Biomedical subjects

A Koizumi

Publications and source records attributed to A Koizumi.

At least 19 recordsLinked to original sources

PubMed1997

Electrophysiological evidence of an increase in cold tolerance of cardiac muscles in mice after energy restriction.

Life-prolonging energy restriction (ER) has been known to extend longevity. The heart was selected as the target organ of ER and the electrophysiological properties of ER on the heart were investigated. Action potential parameters were measured on ventricular papillary muscles of C57BL/6 mice (2-6 months of age). Resting membrane potential (Rm) did not change even when the temperature was lowered to 20 degrees C in ER mice (-67.5 +/- 0.8 mV), however, the membrane was depolarized in the control (-61.1 +/- 1.1 mV). Action potential duration measured at 30 and 50% repolarization was significantly prolonged in ER mice at 20-35 degrees C. Ouabain (10 microM) decreased Rm in ER mice at 20 degrees C (-68.6 +/- 1.0 to -63.6 +/- 0.8 mV), but failed to decrease Rm in the control (-60.6 +/- 1.8 to -62.1 +/- 1.2 mV). There were no significant differences in extracted Na, K-ATPase activity or affinity and binding capacity of ouabain between ER and control hearts. These results indicate that in ER mice the lack of effect of temperature on Rm was not due to a change in the physicochemical properties of Na, K-ATPase. The present study collectively suggests that ER increases cold tolerance in the heart of mice.

Acclimatization↗

PubMed1997

Electrophysiological characterization of cultured hepatic stellate cells in rats.

This study aimed to examine electrophysiological properties of cultured rat hepatic stellate cells (HSCs) using the whole cell configuration of patch-clamp technique. At least three different current components were identified. First, when the membrane was depolarized to voltages more positive than -40 mV, a transient outward K+ current was evoked. Second, membrane hyperpolarization below -60 mV evoked a sustained and inward-rectifying K+ current. The third component was a current flowing outward, which was activated when the cell was depolarized more positively than 0 mV. The channel for this current allowed Na+, K+, and Cl- to pass nonspecifically, suggesting the presence of hemi gap-junctional channel. Furthermore, a laser photobleaching technique revealed the presence of gap junctions between adjacent HSCs. A voltage-gated Ca2+ current, which is known to occur in smooth muscle cells, was searched for but was not detectable. These results suggest that membrane potential of HSCs is determined specifically by the two distinct K+ channels and by an intercellular mechanism involving gap-junctional communication.

Animals↗

PubMed1997

A novel locus, Mody4, distal to D7Mit189 on chromosome 7 determines early-onset NIDDM in nonobese C57BL/6 (Akita) mutant mice.

In this article, we report on a nonobese C57BL/6 (B6) mouse model of NIDDM named Akita mouse, characterized by early age onset and autosomal dominant mode of inheritance. At 7 weeks of age, the mean morning blood glucose levels (mmol/l) under ad libitum feeding conditions were significantly higher (P < 0.01, analysis of variance [ANOVA]) in diabetic mice than in unaffected mice: 27.3 +/- 5.3 for diabetic males (n = 50) and 9.3 +/- 1.2 for unaffected males (n = 50); 13.6 +/- 3.8 for diabetic females (n = 50) and 8.7 +/- 1.1 for unaffected females (n = 50), while corresponding immunoreactive insulin levels in plasma were significantly lower in diabetic mice than in unaffected mice. In vitro insulin secretion was also impaired, even at 4 weeks of age. The 50% survival time for male diabetic mice (305 days) was significantly shorter than that of unaffected counterpart mice but not for diabetic females. Obesity did not occur in diabetic mice. Histological examinations of the pancreas in diabetic mice, from 4 to 35 weeks of age, revealed decreases in the numbers of active beta-cells without insulitis. Morphometry demonstrated specific decreases in immunologically detectable insulin density in islets in diabetic mice, even at 4 weeks of age, without changes of relative islet areas. By linkage analysis, a single locus was identified on the basis of 178 N2 mice [(B6 x C3H/He)F1 x B6 and (B6 x C3H/He)F1 x C3H/He]. This locus, which we named Mody4, was mapped to chromosome 7 in a region 2-8 cM distal to D7Mit189 (logarithm of odds [LOD] score = 15.6 and 10.3).

Alanine Transaminase↗

PubMed1996

A tumor preventive effect of dietary restriction is antagonized by a high housing temperature through deprivation of torpor.

Energy restriction (ER) has proven to be the only effective means of retarding aging in mice. The mechanisms of multiplicity of effects of ER on aging remain, however, fragmentary. ER induces daily torpor, the induction of which is reduced by increasing the ambient temperature to 30 degrees C. The effects of preventing hypothermia in ER animals were studied in terms of the expected consequences of ER on survival, disease pattern and a number of physiological parameters in autoimmune prone MRL/lpr mice and lymphoma prone C57BL, 6 mice. The results demonstrate that torpor plays a crucial role in the prevention of lymphoma development but does not have an affect on other aspects of ER, such as prevention of autoimmune diseases.

Aging↗

PubMed1996

Elevation of serum soluble tumour necrosis factor (TNF) receptor and IL-1 receptor antagonist levels in bronchial asthma.

The specific inhibitor for TNF-alpha activity, soluble form of the 55-kD TNF receptor (sTNF-RI) and soluble form of the 75-kD receptor (sTNF-RII), and the specific inhibitor for IL-1 activity, IL-1 receptor antagonist (IL-1Ra), have been identified. It has been shown that the levels of these inhibitors are elevated in plasma/serum and biological fluids in several diseases, and the protective and inhibitory effect of these inhibitors exist in several inflammatory diseases. In the present study, we measured serum levels of sTNF-RI, STNF-RII and IL-1Ra by ELISA in 36 patients with bronchial asthma (16 atopic and 20 non-atopic) during asthma attacks and in stable conditions in order to assess the state of these inhibitors in allergic inflammation. The levels of sTNF-RI, sTNF-RII and IL-1Ra in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. These findings were obtained regardless of atopic status. These results suggest that higher levels of serum sTNF-RI, sTNF-RII and IL-1Ra may reflect up-regulation of TNF-R expression and IL-1Ra production in allergic inflammation, and sTNF-RI, sTNF-RII and IL-1Ra may contribute to regulating TNF-alpha- and IL-1-mediated production and development of allergic inflammation.

Adult↗

PubMed1996

[Effect of prolonged administration of erythromycin on the drug sensitivity and the biological properties of Streptococcus pneumoniae].

From April 1990 to February 1992 two hundred and ten strains of Streptococcus pneumoniae were isolated in the laboratory of Nara Medical University Hospital. Frequency of erythromycin resistant Streptococcus pneumoniae, prescription mode of macrolide antibiotics and biological properties were investigated. 1. Erythromycin resistant Streptococcus pneumoniae was predominantly isolated from the wards of the respiratory unit of Inter- nal Medicine and Pediatrics. 2. Patients with erythromycin resistant Streptococcis pneumoniae were treated with macrolide antibiotics frequently in the respiratory unit of Internal Medicine and Pediatrics. 3. MIC90 of EM, CLDM, MINO and ABPC for Streptococcus pneumoniae was 8.0, 8.0, 8.0 and 1.0 micrograms/ml, respectively, indicating moderate resistance to penicillin derivatives and high resistance to macrolides, particularly EM; some strains showed high levels of MIC over 400 micrograms/ml. 4. Investigations on biological properties using VITEK GPI cards revealed that some erythromycin resistant strains showed less responsiveness to DEX, LAC, PUL and MEL. 5. The survival rate of mice infected with erythromycin resistant strains was longer than that with erythromycin sensitive strains. These findings suggested that the prolonged administration of erythromycin causes a virulence reduction of the organism.

Adult↗

PubMed1996

Developmental expression of proprotein-processing endoprotease furin in rat pancreatic islets.

The expression of furin in pancreatic beta-cells induces faster cell growth and a decrease in differentiated beta-cell-specific characteristics. During the development of rat pancreatic islets, the prohormone convertases, PC2 and PC3, appear during late gestation and are expressed long after birth. We investigated the developmental change in another yeast Kex2 family endoprotease, furin, in rat islets in relation to islet cell growth. Furin had appeared by gestational day 18 and was distributed in islets as well as exocrine tissues. The expression of furin in islets increased toward the neonatal stage. Bromodeoxyuridine (BrdU) incorporation was also elevated in the perinatal period. On postnatal days 10 and 20, staining characteristics were attenuated. On day 25, immediately after weaning, furin staining began to localize in the beta-cell region, and staining in the alpha-cell region became fainter. On day 270, the staining in the alpha-cell region disappeared, and staining in the beta-cell region remained positive, but was weaker. We conclude that furin expression was greatest during the perinatal period, when BrdU incorporation into islets was maximal. Furin expression continued, however, even after the BrdU incorporation decreased. Thus, furin appears to control the proliferation as well as differentiation of islet cells.

Aging↗

PubMed1996

A novel endogenous mouse mammary tumor virus locus in Asian wild mice and its evolutionary divergency.

The divergency of endogenous mouse mammary tumor virus (MMTV) in European mouse strains indicates acquisition of exogenous MMTV into their genomes during evolution. In the present study, we selected two strains of Asian wild mice, Cas-Hmi (Mus musculus castaneus) and Sub-Kjr (M. m. subspecies) to investigate a possible divergency of endogenous MMTVs among Asian mouse strains. Southern blot analysis and polymerase chain reaction (PCR) demonstrated that Cas-Hmi and Sub-Kjr have the full structure of integrated endogenous MMTVs, suggesting that these mice were diverged during evolution after MMTV endemics.

Animals↗

PubMed1996

An endemic condition of biochemical hypoglycemia among male volunteers.

Biochemical hypoglycemia has attracted attention because it triggers accidents through errors in judgment by impairing cognitive function. Its prevalence and associated risk factors have remained unexplored in the area of occupational health. The present study was designed to investigate its epidemiological aspects in male volunteers. The study population of 76 male volunteers, 63 of whom were firefighters and 13 had other jobs, filled out questionnaires by interview covering 37 factors concerning age, physical parameters, past and current health problems, habits (smoking, drinking, and exercise), food preferences and life style. The participants were asked to measure their blood glucose levels 9 times over a representative workday and holiday and record any symptoms of hypoglycemia at the time of measurement. The body fat ratio of each participant was measured by the bioelectrical impedance analysis method. 22.4% of the participants (17/76) experienced biochemical hypoglycemia (less than 60 mg/dl) at the time of blood glucose monitoring. Those who experienced biochemical hypoglycemia had significantly lower peak, average and nadir blood glucose levels (p < 0.05; 115.1 +/- 18.7 mg/dl, 82.2 +/- 7.0 mg/dl, 52.2 +/- 5.6 mg/dl, respectively) than those who did not (129.9 +/- 26.7 mg/dl, 97.0 +/- 9.9 mg/dl, 75.9 +/- 9.7 mg/dl, respectively). No symptom other than sudden hunger (p < 0.05) was correlated with biochemical hypoglycemia. Lower lean body mass index (lean body mass/height2) was the only statistically significant contributory risk factor (p < 0.05, Odds ratio: 2.91, 95% confidence interval 1.29-6.65) by multiple logistic analysis. Mean blood glucose levels had a positive correlation with lean body mass index (P < 0.0001, r2 = 0.372). The present results suggest that biochemical hypoglycemia is a potential risk problem in occupational settings. Low L.B.M.I. males should be educated about the possibility of biochemical hypoglycemia whoever have experienced a feeling of sudden hunger. Such precautions should be highly recommended to workers under dangerous and/or tense conditions in order to prevent error accidents in occupational settings.

Adult↗

PubMed1996

Epidemiological study on hypoglycemia endemic to female nurses and other workers.

Hypoglycemia has been reported to occur frequently among individuals with health-related occupations, especially hospital nurses. In this study, we investigated the risk factors of hypoglycemia. Both female hospital nurses and other female workers participated in this study, which included questionnaires, and daily blood glucose monitoring. Responses from 3,415 workers were included for analysis. 2,489 workers reported that they had never had hypoglycemic episodes (symptom-free group), while 926 workers reported that they had experienced hypoglycemic symptoms more than once. Of these workers, 207 had had episodes within one year of the study and had experienced them more than once a month (symptomatic group). Thirty-one volunteers were recruited from the above two groups-21 from the latter group and 10 from the former group-and daily blood glucose levels were determined: 6 days for nurses to cover three shifts (dayshift, nightshift and midnightshift) and 2 days for other workers. Nine of 21 volunteers from the symptomatic group had biochemical hypoglycemic reading(s) (< 60 mg/dl) during the monitoring; however, none of 10 volunteers from the symptom-free group had such readings. These nine volunteers were found to have lower mean blood glucose levels (p < 0.05) and lower minimum blood glucose levels (p < 0.05) than other volunteers. Simple logistic analyses revealed multiple risk factors in the symptomatic group. By adjusting the confounding effects, these multiple risk factors were reduced into a small number of risk factors: occupation as a nurse, histories of hypotension and glucosuria, eating snacks, eating deserts, and insomnia. The present report clearly demonstrated that there are hypoglycemic-prone individuals among symptomatic female workers, who were shown to have multiple risk factors for hypoglycemic symptoms.

Adult↗

PubMed1996

[Swyer-James syndrome with bronchial asthma and recurrent spontaneous pneumothorax].

An 18-year-old woman was admitted to our hospital for treatment of the fifth episode of spontaneous pneumothorax. She had a history of repeated pneumonia in childhood and mycoplasma pneumonia at 12 years of age. A chest X-ray film revealed a left-sided pneumothorax, atelectasis of the left upper lobe, and hyperlucency of the left lung. A bronchogram showed poor filling of the peripheral bronchi by contrast medium and mild cylindrical bronchiectasis in the proximal bronchi. Pulmonary arteriography showed small left pulmonary arteries. From these findings, Swyer-James syndrome was diagnosed. This case was complicated by bronchial asthma, with eosinophilia, a high level of IgE, and airway hyperresponsiveness. Atelectasis, multiple bullae, and bronchial asthma had been caused by mycoplasma pneumonia in childhood. Recurrent pneumothorax had been caused by emphysematous changes in the bronchioli and by underdeveloped pulmonary arteries. Surgery to treat the recurrent spontaneous pneumothorax was considered, but was not done because of the risk of relapse and the ventilation-perfusion imbalance due to the Swyer-James syndrome.

Adolescent↗

PubMed1996

[Suppression of experimental autoimmune uveitis by energy restriction].

The effects of energy restriction on experimental autoimmune uveitis (EAU) were investigated. Seven-week-old, male Lewis rats were divided into three groups. Experiment A) A control group was fed ad libitum, a second group was given 50% calorie restricted food from the day of immunization, and a third group was given 50% calorie restricted food from 2 weeks before immunization. Experiment B) A control group was fed ad libitum, a second group was given 25% calorie restricted food from 4 weeks before immunization, and a third group was given 50% calorie restricted food 4 weeks before immunization. All rats were immunized with interphotoreceptor retinoid-binding protein (IRBP). In experiment A), in the group given 50% calorie restricted food from 2 weeks before immunization, and in experiment B), in the group given 50% calorie restricted food from 4 weeks before immunization, the onset of EAU was significantly delayed, the clinical symptoms were lessened, and delayed hypersensitivity against IRBP was suppressed. Clinically and histologically, the severity was also low. In the group given 50% calorie restricted food from 4 weeks before immunization, the titer of anti-IRBP antibody was also significantly lower than in the control group.

Animals↗

PubMed1995

A direct involvement of the central nervous system in hypophagia and inhibition of respiratory rate in rats after treatment with O,O,S-trimethyl phosphorothioate.

O,O,S-Trimethyl phosphorothioate (OOS-TMP) is known to induce unique symptoms, which are characterized by hypophagia, progressive weight loss, and hypothermia. To determine whether there is the possibility of a causal relationship between these toxic symptoms and a direct action of OOS-TMP on the central nervous system, we investigated the development of these symptoms in Fischer 344 female rats after oral or intracerebral treatment with OOS-TMP. Oral administration of OOS-TMP at 20 mg/kg induced marked hypophagia, progressive weight loss and hypothermia. Moreover, inhibition of respiratory rate was observed immediately after treatment. It lasts during the entire experimental period. Profound hypothermia below 34 degrees C was observed more frequently in the rats, which became hypercapnic (PaCO2 > or = 50 mmHg). In contrast, administration of OOS-TMP at 20 mg/kg (as much as the oral dose) into the cerebral lateral ventricle succeeded in inducing hypophagia, progressive weight loss and lowered respiratory rates. On the other hand, by this route of administration, OOS-TMP at 20 mg/kg failed to induce hypothermia, hypercapnia and lung injury. The present results suggest that hypophagia and inhibitions of respiratory rate are attributable to the direct action of OOS-TMP on the central nervous system, while other symptoms are associated with lung injury.

Administration, Oral↗

PubMed1995

Elevation of serum soluble vascular cell adhesion molecule-1 (sVCAM-1) levels in bronchial asthma.

We have previously shown the elevation of serum soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sE-selectin) in patients with bronchial asthma during asthma attacks. In the present study, we extended our earlier study by measuring serum sVCAM-1 levels by ELISA in 45 patients with bronchial asthma (23 atopic and 22 non-atopic) during asthma attacks and in stable conditions in order to assess further the state of adhesion molecules in allergic inflammation of bronchial asthma. The levels of sVCAM-1 in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. These findings were observed regardless of atopic status. To examine the regulatory mechanism in the elevation of serum sVCAM-1 levels, serum tumor necrosis factor-alpha (TNF-alpha) levels were measured by ELISA. TNF-alpha levels in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. The nature of change in serum TNF-alpha levels correlated with the nature of change in serum sVCAM-1 levels, but serum TNF-alpha levels did not correlate with serum sVCAM-1 levels. These results suggest that higher levels of sVCAM-1 during asthma attacks may reflect the up-regulation of VCAM-1 expression in allergic inflammation, and that a soluble form of VCAM-1 molecules may be useful markers for the presence of allergic inflammation. TNF-alpha is shown to enhance the expression and release of VCAM-1 in vitro, however; the regulatory mechanism in the elevation of serum sVCAM-1 levels remains to be clarified.

Adult↗

PubMed1995

Changes in nitric oxide synthase activities in the cerebellum during development and aging of C57BL/6 mice.

Nitric oxide (NO) is one of the neurotransmitters in the cerebellum. Activities of NO synthase and densities of granule cells were determined in the cerebellum in an attempt to elucidate a mechanism of biochemical changes on the anatomical basis during aging. Activities of Ca2+/calmoduline dependent NO synthase were measured in the cerebellum in male and female mice, from 18 gestation days to 28 months of age. There were significant differences in NO synthase activities among the groups of prenatal (18 gestation days), middle aged (5-18 months) and old aged (21-28 months) mice. Between groups of old and middle ages, a significant decrease with aging was found in the mean density of granular cells, which express NO synthase. Changes in NO synthase activities and granule cell densities occurred to a similar degree between old and middle ages. The present data suggest that an age-associated rise and fall of its activities likely occur in parallel with those of granule cell densities, and thus may represent impairment of cerebellar function during aging.

Aging↗

PubMed1995

A mouse model of a sudden death induced by noise exposure is useful to investigate human responses to physical stress.

Stress has become an increasingly important occupational health matter in Japan. We found that noise exposure, 6 kHz wave and its higher harmonics at the sound pressure level of 112 dB, induced typical audiogenic seizures in the MRL/l mouse strain. The seizures are often fatal. Wild running preludes to seizures. Inhibition of wild running by restricting animal's activities successfully prevented the seizures, suggesting that an excessive physical load is a necessary step. The present finding indicates that MRL/l mice may be a useful model for human sudden deaths after excessive work loads.

Acoustic Stimulation↗

PubMed1994

Fighting myths.

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Antidotes↗

PubMed1994

Mercury, not sulphur dioxide, poisoning as cause of smelter disease in industrial plants producing sulphuric acid.

Several episodes of "smelter disease", previously assumed to be caused by sulphur dioxide (SO2) poisoning, have been reported in workers replacing pipes in sulphuric acid manufacturing plants. One such incident, affecting 20 men, was recorded in Akita, Japan, in July, 1993, but the protection these workers used suggested that some cause other than SO2 needed to be looked for. 10 workers were affected despite wearing respirators with SO2 cartridges, the symptoms including dyspnoea, diarrhoea, colicky pain, muscle pain and eczema with erythema. Subsequently 10 other workers using face masks with supplied air were affected, though without respiratory symptoms. Sludge in the piping contained mercuric sulphate, and mercury fumes resulted when pipes were cut with gas burners. Blood and urine measurements confirmed heavy exposure to the metal, and simulation experiments in rats showed that skin absorption was likely too. The masks with supplied air ought to have excluded both SO2 and mercury fumes. The only way to avoid smelter disease reliably is to wear an encapsulated suit that prevents inhalation and skin absorption of industrial toxins.

Acute Disease↗