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Biomedical subjects

M Nishi

Publications and source records attributed to M Nishi.

At least 145 records · Page 8Linked to original sources

Structure and regional distribution of nociceptin/orphanin FQ precursor.

We have cloned cDNA carrying the entire coding sequence of the precursor protein for nociceptin/orphanin FQ, a neuropeptide-ligand for an opioid-receptor like G-protein coupled receptor. The deduced nociceptin/orphanin FQ precursor shows sequence similarity to the opioid peptide precursors and shares characteristic structural features particularly with preprodynorphin. In situ hybridization analysis of nociceptin precursor mRNA in the mouse central nervous system revealed that it is highly expressed in discrete neuronal sites with the pattern distinct from those of opioid peptides.

Amino Acid Sequence↗

Enhanced synaptophysin immunoreactivity in rat hippocampal culture by 5-HT 1A agonist, S100b, and corticosteroid receptor agonists.

Serotonin (5-HT) has been shown to modulate brain maturation during development and adult plasticity. This effect in the whole animal may be due to activation of 5-HT1A receptors and a corresponding increases in S100b and corticosterone. Synaptophysin, an integral protein of the synaptic vesicle membrane that correlates with synaptic density and neurotransmitter release, is reduced by depletion of 5-HT in the cortex and hippocampus of the adult rat. Injections of a 5-HT1A agonist or dexamethasone can reverse the loss of synaptophysin immunoreactivity (IR). In this study we used morphometric analysis of synaptophysin-IR to study the effects of the 5-HT1A agonist, ipsapirone, and the neuronal extension factor, S100b on hippocampal neurons grown in a serum and steroid free media. Both compounds increased the synaptophysin-IR at doses previously established to be highly specific. Ipsapirone (10(-9)M) was more effective on neuronal cell bodies staining and S100b (10 ng/ml) was more effective in increasing the number of synaptophysin-IR varicosities on neuronal processes. In addition both types of corticosteroid receptor agonists, at previously established specific doses, Ru28362 (10(-8) M) and aldosterone (10(-9) M) produced smaller increases compared to control groups in both the cell body staining and the number of varicosities. The effect of these differentiating factors on the expression of synaptophysin-IR suggests multiple regulation sites for producing and maintaining pre-synaptic elements in the brain.

Animals↗

Severe acute hepatitis A associated with acute pure red cell aplasia.

A rare case of severe acute hepatitis A complicated by pure red cell aplasia (PRCA) is reported. A 60-year-old man with jaundice and hepatomegaly was diagnosed as having acute hepatitis A by positive IgM anti-hepatitis A antibody (anti-HAV). Severe anemia rapidly developed 3 weeks after admission, and the patient was diagnosed with PRCA by both bone marrow smears and erythrocyte survival study. The anemia was transient and bone marrow recovered within 1 week. However, concomitant with bone marrow recovery, the hepatitis worsened. He became drowsy and disoriented and severe jaundice, ascites, prolonged prothrombin time, increased transaminase levels, and abnormal electroencephalogram (EEG) were exhibited. Plasma exchange transfusion and glucagon-insulin (GI) therapy improved the consciousness level, but bilirubin, transaminase levels, and IgM anti-HAV titer remained high. Intravenous administration of lipophilized prostaglandin E1 (lipo-PGE1) was added to the GI therapy. Bilirubin and transaminase levels were normalized in the 8th week after the initiation of this combination therapy (17 weeks after admission). The combined use of lipo-PGE1 with plasma exchange and GI therapy appeared to be useful for the prolonged severe hepatitis in this patient.

Acute Disease↗

Eating habits and pancreas cancer.

BACKGROUND: The eating habits of Japanese people are changing, which may have something to do with the increase in pancreas cancer in Japan. METHODS: Chiefly from the viewpoint of the eating habits, we investigated the etiological factors of this cancer through a community-based case-control study, employing 141 cases and 282 controls (two for each case) matched for sex, age, and place of residence, and through an ecologic study using the official reports of food consumption and deaths from this cancer in Hokkaido Prefecture. RESULTS: The case-control study showed that intake of meats and animal viscera increased the risk of this cancer. On the other hand, vegetables and the traditional Japanese foods, e.g., tofu, deep-fried tofu, raw fish, and tempura, reduced the risk. The controls took more of the traditional Japanese foods than the cases. The ecologic study showed there were significantly negative correlations between the annual consumption of plant foods/plant protein and the annual crude mortality of pancreas cancer. CONCLUSION: The traditional Japanese foods, which include many plant foods, are preventive against the occurrence of pancreas cancer.

Adult↗

Dose-response relationship between coffee and the risk of pancreas cancer.

A case-control study was conducted and previous epidemiological data were reviewed in order to investigate the dose-response relationship between coffee and the risk of pancreas cancer. The case-control study was community-based and was carried out in Hokkaido, Japan, employing 141 patients with pancreas cancer and 282 controls (two for each case) matched for sex, age and place of residence. The dose-response relationship between coffee (cups/day) and the relative risk of this disease formed a U-shaped curve. The lowest relative risks (0.18 for male and 0.53 for female) were found among "occasional" drinkers. Epidemiological articles published between 1981 and 1993 were selected from Index Medicus using the two key words "coffee" and "pancreas cancer". In many of the previous case-control studies the curve of the dose-response relationship was also U-shaped, when the relative risks were calculated specifically using four or five levels of coffee dose. The nadirs of the relative risks, most of which ranged from 0.5 to 0.7, were found most frequently at small doses (1-2 or 3-4 cups/day). The results of meta-analysis of these studies formed a U-shaped curve. Studies of other types showed almost the same results. Thus it appears that small amounts of coffee might prevent pancreas cancer, whereas large amounts might cause the disease.

Case-Control Studies↗

Two-year follow-up study of the effect of acid fog on adult asthma patients.

Acid fog is a complex mixture of atomospheric pollutants containing multiple stimuli that may be capable of inducing bronchoconstriction. To investigate the effect of ambient acid fog on bronchoconstriction, we examined the relation between the hospital visit for asthma symptoms of 102 patients and various meteorological conditions for over the two-year period from January 1992 to December 1993. Dense fog occurs frequently every summer in Kushiro, a city located in Hokkaido, northernmost island in Japan. The acidity of the fog ranged from pH 3.32 to 6.91 (mean pH = 5.05) during this period. A significant increase (p < 0.05) of hospital visits on a foggy day was found in 9 cases, and a tendency (p < 0.10) was found in 10 cases. The odds ratio for a hospital visit on a high water vapor pressure day (> 12 h Pa) was significantly high (p < 0.01) in 5 cases among the above 19 cases. To exclude the effect of high water vapor pressure, the data was restricted to the condition of a foggy day with low water vapor pressure (< 12 hPa); 9 patients had a significant increase (p < 0.05) in hospital visits on such a day. These results indicated that hospital visits for asthma symptoms was increased on acid fog days in 8.8% of adult asthma patients. Inhalation of naturally occurring acid fog may have adverse effects on the respiratory tract of the asthmatic patient.

Acids↗

Beta-thalassemia (beta 90 GAG-->TAG): genetic diagnosis by allele-specific polymerase chain reaction and estimation of mutant mRNA expression by reverse transcription polymerase chain reaction.

Genetic diagnosis of a family of beta-thalassemia (beta 90 GAG-->TAG) was carried out by allele-specific polymerase chain reaction (AS-PCR). The proband, her daughter and granddaughter were proved to be heterozygotes of normal and mutant alleles. As some nonsense mutations express a decreased amount of MrNAs, we determined the expression level of the mutant mRNA of beta-thalassemia (beta 90 GAG-->TAG), by application of a combination method of reverse transcription PCR (RT-PCR) and dot-blot hybridization with allele-specific oligonucleotides. The mutant mRNA was not markedly reduced. In conclusion, 1) individuals with the mutant beta-globin gene were diagnosed successfully by AS-PCR, and 2) a significant amount of the mutant beta-globin mRNA was synthesized.

Alleles↗

Flushing pattern and idiopathic avascular necrosis of the femoral head.

A cooperative hospital-based case-control study of idiopathic avascular necrosis of the femoral head (IANF) was carried out to clarify the involvement of smoking, drinking, flushing pattern, and other factors in the development of IANF comparing 90 cases (64 males and 26 females) without history of systemic corticosteroid use with 180 matched controls (128 males and 52 females). The results of analyses were represented only for male subjects because of small number of female cases. There was no significant difference in smoking habits, daily and cumulative number of cigarettes smoked between case and control groups. Current drinkers had obviously higher risk (OR = 11.47) of IANF compared to nondrinkers or exdrinkers. In addition, there was a consistent risk increase with increasing alcohol consumption and the highly significant dose-response relationship remained unchanged after adjustment for all other factors (chi 2 = 14.33, p < 0.001 and chi 2 = 13.24, p < 0.001 for daily and cumulative alcohol consumption, respectively). For flushing pattern, although nonflushers had a significantly elevated risk (OR = 2.08) in the univariate analysis, the association disappeared (OR = 0.73) after adjustment for alcohol and other factors. Since nonflushers tend to be heavy drinkers, perhaps, an apparent risk increase among nonflushers may be due to alcohol drinking. Body mass index (BMI) was inversely related to the development of IANF. The risk reduction was found among subjects with higher BMI and an adjusted linear trend of OR was significant (chi 2 = 6.65, p < 0.05). However, further studies were required regarding the association between flushing pattern or BMI and IANF because of a few reports. History of liver diseases and occupational history were not significantly associated with the development of IANF after adjustment for other factors.

Adult↗

Efficacy of mandibular topical anesthesia varies with the site of administration.

This study compared the threshold of pain sensitivity in the anterior mandibular mucobuccal fold with the posterior. This was followed by a comparison of the reduction of needle insertion pain in the anterior mucobuccal fold and the pterygo-temporal depression by either topical anesthesia or nitrous oxide inhalation. The pain threshold was determined by an analgometer, a pain-measuring device that depends on pressure readings; additionally, pain caused by a needle inserted by a normal technique was assessed using a visual analog scale (VAS). The threshold of pain was significantly lower in the incisor and canine regions than in the premolar and the molar regions (P < 0.001). Compared to a placebo, topical anesthesia significantly reduced the pain from needle insertion in the mucobuccal fold adjacent to the mandibular canine (P < 0.001), but did not significantly reduce pain in the pterygotemporal depression. The addition of 30% nitrous oxide did not significantly alter pain reduction compared to a control of 100% oxygen. These results suggest that topical anesthesia application may be effective in reducing the pain of needle insertion in the anterior mandibular mucobuccal fold, but may not be as effective for a standard inferior alveolar nerve block. The addition of 30% nitrous oxide did not lead to a significant improvement.

Adult↗

Localization of recurrent disease after extended lymph node dissection for carcinoma of the thoracic esophagus.

BACKGROUND: The role of aggressive locoregional dissection in the treatment of carcinoma of the thoracic esophagus is controversial. The extent of disease spread for which resection can be performed is not yet fully established. STUDY DESIGN: Of 230 patients who underwent extended lymph node dissection, including the cervical nodes, the overall hospital mortality rate was 4.8 percent. Recurrent carcinoma was clinically confirmed by periodic follow-up examination with diagnostic imaging in 83 patients. We examined the exact anatomic sites of recurrent lesions and the clinical courses of patients. Recurrence patterns were classified into locoregional, distant, and mixed types. RESULTS: Recurrence of the carcinoma was locoregional in 35 patients, distant in 38 patients, and mixed in ten patients. The frequency of locoregional recurrence was significantly lower in patients with less than eight positive nodes and in patients without invasion of neighboring organs. Locoregional recurrence in the dissected area was mainly found in the region around the recurrent nerves and the main bronchi. Lymph nodes outside of the dissected area developed recurrence only in cases of markedly advanced disease apart from the abdominal para-aortic nodes. The group with locoregional recurrence and the group with distant recurrence had similar clinical courses over time. In patients in whom recurrent lesions could be treated with resection and adjuvant therapy, the one-year survival rate after recurrence was 83 percent. CONCLUSIONS: Unless the disease was markedly advanced, systematic lymph node dissection in our procedures yielded good locoregional control. The relatively low rate of distant recurrence with acceptable hospital mortality rates favors an extensive operation. When recurrent lesions were localized macroscopically, surgical removal of the recurrent lesions offered good palliation.

Carcinoma↗

[Chemical constituents in the bark of Illicium jadifengpi B. N. Chang].

Four compounds were isolated from the bark of illicium jadi feng pi for the first time. Their structures were identified as 4-epi-isopimaric acid, 8,11,13,15-abietatetran-19-oic acid, 15-hydroxydehydroabietic acid and beta-sitosterol by physico-chemical constants and specral analyses.

Carboxylic Acids↗

The POU domain transcription factor Brn-2 is required for the determination of specific neuronal lineages in the hypothalamus of the mouse.

We generated mice carrying a loss-of-function mutation in Brn-2, a gene encoding a nervous system specific POU transcription factor, by gene targeting in embryonic stem cells. In homozygous mutant embryos, migratory precursor cells for neurons of the paraventricular nuclei (PVN) and the supraoptic nuclei (SO) of the hypothalamus die at approximately E12.5. All homozygous mutants suffered mortality within 10 days after birth, possibly because of a complete deficiency of these neurons in the hypothalamus. Although neither developmental nor histological abnormalities were observed in heterozygous mice, the levels of expression of vasopressin and oxytocin in the hypothalamus of these animals were half these of wild-type mice. These results strongly suggest that Brn-2 plays an essential role in the determination and development of the PVN and SO neuronal lineages in the hypothalamus.

Animals↗

Ca(2+)-induced Ca2+ release in myocytes from dyspedic mice lacking the type-1 ryanodine receptor.

While subtypes 1 and 2 of the ryanodine receptor (RyR) function as intracellular Ca2+ release channels, little is known about the function of the third subtype (RyR-3), first identified in brain. Myocytes from mice homozygous for a targeted mutation in the RyR-1 gene (dyspedic mice) can now be used for a study on the function of RyR-3, which is predominantly expressed in these cells according to our reverse transcription-polymerase chain reaction analysis. We here demonstrate in these myocytes caffeine-, ryanodine- and adenine nucleotide-sensitive Ca(2+)-induced Ca2+ release with approximately 10 times lower sensitivity to Ca2+ than that of RyR-1. Although RyR-3 does not mediate excitation-contraction coupling of the skeletal muscle type, we propose that RyR-3 may induce intracellular Ca2+ release in response to a Ca2+ rise with a high threshold.

Adenine Nucleotides↗

Abnormal junctions between surface membrane and sarcoplasmic reticulum in skeletal muscle with a mutation targeted to the ryanodine receptor.

Junctions that mediate excitation-contraction (e-c) coupling are formed between the sarcoplasmic reticulum (SR) and either the surface membrane or the transverse (T) tubules in normal skeletal muscle. Two structural components of the junctions, the feet of the SR and the tetrads of T tubules, have been identified respectively as ryanodine receptors (RyRs, or SR calcium-release channels), and as groups of four dihydropyridine receptors (DHPRs, or voltage sensors of e-c coupling). A targeted mutation (skrrm1) of the gene for skeletal muscle RyRs in mice results in the absence of e-c coupling in homozygous offspring of transgenic parents. The mutant gene is expected to produce no functional RyRs, and we have named the mutant mice "dyspedic" because they lack feet--the cytoplasmic domain of RyRs anchored in the SR membrane. We have examined the development of junctions in skeletal muscle fibers from normal and dyspedic embryos. Surprisingly, despite the absence of RyRs, junctions are formed in dyspedic myotubes, but the junctional gap between the SR and T tubule is narrow, presumably because the feet are missing. Tetrads are also absent from these junctions. The results confirm the identity of RyRs and feet and a major role for RyRs and tetrads in e-c coupling. Since junctions form in the absence of feet and tetrads, coupling of SR to surface membrane and T tubules appears to be mediated by additional proteins, distinct from either RyRs or DHPRs.

Animals↗