Biomedical subjects
Publications and source records attributed to K Goto.
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CT findings in 6 autopsy cases of subcortical arteriosclerotic encephalopathy (SAE) are reported. A diffuse area of nonhomogeneous decreased density was observed in the deep white matter of both cerebral hemispheres, together with moderate dilatation of the lateral ventricles and ragged margins. The most characteristic pathological findings at autopsy were a diffuse area of incomplete infarction containing multiple small infarcts as well as cyst formation and marked stenotic atherosclerotic changes in the medullary arteries. Clinical features included patchy mental lapses, frontal-lobe syndromes, minor motor signs, and hypertension. The authors feel that SAE or a similar disease might occur in most cases of multi-infarct dementia.
Participation of histamine H1- and H2-receptors in the bronchial musculature and vasculature of the dog was investigated by using the method for evaluating airway responses. A peristaltic pump and a Starling pneumatic resistance were used for a constant pressure perfusion. Dogs given 0.1 - 10 micrograms histamine by a close intraarterial injection showed increases in ventilation overflow (bronchoconstriction) and in blood flow (bronchial vasodilatation) in a dose-dependent manner. The bronchoconstriction produced by histamine was antagonized strongly by chlorpheniramine, a H1-receptor antagonist, but not modified by cimetidine, a H2-receptor antagonist. The bronchial vasodilation produced by histamine was antagonized by both chlorpheniramine and cimetidine. These results suggest that histamine evokes bronchoconstriction through H1-receptors and bronchial vasodilatation through H1- and H2-receptors.
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A new, non-invasive method for the estimation of the human pulmonary blood volume (PBV), existing between the pulmonary artery bifurcation (PAB) and the left atrium (LA), has been developed in this laboratory, in the form of PBV = PPTRCG x 0.77 x CO, equation (6), given in Appendix. This was an extension of the classical Stewart-Hamilton method of indicator dilution, applied to radioisotope angiocardiography. Using a gamma-camera, the radio-isotope (99m Tc-albumin) dilution curves were recorded externally at the region of PAB, LA and LV (left ventricle), among other things, in human subjects in supine position. The mean transit time (MTT) was determined for each region, and the difference in MTT, e.g., delta MTTPAB-LA, was measured. We calculated PBV between PAB and LA as PBV = delta MTT PAB-LA x CO, equaton (1) given in Appendix. Empirical time relations between delta MTTPAB-LA and PPTRCG were examined in mechanical models and human subjects, through several steps represented by equations (2) to (5), given in Appendix, and our tentatively final formula was equation (6). The values of PBV estimated in this way were in good agreement with those of PBV measured invasively in the past, using two injection sites (PA and LA) and one sampling site (artery).
The tubulin content and biochemical components were determined in the cerebrum, cerebellum and hypothalamus from intact and T3-treated male and female rats during early life. T3-treatment between 0 and 9 days of age increased soluble protein, RNA DNA and tubulin content (mg per g tissue) in the 10-day-old male cerebellum but not in the cerebrum and hypothalamus except for soluble protein and tubulin (mg per g tissue), respectively. Intracellular tubulin content (mg per mg DNA) was increased by the T3-treatment in the 10-day-old male hypothalamus but not the other regions. When T3 was administered between 10 and 19 days, there was little effect of the treatment; increased tubulin (mg per g tissue) in the cerebrum and decreased RNA (mg per g tissue) and a ratio of tubulin to protein in the cerebellum from 20-day-old males. Less response to T3-treatment was observed in female cerebrum and hypothalamus but not in the cerebellum, compared with the male. These results suggest that the effect of T3-treatment on brain is modified by several factors such as tissue specificity, age-dependency and sexual differences. Modification by these factors might depend, at least in part, on changes in the number of T3-receptors due to the hormone treatment.
Cell-sized bilayer liposomes have been visualized directly in the electron microscope by a thin section method. Fixation in lanthanum nitrate plus potassium permanganate has made this visualization possible. Trilamellar images were seen in thin sections of the fixed liposomes; measurements made from microdensitometer tracings revealed a thickness (peak-to-peak distance) ranging from 25.3 to 55.3 A. The mean peak-to-peak distance of 35.6 +/- 8.2 A (+/- S.D.) was in good agreement with the value obtained by Robertson from typical myelin figures.
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Y-12, 141 (0.1 approximately 0.3 mg/kg) given i.v. 1 min before the antigen challenge inhibited both the 48-hour passive cutaneous anaphylaxis (PCA) and active anaphylactic bronchoconstriction of rats mediated by IgE-like antibody. The anti-PCA activity of Y-12, 141 (0.3 mg/kg i.v.) given 1 min before the antigen challenge decreased significantly by predosing with Y-12, 141 (1 approximately 3 mg/kg i.v.) 60 min before the antigen challenge. The induction of tachyphylaxis in the PCA test appeared to depend on the doses in internal between predosing and second dosing. The anti-PCA activity of disodium cromoglycate (DSCG) at a dose of 1 mg/kg i.v. decreased significantly by predosing with DSCG (10 mg/kg i.v.) 30 min before the antigen challenge. Cross-tachyphylaxis between Y-12, 141 and DSCG was observed in the PCA test. The tachyphylaxis to Y-12, 141 was more readily induced in the PCA than in the bronchoconstriction. The inhibitory activity of Y-12, 141 (0.3 mg/kg i.v.) given 1 min before the antigen challenge in the PCA and bronchoconstriction was not affected by predosing with Y-12, 141 (1 mg/kg p.o. or s.c.) for 7 days.
Mice were immunized with sheep red blood cells (SRBC) at day 0, and hemagglutinin (HA) titer of the serum, hemolytic plaque forming cells (HPFC) in the spleen cells and rosette forming cells (RFC) in both the spleen and thymus cells were assayed at day 5. The immune responses in the mice immunized with 1 X 10(8) SRBC intravenously were not affected by Y-12, 141 given orally for 5 days (0 approximately 4 days) at doses of 30 approximately 100 mg/kg, but were suppressed by cyclophosphamide (10 approximately 30 mg/kg p.o.) and D-penicillamine (100 mg/kg p.o.). The treatment of the mice with levamisole (1 approximately 30 mg/kg p.o.) resulted in the increase of RFC number in the spleen. Levamisole increased the number of RFC in the mice immunized with 5 X 10(6) approximately 10(8) SRBC. On the other hand, Y-12,141 (10 approximately 30 mg/kg p.o.) increased spleen RFC number in the mice immunized with 5 approximately 10 X 10(6) SRBC. Y-12,141 and levamisole given orally on day 0, 1 or 2 increased spleen RFC number in the mice immunized with 5 X 10(6) SRBC. D-Penicillamine given orally for 3 days (-2 approximately 0 days) also potentiated spleen rosette formation. The decreased number of RFC in the spleen and thymus by cyclophosphamide given orally in a dose of 20 mg/kg was restored by the treatment with Y-12,141 (3 approximately 30 mg/kg) and levamisole (1 approximately 30 mg/kg). In addition, these agents suppressed 19S HA titer, and elevated 7S HA titer in the cyclophosphamide-treated mice. Prednisolone given orally in a dose of 30 mg/kg also decreased the number of RFC in the spleen. This decrease was restored by the treatment with Y-12,141 and levamisole. These findings suggest that Y-12,141 has a capacity to potentiate the immune response in mice immunized with low doses of SRBC and to restore the decrease of immune response caused by immunosuppressive drugs such as cyclophosphamide and prendisolone.
Anti-inflammatory activity of 2-[p-(2-imidazo[1,2-a]pyridyl) phenyl]propionic acid (Y-9213, miroprofen) was studied on various experimental models. Miroprofen was found to be as active as indomethacin against the exudative inflammation such as pleuritis in rats induced by Evans blue-carrageenin and the peritonitis in mice induced by acetic acid, and against the local Shwartzman reaction in rabbits. Miroprofen also inhibited the formation of edema induced by carrageenin or kaolin in rats' paws at lower doses. Against the proliferation of connective tissues, miroprofen showed the inhibitory action at higher doses. The ulcerogenic activity of miroprofen in rats was less potent than that of indomethacin, and as active as that of phenylbutazone. These findings indicate that miroprofen may be more effective in suppressing pain responses and acute inflammation accompanied with increased vascular permeability.
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Local application of colchicine to the hypogastric plexus produced degenerative changes in about 40% of adrenergic nerve endings and a decrease in the neuromuscular transmission in the rat vas deferens. Unlike after denervation, both decreases in the number of normal nerve terminals and neuromuscular transmission induced by colchicine were incomplete and reversible. Although the time course of these changes was apparently related to that of the development of supersensitivity after colchicine treatment, the degeneration of adrenergic nerves does not seem to be an essential factor for the manifestation of colchicine-induced supersensitivity which is quantitatively and qualitatively identical to that induced by denervation. It is suggested that some neurotrophic factor(s) may contribute to the control of responsiveness of the smooth muscle and that the denervation-like supersensitivity is induced by colchicine through an interference of axonal transport in adrenergic nerves.
A comparison of the effects of caffeine on ultraviolet (UV)-induced sister-chromatid exchanges (SCEs) and 6-thioguanine-resistant (6-TGr) mutations was attempted in order to study how the SCE mechanism correlates with mutagenesis. The linear UV dose-mutation relation indicated that the presence of 1mM caffeine during the 6-day expression period prior to the 6-TG selection did not alter the 6-TGr mutation induction rate. However, 1mM caffeine synergistically elevated the rate of UV-induced, immediate SCE formation, but did not alter the delayed SCE frequency in the 6-day survivors. These results indicate a clear dissociation of SCE from mutation, and suggest that SCE formation may not primarily involve the mutagenic process, but may rather be an error-proof mechanism that can tolerate some of DNA lesions.
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As a first step in the isolation of a stable Na+/H+ antiporter, its reaction in sonicated membrane vesicles of thermophilic bacterium PS3 has been characterized. The sonicated vesicles showed quenching of quinacrine fluorescence in either NADH oxidation or ATP hydrolysis. The quenching was reversed by the addition of Na+, Li+, Mn2+, Cd2+, and Co2+, but not of choline+ or Ca2+, regardless of their counter anions. 22Na+ was taken up into the vesicles by NADH oxidation, and the 22Na+ uptake was inhibited by the addition of an uncoupler. H+ release was observed on addition of Na+ to sonicated vesicles. The magnitude of the pH difference across the membrane induced by NADH oxidation was constant at pH 7.0 to 9.1, but the Na+/H+ antiport was affected by the pH of the medium (optimum pH-8.5). The Km's of the antiporter for Na+ and Li+ were 2.5 and 0.1 mM, respectively, but the Vmax values for the two ions were the same at pH 8.0. In the presence of Li+, no further decrease of fluorescence quenching was observed on addition of Na+ and vice versa. The Na+/H+ antiporter activity in PS3 was stable at 70 degrees C, and the optimum temperature for activity was 55-60 degrees C. In contrast to mesophilic cation/H+ antiporters, this antiporter was not inhibited by a thiol reagent.
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1. The supersensitivity in smooth muscle of the rat vas deferens induced by local application of colchicine to the hypogastric plexus was investigated electrophysiologically. 2. Spontaneous junction potentials could be detected in nearly all of the impaled cells, but they occurred with lesser frequency and smaller amplitude in the colchicine-treated rat vas deferens than in the control tissue. However, this clearly demonstrated that, although attenuated, neuromuscular transmission still persisted after colchicine treatment. 3. The mean resting potential of smooth muscle cells of the colchicine-treated vas deferens (58.2 +/- 0.3 mV, n - 146) was not significantly different from that of the cells of the contralateral control tissue (58.1 +/- 0.2 mV, n = 130). 4. The threshold potential for action potentials induced by either nerve stimulation or extracellular current application was more negative by approximately 10 mV in the colchicine-treated vas deferens in comparison with the control tissue. 5. Externally applied current pulses of long duration failed to produce electrotonic potentials in any smooth muscle cell of normally innervated rat vas deferens which was located more than 0.5 mm from the partition electrode. In the colchicine-treated tissue, however, electrotonic potentials in the smooth muscle cell could be detected for a distance up to 2.5 mm from the partition electrode. The space constant in the colchicine-treated tissue was determined to be 0.79 +/- 0.02 mm (n = 10). 6. It is concluded that (i) the magnitude of depolarization from resting to threshold potentials in the colchicine-treated vas deferens was significantly smaller than that in the contralateral control tissue and (ii) that the current spread in a longitudinal direction was improved following colchicine treatment.