Search PubMed⌕ Search

Biomedical subjects

M Nishi

Publications and source records attributed to M Nishi.

At least 109 records · Page 6Linked to original sources
PubMed1998

Enhancement of spatial attention in nociceptin/orphanin FQ receptor-knockout mice.

We isolated genes for the opioid receptor homologue MOR-C, namely nociceptin receptor (designated alternatively as orphanin FQ receptor) and generated nociceptin receptor-knockout mice. Previously, we have reported that the nociceptin system appears to participate in the regulation of the auditory system. However, the behavior of the nociceptin receptor-knockout mice has yet to be fully characterized. In the present study, we investigated changes in several behavioral performances in mice which lack nociceptin receptor. Nociceptive thresholds of nociceptin receptor-knockout mice were unchanged in the hot-plate and electric foot-shock tests as well as tail-flick and acetic-acid-induced writhing tests compared to those of wild-type mice. The nociceptin receptor-knockout mice did not show any behavioral changes in the elevated plus-maze task. Surprisingly, in the water-finding test, the nociceptin receptor-knockout mice showed an enhanced retention of spatial attention (latent learning) compared to wild-type mice. In a biochemical study, dopamine content in the frontal cortex was lower in nociceptin receptor-knockout mice than wild-type mice. These results suggest that nociceptin receptor plays an important role in spatial attention by regulating the dopaminergic system in the brain.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Frequent loss of gelsolin expression in non-small cell lung cancers of heavy smokers.

Most lung and bladder cancers have been shown to be associated with smoking. We have previously demonstrated the frequent loss of gelsolin expression and its tumor suppressor activity in bladder cancer (M. Tanaka et al., Cancer Res., 55: 3228-3232, 1995). Here, we examined gelsolin expression in 12 cultured non-small cell lung cancer (NSCLC) cell lines. Furthermore, we analyzed gelsolin expression in relation to patients' smoking habits in 88 surgically resected NSCLCs to investigate whether gelsolin could be a molecular target for tobacco-induced carcinogenesis of lung cancer. All 12 NSCLC cell lines showed low-to-undetectable expression of the gelsolin gene, compared to that in normal lung tissue, by Northern blot analysis. On the other hand, Southern blot analysis of genomic DNA did not show any gross rearrangements or deletions of the gene in the NSCLC cell lines. Western blot analysis of gelsolin expression showed low-to-undetectable gelsolin expression in all 12 NSCLC cell lines, compared to normal lung tissue. Immunocytochemical analysis of gelsolin expression in NSCLC cell lines showed results that were consistent with those obtained by Western blot analysis, using normal bronchial epithelial cells as a positive control: two cell lines with lower gelsolin expression by Western blot analysis had reduced but positive cytoplasmic immunostaining of gelsolin, compared with primary normal bronchial epithelial cells, whereas no such immunostaining was observed in two cell lines with much lower or undetectable gelsolin expression by Western blot analysis. Therefore, gelsolin expression was analyzed in surgically resected NSCLCs by immunohistochemistry. Reduced or undetectable gelsolin expression was observed in 48 of 88 (55 %) resected NSCLCs. Such altered gelsolin expression significantly correlated with heavy smoking of patients (> or =20 pack-years; P = 0.008 by the chi2 test and P = 0.03 by multivariate logistic regression analysis), whereas there was no significant correlation between gelsolin expression and histological type, pathological tumor-node-metastasis (pTNM) stage, or survival. These findings suggest that the frequent loss of gelsolin expression may be involved in the development of NSCLCs as a potential molecular target of tobacco-induced carcinogenesis.

Aged↗
PubMed1998

Surgical treatment for carcinoma of the thoracic esophagus with major involvement in the neck or upper mediastinum.

BACKGROUND AND OBJECTIVES: In carcinoma of the thoracic esophagus, most surgeons consider that esophagectomy is contraindicated in patients with clinical evidence of major extraesophageal involvement in the lower neck or peritracheal regions. However, metastases to these regions are commonly found even in early phases of carcinoma invasion. With recent progress in preoperative assessment, operative technique and adjuvant therapy, esophagectomy could possibly benefit appropriately selected patients. METHODS: We retrospectively analyzed results in 42 patients who had major involvement in the neck or upper mediastinum and who underwent esophagectomy with systematic lymph node dissection. We operated upon patients unless lesions were assessed as definitely unresectable. Preoperatively, 32 had enlarged peritracheal nodes greater than 15 mm in diameter on computed tomography, 18 had hard unmobile tumors in the lower neck, 9 had recurrent laryngeal nerve palsy, and 10 had findings suggestive of tracheal invasion. Preoperative radiotherapy and/or chemotherapy was given to 32 low-risk patients. RESULTS: The hospital mortality rate was 4%. Bowel reconstruction was completed in all cases. No macroscopically recognizable lesion remained after operation in 35 patients. Eight patients were alive 5 years after esophagectomy, including 2 who had had tracheal invasion and 1 with recurrent nerve palsy. The cumulative 5-year survival was 38%. CONCLUSIONS: Evidence of major involvement of the neck and/or upper mediastinum does not always contraindicate resection. Aggressive esophagectomy combined with perioperative adjuvant therapy yielded acceptable palliation and occasional cure in cases with technically resectable lesions.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Steroid hormones and their receptors in the brain.

Steroid hormones regulate several important functions of the brain by altering the expression of particular genes through their receptors. First in this paper the localization of glucocorticoid receptor immunoreactivity and mRNA in the brain was examined. Second biphasic effects of glucocorticoid on the hippocampus was described and particular emphasis was given on the apoptosis. Third the significance of estrogen receptor in the sexually dimorphic areas was discussed. These results suggest that steroids modulate the gene expression along with the alteration of cell structures in a different manner in a tissue-specific pattern.

Animals↗
PubMed1998

Cervicothoracic approach for total mesoesophageal dissection in cancer of the thoracic esophagus.

BACKGROUND: The clinical significance of lymph node involvement along the recurrent laryngeal nerves in cancer of the thoracic esophagus is still controversial. Although these lymph nodes are anatomically located in a well-defined compartment (proximal mesoesophagus), appropriate procedures for dissecting them are not well established. STUDY DESIGN: We retrospectively investigated clinical results over the past 10 years in 276 patients who underwent systematic dissection of cervical, mediastinal, and upper abdominal lymph nodes. We routinely performed the cervical procedure before thoracotomy for total dissection of the proximal mesoesophagus and to minimize the operative risk. RESULTS: All macroscopically recognizable lesions were resected in 94% of the patients. The hospital mortality rate was 2.5%. Recurrent nerve palsy developed in 59 patients, but it was successfully managed without prolonged hoarseness in 50 of them. The recurrent nerve node group was most frequently involved (frequency of 25% in superficial cancer, 57% in non-superficial cancer). Supradiaphragmatic lymph node involvement was limited to the recurrent nerve nodes in 25% of the patients with positive supradiaphragmatic node. The 5-year survival rate in patients with positive recurrent nerve nodes was 34%. CONCLUSIONS: Dissection of the recurrent nerve lymph nodes is essential for curative esophagectomy even in the early phase of cancer invasion. Our cervicothoracic approach for total dissection of the proximal mesoesophagus yielded acceptable outcomes.

Carcinoma, Squamous Cell↗
PubMed1998

Diversity and intensity of adverse events in the treatment of hypertension with barnidipine.

Calcium antagonists (CaAs) are divided into three structural classes, typically represented by verapamil, diltiazem and nifedipine. As a group, the principal (type I) adverse effects of these drugs relate to the pharmacological action of calcium channel blockade, namely vasodilation, and include dizziness, flushing, palpitations and peripheral oedema. The clinical safety of the new dihydropyridine CaA, barnidipine, has been assessed in more than 12 clinical trials, including 2041 patients who have been treated with one or more doses of barnidipine (dose of up to 50 mg). Adverse events with barnidipine are of mild to moderate intensity, most commonly of type I, occurring in the early phase of treatment. The incidence of serious adverse events and the rate of withdrawals are low. Hence, barnidipine is likely to be well tolerated in general clinical use.

Aged↗
PubMed1998

Squamous cell carcinoma of the skin associated with sarcoid reactions in the regional lymph nodes.

Sarcoid reactions in lymph nodes with or without metastasis from a primary malignant neoplasm are well-known. However, it is extremely rare to find these reactions associated with cutaneous solid tumors; only one such case has appeared in the literature. Here we describe a case of an 83-year-old man with cutaneous squamous cell carcinoma accompanied by sarcoid reactions and metastatic foci in the regional lymph nodes. The possibilities of systemic sarcoidosis and tuberculosis were excluded after extensive examinations specific for these diseases. Some authors regard the sarcoid reaction to be a sign of a good prognosis on the basis of studies of a few patients with solid tumors. In our case, however, the patient died of pulmonary metastasis with pleuritis carcinomatosa shortly after surgery. Systematic analysis of a sufficient number of cases should be carried out to evaluate the clinical significance of this type of reaction.

Aged↗
PubMed1998

Mucin-producing pancreatic tumors: comparison of MR cholangiopancreatography with endoscopic retrograde cholangiopancreatography.

PURPOSE: To compare magnetic resonance cholangiopancreatography (MRCP) with endoscopic retrograde cholangiopancreatography (ERCP) in the detection of mucin-producing pancreatic tumors. MATERIALS AND METHODS: The authors retrospectively reviewed MRCP and ERCP images obtained in 28 patients with mucin-producing pancreatic tumors. Detectability of the pancreatic duct and its branches, intraductal cystic lesions, and intracystic nodules or septa was assessed. RESULTS: MRCP depicted cystic dilated ductal branches significantly better than did ERCP (P < .001). The difference in the number of nodules or septa detected with MRCP compared with ERCP was not significant. MRCP, however, simultaneously showed not only the main pancreatic duct but also the cystic lesions; this was not always possible with ERCP. CONCLUSION: MRCP appears to be more effective and less invasive than ERCP to evaluate changes in the size and extent of tumors and to determine if new lesions appear, as well as to follow up mucin-producing pancreatic tumors.

Adenocarcinoma, Papillary↗
PubMed1998

Acid fog and hospital visits for asthma: an epidemiological study.

The aim of this study was to elucidate the adverse respiratory effects of naturally occurring acid fog. In total, 102 adult asthmatic patients (44 nonatopic and 58 atopic) were studied for a 2 yr period (January 1992 to December 1993) in Kushiro, a city with only a small industrial area, located in the northern-most island in Japan. Fog occurred on 378 out of 731 days, and the acidity of the fog ranged from pH 3.32 to 6.91 (mean pH 4.95). The association between hospital visits for asthma and meteorological factors or air pollutants was investigated. In nonatopic patients, fog, high ozone and water vapour pressure, low day-to-day temperature differences, low concentrations of atmospheric NO and NO2 contributed significantly (p<0.05) to increasing hospital visits. In atopic subjects, fog, high water vapour pressure, low levels of atmospheric NO2 and SO2 contributed significantly to hospital visits (p<0.05). In Poisson regression analysis the remaining factors of significance (p<0.01) for nonatopic asthma were fog and low NO and for atopic asthma were high water vapour pressure and low SO2 (p<0.05). A weak but significant correlation was observed between the number of hospital visits and the mean pH of the foggy day (r=-0.38, p<0.05) in nonatopic asthmatic patients, not in atopic asthma. On foggy days, gaseous air pollutant levels were significantly (p<0.01) lower than on fog-free days. It was concluded that, naturally occurring acid fog may have a weak bronchoconstrictive effect which appears to be more influential in nonatopic asthmatic subjects than in atopic subjects.

Adolescent↗
PubMed1998

Body fat distribution and uterine leiomyomas.

PURPOSE: Investigation of the etiological relationship between body fat and uterine leiomyomas. SETTINGS: This was a case-control study. Percent body fat was measured bioelectrically with a body fat analyzer. SUBJECTS: In Sapporo City, Japan, 100 women with uterine leiomyomas (pathologically diagnosed) and 200 controls who were confirmed to have no uterine leiomyomas by clinical examination. RESULTS: Among the four types classified by BMI (over/under 24.0) and percent body fat (over/under 30%), the occult obesity type (BMI < 24.0 and percent body fat > or = 30%) had the highest risk. There were no patients of muscular type (BMI > or = 24.0 and percent body fat < 30%). Women with more than 0.80 of waist-to-hip ratio were also at significantly higher risk. CONCLUSIONS: Occult obesity and upper body fat distribution may lead to the development of uterine leiomyomas.

Adipose Tissue↗
PubMed1998

Clinicopathologic study of multiple primary superficial carcinoma of the esophagus.

Endoscopic examination with iodine staining has led to the easy detection of multiple superficial esophageal carcinoma (MSEC). The purpose of this study was to better understand the characteristics of MSEC. Of 49 patients with multiple esophageal carcinomas, 19 had superficial carcinoma. Multiple esophageal carcinomas were more often found in superficial carcinomas (31.1%) than in advanced carcinomas (14.4%). Comparing the depth of invasion of multiple esophageal carcinomas, the secondary lesions represented relatively early stages. Ki-67-positive cells were seen significantly more frequently in the main lesion of MSEC than in the secondary lesions, but proliferating cell nuclear antigen positivity and p53 expression did not differ significantly. Since multiple carcinoma occurs more frequently, care should be taken to look for small secondary lesions when treating superficial esophageal carcinoma. Ki-67 immunohistochemistry suggested that tumor cells proliferate more slowly in secondary lesions than in main lesions of MSEC.

Antibodies, Monoclonal↗
PubMed1998

[Results of treatment of cancer of the cardia].

Cancer of the cardia is traditionally discussed with cardiac cancer of the lower portion of the esophagus and upper gastric cancer invading the esophagus, and the specific characteristics of cancer of the cardia have never been clearly defined. We reviewed the outcome of 172 patients with adenocarcinoma of the cardia who had undergone radical surgery between 1949 and 1994 in the Division of Gastrointestinal Surgery of the Cancer Institute Hospital. The centers of the tumors were located within 2 cm above and below the boundary between the esophagus and the stomach, and their longitudinal diameter was less than 8 cm. We divided the patients into an early period (1949-1979; n = 79) and a late period (1980-1994; n = 93), and focused on the historical transition. There were no differences in patient gender or histology between the two periods. However, the late period was associated with fewer cases of esophageal invasion and shorter longitudinal diameter, as the age of the population advanced. The number of advanced cancers such as the localized and infiltrative type had decreased, and early cancer and early clinical stage had become more common, but despite the fact that the number of early cancers had increased, extended dissection, such as thoracic and paraaortic lymph node dissection, was performed more frequently. By clinical stage, the long-term outcome markedly improved in Stage I patient in the late period, and tended to improve in Stage II and III patients. This appears to have been attributable to the prevention of micrometastasis by extended dissection, although the number of early cancers is another major potential cause. There were no differences in the outcome of Stage IV patients between the two periods, and further advances in multimodality therapy must be awaited. The range of resection is basically proximal gastrectomy, and if there are adequate indications, the prognosis is favorable. In view of the status of lymphatic flow and lymph node metastasis, and long-term results, lateroaortic lymph node dissection is important. Since the number of early cancer patients has been increasing, if intraabdominal recurrence is prevented, intrathoracic lymph node dissection will contribute greatly to the outcome of such patients.

Adenocarcinoma↗
PubMed1997

Partial loss of tolerance liability to morphine analgesia in mice lacking the nociceptin receptor gene.

In mice lacking the nociceptin (or orphanin FQ) receptor gene, when 10 mg/kg of morphine was subcutaneously given, a potent analgesia in the tail pinch test was observed. The analgesic effect of morphine was equivalent among wild-type, heterozygous and homozygous mutant mice. When morphine was given to such mice in a dose of 10 mg/kg once per day for 5 days, wild-type and heterozygous mice showed marked tolerance or reduction in the morphine analgesia on the 5th day, while homozygous mice showed only 50% reduction in the peripheral analgesia of morphine. These findings suggest that nociceptin or its receptor plays important roles in the in vivo mechanism for the development of morphine tolerance.

Analgesics, Opioid↗
PubMed1997

S100beta promotes the extension of microtubule associated protein2 (MAP2)-immunoreactive neurites retracted after colchicine treatment in rat spinal cord culture.

S100beta, a glial derived calcium-binding protein with neurotrophic activity in the central nervous system, stimulates neurite extension of fetal raphe, cortex, spinal cord, and dorsal root ganglion neurons. The effects of S100beta on neurite length and microtubule associated protein2 (MAP2) immunoreactivity (IR) after microtubule disruption with colchicine were investigated in primary rat spinal cord culture. The incubation with S100beta (20 ng/ml) for 3 h after exposure to colchicine (10(-6) M) for 30 min altered the distribution of MAP2-IR. The length of MAP2-IR neurites increased by 65% compared to that in colchicine treatment alone. MAP2-IR intensity in the cell body was reduced by 26% compared to that in colchicine treatment alone. These results indicate that neurites shrink when the microtubular cytoskeletal system is disrupted and S100beta rapidly promotes re-assembly and/or stabilization.

Animals↗
PubMed1997

Functional and morphological features of skeletal muscle from mutant mice lacking both type 1 and type 3 ryanodine receptors.

1. We generated mice with targeted disruptions in the genes for both ryanodine receptor type 1 (RyR-1) and type 3 (RyR-3) to study the functional roles of RyR subtypes in skeletal muscle. 2. In permeabilized myocytes lacking both the RyRs, the Ca(2+)-induced Ca2+ release (CICR) mechanism was completely lost, and caffeine failed to induce Ca2+ release. 3. Replacement of potassium methanesulphonate in an experimental intracellular solution with choline chloride resulted in Ca2+ release in the wild-type muscle but not in the mutant muscle lacking RyR-1. 4. The double-mutant mice exhibited more severe muscular degeneration than RyR-1-deficient mice with formation of large vacuoles and swollen mitochondria while structural coupling between T-tubules and the sarcoplasmic reticulum was retained. 5. These results demonstrate that CICR is mediated solely by RyR-1 and RyR-3 in skeletal muscle cells, and suggest that RyR-1 is involved in Cl(-)-induced Ca2+ release. The results also suggest the presence of molecular components other than RyRs responsible for the triad formation. RyR-3 may have a role in the normal morphogenesis of skeletal muscle cells, although functionally it can be replaced by RyR-1.

Animals↗
PubMed1997

Mass screening for neuroblastoma and mortality in birth cohorts.

Mortality resulting from neuroblastoma in birth cohorts in both Sapporo City and the whole of Japan was investigated to evaluate the effects of a high-performance liquid chromatography (HPLC) mass screening program, targeting on 6 month-old infants. In Sapporo City, the non-HPLC screened cohort showed no reduction in mortality at 4 years of age compared with the pre-screening cohort. However, the HPLC screened cohort showed a reduction of 69% in mortality compared with the pre-screening cohort. On a nation-wide scale, there was a significant decline in mortality for the non-HPLC screened cohort compared with the pre-screening cohort; for the HPLC screened cohort for 1989-1991, there was also a reduction in mortality for children younger than 2 years of age. The incidence of neuroblastoma at 1-4 years of age in the HPLC cohort in Sapporo City was about half that in the pre-screening cohort, along with and probably because of an increasing incidence among infants in the same cohort. Our findings suggest that HPLC screening may detect some poor-prognosis neuroblastoma cases at early stages, thus providing for more favorable therapy.

Adolescent↗
PubMed1997

Unrestrained nociceptive response and disregulation of hearing ability in mice lacking the nociceptin/orphaninFQ receptor.

In the G-protein-coupled receptor superfamily, the opioid receptor subfamily is constituted of the three distinct opioid receptors (namely delta-, mu- and kappa-subtypes) and the receptor for nociceptin (also designated orphaninFQ). The members of the opioid receptor subfamily were known to mediate a variety of cellular inhibitory effects. The three opioid receptors are known to play central roles in mediating analgesia and many other physiological activities; however, the nociceptin receptor was identified recently and less is known about its physiological roles. Here we report the generation and characterization of mice lacking the nociceptin receptor. The knockout mice showed no significant differences in nociceptive threshold and locomotor activity compared with control mice, but they lost nociceptin-induced behavioral responses. These results indicate that the nociceptin system is not essential for regulation of nociception or locomotor activity. On the other hand, we found insufficient recovery of hearing ability from the adaptation to sound exposure in the mutant mice. Thus, the nociceptin system appears to participate in the regulation of the auditory system.

Animals↗