Biomedical subjects

M Nishi

Publications and source records attributed to M Nishi.

At least 91 records · Page 5Linked to original sources

PubMed1999

Real-time imaging of glucocorticoid receptor dynamics in living neurons and glial cells in comparison with non-neural cells.

To investigate the intracellular trafficking of glucocorticoid receptor (GR) in response to various conditions in a single living cell, a green fluorescent protein (GFP) and rat GR chimera construct (GFP-GR) was prepared. We transiently transfected GFP-GR into primary cultured rat hippocampal neurons, cortical glial cells, and non-neural cells, e.g. COS-1 cells and CV-1 cells, and compared the dynamic changes in subcellular localization of GFP-GR in these cells. When GFP-GR was expressed in the cells, GFP-GR efficiently transactivated the mouse mammary tumour virus promoter in response to dexamethasone (DEX). The cytoplasm-to-nuclear translocation of GFP-GR induced with 10(-7) m DEX, a specific agonist of GR, at 37 degrees C was completed within 30 min in all cell types used, and the rate of nuclear translocation was dependent on the ligand dose. The translocation of GFP-GR into the nucleus from the cytoplasm was induced in a ligand-specific manner, similar to that of the native GR. The disruption of microtubules by colchicine or nocodazole showed no significant effect on the DEX-induced GFP-GR translocation from the cytoplasmic region to the nuclear region. The cells were not deteriorated during time-lapse imaging analysis for 1 h at 37 degrees C. The present findings suggest that the subcellular localization of GFP-GR is dynamically changed in response to extracellular and intracellular conditions, and that there are no conspicuous variations in the manner of trafficking of GR among different types of cells in vitro.

Animals↗

PubMed1999

The location of positive nodes partly influences the prognostic value of the number of positive nodes in breast cancer patients.

BACKGROUND: The aim was to determine whether the number of positive lymph nodes or the location of lymph node metastasis (location number) would permit a more accurate prediction of prognoses. METHODS: We compared the survival rates of 3922 patients with primary breast cancer in relation to the location number and the number of positive lymph nodes. Survival rates were calculated by the Kaplan-Meier method and analyzed using the log rank test. RESULTS: Within the n1 alpha group, the presence of one or two positive nodes was associated with significantly better survival than the presence of three positive nodes. These groups should therefore be distinguished. Within the n1 beta group, there was no significant difference in survival between patients with four and those with seven or more positive nodes. Comparisons of n1 beta and n2 patients after subgrouping by the number of positive nodes (4-9 and 10 or more) revealed a significantly poorer prognosis in the n2 group. CONCLUSIONS: When the prognosis of breast cancer is considered from the viewpoint of lymph node metastasis, the location number as described in the General Rules is an excellent classification. However, we should be aware of possible differences in the prognosis depending on the number of positive nodes, as this is masked by the location number.

Adult↗

PubMed1999

Epidemic of gastrointestinal tract infection including hemorrhagic colitis attributable to Shiga toxin 1-producing Escherichia coli O118:H2 at a junior high school in Japan.

BACKGROUND: An epidemic of gastrointestinal disturbances related to food ingestion occurred at a junior high school in Komatsu, Japan, and was caused by specifically Shiga toxin (Stx) 1-producing Escherichia coli O118:H2, which has not been reported previously in humans. No outbreak of E coli-producing Stx 1 alone had occurred. METHODS: A total of 526 students and 35 adult staff members who ate the same food at lunch in the school were investigated. Questionnaires about food consumption at lunch were given to all 561 subjects as well as to clinics and hospitals that had treated 79 patients. Stool specimens from 525 subjects, and food, water, and environmental specimens, including cooking utensils, were collected in an attempt to identify the pathogen. RESULTS: A total of 126 subjects (22.5%) developed a diarrheal illness. The pathogen was isolated from the stool in 131 subjects, 49 of which were asymptomatic, and from a dipper. Salads served over several days were identified as high-risk from food analysis. Gastrointestinal symptoms resembled those associated with previous infections of Stx-producing E coli, but were mild. No cases of the hemolytic-uremic syndrome developed. Headache was present in 87 patients. Three patients underwent surgery for acute appendicitis during this epidemic. Four of five carriers had received an antibiotic effective against the pathogen. CONCLUSIONS: This outbreak of E coli O118:H2 demonstrated the clinical and epidemiologic features of infection by E coli that produces Stx 1 alone. Infections with such organisms are being recognized increasingly, and the pattern of disease observed may differ from the pattern observed with E coli O157:H7.

Acute Disease↗

PubMed1999

Zung's depression scale as a predictor of death in elderly people: a cohort study in Hokkaido, Japan.

The relation between each question in the Self-rating Depression Scale (SDS) of Zung and mortality in elderly people was investigated. Subjects were 2,166 inhabitants aged from 60 to 74 years in the Hidaka district of Hokkaido Prefecture, Japan, who were the same as in our previous prospective study concerning mental depression and mortality (J. Epidemiol. 1997). They were followed until February 1996. Among the original 20 questions of the SDS, 12 ones showed significant risk ratio for mortality (those whose score was 3 or 4 vs 1 or 2; P < 0.01). The mortality of those whose average score of the 12 questions was more than 2.4 (severe depression) was 157.2 per 1,000, which was about 5.8 time as high as that of those who were not depressive (average score < 2.0). The 12 questions showed different risk ratios concerning the mortality of cancer, heart disease and cerebrovascular disease. The questions "Morning is when I feel the best" and "My heart beats faster than usual," e.g., showed a significant risk ratio only for the mortality of heart disease (3.96) and for that of cerebrovascular disease (16.49), respectively (P < 0.01). Similar results were obtained from the subjects without respective diseases at the time of survey. Using these 12 questions, the risk for death and its cause can be estimated to a certain extent, and consequently, social supports can be given more effectively and more carefully.

Aged↗

PubMed1999

Life span of Japanese male medical doctors.

There have been few reports with regard to the life spans of medical doctors. The status of the medical doctors graduating from 1926 to 1974, alive or dead as of October 1996, was ascertained on the basis of the list of graduates from the School of Medicine, Hokkaido University. Excluding data on female doctors and those who died in battle during World War II, data on a total of 3,982 doctors were available for study. Their mortality as of October 1996 decreased in parallel with the graduation year. Their mean future life span at graduation was estimated to be about 52.88 years (95% CI, 52.45-53.31) through linear regression (r = 0.992). Their mean age at graduation was 25.17 years. This was not different from the future life expectancy at 25 years of age of the general population (52.35 years). The future life span of surgeons and gynecologists-obstetricians was shorter than that of the doctors of basic medical sciences and internal medicine. This difference might be accounted for by factors peculiar to each speciality (e.g., exposure to blood) or by the degree of stress from work.

Age Factors↗

PubMed1999

Epidemiology of childhood brain tumors in Japan.

Using the vital statistics issued annually by the Japanese Government from 1960 to 1994, the mortality of brain tumors during childhood (0-14 years of age) in Japan was estimated. Since there are few nationwide registries of childhood cancers with a sufficiently high registration rate, the incidence of brain tumors was calculated using the Registry of Childhood Malignancies in Hokkaido Prefecture from 1969 to 1996. Though the mortality due to malignant diseases as a whole during childhood has been decreasing, and though there should be progress in therapeutic methods, the mortality due to brain tumors in children has been increasing. The incidence of brain tumors in Hokkaido Prefecture has been increasing as well. There was no tendency for the incidence of medulloblastoma to decrease. The incidence of childhood brain tumors has been increasing in Japan, though the cause is unknown. The period of the present study corresponded to a period of high economic growth. Thus, a study on environmental factors would be interesting.

Adolescent↗

PubMed1999

[Appropriate duration of postoperative pain relief by continuous epidural infusion in patients receiving hysterectomy or ovarian tumor resection: comparison of three methods].

We evaluated effects of continuous epidural infusion on postoperative pain, and frequency of its side effects. Patients who had undergone elective gynecological operations were randomly allocated into three groups by difference in duration of indwelling of epidural catheters: patients receiving epidural block only during operations (group M); patients receiving continuous epidural infusion for 2 postoperative days (group B 2); patients receiving continuous epidural infusion for 4 postoperative days (group B 4). In group M, morphine 3 mg and 1 or 2% lidocaine 5-7 ml were given before the start of operation, and epidural catheter was removed after the end of operations. In group B 2 and B 4, morphine 2 mg and 1 or 2% lidocaine 5-7 ml were given before the start of operation, and morphine 8 mg in 50 ml of 0.25% bupivacaine was continuously infused at a rate of 0.5-1 ml.hr-1. We evaluated visual analogue scale (VAS) at rest and moving, and verbal descriptor pain score. Frequencies of supplementary analgesics, vomiting and nausea, residual urine volume after removal of bladder catheter, and timing to initiation of bowel movement after operation were also recorded. VAS at rest was significantly higher in group M than in groups B 2 and B 4 for 2 postoperative days, but no significant difference was seen between the three groups for three postoperative days. VAS at moving did not differ between the 3 groups. Verbal descriptor pain score was significantly higher in group M than in groups B 2 and B 4 for 3 postoperative days, but it was not different between groups B 2 and B 4. In group B 2, patients complained increased abdominal pain after removing catheters. Frequencies of supplementary analgesics were 3.7, 0.6 and 0.4 times in group M, B 2, B 4, respectively. Times to initiation of bowel movement after operation were 39.8, 46.5 and 61.7 hrs in group M, B 2, and B 4, respectively, and most patients in group B 4 felt uncomfortable. These results suggest that continuous epidural analgesia for 2 postoperative days is appropriate, but the duration should be determined according to patient's conditions and complications.

Adult↗

PubMed1999

[A comparative study of a thick and standard loop in transurethral resection of the prostate].

We compared the safety and efficacy of transurethral resection of the prostate (TURP) with a thick loop and with a standard loop. We compared 36 consecutive men (median age, 70 years) with symptomatic benign prostatic hyperlasia (BPH) treated by TURP with a thick loop to a cohort of 36 men (median age, 72 years) treated by TURP with a standard loop. The safety parameters of evaluation included the operative time, blood loss, chronological changes in serum sodium, and complications. The efficacy parameters of evaluation included International Prostate Symptom Score, quality of life assessment, peak urinary flow rate, and post-void residual urine volume. The operative time (median, 49.5 versus 43.5 minutes), blood loss (median, 179 versus 127 ml), and change in serum sodium (median, -4.0 versus -6.0 mEq/L) were not significantly greater in the thick loop group than in the standard loop group, respectively. There were no major complications in either group. Clinically significant improvement was observed in all efficacy parameters in both groups, with no difference between the two groups. These results suggest that TURP with a thick loop is not necessarily superior to TURP with a standard loop in terms of decreasing the blood loss and decreasing the operative time.

Aged↗

PubMed1999

[Complications of extraintestinal endocrine disease associated with ulcerative colitis--association of ulcerative colitis and autoimmune thyroid disease].

We experienced a rare case of Basedow's disease followed by ulcerative colitis (UC). The association of UC and autoimmune thyroid disease was reviewed and discussed. A high frequency of endocrine autoimmunity, especially autoimmune thyroid disease, was reported in patients with UC. But prevalence of autoimmune thyroid disease associated with UC varies widely in different studies. Some authors described that it was impossible to say that the observed numbers of UC associated with thyroid disease exceed to those to be expected in a random sample of the general populations. The hypothesis that autoimmunity is important in the pathogenesis of UC and thyroid disease continues to stimulate interest. But the evidence for autoimmunity acting in these diseases is not quite as convinced. Further investigation is warranted to clarify the exact relationships between UC and thyroid disease.

Adult↗

PubMed1998

Mitsugumin23, a novel transmembrane protein on endoplasmic reticulum and nuclear membranes.

We report the identification using monoclonal antibody and the primary structure by cDNA cloning of mitsugumin23, a novel transmembrane protein with a molecular mass of approximately 23 kDa from skeletal muscle sarcoplasmic reticulum. Mitsugumin23 possesses three putative transmembrane segments, and its carboxy-terminal hydrophilic region exhibits sequence similarity with the tail-end portion of the myosin heavy chain. Immunochemical analysis showed that this protein is distributed throughout the outer nuclear membrane and the sarcoplasmic reticulum including the terminal cisternae at the triad junction in skeletal muscle cells. Furthermore, RNA blotting and immunohistochemical experiments demonstrated that mitsugumin23 is distributed among a wide variety of cell types in various tissues. The distribution and primary structure indicate the possibility that mitsugumin23 interacts with cytoplasmic protein(s) and participates in a housekeeping function on the intracellular organelle membranes.

Amino Acid Sequence↗

PubMed1998

Facilitation of long-term potentiation and memory in mice lacking nociceptin receptors.

The peptide nociceptin (also named orphanin FQ) acts in the brain to produce various pharmacological effects, including hyperalgesia and hypolocomotion. The nociceptin receptor uses guanine-nucleotide-binding proteins to mediate the inhibition of adenylyl cyclase, the activation of potassium channels and inhibition of calcium channels. It has been shown using knock-out mice that the nociceptin receptor is not required for regulation of nociceptive responses or locomotion activity, but modulates the auditory function. Here we show that mice lacking the nociceptin receptor possess greater learning ability and have better memory than control mice. Histological analysis revealed the expression of both the nociceptin precursor and the nociceptin receptor in the hippocampus, thought to take part in aspects of learning and memory. Moreover, the receptor-deficient mice showed larger long-term potentiation in the hippocampal CA1 region than control mice, without apparent changes in presynaptic or postsynaptic electrophysiological properties. These results show that the loss of the nociceptin receptor results in a gain-of-function mutation in both the memory process and the long-term potentiation mechanism in CA1, perhaps as a result of altered intracellular signal transduction systems in neurons.

Animals↗

PubMed1998

Structure and expression of mitsugumin29 gene.

Recently mitsugumin29 unique to the triad junction in skeletal muscle was identified as a novel member of the synaptophysin family; the members of this family have four transmembrane segments and are distributed on intracellular vesicles. In this study, we isolated and analyzed mouse mitsugumin29 cDNA and genomic DNA containing the gene. The mitsugumin29 gene mapped to the mouse chromosome 3 F3-H2 is closely related to the synaptophysin gene in exon-intron organization, which indicates their intimate relationship in molecular evolution. RNA blot hybridization and immunoblot analysis revealed that mitsugumin29 is expressed abundantly in skeletal muscle and at lower levels in the kidney. Immunofluorescence microscopy demonstrated that mitsugumin29 exists specifically in cytoplasmic regions of the proximal and distal tubule cells in the kidney. The results obtained may suggest that mitsugumin29 is involved in the formation of specialized endoplasmic reticulum systems in skeletal muscle and renal tubule cells.

Amino Acid Sequence↗

PubMed1998

Loss of antinociception induced by naloxone benzoylhydrazone in nociceptin receptor-knockout mice.

Nociceptin and nociceptin receptor, which show structural similarities to opioid peptides and opioid receptors, respectively, have been recently found to constitute a novel neuromodulatory system. In the brain, however, the physiological role of the modulation via the nociceptin receptor is still unclear. Administered nociceptin produces hyperalgesia and hypolocomotion, whereas the nociceptin receptor-knockout mice show no significant abnormalities in nociceptive thresholds and locomotion. To clarify possible involvement of the nociceptin receptor in the regulation of nociception and locomotion, we made use of the knockout mice and naloxone benzoylhydrazone (NalBzoH) identified originally as a ligand for opioid receptors. Experiments on the cultured cells transfected with the nociceptin receptor cDNA showed that NalBzoH competed with [3H]nociceptin binding and attenuated the nociceptin-induced inhibition of cAMP accumulation. Furthermore, behavioral studies demonstrated that NalBzoH completely inhibited nociceptin-induced hyperalgesia and hypolocomotion. It is therefore likely that NalBzoH can act as a potent antagonist for the nociceptin receptor in vivo. In wild-type mice, NalBzoH induced antinociception but did not affect locomotor activity. In contrast, in the knockout mice, no significant changes in nociception and locomotion were induced by NalBzoH. These results clearly suggest that the nociceptin system takes part in the physiological regulation of nociceptive thresholds but not in the basal modulation of locomotion.

Animals↗

PubMed1998

Magnitude of skin vasomotor reflex represents the intensity of nociception under general anesthesia.

Because nociceptive stimuli induce the skin vasomotor reflex (SVmR), the assessment of the SVmR would be a useful indicator to represent nociception. We examined 39 adult patients for the relationship between the magnitude of the SVmR and the intensity of nociceptive stimulus that induced the SVmR. Under oxygen-nitrous oxide (50%) and sevoflurane anesthesia, the SVmR was induced by an electrical impulse to the ulnar nerve and detected by a laser Doppler flowmeter. Study 1: under the end-tidal concentrations of sevoflurane at 1.2% (n = 10), 1.7% (n = 9) or 2.2% (n = 10), the SVmR was tested by a 2-s, 50-Hz tetanic electrical impulse with a current intensity changing (40, 50 or 60 mA) in a randomized order. Study 2: under the end-tidal concentration of sevoflurane at 1.7% (n = 10), the SVmR testing was performed with a 50-mA, 50-Hz tetanic electrical impulse with the current duration changing (2, 3 or 4 s) in a randomized order. The studies demonstrated significant correlations of (1) the current intensity which induces the skin vasomotor reflex (SVmR) vs. the magnitude of the SVmR under the three different anesthesia depths, (2) the anesthesia depth vs. the magnitude of the SVmR (inverse proportion) under the same current intensity and (3) the duration of electrostimulation vs. the magnitude of the SVmR. Thus, the SVmR could be helpful for the objective assessment of nociception and anti-nociceptive effects in individual cases.

Adult↗

PubMed1998

A tumor profile in Down syndrome.

We conducted a review of cancers in Down syndrome (DS), because solid tumors are poorly understood in DS. Cancers are in excess in this condition because of the 20-fold excess of leukemias, whereas malignant solid tumors seem to be globally underrepresented as compared with those in the general population. However, among these tumors, some tumors are in excess: lymphomas, gonadal and extragonadal germ cell tumors, and possibly retinoblastomas and pancreatic and bone tumors. Neoplasms in excess are seen earlier, sometimes in fetal life (leukemias and testicular germ cell tumors) or neonatally (leukemias and lymphoma) and affect mainly male subjects. There seems to exist an excess of rare karyotypes. Other tumors are underrepresented, particularly neuroblastomas and nephroblastomas, in young children, and perhaps common epithelial tumors in adults. These observations suggest that DS has a particular tumor profile, with some tissues more affected by malignant diseases (hematopoietic tissue and germ cells) and others that seem to be protected (central and peripheral nervous system, renal tissue, and epithelial tissues). The mechanism is mainly genetic, but differences in exposure to exogenous agents compared with the general population must be kept in mind. These findings are of interest for the management of these patients and early detection of cancers. Better knowledge of this tumor profile could help us to understand the mechanisms of carcinogenesis and should be compared to the current knowledge of genes on chromosome 21.

Adult↗

PubMed1998

Embryonic lethality and abnormal cardiac myocytes in mice lacking ryanodine receptor type 2.

The ryanodine receptor type 2 (RyR-2) functions as a Ca2+-induced Ca2+ release (CICR) channel on intracellular Ca2+ stores and is distributed in most excitable cells with the exception of skeletal muscle cells. RyR-2 is abundantly expressed in cardiac muscle cells and is thought to mediate Ca2+ release triggered by Ca2+ influx through the voltage-gated Ca2+ channel to constitute the cardiac type of excitation-contraction (E-C) coupling. Here we report on mutant mice lacking RyR-2. The mutant mice died at approximately embryonic day (E) 10 with morphological abnormalities in the heart tube. Prior to embryonic death, large vacuolate sarcoplasmic reticulum (SR) and structurally abnormal mitochondria began to develop in the mutant cardiac myocytes, and the vacuolate SR appeared to contain high concentrations of Ca2+. Fluorometric Ca2+ measurements showed that a Ca2+ transient evoked by caffeine, an activator of RyRs, was abolished in the mutant cardiac myocytes. However, both mutant and control hearts showed spontaneous rhythmic contractions at E9.5. Moreover, treatment with ryanodine, which locks RyR channels in their open state, did not exert a major effect on spontaneous Ca2+ transients in control cardiac myocytes at E9.5-11.5. These results suggest no essential contribution of the RyR-2 to E-C coupling in cardiac myocytes during early embryonic stages. Our results from the mutant mice indicate that the major role of RyR-2 is not in E-C coupling as the CICR channel in embryonic cardiac myocytes but it is absolutely required for cellular Ca2+ homeostasis most probably as a major Ca2+ leak channel to maintain the developing SR.

Animals↗

PubMed1998

Mass screening for neuroblastoma targeting children age 14 months in Sapporo City: a preliminary report.

BACKGROUND: In Sapporo City a mass screening program for neuroblastoma targeting children age 6 months (6-MS) was initially introduced in 1981. Since April 1991, an additional program has been implemented, aimed at children age 14 months (14-MS). METHODS: High performance liquid chromatography was employed in the 14-MS. Identification of cases was dependent on the Registry of Childhood Malignancies in the Hokkaido Prefecture. RESULTS: Of the 85,783 live births in Sapporo City during the period 1990-1994, a total of 56,444 participated in the 14-MS (compliance rate, 65.8%). By the end of 1996, of 48,448 children who had previously taken part in the 6-MS, 6 cases were identified in the 14-MS, and 1 additional case screened negative but was later diagnosed clinically. Two more cases were detected in the 14-MS among the 7996 children who had not participated in the 6-MS. Though the incidence of cases identified by the 14-MS was much higher than expected, several true-positive cases had unfavorable histology (as defined by Shimada's classification), a high dopamine level, and/or a high homovanillic acid/vanillylmandelic acid ratio. CONCLUSIONS: Mass screening of children age 14 months for neuroblastoma detects cases missed or unscreened at age 6 months, though the detection rate appears to be in excess of what would be expected from natural incidence.

Cross-Sectional Studies↗

PubMed1998

Mitsugumin29, a novel synaptophysin family member from the triad junction in skeletal muscle.

In skeletal muscle, excitation-contraction (E-C) coupling requires the conversion of the depolarization signal of the invaginated surface membrane, namely the transverse (T-) tubule, to Ca2+ release from the sarcoplasmic reticulum (SR). Signal transduction occurs at the junctional complex between the T-tubule and SR, designated as the triad junction, which contains two components essential for E-C coupling, namely the dihydropyridine receptor as the T-tubular voltage sensor and the ryanodine receptor as the SR Ca2+-release channel. However, functional expression of the two receptors seemed to constitute neither the signal-transduction system nor the junction between the surface and intracellular membranes in cultured cells, suggesting that some as-yet-unidentified molecules participate in both the machinery. In addition, the molecular basis of the formation of the triad junction is totally unknown. It is therefore important to examine the components localized to the triad junction. Here we report the identification using monoclonal antibody and primary structure by cDNA cloning of mitsugumin29, a novel transmembrane protein from the triad junction in skeletal muscle. This protein is homologous in amino acid sequence and shares characteristic structural features with the members of the synaptophysin family. The subcellular distribution and protein structure suggest that mitsugumin29 is involved in communication between the T-tubular and junctional SR membranes.

Amino Acid Sequence↗