a combination in which T lymphocytes, as responding cells, and B lymphocytes, as stimulating cells, were utilized. No significant mixed lymphocyte reaction was noted in the other three combinations of cells, using T or B lymphocytes as responders and T lymphocytes as stimulators, and also B lymphocytes as both responders and stimulators. Mixed lymphocyte reactions between T lymphocytes as responders (at constant concentration) and T and B lymphocytes as stimulators (varying proportions) showed that the response decreased proportionately with decreasing numbers of B cells and increasing numbers of T cells used as stimulators. Addition of increasing numbers of stimulating T cells to a constant number of stimulating B cells did not suppress or enhance the T-cell response to B cells. These observations indicate that the human peripheral blood T and B lymphocytes play an exclusive role as responding cells and stimulating cells, respectively.


A new framework for health.

A new framework for health. In summary, it has been proposed that the concept of health be conceived of not as a single continuum, but rather in terms of a two-dimensional space whose dimensions are defined in relation to the two underlying system processes that they reflect. Such a conceptualization has several important implications. First, it views health as a function of the operation of system processes, and is conceptually isomorphic to a more general theory of systems. That is, health is seen as the result of the operation of system processes; and the definition is consistent with a theory of system processes. The traditional one-dimensional conception of health ignores the distinction between the two fundamentally different processes and treats them as though they were the same. This inattention to the nature of the processes whose operation results in health as an outcome has created much of the conceptual confusion--i.e., it has led to situations in which the conceptualization is not powerful enough to account for observed variability. For example, it is obvious to all concerned that all people who have no detectable morbidity are not equally healthy, although a disease-oriented definition of health (e.g., health as the absence of disease) offers no way of differentiating conceptually between such people. A second implication of the conceptualization is that it eliminates some of the contradictions between one-dimensional definitions and real-world experiences. Health need no longer be seen as either the absence of disease or the expression of developmental processes. Under the proposed conception, the contributions of both negative and positive forces are acknowledged as vital components of general health. Furthermore, analogies drawn from work in other areas suggest a model of how the processes underlying the dimensions interact--that actualization becomes possible when equilibrium is reasonably well maintained. Probably the most far-reaching implication, however, involves the broadening of the scope of the term "health" and the potential impact of the potential impact of that broadening on the kind of data used in making community health level assessments. The measurement of health levels in the past has centered on aggregate mortality and morbidity rates as surrogates for "health9" In terms of the proposed framework, such measures may provide some insight into the equilibrium dimensions but are clearly inadequate for assessing actualization.


Maximizing health system output with political and administrative constraints using mathematical programming. Decisions about delivery programs to improve health status are characterized by indivisibilities or "lumpiness," interdependencies between case types with varying health output, high fixed costs, administrative constraints, and qualitative quity and political considerations. The nature of the constraints and the goal of health services strongly suggest a mathematical programming model to maximize a comprehensive measure of health status. In a previously unreported development, binary integer programming can be extended to consider shared fixed costs, a widespread problem in optimizing effectiveness measures such as health status. The model proposed here applies conceptually across all target populations and health programs and could be used to optimize the output of a total health system. The effects of such optimization would be appropriately reflected in the weighted life expectancy computed as a social indicator.


Spectinomycin - experimental investigations on possible side-effects. Experimental investigations were performed to elaborate the immunogenic and anaphylactoid properties of spectinomycin. In guinea-pigs, no allergy against spectinomycin could be elicited. Furthermore, the absence of immunologic cross-reactions between spectinomycin and penicillin could be confirmed. The anaphylactoid activity of spectinomycin was found to be of very low order. No mast cell degranulating action could be observed. The data collected in this study permit the statement that - as far as acute unwanted actions of antibiotics are concerned - spectinomycin is an extremely safe drug.


Integration and control of circulatory function. In this chapter we have emphasized especially the intrinsic controls of the circulation, such as the autoregulation mechanism for control of local blood flow, automatic control of cardiac output, long-term control of arterial pressure, long-term control of blood volume, and automatic distribution of fluids between the circulation and the interstitial spaces. The reasons for emphasizing these mechanisms are several: first, many experiments have now shown that the intrinsic mechanisms can provide highly stable long-term control of the circulation. Second, the value of the nervous and hormonal controls have probably been greatly overemphasized in the past. And, third, there are special complexities of the intrinsic controls--such as nonlinearities, delay in responses, and other effects--that have made these difficult to understand; it is probably these difficulties that have led to their underemphasis. However, we have not meant to take from the nervous and hormonal systems their true importance in circulatory control. For instance, intrinsic mechanisms have almost no capability for acute arterial pressure control (only for long-term control), and they have no mechanism for providing the drive necessary to make the animal ingest water and electrolytes. These require the nervous controls. Also, nervous reflexes are important in enhancing the effectiveness of blood volume control and control of cardiac pumping. Among the hormonal mechanisms, the renin-angiotensin system can provide a modest degree of arterial pressure control when the pressure falls below normal by eliciting a vasoconstrictor response in the peripheral blood vessels. However, this system seems to have an even more important renal function, a direct effect on kidneys to cause fluid retention; this in turn increases the body fluid volume and in this way increases the arterial pressure. Finally, the roles of ADH and aldosterone in the control of blood volume have probably been greatly overemphasized. On the other hand, both clinical experience and experimental studies are beginning to demonstrate that the thirst/ADH system is probably by far the most potent mechanism that we have for control of extracellular fluid sodium ion concentration. On the other hand, the aldosterone mechanism seems to be our primary control system for maintaining a normal extracellular fluid concentration of potassium.


On-line impedance analysis system for studying the pulmonary vascular response to hypoxia. The response of the pulmonary circulation to hypoxia is generally assessed in terms of cardiac output and pulmonary vascular resistance. However, due to pulsatility, the opposition to blood flow can be described accurately only by the input impedance to the pulmonary bed. For assessment of impedance, a system was developed consisting of implantable pressure transducers and an improved muitichannel continuous wave Doppler flow meter. A computer system was used to analyze the data, which was based on power output of the right heart, power dissipation in the pulmonary circulation, and impedance spectra. Data have been obtained from dogs exposed to various levels of acute hypoxia.


The innervation of muscle spindles in the snake, Elaphe quadrivirgata. The morphology and distribution of sensory endings in snake (Elaphe quadrivirgata) muscle spindles was studied in silver preparations. The sensory axon supplying long-capsule spindles often bifurcates before or after penetrating the capsule and runs for some distance along the intrafusal fibre. The sensory axon supplying short-capsule spindles penetrates the capsule at a sharp angle, and, without ramification, terminates abruptly on the intrafusal fibre. The sensory terminal is composed of terminal bulbs and small links. In long-capsule spindles the sensory ending is arranged longitudinally in one or two rows. The sensory ending in short-capsule spindles ramifies extensively, covering densely the intrafusal fibre. The area occupied by sensory bulbs was estimated to be slightly higher in short-capsule (15-17?) THAN IN LONG-CAPSULE SPINDLES (12-13). The functional significance of these findings is discussed. Motor innervation of muscle spindles in the snake Elaphe quadrivirgata was studied using AchE staining for light microscopy in conjection with electron microscopy. In the polar region of either type of spindle, the majority of the motor endings are of grape type. In long-capsule spindles plate endings may occur in the spindle pole as well as in the capsular region. Motor endings in the capsular region are mostly of plate type. Plate endings rarely occur in short-capsule spindles. Identified single motor endings were studied by electron microscopy. Intrafusal grape endings are characterized by a smooth post-synaptic membrane. Intrafusal plate endings in the polar region are characterized by junctional folds or gutterings; plate endings in the capsular region show less developed gutterings or indentations. The distribution of intrafusal motor endings was examined along the length of single intrafusal fibres. The long-capsule spindle often receives asymmetrical motor innervation around the capsular region, whereas motor endings in the short-capsule spindle distribute more symmetrically.


Inhibition of glucose metabolism by n-hexadecane in Cladosporium (Amorphotheca) resinae. When Cladosporium resinae is provided with n-hexadecane and glucose, n-hexadecane is used preferentially. Studies using [14C]glucose indicated that n-hexadecane did not inhibit glucose uptake but did retard oxidation of glucose to CO2 and assimilation of glucose carbon into trichloroacetic acid-insoluble material. Glucose could be recovered quantitatively from hydrocarbon-grown cells that had been transferred to glucose. Four enzymes that may be involved in glucose metabolism, hexokinase, glucose-6-phosphate dehydrogenase, glucose-phosphate isomerase, and succinate dehydrogenase, were not detected in cells grown on hexadecane but were present in cells grown on glucose. Addition of hexadecane to extracts of glucose-grown cells resulted in immediate loss of activity for each of the four enzymes, but two other enzymes did not directly involved in glucose metabolism, adenosine triphosphatase and alanine-ketoacid aminotransferase, were not inhibited by hexadecane in vitro. Cells grown on hexadecane and transferred to glucose metabolize intracellular hexadecane; after 1 day, activity of hexokinase, glucose-6-phosphate dehydrogenase, glucosephosphate isomerase, and succinate dehydrogenase could be detected and 22% of the intracellular hydrocarbon had been metabolized. Hexadecane-grown cells transferred to glucose plus cycloheximide showed the same level of activity of all the four enzymes as cells transferred to glucose alone. Thus, intracellular n-hexadecane or a metabolite of hexadecane can inthesis of those enzymes is not inhibited.


Transport of vitamin B12 in tonB mutants of Escherichia coli. It is known that the tonB mutation in Escherichia coli is responsible for a defect in the transport of iron chelates. These are transported by systems that involve outer membrane components. We found that tonB mutants were also deficient in the secondary, energy-dependent phase of vitamin B12 transport, although the mutants have normal levels of B12 receptors on their cell surface. In addition, tonB mutants derived from vitamin B12 auxotrophs required elevated levels of B12 for normal growth. Maltose uptake, mediated by another transport system involving an outer membrane component, was unaffected by the tonB mutation.


Properties of Escherichia coli mutants with alterations in Mg2+-adenosine triphosphatase. A mutant Escherichia coli, selected for resistance to the antibiotic neomycin, was unable to utilize nonfermentable carbon sources for growth. Two strains were selected from this mutant on the basis of their ability to grow utilizing succinate as a carbon source. All three strains had approximately equal amounts of the Mg2+-adenosine triphosphatase (ATPase) (EC 3.6.1.3) protein, but the activity of the enzyme differed in each strain. The Mg2+-ATPase from each of the three strains lost activity upon solubilization and appeared to undergo rapid dissociation once solubilized. This dissociation is similar to that described for the wild type after cold exposure.