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Biomedical subjects

Y Yamamura

Publications and source records attributed to Y Yamamura.

At least 217 records · Page 12Linked to original sources

Kinetic analysis of glycyrrhetic acid, an active metabolite of glycyrrhizin, in rats: role of enterohepatic circulation.

The role of enterohepatic circulation of glycyrrhetic acid (GA) in rats was determined by kinetic analysis of GA. The concentrations of GA in the plasma of the control rat (without bile duct cannulation) during the first 5 h after intravenous (iv) administration of GA (2, 5, 10, and 20 mg/kg) were similar to those in the bile duct-cannulated rat at each dose. No significant difference was observed in the values of the terminal half-life, the total body clearance, the distribution volume at steady state, the area under the curve of concentration in plasma versus time, and the mean residence time in each dose between both groups. When GA (2, 5, 10, and 20 mg/kg) was administered i.v. to the bile duct-cannulated rat, excretion of unchanged GA in bile was < 1% of each dose, that of the acid-hydrolyzed products was 14-16%, and that of GA-3-O-glucuronide was only 1-2%. In the control rat, a secondary peak of GA concentration was observed 12 h after i.v. administration of GA (20 mg/kg). The enterohepatic circulation of GA was confirmed by the linked-rat method in which bile of the donor rat after i.v. administration of GA (20 mg/kg) was allowed to flow directly into the duodenum of the recipient rat. GA was found in the plasma of the recipient rat after 6 h, and its concentration reached the maximum (approximately 0.5 microgram/mL) 8-12 h after dosing the donor rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Changes in histopathological features of gastric carcinoma over a 26-year period (1965-1990).

Epidemiological study has shown that the incidence rate of gastric carcinoma in Japan has declined recently. To explore the factors that have influenced this decrease, the changing pattern in clinico-pathological features of gastric carcinoma was studied from the epidemiological point of view. The 5,015 cases of gastric carcinoma treated with gastrectomy at Aichi Cancer Center Hospital from 1965-1990 were divided into two histopathological types: the well-differentiated and other types. Proportional distribution was compared over the three different periods (1965-1973, 1974-1982, 1983-1990) according to the clinico-pathological features of the gastric carcinoma, i.e., sex, age, lesional location, etc. The recent relative decline of gastric carcinoma is due mainly to the decline of carcinoma of the well-differentiated type. This decline has been highly correlated to the decline in carcinoma of the antrum, which has been the most common in Japan. This changing pattern of clinicopathological features of Japanese gastric carcinoma might be affected by the change of exposure patterns to epidemiological factors, i.e., a Westernizing diet.

Age Factors↗

Generation of monoclonal antibodies to the rabbit interleukin-2 receptor alpha chain (CD25) and its distribution in HTLV-1-transformed rabbit T cells.

Rabbits can be infected with human retroviruses such as human T-cell leukemia virus-1 (HTLV-1) and human immunodeficiency virus (HIV), and provide useful animal models to study retroviral diseases such as adult T-cell leukemia and HIV. Previously we have succeeded in generating monoclonal antibodies (mAbs) against rabbit CD4, CD5 and CD11a antigens. To make this animal species more amenable to cellular and molecular studies, we have attempted to extend the panel of mAbs against rabbit CD antigens. Here we report on the generation of three neutralizing mAbs against interleukin-2 receptor alpha chain (IL-2R alpha) (CD25), Kei-alpha 1 (IgG2b), Kei-alpha 2 (IgG2a) and Kei-alpha 3 (IgG1). They specifically recognize the rabbit Mr 55,000 IL-2 binding protein, IL-2R alpha, and completely inhibit both high- and low-affinity IL-2 binding to F648b cells that express IL-2R alpha as well as IL-2R beta. The use of mAb Kei-alpha 1 confirmed that the rabbit IL-2R alpha is not only a low-affinity IL-2R on its own but also an essential component of high-affinity IL-2R as found in other animal species, and that rabbit activated T cells including HTLV-1-transformed cell lines express high levels of the IL-2R alpha. Together with mAbs against various rabbit CD antigens that we reported previously, these neutralizing mAbs to IL-2R alpha will be valuable for studies of human retrovirus infections, such as those induced by HTLV-1 or HIV, in rabbits.

Animals↗

Arginine vasopressin produces renal vasodilation via V2 receptors in conscious dogs.

In conscious dogs, 36-h water deprivation induced a significant increase in renal blood flow (RBF) with elevation of the plasma arginine vasopressin (AVP) concentration to 9.6 +/- 1.8 pg/ml. To simulate such a condition, a mild elevation of plasma AVP was produced by infusing AVP intravenously at a dose of 0.1 ng.kg-1.min-1 for 20 min. The plasma AVP concentration then increased to 6.8 +/- 0.7 pg/ml. This dose of AVP increased the RBF by 21.7 +/- 2.6% and decreased the renal vascular resistance by 18.1 +/- 2.3% without significant changes in mean arterial pressure, cardiac output, or heart rate. The mechanism of this renal vasodilatory action was examined using newly developed, orally effective, selective AVP antagonists OPC-21268 (a V1-receptor antagonist) and OPC-31260 (a V2-receptor antagonist). In 36-h water-deprived dogs, V2-receptor blockade with OPC-31260 significantly decreased the RBF by 20.5 +/- 2.6% without significant changes in cardiac output. The exogenous AVP-induced renal vasodilatory response tended to be augmented when V1 receptors were blocked by pretreatment with OPC-21268, but the change did not achieve statistical significance. On the other hand, V2-receptor blockade by either pretreatment with OPC-31260 or simultaneous infusion of OPC-31260 inhibited this vasodilatory response. Furthermore, intravenous infusion of 1-desamino-8-D-arginine vasopressin (DDAVP) at a dose of 0.3 ng.kg-1 x min-1 for 20 min significantly increased the RBF by 36.5 +/- 1.7%, and this DDAVP-induced renal vasodilation was inhibited by simultaneous infusion of V2-receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Clinical evaluation of rapid serodiagnosis of pulmonary tuberculosis by ELISA with cord factor (trehalose-6,6'-dimycolate) as antigen purified from Mycobacterium tuberculosis.

Immunoglobulin G (IgG) antibodies against purified cord factor (trehalose-6,6'-dimycolate) prepared from Mycobacterium tuberculosis H37Rv were determined by enzyme-linked immunosorbent assay (ELISA), and its diagnostic usefulness was evaluated. Serum specimens from 65 patients with active pulmonary tuberculosis, 58 patients with inactive pulmonary tuberculosis, 36 patients with diseases other than tuberculosis, and 66 healthy adults were examined. Patients with active pulmonary tuberculosis showed significantly higher titers of IgG antibodies against cord factor than did other groups (p < 0.001). The antibody titer greater than 0.29 in absorption difference (492 to 630 nm) of 160-times diluted serum was set as positive in ELISA. For patients with active and untreated pulmonary tuberculosis, the ELISA had a sensitivity of 81% and a specificity of 96%. From these results, it was concluded that the detection of IgG antibodies against cord factor is useful for serodiagnosis of active pulmonary tuberculosis. It was also indicated that the anticord factor antibody titers decline to the normal level as a result of antituberculosis chemotherapy.

Adult↗

Potent aquaretic agent. A novel nonpeptide selective vasopressin 2 antagonist (OPC-31260) in men.

Solute-free water diuretics (aquaretics) by antagonizing hydrosmotic vasopressin receptors (V2) may be useful in treating water-retaining diseases. The effects of intravenous administration of a newly developed nonpeptide, selective V2 antagonist, OPC-31260, at doses ranging from 0.017 to 1.0 mg/kg to groups of healthy, normally hydrated men were compared with those of 0.33 mg/kg furosemide and placebo. OPC-31260 increased the hypotonic urine volume dose dependently for the first 4 h, while furosemide induced sodium diuresis for 2 h. The absolute increase in the cumulative response in the urine to the highest doses of OPC-31260 was not significantly different from that to furosemide. The higher doses of OPC-31260 rapidly lowered urine osmolality for 2 h, particularly between minutes 15 and 45 (e.g., 1.0-mg/kg dose: 63 +/- 2 mOsm/kg in urine collected between minutes 30 and 45). In a marked hypotonic diuresis, mean free water clearance of the 4-h urine increased dose proportionally into the positive range, reaching 1.80 +/- 0.21 ml/min at 1.0 mg/kg. Whereas furosemide induced marked Na and K diuresis, OPC-31260 increased urinary Na excretion only slightly. At 4 h, 0.75 and 1.0 mg/kg of OPC-31260 almost doubled the plasma arginine vasopressin; and the higher doses increased plasma osmolality and plasma Na slightly, but did not alter plasma K, blood pressure, or heart rate. OPC-31260 thus safely induced a potent aquaretic effect in men.

Adult↗

[A study on acute organophosphorus poisoning--changes in the activity and isoenzyme patterns of serum cholinesterase in human poisoning].

Various organophosphorus compounds with low acute toxicity levels are widely used as insecticides. Human acute poisoning by organophosphates has often occurred accidentally. We determined the activity and isoenzyme patterns of serum cholinesterase (ChE) obtained from 13 human patients who attempted suicide with various organophosphates, i.e. Fenitrothion, Malathion, Isoxathion, Pyridaphenthion and Trichlorfon, and studied on the changes in the activity and isoenzyme patterns of serum ChE after ingestion. The following results were obtained. 1) Twenty ChE isoenzyme bands from normal human serum were detected by electrophoretic separation on polyacrylamide gradient gel. The main bands in the ChE isoenzyme pattern in normal serum were bands 4 and 5 which had the highest activity of acetylcholinesterase (AChE) with a molecular weight of 600,000-800,000, and bands 7, 12, 14, 17 and 18. 2) Inhibition of serum ChE activity was more severe as the amount ingested increased in patients who took Fenitrothion and Malathion. Reactivation of serum ChE activity was very slow in patients treated with PAM (2-pyridine aldoxime methiodide) in the late stage of ingestion or whose symptoms reappeared. 3) There were no differences in the patterns of serum ChE isoenzyme by organophosphorus compound. Band 7 disappeared in the serum ChE isoenzyme of almost every patient, and bands 12, 18, 14 and 17 of the serum ChE isoenzyme disappeared successively with the decline of serum ChE activity. Only band 5 of the isoenzyme remained in cases who had serum ChE activity lower than 5% of normal. 4) All 13 patients were treated with PAM and atropine immediately after being admitted to hospitals. We could not clearly determine the efficacy of PAM on reactivation of serum ChE activity and isoenzyme, because it was impossible in human poisoning to compare PAM efficacy with no treatment and with pre- and post-PAM treatment. 5) The activity and isoenzyme patterns of serum ChE recovered rapidly after combined hemoperfusion and hemodialysis treatment (HP-HD treatment) of the patients poisoned with Malathion. But HP-HD treatment had no effect on poisoning by Fenitrothion and Isoxathion. These findings demonstrated the changes in the activity and isoenzyme pattern of serum ChE in patients poisoned with several organophosphates after PAM and HP-HD treatment.

Acute Disease↗

Selective IgM deficiency in a patient with Hashimoto's disease.

A 70-year-old man with Hashimoto's disease had selective IgM deficiency, while other immunoglobulin levels were normal. In vitro mixing experiments were carried out in which B cells and T cells from the patient and from a healthy control donor were co-cultured in the presence of pokeweed mitogen, in order to investigate the etiology of IgM hypoproduction. The results indicated that the patient had B-cell dysfunction, involving the impairment of B-cell differentiation. In addition, both IgG of the healthy control donor and thyroid hormone may play important roles in the pathogenesis of this case.

Aged↗

[Expression of the blood group related antigens (Lewis(a), Lewis(b), Lewis(x), Lewis(y), and other gastroenterological tissue related antigens(CEA, APF, and NSE) in poorly differentiated adenocarcinoma of gastric cancer with medullary growth pattern].

To clarify the clinico-pathological characteristic of poorly differentiated adenocarcinoma of gastric cancer with medullary growth pattern, the immunohistochemical study was performed using antibodies against blood group related antigens (Lewis(a), Lewis(b), Lewis(x), Lewis(y)) and gastrointestinal tissue related antigens (CEA, AFP and NSE). The following results were obtained. 1. Foveolar epithelium of normal gastric mucosa has type 1 blood group associated antigen (Lewis(a), Lewis(b)) and deep gland has type 2 antigen (Lewis(x), Lewis(y)) respectively, as the differentiation antigens. 2. Expression of Lewis(a) and Lewis(b) are more often observed in poorly differentiated adenocarcinoma with medullary and scirrhous growth pattern than in well and moderately differentiated adenocarcinoma. Poorly differentiated adenocarcinomas postulated to have closer relation with normal gastric deep gland in terms of antigen expression. 3. Poorly differentiated adenocarcinoma with medullary growth pattern is characterized as more differentiated type cancer than scirrhous type with respect to expression of blood group related antigen. 4. Poorly differentiated adenocarcinoma with medullary growth pattern may be divided into 3 subgroups by each antigen expression of CEA, NSE, and AFP.

Adenocarcinoma↗

[Early-onset parkinsonism with diurnal fluctuation--clinical and pathological studies].

The literature regarding parkinsonism of early-onset indicates that it encompasses several diseases differing in their clinical and pathological features. Since 1968 we have reported cases of early-onset parkinsonism with diurnal fluctuation of symptoms (abbrev. as EPDF). Attention has been focused on its similarities to or differences from Parkinson's disease (PD), juvenile parkinsonism of Yokochi, and hereditary progressive dystonia (HPD) of Segawa et al. In this paper we report the clinical and pathological characteristics of EPDF to facilitate its nosological identification. We examined the pathological features of EPDF in two cases. Case 1 was a 52-year-old female with consanguineously related parents and two other affected sisters. The disease began at the age of 20, and she had marked diurnal fluctuation of symptoms. With the assistance of L-dopa and bromocriptine, she was able to enjoy relatively satisfactory daily life activity until the age of 50. In the last two years she was bed-ridden with advanced parkinsonism. Case 2 was a 56-year-old man without any contributing family history. His disease started at age 26 and his symptoms showed slight fluctuation during the earlier stages of the disease. Treatment with L-dopa and bromocriptine was associated with marked up-and-down phenomenon and choreatic dyskinesia. Pathological study in the two cases revealed marked cell loss in the substantia nigra zona compacta, especially in the area A9, while the neuronal cell population of the ventral tegmental area (A10), locus caeruleus, superior raphae nucleus, and substantia innominata was relatively well preserved. There were no Lewy bodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗

[Acrodystrophic neuropathy in an alcoholic].

The patient was a 48-year-old alcoholic man with no contributory family history. At age 36 he had developed sensory dominant polyneuropathy with highly impaired temperature sensation and deep sensation in the lower extremities, recurrent ulcers of the toes, and sexual impotence. A sural nerve biopsy at this time revealed marked loss of myelinated fibers with relative preservation of the population of unmyelinated fibers. Subsequently, he developed muscle atrophy of the lower thighs, urinary incontinence, and Wernicke's encephalopathy, and became non-ambulatory at age 44. The peripheral nerve conduction findings suggested predominantly axonal degeneration. The entire course was characterized by alternative progression and partial recovery influenced by his alcohol intake and nutritional state. Alcoholic neuropathy is a major cause of solitary acrodystrophic neuropathy (ADN). Manifestations of autonomic and motor neuropathy are more marked in alcoholic ADN than in HSAN-I, and central nervous system involvement is the hallmark of alcoholic ADN. In the treatment of patients with alcoholic ADN, attention should be paid to diabetes mellitus, malnutritional state, and vitamin deficiency, which frequently complicate alcoholism.

Alcoholism↗

[Coagulation and fibrinolytic parameters in patients with various angiopathies--analysis in cerebral thrombosis, diabetic and vasculitic neuropathies].

We measured the coagulation and fibrinolytic parameters in patients with various angiopathies to clarify the usefulness of the parameters for the evaluation of vascular involvement. The study included 65 patients with cerebral thrombosis at the chronic stage, 47 diabetics with neuropathy associated with diabetic microangiopathy, 15 diabetics without neuropathy, and 16 patients with vasculitic neuropathy associated with collagen diseases. Control subjects were 45 patients with other neurological disorders without symptomatic angiopathies. In cerebral thrombosis at the chronic stage, the coagulation factor VIII (FVIII), von Willebrand factor (vWF), and platelet factor IV were elevated significantly as compared with age-matched controls. Diabetics with neuropathy showed significantly elevated FVIII and vWF in comparison with diabetics without neuropathy and controls. No significant difference in parameters concerning glucose metabolism was observed between the two groups of diabetics. These findings suggest that elevated activities of the coagulation parameters reflect not merely the abnormalities in glucose metabolism but also the presence of microangiopathy which causes diabetic neuropathy. The patients with vasculitic neuropathy exhibited significantly elevated FVIII, vWF and fibrin/fibrinogen degradation products (FDP). The present study demonstrated that FVIII and vWF are useful parameters for the evaluation of the extent of vascular involvement in angiopathies of different etiologies. It is important for the treatment of patients with the angiopathies, to monitor the coagulation parameters which reflect vascular involvement in addition to parameters for the disease activity.

Aged↗

Distribution of epidermal growth factor receptors in rabbit lens epithelial cells.

PURPOSE: This study examined the growth-promoting effect of epidermal growth factor (EGF) on rabbit lens epithelial cells and the distribution of EGF receptors in these cells. METHODS: Rabbit lens epithelial cells were cultured in TC-199 medium containing 0.5% fetal bovine serum and EGF for 1 to 5 days, and the growth-promoting effects of EGF were calculated with absorbance of methylene blue staining method. EGF receptors in the cells were analyzed by Scatchard plots using 125I-EGF in serum-free culture. RESULTS: EGF, which enhanced the cell growth in a dose-dependent manner, was stimulatory at 0.1-100 ng/ml and maximal (328.2%) with 10 ng/ml on day 5. The cells had two different affinity receptors. The number and the dissociation constant of the low affinity receptors were 5.81 x 10(4)/cell and 1.488 nM, respectively, and those of the high affinity receptors were 1.53 x 10(4)/cell and 0.159 nM, respectively. CONCLUSION: EGF may contribute to the development of living lenses.

Animals↗

Lewis blood group-related antigen expression in normal gastric epithelium, intestinal metaplasia, gastric adenoma, and gastric carcinoma.

The expression of blood group-related antigens of the Lewis system in normal gastric mucosa, intestinal metaplasia, gastric adenoma, and gastric carcinoma was examined. Ninety-five percent of normal foveolar epithelial samples stained positive for Lewis(b) antigen, whereas only 10.0% expressed Lewis(a) antigen. In contrast, intestinal metaplasia specimens had increased Lewis(a) antigen expression and slightly decreased Lewis(b) antigen expression. A similar pattern of Lewis(a) and Lewis(b) expression was observed in gastric adenomas and intestinal type adenocarcinomas. Lewis(x) and Lewis(y) were detected in all normal deep glands, but were not expressed in the majority of intestinal metaplasia specimens. In addition, only 20-40% of gastric adenomas and gastric carcinomas expressed Lewis(x) and Lewis(y) antigens. These changes in Lewis antigen expression in intestinal metaplasia, adenomas, and intestinal type adenocarcinomas suggest that altered expression of Lewis blood group-related antigens may correlate with cell transformation processes.

Adenocarcinoma↗

Distinct downstream signaling mechanism between erythropoietin receptor and interleukin-2 receptor.

Erythropoietin receptor (EPOR) and interleukin-2 receptor beta chain (IL-2R beta) belong to the same cytokine receptor superfamily and have highly conserved sequences in their intracellular signaling domain. However, common downstream signaling pathways of these receptors have not been demonstrated. In the present study, we introduced and expressed the murine EPOR in murine IL-2-, IL-3- and IL-5-dependent cell lines and analyzed their growth response to EPO. We found that the expression of EPOR induced EPO dependence in IL-3-dependent BAF-B03 and IL-5-dependent Y16 cells but not in IL-2-dependent CTLL-2 cells, although the EPOR-expressing CTLL-2 cell lines could bind and internalize EPO as efficiently as the BAF-B03-derived cell lines. Additional expression of AIC2B, a common signal transducer for IL-3R, IL-5R and GM-CSFR, made no difference to the EPO responsiveness of the EPOR-expressing CTLL-2 cell lines. These results suggest that the cellular components required for the transduction of EPOR signal and IL-2R signal are at least partially different, and this difference cannot be explained solely by the absence of AIC2B.

Animals↗

Pharmacokinetic profile of glycyrrhizin in healthy volunteers by a new high-performance liquid chromatographic method.

An improved high-performance liquid chromatographic method was developed for the quantification of glycyrrhizin and its metabolites in human plasma. The improved method was selective and made it possible to determine precisely glycyrrhizin at levels as low as 500 ng/mL. The pharmacokinetic behavior of glycyrrhizin and its metabolites after oral and intravenous administration of glycyrrhizin to normal subjects was investigated. After oral administration of glycyrrhizin (100 mg) to three normal subjects, the major metabolite of glycyrrhizin (glycyrrhetic acid) appeared in plasma (less than 200 ng/mL), but glycyrrhizin was not found. On the other hand, glycyrrhizin was found in urine, and the amount excreted was 1.1-2.5% of the dose. This finding suggests that glycyrrhizin is partly absorbed in the intact form from the gastrointestinal tract. The concentration of glycyrrhizin in plasma after intravenous administration of glycyrrhizin (40, 80, and 120 mg) showed biexponential profiles during the 24-h period after administration of each dose. The glycyrrhizin metabolites, glycyrrhetic acid and glycyrrhetic acid-3-O-glucuronide, were not detected in either plasma or urine. The terminal half-life of glycyrrhizin, the apparent volume of the central compartment, the steady-state distribution volume, and the total body clearance in three dosing experiments were 2.7-4.8 h, 37-64 mL/kg, 59-98 mL/kg, and 16-25 mL/kg/h, respectively. Glycyrrhizin was not detected in plasma after oral administration of the usual therapeutic dose of glycyrrhizin, and no dose dependency of the drug was observed in the dose range of 40-120 mg.

Administration, Oral↗

Effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on cytotoxicity of PSK-induced peritoneal polymorphonuclear leukocytes (PMNs).

We investigated whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) enhanced the cytotoxicity of PSK-induced polymorphonuclear leukocytes (PMNs) in the peritoneal cavity. Male C3H/He mice, 8- to 10-week-old, received single subcutaneous (s.c.) or intraperitoneal (i.p.) injection of 2.5 micrograms/animal of rhG-CSF at different time points before or after an i.p. administration of PSK. In other experiments, mice were s.c. or i.p. treated with the same dosage of rhG-CSF every day for 7 or 14 consecutive days and i.p. injected with 2.5 mg/animal of PSK on the last day. Peritoneal PMNs were harvested 6 hrs after the administration of PSK and purified to more than 95% by Ficoll-Paque for in vitro cytotoxic assay. In vitro cytotoxic assays with 51Cr labeled MM46 mammary carcinoma cells were added with 5-20 micrograms/ml of Nocardia rubra cell wall skeleton (N-CWS) at the beginning of the assay to augment the cytotoxic activity of PMNs. In vitro addition of rhG-CSF to the assay did not enhance the cytotoxicity of PSK-induced PMNs. However, the cytotoxicity was significantly increased when rhG-CSF was s.c. administered 12 hrs before a PSK injection or 2 or 5 hrs after that. On the other hand, the cytotoxicity was rather weak when mice s.c. or i.p. received consecutive injections of rhG-CSF. This cytotoxicity may be mediated by H2O2, since H2O2 production of PMNs during the cytotoxic assay appears to correlate with the levels of cytotoxicity under suppressed H2O2 generation by catalase or enhanced generation by rhG-CSF. These results suggest that rhG-CSF augments the cytotoxicity of PSK-induced PMNs when administered in vivo timely.

Animals↗