Biomedical subjects
Publications and source records attributed to M Igarashi.
A novel antifungal antibiotic, formamicin, was isolated from the culture broth of Saccharothrix sp. MK27-91F2. The absolute structure of formamicin was determinated by spectroscopic and X-ray crystallographic analysis and degradation study.
To investigate the prevalence of hepatitis C virus and human immunodeficiency virus infection in female inmates, 504 out of 513 female inmates in a certain female prison in Japan were tested for anti-hepatitis C virus, anti-hepatitis B virus, anti-hepatitis A virus and anti-human immunodeficiency virus makers. They were also interviewed with regard to past history of blood transfusion, tattooing, acupuncture, intravenous drug abuse, and psychiatric disease. Prevalence of seropositives for anti-hepatitis C virus antibody was found to be significantly higher in prisoners who had a history of intravenous drug abuse (63%) compared to the controls (4.5%). There was no difference between the two groups in prevalence of seropositivity for anti-hepatitis B, anti-hepatitis A and anti-human immunodeficiency virus. Of all inmates who had a history of intravenous drug abuse, anti-hepatitis C positives used drugs longer and in greater quantities than anti-hepatitis C negatives. From these results it is concluded that intravenous drug abuse is a predominant risk factor for hepatitis C virus infection.
We studied low flow anesthesia using ACOMA ACM-10 anesthesia machine in 39 patients undergoing elective surgery. Randomly, 29 patients were allocated to low flow anesthesia group and 10 patients were allocated to high flow anesthesia group. After the induction, anesthesia was maintained with 2 l.min-1 of oxygen, 4 l.min-1 of nitrous oxide and sevoflurane (high flow anesthesia). After 15 minutes of high flow anesthesia, the total gas flow was reduced to 300 ml.min-1 of oxygen, 300 ml.min-1 of nitrous oxide or reduced to 400 ml.min-1 of oxygen, 200 ml.min-1 of nitrous oxide in the low flow anesthesia group. In the high flow anesthesia group, the high flow was maintained. The inspiratory oxygen concentration was maintained during anesthesia more than 35% in the low flow group and 33% in the high flow group. The absolute humidity in the inspiratory gas and the soda lime temperature were significantly higher during low flow anesthesia. The sevoflurane consumption in the low flow anesthesia group was reduced to less than 1-8th that of high flow anesthesia group. In conclusion, we could perform low flow anesthesia safely and economically with the ACM-10 anesthesia machine.
Factor VII coagulant activity (FVIIc) and fibrinogen (Fbg) levels have been investigated as cardiovascular risk factors. We studied these two factors with stratification for age, sex and blood pressure, and the relation with other atherosclerotic risk factors in a Japanese general population. The subjects were 3,139 Japanese (1,315 males and 1,824 females) aged 30 to 89 in 1992 and 1993. A linear increase with age was observed in the levels of Fbg in both men and women, but no differences were observed between men and women in each age group. A linear increase with age was also seen in the levels of FVIIc in women, but the levels of FVIIc in men were significantly higher for the age group 40-49 years than for any other age group. The levels of FVIIc in women were significantly higher than in men at age > or = 60 years. As concerning the effect of alcohol intake status, Fbg had a tendency to decrease with alcohol intake. Fbg and FVIIc levels were associated with an increase in smoking status in men, but no association was seen in women in either Fbg or FVIIc. FVIIc was positively correlated with age, body mass index, total cholesterol, triglycerides and fasting insulin level. Fbg was positively correlated with age, systolic blood pressure, diastolic blood pressure, total cholesterol, LDL-cholesterol and triglycerides in women, but Fbg had few positive correlations with risk factors in men. A comparison with previous Western studies showed that the Fbg levels of our Japanese population were lower than those of the Caucasians studied, but the present FVIIc levels were nearly the same level or slightly higher than theirs. The association of Fbg and FVIIc and with other cardiovascular risk factors in Japanese was similar to those observed in Caucasians.
Melanosomes of the stria vascularis in gentamycin (GM)-intoxicated guinea pigs were examined ultrastructurally. Experimental animals were given GM sulfate intramuscularly in a daily adjusted dose of 100 mg/kg for 15 consecutive days (group A), and 150 mg/kg for 5 consecutive days (group B). Melanosomes of the intermediate cells in group B significantly increased in number in comparison with those in group A and the control group. Melanosomes in the apical turn outnumbered those in the basal turn in all three groups. Cytochemically, Na+, K(+)-ATPase activity was also demonstrated in the marginal cells. There was little difference in the degree of enzyme activity between groups A, B and the control group. The role and significance of melanosomes of the stria vascularis are discussed.
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Positron emission tomography (PET) was used to demonstrate temporary down-regulation of visual cortex activities associated with eye movements. The aim of the present study was to test this paradigm with visual evoked potentials (VEPs) in the visual cortex of 7 healthy human subjects during caloric nystagmus. Caloric stimulation was performed by irrigating the right or left external ear canals with 100 ml of warm water at 44 degrees C for 50 s with a head position of 60 degrees tilted backward in order to stimulate the horizontal semicircular canal. The subjects kept their eyes closed during and after caloric stimulation. For recording the VEPs, the flashlight was used for activating the visual cortex with the subject's eyes closed. In the 7 subjects, no significant difference was detected between the VEPs induced with and without caloric stimulation.
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beta2-Glycoprotein I (beta2-GPI) consists of five repeats of a homologous domain. We designed a series of human beta2-GPI mutant genes, ie, three mutant genes lacking the domain(s) present in the NH2-terminal region and two of those present in the COOH-terminal region. These mutant genes were expressed in Spodoptera frugiperda insect cells (Sf9) infected with recombinant baculoviruses and the mutant proteins were secreted into the culture medium. The molecular mass of the purified mutant proteins, estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was fairly consistent with the size calculated from their nucleotide sequences. Binding of beta2-GPI to solid-phase cardiolipin (CL) was diminished by the deletion of the fifth domain (domain V) from its complete structure. Thus, the phospholipid binding site of beta2-GPI is located on its domain V. Monoclonal anti-CL antibodies (aCL) derived either from NZW x BXSB (WB) F1 mice or from patients with antiphospholipid syndrome bound directly to the domain V-deleted mutant protein (DI-IV) absorbed not only on an oxygenated but also on a plain polystyrene surface. We conclude from this study that the epitope for aCL is exposed on a conformationally changed structure of beta2-GPI by interacting with negatively charged phospholipid or on the mutant protein, DI-IV.
Hepatic glucoreceptor-vagal afferent inputs to the central nervous system and pancreatic vagal efferent stimuli are important for insulin secretion. In the present study, we examined the effect of intracerebroventricular (i.c.v.) injection of atropine methyl bromide (methylatropine) on the insulin response following glucose ingestion in rats. When rats were injected with methylatropine i.c.v., the plasma glucose concentration increased, the insulin response reduced, and glucagon-like peptide-1 (7-36) amide (tGLP-1) was unchanged following an oral glucose load, compared with the controls. The plasma insulin response following an intravenous glucose load was not affected by i.c.v. or intraperitoneal injection of methylatropine. A transient increase in plasma insulin after selective hepatic vagotomy was inhibited by i.c.v. injection of methylatropine. Arterial blood pressure or pulse rate was not changed by i.c.v. injection of methylatropine. These results show that the central nervous system plays an important role in the vagal control of the insulin response to glucose ingestion. In rats, for the insulin response soon after glucose ingestion (early phase insulin response), direct neural control (hepatic vagal afferent-central nervous system-pancreatic vagal efferent) of the islet B cells seems more important than the intestinal insulinotropic hormone, tGLP-1.
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A dual-energy (DE) quantitative computed tomography (QCT) method, the four-equation four-unknown method (DEQCT 4E-4U), was assessed and compared to single-energy (SE) QCT and standard DEQCT (two-line method). The results of this study indicate that bone mineral density (BMD) was more accurately estimated by the present method than by the SEQCT or standard DEQCT techniques on the basis of a phantom study when a large fat content was present. The results of both the phantom study and a human study also showed that the present method corrected for fat in estimating BMD in the presence of high-fat content. These findings suggest that use of this method for estimating BMD can provide useful information in studies assessing the metabolic state of bone. We propose that CT numbers estimated from excised vertebral bone marrow can serve as a soft-tissue correction for the present method.
The growth cone is responsible for axonal elongation and pathfinding by responding to various modulators for neurite growth, including neurotransmitters, although the sensor mechanisms are not fully understood. Among neurotransmitters, GABA is most likely to demonstrate activity in vivo because GABA and the GABAA receptor appear even in early stages of CNS development. We investigated the GABAA receptor-mediated signaling pathway in the growth cone using isolated growth cones (IGCs). Both the GABAA binding site and the benzodiazepine modulatory site were enriched in the growth cone membrane. In the intact IGC, GABA induced picrotoxin-sensitive Cl- flux (not influx but efflux) and increased the intracellular Ca2+ concentration in a picrotoxin- and verapamil-sensitive manner. Protein kinase C (PKC)-dependent phosphorylation of two proteins identified as GAP-43 and MARCKS protein was enhanced in the intact IGC stimulated by GABA, resulting in the release of MARCKS protein and GAP-43 from the membrane. Collectively, our results suggest the following scheme: activation of the functional GABAA receptor localized in the growth cone membrane-->Cl- efflux induction through the GABAA-associated Cl- channel-->Ca2+ influx through an L-type voltage-sensitive Ca2+ channel-->Ca(2+)-dependent phosphorylation of GAP-43 and MARCKS protein by PKC.
The growth cone is responsible for axonal growth, where membrane expansion is most likely to occur. Several recent reports have suggested that presynaptic proteins are involved in this process; however, the molecular mechanism details are unclear. We suggest that by cleaving a presynaptic protein syntaxin, which is essential in targeting synaptic vesicles as a target SNAP receptor (t-SNARE), neurotoxin C1 of Clostridium botulinum causes growth cone collapse and inhibits axonal growth. Video-enhanced microscopic studies showed (a) that neurotoxin C1 selectively blocked the activity of the central domain (the vesicle-rich region) at the initial stage, but not the lamellipodia in the growth cone; and (b) that large vacuole formation occurred probably through the fusion of smaller vesicles from the central domain to the most distal segments of the neurite. The total surface area of the accumulated vacuoles could explain the membrane expansion of normal neurite growth. The gradual disappearance of the surface labeling by FITC-WGA on the normal growth cone, suggesting membrane addition, was inhibited by neurotoxin C1. The experiments using the peptides derived from syntaxin, essential for interaction with VAMP or alpha-SNAP, supported the results using neurotoxin C1. Our results demonstrate that syntaxin is involved in axonal growth and indicate that syntaxin may participate directly in the membrane expansion that occurs in the central domain of the growth cone, probably through association with VAMP and SNAPs, in a SNARE-like way.
Complementary DNA clones for three different beta-tubulin isotypes (ZeTubB1, ZeTubB2 and ZeTubB3) were isolated from a cDNA library generated from RNA of cultured mesophyll cells of Zinnia elegans that were differentiating into tracheary elements and/or dividing. Sequence analysis revealed that the proteins encoded by ZeTubB1 and ZeTubB3 and that encoded by ZeTubB2 were each homologous to two of three groups of beta-tubulin isotypes in Arabidopsis. RNA gel blot analysis of the expression of the ZeTubB transcripts indicated that transcripts that corresponded to each clone were differently expressed during culture of Zinnia mesophyll cells. In particular, the level of expression of ZeTubB1 and ZeTubB3 transcripts increased rapidly prior to cell division and secondary wall formation, and such expression was promoted by combinations of auxin and cytokinin that induced tracheary element differentiation as well as cell division. Results of an in situ hybridization experiment with an antisense RNA probe derived from ZeTubB1 cDNA suggested the preferential expression of ZeTubB transcripts in differentiating xylem cells, as well as in the ground meristem and the procambium, of Zinnia seedlings.
Left ventricular myocardial disorders due to volume overload were investigated by Tl-201 myocardial SPECT (Tl-201 SPECT) in patients with aortic or mitral regurgitation, and its utility for timing cardiac valve replacement was studied. There were significant correlations between Tl-201 scores and electrocardiographic changes and the New York Heart Association classification. There also were favorable correlations between Tl-201 scores and the left ventricular end-diastolic dimension and between Tl-201 scores and left ventricular ejection fraction, and a close relationship between the presence of a left ventricular myocardial disorder and left ventricular diameter. These results suggest that myocardial perfusion abnormalities and left ventricular myocardial disorders may accompany left ventricular dilatation owing to volume overload. After valve replacement, left ventricular end-diastolic dimension normalized, and Tl-201 scores improved slightly, suggesting normalization of myocardial perfusion. When moderate or more severe Tl-201 defects are present on Tl-201 SPECT images, in addition to inverted Tl-201 waves on the electrocardiogram or a left ventricular end-diastolic dimension of 65 mm or more, cardiac valve replacement should be considered.
Heterogeneity of zonal hepatocytes is important to elicit specific liver function. We investigated the distribution of glucose transporter 2 (GLUT-2) in normal rat liver by immunostaining and Northern blot analysis. GLUT-2 stained by immunohistochemistry was distributed predominantly in the periportal hepatocytes and gradually thinned towards the perivenous zone. Ultrastructural immunostaining of GLUT-2 showed that it was localized on microvilli of the sinusoidal plasma membrane of hepatocytes but not on the basolateral plasma membrane. Consistent with the distribution of GLUT-2 protein, the level of GLUT-2 mRNA in periportal hepatocytes was 1.9-fold higher than in perivenous hepatocytes selectively isolated by the differential isolation technique. In addition, the mRNA level of phosphoenolpyruvate carboxykinase, one of the key enzymes of gluconeogenesis, was also twofold higher in the periportal hepatocytes. These results suggest that GLUT-2 contributes to the functional difference between periportal and perivenous hepatocytes in glucose metabolism of the liver.