The effect of thymoxamine and cromolyn sodium on postexercise bronchoconstriction in asthma. Of the 22 patients with extrinsic bronchial asthma, 13 patients developed post-exercise bronchoconstriction after treadmill exercise, whereas in 9 patients treadmill exercise had no effect on the ventilatory capacity. No statistical difference in the resting lung volumes and CO transfer factor was found between the two groups. A significant inhibition of postexercise bronchoconstriction was observed in 12 of 13 patients following thymoxamine or cromolyn sodium inhalation. Inhibition of postexercise bronchoconstriction by alpha blockade with thymoxamine suggests that increased alpha adrenergic activity in the presence of diminished beta receptor responsiveness to catecholamines, norepinephrine released during exercise could have a marked alpha agonistic effect giving rise to bronchoconstriction. It has been suggested that cromolyn sodium has a cyclic phosphodiesterase inhibiting action. This might increase levels of AMP and restore the beta receptor responsiveness to catecholamines.


Inhibition of hypersensitivity reactions by a new drug, N(3',4'-dimethoxycinnamoyl) anthranilic acid (N-5'). N (3', 4'-dimethoxycinnamoyl) anthranilic acid (N-5'), a new antiallergic drug, can be taken orally, has low toxicity, and is a potent inhibitor of homologous passive cutaneous anaphylaxis (PCA) both in rats and in guinea pigs. Anaphylactic mediator release from guinea pig lung was decreased by the drug in vitro. Although reversed cutaneous anaphylaxis and Arthus type reactivity were moderately inhibited with N-5', this agent did not inhibit the Forssman systemic reaction or contact dermatitis. N-5' is considered to be clinically applicable to certain allergic-related diseases, in particular asthma caused by reaginic antibody.


Magnitude, direction and location of the resultant dipole moment of the pig heart. Vectorcardiograms were obtained from 50 young domestic pigs using the Nelson lead system. Compensation for body size and shape is achieved and the resultant dipole moment magnitude reflects heart size. A strong relationship was found between heart size and maximum magnitude. Dipole moment magnitude increased as four pigs increased from five to ten weeks of age. The dipole moment during QRS is considered in light of known pig heart excitation pattern. Dipole locations during QRS, calculated by computer solution of the Gabor-Nelson equations, were in agreement with heart location and excitation data.


Theoretical considerations on the electrocardiogram of ventricular hypertrophy. The electrical effect of ventricular hypertrophy is evaluated with an idealized model. Perfectly symmetrical hypertrophy is expected to enlarge the QRS complex with a certain proportion of the amplitude and duration. If the conduction velocity is unaltered, the QRS area will be increased proportionally to the myocardial mass. 2) Based on the preservation of the ventricular gradient, the secondary T change is expressed as a function of the QRS and G vectors. A theoretically interesting parameter, G/QRS ratio, is defined as a measure of the "ventricular gradient density," which is important for the over-all recovery pattern. This ratio is decreased in ventricular hypertrophy and is closely related to the QRS-T angle. 3) From the viewpoint of the theory, clinical cases with left ventricular hypertrophy are examined. The theory describes the cases with uncompicated hypertension fairly well, although variations from case to case are not small. Underlying assumptions and causes of deviations in actual cases are discussed.


Secondary cell-mediated lympholysis: importance of H-2 LD and SD factors. Lymphocytes stimulated in mixed leukocyte cultures and left for 13-17 days, i.e. beyond their peak proliferative and cytotoxic reactivities, can be restimulated to give a  secondary-type rapid and strong proliferative and cytotoxic response when confronted with cells of the original sensitizing cell donor. We have concerned ourselves primarily with the requirements  of restimulation for the presence of LD and/or SD stimuli on the restimulating cells. (a) The low level cell-mediated lympholysis (CML) associated with LD differences in a primary CML can be restimulated to give a secondary-type response by those same LD antigens. (b) If the original sensitizing cells differ from the responding cells by both LD and SD antigens, restimulation with only the LD antigens, or third-party cells presumably carrying cross-reactive LD antigens, can restimulate the secondary CML responses directed against the SD antigens on the original sensitizing cells. (c) The presence of SD antigens on the restimulating cells that are cross-reactive with the primary sensitizing SD antigens (as determined in a primary CML) leads to the preferential activation of cytotoxic T lymphocytes reactive to those antigens although maximum cytotoxicity is still directed at cells carrying the original sensitizing SD antigens. A model to explain these results is presented.


Lymphocyte transformation induced by autologous cells. IV. Human T-lymphocyte proliferation induced by autologous or allogeneic non-T lymphocytes. An autologous mixed lymphocyte reaction was demonstrated between T and non-T lymphocytes. Sheep erythrocyte rosetting was used to separate human lymphocytes into T and non-T lymphoid preparations. Non-T lymphocytes stimulated the proliferation of autologous T lymphocytes. The cell in this preparation that was most stimulatory had the characteristics of a K lymphocyte. The allogeneic mixed lymphocyte reaction was also shown to reflect the proliferation of T lymphocytes stimulated by allogeneic non-T lymphocytes. Proliferation of T lymphocytes in the allogeneic mixed lymphocyte culture probably reflects a response to both foreign histocompatibility determinants and determinants present on non-T lymphocytes. It is suggested that the proliferative response of T lymphocytes to autologous non-T lymphocytes may be a step in the process by which T lymphocytes regulate immunity.


Suppressor cell activity after concanavalin A treatment of lymphocytes from normal donors. Pretreatment of normal human peripheral blood lymphocytes with the plant lectin, concanavalin A (Con A), results in inhibition of blast transformation and [3H]thymidine incorporation by untreated allogeneic lymphocytes from healthy volunteers donors in one-way mixed leukocyte culture. Similarly, responses to mitogens, certain microbial antigens, and allogeneic lymphocytes are inhibited by Con A-treated allogeneic cells. Con A pretreated autologous lymphocytes can also be induced to manifest suppressor activities. This antimitotic effect occurs without evidence of cytotoxicity and is active on de novo lymphocyte responses and does not require prior sensitization of the cells being tested. Suppression of the lymphocyte response to pokeweed mitogen, a potent B-cell stimulator, by Con A-pretreated suppressor cells was not as consistent as was inhibition of response to other mitogens, including phytohemagglutinin and Con A. Furthermore, suppression of lymphocyte transformation to the microbial antigens, tuberculin purified protein derivative, and Canadida albicans extracts could be similarly induced by Con A pretreatment of either allogeneic or autologous cells. Induction of autologous suppressor activity in lymphocytes from healthy donors is compatible with a model that includes a role for suppressor cells in the modulation of the normal immune response.


Antigen-initiated B-lymphocyte differentiation. VIII. Sedimentation velocity and buoyant density characterization of virgin antibody-forming cell progenitors in the adoptive immune response of unprimed CBA mice to 4-hydroxy-3-iodo-5-nitrophenylacetic acid-polymerized bacterial flagellin antigen. The characteristics of antibody-forming cell (AFC) progenitors lacking previous contact with specific antigen (virgin AFC progenitors) has been studied using sedimentation velocity and buoyant density separation for the investigation of physically distinct B-cell subpopulations. Functional characterization of isolated subsets was made using a quantitative adoptive immune assay for the IgM AFC progenitors responding to the antigen 4-hydroxy-3-iodo-5-nitrophenylacetic acid conjugated polymerized bacterial flagellin. Extensive heterogeneity is present among B lymphocytes, only some subpopulations of which exhibit AFC progenitor function. In the spleen of adult conventional CBA mice, atypically fast sedimenting cells of low buoyant density are active, while typical small B lymphocytes do not appear to be progenitors of IgM AFC. Spleen of adult specific pathogen-free (SPF), germfree, and athymic nude mice give similar results, although a minor population of typical slowly sedimenting dense cells are active in the latter two sources. Adult conventional bone marrow cells are as physically and functionally heterogeneous as splenic B cells, and although a significant proportion of AFC progenitor activity is found among dense, slowly sedimenting cells, most of the activity is among low density, faster sedimenting cells. In contrast to this situation in adult animals, where most of the unprimed AFC progenitors are large, atypical B cells, the spleens of neonatal mice provide a site where virgin AFC progenitors with the physical properties of typical small B lymphocytes are found. While being present in conventional and SPF neonatal spleens, these virgin cells are predominant in 7-day-old germfree mouse spleen. These findings suggest that the newborn virgin B cell is a typical small lymphocyte. However, few cells of this type are found in the adult animal. The unprimed AFC-progenitor population in the adult consists of large, fast sedimenting, low buoyant density, adherent cells, the physical properties of which are characteristic of activated B lymphocytes. It is suggested that these atypical cells are derived from the small newborn virgin B cell by the nonspecific effects of environmental antigenic stimuli.


The sulfatides and some histochemical correlations of the lachrymal glands involved in salt secretion in Chelonia. High concentrations of sulfolipids (four fractions having different hexose/sulfate ratio), intense enzyme activity (ATPase, oxoreductases) and evidence of mucines (staining with PAS and Alcian blue) in intercellular spaces were found in the lachrymal glands of Caretta caretta and Malaclemys terrapin adapted to sea water. In addition, the supranuclear region of the gland cells in Malaclemys terrapin is filled with mucin granules. These biochemical and histochemical observations indicate that these glands have a function in salt secretion in both species and are also consistent with a function of mucous secretion exclusively in Malaclemys terrapin. Limited signs of hypotrophy are not accompanied by changes in concentrations of sulfolipids in Malaclemys terrapin adapted to fresh water; only the reactions for enzyme activities are less intense. The mucous secretion is not affected, whereas, in correlation with changes in salt secretion, the change in ATPase activity is mot conspicuous. The correlations between the different components of the gland and salt secretion are compared with salt glands of birds and elasmobranchs.


The relationship between independent neuropsychological and neurological detection and localization of cerebral impairment. Seventy-eight patients referred to the Neurology Service of St. Louis Veterans Administration Hospital were independently diagnosed by a neurologist and a psychologist. The latter utilized the Halstead Neuropsychological Test Battery, a series of tests known to be a sensitive indicator of the presence and localization of cerebral impairment. The following diagnostic categories were used: no brain damage, localized left hemisphere impairment, localized right hemisphere impairment, diffuse, diffuse with greater left hemisphere impairment, and diffuse with greater right impairment. Diagnostic agreement was present in all but five cases. Statistical analyses of data from the Halstead Battery supported the clinical analyses in terms of indicating both the presence and, to a lesser degree, the location of organic impairment. Advantages of describing the consequences of organic impairment in objectively measured, quantifiable behavioral terms were discussed and an illustrative case history was presented. It was concluded that psychological test data are a clinically useful supplement to neurological diagnostic information.


Adaptive transformation of rat soleus motor units during growth. Soleus motor units of 5 and 34 week-old rats, weighing 150 and 520 g respectively, were examined for contraction time at 36 degrees C, innervation ratio as well as cross-sectional area, ATPase and SDH activity of fibres. The muscle was continuously adjusted to the growth of the animal. Between 5 and 34 weeks the proportion of Type II fibre units with 15-26 msec contraction time decreased from 33% to 10% and Type I fibre units with 27-40 msec contraction time thus increased from 67 to 90%. This was parallelled by approximately the same relative changes in number of Type II and Type I fibres.


Mucin histochemistry of human cholangiocarcinoma. Histochemical studies of mucins were carried out on 17 autopsy specimens of cholangiocarcinomas associated with clonorchiasis. All tumours produced epithelial mucins which were mixtures of neutral and acid mucopolysaccharides without any histochemically demonstrable components of sialic and uronic acids. The mucins were qualitatively similar to that secreted by normal and Clonorchis-infested bile ducts. However carboxymucins were reduced and sulphomucins were absent or present only in trace amounts in the neoplastic epithelium; in the hyperplastic epithelium in clonorchiasis sulphomucins were abundant. The HID-AB technique for sulphomucins is valuable in differentiating hyperplastic bile ducts and cholangiocarcinoma.


Immunization for kidney worm disease (stephanuriasis) of swine I. Somatic antigens. Nine somatic antigens derived from the excretory gland cells of adult Stephanurus dentatus were evaluated as vaccines for stephanuriasis of swine. Antigens were mixed v/v with Freund's complete adjuvant and  administered intramuscularly or subcutaneously. Efficacy was evaluated by counting and comparing lesions and worms in the lymph nodes, livers, and kidney regions of principals and controls necropsied after oral challenge with infective S. dentatus larvae or after exposure to pastures naturally contaminated with such larvae. Against oral challenge, 6 vaccines produced statistically significant reductions in worm burdens of principals; 5 were significant at the 1% level and 1 at the 5% level. Two of these vaccines also reduced liver lesions significantly (P less than 0.05). Results of the natural challenge were inconclusive; small worm burdens were found in both principals and controls. None of the vaccines completely prevented migration to the liver or subsequent development and migration of a few worms to the kidney region. However, since worm burdens were reduced by as much as 92%, the vaccines could be useful in combating the disease, especially if combined with other control measures.


Transport of organic cations and anions by choroid plexus. The accumulation of organic cations and anions by the isolated rabbit choroid plexus was measured and the results were considered in comparison to in vivo measurements of transport using the ventriculocisternal perfusion technique also in rabbits. The accumulation in vitro of 3H-p-aminohippurate (PAH) and 14C-N1-methylnicotinamide (NMN) was shown to be organic anion and cation specific and dependent upon oxidative metabolism since tissue/medium ratios were reduced by competitive inhibitors including dibenamine and mepiperphenidol for cation transport and probenecid for anion transport and were also reduced by cyanide and dinitrophenol. Rabbits pretreated with chlorpromazine and anesthetized with pentobarbital were perfused lateral ventricle to cisterna magna with artificial cerebrospinal fluid containing inulin, 3H-PAH and 14C-NMN. Ratios of concentrations of these substances in the perfusate to those infused were calculated. Significant reductions in the ratios for PAH and NMN compared to unulin were obtained when low rates of perfusion, 40mul/min, were employed with low concentrations of PAH (2 mug/ml) and NMN (0.2 mug/ml). Probenecid (10(-3)M) specifically increased the ratio for PAH without affecting the NMN ratios. Mepiperhenidol (10(-o) M) blocked NMN transport but no PAH. The data and calculated clearances indicate that these prototype anions and cations may be actively transported out of cerebrospinal fluid, but for cations only at a low rate.


The effect of low amplitude muscle vibration on the discharge of fusimotor neurones in the decerebrate cat. 1. Longitudinal vibration (50-100 mum, 100-300 Hz) has been applied to the triceps surae tendon to examine its effect on the tonic discharges of gastrocnemius medialis fusimotor neurones in the decerebrated cat. 2. For nineteen out of twenty-seven fusimotor neurones vibration consistently caused a small rise in discharge frequency. The remaining eight neurones showed no respose to the vibration which always evoked a considerable discharge in alpha motoneurones. 3. The reflex excitation of fusimotor neurones is attributed to activity in primary endings of muscle spindles since control experiments confirmed that these receptors were powerfully excited by the vibration used whereas secondary endings and Golgi tendon organs remained unaffected. 4. Tonic discharges of fusimotor neurones of unknown destination were also recorded from lumbar 7 and sacral 1 ventral root filaments in decerebrated cats. Of thirty cells, seven were inhibited, five were excited and the remaining eighteen units were unaffected by vibration of the triceps surae. 5. These findings are discussed in relation to the role of muscle stretch receptors in the autogenetic control of fusimotor neurones.


Environmental salinity and sodium and chloride exchanges across the gill of Tilapia mossambica. 10 Freshwater-(FW)-adapted, one-third seawater (1/3 SW)-adapted and seawater (SW) adapted Tilapia mossambica were compared for their branchial Na+ influx and efflux as well as Cl- efflux. Na+ and Cl- effluxes were identical. Rates of effluxes were in 1/3 SW- and in SW-adapted fish 10 times and 200 times higher respectively than in FW specimens. 20 Shock due to handling and transfer to small experimental chambers induced, within 20 to 45 min., a considerable increase in Na+ efflux and a more discrete augmentation of the Na+ influx. 30 Branchial Mg++-and Na+-K+ activated ATPase activities increased significantly upon adaptation from FW to 1/3 SW. No significant increase was apparent upon adaptation from 1/3 SW to SW. 40 The trans-branchial potential observed in SW Tilapia resembled the pattern previously described in other species of teleosts.


Effects of Ba ions on frog's isolated muscle spindle. Dilute solutions of Barium Chloride have been tested on frog's isolated muscle spindles with the aim of clarifying the processes leading to the afferent discharge. In the presence of Ba++ the spindle properties are modified as follows: 1. The discharge of slack spindles increases and becomes extremely regular. 2. The phasic response to stretching is enhanced, the tonic responses being on the contrary virtually suppressed. Under Ba-treatment therefore the spindle changes from a phasic-tonic receptor to a merely phasic receptor. 3. The "silent period" following every propagated spike is prolonged while the safety margin of the "abortive" into propagated spike conversion becomes maximal under Ba-treatment. Additionally, this analysis showed that, when a "true" action potential arises in the spindle, it propagates not only to the stem fibre, but also to all the sensory endings in the spindle intracapsular network. Comparison between the effects of Ba++ and those produced by TEA and ouabain indicates that the action of Ba++ on muscle spindles results from conjunction of two factors : a) reduction of K permeability, and b) enhanced efficiency of an electrogenic Na/K-pump in spindle nerve membranes.


Temperature gradients at various points within the human pelvis as measured during laparoscopy. Temperatures have been measured during pelvic laparoscopy, under general anesthesia, in 59 women. Temperatures on the serosal surface of the rectum, the mesovarium, the ovarian arteries and the surface of the external iliac artery have been compared with the temperature deep in the rectal cavity on the rectal mucosa. The mean temperatures recorded at all sites within the pelvic cavity were lower than the mean temperatures recorded on the rectal mucosa. The mean differences between rectal mucosa and the other pelvic sites are: rectal mucosa -0.20 +/- standard error of the mean (SEM) 0.03C, mesovarium -0.28 +/-SEM 0.04C, ovarian artery -0.35 +/- SEM 0.05C and external iliac artery -0.44 +/- SEM 0.06C. All differences are highly significant from zero and do not appear to be related to the time from the onset of anesthesia, the temperature of the gas used to fill the abdominal cavity, the time from the last menustrual period and any pathology present in the pelvis. The results are consistent with a previous suggestion, by Grayson,2 that the human rectal mucosa may be an organ of heat production and that arterial blood within the pelvis may be precooled by counter current heat exchange with veins draining cold blood from the extremities.


Multipronged laparoscopic forceps.

Multipronged laparoscopic forceps. Use of conventional two-pronged forceps in laparoscopic surgery can be problematic. Fallopian tubes tend to slip and ovaries are difficult to grasp securely. In addition, when removing the forceps to obtain an ovarian biopsy specimen prior to cauterization of the biopsy site, the ovary must be released; it is the often difficult to regrasp promptly. Spring-loaded laparoscopic instruments that are provided with multiple prongs offer certain advantages. These instruments hold tissue more securely and with even tension, and with them it requires a minimal effort to maintain tissue in a stable position. The author designed multipronged forceps, which were used for tubal sterilization and ovarian mobilization and biopsy in a series of more than 125 cases. No complications were noted from the use of the forceps.


The control of adult parasitic nematodes of cattle with morantel tartrate. The anthelmintic efficacy of morantel tartrate at 5mg/kg bodymass was investigated in three separate controlled trials comprising 68 calves. High anthelmintic activity was established against adult Haemonchus placei, Ostertagia ostertagi, Cooperia spp. (C.pertinata and C. punctata), Bunostomum phlebotomum and Oesophagostomum radiatum.


Location of the coagulase gene in Staphylococcus aureus. Evidence is presented for the chromosomal location of the coagulase determinant in most strains of Staphylococcus aureus. By the use of a pour-plate technique, transduction of the capacity to produce coagulase to a coagulase-negative mutant of S. aureus was studied. The frequencies of transduction were low unless the transducing phage was exposed to ultraviolet irradiation and the recipient was lysogenised with the transducing phage. Attempts to transfer the coagulase gene from S. aureus to S. epidermidis were not successful.


Possible evolutionary relationships of the nitrogenase proteins. Comparisons of the amino acid compositions of the nitrogenase proteins from different organisms and their correlation with cross-reactivities and taxonomical data suggest an evolution within bacterial genomes rather than within plasmids. Comparisons of the amino acid compositions of nitrogenases and other ATP-ases show similarities which might be due to the evolution of these ATP-ases from a common ancestral protein.


Studies on neuronal lipid.

Studies on neuronal lipid. The procedure for bulk preparation of nerve-cell perikarya from pig brain-stem is briefly described. This method has definite merits with regard to the preservation of the intracellular structures as well as the preservation of the processes. The chemical composition of the isolated nerve-cell perikarya is presented. The nerve-cell perikarya are characterized by the absence of cerebroside and sulfatide. Diffuse distribution of ganglioside on the cell surface is suggested. The lipid content of the nerve-cell perikarya isolated by different methods is discussed. Lipid composition of the invertebrate nervous tissue is discussed. The submicrosomal membranes of rat brain are isolated, and their chemical and morphological properties are discussed. Ribosome-free membranes are characterized by the high content of glycolipids including gangliosides, as well as by the high activity of Na, K-ATPase, whereas ribosome-bound membranes are characterized by the absence of glycolipids, as well as by the low activity of Na, K-ATPase. The molecular organizations of lipid in submicrosomal membranes are demonstrated.


Increased prolactin levels during reserpine treatment of hypertensive patients. Serum prolactin levels are significantly greater among hypertensive patients receiving reserpine as compared to levels six weeks after discontinuing the treatment (P less than .005). This association between regular, long-term reserpine use and greater prolactin levels may be clinically significant, since an increased incidence of breast cancer has been reported among hypertensive patients receiving reserpine.


Effects of La+++, Mn++ and ruthenium red on Mg-Ca-ATPase activity and ATP-dependent Ca-binding of the synaptic plasma membrane. The effects of La+++, Mn++ and ruthenium red (R.R.) on Ca-uptake of synaptic plasma membranes (S.P.M.) were investigated. La+++ (0.1 mM), Mn++ (0.2 mM) and R.R. (0.1 mM) selectively inhibited Mg-Ca-ATPase but did not significantly affect Mg-ATPase activity. The apparent Ki values of La+++, Mn++ and R.R. for Mg-Ca-ATPase were 0.05, 0.06 and 0.03 mM, respectively. La+++, Mn++ and R.R. did not affect Ca-uptake at concentrations which strongly inhibited Mg-Ca-ATPase activity. These results indicate that Ca-uptake by S.P.M. differ from that by sarcoplasmic reticulum.


[Electron-microscopic study of the left heart ventricle of rats in the advanced stage of myocardial hypertrophy]. The ultrastructure of the left ventricle was studied in 10 rats, 5 of whom were subjected to partial ligation of the aortic isthmus 9 months prior to the procurement of the material. In 3 of the operated rats cardiac insufficiency was induced by means of additional exercises. Three normal rats could swim for 5 hours running before they got exhausted, 2 rats were intact. The operated animals with signs of cardiac insufficiency exhibited highly distinct ultrastructural changes that did not differ qualitatively from those observed in the acute phase of myocardial hypertrophy. No alterations were noted in the mitochondria, which does not permit to interpret the disorders in the energy balance of the cell as the leading cause of chronic cardiac insufficiency. In chronic cardiac insufficiency the myocardial cells seem to develop physiological disturbances undetectable by electron microscopy that may be the cause of cardiac failure. This is supported by the appearance of gross changes in the myocardium on the advanced stages of hypertrophy even after insignificant additional exercises.


[The effect of sudden changes in the stimulation rate of the heart on peak systolic pressure (author's transl)]. The changes in systolic pressure were studied in 48 patients during artificially (by electrical stimulation) induced sudden increases and consecutive decreases in heart rate. Various patterns could be separated respective to phase A (sudden switch from low (80-120 impulses/min) to higher heart rate (140-180 impulses/min)) and to phase B (sudden switch-back from high to lower (control) beating rate): AI) The systolic peak-pressure of the first contraction after the shortened stimulation interval is very low and often stays ineffective (below the aortic opening pressure). The second contraction develops already a higher pressure than the first one, during the consecutive beats the systolic pressure increases gradually until a new steady state is reached, which is usually lower than the systolic pressure during the foregoing lower beating rate. Sometimes however it can be equal or even higher. Accordingly after an elevation of heart rate arterial mean pressure can drop, stay constant or increase. AII) The systolic peak-pressure of the first contraction after the shortened stimulation interval stays relatively high and drops continuously with the succeeding contractions until a new steady state is reached according to the higher heart rate, it is however always lower than the one at a lower stimulation rate. Therefore arterial mean pressure is always decreased. AIII) Finally we observed changes in arterial systolic pressure in some patients that could not be grouped according to one or to the other pattern described above.- BI) The systolic peak of the first contraction after the switch-back from the high to the lower (control) rate is much higher than that of the last at the higher rate. The peak pressures of the consecutive contractions are then dropping continuously to the new steady-state, that can be higher, equal or lower than that at the higher stimulation rate. BII) ....


Transmissible mink encephalopathy. Reduced spongiform degeneration in aged mink of the Chediak-Higashi genotype. Mink which are 18 months or older and are dying of transmissible mink encephalopathy (TME) have been found to have a marked reduction in spongiform degeneration of the brain if they are homozygous for the Aleutian gene and thus exhibit the autosomal recessive disorder known as the Chediak Higashi (CH) syndrome. CH mink younger than 1 year, and young or old non-CH mink have a typical lesion profile with widespread microvacuolation of the neuropile. Whereas aged CH mink have reduced spongiform degeneration at both the light and electron microscopic level, there is no other apparent alteration in the TME disease process. The length of incubation, clinical signs, astrocytic response, and brain concentration of the TME agent are comparable to those seen in non-CH mink. We conclude that spongiform degeneration is a secondary change in TME and speculate that vacuolation may be the result of lysosomal enzymes causing an increase in ganglioside catabolism.


Disposable filters for microaggregate removal from extracorporeal circulation. A comparative study of three commercially available blood filters for use in extracorporeal circuits was made in dogs. All filters were efficient in removing infused microclots from the circulation, but all caused mild thrombocytopenia and two produced minimal hemolysis. In dogs infused with microclots, only those animals without blood filters in the infusing circuit showed evidence of pulmonary microembolism at autopsy. It was concluded that while the filters have minimal disadvantages, their potential in reducing microembolism in extracorporeal circuits far outweighs these disadvantages.


Cor triatriatum: echocardiograhic findings. The echocardiographic findings in a patient with cor triatriatum are presented. The preoperative echocardiogram demonstrated an unusual structure behind the mitral valve that moved anteriorly during atrial systole. There was also echocardiographic evidence of abnormalities of mitral valve motion, right ventricular and left atrial enlargement,  and pulmonary hypertension. Postoperatively, the unusual echo behind the mitral valve had disappeared and the mitral valve appeared more normal. Left atrial and right ventricular dimension had decreased and the pulmonary valve appeared more normal. Fine diastolic mitral valve fluttering, an abnormal echo behind the anterior mitral valve leaflet moving anteriorly with atrial systole, an abnormal pulmonary valve echogram suggesting pulmonary hypertension, and marked right ventricular and left atrial enlargement were the main echocardiographic findings in our patient.


A multifactorial system controlling myeloid cell differentiation and division. It has been demonstrated that mature granulocytes contain two stimulatory and three inhibitory factors of cell proliferation. Consequently, beyond the negative feedback inhibitor (chalone), myeloid cells are controlled presumably by other negative (inhibitory) and positive (stimulatory) mechanisms, in addition.


Enzymes related to lipogenesis in the adipose tissue of obese subjects. In a group of ten adult obese subjects, maintained for 15 days on a normal caloric intake and balanced diet, the activity of hexokinase (EC 2.7.1.1),6-phosphofructokinase (EC 2.7.1.11), and ATP citratelyase (EC 4.1.3.8) in the adipose tissue was significantly increased, both on a protein and on a fat cell number basis, compared to matched normal subjects. The activity of glucose-6-phosphate dehydrogenase (EC 1.1.1.49), malate dehydrogenase (EC 1.1.1.37), and malate dehydrogenase (decarboxylating) (NADP) (EC 1.1.1.40), on the other hand, was unchanged. Since both hexokinase and 6-phosphofructokinase are rate-limiting in glycolysis, their enhanced activity would indicate the occurrence of an increased capacity to metabolize glucose and therefore to generate alpha-glycerophosphate. The elevation of ATP citrate-lyase would suggest increased lipogenesis, owing to the regulatory role that this enzyme plays in fatty acid synthesis. The normal activity of glucose-6-phosphate dehydrogenase and malate dehydrogenase (decarboxylating) (NADP), which supply NADPH for the reduction of acetyl-CoA to fatty acids, would suggest that the change in lipogenesis is of moderate degree, thereb) affecting only the most rate-limiting enzyme, ATP citrate-lyase. These data, on the whole, are consistent with the occurrence of enhanced triglyceride formation. Whether the enzyme changes observed are adaptive or genetic in nature remains to be clarified.


Non-steroid skin cream in traumatic dermatoses: A clinical open evaluation. Attention is drawn to the unwanted side effects of the long-term topical use of steroids on the skin. The topical use of steroids in conditions in which immunological factors are not involved is not necessary. An open clinical evaluation demonstrated that simple protective applications are quite effective in these conditions.


Clonazepam in the treatment of choreiform activity. In a limited study, clonazepam, a new benzodiazepine derivative, has been found to be effective in suppressing choreiform movements in three patients with Huntington's chorea, three patients with non-familial chorea, and in one patient with senile chorea. In two patients with chorea of doubtful aetiology the response was not very satisfactory. A simple method was used to assess objectively the effect on choreiform movements. The effective dose varied from 3-5 to 5-5 mg a day. The drug was well tolerated by most of the patients.


Amino acid replacement in the protein S5 from a spectinomycin resistant mutant of Bacillus subtilis. Ribosomal protein S5 was isolated from wild type Bacillus subtilis ATCC 6633 and from a spectinomycin resistant mutant (BSPC 111) derived from spectinomycin sensitive to resistance is accomtrypsin and all the tryptic peptides were isolated by column- and paper-chromatography. By comparative amino acid analyses of the peptides, it was demonstrated that the S5 from the mutant differs from the wild type S5 by a replacement of one amino acid, namely lysine by isoleucine in the peptide T9. The results are compared with E. coli spectinomycin resistant mutants.


Relationships between specialized cells, capillaries and intermediary cyto-fibrillary stroma. Note 6. The capillary stereotype and the factors which influence it. The human skin and the mammary gland in the woman and the man--all of them ectoblastic-origin tissues, rich in stromal structures and belonging to the IIIrd step of Mârza's classification (Vth note) -- were investigated using the method of the microscopic conventional fields. The normal skin (Ist lot), the skin from the vicinity of basaliomatous nodules (II--A), of incipient basaliomatous nodules (II--B), of completely developed (II--C), of the skin during irradiation (II--D) and after irradiation (II--E), as well as the pemphigus skin were studied. In the woman the mammary gland was investigated in the little girl (GMF), in the adult nonpregnant woman (GMA), during the first trimester of pregnancy (GMG), during lactation (GML), during climacterium (GMM), in glandular carcinomas of the adult female (GMAC) and during menopause (GMMC). In the man, the normal gland (GMB) and the hypertrophied one (gynecomastia) (GMBH) were studied.


Researches on the macrophage reaction in embryonic necrotic foci by means of cell cultures. Macrophage transformation of the fibroblasts and the attraction of macrophages in cell cultures of chick embryo have been investigated. Cultures were treated with choline hydrochloride, DNA, lactalbumine hydrolysate, lysine, peptone and ATP. An intense agglomeration of macrophages in the contact area with the agar gel containing choline could be observed. Cultures treated with DNA have a great number of macrophages together with a numerous fibroblast population. In cultures treated with the other substances, macrophages also appear, yet their number is not so great. The results obtained plead for a triggering of the macrophage reaction and of the necrosis in embryo tissues and organs by substances identical or similar to those used in our cultures.


In vitro growth peculiarities of some human ovarian tumours. The possibility of applying a short duration method of in vitro cultures for detecting malignancy of ovarian tumours with borderline lesions and with incipient malignant ones was investigated in 24 ovarian tumours. Three main types of histocultures were described in relation with the in vitro behaviour of ovarian tumours and their cytomorphology (atypic growth, mixed growth and normal one). The category of mixed type growth cultures is discussed, corresponding to ovarian tumours with histopathological borderline lesions, with incipient malignancy, as well as two cilio-epithelial cystadenomae rendered malignant with peritoneal seedings.


Relationships between the lung mesenchymal cell populations: concurrent elicitation by air and blood ways of the lung reacting cell systems. Some relationships between the lung reacting cell populations connected to the air and blood ways are investigated by elicitation with proteins in Freund's adjuvant and with SiO2. The agents were intratracheally and respectively intravenously injected into rabbits concomitantly or in different orders and times. The developmental analysis of the alveolar silicotic nodules and of the proteolipidic perivascular ones pointed out the involvement of both reacting cell systems in relation with the administration route, the involvement of local cells only, when the agent is less active and the arrival of blood mononuclears when the agent is more active. A concurrent taking part of the reacting cell systems in the process is demonstrated. The immune phenomena developed by both the used agents also elimine numerous cells from the formation process of nodules, and allow the production of hypersensitive reactions of the immediate and cellular type which influence the integrity and cellularity of formed nodules. The relationships between these two reacting cell systems of the lung appear to be not only quantitative but also qualitative.


[Alcoholic Cardiomyopathy (author's transl)]. Alcoholic cardiomyopathy is a consequence of toxic effects of ethyl alcohol. Acute effects must be distinguished from chronic effects over many years. Chronic abuse of alcohol of 1.5-2 g ethyl alcohol per kg body weight (i.e. about 100-150 g/70 kg) per day for years can cause congestive cardiomyopathy in predisposed persons, usually between 30 and 50 years of age. The diagnosis is associated with some criteria for exclusion, i.e. coronary heart disease, hypertension, valvular heart disease, in addition all obstructive and restrictive cardiomyopathy must be excluded. On the other hand, a specific constellation of findings can be considered characteristic of alcoholic cardiomyopathy, namely the coincidence of a radiologically established cardiomegaly in the form of a congestive cardiomyopathy with a raised serum concentration of immunoglobulin A and a negative myocardial immunofluorescence test. Therapeutically, in addition to the classical principles of the treatment of heart failure, absolute abstention from alcohol and physical stress seemed to be effective.


Enrichment for auxotrophic and heat-sensitive mutants of Neurospora crassa by tritium suicide. Tritium suicide is shown to be an effective technique for mutant enrichment in Neurospora crassa. When mutagenized conidia were labelled to a high specific radioactivity either with a tritiated amino acid mixture or with [5-3H]uridine at a non-permissive temperature and stored at 4 degrees C to accumulate decays, there was a 13-15 fold enrichment for temperature-sensitive mutants relative to the original mutagenized cultures. For a wild type culture of Neurospora crassa labelled with [5-3H]uridine at 35 degrees C the probability of cell killing per tritium decay was calculated to be 3.64 X 10(-5).


Functional and metabolic studies on red blood cell sodium transport in chronic uremia. Red blood cells from 7 out of 13 patients with chronic uremia were found to have increased intracellular concentrations of sodium associated with a reversible inhibition of ouabain-sensitive Na efflux when incubated in control plasma. Although mean Na-K-ATPase activity of RBC hemolysates was only moderately decreased (21.8 +/- 1.5 vs. 26.5 +/- 1.8 nmol Pi/mg protein/h), enzyme kinetics revealed a significant increase in KmATP values for this enzyme in uremic RBCs (1.01 +/- 0.1 vs. 0.58 +/- 0.03; p less than 0.001) which was closely correlated to serum creatinine concentration (r = 0.9034). While aerobic glycolysis was unaltered, an increase in glucose-6-phosphate dehydrogenase activity was observed, i.e. the enzyme initiating the pentose-phosphate cycle. In addition, intracellular ATP concentrations of uremic RBCs were significantly higher than ATP concentrations of control RBCs (2.13 +/- 0.22 vs. 1.32 +/- 0.06 mmol/l RBC; p less than 0.01). These data suggest that high intracellular concentrations of Na and ATP in uremic RBCs partially result from a competitive reversible inhibition of the transport ATPase by uremic toxins.


Endemicity of multiple staphylococcal phage types: relation of two common source outbreaks. An outbreak of Staphylococcus aureus bacteremia occurred among patients treated in the hemodialysis unit in 1971. A second outbreak of S. aureus peritonitis occurred in 1973 in patients with chronic indwelling peritoneal catheters cared for together in the medial intensive care unit. Although the attending personnel, patients, and geographical locations were different in each outbreak, the following similarities were notes: (1) more than one phage type was epidemic: (2) an exogenous mode of spread with cross-contamination between personnel and patient as well as between patient and patient, and (3) breaks in sterile technique when handling the arteriovenous shunt site or the peritoneal catheter were made without the staff conducting the procedure being aware of their occurrence. Culture surveys of the same phage types found during the two epidemics. Thus, an endemic reservoir of several different staphylococcal phage types was present. Careful, consistent application of aseptic technique when handling either arteriovenous shunts or peritoneal catheters and hand washing in between patients was required to prevent the endemic strains from becoming epidemic.


Regression of Polycystic Ovaries by Estrogen Therapy. Adolescent girls and single women with progressive hirsutism due to polycystic ovaries present a therapeutic dilemma. Clomiphene citrate is useful only to induce ovulation and has no beneficial effect on hirsutism. Surgical wedge resection of these ovaries usually arrests progression of hirsutism and restores ovulatory menses. Such treatment, however, is best reserved until such time as pregnancy would be an equal objective. Treatment of 5 patients by hypothalamic-pituitary-ovarian suppression with 100-mg estradiol pellets implanted subcutaneously every 6 months reduced ovarian size in all 5 patients and halted the progression of hirsutism.


Biochemical and Clinical Effect of Ovarian Wedge Resection in the Polycystic Ovary Syndrome. Twelve patients with histologically verified polycystic ovary syndrome were investigated with special regard given to the effect of wedge resection on androgen status. Adrenal disorders were excluded in every case by determination of cortisol and corticosterone metabolites. Prior to and at least 6 months after surgery all patients were subjected to adrenal stimulation followed by adrenal suppression and ovarian stimulation. Comparison between pre- and postoperative studies revealed that only an insignificant reduction in the excretion of 17-ketosteroid had occurred and, although at lower levels, the stimulatory effect of hCG on ovarian androgens was still present. Clinically, 10 patients had had regular periods at followup, and 3 had become pregnant. In no case had hair growth slowed, bu the rate had declined. Seemingly, wedge resection does not significantly influence the biochemical pattern connected with the polycystic ovary syndrome.


Omental herniation. An unusual fetal complication of intrauterine transfusion. Amniocenteses in an Rh-sensitized woman revealed the need for intrauterine transfusion to improve fetal status. Following delivery of the infant by cesarean section 7 weeks later, herniation of a segment of omentum through the anterior abdominal wall was noted. The injury was due to needle puncture during the intrauterine transfusion. The injury was repaired, and the infant recovered.


Laparoscopy. A clinical sign for intraperitoneal needle placement. Experience with a new clinical sign for proper Verres needle placement is reported. Although the use of one or more tests to confirm accurate needle position have become standard, most complications associated with laparoscopy still result from inaccurate or extraperitoneal needle placement. This new sign, when present, has proven completely reliable and should aid laparoscopists in reducing the incidence of needle complications.


Birth defects involving the spine.

Birth defects involving the spine. There is a multiplicity of birth defects of the spine occurring as isolated anomalies or as aspects of multifaceted syndromes. The clinical significance of these anomalies varies from the asymptomatic to the life threatening. Symptoms and signs may present at birth or not until years later. The optimal clinical result for the patient requires a careful history and physical examination, appropriate routine and specialized roentgenograms, laboratory data, and a high index of suspicion for signs or symptoms of neurological dysfunction. When the diagnosis is made, conservative or surgical treatment may be instituted as appropriate.


[Production of antihaptene antisera. Comparison of methods of immunisation (author's transl)]. Five immunogenic substances were injected to rabbits. The method of immunisation by the intradermal route at 30 to 50 different points, with low doses of immunogen, without booster, does not seem to lead to production of antiserum of great specificity. The choice of the dose of immunogen to be injected is difficult, owing to our ignorance of the immunogenic dose for a given immunogen. The method of immunisation by the subcutaneous route with high doses followed by a booster, leads to more constant results, comparable to those obtained by the first method to which one may associate boosters by the subcutaneous route. The titers, affinities and specificities of the antisera thus produced are sufficient for the development of radio-immunoassay. The characteristics of the antisera obtained, related to the quality of the immunogen, do not seem to depend on the method of immunisation.


On deciding the care of severely handicapped or dying persons: with particular reference to infants. Two philosophies of deciding the care of severely handicapped or dying persons are commonly used. The first is "disease-oriented" which places death in the extreme negative position. The second is "person-oriented" which regards some kinds of severely compromised living as worse than death. The first philosophy is convenient for the development and the use of medical technology but its unbridled application commonly dehumanizes patients and aggravates suffering. The second philosophy may protect persons from the indignities of pointless treatment or the cruelties of disease. But its use in some respects is illegal and may be unwise; also, in caring for infants, children, and incompetent adults, the second philosophy creates special problems since the patient himself cannot participate in decision-making. In deciding which philosophy to follow in a given situation we believe the patient (when able), the sorrowing family, and the concerned physician are the best judges. Since these persons vary widely, they must be entrusted with more freedom to change or to ignore commonly accepted principles if the values of patients and families in the many unique situations of living, illness, and dying are to be protected. We believe with few exceptions that these persons are now worthy of this trust and with experience they would use it with growing wisdom.


A comparative study of skeletal and cardiac tropomyosins: subunits, thiol group content and biological activities. The subunit composition, the thiol group content and the biological activities of cardiac tropomyosins (TM) of various animal species were compared. Cardiac TM from small animals such as rabbit, guinea-pig, rat and dog contain 2 SH/mole and were resolved into one band on SDS and acid urea electrophoresis and into two bands on alkaline urea electrophoresis. Chicken cardiac TM likewise gave one band and it contains 4 SH/mole. In contrast pig, sheep and human cardiac TM contain respectively 2.6, 2.4, and 2.4 SH/mole and were resolved into two bands alpha and beta on the different electrophoresis systems used, with a beta:alpha ratio respectively of I:4.2, I:4.6, I:4.8. The alpha-TM components from sheep skeletal and pig and sheep cardiac muscles were more positively charged than the rabbit skeletal alpha-TM component, as shown in alkaline urea electrophoresis system. The alphaalpha and alphabeta combinations of dimers found for skeletal muscle by other authors, were also found for cardiac pig TM. All the TM have the same effect on the Ca2+-stimulated ATPase activity of desensitized actomyosin (DAM) and on the Mg2+-stimulated ATPase activity of DAM with troponin-complex. This work suggests that the subunits of the TM from skeletal and cardiac muscles are heterogenous in their M.W. and their charges and that in the heart as well as in skeletal muscle a relationship seems to exist between the amount of the beta component and the speed of contraction of the muscle: a higher amount of this component was found in the bulky hearts which are also those which contract slower.


Extracorporeal magnet perivascular electromagnetic flow meters. The "interrupted resonance" circuit proved effective in combination with an extracorporeal magnet in permitting electromagnetic blood flow measurements to be made in branch arteries of dogs by application of perivascular cuffs equipped with pick-up electrodes contacting the vessel wall. A four-turn coil, acting as a transformer secondary measures the amplitude of the magnetic field component which is effective in inducing the flow signal and thus permits calibrations for arbitrary orientations of the perivascular cuff relative to the magnetic field of the extracorporeal magnet. Recordings of mean and phasic blood flow in dogs' arteries provide illustrations of effectiveness in pharmacological studies and exhibit the reliability of the non-occlusive zero-flow base line obtained by de-energizing the magnet.


Comparison of two concentrations of tretinoin solution in the topical treatment of acne vulgaris. In patients with facial acne good results were obtained by topical treatment with a 0-05 per cent solution of retinoic-acid (tretinoin) solution and with a 0-025 per cent solution. The improvement was judged by clinical assessment and by counts of comedones, papules and pustules before and after the 12-week trial. Side-effects such as irritation and erythema were less with the 0-025 per cent solution. The use of swabs impregnated with a constant volume of solution and sealed in a sachet proved to be a convenient method of application.  In the placebo group, swabs impregnated with the solvent only showed virtually no effect on facial acne.


The value of electrocardiography in routine health screening. Electrocardiograms recorded at rest in 4000 consecutive subjects who were clinically well at the time when they first attended a health screening centre for routine medical examination were analysed. In 9.5 per cent there were electrocardiographic abnormalities. The number in whom this abnormality was previously unsuspected represented 8.5 per cent of the total number of subjects. Previously undiagnosed ischaemic heart disease was found in 1.9 per cent but, excluding the subjects with chronic ischaemic heart disease, 1.8 per cent of all those who attended the Centre derived benefit from this single test, as it directly influenced their future clinical management.


Hypertrophy and hyperplasia of somatostatin-containing D-cells in diabetes. Insulin-, glucagon-, and somatostatin-contianing cells, identified by immunofluorescent staining, were quantitated morphometrically in sections of pancreas obtained from diabetic and nondiabetic humans and rats. Both the volume density and number of somatostatin- and glucagon-containing cells were significantly increased in the islets of juvenile-type human diabetics and of streptozotocin diabetic rats.


In vitro correction of Hurler fibroblasts with bovine testicular hyaluronidase. Bovine testicular hyaluronidase (endo-beta-N-acetyl hexosaminidase) has a significant corrective effect on cultured Hurler fibroblasts. Nonspecificity of this effect is indicated by its equally strong corrective effect on Hunter fibroblasts. Although all specimens of hyaluronidase also possessed iduronidase activity, a separate corrective effect could be attributed to the endo-N-acetyl hexosaminidase activity of at least one hyaluronidase (Wyeth M-151) for four reasons: (i) its very low content of iduronidase activity; (ii) a decrease in intracellular macromolecular mucopolysaccharides (believed to be largely dermatan sulfate) with a corresponding increase in intracellular and extracellular oligosaccharides; (iii) no measurable increase in iduronidase activity of hyaluronidase-treated cells despite near maximal correction; (iv) direct correlation between Hurler cell correction and hyaluronidase activity when enzymes of different strength were used at less than maximal correction.


Biochemical and ultrastructural correlates of substrate stimulation of renal organic anion transport. Penicillin pretreatment enhanced the rate of PAH uptake into separated proximal tubules (collagenase digestion) from 2-week New Zealand white rabbits. A double reciprocal plot of these data suggests that penicillin increases the maximal velocity of PAH uptake. Na, K-ATPase was less in adult tissue but was unaffected by penicillin. No ultrastructural changes could be attributed to the treatment. Thus substrate stimulation of PAH transport does not involve Na, K-ATPase and probably involves soluble, rather than structural proteins.


Effect of calcium on RNA and protein synthesis in the hypertrophied myocardium. Myocardial protein synthesis was elevated 7 days after rats were subjected to experimental aortic outflow obstruction. Although RNA synthesis was not increased at this time, RNA concentration was elevated and may have provided for the observed increase in protein synthesis. A possible basis for the persistence of the high RNA levels was a decrease in the degradation of RNA. The increase in intracellular calcium observed in hypertrophied tissue may be involved in the maintenance of RNA concentration and in the increased rate of protein synthesis.


Effect of harmine and brain lesions on apomorphine induced motor activity. Application of harmine (10 mg/kg IP) 30 min before apomorphine decreased the motoric effects of the latter. Following harmine an increase in 5-HT and a decrease in 5-HIAA in different brain regions have been found. Injection of 5,6-DHT into nucleus medianus raphe 7 days before the experiment caused a significant increase of the apomorphine effect. Harmine pretreatment reduced this escessive motility as well as additional lesion of the substantia nigra with 6-OH-DA. Lesion induced by 6-OH-DA alone was without significant effect on the hypermotility following apomorphine. Application of PCPA 3 days before testing elicited an increase of apomorphine-induced hypermotolity which could be abolished by preceding harmine application. The experiments demonstrate the inhibitory effect of the central serotoninergic system on the apomorphine syndrome as well as the serotoninergic-dopaminergic interaction in hypermotility.


Effects of p-chlorophenylalanine on the predatory behavior of Onychomys torridus. Adult male and female grasshopper mice, Onychomys torridus, were treated over a 5 day period with p-chlorophenylalanine (50 mg/kg daily), a depletor of brain 5-HYDROXYTRYPTAMINE (5-HT). These mice exhibited a significant decrease over the 5 day test interval in predation time and predation score in encounters with cricket prey, However, the basic pattern and frequency of attacks for drug-treated mice remained similar to saline controls. The relation between the various brain amine systems and predatory behavior is discussed and the utility of the grasshopper mouse as a laboratory model for the study of predatory behavior is emphasized.


Effects of vestibular stimulation on nystagmus response and motor performance in the developmentally delayed infant. The effects were studied of 10 days' exposure to daily repetitive, specific vestibular stimulation on motor performance of children with Down's syndrome and normal children. A quantitative assessment of vestibular function was made in these children including the habituation response of postrotatory nystagmus. Control groups were included. Both the children with Down's syndrome and the normal children who received vestibular therapy demonstrated positive effects when evaluated using a quantitative motor skills assessment test. Control and treatment children showed vestibular habituation, with treatment children evidencing the greater change. This change may reflect the acquisition of an increased level of central nervous system inhibitory control.


Effects of parachlorophenylalanine and amphetamine on habituation of orienting. Parachlorophenylalanine significantly reduced the orienting response to the first presentation of a tone but did not alter the size of responses to subsequent tone presentations nor the rate of habituation. In contrast amphetamine did not alter the orienting response but significantly impaired habituation. It was concluded that there was little evidence for a serotonergic involvement in behavioral habituation, although a role for the catecholamine system could not be excluded.


Effect of sodium intake on aldosterone and corticosterone production, the serum sodium concentration and body weight in infant rats during weaning period. 1. The effect of a low salt (LS, 0.3% NaC1) and control (HS, 1% NaC1) diet on in vitro aldosterone and corticosterone production, the serum corticosterone level, the serum sodium concentration and adrenal and body weight was studied in 30-day-old male rats, some of which were weaned prematurely at the age of 15 days (PW) and some left with the female up to the end of the experiment (NW). 2. Aldosterone production in the control (HS-NW) animals was 1.07+/-0.07 mug/100 mg adrenal/hour (mean +/-S.E.M.), in HS-PW animals 0.6+/-0.07 (P less than 0.01), while in LS-NW and LS-PW animals it rose to 1.59+/-0.1 and 1.81+/-0.14 respectively. The effect of the salt regimen was significant in both the NW group (P less than 0.01) and the PW group (P less than 0.01). Premature weaning did not inhibit aldosterone production in LS-PW animals. 3. Corticosterone production in animals fed on the control diet was 1.81+/-0.16 mug corticosterone/100 mg adrenal/hour in HS-NW rats and 0.91+/-0.09 in the HS-PW group (P less than 0.01). On the low salt diet it fell to 1.4+/-0.11 in LS-NW rats (HW-NW) vs LS-NW: P less than 0.01) and to 0.4+/-0.06 in LS-PW animals (HS-PW vs LS-PW: P less than 0.01). The difference between LS-NW and LS-PW was likewise statistically significant (P less than 0.01). Changes in production were not accompanied by parallel changes in the serum corticosterone level, where an analysis of variance showed no significant difference. 4. The low salt diet reduced the serum sodium concentration in both NW and PW animals (HS-NW 132.9+/-0.86 mEd HS-PW 132+/-0.86, LS-PW 128.5+/-1.16: P less than 0.01). The differences between NW and PW animals were not significant. 5. A low salt intake also reduced the body weight both of animals left with the female (HS-NW vs LS-NW: P less than 0.01) and of prematurely weaned animals (HS-PW vs LS-PW: P less than 0.01). Early weaning significantly affected body weight in LS animals only, the body weight of LS-PW animals being significantly lower than that of LS-NW animals (P less than 0.02). 6. The results show that infant rats are hypersensitive to a low salt intake at the end of the weaning period and that this phenomenon is not mediated by lower reactivity of the zona glomerulosa and of its regulation.


Foetal and neonatal development of evoked responses in guinea-pig auditory cortex. Development of the response of the auditory cortex to unilateral acoustic stimulation by a chick was studied in guinea-pig foetuses from the 50th day to the end of gestation and in newborn animals. The first cortical response appeared on the 52nd to 53rd day of gestation. The maximum responses were concentrated in the temporal cortex, between the somatosensory (parietal) and optic (occipital) area. The progressive development of the latent period of the cortical response and of its various components distinctly slowed down on the last days of gestation. At the same time, the amplitude of the cortical response was temporarily augmented. The cortical response developed from a simple negative wave in the youngest embryos into an intricate complex with an initial positive component in newborn guinea-pigs. The basic components of this complex were already discernible on the 64th to 65th day of gestation. The ability to react to repeated peripheral stimulation of 0.1-2 c/s frequency increased with foetal age, with temporary deterioration on the last days of gestation. Resistance of the cortical auditory response to cerebral anoxia rose up to term, with a temporary drop from the 64th day of gestation. After the initiation of independent respiration, cerebral hypoxia and bilateral vagotomy chiefly influenced the stability of the more recent components of the cortical auditory response in mature foetuses.


Effect of long-term hypoxia upon the activity of some enzymes in the brain of rats during early postnatal ontogenesis and in adulthood. Enzymatic activities were determined in the prosencephalon of rats which had been exposed repeatedly for 8 hrs, either from the age of 1 to 17 days or in adulthood, to an altitude of 7,000 m in a barometric chamber (up to a total of 104 hrs). The activity of enzymes was assayed 20 hrs after the last exposure. The results were compared with values obtained 20 hrs after a single 8-hour exposure to a stimulated altitude of 7,000 m in 17-day-old and adult rats. In young rats a single exposure to hypoxia, the most elevated was the activity of LDH and isoCDH, while GPT and CPK were decreased. After repeated hypoxia, the most significant increasw was noted in the activity of PK and again a decrease in GPT and CPK. In adulthood, a single exposure to hypoxia causes the greatest increase in CPK, while LDH and GOT are reduced. Following repeated hypoxia, none of the enzyme activities were increased by more than 20%, while LDH, GOT, GIDH and CPK were again lower. It is concluded from these results that a single exposure to hypoxia increases anaerobic glycolysis in the immature nervous tissue and improves its oxygen utilization. The relationship between glycid and amino acid metabolism are not appreciably altered. On the other hand, a general reduction of bioenergetics and biosynthesis occurs in adulthood. Repeated hypoxia, on the contrary, has similar after-effects in both age groups, namely inhibition of aerobic metabolism and of the relations between glycid and amino acid metabolism.


Effect of stagnant hypoxia on acid ribonuclease activity in the rat prosencephalon during ontogenesis. In the rat prosencephalon it proved possible to differentiate lysosomal ribonuclease from alkaline ribonuclease activity, which could be detected only in the presence of p-chlormercuribenzoate. Acid RNase activity related to the amount of protein in the prosencephalon fell during ontogenesis. It was not significantly affected by four hours' stagnant hypoxia induced by ligation of both carotids. Its release from the lysosomes rose, however (when isotonic homogenates were spun at 20,000 g, acid ribonuclease activity in the supernatants was elevated). The absence of correlation between this activation and the degree of maturity of the nervous tissue refutes the hypothesis that regulation of this enzyme is per se responsible for the known changes induced by hypoxia in the RNA content of the prosencephalon of rats of different ages. On the contrary, the results indirectly support studies which demonstrate changes in the extent of RNA synthesis after hypoxia.


Changes in the activities of blood and tissue adenosinetriphosphatase and lactate dehydrogenase after exposure to 60Co gamma-rays in association with some drug treatments. Experiments in rats exposed to a moderate dose of 60Co gamma-radiation and treated with either cystamine, AET, complamin or alpha-methyldopa suggested that the efficiency of a radioprotective drug might be related to its ability to maintain low levels of ATP-ase activity in blood and tissues after irradiation.


Effect of different environmental temperatures on the serotonin concentration and turnover in the brain stem of a hibernator. The serotonin (5-HT) and 5-hydroxyindoleacttic acid (5-HIAA) levels and 5-HT turnover were studies in the brain stem of warm- (+30 degrees C) and cold- (+6 degrees C) acclimated golden hamsters, exposed for 3 hours to temperatures of +6 degrees C, +30 degrees C and +37 degrees C, respectively. In war-acclimated hamsters kept under conditions the 5-HT level in the brain did not change significantly during the year. The 5-HIAA level was slightly higher in the winter. The 5-HT turnover varied within limits of 0.071 to 0.180 mug/g/hour-1. Three hours' exposure of warm-acclimated golden hamsters to cold (6 degrees C) increased the concentrations of 5-HT and 5-HIAA and the 5-HT turnover in the brain. After long-term adaptation to cold (6 degrees C) the 5-HT level, and the 5-HT turnover returned to the original level. Three hours' exposure of golden hamsters to higher environmental temperatures (warm-acclimated individuals to 37 degrees C and cold-acclimated individuals to 30 degrees C) also increased the 5-HT turnover. The concentrations of 5-HT and 5-HIAA increased in cold-acclimated golden hamsters exposed to 30 degrees C and was not changed in warm-acclimated ones, exposed to 37 degrees C. Although the elevated temperatures induce greater changes in serotonin metabolism than lowered temperatures, the serotonin pathways in the brain do not seem to be affected by short-term temperature changes specifically. The findings are rather indicative that changes in 5-HT turnover may be the primary reaction to stressful conditions.


Independence of changes in contraction properties and myofibrillar ATPase activity of denervated mammalian muscle on length of nerve stump. 1. Contractile properties of the fast extensor digitorum longus of one-month-old rats and of the fast peroneus longus muscles of adult rabbits were studied in vitro at 36 degrees C after nerve section close to the muscle. Changes in contraction properties (prolongation) are not observed until 48 hours after denervation in the rat and 14-30 days in the rabbit. 2. At no period after denervation are differences in twitch isometric contraction properties dependent on the length of the sectioned nerve stump. This lack of dependence of contractile behavior after denervation is in contrast to many metabolic changes which show a clear dependence on the length of the nerve stump. 3. It is concluded that the onset of denervation changes in contractile behavior are related to the loss of nerve-impulse activity, while the transient early metabolic changes are related to changes of fast axoplasmic flow, initiated after nerve section and therefore dependent on length of sectioned nerve stump.


Interaction of visceral and somatic afferentation at the level of postsynaptic spinal cord elements. The interaction of visceral and somatic afferentation at the level of postsynaptic spinal cord elements was studied in cats. The effect of conditioning stimuli on the propriospinal (PS) and suprasegmental (SS) component of the tested unit responses was compared. Afferentation from the splanchnic nerve completely inhibited the SS component of somatomotor motoneuronal responses; the PS component was only partly inhibited. Inhibition persisted even after the conditioning stimulus-induced changes in the membrane potential of the motoneurones had disappeared. The activity of the interneurones responsing synchronously with the SS component of the efferent discharges was also completely inhibited in the same intervals. The inhibitory effect of splanchnic afferentation on the PS component of interneuronal discharges evoked by the stimulation of somatic afferents was significantly less effective. The results of interaction for test responses from the cutaneous and muscular nerves was the same. When splanchnic responses were tested during conditioning from somatosensory areas, inhibitory control was found to be reciprocal. The authors discuss the question of the structures and mechanisms participating in functional relations between the autonomic and somatic nervous system in the spinal cord.


Cortical afterdischarges during Leao's cortical spreading depression. Cortical spreading depression (CSD) has been employed in unanesthetized curarized rats, in order to analyse the role of the cerebral cortex in the generation of epileptic self-sustained parozysms produced by direct cortical electrical stimulation. CSD was preferred because it is reversible and may be repeated several times in the same animal. CSD evoked in the hemisphere contralateral to the stimulated cortex decreased the duration of the afterdischarge by 40% and modified its form and amplitude both at the cortical and reticular levels. The possible role of cortical and subcortical structures in the development of after-discharges is discussed.


Effect of insulin hypoglycaemia on adrenocortical function and blood plasma vitamin E and cholesterol levels in suckling and weaned piglets. Suckling piglets aged 28-31 days and weaned piglets aged 46-60 days were injected with insulin at a rate of 1 U/kg body weight to induce hypoglycaemia. All the animals were blood-sampled before and 45 and 90 minutes after the insulin injection. Both groups developed a marked adrenocortical response without any significant differences, though the rise in plasma 17-hydroxycorticosteroid (17-OHCS) levels of weaned piglets was slightly delayed. Plasma vitamin E concentration showed a significant rise in suckling piglets and a slight rise in weaned animals; it was not accompanied by an increase in total cholesterol levels. The results suggest that glucocorticoids affect vitamin E metabolism. The values of plasma 17-OHCS, cholesterol and vitamin E levels as well as of blood glucose levels and circulating eosinophil leucocyte counts confirmed differences in these parameters between suckling and weaned piglets.


Trypsin and chymotrypsin activity of the intestinal content in germfree, monoassociated and conventional rabbits. Trypsin (T) and chymotrypsin (CHT) activities in luminal contents of the ileum, caecum and sigmoideum were followed in conventional (6 animals), monoassociated (5) and germfree (5) rabbits by pH-stat automatic titration using p-toluenesulphonyl-L-arginine methylester and acetyl-L-tyrosine ethylester as substrates. In conventional rabbits with complete microbial flora an aborally increasing decline of both proteolytic activities of luminal contents was determined (ileum T 198.2 - CHT 100.0; signmoideum T 10m.2 - CHT 68.8 mrg/g of intestinal content). Monoassociated animals represent a group different from both germfree and conventional animals. Trypsin and chymotrypsin of  intestinal contents were not significantly altered by the presence of megacaecum in germfree rabbits (ileum T 219.2 - CHT 160.2; sigmoideum T 208.8 - CHT 110.8 mug/g of intestinal content). Chymotrypsin in the intestinal contents appears more labile and more affected by microbial flora than trypsin.


Choline acetyltransferase activity in the atria of the rat heart during training bradycardia. The resting heart rate of rats trained for 19 weeks by swimming fell by 24% and the weight of their atria rose by 22%. Choline acetyltransferase in the atria did not alter significantly, however. In association with other findings, this observation supports the view that the bradycardia of training is not due to increased activity of cholinergic cardioninhibitory nerves.


Evaluation of pulse wave morphology by Fourier's harmonic analysis: methodological procedure and results of a physiological test. Evaluation of the pulse wave on five segments of the lower limb by means of Fourier's harmonic analysis showed that the following phenomena can be observed in resting (recumbent) healthy subjects: 1) Almost constant, marked accentuation of the amplitude of the second harmonic in every single spectrum. Tjis can evidently be attributed to the resonance properties of the arterial pathway, as a mechanical oscillating circuit; 2) Distinct dimunution of the amplitudes of further, higher harmonics; 3) When studying the reciprocal amplitude ratio in every single harmonic, from the proximal to the distal segment of the limb, we can observe striking relative augmentation of amplitude in a distal direction, as a manifestation of mounting impedance towards the periphery. This provides good conditions for the prevention of rebounds and of undesirable stationary waves.


The hair melanosome: another tissue reservoir of zinc. Melanosomes were isolated from human and dog hairs and their Zn content was determined. The mean Zn concentrations, in mug Zn/g dry weight, were 687 (men's melanosomes), 641 (women's melanosomes) and 691 (dog melanosomes). These values rank melanosomes from pigmented keratinous structures among the structural elements with the highest Zn content. An interpretation of the possible causes of this accumulation was submitted. By means of the conversion factor between hair length and weight (determined at 0.004), it was estimated that daily Zn lossess via hair vary in the region of 19 mug. In detailed studies of Zn metabolism, excretion via pigmented keratinous structures ought not to be neglected.


Acoustic and somatosensory evoked responses in the brain hemispheres of chick embryos. The author explored the auditory projection in the brain hemispheres of 16- to 21-day-old chick embryos, using biaural stimulation, and the somatosensory projection, using electrical stimulation of the contralateral sciatic nerve. The first auditory evoked responses appeared on the surface of the hemisphere at the beginning of the 18th day of incubation and were localized in its mediolateral part. Up to hatching, the latent period of the surface response shortened from 76.3 msec to 28.9 msec and its amplitude augmented from 10.6 muV to 36.2 muV. If the electrode was plunged into the tissue, the evoked responses with the optimum latent period and amplitude parameters were recorded at a depth of 2-2.5 mm (latent period 20.2 msec, amplitude 40-45 muV). The maximum surface somatosensory responses were found in the medial occipital quadrant of the contralateral hemisphere. They developed from the second half of the 17th day of incubation. Up to the end of incubation the mean latent period shortened from 58.3 msec to 21.6 msec and the mean amplitude increased from 11.8 muV to 28.7 muV. What was at first a simple negative wave developed into a positive-negative complex by the end of incubation. Evoked responses at a depth of about 3.5 mm from the surface of the hemisphere had the optimum parameters (latent period 18.4 msec, amplitude 30.2 muV).


Influence of nasal respiration upon normal EEG and epileptic electrographic activities in frog and turtle. The electrographic respiratory response (ERR) was elicited by nasal air flow in the brain of the frog and turtle. It had the shape of a spindle of high voltage rhythmic activity and was propagated from the olfactory bulb predominantly into the ipsilateral hippocampal region in the frog and into the pyriform cortex in the turtle. In both animals, thalamic propagation of the ERR was also found. In both animals epileptic electrographic phenomena, were enhanced, created by local penicillin application. In the turtle epileptic electrographic manifestations were also elicited in the intact brain by simple nasal air insufflation. Diazepam (intraperitoneal administration) had no effect either on the ERR or on its triggering effect on epileptic phenomena. The possible physiological and pathophysiological interpretations of these findings are discussed.


Optimum conditions for the oxidation of palmityl-carnitine by the mitochondria of rat brown adipose tissue. The optimum conditions for maximum oxidation of palmityl-carnitine by mitochondria isolated from the brown adipose tissue of 10-day-old rats was studied. The findings were as follows: 1. Reduction of the sucrose osmolar concentration to below 100 mM activates the rate of palmityl-carnitine oxidation, the maximum effect being achieved with 25 mM sucrose. These hypotonic conditions lead to enlargement of the matrix compartment, but not to swelling of the whole mitochondria. The maximum respiration rate in 25 mM sucrose can be measured only with fresh mitochondria isolated less than 1 hour previously, which must be preincubated 5 minutes in hypotonic sucrose before adding palmityl-carnitine. 2. When inducing the maximum palmityl-carnitine oxidation rate in 100 mM KC1 medium the preincubation time must be prolonged to at least 8 minutes. The length of time for which the mitochondria are stored in isotonic sucrose at 0 degrees C does not affect the respiration level in the presence of K+ ions. 3. The optimum palmityl-carnitine concentration is the same for oxidation measured in hypotonic sucrose and in KC1 medium and ranges from 15 to 50 muM. 4. If the above conditions are observed, the maximum palmityl-carnitine respiration values in hypotonic sucrose and medium with K+ ions are the same, whereas in isotonic sucrose respiration is inhibited. The same applies to the oxidation of endogenous fatty acids by the carnitine route and to alpha-ketoglutarate respiration, while the oxidation of alpha-glycerolphosphate is not affected by the osmotic conditions and its respiration is the same in both hypotonic and isotonic sucrose media.


Effect of glucose utilization inhibitor isolated from the serum and urine of patients with chronic renal failure on the free fatty acid metabolism in rat kidney cortex slices. The authors studied interference by the inhibitor of glucose utilization with free fatty acid (FFA) metabolism in rat kidney cortex slices. They found that FFA uptake by the kidneys, their incorporation into triglycerides (TG) and oxidation to 14CO2 were lower when the inhibitor was present in the incubation medium. The findings show that the inhibitor, as well as inhibiting glucose utilization in various tissues, interferes directly with fat metabolism.


Pattern of breathing in the rat.

Pattern of breathing in the rat. The basic ventilation values - tidal volume (VT), breathing frequency (f), minute ventilation (VE) and the duration of inspiration (TI) and expiration (TE) -- were determined in adult male rats. The range of these values is given and the pattern of breathing is defined as the relationship between VE and VT, which in the rat is linear throughout its entire range. The role of TI and TE in changing f in the rat were evaluated. The breathing pattern of the rat was compared with data for the rabbit and man, using percentual expression of the basic values. A shift of the breathing pattern to higher f values was observed in rats with experimental lung diseases. In these rats, the inhalation of 100% O2 shifted the pattern of breathing markedly to lower VE values, though not to values comparable with the controls. Bilateral cervical vagotomy was followed by a pronouced decrease in f, an increase in VT and T1 persisted even after vagotomy, however; it can be assumed that this relationship is effected either by means of receptors in the chest muscles, or by the direct action of CO2 which is used to stimulate breathing, on the bulbopontine pacemaker.


Experimental hypersplenism in mice.

Experimental hypersplenism in mice. The authors induced experimental hypersplenism in mice with repeated intraperitoneal injections of methylcellulose ("Tylosa", Messrs. Kabl). Detailed haematological tests of the peripheral blood, a cytomorphological examination of bone marrow and spleen from puncture material and histological tests of the bone marrow, spleen, lymph nodes, thymus, liver, kidneys and lung tissue of hypersplenic mice were carried out. Among the haematological results, apart from findings of marked erythrocyto-, leucocyto- and thrombocytopenia, attention is drawn to the finding, not previously described in the literature, of lowered osmotic resistance and elevated phagocytic activity of the leucocytes of hypersplenic mice.


The effect of Ca2+, temperature and sucrose upon potassium contracture of the isolated rat right ventricle. Potassium (100 mM KC1) contracture of the isolated rat right ventricle was lower in Tyrode solution (37 mM Na)  than on substituting sucrose (270 mM) for NaC1 and was biphasic in 70% of the experiments. As in slow (tonic) skeletal muscle, the maximum contracture value persisted as long as a raised KC1 concentration was maintained. Even after complete potassium depolarization it changed when Ca was altered. At 37 degrees C, the second phase of potassium contracture was higher than at 34 degrees C (p less than 0.01). The effect of K+ and Ca2+ was inhibited if the ions were added after adding sucrose to the Tyrode solution. Contracture of the rat ventricle resembled contracture of slow (tonic) skeletal muscle.


The effect of SO24-, NO-3, Ca2+ and temperature upon sodium-free contracture, isotonic and isometric contraction of the isolated rat right ventricle. Sodium-free contracture was directly dependent on the presence of Ca2+ in Tyrode sulphate solution. The first phase of contracture increased in Tyrode nitrate solution more quickly than in sulphate solution, while the second phase was the same. Higher amplitude of isotonic contractions was observed on substituting nitrates for chlorides in the Tyrode solution than in sulphate substitution. In Tyrode sulphate solution, spontaneous contractions appeared in 50% of the experiments. The relationship between the duration and tension of isotonic contraction, given the same pre-loading, showed greater diminution of the contractions, at the lower temperature (22 degrees C) than at the higher temperature (35 degrees C), whereas passive stretching of the muscle was not influenced by the temperature. Isometric contrations lasted longer at the lower temperature. The amphlitude of isometric contractions was directly correlated to the frequency of electrical stimulation at a constant temperature (22 degrees C). The results showed that shifts of the calcium participating in contraction of the rat ventricle are influenced both by the anion and cation content of the medium and by its temperature.


The effect of single dose of oestrogens administered during the early postnatal period on the DNA content of rat bone epiphyses. It has been shown previously that the administration of a single dose or oestrogens to male rats during the early postnatal life retards growth, after a latent period lasting several weeks, [slowing down of body weight and body lenth increments]. We therefore studied the effect of a single subcutaneous dose of oestrogens (1.25 mg oestradiol dipropionate) administered on the 5th postnatal day on the DNA content and DNA concentration in the parts of long bones associated with growth (distal epiphysis of the femur, and proximal and distal epiphyses of the tibia together with the epiphyseal plates). The rats were decapitated at the age of 18, 25 and 40 days, the given parts of the bones were immediately dissected out, weighed and their absolute DNA content and DNA concentration were analyzed. The weight of the distal femoral epiphysis of oestrogen-treated rats was found to be significantly lower at 40 days than in the controls. At the same age, its DNA content and concentration were likewise significantly lower in animals given oestrogens on the 5th day of life. The weight of the proximal tibial epiphysis of oestrogen-treated rats was significantly lower from the 25th day, while its DNA content was already significantly lower on the 18th day and the difference was maintained up to the 40th day of life. A significant decrease in the DNA concentration in oestrogen-treated rats did not appear until the 40th day. The weight of the distal tibial epiphysis of experimental rats was also significantly lower from the 25th postnatal day onwards and its DNA content was significantly lower by the 18th day. At 25 days, the DNA content was slightly lower in oestrogen-treated rats, but the significance of the difference disappeared, although it re-appeared on the 40th day of life. As in the two preceding epiphyses, the DNA concentration in the distal tibial epiphysis was not significantly lower in oestrogen-treated animals before the 40th day of life. The results show that the administration of oestrogens in the early postnatal period significantly affects both the absolute DNA content and the DNA concentration in all the epiphyses in question. The reaction does not appear in all the epiphyses at the same time, however. Differences in the degree of maturity of the epiphyses are evidently responsible for the variability of the response as regards the time at which the above changes occur.


Genetic counseling by the primary care physician. This paper has presented, in a rather concise and limited form, an outline of basic genetic principles which are necessary for the primary physician to provide good genetic counseling and good patient care. The assistance of a genetic center with prenatal diagnostic facilities allows consultation to proceed in a logical and constructive manner. The primary physician is in an excellent position to determine the pedigree, especially if he has the opportunity to examine the proband's immediate family and close relatives. The diagnosis may be easily made by the primary physician or it may require the combined efforts of the genetics clinic and the primary physician. In either case, the decision to terminate future pregnancies or to limit future offspring is made by the proband and his family, not the physician. The decision-making process may be affected by the primary physician who provides a sufficient amount of relevant information to his patients and allows them to reach a rational decision. Whether the decision appears rational to the physician or not, he must help his patients deal with it.


Use of synthesis inhibitors in defining a role for biogenic amines during imipramine treatment in depressed patients. Endogenously depressed patients who showed an antidepressant response to the tricyclic drug imipramine continued to show sustained well being after alpha-MPT was added whereas depression returned when small doses of PCPA were added for brief periods. In one patient the antidepressant response to imipramine occurred after pre- and continued treatment with alpha-MPT. Urinary excretion levels of MHPG in one of the patients studied longitudinally did not correspond to the direction of clinical affective state but did reflect anticipated changes during alpha-MPT treatment. Implications are that serotonergic mechanisms are likely involved in the anti-depressant effects of imipramine in man.


Further studies on the mechanism of the carbon tetrachloride induced polysome breakdown. CCl4 ability to cause polysome breakdown in liver is age-dependent being negligible in the 7 days old rat and abruptly changing to adult values after 14 days of age. The CCl4 induced polysome breakdown process is more intense in the phenobarbital treated than in control rats while the 3-MC prior treatment does not modify its intensity. Prior treatment with SKF 525A increases the intensity of the polysome breakdown process while Sch 5705 or Sch 5706 administration do not modify it. Aminotriazole or cycloheximide pretreatment but not pyrazole administration decrease the intensity of polysome rupture caused by CCl4. The CCl4 deleterious action on strain A/J mouse liver polysomes is as intense as is in the rat liver. Results are discussed in relation to the role of either the irreversible binding of CCl4 components to ribosomes or lipid peroxidation as reponsible for the breakdown process.


[Studies concerning the usefulness of catgut, PGA and polyester for abdominal fascia closure (author's transl)]. The abdominal fascia incisions of 133 rabbits were closed either with plain gut, chromic gut, PGA or polyester threads. The breaking strength of the wounds were determined tensiometrically at different time intervals and the tissue was examined histologically. For a three-week period the strength of the abdominal wall depends significantly on the intactness of the threads. PGA produces minimal inflammatory reactions, but loses its strength after a fortnight. Since longitudinal incisions are endangered by severe muscle pull, this material cannot be recommended because of the possibility of wound disruption and the formation of hernias. The loss of strength of catgut plain and catgut chromic starts later. Catgut causes inflammatory reactions within the wound area leading to loss of strength of the sutured tissue. Thus incisions of the abdominal fascia should not be closed with catgut. The non-resorbable suture material polyester shows satisfactory strength and minimal tissue reaction. As long as there is no synthetic suture material with mild tissue reaction and late resorption the fascial closure should be sutured with polyester.


[Non-hormonal drug treatment in Paget's disease]. The activity of a therapeutic drug against Paget's disease is judged by a reduction in the level of hydroxyprolinuria and of alkaline phosphatasaemia, these being the metabolic signs of the bone changes, and by a decrease in bone pain which may accompany the bone changes in Paget's disease. The effect of aspirin is only moderate and is produced only with large doses that are often not well tolerated. The cortisone drugs are also active only at high doses that should be avoided. The action of sodium fluoride is uncertain. Mithramycin is always effective; it leads to a decrease in the levels of hydroxyprolinuria and of alkaline phosphatosaemia and to disappearance of the pain. At the dose levels used by the authors, mithramycin induces only certain metabolic anomalies (rise in transaminases, decrease in the prothrombin level...) which return to normal at the end of treatment. However, the long-term tolerance of mithramycin is unknown and the authors think that its use in cases of Paget's disease should be severely restricted. Sodium etidronate, a diphosphonate that inhibits both bone resorption and osteoformation also decreases regularly the levels of hydroxyprolinuria and of alkaline phosphatasemia and often decreases the pain. It is usually well tolerated. However at the dose rate of 20 mg/kg/day it may lead to the development of osteomalacia.


[Biological exploration of Paget's disease]. The laboratory investigation of cases of Paget's disease has revealed results of three types :--small increases in the sedimentation rate, in the ceruloplasmin level, in the average corpuscule volume, and in uricaemia. These changes are of little practical value;--a considerable increase in the common stocks and in the turn-over of calcium, a frequently negative assessment with a parathyroid hormone level at the lower limit of normality. The levels of calcaemia and calciuria, little changed on average, may increase slightly after hospitalization. The use of these parameters is valuable but they are sometimes difficult to interpret;--an increase in the levels of alkaline phosphatases and of urinary hydroxyproline, in relation to the extent and the activity of the disease, and also of certain parameters of calcium-45 and of quantitative histology. A statistical study of the spontaneous evolution of hydroxyprolinuria in 50 patients with Paget's disease who were not treated for less than 3 years, allowed the authors to establish in what conditions a change induced by calcitonin or mithramycin is significant.


[Multicentric reticulohistiocytosis (lipoid dermato-arthritis). Apropos of a case with fatal outcome]. The authors report the case of a 37-year-old man affected by a seronegative polyarthritis associated at first with erythroderma and then with cutaneous and subcutaneous papulo-nodular structures and a xanthomatous eryption. Histological examination of the cutaneous nodules and of the synovial membrane confirmed the diagnosis of multicentred reticulohistiocytosis by showing the presence of lipid infiltrates in the histiocyte cells and of multinucleate giant cells. A study of the ultrastructure of the histiocytes revealed the presence of numerous intracytoplasmic vacuoles. In spite of antimalaria treatment, with cortisone and then with immuno-depressants, the outcome was fatal with a picture of acute reticulosis and neurological disorders. In discussing this case, the authors also make a general review of the subject.


A cellular-biochemical evaluation of gastric body mucosa and muscular layer in patients with different basal acid outputs. The membrane (Na+-K+ -dependent) ATP-ase (EC 3.6.1.3.), adenine-adenosine, adenosine monophosphate (AMP), adenosine diphosphate (ADP), adenosine triphosphate (ATP), phospholipid phosphates (lipid-P), ribonucleic acid (RNA), and deoxyribonucleic acid (DNA) were extracted and measured in the patients' gastric body mucosa and muscular layer with different basal acid outputs. It was observed that the Na+-K+ -dependent ATP-ase activity, tissue adenine adenosine, AMP, ADP, ATP, lipid-P, and RNA - in correspondence to 1.0 mg DNA - significantly increased in the gastric corpus mucosa, with an increase of basal acid output. No significant changes of these parameters were found to be present in the gastric body muscular layer of patients with different basal acid output. It has been concluded: 1) the energy requirement for H+ secretion, from the point of view of basal acid output, is given by the transformation of ATP into ADP; 2) the biochemical building up of the human gastric mucosa is different in patients with decreased, normal and increased BAO values; 3) no significant difference is found between the biochemical structures of gastric muscular layer in patients with different basal acid output values.


Immunopathologic mechanisms of renal disease. Anti-GBM antibodies and glomerular deposition of circulating immune complexes are responsible for the immunopathogenesis of about 5% and 75% of human glomerulonephritides, respectively. Anti-GBM antibodies most frequently cause rapidly progressive glomerulonephritides, respectively in about half of the patients with pulmonary hemorrhage, the Goodpasture's syndrome. Immune complexes cause a wide variety of glomerulonephritides, including diffuse and focal proliferative, membranous, membranproliferative and rapidly progressive morphologic varieties often accompanied by nephrotic syndrome. Immune complexes cause a wide variety of glomerulonephritides, including diffuse and focal proliferative, membranous, membranoproliferative and rapidly progressive morphologic varieties often accompanied by nephrotic syndrome. Immunopathologic tubulo-interstitial renal injury can be caused by antibodies reacting with TBM or by deposition of immune complexes in tubulo-interstitial tissue. Immunofluorescence studies of renal tissue supplemented by detection of circulating anti-basement membrane antibodies and immune complexes are essential in differentiating the immunopathologic mechanisms of glomerular and tubular injury, and are necessary adjuncts in evaluating patients with glomerulo- and tubulo-interstitial nephritis.


Uremia as a state of immune deficiency.

Uremia as a state of immune deficiency. This study dealt with the in vitro immune responses to stimulation with phytohemagglutinin, pokeweed mitogen, concanavalin A, and purified protein derivative in lymphocytes taken from uremic patients before and after hemodialysis and in normal lymphocytes in the presence of plasma from uremic patients before and after hemodialysis and normal AB serum, as well as the influence of the same plasma factors on one-way mixed lymphocyte culture (MLC) responses of uremic/normal and normal/normal lymphocytes. The results obtained show that uremic plasma contains nondialyzable factors that can suppress both uremic normal and normal/normal lymphocyte responses in MLC and that uremic and normal lymphocytes show asynchronic MLC culture kinetics, thus indicating a changed immune status of uremic patients manifested both at the cellular and at the humoral level.