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Biomedical subjects

M Ishida

Publications and source records attributed to M Ishida.

At least 91 records · Page 5Linked to original sources
PubMed1999

Cloning and sequencing of a protein involved in phagosomal membrane fusion in Paramecium.

An mAb was raised to the C5 phagosomal antigen in Paramecium multimicronucleatum. To determine its function, the cDNA and genomic DNA encoding C5 were cloned. This antigen consisted of 315 amino acid residues with a predicted molecular weight of 36,594, a value similar to that determined by SDS-PAGE. Sequence comparisons uncovered a low but significant homology with a Schizosaccharomyces pombe protein and the C-terminal half of the beta-fructofuranosidase protein of Zymomonas mobilis. Lacking an obvious transmembrane domain or a possible signal sequence at the N terminus, C5 was predicted to be a soluble protein, whereas immunofluorescence data showed that it was present on the membranes of vesicles and digestive vacuoles (DVs). In cells that were minimally permeabilized but with intact DVs, C5 was found to be located on the cytosolic surface of the DV membranes. Immunoblotting of proteins from the purified and KCl-washed DVs showed that C5 was tightly bound to the DV membranes. Cryoelectron microscopy also confirmed that C5 was on the cytosolic surface of the discoidal vesicles, acidosomes, and lysosomes, organelles known to fuse with the membranes of the cytopharynx, the DVs of stages I (DV-I) and II (DV-II), respectively. Although C5 was concentrated more on the mature than on the young DV membranes, the striking observation was that the cytopharyngeal membrane that is derived from the discoidal vesicles was almost devoid of C5. Approximately 80% of the C5 was lost from the discoidal vesicle-derived membrane after this membrane fused with the cytopharyngeal membrane. Microinjection of the mAb to C5 greatly inhibited the fusion of the discoidal vesicles with the cytopharyngeal membrane and thus the incorporation of the discoidal vesicle membranes into the DV membranes. Taken together, these results suggest that C5 is a membrane protein that is involved in binding and/or fusion of the discoidal vesicles with the cytopharyngeal membrane that leads to DV formation.

Amino Acid Sequence↗
PubMed1999

Inhibition of hepatocellular carcinoma by glycyrrhizin in diethylnitrosamine-treated mice.

Glycyrrhizin (GL) is widely used in Japan as a therapeutic agent for chronic active liver diseases. However, its action on hepatocarcinogenesis remains to be elucidated. To clarify its effect, mice treated with diethylnitrosamine (NDEA) with or without GL were analyzed. Five-week-old male BALB/c mice were divided into two groups, GL (n=50) and C (n=47). Mice in the GL group intramuscularly received 2 mg of GL 3 days a week, and mice in the C group received the same volume of saline in the same way. After 2 weeks, the mice were treated with an i.p. injection of 75 mg/kg body wt of NDEA weekly for 3 weeks and 100 mg/kg body wt of NDEA weekly for the following 3 weeks. Thirty additional mice that did not receive NDEA treatment were divided into two groups, GC (n=15) and SC (n=15). They received GL or saline, respectively. Mice in the 4 groups were killed every 5 weeks after the last injection of NDEA from 7 weeks to 32 weeks. Liver function tests such as AST and albumin were significantly improved in the GL group compared with the C group (P < 0.05, each). Although liver nodules appeared in the C group at 22 weeks, they were not observed until 32 weeks in the GL group. At 32 weeks, the mean number of liver tumors, composed of adenoma and hepatocellular carcinoma (HCC), in the GL group was 0.71, which was significantly decreased compared with 1.64 of the C group (P < 0.05). The mean number of HCC in the GL group was 0.29/liver, which was lower than 0.82/liver in the C group (P < 0.05). The incidence rate of HCC at 32 weeks was 64% in the C group and 21% in the GL group (P < 0.05, C versus GL group). Our results suggest that GL treatment inhibits the occurrence of HCC.

Adenoma↗
PubMed1999

Corticocortical associative neurons expressing latexin: specific cortical connectivity formed in vivo and in vitro.

Latexin, a carboxypeptidase A inhibitor, is expressed in a subset of neurons in the infragranular layers of the lateral cortex in the rat. We here show that latexin-expressing neurons exhibit ultrastructural features common to cortical pyramidal neurons. We show in combined retrograde tracing and immunofluorescent experiments that latexin-expressing neurons contribute to specific corticocortical pathways. Thus, injections of the retrograde tracer fluorogold into either the primary somatosensory (SI) or the primary motor (MI) cortical area labeled many latexin-expressing neurons in the infragranular layers of the secondary somatosensory (SII) and visceral sensory (Vi) areas. In contrast, tracer injections involving the thalamus, striatum, or contralateral SII and Vi exclusively labeled latexin-nonexpressing neurons in both the SII and Vi. Finally, we show that the correct corticocortical projections can be formed in organotypic slice cultures in vitro from latexin-expressing neurons: when slices of developing SII were cocultured with those from the SI and the thalamus, latexin-immunoreactive neurons in the SII projected preferentially to their normal SI target. The specific connectivity formed in vivo and in vitro by this molecularly distinct neuronal population reveals its characteristic manner of cortical organization and provides a unique model system to analyze mechanisms underlying the formation of precise corticocortical pathways.

Age Factors↗
PubMed1999

The relationship between waist-to-hip ratio and occupational status and life-style factors among middle-aged male and female Japanese workers.

As a marker of body fat distribution and therefore level of obesity, the waist-to-hip ratio (W:H) is a good indicator of coronary heart disease risk status. The present study investigated the association between occupational status and life-style factors, and W:H of middle-aged Japanese male (n = 2,550) and female (n = 1,283) workers in a metal-products factory. A higher W:H was observed in the management level males as compared with the other male workers and we suggest this was promoted by the sedentary aspect of their work, as well as their higher levels of alcohol consumption and lower levels of leisure-time physical activity. In contrast, a higher W:H was recorded in female labourers, whose work was typically less sedentary as compared with female managers. Life-style factors included in the study were not related to this observation. We conclude that other unmeasured psychosocial factors may be important in promoting higher W:H in female labourers.

Adult↗
PubMed1999

Characteristics and risk factors of acute dystonia in schizophrenic patients treated with nemonapride, a selective dopamine antagonist.

The occurrence of acute dystonia was prospectively monitored in 39 schizophrenic patients (18 male and 21 female) treated with 9 to 27 mg/day of nemonapride, a selective dopamine antagonist, and the relationship of acute dystonia with characteristics of patients and plasma concentrations of the drug and prolactin was investigated. Twenty (51.3%) of 39 patients had dystonic reactions, the onsets of which occurred within 3 days after the initiation of treatment in 90% of dystonic patients. The incidence of acute dystonia was significantly higher in male than in female patients (77.8% vs. 28.6%, p < 0.05). Younger male patients (< or = 30 years) especially had an extremely high incidence of this side effect (91.7%). A positive correlation between prolactin response after 1 week of treatment and dystonia rating scores was found in male (Spearman rank correlation: r(s) = 0.606,p < 0.01) but not in female patients (r(s) = -0.378,p = not significant). These results suggest that young male patients have the highest risk of neuroleptic-induced dystonia. Prolactin response after 1 week of treatment as an index of dopamine blockade may reflect vulnerability to the development of acute dystonia at least in male patients treated with nemonapride.

Acute Disease↗
PubMed1999

No pharmacokinetic but pharmacodynamic interactions between cisapride and bromperidol or haloperidol.

Pharmacokinetic and pharmacodynamic interactions between the gastrokinetic drug cisapride and the antipsychotic drugs bromperidol and haloperidol were studied in 29 schizophrenic inpatients. Fourteen patients were taking bromperidol (12-24 mg/d), and 15 were taking haloperidol (12-36 mg/d). Cisapride 10 mg/d was coadministered for 1 week, and blood sampling was performed before cisapride treatment, 1 week after starting cisapride treatment, and I week after stopping cisapride treatment. On the same days as the blood sampling, psychotic symptoms and side effects were evaluated using the Brief Psychiatric Rating Scale (BPRS) and the Udvalg for Kliniske Undersøgelser (UKU) side effect rating scale (UKU), respectively. Plasma concentrations of bromperidol, haloperidol, and their reduced metabolites were measured by high-performance liquid chromatography. The mean BPRS scores after adding cisapride were significantly higher than those before cisapride (p<0.01) and after stopping cisapride (p<0.001) in the haloperidol group in this uncontrolled study. A similar tendency was observed in the bromperidol group, although it did not reach statistical significance (p = 0.08). Cisapride coadministration caused no significant changes in the mean plasma concentrations of bromperidol, haloperidol, and their reduced metabolites or in the mean UKU score. The present study suggests that there is no significant pharmacokinetic interaction between cisapride and bromperidol or haloperidol, but cisapride appears to deteriorate psychotic symptoms by a pharmacodynamic interaction in schizophrenic patients treated with haloperidol.

Antipsychotic Agents↗
PubMed1999

[Microbiological and clinical studies with Streptococcus pneumoniae isolated in 5 Kitakyushu municipal hospitals].

Epidemiological and microbiological studies were carried out using 200 strains of pneumococci isolated from clinical specimens in 5 Kitakyushu municipal hospitals, between October 1994 and July 1995. Eighty nine percent of pneumococci were detected in the specimens from the respiratory tract. Pneumococci were isolated mainly from infants under 3-years of age and adults over 50-years of age, and the rates of isolation were 40.5% and 39.5%, respectively. MICs of 8 antimicrobial agents, such as PCG, NFLX, CPFX, LFLX, FLRX, TFLX, SPFX, LVFX, were determined using broth microdilution methods. According to NCCLS standard (1997), recovery rates of PSSP, PISP and PRSP were 48.0%, 39.5% and 12.5%, respectively. Among 7 quinolones, TFLX, SPFX and LVFX were effective so far examined, except for a few resistant strains. Four cases in which quinolones resistant pneumococci were isolated were reviewed retrospectively. Among them 3 cases had been given quinolones before the strains were detected.

Adolescent↗
PubMed1999

Agonist-stimulated cytoskeletal reorganization and signal transduction at focal adhesions in vascular smooth muscle cells require c-Src.

Thrombin and angiotensin II (angII) have trophic properties as mediators of vascular remodeling. Focal adhesions and actin cytoskeleton are involved in cell growth, shape, and movement and may be important in vascular remodeling. To characterize mechanisms by which thrombin and angII modulate vessel structure, we studied the effects of these G protein-coupled receptor ligands on focal adhesions in vascular smooth muscle cells (VSMCs). Both thrombin and angII stimulated bundling of actin filaments to form stress fibers, assembly of focal adhesions, and protein tyrosine phosphorylation at focal adhesions, such as p130Cas, paxillin, and tensin. To test whether c-Src plays a critical role in focal adhesion rearrangement, we analyzed cells with altered c-Src activity by retroviral transduction of wild-type (WT) and kinase-inactive (KI) c-Src into rat VSMCs, and by use of VSMCs from WT (src+/+) and Src-deficient (src-/-) mice. Tyrosine phosphorylation of Cas, paxillin, and tensin were markedly decreased in VSMCs expressing KI-Src and in src-/- VSMCs. Expression of KI-Src did not inhibit stress fiber formation by thrombin. Surprisingly, actin bundling was markedly decreased in VSMCs from src-/- mice both basally and after thrombin stimulation, compared with src+/+ mice. We also studied the effect of KI-Src and WT-Src on VSMC spreading. Expression of KI-Src reduced the rate of VSMC spreading on collagen, whereas WT-Src enhanced cell spreading. In conclusion, c-Src plays a critical role in agonist-stimulated cytoskeletal reorganization and signal transduction at focal adhesions in VSMCs. c-Src kinase activity is required for the cytoskeletal turnover that occurs in cell spreading, whereas c-Src appears to regulate actin bundling via a kinase-independent mechanism.

Angiotensin II↗
PubMed1999

Cerebral cortical specification by early potential restriction of progenitor cells and later phenotype control of postmitotic neurons.

Neurons expressing latexin, a carboxypeptidase A inhibitor, are restricted to lateral areas in the cerebral cortex of adult and early postnatal rats. To address the precise timing of cortical regional specification at the cellular level, we monitored latexin expression in developing cortical cells under specific conditions in vitro. Individual cortical cells were labeled with 5-bromo-2'-deoxyuridine in vivo, dissociated and exposed to a defined new environment in a monolayer or a reaggregated-cell culture system. While a substantial fraction of early progenitor cells derived from the lateral cerebral wall became latexin-expressing neurons in both systems, far fewer progenitors from dorsal cortex did so under the same environmental conditions, indicating early establishment of cortical regional specification at the progenitor cell level. Furthermore, it was shown that the probability for postmitotic cells within lateral cortex to become latexin-expressing neurons was influenced by temporally regulated regional environmental signals. These findings suggest that developing cortical cells are progressively specified for a regional molecular phenotype during both their proliferative and postmitotic periods.

Animals↗
PubMed1999

Linear SRY transcript in equine testis.

Employing a combination of reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) techniques, the complete coding sequence of cDNA for the equine SRY gene was determined. We also attempted to make clear whether the equine SRY gene transcript is expressed in the adult testis, and whether the type of transcript is expressed as linear or circular RNA. As a result, in total a 1420 bp cDNA sequence was determined. Accomplishment of 3' RACE infers that equine SRY gene was expressed as a linear RNA transcript in testicular tissue just after puberty, in contrast to the situation in mice.

Amino Acid Sequence↗
PubMed1999

Recent aspects in the genetic renal mechanisms involved in hypertension.

The kidney plays an important role in the blood pressure regulation primarily by modulating tubular sodium reabsorption. Various hormones, vasoactive peptides, autacoids and transporters or channels in renal tubules are involved in this process. Genes associated with renal tubular sodium handling are possibly related to the development of hypertension. Genes of the renin-angiotensin-aldosterone system are thought to be especially important as causal genes of hypertension. Na-K-ATPase, biochemically equal to Na pump, exists on the basolateral membrane of renal epithelial cells. It plays a central role in Na reabsorption and creates a driving force for transepithelial transport. Na-K-ATPase activity is regulated by adducin, a membrane-bound skeletal protein, as well as by several hormones such as dopamine, endogenous ouabain-like factor or cytochrome P450 metabolites. Genes of these factors involved in Na-K-ATPase regulation should be related to the development of hypertension. The endothelin system, atrial natriuretic peptide and nitric oxide regulate the tonus of blood vessels as well as renal sodium excretion. Several reports have indicated that genes of these substances are crucial in the pathogenesis of hypertension.

Animals↗
PubMed1999

[Thermo-chemotherapy using low-dose CPT-11 in a patient with local recurrence of rectal cancer].

We report a case of pelvic recurrence of advanced rectal carcinoma, presenting a favorable response with a low dose (25 mg/m2) of CPT-11 (Irinotecan) combined with topical hyperthermia for relapse after treatment with 4 cycles of high-dose (100 mg/m2) CPT-11 chemotherapy alone. This combination therapy was safely carried out on an outpatient basis. The degrees of recovery of the left lower limb pain and edema, and of serum CEA reduction were comparable to those in high-dose chemotherapy alone. No significant adverse effects were encountered in the thermo-chemotherapy attempted. Since hyperthermic treatment enhances the cytotoxic effects of CPT-11 in vitro, topical hyperthermia with low-dose CPT-11 therapy may produce a response comparable to that in high-dose CPT-11 chemotherapy alone. However, an optimal dose and comparative study with other chemotherapeutic agents would be needed. This regimen may be advantageous in the maintenance of quality of life for the palliation of postoperative pelvic recurrence since this treatment can be performed on an outpatient basis.

Adenocarcinoma↗
PubMed1999

Factors influencing late survival after abdominal aortic aneurysm repair in Japanese patients.

BACKGROUND: To determine the factors influencing the prognosis of patients with abdominal aortic aneurysms (AAA), the clinical characteristics and long-term survival of 366 consecutive patients were examined and compared with those in previous Western studies. METHODS: During the period from January 1979 to December 1995, 376 patients with AAA were admitted to our hospital. Among these, 332 consecutive patients underwent elective reconstruction of infrarenal AAAs. The remaining 44 patients were not surgically treated. With use of the data from the patients who underwent AAA resection, the relationship of various risk factors, such as cardiac dysfunction, hypertension, renal dysfunction, pulmonary dysfunction, and age, to survival rate was investigated by univariate and multivariate analysis. RESULTS: The operative mortality rate was 0.6%. The survival of the patients who underwent the operation at 5 years was 71.0% and at 10 years 51.8%. The survival rate of the patients who were not surgically treated at 5 years was 26.0% and at 10 years 14.9%. There was a significant difference between the 2 groups. A univariate analysis was performed on each possible risk factor affecting survival rates. In relation to the survival rate of 5 and 10 years, there was no statistical significant difference between patients with or without heart disease or hypertension. By contrast, factors influencing long-term survival were associated with renal dysfunction, pulmonary dysfunction, and age at time of surgery. Multivariate analysis of risk factors affecting survival rates demonstrated that renal dysfunction, pulmonary dysfunction, and age at the time of operation were found to be significant, respectively. The main cause of the death for the long-term survival patients with AAA repair was malignancy, whereas that in the patients without repair was rupture. CONCLUSIONS: Risk factors influencing survival after AAA repair were renal dysfunction, pulmonary dysfunction, and advanced age in Japanese patients. In addition, the main cause of death after aneurysmal resection was malignancy. These results were different from outcomes in Western patients. We need to carefully watch out for malignancy during the follow-up period after AAA resection.

Aged↗
PubMed1999

[Vitrectomy for proliferative diabetic retinopathy associated with iris rubeosis].

OBJECT: To compare the results of vitrectomy for phakic cases and those of aphakic cases with proliferative diabetic retinopathy (PDR) accompanied by rubeosis iridis. MATERIALS & METHODS: We reviewed 34 eyes of 24 cases that underwent vitrectomy for proliferative diabetic retinopathy with rubeosis iridis. RESULT: Phakic eyes needed significantly more reoperations (p < 0.001) than aphakic eyes. Aphakic eyes had significantly more successful visual results (p < 0.05) and better control of intraocular pressure (p < 0.005) than phakic eyes. CONCLUSION: This study showed the possibility that phakic eyes had more ischemic retina producing more angiogenic factors than aphakic eyes which had the same grade of rubeosis iridis. Phakic eyes with pre-operative rubeosis iridis need thorough clearance of ocular ischemia by panretinal photocoagulation.

Diabetic Retinopathy↗
PubMed1999

[A case of Fabry's disease with chronic renal failure].

Fabry's disease is a genetic disorder caused by the absence of alpha-galactosidase (alpha-Gal), the gene of which is carried on the long arm of the X chromosome. This enzymatic defect leads to an accumulation of glycosphingolipids in the plasma and lysosomes of endothelial, perithelial, and smooth muscle cells, especially involving those of the cardiovascular, renal and cerebrovascular systems. We report one male case of Fabry's disease with renal deterioration. A 36-year-old man who was a classic case with acroparesthesia, angiokeratoma, and hypohidrosis from 10 years of age, was diagnosed to be a hemizygote of Fabry's disease at 27 years as a result of severe decreased alpha-Gal activity of his peripheral white blood cells. This patient was found to have a point mutation of a G to A transition in exon 1. In May, 1989, he was reported to have proteinuria with normal renal function and admitted to our hospital due to renal deterioration in September, 1993. Laboratory examinations revealed a serum urea nitrogen of 65 mg/dl and creatinine value of 6.9 mg/dl. Urinary protein excretion was 3.9 g/day and urinary sugar was negative. On the renal biopsy specimens, light microscopic examinations revealed multiple sclerosing and collaptic lesions in glomeruli without severe tubulo-interstitial damage, but with stenotic change of the small arteries and arterioles. Electron microscopic examinations revealed a large number of electron dense deposits in the tubules. We diagnosed this case as Fabry's disease with chronic renal failure, however the pathogenesis of this renal progressive deterioration remained obscure. In this case, degenerative changes in the renal vessels due to Fabry's disease may be associated with rapid deterioration in renal function.

Adult↗
PubMed1999

[Usefulness of endovascular grafting for abdominal aortic aneurysm].

The purpose of this study was to determine the usefulness of endovascular grafting for abdominal aortic aneurysm (AAA) compared to conventional open repair. During the period from May 1998 through to April 1999, 16 patients (control group) with AAA underwent conventional open surgery and 6 patients (stent group) underwent endovascular grafting. Surgical data including operative time and intraoperative blood loss did not differ between the two groups. However, the postoperative parameters including the initiation of oral intake, the onset of flatus and the permission to walk were significantly sooner in the stent group than the control group. The postoperative changes of coagulopathy-fibrinolytic factor were comparable between the two groups. We conclude that the endovascular grafting is minimally invasive compared to conventional open surgery. In addition, there was no consumption coagulopathy in the endovascular grafting. However, it was necessary to develop new approach with new devices in order to perform endovascular grafting more safely.

Aged↗