Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 829 records · Page 46Linked to original sources

PubMed1993

Factors influencing the twin-pulse facilitation of the release of transmitter at the mouse neuromuscular junction.

1. The effects of several conditions and agents on the twin-pulse facilitation of the release of transmitter at the mouse neuromuscular junction in low-Ca2+ high-Mg2+ bathing solutions were examined. 2. Twin-pulses gave two endplate potential (epps) with first (m2) and second (m2) quantal contents. The ratio of m2/m1 was taken as a measure of the degree of facilitation. 3. The mean value of this ratio was > 1. Individual ratios fluctuated widely at junctions with smaller values of m1 but were focused around 1 at junctions with larger values of m1. Thus, some populations of junctions with smaller values of m1 contributed to an increment in the mean ratio. 4. The mean ratio was virtually constant irrespective of changes in the spontaneous and evoked release of transmitter at temperatures between 20 and 36 degrees C and at external concentrations of Ca2+ from 0.4 to 0.8 mM. 5. 4-Aminopyridine(4-AP) slightly but significantly increased this ratio with increases in m1 and m2 at temperatures of 24 and 36 degrees C. Ouabain slightly but significantly reduced the ratio, with increases in m1 and m2. The steadiness of the ratio was maintained in the presence of caffeine, high K+, neomycin or omega-conotoxin irrespective of changes in m1 and m2, except in the case of omega-conotoxin. 6. Spontaneous output at 36 degrees C increased in the presence of 4-aminopyridine, ouabain, caffeine, high K+ or neomycin. 7. These results indicate that maintenance of a stable value of the ratio of m2 to m1 is a dominant feature.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Detection of hepatitis C viral RNA in sporadic acute non-A, non-B hepatitis by polymerase chain reaction. Its usefulness for the early diagnosis of seronegative infection.

To determine the prevalence of hepatitis C viral infection in patients with sporadic non-A, non-B (NANB) acute hepatitis, hepatitis C viral RNA was studied in the plasma of 15 patients by reverse transcription-polymerase chain reaction assay. Plasma samples were sequentially obtained from 15 patients, and polymerase chain reaction was performed with two nested pairs of primers deduced from the 5'-non-coding region of hepatitis C viral sequences. Anti-C100 and anti-GOR antibodies were also measured with an enzyme-linked immunosorbent assay system. Plasma hepatitis C viral RNA was detected transiently in 7 of 15 patients (47%) at an early phase of the clinical course, while anti-C100 antibodies were detectable in only 2 (29%) of hepatitis C viral RNA-positive patients, and in 1 (13%) of the negative patients. Of 7 patients that were positive for plasma hepatitis C viral RNA, 4 (57%) had relapsing or protracted courses. In contrast, in all patients with undetectable hepatitis C viral RNA, hepatitis C viral RNA recovered and remained normal for at least 1 year. Thus, hepatitis C viral infection represents almost half the patients with acute sporadic NANB hepatitis, and detection of hepatitis C viral RNA in an early clinical phase is superior to anti-C100 measurement for diagnosing acute sporadic hepatitis C viral infection.

Adult↗

PubMed1993

Vesicle transport and processing of the precursor to 2S albumin in pumpkin.

Cell fractionation of pulse-chase-labeled developing pumpkin cotyledons demonstrated that proprotein precursor to 2S albumin is transported from the endoplasmic reticulum to dense vesicles and then to the vacuoles, in which pro2S albumin is processed to the mature 2S albumin. Immunocytochemical analysis showed that dense vesicles of about 300 nm in diameter mediate the transport of pro2S albumin to the vacuoles. The primary structure of the precursor (16,578 Da) to pumpkin 2S albumin has been deduced from the nucleotide sequence of an isolated cDNA insert. The presence of a hydrophobic signal peptide at the N-terminus indicates that the precursor is a pre-proprotein that is converted into pro2S albumin after cleavage of the signal peptide. N-terminal sequencing of the pro2S albumin in the isolated vesicles revealed that the signal peptide is cleaved off cotranslationally on the C-terminal side of alanine residue 22 of prepro2S albumin. By contrast, posttranslational cleavages occur on the C-terminal sides of asparagine residues 35 and 74, which are conserved among precursors to 2S albumin from different plants. Hydropathy analysis revealed that the two asparagine residues are located in the hydrophilic regions of pro2S albumin. These findings suggest that a vacuolar processing enzyme can recognize exposed asparagine residues on the molecular surface of pro2S albumin and cleave the peptide bond on the C-terminal side of each asparagine residue to produce mature 2S albumin in the vacuoles.

Albumins↗

PubMed1993

Islet amyloid polypeptide/amylin contents in pancreata increase in genetically obese and diabetic mice.

To search for a possible relationship between islet amyloid polypeptide (IAPP)/amylin and the pathophysiology of type 2 diabetes mellitus, we examined IAPP contents in the pancreata of genetically obese and diabetic mice (C57BL/6J ob/ob and KK mice), at 24 weeks of age, using a specific radioimmunoassay. IAPP and insulin contents were noticeably increased in the ob/ob mice with marked obesity and moderate hyperglycemia. These contents slightly, but significantly increased in the KK mice with mild obesity and hyperglycemia. Thus, IAPP production is possibly influenced by factors coded by mutant genes and a possible relationship between IAPP and hyperglycemia in the strains of mice deserves further attention.

Amyloid↗

PubMed1993

HTLV-II infection in Florida Indians.

A significantly increased prevalence of antibodies to human T-cell leukemia virus (HTLV) has been described in several native American populations in the United States and Latin America. Initial virologic studies indicate that HTLV-II is the predominant virus responsible for this antibody pattern. We obtained blood samples from 106 Seminole Indians living on four reservations in Southern Florida. Seropositivity to HTLV-I/II was found in 14 (13.2%) of these individuals. Polymerase chain reaction (PCR) documented HTLV-II and the absence of HTLV-I in 7 of the 9 donors available for follow-up testing of white blood cells. Evaluation of various risk factors excluded blood transfusion or intravenous drug use as an important contributing factor to the HTLV-II seroprevalence rate. These studies support the hypothesis that HTLV-II is endemic in many native American tribes in the Western hemisphere.

Florida↗

PubMed1993

Alterations in pain threshold and psychomotor response associated with subanaesthetic concentrations of inhalation anaesthetics in humans.

We studied the effects of six inhalation anaesthetics at subanaesthetic concentrations of 0.2 MAC on pain threshold and psychomotor function in six healthy volunteers. When compared with 100% oxygen inhalation, nitrous oxide and methyoxyflurane significantly increased pain threshold as measured by a radiant heat algometer, and prolonged the response time to auditory stimuli. In contrast, halothane, enflurane, isoflurane and sevoflurane produced prolongation of the response time to auditory stimuli but did not influence pain perception. The pain threshold with nitrous oxide remained significantly increased 30 min after its discontinuation, while the response time returned to the preinhalation value. We conclude that nitrous oxide and methoxyflurane possess both analgesic and hypnotic actions but halothane, enflurane, isoflurane and sevoflurane do not have an analgesic action at subanaesthetic concentrations, and the analgesic action of nitrous oxide persists after its elimination.

Adult↗

PubMed1993

Mechanism of mitochondrial enzyme leakage during reoxygenation of the rat heart.

OBJECTIVE: The aim was to clarify the factors that induce enzyme release from mitochondria during anoxia and reoxygenation. METHODS: Isolated perfused hearts or isolated mitochondria were prepared from hearts excised from rats. The amounts of lactate dehydrogenase, cytoplasmic aspartate aminotransferase, and mitochondrial aspartate aminotransferase released into the coronary effluent from perfused heart preparations were measured. To distinguish the effect of mechanical stress from that of reoxygenation, a latex balloon was placed in the left ventricular cavity to impose mechanical stress and the heartbeat was controlled with a high K+ medium. A digitonin infusion technique was used to obtain only the cytosolic compartment of the cells for analysis of the amounts of mitochondrial enzymes released into the cytosol. The effect of anoxia followed by reoxygenation on enzyme release from isolated mitochondria was studied. RESULTS: On reoxygenation, mitochondrial aspartate aminotransferase was released as well as cytoplasmic enzymes, but, unlike cytoplasmic enzymes, the release was not influenced by mechanical stress. Mitochondrial injury by reoxygenation depended on the duration of the preceding anoxia. Reoxygenation of isolated mitochondria also induced enzyme release and the presence of ATP in the extramitochondrial space reduced the release of this enzyme. CONCLUSIONS: Enzyme leakage from mitochondria of myocardial cells occurs during reoxygenation, irrespective of mechanical stress, and this vulnerability to oxidative stress depends on the duration of the preceding anoxic period or the concentration of cytosolic ATP.

Adenine Nucleotides↗

PubMed1993

Digoxin-like immunoreactivity may contribute to hyperinsulinemia-associated hypertension in patients with glucose intolerance.

The role of endogenous digitalis-like factors in the pathogenesis of the hypertension associated with impaired glucose tolerance was investigated by measuring plasma digoxin-like immunoreactivity (DLI). Mean blood pressure correlated significantly with the obesity index, serum insulin-like immunoreactivity (IRI), and plasma DLI concentrations in subjects with impaired glucose tolerance (IGT). Plasma DLI concentrations also correlated significantly with the obesity index and serum IRI concentrations. Because increased insulin has been proposed to promote sodium reabsorption, sodium retention in turn has presumably caused an increase of natriuretic, digitalis-like factors reflected by the increased plasma DLI concentrations in patients with IGT. Consequently, increased DLI may contribute to the elevated arterial pressure in patients with hyperinsulinemia.

Adult↗

PubMed1993

Establishment of human minor histocompatibility antigen-specific cytotoxic T cell clones restricted by HLA-DR9.

Cytotoxic T lymphocyte clones specific for human minor histocompatibility (hmH) antigens were generated in vitro from PBL, of a healthy female donor, which had been repeatedly stimulated with PBL MHC antigens of her healthy, genotypically identical brother (HLA type of the siblings was A11/A2 B35/B62 Cw4/Cw- DR4.2/DR9 DQ3/DQ- DPB1*0102/DPB*0501). Two clones were obtained that had specific killing activity against PBL- or EBV-transformed B cell line (BCL) derived from stimulator, but not from autologous cells. A panel study of the killing patterns of these two clones, using various HLA phenotype BCLs (33 BCLs) generated from healthy donors as targets, revealed that these two clones killed some DR9-bearing BCLs (5 in 20 BCLs), but did not kill the remaining DR9-bearing BCLs (15 in 20 BCLs) or other DR-type BCLs (13 BCLs). Furthermore, the killing activities of these two clones were greatly inhibited by pretreatment of the target stimulator-derived BCL with anti-HLA DR mAb. It was thus concluded that these two clones recognized hmH antigens in HLA DR9 in a restricted manner.

Antibodies, Monoclonal↗

PubMed1993

Molecular characterization of a vacuolar processing enzyme related to a putative cysteine proteinase of Schistosoma mansoni.

Proproteins of various vacuolar proteins are post-translationally processed into mature forms by the action of a unique vacuolar processing enzyme. If such a processing enzyme is transported to vacuoles together with proprotein substrates, the enzyme must be a latent form. Immunocytochemical localization of a vacuolar processing enzyme, a 37-kD cysteine proteinase, in the endosperm of maturing castor bean seeds places the enzyme in the vacuolar matrix, where a variety of proproteins is also present. To characterize a molecular structure of vacuolar processing enzyme, we isolated a cDNA for the enzyme. Deduced primary structure of a 55-kD precursor is 33% identical to a putative cysteine proteinase of the human parasite Schistosoma mansoni. The precursor is composed of a signal peptide, a 37-kD active processing enzyme domain, and a propeptide fragment. Although the precursor expressed in Escherichia coli has no vacuolar processing activity, a 36-kD immunopositive protein expressed in E. coli is active. These results suggest that the activation of the vacuolar processing enzyme requires proteolytic cleavage of a 14-kD C-terminal propeptide fragment of the precursor.

Amino Acid Sequence↗

PubMed1993

Cryosurgery and topical fluorouracil: a treatment method for widespread basal cell epithelioma in basal cell nevus syndrome.

A 58-year-old man with basal cell nevus syndrome had variously sized basal cell epitheliomas (BCEs), mostly of the superficial type, on his chest, back, and lumbar areas. BCEs on the lumbar area were treated with 5-fluorouracil (5-FU) cream which was applied daily under occlusive dressings (ODT). Complete erosion occurred in the center, but not at the periphery of the lesions. In the latter regions, BCE remained. Then cryosurgery (cryo) followed by topical 5-FU (cryo + 5-FU) was tried to treat the peripheral, non-eroded lesions; this caused complete erosions. Biopsy specimens obtained 6 months after epithelization did not show any evidence of recurrence. We also tried either cryo alone or cryo + 5-FU on the chest lesions, and either 5-FU alone or cryo + 5-FU on the abdominal lesions. Cryo alone or 5-FU alone could not clear BCE, but cryo + 5-FU could. These results suggest that the cryo + 5-FU was the most effective of these therapies.

Administration, Topical↗

PubMed1993

Complete recovery of cytochrome oxidase and superoxide dismutase activities in the brain of brindled mice receiving copper therapy.

To elucidate the roles played by copper-containing enzymes in the brain degeneration associated with Menkes disease, the brains of brindled mouse hemizygotes (BMs) were studied histochemically and biochemically before and after copper therapy. Light and electron microscopic histochemistry revealed that, while neuronal mitochondria in BM brains demonstrate only a weak diaminobenzidine reaction for cytochrome oxidase, these exhibit strong activity after therapy and in control mice. Biochemical assays of enzyme activity revealed only 30% of the normal level before a single subcutaneous application of 50 micrograms of CuCl2, whereas neuronal mitochondria of BMs surviving 8 months after the copper therapy displayed essentially no difference from the controls. Similar results were also gained for superoxide dismutase activity, although the reduction was less marked. The present findings provide direct support for decreased activities of copper-containing enzymes being responsible for the mitochondrial abnormalities and brain degeneration associated with Menkes disease.

Animals↗

PubMed1993

Effects of naloxone on the sensation of dyspnea during acute respiratory stress in normal adults.

To clarify whether endogenous opioids modulate the dyspnea intensity and, if so, by what mechanism they act on it, we examined 12 healthy male volunteers aged 19-27 yr for ventilatory and peak mouth pressure (Pm) responses to hypoxic progressive hypercapnia with inspiratory flow-resistive loading after the intravenous infusion of 3 mg of naloxone or saline. The intensity of dyspnea was simultaneously assessed by visual analogue scaling every 15 s. Naloxone administration increased both ventilatory and Pm responses to hypoxic progressive hypercapnia (P < 0.05 for both). The increase in dyspnea intensity for a given increase in end-tidal PCO2 was significantly greater after naloxone infusion than after saline (P < 0.05). However, there were no differences in the increase in dyspnea intensity for a given increase in minute ventilation or Pm. These results suggest that the endogenous opioid system suppresses the respiratory output under a strong, acute respiratory stress in normal adults and that this system may relieve the dyspnea sensation secondary to the suppression of the brain stem respiratory center without specific effects on the processing of respiratory sensations in the higher brain.

Adult↗

PubMed1993

Effect of theophylline on brain tissue oxygenation during normoxia and hypoxia in humans.

Although theophylline, an adenosine receptor antagonist, is known to reduce cerebral blood flow, little clinical attention has been paid to this adverse effect. This study was designed to examine the effect of theophylline on brain tissue oxygenation for a wide range of arterial PO2 in healthy volunteers. Partial gas pressures and O2 saturation in an artery (SaO2) and the internal jugular vein (SjO2) were simultaneously measured while subjects (n = 6) were breathing room air and then exposed to two levels of isocapnic hypoxia (arterial PO2 = 60 and 45 Torr) before and after infusion of theophylline (6 mg/kg of aminophylline). For the same levels of arterial oxygenation, jugular vein PO2 markedly dropped, by 3-5 Torr, after theophylline infusion, as did SjO2, by as much as 6-10%, under the arterial PCO2, which was slightly lower by 1-2 Torr in the theophylline study. By use of the linear regression lines obtained from the relationship between SaO2 and SjO2 in each study, it was calculated that the SjO2 with theophylline, while SaO2 was 95, 90, and 80%, was comparable to that without theophylline when SaO2 was 81, 78, and 73%, respectively. On the basis of the assumption that partial gas pressures and SjO2 reflect brain tissue oxygenation, these data suggest that the effect of theophylline on brain tissue oxygenation should not be ignored in some clinical settings. The effects of chronic administration remain to be studied.

Adult↗

PubMed1993

Interstrain differences in murine daunomycin-induced nephrosis.

Examining 8 inbred murine strains [A/J, BALB/c, SM/J, C3H/J, SWR/J, C57BL/6J (B6), DBA-2, B10D2/old (B10D2/o)] for urinary albumin excretion after a single daunomycin (DM) injection (20 mg/kg), we found strain specificity in susceptibility to DM nephrosis. This specificity did not relate to the serum disappearance rate of this drug. A/J and BALB/c were highly susceptible to the nephrosis while C57BL/6J, DBA-2 and B10D2/o were completely resistant to it. Chronological observation revealed that A/J mice had significant proteinuria at 2 weeks after injection, and it persisted for the remaining 4 weeks of this experiment, while C57BL/6J showed no increase over the experimental period. Using segregants obtained from an A/J and B6 backcross, it has been shown that susceptibility is inherited as an autosomal recessive trait and involves approximately three genes. Neither a C5 deficiency, H-2 type nor coat color gene (c-locus) was related to this susceptibility. This strain difference in nephrotoxicity would be a promising way to investigate its subcellular mechanism.

Albuminuria↗

PubMed1993

Supernormal histamine release and normal cytotoxic activity of beige (Chédiak-Higashi syndrome) rat mast cells with giant granules.

The beige rat is an animal model of the Chédiak-Higashi syndrome. Since mast cells can be easily purified from the peritoneal cavity of rats, we investigated the function of beige rat mast cells with giant granules by using quantitative methods. Beige and normal rat mast cells were sensitized with anti-dinitrophenol (DNP) IgE antibodies and stimulated by DNP conjugated with human serum albumin. The proportion of histamine released to total histamine was significantly greater in beige rat mast cells than in normal rat mast cells. Since the supernormal histamine release of beige rat mast cells was observed after treatment with 12-O-tetradecanoylphorbol 13-acetate, calcium ionophore A23187, substance P or compound 48/80, it appeared to be attributable to the enlargement in granules in beige rat mast cells. Spontaneous cytotoxic activity of mast cells was assayed by incubating purified mast cells with 51Cr-labelled WEHI-164 cells. Both beige and normal rat mast cells showed significant cytotoxic activity, but no significant difference was detectable between beige and normal rat mast cells. Even after IgE-mediated stimulation, no significant difference in cytotoxic activity was detectable between beige and normal rat mast cells either. Giant granules of beige rat mast cells did not appear to influence the cytotoxic activity of mast cells.

Animals↗

PubMed1993

Dyspnea sensation and chemical control of breathing in adult twins.

To examine possible genetic influence on the sensation of dyspnea and on load compensation, we conducted a twin study using healthy adult pairs (10 monozygotes, MZ, and 9 dizygotes, DZ). The ventilatory response to progressive hypercapnia (HCVR) was examined under three different conditions: hyperoxia (PETO2 > 150 mm Hg), hypoxia (PETO2 maintained at 50 to 55 mm Hg), and hyperoxia with an inspiratory flow-resistive load (17 mm H2O/L/s), with simultaneous assessment of the dyspnea sensation by visual analog scale (VAS). Although the VDZ/VMZ ratio (VMZ and VDZ are within-pair variances in MZ and DZ, respectively) for the slope value of the minute ventilation-PETCO2 regression line was not different from 1 in hyperoxia either with or without an inspiratory load, it was significantly larger than 1 in hypoxia (F = 5.17, p < 0.05), suggesting that a genetic influence on HCVR existed only in the presence of hypoxia. During 3% CO2 inhalation, the VDZ/VMZ ratio for the tidal volume (VT) was larger than 1 in hyperoxic HCVR with loading (F = 7.89, p < 0.01), and that for respiratory frequency (f) was larger than 1 only in hypoxic HCVR (F = 3.59, p < 0.05). At a PETCO2 of 55 mm Hg, the VT ratio was larger than 1 under all conditions (F = 5.91, p < 0.05; F = 6.99, p < 0.05; F = 3.75, p < 0.05; respectively), and the f ratio was significantly larger than 1 again only in hypoxic HCVR (F = 3.48, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Effects of aging on respiratory load compensation and dyspnea sensation.

To clarify effects of aging on the load compensation response and the sensation of dyspnea, we examined 28 healthy male volunteers for ventilatory and P0.1 responses to hyperoxic progressive hypercapnia with and without inspiratory flow-resistive loading (17 cm H2O/L/s) while the intensity of dyspnea was simultaneously assessed by visual analogue scaling every 15 s. Of the 28 subjects, 14 were 61 to 79 yr of age and were classified as the older group; the others, 19 to 48 yr of age, were classified as the control group. Neither delta VE/delta PETCO2 nor delta P0.1/delta PETCO2 was different between the two groups without loading. In the control group, the delta P0.1/delta PETCO2 increased with loading (p < 0.01) without a change in the delta VE/delta PETCO2. In the older group, the delta P0.1/delta PETCO2 did not change with loading so that the delta VE/delta PETCO2 decreased with loading (p < 0.01). In the 28 subjects as a whole, the percent change in delta P0.1/delta PETCO2 with loading was inversely correlated with age (r = -0.53, p < 0.01). At PETCO2 levels of 45, 50, and 55 mm Hg, irrespective of loading, the dyspnea intensity was greater in the older group than in the control group, whereas the P0.1 expressed as its ratio to the predicted maximal inspiratory mouth pressure was not different between the two groups. We conclude that aging attenuates the compensatory response to inspiratory flow-resistive loading and it increases the intensity of dyspnea for a given level of PETCO2.

Adult↗