Effect of chronic metoclopramide therapy on serum pituitary hormone concentrations. The effect of chronic (3--9 months) therapy with metoclopramide on serum levels of pituitary and thyroid hormones was studied in 4 males and 1 female. The mean serum prolactin concentration during metoclopramide therapy was significantly higher than after discontinuation of metoclopramide. Serum prolactin concentrations increased acutely after each dose of metoclopramide. Serum prolactin concentrations increased acutely after each dose of metoclopramide, and gradually returned to normal by 6--12 h. There was no sifgnificant differences in the serum TSH, T3, T4, GH, and gonadotrophin levels during and after metoclopramide administration. In the male subjects the mean serum testosterone was normal, but significantly lower during metoclopramide therapy.


[Vinblastine-loaded platelets and their effect in a case of idiopathic thrombocytopenic purpura (author's transl)]. The successful treatment of a patient with idiopathic thrombocytopenia (ITP) by vinblastine-loaded platelets (VMT) is described. Serum autoantibodies and platelet-bound IgG disappeared after treatment. We infer that this type of therapy does not oeprate on the level of platelet destroying cells but rather affects antibody producing cells. Since there was also a T-cell sensitization versus VMT we favour the hypothesis of a modified self alteration as the cause of the disease and its recovery of VMT.


IgA-containing cells in the ruminant intestine following intraperitoneal and local immunization. Experiments are described which demonstrate that a single intraperitoneal (i.p.) injection of antigen in Freund's complete adjuvant results in the appearance of IgA-specific antibody-containing cells (ACC) in the intestinal lamina propria of sheep and that these cells reach the intestine via the intestinal lymph and blood circulation. Following intraintestinal administration of antigen to sheep immunized i.p. 2 weeks previously, an enhanced ACC response occurs in the intestine but cannulation and drainage of the intestinal duct does not interfere with this enhancement. Evidence is presented which suggests that the enhanced ACC response may be accounted for by antigen-induced local proliferation of ACC in the lamina propria of the intestine.


Replication of porcine parvovirus in peripheral blood lymphocytes, monocytes, and peritoneal macrophages. Porcine peripheral blood lymphocytes (PBL), peripheral blood monocytes, and peritoneal macrophages were examined for their ability to support porcine parvovirus (PPV) replication. The cell cultures were infected with the NADL-2 strain of PPV at 0.1 multiplicity of infection. PBL cultures were stimulated with the following phytomitogens: phytohemagglutinin M, concanavalin A, and pokeweed mitogen. Unstimulated PBL cultures infected with PPV and uninfected PBL stimulated with phytomitogens served as controls. All cultures were examined daily for PPV-specific immunofluorescence and hemagglutinin. PPV replicated in PBL cultures stimulated with all phytomitogens. Both viral hemagglutinin in culture fluids and nuclear immunofluorescence in cells were detected. In contrast, unstimulated PBL did not support viral replication; however, PPV antigen was detected in the cytoplasm. PPV persisted in unstimulated PBL for 21 days (duration of the experiment) without replication, but replicated each time with the addition of phytohemagglutinin M at 0, 3, 7, 14, and 21 days after infection. Uninfected PBL stimulated with phytomitogens lacked both viral hemagglutinin and immunofluorescence. Simultaneous detection of lymphocyte surface marker and viral antigens in pokeweed mitogen-stimulated PBL revealed that both T and non-T cells (B and null cells) are able to support PPV replication. Peripheral blood monocytes and peritoneal macrophages phagocytized PPV but did not support virus replication.


Influence of encapsulation on phagocytosis of Pasteurella multocida by bovine neutrophils. The effect of encapsulation on phagocytosis of Pasteurella multocida by bovine neutrophils was examined by using two encapsulated strains, NA77 (capsular type A) and C42 (capsular type B), and comparing them with an unencapsulated counterpart strain, 1173. The uptake of [(3)H]thymidine-labeled bacteria by neutrophils was quantitatively measured after incubation of the bacteria in normal bovine serum, heat-inactivated serum, and hyperimmune sera (anti-NA77 and anti-C42). Results showed that all three strains of P. multocida were ineffectively opsonized by the heat-labile serum complement system. The unencapsulated strain was completely phagocytized in the presence of heat-stable opsonins found in normal serum. Although encapsulation of strain C42 was found to interfere with opsonization by normal serum, this strain was completely phagocytized when hyperimmune serum (anti-C42) was used as the opsonin source. These results suggest that specific anticapsular antibodies found in the hyperimmune serum readily opsonized the encapsulated strain C42 and enhanced phagocytosis. The presence of a thick capsule on strain NA77 interfered with phagocytosis in the presence of normal or hyperimmune serum (anti-NA77). This interference was due to the presence of hyaluronic acid which was a major component of the capsule. Treatment of this encapsulated strain with hyaluronidase decapsulated the bacteria. Bacteria treated in this way were almost completely phagocytized (90%) in the presence of heat-stable opsonins. The exact mechanism by which the capsule of P. multocida NA77 interfered with phagocytosis was not demonstrated; perhaps the slimy nature of the hyaluronic acid makes the phagocytic act difficult by changing the physiochemical surface properties, or it may prevent opsonization.


Interferon enhanced human natural killer and antibody-dependent cell-mediated cytotoxic activity. Preincubation of normal human lymphocytes with human interferon for 18-24 h at 37 degrees C resulted in an increase of the activity of both natural killer (NK) cells and antibody-mediated cytotoxic cells (ADCC). The human myeloid line, K-562, which is highly susceptible to NK cells, was employed. ADCC was assessed with antibody-coated chick erythrocytes as targets. NK cells and ADCC were detected in a 4-hour 51Cr release assay. The magnitude of the enhancement was proportionate to the amount of interferon used in preincubation of the effector cells. Preincubation of tumor-target cells with interferon does not increase their susceptibility or resistance to lysis. The major effect of interferon on the cellular metabolism of the tumor-target cell is inhibition of DNA synthesis, but no direct cytotoxic effect was detected. Our findings may be important in understanding the mode of action of interferon in increasing host resistance to a variety of pathogens and tumors. This may be accomplished by inhibiting the growth of the tumor while simultaneously enhancing the natural killing mechanism for immunosurveillance.


Time dependent changes in the pharmacokinetics of aspirin. In an experiment carried out on six volunteers, measurement of total serum salicylate concentration was used to describe aspirin kinetics after a single 1500 mg oral dose. The availability of the drug was significantly better when it was administered at 6(00) than at 18(00) or 22(00). Also a significant time-dependence was found between the morning and evening values of both the serum half-life time of salicylate and kel. The possible relation between these results and the appearance of undesirable side effects in patients should be examined.


Incidence and complications of ureteral stump pathology. The authors report on 58 patients with ureteral stump disease. Therapeutic errors, certain specific conditions, but also nephrectomies done for diseases other than pyelo-calyceal tumors and tuberculosis may increase the severity of ureteral stump pathology. The clinical symptoms are often vague, and are demonstrated too late. The incidence may be reduced and the outcome improved by removal of the ureter whenever favourable conditions for development exist, and by looking for them by efficient exploration and complete excision, if nephrectomy is followed by even less marked changes.


The effect of dantrium on the canine urethral pressure profile. The effects of dantrolene sodium and tubocurarine on the urethral pressure profile were investigated in anesthetized dogs. A model of urethrovesical separation was used to prohibit transmission of pressure changes between the bladder and urethra. Intravesical pressure (representing smooth muscle activity) and arterial blood pressure (for cardiovascular effects) were recorded simultaneously. Tubocurarine and dantrolene sodium in pharmacologic doses had equally depressive effects on the urethral pressure profile at its distal three-fifths although a longer duration of action was observed with dantrolene. The depressive effect of dantrolene was dose-dependent. Although dantrolene sodium had no effect on blood pressure or heart rate, it did depress intravesical pressure at the 15 mg per kg of body weight dose. These findings would seem to suggest the use of dantrolene sodium in urodynamic experimental studies.


Differentiation of the formaldehyde-induced fluorescent products of noradrenaline and dopamine by microspectrofluorometry. The influence of concentration of dopamine and noradrenaline on the spectral characteristics of their formaldehyde-induced fluorophore, together with the influence of duration of reaction with formaldehyde, has been investigated in a model system. No substantial differences between fluorescence spectra of the amine fluorophores were observed. Accordingly, the influence of hydrochloric acid and ammonia vapours on the fluorophores was investigated. A shift to shorter wavelengths in the excitation maximum of each fluorophore was observed after a brief exposure to hydrochloric acid vapour; more prolonged exposure resulted in a pronounced shift back to longer wavelengths in the case of noradrenaline but no substantial change was observed with dopamine. Brief exposure to hydrochloric acid vapour resulted in a substantial increase in the rate of fading of the noradrenaline fluorophore on exposure to exciting radiation. It is suggested that this offers a convenient way of differentiating the amines.


A quantitative cytochemical study of glucose-6-phosphate dehydrogenase and delta 5-3 beta-hydroxysteroid dehydrogenase activity in the membrana granulosa of the ovulable type of follicle of the rat. During the last four days of follicular development prior to ovulation, the activities of delta 5-3 beta-hydroxysteroid dehydrogenase (3 beta OHD) and glucose-6-phosphate dehydrogenase (G-6-PD) were quantified in cryostat sections of the rat ovary. The product of the enzyme reactions were measured using a scanning and integrating microdensitometer. The enzyme activity was measured in the peripheral region, the antral region and the cumulus of the membrana granulosa (MG) of these follicles on the morning of each of the four days of the estrous cycle. G-6-PD activity was measured in the presence and absence of an intermediate hydrogen acceptor, phenazine methosulphate, to provide a measure of the quantity of Type I and Type II Hydrogen (H) generated: Type I H is considered to be related to hydroxylating reactions such as those of steroids and Type II H to other general biosynthetic activities of cells. In all three regions of the MG of follicles of the ovulable type, 3 beta OHD activity was lowest in estrus and diestrus-1, increased on diestrus-2 and peaked in proestrus. In estrus and diestrus-1, the level of 3 beta OHD activity in the three regions was comparable. However, by diestrus-2, and even more conspicuously in proestrus, enzyme activity was significantly greater in the peripheral region than in the antral region or in the cumulus. During the same period, the level of enzyme activity remained comparable in the last two regions. Throughout the estrous cycle, both Type I and Type II H generation from G-6-PD was greatest in the peripheral region, less in the antral region and least in the cumulus. In the eripheral region, Type I H generation increased progressively after diestrus-1, to reach a maximum in prestrus. In the antral region, Type I H generation increased between diestrus-1 and diestrus-2 and then remained unchanged through proestrus. In the cumulus, Type I H generation remained at levels seen in estrus throughout the remainder of the cycle. Generation of Type II H, in the peripheral region was constant throughout the estrous cycle. In contrast, in the antral region and cumulus, Type II H generation was greater in diestrus-1 and diestrus-2 than on either proestrus or estrus.


Fatal thrombocytopenic hemorrhagic diathesis associated with dapsone administration to a dog. Dapsone was given for six days to a dog with chronic skin disease. The dog then became weak and anorectic, and it vomited and had purpura caused by severe thrombocytopenic hemorrhagic diathesis. Despite treatment, the dog died a week later. There were clinical and pathologic evidence that the dog's platelets and megakaryocytes had been destroyed during the first few days of dapsone therapy. It was concluded that the syndrome was dapsone-induced and that thrombocytopenia should be considered among the adverse reactions to dapsone in the dog.


Atypical salmonellosis in horses: fever and depression without diarrhea. Salmonellosis in horses may result in fever, anorexia, and depression without concurrent diarrhea or other obvious gastrointestinal abnormalities and should be considered in cases of fever of unknown origin. The syndrome also is characterized by neutropenia, usually with a left shift, and growth of small numbers of salmonella from feces cultured in selenite enrichment broth. Repeated culturing may be necessary to isolate the organism. All six affected horses of this report recovered in 3 to 7 days without specific therapy.


Scanning electron microscopy of surface ultrastructure changes during meiosporangium maturation and meiospore liberation in the aquatic fungus Allomycpes arbuscula. Alterations in wall ultrastructure accompanying resistant sporangium maturation and meiospore liberation in Allomyces arbuscula were examined by scanning electron microscopy. Three discrete wall layers were identified, each of which underwent marked changes during processes leading to zoospore release. The outermost wall layer, the hyphal sheath continuous with the hypha, was physically altered during the maturation process preparatory to induction and release of meiospores. The integrity of this wall layer was broken, and it was no longer closely juxtaposed to the heavy pitted wall layer that lay beneath it. A fibrillar matrix seemed to cement the two layers to one another before this desiccation. A single, raised, longitudinal dehiscence ridge on each meiosporangium appeared to be a structurally differentiated region of the pitted wall layer at which sporangium rupture occurred to permit emergence of the protoplast. By its thickness the pitted wall layer was likely to provide mechanical rigidity to the meiosporangium. Beneath the pitted wall layer, another thin, flexible wall layer surrounded the protoplast. From this structure, a single exit papilla was cleaved at the apical region to effect the release of meiospores from the protruding protoplast. Thus a sequence of structural changes in well-differentiated multiple wall layers is implicated in the sporulation process in this organism.


Angiosarcoma of the maxillary sinus: literature review and case report. A rare case of angiosarcoma of the maxillary sinus is reported. Review of the literature concerning angiosarcoma of the head and neck revealed 14 previously published cases involving the nose, nasal sinuses, and nasopharynx. Angiosarcoma of the skin and soft tissues of the head and neck differs in behavior from that affecting the nose, nasal sinuses, and nasopharynx. The case reported presents the protracted clinical course of this malignant tumor.


Creatine phosphate inhibition of heart lactate dehydrogenase and muscle pyruvate kinase is due to a contaminant. Previously reported inhibitions of heart lactate dehydrogenase (Guppy, M., and Hochachka, P.W. (1978) J. Biol. Chem. 253, 8465-8469) and muscle pyruvate kinase (Kemp, R.G. (1973) J. Biol. Chem. 248, 3963-3967) by creatine phosphate are due to oxalate which is a contaminant found in some commercial preparations of creatine phosphate.


Binding of alkylisocyanides with soybean leghemoglobin. Comparisons with sperm whale myoglobin. The binding of various linear and branched chain alkylisocyanides to soybean leghemoglobin has been studied with respect to association and dissociation kinetics and the results compared with those obtained in parallel on sperm whale and horse heart myoglobins; the linear ligands used (methyl to n-heptyl) cover a greater distribution of chain lengths than hitherto used. The association rate constants are much higher for leghemoglobin than for myoglobin, while the dissociation rates are slower. For a given protein, the dissociation rate constants are not much different when different isocyanides are used (except for methyl), whereas the association rates show complex behavior in relation with the alkyl chain length; singular differences are observed between leghemoglobin and sperm whale myoglobin in this regard. For myoglobin, the binding rate constants decrease from methyl to n-propyl, but remain approximately the same when the ligand carries a still longer alkyl chain. In contrast, for leghemoglobin, although the rate constants decrease from methyl to n-propyl, they show a progressive and important rise with longer alkyl substituents: n-butyl and n-pentyl.


Isolation and partial characterization of the multiple forms of deoxyribonucleic acid-dependent ribonucleic acid polymerase in the fungus Podospora anserina. Three DNA-dependent RNA polymerases have been isolated and partially purified from the mycelium of the fungus Podospora anserina. Separated by DEAE-Sephadex chromatography, they have been designated RNA polymerases I, II, and III according to their order of elution. Their catalytic properties and alpha-amanitin sensitivity are in agreement with those of the homologous enzymes found in other eukaryotic organisms. The three enzymes exhibit rather sharp monophasic ammonium sulfate dependence with optima which are, respectively, 0.035 M, 0.050 M, and 0.075 M. Enzyme I has the largest Mn2+/Mg2+ activity ratio, shows a marked preference for native DNA, and is insensitive to alpha-amanitin. Enzyme III uses poly(dA-dT) in preference to native DNA as template and is only partially sensitive to alpha-amanitin. Enzyme II is sensitive to alpha-amanitin, but high concentrations of the toxin are required for inhibition compared to other eukaryotic class II enzymes. Three similar RNA polymerases with comparable levels of activity were found in the temperature-dependent VR strain when cellular incompatibility, leading to a rapid cessation of RNA synthesis, was induced.


Exposure of platelet fibrinogen receptors by ADP and epinephrine. The role of fibrinogen as a cofactor for platelet aggregation was examined by measuring the binding of 125I-labeled human fibrinogen to gel-filtered human platelets both before and after platelet stimulation by ADP and epinephrine. Platelet stimulation by ADP resulted in the rapid, reversible binding of fibrinogen to receptors on the platelet surface. Fibrinogen binding increased as the concentration of ADP was increased from 0.1 to 2 microM, reaching a plateau at higher ADP concentrations. Binding occurred only after platelet stimulation and in the presence of divalent cations. However, fibrinogen binding did not occur to ADP-stimulated platelets from three patients with Glanzmann's thrombasthenia. Analysis of fibrinogen binding as a function of increasing fibrinogen concentration demonstrated that maximal platelet stimulation exposed approximately or equal to 45,000 binding sites per platelet with a dissociation constant of 80--170 nM. These fibrinogen binding parameters were essentially the same whether ADP or epinephrine was the platelet-stimulating agent. Thus, these studies demonstrate that platelet stimulation by ADP and epinephrine exposes a limited number of fibrinogen receptors on the platelet surface. Furthermore, these data suggest that the fibrinogen molecules bound to the platelet as a consequence of platelet stimulation are directly involved in the platelet aggregation response.


Effect of soy protein on intestinal absorptive ability of calves by the xylose absorption test. Five calves per group were fed whole milk (control) or one of three milk replacers with one-thrid of the total protein provided by a soy product. Soy products were Promocaf (a commercial soy protein concentrate), an experimental soy flour. After a 24-h fast, calves were fed xylose solution. Urine was collected for 5 h. Jugular blood was sampled at 0, .5, 1, 1.5, 2, 2.5, 3, 4, and 5 h after xylose administration. Xylose tests were weekly on each calf through 5 wk of age. Urinary xylose excretion, as a percentage of xylose fed, was higher in the control group during the last 4 wk than in groups fed milk replacers. Mean urinary xylose excretions during 5 wk from calves sampled 5 h after xylose administration were 12.4, 4.2, 4.2, and 4.3% of xylose administered for calves fed milk, soy flour, soy protein concentrate, and Promocaf, respectively. Mean increases in peak of xylose concentration in plasma were 55.7, 44.4, 42.8, and 45.3 mg/100 ml. Peak values for control calves were higher than those for calves fed soy products at wk 4 and 5. Times required to reach peak value did not differ significantly. Neither xylose concentration of plasma nor urinary xylose excretion differed among the groups fed soy products.


Influence of percent egg yolk during cooling and freezing on survival of bovine spermatozoa. The influence of percent egg yolk during cooling from 37 to 5 C on ability of sperm to withstand subsequent freezing was studied with semen from each of eight bulls. Treatments were arranged factorially and included .5, 1, 2, 4, 8, 16, and 32% egg yolk, cooling times of .5, 1, 2, and 4 h, and freezing in ampules and straws. Percent egg yolk did not influence motility or percent intact acrosomes when semen was frozen in ampules. For sperm in straws, both post-thaw percentages of motile sperm and intact acrosomes were similar for sperm cooled with .5, 1, 2, 4, or 8% egg yolk and greater than with 16 or 32% egg yolk. Optimal egg yolk during cooling was not dependent upon rate of cooling, regardless of how semen was packaged for freezing. The influence of percent egg yolk during freezing was investigated in a second study. Treatments included eight bulls; 1, 2, 4, 8, 16, and 32% egg yolk; freezing times from +5 to -130 C of 3.5, 20, and 40 min; and freezing in ampules or straws. Optimal egg yolk during freezing in either ampules or straws was independent of the rate of freezing. For sperm frozen in ampules, differences in motility or the percent intact acrosomes due to egg yolk were small. However, the use of only 1 or 2% egg yolk depressed motility whereas 16 or 32% egg yolk decreased the percentage of intact acrosomes. Thus, extremely high or low egg yolk should be avoided. For sperm in straws, survival was optimal when the extended semen contained 4 to 32% egg yolk during freezing.


Flavor quality of antioxidant-treated, cooked, ground beef patties. The antioxidant tertiary-butylhydroquinone (TBHQ) reduced flavor deterioration and oxidative rancidity in cooked ground beef patties stored up to seven days at refrigerator (2.8 degrees C.) temperatures and up to twenty-one days at freezer (--20.5 degrees C.) temperatures. Freezer conditions maintained flavor quality more effectively than refrigerator temperatures in both TBHQ-treated and untreated samples.


Induction of lysosomal enzyme secretion by alveolar macrophages in response to the purified complement fragments C5a and C5a des-arg. Purified C5a and its "inactive" form, C5a des-arg, were shown to induce secretion of acid hydrolases from rabbit alveolar macrophages (AM) in a concentration-dependent manner. Secretion increased with time to 5 times above controls by 72 hr. Concentrations of these enzymes in the cell lysates did not decrease during the incubation, suggesting that synthesis of new enzyme was occurring. The lysosomal enzyme secretion was accompanied by increased pinocytosis and release of proteolytic enzymes from the macrophages. At no time was significant lactic dehydrogenase liberated, indicating that secretion was selective and not due to cell death. Data presented also suggest that C5a des-arg induced secretion from the macrophages of a chemotactic factor for neutrophils. It was concluded that C5a and C5a des-arg may play a role in lung injury by interactions with AM, inducing the secretion of acid hydrolases and proteolytic enzymes that can cause tissue damage, and by regulating the influx of other inflammatory cells into the interstitium and air spaces.


An improved method for the isolation from Naja naja venom of cobra factor (CoF) free of phospholipase A. An improved method is reported for the isolation from cobra (Naja naja) venom of cobra factor (CoF), the anticomplementary protein which is derived from cobra C3. Sequential chromatography on DEAE-Sepharose, Sephacryl-S200, and finally hydroxylapatite yielded 6.25 mg CoF per gram of crude venom. The purified CoF had 1 unit of functional anticomplementary activity per 1--2 micrograms of protein, and was homogeneous on gradient and non-reduced sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis (PAGE). In SDS-PAGE after reduction with mercaptoethanol there were two major bands (M.W. 75,000 and 51,000 daltons), three minor bands (M.W. 29--31,500 daltons) and two trace bands (36,500 and 41,500 daltons). By analogy with mammalian C3 it is suggested that the CoF consists of two polypeptide chains linked by disulphide bridges, one of which undergoes cleavage of the peptide chain at several points either in vivo or in vitro.


A new rapid rosette-forming cell micromethod for the detection of antibody-synthesizing hybridomas. The method reported here describes a microrosetting assay which allows the early detection of antibody-synthesizing hybridomas. This method is specific, requires very few hybridoma cells and avoids artifacts resulting from the presence of antibodies secreted by spleen cells in the primary hybridoma cultures. It is easy to perform and allows the screening of more than one hundred independent clones within a few hours.


Endemic human plague in New Mexico: risk factors associated with infection. A retrospective case-control study was conducted to identify risk factors, other than contact with infected animal tissues, for infection caused by Yersinia pestis in non-Indian residents of areas with endemic sylvatic plague in New Mexico. The study group consisted of 16 persons who had bacteriologically confirmed cases of plague in the period 1975-1976 and 45 controls who were matched by age, sex, and location of residence. Participants were questioned about outdoor activities, environmental conditions in and around the home, procedures of pet care, exposure to animals and insects, and medical history. The availability of harborage and food sources for wild rodents as a result of human activity in the immediate home environment was associated with risk of infection. Failure to take steps to control fleas on dogs and cats also appeared to be a possible risk factor. No other significant differences were found between patients and controls. Plague in New Mexico appears to result primarily from entry of the reservoir host into the habitat of the human rather than from entry of the human into the sylvatic habitat of the reservoir host.


Radioimmunoassay of nortestosterone and related steroids. A radioimmunoassay of nortestosterone and related steroids, including its principal metabolities, is described and evaluated. Antisera against nortestosterone-17 beta-hemisuccinate- and nortestosterone-3-carboxymethyloxime-bovine serum albumin were raised in goats. By using a mixture of such antisera with different selectivity, the cross-reactions of several naturally occurring steroids can be reduced. The method can be applied for the detection of nortestosterone in both unprocessed or hydrolyzed urine extracts and also in plasma. It has been used as a screening test for anabolics in doping control.


Replication of two influenza virus strains and a recombinant in HEF and LEP cells. The replication of influenza viruses A/NWS-D, A/WS-MK and their r12 recombinant in human embryo fibroblast (HEF) and human diploid fibroblast (LEP) cell lines was studied. In HEF cells virus NWS-D and recombinant r12 induced synthesis of virus-specific macromolecules and produced infectious virions; virus WS-MK induced synthesis of virus complementary RNA (cRNA), virion RNA (vRNA), protein, RNP and non-infectious virions, but haemagglutinin cleavage was impaired and the virions formed contained uncleaved haemagglutinin. In LEP cells, infectious virions were formed only by virus NWS-D; viruses WS-MK and r12 induced synthesis of virus cRNA, vRNA, proteins and RNP; virus r12 had the haemagglutinin cleaved, whereas in virus WS-MK this process was impaired; neither virus WS-MK nor r12 was capable of forming virions. Analysis of the recombinant r12 genome showed that it had only inherited a single gene from NWS-D, the one coding for neuraminidase, having inherited all others (P1, P2, P3, HA, NP, M, NS) from WS-MK. The data obtained suggested that the inability of virus WS-MK to form infectious virions in HEF cells is due to the character of its neuraminidase, which is incapable of participating in haemagglutinin cleavage. The deficient reproduction of this virus in the other host-cell system (LEP) is apparently associated with some characteristics of another protein (other proteins) of this virus.


Amantadine antagonism of oxotremorine effects. Administration of oxotremorine to mice produced centrally-mediated effects, such as catalepsy and tremor, and peripheral muscarinic actions, such as diarrhoea and lachrymation. Pretreatment with amantadine (25--200 mg/kg) prevented these oxotremorine-induced effects in mice. Catalepsy was most susceptible and tremor most resistant to the administration of amantadine. The possible mechanisms involved are discussed. Our results validate the use of the oxotremorine model in the search for novel antiparkinsonian drugs.


Oscillations in tissue uptake of 75Se-L-selenomethionine in rats and mice adapted to controlled feeding schedules. The amino acid 75Se-L-selenomethionine was used to study variations in amino acid uptake by various tissues of rats and mice adapted to a schedule of controlled feeding and lighting conditions. Food only became available for an 8-hour period at the beginning of the 12-hour dark period of the 24-hour cycle. Systematic oscillations were observed in the uptake of selenomethionine by the liver, pancreas, blood, kidneys, skeletal muscle, bone and brain of both rats and mice but only very small changes were noted in the spleen, lung and heart. The level of the uptake into the liver and pancreas and possibly the kidney appear to be related to the dietary state of the animals.


Relationships between plasma corticosteroids and benzodiazepines in stress. Forcing a rat to swim in a situation from which there is no escape results in an increase in plasma corticosteroid level. This rise was selectively inhibited by benzodiazepines, phenobarbital and meprobamate but not by other psychotropic drugs like trycyclic antidepressants, monoamine oxidase inhibitors, neuroleptics and amphetamines. This effect of benzodiazepines is of central origin since diazepam did not block the rise in plasma corticosteroid level produced by adrenocorticotrophic hormone. Diazepam also had no effect on plasma corticosteroid levels in hypophysectomized rats or in rats treated with betamethasone. Brief stress did not alter binding of [3H]diazepam in vitro nor binding of [3H]flunitrazepam in vivo.


Influence of a phosphodiesterase inhibitor on the chronotropic effects of glucagon and norepinephrine in fetal mouse hearts. Fetal mouse hearts develop tachycardia in response both to norepinephrine and to glucagon, but although adenylate cyclase is stimulated and adenosine 3':5'-monophosphate (cyclic AMP) elevated by norepinephrine, no measurable changes are produced by glucagon. To test further the possible independence of glucagon chronotropy from the cyclic AMP system, the effects of a phosphodiesterase inhibitor were evaluated. The dose-response curve to norepinephrine was shifted to the left by the phosphodiesterase inhibitor 4-(3,4-dimethoxybenzyl)-2-imidazolidinone (Ro7-2956), but the dose-response curve to glucagon was unaltered. Thus, 10(-6) M norepinephrine produced an increase of 40 +/- 5 beats/min in hearts pretreated with Ro7-2956, as compared to an increase of 22 +/- 3 in control hearts (P less than .01). In contrast, 10(-6) M glucagon produced a rate increase of 25 +/- 4 beats/min in treated hearts vs. 26 +/- 4 beats/min in controls. These data are compatible with the hypothesis that adenylate cyclase and cyclic AMP are involved in the chronotropic response of the fetal mouse heart to norepinephrine but not to glucagon.


Changes in plasma corticosterone levels as a measure of acute dependence upon levorphanol in rats. Changes in plasma corticosterone levels have been utilized as a sensitive and reliable indicator of opiate withdrawal. By using rats prepared with chronic indwelling i.v. catheters, drug injections and sequential blood sampling were accompanied in conscious undisturbed animals. Acute administration of levorphanol tartrate (LT) at 0.5, 1.0 or 2.0 mg/kg b.wt. caused an elevation in circulating corticosterone. With the lowest dose of LT, hormone levels returned to pretreatment values by 180 min. Naloxone hydrochloride (NX), 0.4 mg/kg, administered 3 hr after pretreatment with LT, 0.5 mg/kg, produced a significant elevation in plasma corticosterone. In contrast, animals pretreated with saline did not show the same increase in hormone levels after NX. NX, administered at several doses, along with LT, suppressed the plasma corticosterone increase which is normally observed when LT is given acutely. When NX is administered at sufficient dosage, along with LT pretreatment, the subsequent administration of the antagonist did not elicit the withdrawal response. These data indicate that a similar increase in plasma corticosterone, upon challenge with NX after a single dose of morphine, generalizes to other opiates. Blockade of the initial rise in plasma corticosterone and subsequent increase upon injection of the antagonist speak to the probability of the responses being related and opiate specific.


Location of CNS neurons mediating the blood pressure fall after shock-induced fighting in the rat. Previous research has demonstrated a fall in systolic blood pressure in the rat measured 2--5 min following shock-induced fighting. This blood pressure fall appears to depend on intact CNS catecholamine neurons. The locus coeruleus is known to supply noradrenergic neuron terminals to much of the brain. In this study, we attempted to identify the location of the CNS catecholamine neurons mediating the blood pressure response to fighting by studying the blood pressure response to shock-induced fighting in locus coeruleus-lesioned and shamlesioned rats. The locus coeruleus-lesioned animals showed a blood pressure increase after fighting on the average across 2 days of testing, while sham-lesioned animals showed a blood pressure decrease after fighting. The difference between the blood pressure responses of the two groups was highly reliable. Since both histofluorescence and biochemical studies indicated that CNS norepinephrine levels were decreased in lesioned as compared to control animals, the findings are interpreted as showing that noradrenergic neurons originating in the locus coeruleus play an important role in mediating aspects of the relationship between fighting behavior and blood pressure response.


Macromolecular synthesis in cells infected by frog virus 3. XII. Viral regulatory proteins in transcriptional and post-transcriptional controls. Using fluorophenylalanine (FPA) to interfere with functional viral protein synthesis, we have investigated the complex transcriptional and post-transcriptional controls that operate in cells infected with frog virus 3. Our previous data, obtained by polyacrylamide gel electrophoresis of viral RNAs and proteins, showed that the addition of FPA at the beginning of infection completely prevented the synthesis of late viral RNAs and late viral proteins and blocked the normal progressive decline in the rates of synthesis of two quantitatively different classes (class I and class II) of early proteins. These results indicated that the initiation of late RNA and late protein syntheses, as well as the post-transcriptional regulation of early protein synthesis, was under the control of virus-specific proteins (D. B. Willis, R. Goorha, M. Miles, and A. Granoff, J. Virol. 24:326-342, 1977). In this communication, we show that the viral protein required to "turn on" the synthesis of late RNAs and late (class III) proteins was made within 1 to 1.5 h postinfection (p.i.); when we added FPA after this time, we observed the synthesis of all of the late macromolecules. The data also suggest that another viral protein, separate from the "turn-on" protein, controlled the abundance of late RNAs. In addition, at least two separate proteins were involved in the post-transcriptional regulation of two classes of early proteins. When FPA addition was delayed until 2 h p.i., the rate of synthesis of class I proteins (which normally peaked at 2 h p.i.) was reduced by 6 h p.i. just as in a normal infection, but the rate of synthesis of class II proteins (which normally reached a maximum at 4 h p.i. before declining) was reduced only when we waited until 3 or 4 h p.i. to add FPA. These experiments corroborate and extend previous evidence for the existence of numerous viral regulatory proteins in the control of frog virus 3 gene expression at the transcriptional and post-transcriptional levels.


Helminth parasites of fisher Martes pennanti (Erxleben) from Manitoba, Canada. Seven species of helminths were recovered during a survey of 162 fisher (Martes pennanti) from four areas of Manitoba: Baylisascaris devosi in 52 fisher; Taenia sibirica in 25; Physaloptera sp. in nine; Alaria mustelae in two; Metorchis conjunctus in one; Trichinella spiralis in one of 81; Molineus sp. in one. B. devosi was the most prevalent parasite and differences in its geographical distribution were possibly related to population density of fisher. The prevalence of other parasites did not appear to be related to density of fisher.


Hodgkin disease in monozygotic twins: a case report. Presented are the case histories of monozygotic male twins concordant for Hodgkin disease. This is believed to be the third such case report in the world literature. Its significance as it relates to the role of heredity in carcinogenesis is discussed.


Adverse effects of lidocaine and methylparaben on tracheal ciliary activity. The effect of standard concentrations of lidocaine HCl and methylparaben (preservative) on the ciliary activity of ferret tracheal rings in organ culture was assessed. Pure lidocaine concentrations as low as 0.5% caused complete ciliostasis which was reversible after removal of the drug. One percent and two percent effects were not completely reversible. Pure methylparaben concentrations as low as 0.06 mg/ml paralyzed cilia; and, at concentrations of 0.5 mg/ml or higher, adverse effects were not completely reversible. When lidocaine and methylparaben were combined at the same ratio used in commercial preparations, their ciliotoxic effects were additive. These data suggest that topical respiratory anesthesia may result in prolonged ciliary paralysis.


Middle ear ventilation in conjunction with adenotonsillectomy. This report continues the evaluation of the use of a ventilation tube in the middle ear at the time of adenotonsillectomy. This series of 72 cases has been followed for 1 to 3 years. Each patient had bilaterally similar middle ear effusions. A myringotomy was performed in both ears. In one of the ears a ventilation tube was inserted, the other ear acting as a control. In 3 out of 4 of the patients in this study, adenotonsillectomy and evacuation of the middle ear fluid were sufficient to clear the middle ear indefinitely, and the use of the ventilation tube was redundant.


[Activity and substrate specificity of the alcohol dehydrogenases of n-alkane oxidizing yeasts]. The activity and substrate specificity of alcohol dehydrogenases (ADH) in the fractions of cytosol and membrane particles were compared in the yeasts Torulopsis candida, Candida lipolytica and Candida tropicalis grown in media with glucose and hexadecane. In all studied yeast cultures growing in the medium with hexadecane, NAD-dependent ADH specifically dehydrogenating only medium and higher alcohols are induced in the membrane structures of the cells. Soluble ADH are found in the cytosol of the cultures grown either on glucose or on hexadecane. These ADH oxidize all alcohols with the carbon chain length from C2 to C16. As was found by electrophoresis in polyacrylamide gel, the number of ADH molecular forms in the cytosol fraction of the cultures depends on the carbon growth substrate being used and the peculiarities of yeast culture.


Induction of vitellogenin and growth of implanted oocytes in male cockroaches. Vitellogenins are yolk protein precursors that are synthesised in the liver of lower vertebrates in response to ovarian hormones, and in the fat body tissue of insects, under the influence, in most species, of juvenile hormone (JH) from the corpora allata (CA). Vitellogenins are normally restricted to females, although in male amphibians and roosters their synthesis can be induced artificially by the injection of oestrogens. Thus female specificity is maintained by hormonal differences between adult males and females. In insects, on the other hand, because the CA of adults of both sexes are active, it appeared that male fat body could not normally respond to JH by synthesising vitellogenin. However, precise JH synthetic rates of male CA are only known in Schistocerca gregaria and Diplopterapunctata, in which species they are low compared to the rates in the female glands. The absence of vitellogenin in adult males could thus be due to inadequate JH titres. We report here that synthesis of vitellogenin can indeed be induced in males of Diploptera by implantation of female CA or application of Diploptera by implantation of female CA or application of a JH analogue, ZR512 (Zoecon), and that implanted oocytes take up the vitellogenin.


Intranuclear injection of anti-actin antibodies into Xenopus oocytes blocks chromosome condensation. The role of contractile proteins in the structural organisation of the interphase nucleus and of metaphase chromosomes is largely unknown. Actin has been found in interphase nuclei of different species, especially in association with condensed chromatin. In the germinal vesicle (nucleus) of Xenopus oocytes, actin has been localised in the nuclear gel supporting the chromosomes and the extrachromosomal nucleoli. It has been reported that the premeiotic lampbrush chromosomes in these germinal vesicles are positively stained for actin and tubulin by the immunoperoxidase technique. Moreover, the longitudinal contraction of these chromosomes is ATP dependent. Therefore it has been suggested that actin participates in the structural organisation of the highly specialised lampbrush chromosomes. However, actin is not a major component of the metaphase chromosome scaffold. The results reported here suggest that actin is involved in the condensation of Xenopus chromosomes.


Effect of haloperidol on reflex activation of rat alpha-motoneurones. A possible explanation for akinesia and catalepsy? Effects of haloperidol on rat flexor and extensor alpha-motoneurones were studied in ventral roots of laminectomized rats under halothane anesthesia. The alpha-motoneurones were activated by tetanic stimulation of low-threshold afferents (group I and II), either of the ipsilateral peroneal nerve ("flexor alpha-motoneurones") or gastrocnemius-soleus nerve ("extensor alpha-motoneurones"). Haloperidol, given in the doses of 0.075, 0.15 and 0.30 mg/kg i.p. inhibited the reflex activation of flexor alpha-motoneurones; higher doses seemed to be more effective than lower ones. Apomorphine (2 mg/kg s.c.) partially antagonized the inhibitory action of haloperidol with some latency. Higher doses of haloperidol (0.15-0.60 mg/kg i.p.) also inhibited the reflex activation of extensor alpha-motoneurones; this inhibitory effect was, at least for a short time, antagonized by apomorphine (2 mg/kg s.c.). The threshold for reflex activation both of flexor and extensor alpha-motoneurones was raised by haloperidol and lowered by a subsequent administration of apomorphine. Our results suggest that akinesia and catalepsy, induced in rats by haloperidol might be, at least in part, due to a decrease in sensitivity of alpha-motoneurones to proprioceptive stimuli.


Alcohol intake, ethanol-induced narcosis and intoxication in rats following neonatal 6-hydroxydopamine or 5, 7-dihydroxytryptamine treatment. Newborn rats were treated with 5,7-dihydroxytryptamine (5,7-HT; 2 x 100 mg/kg s.c., 24 h interval) after pretreatment with desipramine (20 mg/kg s.c.) for depletion of brain 5-hydroxytryptamine (5-HT) or with 6-hydroxydopamine (6-OHDA; 3 x 100 mg/kg s.c., 24 h interval) for selective reduction of brain noradrenaline (NA). The 5,7-HT treatment resulted in a 53% reduction in endogenous 5-HT in the cerebral cortex and a 60% increase in the pons-medulla when determined in adult rats. The 5-HT content in the midbrain was not affected. Endogenous NA in the 6-OHDA treated animals was selectively reduced by 100% in the cerebral cortex, 35% in the midbrain and increased by 117% in the pons-medulla. No difference was found between the voluntary ethanol selection of these groups and that of the controls when measured at the age of 3 months. In a tilting-plane test, ethanol (2 g/kg i.p.) impaired the performance of the 6-OHDA treated rats significantly more than that of the controls. Moreover ethanol (4 g/kg e.p.) produced significantly longer narcosis in these rats. In contrast, the 5,7-HT treated rats were not affected significantly more than the controls in these tests. These results suggest that catecholamine neuronal systems interact with the expression of alcohol intoxication.


Neonatal ablation of the suprachiasmatic nucleus. Effects on the development of the pituitary-gonadal axis in the female rat. Ablation of the suprachiasmatic nucleus (SCN) at 2 days of age, prior to the formation of the retinohypothalamic projection, produces a permanent state of constant vaginal estrus in the postpubertal female rat. Although such lesions do not alter the onset of puberty in sighted rats, they do compensate for the delay in vaginal opening induced by neonatal binding. The ovaries of sighted and blinded SCN-lesion rats are small and polyfollicular and the pituitaries of blinded SCN-lesion rats are abnormally large. Sampling of plasma in the morning and afternoon for up to 12 consecutive days in sighted SCN-lesion rats reveals continuously low luteinizing hormone levels. This constellation of endocrine alterations does not correlate with damage to any structures outside the SCN. Since the organization of the rodent estrous cycle is circadian, these results emphasize further the importance of the SCN in circadian rhythm generation. The necessity of an intact SCN for the development of normal, cyclic reproductive function implies that sparing or recovery of function does not occur.


Phenobarbital dosage for control of neonatal seizures. The relationship of the initial phenobarbital dose to weight, gestational age, blood level, and seizure control was studied in 39 neonates. The blood proportional to the dosage per kilogram, and was not related to weight or gestational age. Seizures remitted only at blood phenobarbital concentrations above 16.9 micrograms per milliliter. Therapeutic levels can be achieved by the intravenous or intramuscular administration of 16 to 23 mg per kilogram of phenobarbital.


Experimental cerebral ischemia produces platelet aggregates. Human studies indicate that transient platelet abnormalities accompany acute cerebral ischemia. Although these abnormalities may precipitate the ischemi process, ischemia could also alter platelet function. Platelets were therefore studied in gerbils subjected to 1 hour of unilateral carotid artery occlusion. Venous blood from five clinically affected gerbils contained more aggregated platelets (37.8% +/- 6.4) than did blood from eight unaffected animals (11.1% +/- 3.0; p less than 0.01). Platelets labeled with 3H-serotonin were increased in ischemic brain; the ratio of radioactivity in the ipsilateral versus contralateral hemisphere was greater in eight affected (1.09 +/- 0.03) than in 19 unaffected (1.00 +/- 0.01; p less than 0.02) animals. The radioactive serotonin was located predominantly within blood vessels. Cerebral ischemia thus stimulated the formation of platelet aggregates, a response which could contribute to the ischemic process.


Seizure disorders and trace metals: manganese tissue levels in treated epileptics. We determined the concentrations of manganese in whole blood and hair in 52 epileptics, 6 blood relatives, and 24 normal controls. Blood, and possibly hair manganese content, was significantly lower in treated epileptics than in controls (p less than 0.002). Although not all patients showed reduced tissue manganese levels, most of those with frequent seizures had manganese levels falling below the lowest control level, suggesting a relationship between manganese tissue levels and high seizure activity. These differences in manganese levels were not correlated with the type, dose, or plasma levels of anticonvulsant medication. Reduced manganese availability at the neuronal level, where Mn++ stabilizes membrane excitability, may affect epileptogenic lesions to increase the likelihood of seizure activity.


Intravenous phenytoin in acute treatment of seizures. Large doses of phenytoin were administered on 159 occasions to 139 adult patients. Most patients had had more than three seizures or were in status epilepticus. Based on response to treatment, patients could be divided into two groups. Those with excellent response (recurrent seizures, 10%; mortality, 1%) included known epileptics with exacerbation of seizures (n = 75), atypical alcohol withdrawal (6), or miscellaneous conditions (17). Those with poor results (recurrent seizures, 57% mortality, 38%) included patients with anoxic or metabolic encephalopathy (14), stroke or other vascular disease (14), brain tumor (5), or trauma (5).


Phenytoin hypersensitivity: 38 cases.

Phenytoin hypersensitivity: 38 cases. To determine the frequency and severity of hypersensitivity reactions to phenytoin, we reviewed 38 cases of proven reactions. Patients were included only if no other drugs, including other anticonvulsants, were in use at the time of the reaction. Rashes were most frequent, followed by fever, lymphadenopathy, eosinophilia, abnormal liver function tests, blood dyscrasias, serum sickness, renal failure, and polymyositis. The pseudolymphoma syndrome, (fever, rash, and lymphadenopathy) occurred in nine patients. Thirty-five of the 38 reactions occurred within 2 months of the start of therapy. Phenytoin sensitivity accounted for 467 inpatient days during the 14 years of study. Early recognition of phenytoin reactions, prompt drug withdrawal, and appropriate therapeutic measures were necessary to prevent serious morbidity from phenytoin hypersensitivity.


Muscular dystrophy in six young girls.

Muscular dystrophy in six young girls. Clinical and genetic studies were made on progressive muscular dystrophy in six young girls. No chromosome abnormality was observed in these patients. The pedigree of one case implied a sex-linked recessive trait, and clinical features were identical with Duchenne dystrophy. The clinical manifestations of two sisters in another family were less severe than in their brother with Duchenne dystrophy. The clinical differences among these three cases are well explained by the Lyon hypothesis. Three other cases were compatible with childhood muscular dystrophy of autosomal recessive inheritance.


Pyruvate oxidation in Charcot-Marie-Tooth disease. Significant differences were found in pyruvate oxidation of disrupted skin fibroblasts from patients with Charcot-Marie-Tooth disease (CMT) or neuromuscular disease controls and normal controls, but there was a similar oxidative defect in both disease groups. "Heritable heterogeneity in situ" and additional enzyme faults may explain the normal activity of pyruvate dehydrogenase in some explants, and the lack of correlation between enzyme activity and CMT symptoms. Since experimental, histochemical, and microscopic studies support the concept of localized hypoxia in perineural or neural cells in CMT, the peripheral location of the defect suggests an inherited susceptibility to environmental influences in these cells.


EEG activation and mathematical calculation. Activation of epileptic seizures of epileptiform EEG abnormalities by specific types of intellectual activity has been documented only rarely. Despite infrequent occurrence, these cases are of interest in the study of epileptic mechanisms and cerebral integrative systems. We describe a 67-year-old woman with long-standing seizures who consistently activated right frontal spike discharges in the EEG when she attempted to perform mental arithmetic. The activating effect was not precisely related to the difficulty of the mathematical problem, nor to alerting or concentrated attention. No EEG activation resulted from reading, writing, reciting, revisualizing, or recalling numbers or other symbols.


Lymphocytes in multiple sclerosis: correlation with CSF immunoglobulins and cold-reactive lymphocytotoxic antibodies. Lymphocyte profiles were studied in patients with multiple sclerosis (MS) and normal controls. Apart from cold-reactive lymphocytotoxic antibodies (LCA), which were elevated in MS patients, there was no difference between MS patients and normal controls in terms of lymphocyte subpopulations, serum immunoglobulins, or responses to mitogens. There was no correlation between LCA and any of the immunologic characteristics measured. However, there was a correlation between immunoglobulin-bearing cells in the peripheral blood of MS patients and cerebrospinal fluid (CSF) levels of immunoglobulin and CSF viral antibodies. These results suggest that cold-reactive lymphocytotoxic antibodies do not affect lymphocyte function in patients with MS, that antigens stimulating "local" central nervous system (CNS) antibody production may be located outside the CNS and that locally produced CNS antibody may be made by immunoglobulin-bearing cells that migrate to the CSF from the periphery after exposure to antigen.


Neurological education of nonneurologists. In 1975, the Joint Commission of Neurology, created by the American Academy of Neurology and the American Neurological Association, published its report including recommendations on neurological education. Commission data indicated that although neurologists constitute less than 1% of all physicians, at least 5% of all ambulatory patients and 13% of all hospitalized patients had primary or secondary neurologic diagnoses, or both. Thus, the commission recommended a major effort in the education of general physicians in neurology. That advice is apparently being ignored. This situation poses a serious health care problem and urgent steps are indicated to reverse this trend.


The "hypernormal" CT scan in dementia: bilateral isodense subdural hematomas. Enlarged ventricles and prominent sulci are common findings on computed tomography (CT) in elderly demented patients. Three such patients were found to have small, symmetric ventricles and minimal sulci on tomography; these CT scans were considered "hypernormal" for the patients' ages and clinical syndromes. Bilateral isodense subdural hematomas were subsequently diagnosed by isotope brain scans in two cases and by angiography in the third. A "hypernormal" CT scan in an elderly demented patient suggests the possibility of bilateral isodense subdural hematomas, and requires further evaluation with isotope brain scan and, if necessary, angiography.


Phosphenes induced by sound.

Phosphenes induced by sound. Three adults with acquired unilateral visual impairment noticed phosphenes when they heard noises. They witnessed them only when resting in a dark or dimly illuminated room. The hallucinations persisted for days in a postkeratoplasty patient, for weeks in a patient with optic neuritis, and for months in a patient with compression of the optic nerve. The sound-induced phosphenes in these cases seemed to be a pathologic variety of hypnagogic hallucination. We theorize that under conditions of altered excitability and visual deafferentation of the brain, cells capable of responding to both visual and auditory stimuli become hyperresponsive to sounds.


Computerized tomography in central pontine myelinolysis. We describe an autopsy-proven case of central pontine myelinolysis (CPM) with premortem computerized tomographic (CT) visualization of the lesion on two scans, performed with an interval of 2 weeks. This case demonstrates the capability of CT to support the clinical diagnosis of central pontine myelinolysis. Identification of the condition should facilitate prompt initiation of aggressive supportive care.


Intramedullary spinal cysticercosis.

Intramedullary spinal cysticercosis. Intramedullary cysticercosis of the spinal cord is rare; there have been only 26 previous cases. We describe a patient with low back pain, paraparesis, lumbosacral sensory loss, and signs of meningeal irritation. The clinical diagnosis was spinal cord tumor, but at surgery there was a cysticercus cyst within the lumbosacral cord. Careful search did not reveal the parasite in any other part of the body. This is the first case of spinal cysticercosis reported in Japan.


Ulnar-to-median nerve anastomosis in the forearm: electromyographic studies. A patient with muscle weakness was studied electromyographically. An ulnar-to-median-nerve communication in the forearm on one side was an incidental finding. The electrophysiologic features are described and contrasted to those seen in the common Martin-Gruber anastomosis.


Visual evoked potentials in infants with hydrocephalus. Visual evoked potentials to flash stimuli were recorded in 15 infants with hydrocephalus. All demonstrated increased latencies for the prominent positive component (P2) of the response, compared to the mean value for age-matched controls. In nine infants studied prior to and 1 week after shunt procedure, the P2 latency decreased.


Progressive supranuclear palsy and normal-pressure hydrocephalus. In three patients who fulfilled the clinical criteria of progressive supranuclear palsy, radiologic investigations suggested normal-pressure hydrocephalus. Shunt procedures in all three resulted in temporary improvement of gait, mentation, and bladder control, but gaze paralysis and extrapyramidal findings did not change.


Left-to-right transfer of language dominance: a case study. Partial recovery from aphasia was documented in an individual rendered hemiplegic and globally aphasic by embolic infarction in the distribution of the left middle cerebral artery. Computed tomography showed total destruction of the classical left hemisphere language areas, indicating that the right hemisphere was responsible for the improved linguistic function. This observation is consistent with right hemisphere language capacity demonstrated after left hemispherectomy or commissurotomy. Right hemisphere language function may underlie much of the recovery from aphasia after injury of the left hemisphere.


Conversion of photosensitive to scotosensitive epilepsy: report of a case. A 13-year-old girl had had two grand mal attacks induced by viewing television when she was aged 10 and 11 years, and again a year later. Clinical and electroencephalographic (EEG) findings were typical of photosensitive television epilepsy. However, a further grand mal seizure when the patient was age 13 years occurred in darkness. Two additional EEG studies showed continuous paroxysmal activity during darkness. The epileptiform discharges were abolished by light and eye opening.


HLA types and immunity in multiple sclerosis. HLA types and levels of humoral and cell-mediated immune responses to several antigens were studied in a large group of patients with multiple sclerosis, and in controls. Patients were more likely than controls to have the DRw2 antigen. They had higher mean antibody titers to measles but not to cytomegalovirus, herpes 1, or herpes 2, and had less competent cell-mediated responses. Antibody titers to measles were lower and cell-mediated immune responses were more effective in patients with the DRw2 antigen in patients than in patients without it. This apparent specificity for measles suggests that the etiology of multiple sclerosis is related to the immune response to measles or related viruses.


Clinical manifestations of eosinophilic memingitis due to Angiostrongylus cantonensis. Between 1959 and 1976, 34 patients were seen in Hawaii with eosinophilic meningitis. Angiostrongylus cantonensis was recovered from two of these patients. The remaining cases were presumed to be due to this parasite because of clinical and epidemiologic findings. The most likely source of infection for eight patients was ingesting raw terrestrial snails or slugs, and for six patients eating raw or poorly cooked crustaceans. Patients typically presented with severe headache; neck stiffness and fever were usually mild or absent. Paresthesias were noted by most adults. The cerebrospinal fluid (CSF) cell count ranged from 150 to 1500 leukocytes per cubic millimeter, with a mean eosinophil percentage of 38. CSF IgE levels were not abnormal in four patients so studied. Although two deaths occurred, the illness was typically self-limited, resolving completely with no specific treatment.


Fatal ataxic encephalopathy and carnitine acetyltransferase deficiency: a functional defect of pyruvate oxidation? A 3-year 8-month-old girl died after 14 months of illness characterized by episodes of intermittent ataxia associated with oculomotor palsy, hypotonia, mental confusion, and disturbances of consciousness. In the last 4 months of life, there were signs of liver dysfunction. Pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase activities were normal in autopsy brain specimens and in cultured fibroblasts from the patient. Carnitine acetyltransferase was deficient in liver, brain, kidney, and cultured fibroblasts. Medium- and long-chain carnitine acyltransferase activities were normal. It is proposed that a functional defect of acetyl-coenzyme A (acetyl-CoA) utilization in brain mitochondria accompanies the carnitine acetyltransferase deficiency.


Levodopa with benserazide or carbidopa in Parkinson disease. Plasma levodopa and therapeutic responses to treatment with levodopa in combination with benserazide or carbidopa were studied in 49 patients with Parkinson disease not previously treated with levodopa in a blind randomized crossover trial. The treatment periods were 12 weeks; similar dosage schedules were used, with doses that induced equal levels of plasma levodopa in both combinations. In pretrial studies of plasma levodopa responses, 200 mg of levodopa and 50 mg of benserazide was equal to 250 mg of levodopa combined with 25 mg of carbidopa. Equal plasma levodopa responses to both combinations were also found during the trial. There was no significant difference between the treatment groups in beneficial effects on parkinsonian disability and individual symptoms or in the frequency of involuntary movements. However, nausea and vomiting occurred significantly more often during treatment with levodopa and carbidopa than during treatment with levodopa and benserazide. This difference was probably due to inadequate inhibition of peripheral decarboxylase inhibitor by the 1:10 ratio of carbidopa to levodopa.


Sensory kindling: implications for development of sensory prostheses. In designing sensory prosthetic implants that operate on the basis of direct electrical stimulation of the brain, the question of the plasticity of the tissue's response to the stimulation arises. Especially relevant is the kindling phenomenon, in which convulsions develop in response to repeated low-level electrical stimulation of the brain, including thalamic or neocortical primary sensory structures. Therefore, caution should be exercised in the development and application of prosthetic devices that directly activate brain tissue for long periods of time.


The importance of studying sural nerve conduction and late responses in the evaluation of alcoholic subjects. Motor conduction velocities of median, ulnar, peroneal, and tibial nerves and sensory conduction velocities of median and ulnar nerves were studied in 30 alcoholic subjects and a similar group of control subjects. The results were compared to sural nerve conduction velocities and late response latencies (H reflex, F response). The latter two techniques improved the diagnostic yield by 20%: Whereas 73% of our patients showed an abnormality of conduction with conventional techniques, 93% had an abnormality of sural nerve conduction, late response latencies, or both. Abnormalities of motor and sensory conduction, which were more prominent in the lower limbs than the arms, could be documented in patients who did not have any clinical evidence of peripheral neuropathy. The electrophysiologic studies performed in the present study suggest that "axonal degeneration" is the underlying pathologic process in alcoholic peripheral nerve disease.


Chorea induced by oral contraceptives.

Chorea induced by oral contraceptives. A rare complication of oral contraceptive therapy is the induction of chorea. We here describe five cases of chorea in patients receiving low- or high-dose estrogen-containing contraceptives. All patients were nulliparous, young (average age 19 years), and became symptomatic shortly (average of 5 weeks) after initiation of contraceptive therapy. Two patients previously suffered an episode of Syndenham chorea; one experienced chorea in the course of Henoch-Schönlein purpura; and two had a history of congenital cyanotic heart disease without chorea. Dyskinesia resolved in all patients upon discontinuing the medication. Patients with preexisting striatal abnormalities appear more susceptible to oral contraceptive-induced chorea which is reversible on drug discontinuation. The mechanism of oral contraceptive-induced chorea is unknown, but clinical and experimental data suggest that it involves altered central dopaminergic activity.


Isaacs syndrome with laryngeal involvement: an unusual presentation of myokymia. A woman with widespread myokymia presented initially at age 19 with hoarseness and mild dyspnea on exertion. The diagnosis of Isaacs syndrome was suggested by the clinical findings of widespread continuous muscle activity and depressed tendon reflexes, although she lacked the usually prominent increased muscle tone. The diagnosis was confirmed by the electromyographic demonstration of continuous spontaneous muscle action potentials that were abolished by neuromuscular blockade but not by local nerve blockade. Pulmonary function tests were consistent with fixed extrathoracic obstruction. The vocal cords were closely approximated. Electromyographic studies of the laryngeal muscles under general anesthesia revealed continuous muscle activity, which accounted for the hoarseness and much of the exertional dyspnea. The patient responded well to treatment with phenytoin and carbamazepine. This unusual syndrome should be considered in the differential diagnosis of patients with respiratory complaints and muscle fasciculations, even though they have normal muscle tone.


Poriomania.

Poriomania. Three patients with complex partial seizures experienced prolonged episodes of aimless wandering followed by retrograde amnesia for the experience, a phenomenon called poriomania. Our experience and the literature suggest that this behavior is a prolonged postictal automatism and is not psychogenic. Adjustments of anticonvulsant therapy eliminated this behavior in all three of our patients.


Acute multiple brachial neuropathy and Ehlers-Danlos syndrome. Although acute brachial neuritis is a well-known syndrome, factors that contribute to its pathogenesis are not yet understood. Only once before has this syndrome been reported in connection with Ehlers-Danlos syndrome. We describe here a 24-year-old man who suddenly developed acute multiple brachial neuritis of the right shoulder and on neurologic examination showed an associated finding of Ehlers-Danlos syndrome. The latter syndrome was also confirmed in other members of his family. This combination may have been overlooked previously. Mechanical and traumatic factors may play an important role in both pathogenesis and therapy.


Brachial plexus neuropathy as the initial presentation of systemic lupus erythematosus. A patient presented with bilateral brachial plexus neuropathy which 2 weeks later evolved into a polyneuropathy involving all four extremities. On further investigation, the patient was found to have systemic lupus erythematosus. Treatment with steroids was accompanied by complete resolution of the neurologic findings.


The dizzy, the giddy and the vertiginous. For optimal examination of the giddy patient the case history is the best basis. The description of what the patient feels is not as important as has been stated rather often. The words dizzy, giddy and vertiginous from a patient do not really mean different things - they only mean: I feel unbalanced or disequilibrated. In the anamnesis it is much more important to find out firstly whether the disturbances are: (1) paroxysmal; (2) one acute attack; (3) chronic, (4) positional (positioning), and secondly whether the giddy feeling is accompanied by other disturbances (deafness, headache, pains, palsies, etc.). Some tables are presented that give a survey of the combination of some of these data and that facilitate the further examination towards the goal of the right diagnosis.


Antecedent factors and outcome in amenorrhea-galactorrhea. One hundred seventeen patients with amenorrhea and galactorrhea or hyperprolactinemia were evaluated with regard to antecedent factors, results of investigations, and management. Full details of the outcome of prolonged follow-up were available for 104 patients. Patients who developed amenorrhea-galactorrhea after withdrawal of oral contraceptives or postpartum had a lower incidence of pituitary adenomas than did those who developed amenorrhea-galactorrhea spontaneously. Six of a total of 40 tumors were detected only during the follow-up period. This study suggests that patients with spontaneous amenorrhea-galactorrhea have a greater risk of developing a detectable pituitary adenoma than do those with postpill or postpartum symptoms. However, patients with a microadenoma are more likely to have had postpill onset of hyperprolactinemia. Plasma prolactin (PRL) in patients with postpill amenorrhea-galactorrhea increased in proportion to the duration of oral contraceptive use.


Histological and ultrastructural changes in idiopathic facial palsy. Light- and electron-microscopic findings in the facial nerve are reported in a patient who died 8 months after the onset of acute idiopathic facial palsy. There were signs of regeneration after axonal destruction, and inflammatory infiltrates confined to the intracanalicular part of the nerve were found. These findings suggest a viral or immunological etiology, which may become pathogenetic due to the length and narrowness of the Fallopian canal.


Pressure-regulating mechanisms in the inner ear. The perilymphatic pressure was studied in relation to pressure step variations in the external ear canal and in the middle ear. The transfer of pressure via the ossicular chain reached its limiting value at quite low pressures. When pressure steps were applied directly to the middle ear, there was almost a direct transfer of pressure for positive changes. Nonlinearities were shown between positive and negative pressure steps. The pressure-regulating ability of the inner ear was illustrated by means of calculating the time constants of the pressure transfer curves.


Indirect measurement of laryngeal and tracheal resistance. We used a body plethysmograph to determine airway resistances in 485 cases of laryngeal and tracheal stenoses. 143 cases who had resistances exceeding 60 mm H2O/l.a.sec underwent surgery. A vocal cord was laterally fixed in 49 patients suffering from bilateral recurrent paralysis. Optimal results were obtained at a postoperative resistance level of 30 mm H2O/l.a.sec (standard value: 14.77 +/- 6.53 - n - 387). The patients could carry out work of medium intensity and had a steady voice. We performed tracheal interventions in 94 cases of tracheal stenoses. A mean postoperative resistance of 29.9 mm HWO/l.a.sec, with a tracheal diameter of 7-8 mm was attained. In practice, only a few patients found the remaining obstruction a hindrance, during work of maximal intensity. No recurrences were observed after treatment. Airway resistance exceeding 150 mm H2O/l.a.sec were found in 13 new admissions and 73 times in those undergoing therapy. In these cases asphyxiation threatens. These patients must be tracheotomized or intubated immediatly.


Intrathoracic goitre with the superior vena cava syndrome, hoarseness and acute stridor. A 69-year-old man presented with acute stridor and was found to have the superior vena cava syndrome and bilateral laryngeal paresis. A clinical diagnosis of malignancy was made, but before any definite investigations could be made an emergency operation had to be performed to relieve the trachea. On operation the patient was found to have a benign goitre. The literature on the subject is discussed. Since the great majority of cases with the superior vena cava syndrome is caused by malignant diseases, it has been suggested that in acute cases radiation therapy should be started without a microscopic diagnosis if necessary, but such a practice must be warned strongly against.


Lymphocyte-macrophage activity in the endolymphatic sac. An ultrastructural study of the rugose endolymphatic sac in the guinea pig. The irregular epithelial layer which delimits the intermediate part of the endolymphatic sac, and the surrounding perisaccular tissue, were examined morphologically in the guinea pig by transmission electron microscopy. Specialized areas of the epithelium which have previously been designated as "non-vascularized epithelial processes" (NVP) were constantly observed. These proliferative areas showed a close topographical relation to the free luminal cells and contained an abundance of lymphoid cells. Lymphocytes and macrophages were intimately associated with each other in a manner similar to that seen in these two types of cells in antigen-stimulated lymphoid tissues. There was a marked degeneration and phagocytosis of cells. The richly vascularized perisaccular tissue was rich in plasma cells, monocytes, mast cells and lymphocytes. The latter could be seen to migrate through the endothelial cells in the thin post-capillary venules into the sac tissue. The authors consider that the endolymphatic sac plays a role as an immunological defence organ for the internal ear. A hypothetical model concerning circulation and turnover of certain of the free intraluminal cells in presented.


Tympanometry in 3-year-old children. Type of care as an epidemiological factor in secretory otitis media and tubal dysfunction in unselected populations of 3-year-old children. A total of 938 healthy 3-year-old children, divided into two unselected cohorts within the same geographic area, had tympanometric screening and re-screening. The results were assessed according to the parameters: season and the way the children were cared for. In all tests children in day-care centres had the highest prevalence of secretory otitis and tubal dysfunction due rather to an excess of long courses of illness than of an increased incidence. Regardless of the season, 8-13% of all children in day-care centres exhibited persistent secretory otitis through 6 months as compared with 2-4% of children not attending day-care centres. The lowest morbidity rate and the shortest course was found in children cared for at home whose tympanometric results were also to a marked extent independent of the season. Children in family day-care had results which in summer corresponded to those in children cared for at home and in winter approximately to those in the day-care centres. The theoretical and practical implications of the findings are discussed.


Nystagmometry: the art of measuring nystagmus parameters by digital signal processing. A method of nystagmus analysis has been developed for clinical and research purposes. Optimum flexibility of analysis is indicated to cope with the problematic signals frequently encountered in pathology. Different modes of analysis may be obtained, varying from fully automatic to step-by-step interactive analysis. Artifact detection and rejection is performed by means of regression analysis with some additional condition tests. The default conditions may be modified or inactivated. A variety of output and display facilities may be used, including permanent storage of adequately labelled retrievable nystagmus data.


Extracranial meningioma presenting as a nasal polyp. The extracranial occurrence of meningiomas is summarized. A patient suffering from repeated episodes of epistaxis presented with a lobulated nasal polyp which was found to be a meningioma. At subsequent radical removal, the extracranial location in the nose, ethmoidal region and cribriform area was verified.


Effect of dimetridazole on transmission of Histomonas meleagridis by Heterakis gallinarum. The administration of an antihistomonal drug, dimetridazole, at a dose of 0.08% in feed, controlled experimental infections with Histomonas meleagridis in chickens. The treated birds developed no lesions and the duration of infection with H. meleagridis was reduced. This drug regimen, however, did not always prevent incorporation of H. meleagridis into eggs of Heterakis gallinarium; heterakid eggs pooled from medicated chickens in which H. meleagridis had never been detected transmitted the protozoan to 1 of 10 turkeys fed the eggs. Thus, therapeutic treatment of chickens with dimetridazole may reduce, but not eliminate, transmission of H. meleagridis by eggs of H. gallinarum from medicated birds.


Patterns of milk transmission of Strongyloides ratti. Eight days after mother rats were injected with 4000 infective larvae of Strongyloides ratti at different stages of lactation the numbers of adult worms in their intestines were uniformly low (less than 3% of the dose) compared with unmated controls (mean = 25%). Those in their litters varied from 12% on day 5 to a maximum of 47% on day 17 post partum. These data, which do not correlate with lactational performance, imply that parasite movements in lactating rats are controlled by qualitative, not quantitative, consequences of humoral events. The numbers of worms in litters are concluded to be the result of the interaction of dynamic determinants of larval routes in the mother and changes in the suitability of the neonatal gut as an environment for worm development. The timing of events leading to milk-borne infection is defined. Injected larvae were closely synchronized in their movements, which were completed in 36 h. Larvae experimentally diverted into the mother's tissues during her first lactation were not available for the infection of a second litter.


Effect of cigarette smoke exposure on maturation of the antibody response in spleens of newborn mice. Balb/c mice were exposed to smoke from Kentucky Reference IRI cigarettes within 24 hr after birth on a Prototype Mark II Walton Horizontal Smoke Exposure Machine for various periods of time up to 10 wk of age. There was no difference in the magnitude of the splenic plaque-forming cells (PFC) response in smoke-exposed and untreated control animals immunized with sheep red blood cells (SRBC) on sequential days up to day 9 postpartum. However, beginning at day 10 and for each subsequent time period assayed thereafter, there was a statistically significant reduction in the number of splenic PFC observed in the smoke-exposed animals. On day 10, the PFC response of smoke-exposed mice was reduced by 33%, on day 14, there was a 60% reduction, whereas animals exposed to smoke from 4-10 wk showed a 90% reduction of the splenic PFC response.


Angiosarcoma of the head and neck.

Angiosarcoma of the head and neck. Angiosarcomas are uncommon tumors of the skin and soft tissues, but occur in endothelial cells of almost any internal organ. When they occur in the skin, the head and neck are the most common sites of origin. Nothing is pathognomonic about their clinical presentation, and the pathologic diagnosis can only be established by biopsy. The frequent multicentric nature of the tumor and propensity for extensive subcutaneous spread require wide treatment fields, whatever the modality of therapy, and account for the low survival reported. Four cases and their outcome are reported, with only one patient achieving an apparent cure following irradiation therapy. Based on experience and extensive review of the literature, a best therapeutic approach cannot be recommended. Since the outlook for cure is so unfavorable, there appears to be a need for cooperative studies using surgery, irradiation, and perhaps, chemotherapy.


Calorigenic effects of noradrenaline and glucagon on white adipocytes in cold- and heat-acclimated rats. Calorigenic actions of noradrenaline and glucagon on isolated epididymal fat cells from warm-acclimated controls, cold-acclimated and heat-acclimated rats were measured by the use of a twin-type conduction microcalorimeter. Both noradrenaline and glucagon stimulated heat production in isolated adipocytes maximally in doses of 1 microgram/ml and 10 microgram/ml, respectively. Maximal responsiveness of adipocytes per unit cell to noradrenaline was not influenced by cold acclimation, while it was reduced by heat and acclimation. Maximal response in total epididymal fat cells to noradrenaline was increased in cold acclimation and not changed in heat acclimation at increased numbers of adipocytes in both cold-acclimated and heat-acclimated animals. Maximal response per unit cell as well as per total epididymal fat cells to glucagon was increased in cold acclimation and reduced in heat acclimation. The present results indicate that the modified responses of target adipocytes to noradrenaline and glucagon are involved in the development of temperature acclimation.


Influence of physical workload on freerunning circadian rhythms of man. While living under constant conditions and complete isolation from environmental time cues for about 4 weeks, 9 male subjects exercised on a bicycle ergometer seven times per 'day' during two weeks and refrained from physical activities during the other 2 weeks. The freerunning circadian rhythms of wakefulness and sleep and of rectal temperature showed, on the average, no difference between the two sections with regard to the autonomous period and the tendency towards internal desynchronization. Even in the one experiment in which the two rhythms became internally desynchronized, the periods of the rhythms remained unchanged during the time the subject worked on the bicycle. Only in one out of the nine subjects, the autonomous period was considerably longer under the influence of work than without it. The hypothesis is advanced that the period of an autonomous rhythm becomes normally independent of physical workload by way of a compensation mechanism.


Renal blood flow after bilateral ureteral ligation in the rat. Renal blood flow (RBF) in rat was measured by using a noncannulating electromagnetic flowmeter. In the sham control rats, anesthetized with Inactin, RBF averaged 7 ml/min/g KW when arterial blood pressure was above 110 mm Hg. Autoregulation of RBF was observed when the arterial blood pressure was in the range of 110-150 mm Hg. Glomerular filtration rate (GFR), measured by polyfructosan clearance, averaged 1.08 ml/min/g KW. In experimental rats with 24 h of bilateral ureteral ligation (BUL), RBF averaged 38% of control value. During 1/2-3 h following release of the left ureteral occlusion, RBF increased to 60% of control value. The autoregulatory ability of the damaged kidney was reduced during BUL and did not improve after releasing occlusion. During the post-obstructive period arterial blood pressure remained stable. Thus, a high total renal vascular resistance was responsible for the depressed RBF. GRF in these rats averaged only 9% of control value. The reduction in RBF alone does not explain the drastic reduction in GFR in this model of renal failure.


Effects of chloride on the electrical and mechanical properties of guinea pig ventricle. The purpose of this study was to investigate the influence of chloride on the electrical and mechanical properties of the guinea pig ventricular myocardium. Bathing media were made chloride free by substituting the relatively impermeant anion gluconate, isethionate, or sulfate. Removal of chloride increased contractility and decreased the duration of the action potential. Additional experiments explored the influence of chloride free media on electrogenic calcium influx estimated from the magnitude of the action potential in cells partially depolarized by potassium (the slow response). In the absence of chloride, transient increases occurred in the magnitude of the slow response while the positive inotropic effect was maintained. These experiments suggest that the effects of chloride free media are mediated secondarily by an enhanced calcium influx.


Maleic acid induced aminoaciduria, studied by free flow micropuncture and continuous microperfusion. The injection of 200 mg/kg BW maleic acid was found to be a suitable dose for exploring the experimental Fanconi syndrome by micropuncture techniques in rats. In clearance experiments, the fractional excretion of glycine, L-alanine, L-aspartate and taurine was measured. After intraperitoneal administration of maleic acid the excretion of these amino acids was increased in the range between the 20-fold and the 230-fold. Free flow micropuncture experiments showed that the reabsorption of these amino acids is reduced drastically along the whole proximal tubule. Continuous microperfusion experiments lead to the result that, in maleic acid pretreated rats, the reabsorption of 14C-glycine from the proximal convolution was strongly inhibited. It was found, furthermore, that after blocking the saturable glycine transport by L-phenylalanine, the remaining reabsorption of glycine (corresponding to passive diffusion) was exactly the same with and without maleic acid. Microinfusion experiments with 8 mumol.1(-1) L-3H-alanine into the early distal tubule showed a fractional recovery of 103 +/- 4.2% (S.D.) in the control and of 101 +/- 6.5% in presence of maleic acid. It is concluded that maleic acid inhibits the saturable reabsorption mechanism of amino acids along the proximal tubule. Passive permeability of the tubular membrane does not seem to be altered by maleic acid.


Kinetics of L-proline reabsorption in rat kidney studied by continuous microperfusion. Renal tubular reabsorption of 3H and 14C labelled L-proline was measured in vivo et situ by continuous microperfusion of single proximal tubules of the rat. The reabsorption is shown to be saturable. Passive diffusion plays a relatively small role in the reabsorption. A maximum possible permeability coefficient of 25 micrometers 2.s-1 for proline was calculated. Two transport systems were found, one with a small affinity and a high capacity, the other with a very high affinity and a small capacity. The following values were estimated. Jmax 1 = 2.6 +/- 0.28 (SEM) nmol.m-1.S-1 Km1 = 11.8 +/- 1.7 (SEM) mmol.1-1 Jmax 2 = 9.6 +/- 1.92 (SEM) pmol.m-1.s-1 Km2 = 29.3 +/- 7.8 (SEM) mumol.1-1. Whereas the first system reabsorbs the bulk of the filtered load, the activity of the second system explains the extremely small amount of proline found in the final urine. Diisopropylphosphorofluoridate--a specific inhibitor of dipeptidyl peptidase IV--decreases the reabsorption of L-proline and L-alanine but has no influence on the reabsorption of the basic amino acid L-arginine and the acidic amino acid L-glutamic acid. This result correlates with a recent speculation that dipeptidyl peptidase IV is involved in proline and alanine reabosrption.


Acute effects of hydrocortisone on the reabsorption of inorganic phosphate in normal, adrenalectomized and parathyroidectomized rats. Clearance studies have been performed in order to examine the acute effects of hydrocortisone on the reabsorption of inorganic phosphage (Pi) in normal, acutely adrenalectomized (Adr. X) and acutely parathyroidectomized (PTX) rats. Hydrocortisone increased the glomerular filtration rates in all groups, normalized the capacity to excrete water in the Adr. X animals, did not change consistently the fractional reabsorption of sodium in all series and diminished the fraction reabsorption of inorganic phosphate in Adr. X rats from 91.4 +/- 6.5 (mean +/- S.D.) to 78.2 +/- 8.5% (P less than 0.001). It is concluded that the decrease of the fractional reabsorption of Pi in the Adr. X animals was rather the result of the increased filtered load than a direct effect of hydrocortisone on the Pi transport.


Magnesium dependent contraction of glycerinated smooth muscle. The effect of Mg2+ on the contraction of glycerinated smooth and skeletal muscles was examined. In the absence of Ca2+, glycerinated smooth muscle contracted slowly when exposed to 5 mM adenosine triphosphate (ATP) and Mg2+. The magnitude of this contraction depended on the concentration of Mg2+ in a range of 1--20 mM. When 20 mM Mg2+ was used with ATP, glycerinated smooth muscle contracted almost maximally in a Ca2+ free environment, and it did not contract further on subsequent addition of 0.1 mM of free Ca2+ (EGTA-CaEGTA buffer). In contrast, in skeletal muscle a Ca2+ dependent contraction could always be elicited in the presence of 1--20 mM Mg2+ and 5 mM ATP. Tension development in smooth muscle induced by Mg2+ and ATP was not due to a contamination by Ca2+ or the removal of a Ca2+ sensitive protein. In the present experimental conditions, glycerinated smooth muscle developed a Mg2+-dependent contraction in a Ca2+ free medium, but glycerinated skeletal muscle did not.


Diffusion, pericapillary distribution and clearance of Na-fluorescein in the human nailfold. An intravital fluorescence videomicroscopy technique is described in an attempt to develop non-invasive methods for the study of transcapillary exchange in human physiology and clinical medicine. The apparatus used consists of a Ploemopak incident light fluorescence microscope and a low light level television camera with linear output. After intravenous bolus injection of Na-fluorescein in 12 healthy subjects the movement of the dye particles in the nailfold was observed and stored on video-tape. Immediately after arrival the dye leaks into a halo-like section and later into the more remote parts of the pericapillary space. By moving a densitometric window on an axis transversal to the capillary loop (single frames of the tape), characteristic patterns of fluorescent light intensity distribution were obtained at different time intervals. At the edge to the halo the high pericapillary light intensity decreases abruptly moving further away from the capillary (mean: 10.0 micron) for 20 min and more in each individual indicating the presence of a diffusion barrier at this location between halo and more remote areas. Clearance of the dye is much slower than transcapillary diffusion and lasts approximately 2 h.


The electrical activity recorded from smooth muscle of the circular layer of the human stomach. The membrane properties of circular muscles of 55 human stomachs were investigated by microelectrode and double sucrose gap methods. The membrane potential of the circular muscle of the corpus region was -57 mV and no regional difference was evident as compared with tissues from the antrum and cardia. The stomach muscle presented cable like properties, and the length constant measured in the corpus region was 1.34 mm. The circular muscle of all regions of the stomach exhibited slow waves. The amplitude and duration of slow waves varied markedly (the mean values were 18 mV and 6 s, respectively). The Q10 value for the slow wave was 2.4. The slow wave could be divided into two different components (first and second component) by application of electrical current or by using solutions with various ionic environments. Na ions had more effect on the spike component and Ca ions on the second component. The generation of the first component of the slow wave was blocked by either Na-free, K-free, Ca-free, or Cl-deficient solution but this component reappeared by application of outward current pulse, except in Cl-deficient solution. These results suggest that the generation of slow wave depends on more than one type of ion and that metabolic factors do indeed play a role. Membrane properties of the human stomach were compared with those of the guinea-pig stomach.


Regional blood volume changes of the lungs in response to the vegetative nerves stimulation. Significant regional differences in the values of blood volume change response within one lobe of the lung upon the cervic sympathetic and parasympathetic nerves electrical stimulation have been demonstrated through the use of regional lung electroplethysmography method under the conditions of a minimal surgical trauma in dogs, cats, and rabbits kept in a supine position. The vascular component of the reaction has been isolated. It consists in blood volume increase in the lungs during the vagus stimulation and blood volume decrease during the sympathetic nerves stimulation. This response is very well manifested in central portions of the lung lobes and decreases progressively in peripheral direction. Blood volume changes due to different body positions relative to the gravitation direction have been demonstrated. Mechanisms of regional differences in blood volume changes have been discussed. The gravitation factor has been suggested to be also responsible for the formation of the neurogenic vasomotoric reaction in lungs.


Influence of intratubular pressure on proximal tubular compliance and capillary diameter in the rat kidney. Tubular compliance is the response of tubular diameter to changes in intratubular pressure [7]. Proximal tubular compliance was determined directly by measurements of tubular diameter and pressure and indirectly using a mathematical model of tubular fluid flow based on measurements of the hydraulic pressure gradients along the tubule under free flow conditions and during an induced pressure reduction at the end of the proximal tubule. The two independent methods yielded similar values for compliance. Proximal tubular compliance was found to depend upon the intratubular pressure: tubular compliance was significantly higher (P less than 0.001) when the intratubular pressure was reduced below normal (1.0 micron cm H2O-1) than when the pressure was increased above the control value (0.4 micron cm H2O-1). Almost identical compliance values were measured in sodium pentobarbital and inactin anaesthetized rats (P greater than 0.8). Intratubularpressure changes resulted in inverse changes in the diameters of the adjacent capillaries, suggesting that the peritubular capillaries are distensible structures.


Low impedance coaxial K+ selective microelectrodes. A procedure for preparing coaxial K+ selective microelectrodes with a low longitudinal resistance (Re) of the liquid ion exchanger selective barrel is described. The low resistance was attained by inserting another microelectrode filled with 0.5 mol . 1-1 KCl into the ion-exchanger column (Corning 477317). The lower longitudinal resistance decreases the noise level and consequently increases the resolving power five times. This modification makes it possible to measure small and rapid K+ concentration changes.


Dopaminergic pathways in the rat central nervous system and rotational behavior. Unilateral lesion of substantia nigra or ventral tegmental area causes ipsilateral rotational behaviour after receptor stimulation by apomorphine, whereas contralateral rotations were observed after lesion of globus pallidus. The alterations in dopamine and noradrenaline content of relating structures were determined by radiometric microassay. There is no strong correlation between transmitter depletion and motoric asymmetry. The site and extent of lesion seems to be more determinative to motoric disturbances.