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Biomedical subjects

A Horiuchi

Publications and source records attributed to A Horiuchi.

At least 181 records · Page 10Linked to original sources
PubMed1988

Effect of interferon-gamma on the abnormality of T cell activation in NZB mice.

It is known that New Zealand black (NZB) mice have a defect in the autoantigen recognition mechanism by T cells. The present study was carried out to examine whether the defect could be improved by normalizing the self Ia molecule expression on thymic reticuloepithelial cells (TRC) by using interferon-gamma (IFN-gamma). Syngeneic mixed lymphocyte reaction (SMLR) was used as an indicator of the mechanism of autoantigen recognition. In the reaction, T cells separated from the thymus were used as responders, and machrophages separated from the spleen were used as stimulators. When the responders were cultured with TRC, in which self Ia molecule expressions had been enhanced by IFN-gamma, for activation, the low level of SMLR in NZB mice was elevated close to the normal level. It was suggested, therefore, that IFN-gamma could normalize the defective autoantigen expression on TRC in NZB mice and improve the abnormal T cell activation against autoantigens.

Animals↗
PubMed1988

A new nitrosourea derivative for the treatment of chronic myelogenous leukemia.

A new water-soluble nitrosourea derivative, methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU), was found to be useful for the treatment of chronic myelogenous leukemia (CML) in the chronic phase. To compare the efficacy of MCNU with that of busulfan, patients were randomized. In the 40 patients administered MCNU, the median time to the achievement of a complete remission (CR) was 50 days. This value was shorter than that observed in 37 patients administered busulfan (126 days, p less than 0.05). There were no differences in the rate of CR achieved, mortality, median time to the onset of blast crisis (BC), BC rate, or survival rate during the observation period. The overall incidence of side effects was higher for MCNU (31%) than for busulfan (15%), but the symptoms were mild, transient and tolerable for most patients. These results suggest that MCNU is a safe and valuable addition to the therapeutic repertoire for the control of CML.

Adult↗
PubMed1988

[Efficacy and safety of cefbuperazone in severe infections complicating hematologic diseases Hanshin Infection Study Group].

Cefbuperazone (CBPZ) was administered to patients with severe infections complicating hematologic diseases to assess its efficacy and safety under such clinical conditions. Primary diseases in this series of 78 cases included; acute leukemia in 41 cases, chronic leukemia in 6 cases, other leukemia in 9 cases, malignant lymphoma in 13 cases, multiple myeloma in 3 cases, aplastic anemia in 5 cases and 1 other case. Types of infection included sepsis; proven or suspected, in 59 cases, pulmonary infection in 8 cases, upper respiratory infection in 5 cases, and other cases. CBPZ was infused by an intravenous drip method at a dosage of 4-8 g daily. Patients' ages ranged from 14 to 85 years. Clinical response to the CBPZ regimen was excellent in 24 cases, good in 22 cases, fair in 2 cases, and poor in 30 cases. Thus the overall efficacy rate (percentage of cases showing an excellent or good response) was 59.0%. Efficacy rates for individual types of infection were: documented sepsis 16.7%, suspected sepsis 58.5%, lower respiratory infection 62.5%, and upper respiratory infection 100%. CBPZ also proved to be effective in 61.0% of cases with a neutrophil count of less than 500/mm3 prior to therapy. Side effects encountered were diarrhea in 1 case, gastric discomfort in 1 case and hepatic dysfunction in 5 cases. These side effects, however, were not dose-related, and none were serious. These results indicate that CBPZ has a high therapeutic efficacy even in patient with compromised immunodefenses.

Adolescent↗
PubMed1988

Hematological response to the new synthetic muramyl dipeptide derivative muroctasin after chemotherapy in patients with malignant lymphoma. A randomized crossover trial.

A randomized crossover trial was performed in 20 patients receiving chemotherapy for malignant lymphoma. N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin) at a dose of 200 micrograms was subcutaneously administered after one of two cycles of the same protocol. The administration was started on day 4 after the start of chemotherapy and continued for 10 days. The mean length from the start of chemotherapy to nadir of white blood cell (WBC) was not significantly different between the control and muroctasin cycles. The mean WBC and neutrophil counts at nadir of the control cycle were significantly lower than those at the same point of muroctasin cycle, respectively. A positive effect of muroctasin cycle, defined as WBC count at nadir being increased by 1,000/mm3, WBC count being increased by 1,000/mm3 on two points examined after nadir, or faster reach to nadir and faster recovery to normal range of WBC than in the control cycle, was observed in 7 (35%) of 20 patients. On the other hand, only one (5%) patient showed a superiority of the control cycle over the muroctasin cycle. Toxic effects of muroctasin were observed in 34.8% of patients, but were tolerable for most patients. These results show that muroctasin has a clinical efficacy in the restoration of leukopenia after chemotherapy.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

[Pharmacokinetics of cefmenoxime in renal-failure patients undergoing continuous arteriovenous hemofiltration].

We investigated the pharmacokinetics of cefmenoxime (CMX) administrated to renal-failure patients undergoing continuous arteriovenous hemofiltration (CAVH). CAVH was carried out with a filter (0.5 m2) employing a PAN-50P (hollow fiber type) made of polyacrylonitrile membrane, with a blood flow rate of 100 ml/min and a filtration rate of 1,200 ml/hr. At 5 and 300 minutes after the CMX administration, the concentrations of CMX in the serum were 126.8 mg/L and 31.5 mg/L, respectively. The T1/2 beta was 3.55 hours. In 300 minutes after the administration of CMX, the total amount of CMX contained in the filtrate corresponded to 11.6% of the administered dose.

Acute Kidney Injury↗
PubMed1988

[Pharmacokinetics of cefotiam in patients undergoing continuous ambulatory peritoneal dialysis].

The pharmacokinetics of cefotiam (CTM) was investigated in 7 patients undergoing continuous ambulatory peritoneal dialysis (CAPD). One gram of CTM was infused either intravenously (i.v. group) or intraperitoneally (i.p. group). In the i.v. group, the serum concentration of CTM at 6 hours after infusion was 25.9 mg/L and the half-life value was 5.09 hours, while the peak value of CTM in dialysate was 12.4 mg/L. In the i.p. group without peritonitis, the dialysate concentration of CTM at 6 hours after infusion was 108.6 mg/L. The serum concentration at 15 minutes after infusion was 3.0 mg/L, the corresponding peak value was 14.0 mg/L at 4 and 6 hours after infusion.

Adult↗
PubMed1987

Effects of human atrial natriuretic polypeptide on pancreatic exocrine secretion in the dog.

We examined the effects of atrial natriuretic polypeptide (hANP) on exocrine function in the isolated and blood-perfused dog pancreas in situ. Intra-arterial injection of hANP (1-10 micrograms) resulted in the dose-dependent increases of the pancreatic juice secretion. The secretory activity of 3 micrograms of hANP was approximately equal to one third of the secretory activity of 0.1 units of secretin. The use of hANP increased the concentration of bicarbonate but not that of sodium and protein in the pancreatic juice as compared with the basal values. These secretory responses to hANP were not inhibited by treatment with haloperidol, sulpiride, phentolamine, propranolol, atropine, cimetidine or ethacrynic acid. These results suggest that hANP acts directly on the pancreatic exocrine gland to stimulate pancreatic secretion; without, however, increasing sodium excretion. The mechanism of this effect remains to be elucidated.

Animals↗
PubMed1987

Inhibition of protein synthesis in LLC-PK1 cells increases calcitonin-induced plasminogen-activator gene transcription and mRNA stability.

The peptide hormone calcitonin induces the accumulation of urokinase-type plasminogen activator (uPA) mRNA in pig kidney LLC-PK1 cells. By itself, inhibition of protein synthesis had a negligible effect on uPA mRNA accumulation. Inhibition of protein synthesis led to two superinductive effects: an increase in calcitonin-induced uPA mRNA accumulation over time, and a shift in the dose-response curve so that lower calcitonin doses became more potent. To explain these two superinductive effects of protein-synthesis inhibition on calcitonin treatment, we demonstrated that the inhibition of protein synthesis increased both calcitonin-induced uPA-gene transcription and uPA-mRNA stability. Different protein-synthesis inhibitors had similar actions, arguing against the possibility that the results were attributable to an anomalous action of a particular inhibitor. The superinductive effects of protein-synthesis inhibition could not be mimicked when a tumour promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA), was used instead of calcitonin as an inducer. Calcitonin and TPA exert their effects through different pathways, suggesting a clue to the mechanism of superinduction. Although inhibition of protein synthesis has been reported to increase transcription and mRNA stability in a number of other systems, the one described here appeared unique in combining both effects in the context of hormonal regulation.

Animals↗
PubMed1987

Dexamethasone coordinately inhibits plasminogen activator gene expression and enzyme activity in porcine kidney cells.

The peptide hormone, calcitonin, induces urokinase-type plasminogen activator (uPA) enzyme activity in cultured LLC-PK1 pig kidney cells. This induction occurs as a consequence of transcriptional activation of the uPA gene. Treatment with the synthetic glucocorticoid hormone, dexamethasone, was found to inhibit calcitonin induction of uPA enzyme activity by as much as 80%. The inhibitory effect of dexamethasone was attributed to at least two mechanisms: induction of an inhibitor of uPA enzyme activity, and reduction in uPA mRNA levels. Study on reduction of uPA mRNA levels showed that dexamethasone significantly reduced the transcription rate of the calcitonin-induced uPA gene, without affecting the half-life of uPA mRNA. Although dexamethasone has been reported to induce inhibitors of plasminogen activator enzyme activity and to inhibit transcription of various genes, the system described here appears novel in that both actions are coordinated.

Animals↗
PubMed1987

Central alpha 2 adrenoceptor-mediated pancreatic exocrine response to yohimbine in anesthetized dog.

Effects of yohimbine on the secretion of pancreatic juice in anesthetized dogs were investigated. Intravenous yohimbine (0.1-1 mg/kg) caused dose-dependent increases in the secretion of pancreatic juice and vasodilation. However, intra-arterial yohimbine (0.3-1 mg) did not cause any secretory responses. The secretory activity of 0.3 mg/kg of yohimbine was approximately equal to that of 0.04 U/kg of secretin and 40 mg/kg of 2-deoxy-D-glucose (2-DG). Secretory responses to yohimbine were inhibited by pretreatment with clonidine or atropine and abolished by vagotomy. The concentration of protein in the pancreatic juice induced by yohimbine was increased, but the bicarbonate concentration was scarcely changed. These results indicate that yohimbine stimulates, at least in part, pancreatic exocrine secretion by acting on the central alpha 2 adrenoceptor in the dog.

Animals↗