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Biomedical subjects

Y Nishimura

Publications and source records attributed to Y Nishimura.

At least 541 records · Page 30Linked to original sources
PubMed1995

Inhibitory effect of ethanol and colchicine on the intracellular processing of beta-glucuronidase which occurs in the Golgi complex.

To investigate the effect of ethanol or colchicine on the intracellular proteolytic processing of lysosomal beta-glucuronidase, which is considered to occur in the Golgi complex in the intracellular sorting pathway, three rat liver Golgi subfractions, GF-1, GF-2, and GF-3, were isolated from ethanol- or colchicine-treated rats, and the electrophoretic patterns of the extracted Golgi beta-glucuronidase on polyacrylamide gel were examined. The isolated Golgi subfractions from the drug-treated rats gave a better yield of fraction than that from the control rats. The enzymatic characterization of these three subfractions showed no significant contamination by other subcellular structures such as plasma membranes, microsomes, or lysosomes, and no inhibitory effect of the drugs was observed. On the other hand, suppressed galactosyltransferase activity, a marker enzyme of the Golgi complex, was detected in the colchicine-treated rats. The electrophoretic pattern of Golgi beta-glucuronidase on polyacrylamide gel revealed one major band which moved to the same position as the lysosomal enzyme type in the control rats. In contrast, in the ethanol- and colchicine-treated rats, Golgi beta-glucuronidase was found to have two major bands stained for enzyme activity resulting from a mixture of microsomal- and lysosomal-type enzymes. These results suggested that the post-translational modification step, during conversion from a microsomal-type enzyme to a lysosomal-type enzyme, was apparently inhibited. Taken together, these findings indicated that ethanol or colchicine administration to rats caused an inhibitory effect on the intracellular post-translational modification of Golgi beta-glucuronidase destined for targeting to the lysosomes.

Animals↗
PubMed1995

Inhibitory effect of leupeptin on the intracellular maturation of lysosomal cathepsin L in primary cultures of rat hepatocytes.

To investigate the intracellular processing event for lysosomal cathespin L, we examined the effect of leupeptin, a non-covalent cysteine proteinase inhibitor, on the intracellular processing kinetics of cathepsin L as analyzed by pulse-chase experiments in vivo with [35S]methionine in primary cultures of rat hepatocytes. This revealed that cathepsin L was initially synthesized as proenzyme of molecular weight 39 kDa and the proenzyme was subsequently processed to the mature form of the enzyme, 30 and 25 kDa. In the leupeptin-treated cells, the proteolytic conversion of cellular procathepsin L, of molecular weight 39 kDa, to the mature enzyme was significantly inhibited and considerable amounts of proenzyme were found in the cell after 8 h chase periods. Furthermore, the subcellular fractionation experiment demonstrated that the intracellular processing of procathepsin L in the high density lysosomal fraction was significantly inhibited and that considerable amounts of the procathepsin L form were still observed in the dense lysosomal fraction after a 2 h chase period. These results suggest that leupeptin treatment caused significant inhibition of the intracellular maturation of cathepsin L. These findings show that cysteine proteinase plays an important role in the intracellular proteolytic processing and activation of lysosomal cathepsin L in vivo and that this processing event occurs within the lysosomes.

Animals↗
PubMed1995

Changes of hepatic microsomal oxidative drug metabolizing enzymes in chronic renal failure (CRF) rats by partial nephrectomy.

Male SD rats, 7-weeks-old, were used to investigate the changes in the hepatic drug metabolizing system of chronic renal failure (CRF) model rats. Partial nephrectomy (5/6) was performed in a two-stage surgical procedure. After nephrectomy, the rats were housed under regular conditions at least 21 days. After confirming the CRF states, trimethadione (TMO, 100 mg/kg, i.p.) was administered for evaluation of the hepatic drug metabolizing capacity; the ratio of dimethadione (DMO: the only metabolite of TMO) to TMO (DMO/TMO) in the serum and the dialysate from the blood microdialysis method were ascertained. The hepatic drug metabolizing enzyme contents and activities were also determined. In the CRF rats, the DMO/TMO ratios decreased significantly; total cytochrome P450 (CYP) contents, aminopyrine N-demethylase activity and delta-aminolevulinic acid synthetase activity also decreased significantly in the CRF rats. The extent of the alterations of these enzyme contents and activities correlated well with the severity of the CRF states evaluated by the serum blood urea nitrogen and creatinine concentrations. With Western blot analysis, the levels of CYP2C6, CYP2C11 and CYP3A2 decreased considerably in the CRF rats. These results suggest that CRF states induce not only a reduction of renal function but also an alteration of hepatic metabolism.

Animals↗
PubMed1995

Whole-body retention and fetal uptake of 65Zn in pregnant mice fed a Zn-deficient diet.

Whole-body retention and fetal uptake of 65Zn under a Zn-deficient diet were studied in pregnant mice in the late gestational stage after a single oral administration of 65Zn. Whole-body retentions were much greater in mice given a Zn-deficient diet than in those given a Zn-normal diet. Accordingly, the amount of 65Zn transmitted to the offspring in utero was greater in the Zn-deficient diet group. In another experiment, fetal uptake of 65Zn in dams on gestation day 17 was examined over a period of 24 hr after a single intravenous administration of 65Zn to the Zn-deficient and Zn-normal animals. There was no major difference in fetal uptake between the two groups, indicative that approximately a similar proportion of the 65Zn retained in the maternal body was transmitted to the in utero offspring in both groups.

Animals↗
PubMed1995

Relationship between respiratory muscle strength and lean body mass in men with COPD.

It has been suggested that low body weight may be associated with decreased respiratory muscle function in COPD, but the precise mechanism is not known. Since body compositional change inevitably accompanies body weight change, we decided to study the possible relationship between respiratory muscle strength and body composition in patients with COPD. We studied respiratory muscle strength, pulmonary function, and body composition in 24 Japanese male patients with COPD. Patients were divided into two groups according to their body weight (group A, body weight lower than 80% of ideal body weight vs group B, 80% or more) and a comparison was made together with age-matched controls (group C). Maximal inspiratory mouth pressure (PImax) and maximal expiratory mouth pressure (PEmax) were measured by a previously reported method. Body compositional analysis was performed using dual energy x-ray absorptiometry (DXA; Norland XR26). It showed significantly lower fat body mass (FAT), FAT/body weight%, and lean body mass (LEAN) in group A than those in group B. The PImax in group A was significantly lower than that in group B and C (44.2 +/- 13.8, 76.4 +/- 29.9, and 88.6 +/- 18.1 cm H2O, respectively). PEmax in group A was also significantly lower than that in group B and group C (61.9 +/- 20.1, 86.7 +/- 26.8, and 90.4 +/- 17.6 cm H2O, respectively). Both PImax and PEmax were significantly correlated with LEAN (r = 0.656, r = 0.591, p < 0.01, respectively) in patients with COPD. These results show that respiratory muscle strength is closely associated with body weight and lean body mass in patients with COPD. The present approach to compare respiratory muscle strength with lean body mass should be useful for studying the mechanism of respiratory muscle weakness in patients with COPD.

Absorptiometry, Photon↗
PubMed1995

An adult case of neurohypophyseal ectopy presenting ACTH deficiency and partial GH deficiency.

A case of ACTH deficiency and partial GH deficiency associated with neurohypophyseal ectopy is described. A 42-year-old woman of short stature was admitted for hypoglycemic coma. The patient had hypocortisolemia, an increase in urinary 17-OHCS after consecutive injections of ACTH-Z, and a low plasma ACTH level which showed no response to corticotropin-releasing factor. This indicated the presence of ACTH deficiency. The plasma GH level showed a blunted response to insulin-induced hypoglycemia, but its response to GRF was preserved. Other hypothalamo-pituitary axes were intact. T1-weighted magnetic resonance imaging demonstrated ectopic neurohypophyseal tissue and a tiny anterior pituitary remnant. ACTH deficiency and partial GH deficiency might have developed as a consequence of pituitary stalk injury and inadequate regeneration of the anterior lobe.

Adrenocorticotropic Hormone↗
PubMed1995

Cytosolic free calcium elevation in vascular smooth muscle cells induced by cerebrospinal fluid from patients with subarachnoid hemorrhage--biochemical nature of the calcium-mobilizing factor.

The present study was undertaken to characterize the biochemical nature of the factor in cerebrospinal fluid (CSF) from patients with subarachnoid hemorrhage (SAH) that induces a transient elevation of cytosolic free calcium in cultured vascular smooth muscle cells. Cell-free CSF collected from patients on days 7-10 after SAH was treated in three different ways: heating, ultrafiltration, and salting out with ammonium sulfate. The effects of the resultant solutions on the level of cytosolic free calcium in cultured vascular smooth muscle cells were then examined. Heated CSF and ultrafiltrated solution containing substances with molecular weights of less than 10,000 caused no significant elevation of cytosolic free calcium. Proteins precipitated by 50-75% saturated ammonium sulfate caused an increase in the level of cytosolic free calcium and also produced a rapid accumulation of inositol 1,4,5-trisphosphate in vascular smooth muscle cells. The results indicate that the factor responsible for the increase in cytosolic free calcium in cultured vascular smooth muscle cells is a protein with a molecular weight of more than 10,000, and the factor stimulates receptor-mediated phosphoinositide breakdown.

Calcium↗
PubMed1995

Development and usefulness of the gelatin-particle-agglutination test for titration of antibodies against diphtheria, pertussis and tetanus toxins.

The gelatin-particle-agglutination (PA) test for titrating antibodies against diphtheria, pertussis and tetanus toxins was developed and used for assaying 65 sera from healthy children to assess the antitoxin acquisition in relation to the administration of adsorbed diphtheria-purified pertussis-tetanus (DPT) combined vaccine. The antitoxin titers obtained by the PA test and the conventional methods were correlated well; the correlation coefficient of the diphtheria antitoxin titers between the PA test and the cell culture method was 0.908, that of the tetanus antitoxin titers between the PA test and the passive hemagglutination test 0.968, and that of anti-pertussis toxin titers between the PA test and polystyrene-ball ELISA 0.885. The PA test was shown to be useful in both developed and developing countries, since it is simple to perform, sensitive and specific, and the three antitoxins can be titrated by the same procedure.

Agglutination Tests↗
PubMed1995

Prevention of anti-T-cell receptor alpha beta monoclonal antibody-induced side-effects by treatment with cyclosporin A without interference of monoclonal antibody-induced immunosuppression in mice.

Anti-T-cell receptor (TCR)alpha beta monoclonal antibody (mAb; H57-597) injection in mice caused cytokine (tumour necrosis factor and interferon-gamma) release and clinical side-effects such as piloerection and body weight loss similar to anti-CD3 mAb (145-2C11) injection. Treatment with cyclosporin A (CsA) for 3 days, from day -2 to day 0, prior to anti-TCR alpha beta mAb injection almost completely abolished the mAb-induced cytokine release, and completely inhibited the mAb-induced body weight loss. Furthermore, treatment with CsA from day -2 to day 0 did not inhibit the mAb-induced in vivo immunosuppressive effects, i.e. prolongation of skin allograft and T-cell depletion in the periphery. These results indicate that CsA treatment prior to mAb treatment could effectively inhibit the mAb-induced side-effects without interference of the mAb-induced in vivo immunosuppression. From these results, we propose that CsA treatment prior to injection of anti-TCR alpha beta mAb may be recommended to reduce mAb-induced side-effects.

Animals↗
PubMed1995

Effects of ECS on DNA single-strand breaks in rat brain cells.

We conducted a series of experiments to evaluate possible molecular mechanisms by which electroconvulsive therapy, a commonly used treatment for depression, may exert its adverse effects such as amnesia. We assessed the effects of repeated electroconvulsive shocks (ECS) alone and in combination with low-level radiograph irradiation on DNA single-strand breaks in cells in the rat brain, using a sensitive alkaline microgel electrophoresis assay method. Our results show that ECS, when administered alone, had no significant effects on DNA single-strand breaks in cells in either the hippocampus or the rest of the brain. However, repeated ECS when combined with a low-level radiograph irradiation produced a small but significant increase in DNA single-strand breaks in rat brain cells.

Animals↗
PubMed1995

Pharmacokinetic study of trimethadione and its metabolite in blood, liver and brain by microdialysis in conscious, unrestrained rats.

A microdialysis method has been developed in the past two decades to determine levels of drug and endogenous compounds in several organs under physiological conditions. In this study, we determined the pharmacokinetics of the model drug, trimethadione (TMO), and its only metabolite, dimethadione (DMO), in liver, blood and brain by the microdialysis method in freely-moving rats. Sampling times were extended up to 24 hours. The construction of a newly developed microdialysis probe for liver and blood is described. The elimination patterns of TMO in liver, blood and brain dialyzates were almost identical and the calculated t1/2 was approximately 3 hr in each sample. However, in brain, tmax was delayed compared with the others while the relative concentration of DMO (AUC0-24h) was lower in brain compared with liver and blood. These studies suggest that this concurrent and successive microdialysis sampling method will not only be a useful tool for pharmacokinetic and drug metabolism studies in the organs of small animals but will also decrease the number of experimental animals needed for a study.

Animals↗
PubMed1995

ATL cells recognize self class II HLA antigens: implication to leukemogenesis.

Adult T cell leukemia (ATL) cells show the decreased expression of T cell receptor (TCR)/CD3 complex on their surfaces in vivo. It is well known that excess amounts of antigen modulate TCR/CD3 complex on antigen-specific T lymphocytes. We hypothesized that antigen receptor of ATL cells was down-regulated with some antigenic stimulation in vivo, which might play an important role in leukemogenesis. In order to test this possibility, we studied whether the fresh ATL cells from three cases would respond to autologous and allogeneic lymphoid cell lines. In two of three cases, ATL cells could proliferate in the presence of autologous cell lines. In one case, this proliferation could be completely inhibited by anti-CD3 and anti-human leukocyte antigen (HLA)-DQ monoclonal antibodies, indicating that ATL cells recognized self HLA-DQ. In another case, the proliferation was suppressed by anti-CD3 and HLA-DR antibodies. These findings showed that ATL cells of some cases were derived from autoreactive T lymphocytes and such stimulation via TCR/CD3 complex plays an important role in the leukemogenesis of ATL in vivo.

Autoantigens↗
PubMed1995

Manganese chloride treatment does not protect against acute radiation injury of skin or crypt cells.

Metallothionein (MT), the synthesis of which can be induced by metalloelement administration, is a known radical scavenger. This study investigated the possible protective effect of MT against acute radiation injury. Manganese chloride (10 mg of manganese/kg) was administered intraperitoneally to male C3H/He mice 24 h prior to irradiation. The paw of each mouse was irradiated locally, and the acute skin reaction was scored daily and averaged. Acute radiation injury of the small intestine was studied using an LD50/8 assay and a gut microcolony assay after abdominal irradiation. An LD50/8 value represents the radiation dose required to kill 50% of animals within 8 days. The number of microcolonies per tissue section was counted 3.5 days after irradiation. The level of MT in the liver, skin and intestine was determined by a modified 203Hg-binding assay. Acute skin reaction was not prevented by manganese pre-administration. The LD50/8 values of manganese-pretreated and control mice were 19.4 and 18.4 Gy, respectively. However, the difference was not significant. The number of microcolonies was not significantly different for these two groups in the dose range of 13-19 Gy. The level of MT in the skin and intestine was not increased by administration of manganese, although a sixfold increase was observed in the liver. In conclusion, manganese chloride treatment of mice 24 h prior to irradiation did not significantly protect skin and small intestine against acute radiation injury, because such a treatment did not result in increased levels of MT in the skin and small intestine.

Animals↗
PubMed1995

[Recent progress of thermoradiotherapy in cancer therapy].

The recent progress of thermoradiotherapy for cancer is reviewed. Several biological methods for increasing the effects of heat on tumors have been developed, and some of them are being clinically investigated. Physical progress includes two new heating devices developed in Japan. One is an ultrasound heating system and the other is an intracavitary RF heating applicator in which simultaneous intracavitary irradiation is possible. The negative results of RTOG trial in USA caused a great impact in clinical hyperthermia. Careful analysis of this trial, however, demonstrated the advantages of the use of hyperthermia for those cases in which ther was good quality assurance of hyperthermia. Recent results of ESHO trials in Europe clearly demonstrated the superiority of thermoradiotherapy over radiotherapy alone for several tumors. Various site-specific clinical trials are expected to clarify the indications of thermoradiotherapy in future.

Clinical Trials, Phase III as Topic↗
PubMed1995

[Prolonged muscle paralysis after long-term infusion of muscle relaxants and large doses of steroids].

We have recently encountered three patients who developed prolonged muscle paralysis after long-term infusion of muscle relaxants and administration of large doses of steroids. Among many factors implicated in the cause of this paralysis, steroids and muscle relaxants were suggested to be most likely causative agents. In order to avoid such muscle paralysis, we must be careful to limit the dose of relaxants as small as possible. For this purpose, monitoring of neuromuscular blockade is indispensable.

Female↗
PubMed1995

[Clinical study on incidental renal cell carcinoma].

Between 1985 and 1992, 119 patients with renal cell carcinoma were treated at our hospital. Among these cases, 71 cases (59.7%) were incidentally detected in the absence of any suggestive clinical signs of a tumor, 41 cases (34.5%) presented urological or general signs suggestive of the tumor, and 7 cases (5.88%) were detected by metastatic lesions initially. We reviewed 71 cases of incidental carcinoma compared with 41 cases of symptomatic carcinoma. The ratio of incidental carcinoma has been increasing steadily for 8 years, and it was more than 70% of all cases in the last 3 years. The carcinoma was detected at routine health examinations in 25 cases, and during examination for unrelated diseases in 46 cases. Forty-seven cases (66.2%) were detected by ultrasonography, 24 cases (33.8%) by computerized tomography and none by intravenous pyelography. Tumor extension was within the renal capsule in 94.4% of the incidental carcinoma and the mean diameter was 4.39 cm, which was significantly smaller than that of symptomatic carcinoma (p < 0.0001). Peripheral tumors and clear cell subtype tumors were more frequently detected in incidental carcinoma (p < 0.0001 and p = 0.0018). Tumor stage and grade of tumor cell were significantly lower than symptomatic carcinoma (p < 0.0001). The five-year survival rate in incidental carcinoma was 98.5%. There was a significant difference in survival between the incidental and symptomatic carcinoma (p < 0.001).

Carcinoma, Renal Cell↗