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Biomedical subjects

H Nishimura

Publications and source records attributed to H Nishimura.

At least 847 records · Page 47Linked to original sources

Liberation of serotonin from rabbit blood platelets by bacterial cell walls and related compounds.

A study was made on the activity of various bacterial cell walls and peptidoglycans to liberate serotonin from rabbit blood platelets. All of the test cell walls or peptidoglycans prepared from 27 strains of 21 bacterial species were shown to cause a marked release of serotonin, regardless of differences in types of peptidoglycan and non-peptidoglycan moieties and in some biological properties. The assay made with the water-soluble "digests" of Staphylococcus epidermidis cell wall peptidoglycans, which were prepared by use of appropriate enzymes, revealed that a polymer of peptidoglycan subunits (a disaccharide-stempeptide) was definitely active in the release of serotonin, but a structural unit monomer was inactive. Among a variety of synthetic muramylpeptides and their 6-O-acyl derivatives, only 6-O-(3-hydroxy-2-docosylhexacosanoyl)-N-acetylmuramyl-L-alanyl-D-isoglutaminyl- L-lysyl-D-alanine was found to hold a strong serotonin-liberating activity.

Acetylmuramyl-Alanyl-Isoglutamine↗

Thiamine transport in Saccharomyces cerevisiae protoplasts.

Thiamine was found to be accumulated in protoplasts of Saccharomyces cerevisiae in the same manner as in intact cells, suggesting that a soluble thiamine-binding protein in periplasm may not be an essential component of the thiamine transport system of S. cerevisiae. It was also found that thiamine pyrophosphate cannot be taken up by yeast protoplasts.

Acid Phosphatase↗

Vasopressor and depressor actions of angiotensin in the anesthetized fowl.

Vasopressor and depressor properties of angiotensins (ANG) were characterized in the anesthetized, adult female chicken Gallus gallus. [Asp1,Val5,Ser9]ANG I and [Asp1,Val5]ANG II (native fowl angiotensins) increased blood pressure, and removal or replacement of the amino acid in position 1 decreased pressor potency. The pressor effect of [Asp1,Val5]ANG II was inhibited nearly completely with [Sar1,Ile8]ANG II (5 micrograms.kg-1.min-1) and partially with [Sar1,Thr8]ANG II, [Ile8]ANG III, and [Ile8]ANG I. Phenoxybenzamine, reserpine, or 6-hydroxydopamine reduced the pressor action to one-third. After administration of these compounds [Asp1,Val5]ANG II caused biphasic responses, a depressor followed by a small pressor response. [Sar1,Ile8]ANG II completely, and meclofenamate partially, blocked the depressor response, whereas propranolol, methysergide, vasopressin antagonists, or atropine did not. These results suggest that in fowl 1) the first (Asp) and eighth (Phe) amino acids are important for receptor binding and action, 2) vasopressor action of angiotensin may be primarily caused by release of catecholamines, and 3) angiotensin may exert depressor action possibly by acting directly on the vascular smooth muscle.

Anesthesia↗

Vasodepressor action of angiotensin in conscious chickens.

In chronically cannulated conscious chickens, Gallus gallus, native chicken angiotensin II ([Asp1,Val5]ANG II) caused biphasic blood pressure responses, a depressor followed by a pressor response. The pressor response appears to be mediated primarily by catecholamines. The depressor responses increased with increasing doses and were accompanied by tachycardia. The onset of the depressor action of [Asp1,Val5]ANG II (2.49 +/- 0.22 s) was nearly as quick as that of acetylcholine or histamine. Replacement of aspartic acid in position 1 with sarcosine or asparagine reduced both depressor and pressor potencies, whereas there was no difference either in depressor or pressor potencies between [Asp1,Val5] and [Asp1,Ile5]ANG II. The depressor response to [Asp1,Val5]ANG II was not inhibited by atropine, a vasopressin antagonist, prostaglandin synthetase inhibitors, methysergide, or propranolol but was blocked markedly by [Sar1, Ile8]ANG II and partially by [Sar1,Thr8]ANG II. The results suggest that the vasodepressor action of ANG II is mediated by angiotensin receptors and may possibly be a direct action on the vascular smooth muscle.

Acetylcholine↗

Teratogenicity of di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DBP) in mice.

Di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DBP) were mixed with diet at graded levels of 0.05, 0.1, 0.2. 0.4 and 1.0 wt-% and given to pregnant ICR mice throughout gestation. Maternal weight gain was suppressed and fetal resorption increased at 0.2, 0.4 and 1.0% levels of DEHP and 1.0% level of DBP. All the implanted ova died early in rats fed 0.4 and 1.0% levels of DEHP. External malformations increased significantly by 0.2% DEHP, and 1.0% DBP showed borderline significance. The major malformations in treated groups were neural tube defects (exencephaly and myeloschisis), suggesting that the phthalic acid esters (PAEs) affect neural tube closure in developing embryos. Treatment with the compounds caused intrauterine growth retardation and delayed ossification with an apparently dose-related response pattern. These results indicate that a high dose of DEHP and DBP might be embryotoxic and teratogenic in mice. The maximum nonembryotoxic doses of PAEs in mice were more than 2000 times the estimated level of human intake through the food chain. Thus it is assumed that the current "normal" exposure level of PAEs dose not pose an imminent threat to human fetal development.

Abnormalities, Drug-Induced↗

Decreased suppressor T cell activity in patients with hepatic cirrhosis (HC).

Hypergammaglobulinaemia (HGG) is frequently found in patients with hepatic cirrhosis (HC). Using an assay system of in vitro PWM-stimulated immunoglobulin (Ig) production, the amounts of IgG, IgA, and IgM produced by peripheral blood lymphocytes (PBL) from 15 HBs Ag-negative patients with HC and from 16 age-matched healthy subjects were quantitated by radioimmunoassay. We found that PBL from patients with HC produced significantly greater amounts of IgG (P less than 0.05) but not IgA or IgM than did those from control subjects. This increased IgG production by PBL from patients with HC was attributed to enhanced T helper activity and not to enhanced B cell function. We also searched for defects in naturally occurring suppressor T cell activity which is sensitive to irradiation. Irradiation-induced enhancement for IgG production was significantly lower in patients with HC compared with age-matched control subjects (P less than 0.01). Similarly, we examined the effect of Con A-induced suppressor T cells on the in vitro PWM-stimulated IgG production by allogeneic PBL and observed the decrease of Con A-induced suppressor T cell activity in patients with HC (P = 0.01). We conclude, therefore, that the increased serum levels of Ig, particularly IgG in patients with HC may result from in part on the basis of depressed ability of naturally occurring suppressor T cells or Con A-induced suppressor T cells to suppress Ig production.

Adult↗

Relation of serum alkaline phosphatase to liver scintigram in patients with hepatocellular carcinoma.

Serum Alkaline Phosphatase (ALP) was studied in relation to liver scintigrams of 54 patients with hepatocellular carcinoma. The ALP activity was higher with larger tumors and in multiple tumors. Within the single tumor group, the activity was higher when the tumor was located in the hilum than in the periphery. The incidence of ALP-1 isoenzyme (bile ALP) roughly paralleled the total ALP activity. These results suggest that the variation of serum ALP seen in each individual patients with hepatocellular carcinoma reflects the volume of cholestatic liver tissue, which is changed by the number, size and localization of the tumor nodules in the liver.

Alkaline Phosphatase↗

Increased antitumor activity of Escherichia coli. L-asparaginase by modification with monomethoxypolyethylene glycol.

Escherichia coli L-asparaginase modified with monomethoxypolyethylene glycol, which has no ability to bind to the antibody and almost no immunogenicity, had a longer plasma half-life (32.9+/-2.5 hr) in normal mice than the native enzyme (3.35 +/- 0.45 hr). Preimmunization of mice with the native enzyme greatly shortened the plasma half-life of the native L-asparaginase (less than 0.1 hr) but did not change that of the modified L-asparaginase (32.2 +/- 2.1 hr). Treatment of mice bearing asparaginase-sensitive Gardner lymphoma (6C3HED) with L-asparaginases at various doses showed that the modified enzyme had a greater therapeutic effect than the native enzyme. In addition, preimmunization with the native enzyme prevented the antitumor activity of the native enzyme but did not affect the therapeutic efficacy of the modified L-asparaginase against the lymphoma.

Animals↗

Intrarenal renin-angiotensin system in primitive vertebrates.

Teleost fishes, which have a simpler nephron structure and lack the macula densa, respond to lowered blood pressure by releasing renin. Inhibition of the angiotensin-converting enzyme decreases the resting level of blood pressure, suggesting that the RAS may participate in control of blood pressure in fish. Glomerulotubular balance is poorly developed, and GFR is readily increased by an increase in renal perfusion pressure. It is not clear at present whether angiotensin is involved physiologically in intermittency of glomerular filtration, or whether it controls GFR through its action on systemic blood pressure. Birds appear to have an intermediate form between primitive vertebrates and mammals in terms of morphologic structure of the JG apparatus and nephrons, and in renal function. Fowl, in which angiotensin causes biphasic depressor and pressor responses, do not respond to acute hypotension or hypovolemia by releasing renin unless blood pressure remains low. Unilateral infusion of hypertonic saline into the renal portal system, which perfuses the peritubular sinusoid, increases urinary excretion of sodium chloride in the infused kidney, accompanied by mild diuresis. The slight but significant decrease in PRA occurs after portal infusion of hypertonic saline. Further investigation will be necessary to determine on an individual nephron basis whether an increased tubular sodium or chloride load may alter GFR by a possible tubuloglomerular feedback mechanism.

Angiotensins↗

Squamous cell carcinoma arising from an epidermoid cyst in the ovary of a rat treated with 7,12-dimethylbenz[a]anthracene.

Primary non-teratomatous ovarian squamous cell carcinomas are very rare. A case of rat ovarian squamous cell carcinoma has been found in which the tumor arose from a squamous element in the ovary. Squamous epithelial aggregates were found in the wall of a cyst and on serial section, the cyst was found to be unaccompanied by any teratomatous components and showed a thin squamous epithelial lining with keratinizing debris. On the basis of these findings, it was suggested that the squamous element was a rat ovarian epidermoid cyst from which a squamous cell carcinoma arose, presumably by a direct carcinogenic effect of 7,12-dimethylbenz[a]anthracene.

9,10-Dimethyl-1,2-benzanthracene↗

[The antigastric ulcer activity of succinic acid mono-3-guaiazulenamide (TPH-3) (author's transl)].

Effects of TPH-3 on various experimental gastric ulcers in rats and guinea-pigs were studied and the following results were obtained. In the preventive experiments, such as the Shay's ulcer, pylorus-ligated aspirin ulcer and restraint and water immersion stress ulcer, TPH-3 (200 mg/kg i.d. or p.o.) showed a statistically significant inhibition. TPH-3 markedly inhibited the histamine-induced gastric ulcer in guinea-pigs and a dose-response relationship was obtained for doses of 12.5, 25 and 50 mg/kg p.o. TPH-3 showed the weak inhibition regarding therapy for serosa-seared gastric ulcer and the recovery process of restraint and water immersion stress ulcer in rats. TPH-3, dosing 100 mg/kg intraduodenally, significantly inhibited the gastric secretion in the pylorus-ligated rats. TPH-3 significantly inhibited the histamine, pentagastrin and carbachol-induced acid secretion in the stomach-perfused rats. In particular, TPH-3 showed strong sensitivity to the action of histamine. TPH-3 had no anti-ACh or anti-H1-receptor effects.

Animals↗

Control of renal function in freshwater and marine teleosts.

The glomerular filtration rate (GFR) of teleost fishes is highly variable and is influenced by glomerular intermittency, environmental salinity, renal perfusion pressure, and some hormones. In freshwater (FW) teleosts, the primary function of the kidney is to excrete excess water while retaining most of the filtered solutes, and GFR is a major determinant of urine flow. Low permeability to water prevails in the distal nephron of FW teleosts, and the majority of the filtered Na and Cl is reabsorbed without osmotic accompaniment of water. Prolactin appears to regulate osmotic permeability to water. Isolated and perfused distal tubules from FW teleosts revealed a transepithelial voltage (Vt) that was positive in the lumen. Both Na and Cl participate in generating lumen-positive Vt. Marine teleosts, which are exposed to Na loading and dehydration, ingest seawater to compensate for their osmotic water loss, and secrete divalent ions, mainly Mg and SO4, from the kidney. The urine flow of marine teleosts is primarily determined by fluid secretion accompanied by divalent ions and subsequent isosmotic reabsorption with NaCl. Interdependence of Na and Cl transport has been noted in the urinary bladder of marine teleosts. There is presently no known humoral substance that regulates NaCl and divalent ion transport in the teleost kidney.

Animals↗