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Biomedical subjects

Y Deguchi

Publications and source records attributed to Y Deguchi.

At least 55 records · Page 3Linked to original sources

Production of chitinase and beta-N-acetylglucosaminidase by intestinal bacteria of Pinnipedian animals.

The chitinase- and beta-N-acetylglucosaminidase(GlcNAcase)-producing ability of intestinal bacteria from Pinnipedian animals was determined using fluorogenic 4-methylumbelliferone glycosides of N-acetylglucosamine oligosaccharides. Intestinal microflora of a single Cape fur seal, three California sea lions and three South American sea lions were characterized by a predominance of isolates of the Bacteroidaceae and Enterobacteriaceae families and the genus Clostridium. Of the 711 isolates tested 26.0, 10.0 and 8.7% could hydrolyse 4-MU(GlcNAc)1, 4-MU(GlcNAc)2 and 4-MU(GlcNAc)3, respectively. This result suggests that beta-GlcNAcase producers occur at a higher density than do chitinase producers. Moreover, beta-GlcNAcase, and to a lesser degree, chitinase seem to be efficiently produced by facultative anaerobes in the Cape fur seal and the California sea lion, and by both facultative and obligated anaerobes in the South American sea lion. To our knowledge, this is the first paper to report that isolates of the family Bacteroidaceae and the genus Streptococcus produce chitinase and/or beta-GlcNAcase.

Acetylglucosaminidase↗

Urinary selenium excretion in infancy: comparison between term and preterm infants.

We evaluated the urinary excretion of selenium (Se), an essential component of glutathione peroxidase, in infants aged 1 week and 1, 4, and 7 months and examined the relationship between urinary Se and renal function. Daytime spot urine samples from a total of 80 infants were analyzed. The Se concentration in urine was measured by fluorometry, while the beta 2-microglobulin content, an index of renal tubular function, was determined by radioimmunoassay. In healthy term infants, the urinary Se excretion showed a peak level at 1 month of age. In contrast, the urinary Se concentration rapidly decreased in preterm infants from 1 week to 7 months postnatally. The level at 1 week in preterm infants was significantly higher than that in term infants, although the mean levels at 1, 4, and 7 months were lower in preterm infants. The level of urinary Se did not correlate significantly with the beta 2-micro-globulin concentration, either in term or preterm infants at any age investigated. Our results suggest that the renal excretion of Se probably reflects the body stores of Se and is not related directly to the renal function in infants. Urinary Se, a noninvasive marker of the Se status, may be used for diagnosis and follow-up of Se deficiency in infants.

Aging↗

Selenium and fertility in animals and man--a review.

To evaluate the information on selenium with relation to fertility in animals and man the available literature was reviewed. Selenium is incorporated in the sperm mitochondria capsule and may thus affect the behavior and function of the spermazoon. Se seems to be essential for normal spermatozoa development in both experimental animals and in livestock and probably also in humans. Regarding selenium and female fertility only sparse information exists. In experimental animals a low selenium level affects fertility in males, but little attention has been devoted to female reproductive performance, and the data are insufficient for conclusion. In livestock numerous investigations have been performed and the effects of selenium supplementation often in combination with other antioxidants have been evaluated, but no valid conclusion can be drawn. In general adequate nutritional supply will secure optimal reproduction in both males and females, while additional supplementation seems to have a negative effect. In humans contradictive information is found. Both low and high sperm selenium concentrations are reported to have a negative influence on the number of spermatozoa and on the motility. The optimal sperm selenium concentration waits to be defined. Some evidence indicates that a metabolic defect in a selenium incorporation into sperm cells may be associated with human infertility. No human data relating selenium to female infertility were found.

Animals↗

The Inuit diet. Fatty acids and antioxidants, their role in ischemic heart disease, and exposure to organochlorines and heavy metals. An international study.

Traditional food is culturally, economically and nutritionally important for the Greenlandic Inuit people. In the 1970s the preventive effect of marine fat on cardiovascular disease, thrombosis and atherosclerosis was described. The low incidence of ischemic heart disease among Greenlanders has been related to the high intake of marine food. Since 1990 routine autopsies have taken place in two towns in Greenland, Nuuk and Ilulissat. The autopsies represent 26% of the total number of deaths in these two towns. Samples have been collected from 104 autopsies. International cooperative studies have analysed specimens in relation to ischemic heart disease as a benefit related to diet, as well as the level of heavy metals and organochlorine in organs as a risk related to diet. High amounts of mono-unsaturated and Omega-3 poly-unsaturated fatty acid were found in adipose tissue. Liver analyses of selenium have confirmed the expected high intake among Greenlanders. Reduced atherosclerotic lesions were found in the coronary arteries. Blood pressure levels calculated from renovascholopathia of hypertension indicate prevailing levels similar to those in industrialized countries. Some factors in Greenland may be protecting the coronary arteries, thereby of setting the expected effect of hypertension. The level of methyl mercury in organs is generally high. PCB concentrations found in organs of Greenlanders are higher than among other populations. Health and risk effects of the traditional foods need further investigation.

Adipose Tissue↗

[Relationship of hypertension prevalence in companies to business type and scale--from an analysis of health examination results in Fukui prefecture].

The results of health examinations of 89,299 examines from companies in Fukui Prefecture conducted pursuant to the Occupational Safety and Health Act were analyzed to study the relationship between the prevalence in these companies of hypertension, and company size business type. The Mantel-Haenszel method was utilized to adjust for age structure of the examinees according to gender and the type of business of their companies to compare prevalence of hypertension. The results of the analysis indicated that the prevalence of hypertension was significantly higher in small-scale companies for the female examinees working in pulp/paper processing and motor freight transport business than in large-scale companies, but no significant difference was seen for scale of business when the female examinees were grouped without regard to the business type of their companies. In the case of the male examinees, the analysis results revealed that the prevalence of hypertension was significantly higher in small-scale companies for those working in ceramic/earth/rock, motor passenger transport and hotel/restaurant business than in large-scale industry while the prevalence of hypertension was significantly higher in large-scale companies for those working in non-ferrous metal industry, financial and other types of business. Moreover, the analysis results for the male examinees grouped without regard to the type of business of their companies indicated that the prevalence of hypertension remained significantly higher in small-scale companies. The above also suggests the need for measures for health care of workers that considers business type and scale for the purpose of primary prevention of hypertension.

Adult↗

Regulation and mechanisms of gene amplification.

Amplification in rodent cells usually involves bridge-breakage-fusion (BBF) cycles initiated either by end-to-end fusion of sister chromatids, or by chromosome breakage. In contrast, in human cells, resistance to the antimetabolite N-(phosphonacetyl)-L-aspartate (PALA) can be mediated by several different mechanisms that lead to overexpression of the target enzyme carbamyl-P synthetase, aspartate transcarbamylase, dihydro-orotase (CAD). Mechanisms involving BBF cycles account for only a minority of CAD amplification events in the human fibrosarcoma cell line HT 1080. Here, formation of a 2p isochromosome and overexpression of CAD by other types of amplification events (and even without amplification) are much more prevalent. Broken DNA is recognized by mammalian cells with intact damage-recognition pathways, as a signal to arrest or to die. Loss of these pathways by, for example, loss of p53 or pRb tumour suppressor function, or by increased expression of ras and myc oncogenes, causes non-permissive rat and human cells to become permissive both for amplification and for other manifestations of DNA damage. In cells that are already permissive, amplification can be stimulated by overexpressing oncogenes such as c-myc or ras, or by damaging DNA in a variety of ways. To supplement genetic analysis of amplification in mammalian cells, an amplification selection has been established in Schizosaccharomyces pombe. Selection with LiCl yields cells with amplified sod2 genes in structures related to those observed in mammalian cells. The effect on amplification in S. pombe can now be tested for any mutation in a gene involved in repair of damaged DNA or in normal cellular responses to DNA damage.

Animals↗

Study on brain interstitial fluid distribution and blood-brain barrier transport of baclofen in rats by microdialysis.

PURPOSE: This study was performed to examine the distribution in the brain interstitial fluid (ISF) and the blood-brain barrier (BBB) transport of baclofen in rats by a microdialysis technique. METHODS: Following an i.v. bolus administration and/or the constant i.v. infusion of baclofen to the microdialysis cannula-bearing anesthetized rats, the concentrations of baclofen in the hippocampal ISF, whole brain tissue, cerebrospinal fluid (CSF), and plasma were determined by high-performance liquid chromatography (HPLC). Data were kinetically analyzed to estimate the transport parameters, i.e., the influx clearance (CLin) from plasma to brain and the efflux rate constant (keff) from brain to plasma, and the steady-state volume of distribution in the brain (Vd). RESULTS: The concentrations of baclofen in ISF, whole brain tissue, and CSF at the pseudo-steady state were almost 30-fold lower than the plasma unbound concentration, suggesting the restricted distribution of baclofen in the brain. The estimated values of CLin and keff were 0.00157 +/- 0.00076 ml/min/g of brain and 0.0872 +/- 0.0252 min-1, respectively. The efflux clearance (CLout) calculated by multiplying keff by Vd (0.816 +/- 0.559 ml/g of brain) was 0.0712 +/- 0.0529 ml/min/g of brain, and it was significantly 40-fold greater than the CLin value and fully greater than the convective flow in ISF. Furthermore, no significant concentration gradient was observed between ISF and CSF. These results suggest that the CLout value mainly reflects the efflux clearance through the BBB. Additionally, the hippocampal ISF/plasma concentration ratio of baclofen was markedly increased by both systemic administration of probenecid and its direct instillation into ISF. CONCLUSIONS: The restricted distribution of baclofen in the brain ISF may be ascribed to the efficient efflux from the brain through the BBB which is regulated possibly by a probenecid-sensitive organic anion transport system.

Animals↗

Distribution of Aeromonas species in the intestinal tracts of river fish.

Aeromonas isolates were obtained from fish intestines, water, and sediments from an urban river and identified by the DNA-DNA microplate hybridization method. The isolates were Aeromonas veronii (22%), Aeromonas caviae (18%), Aeromonas hydrophila (13%), Aeromonas sobria (8%), Aeromonas jandaei (7%), and other Aeromonas spp. (33%). Aeromonas species occurred at high densities with high incidences, regardless of season. The results strongly suggest that aeromonads are indigenous in fish intestines, water, and sediments of rivers and have the potential to be predominant in aquatic environments.

Journal Article↗

In vivo evidence for ATP-dependent and P-glycoprotein-mediated transport of cyclosporin A at the blood-brain barrier.

To evaluate the significance of P-glycoprotein (P-gp)-mediated active efflux on the blood-brain barrier (BBB) permeability of cyclosporin A (CsA) in vivo, we investigated the effects of ATP depletion in the brain and of a multidrug-resistant (MDR) reversing agent on the transport of CsA across the BBB. Using transient brain ischemia obtained by 4-vessel occlusion of vertebral and common carotid arteries in rats to deplete ATP content in the brain, the estimated permeability surface area product (PS) value of [3H]CsA was increased 2.7-fold compared with that in normal rats, whereas the PS value of [14C]sucrose was not altered. Additionally, when quinidine hydrochloride (QND) was infused into the brain through a microdialysis probe implanted in the rat hippocampus, the extravascular extraction of CsA was increased to approximately 2.5-fold of the control, whereas no difference in the extravascular extraction between control and normal rats having no implanted dialysis probe was observed. Furthermore, the efflux rate from brain to blood of CsA was decreased remarkably to 5% of control at steady-state by co-administration of CsA with QND directly into the brain through the dialysis probe. The ATP-dependent and QND-sensitive efflux of CsA from the brain strongly indicates that P-gp in the brain capillary endothelial cells functions as an efflux pump under the physiological state, and that P-gp-mediated efflux of CsA is a major mechanism of the restricted transfer from blood into the brain.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

A novel human homeobox gene distantly related to proboscipedia is expressed in lymphoid and pancreatic tissues.

A novel human homeobox gene, HB9, was isolated from a cDNA library prepared from in vitro stimulated human tonsil B lymphocytes and from a human genomic library. The HB9 gene is composed of 3 exons spread over 6 kilobases of DNA. An open reading frame of 1206 nucleotides is in frame with a diverged homeodomain. The predicted HB9 protein has a molecular mass of 41 kilodaltons and is enriched for alanine, glycine, and leucine. The HB9 homeodomain is most similar to that of the Drosophila melanogaster homeobox gene proboscipedia. Northern blot analysis of poly(A) RNA purified from the human B cell line RPMI 8226 and from activated T cells revealed a major mRNA transcript of 2.2 kilobases. Similar analysis of poly(A) RNA from a variety of adult tissues demonstrated HB9 transcripts in pancreas, small intestine, and colon. Reverse transcriptase-polymerase chain reaction was used to examine HB9 RNA transcripts in hematopoietic cell lines. HB9 RNA transcripts were most prevalent in several human B cell lines and K562 cells. In addition, transcripts were detected in RNA prepared from tonsil B cells and in situ hybridization studies localized them in the germinal center region of adult tonsil. These findings suggest the involvement of HB9 in regulating gene transcription in lymphoid and pancreatic tissues.

Adult↗

Factors affecting the efficiency of peripheral blood stem cell collection in children treated with chemotherapy and G-CSF.

This retrospective study attempts to clarify the optimal timing for peripheral blood stem cell (PBSC) collection after conventional chemotherapy followed by granulocyte-colony stimulating factor (G-CSF) administration. Leukapheresis was performed 32 times in nine children with various cancers during bone marrow recovery phase following transient pancytopenia after chemotherapy. (On two occasions, leukapheresis was excluded because many leukemic blasts were included). When the number of white blood cells (WBC) exceeded 1.8 x 10(10)/L after administration of G-CSF (200 micrograms/m2, continuous infusion), many more CD34+ cells were contained in the collected peripheral mononuclear cells (P > 0.02) and a sufficient number of PBSC for transplantation (> or = 10 x 10(8) CD34+ cells/kg) was obtained after one run in 15 of 17 leukapheresis sessions. In contrast, sufficient PBSC were obtained only in one of 13 runs of leukapheresis when the number of WBC was < 1.8 x 10(10)/L. The number of WBC on the day when PBSC were collected correlated with collected nuclear cell number (r = 0.60), but not with the CD34+ cell ratio. The ratio was higher only when both platelets and reticulocytes increased in parallel with WBC. We conclude that sufficient PBSC collection is possible after conventional chemotherapy using G-CSF, when hematopoietic recovery is parallel, without the use of high-dose chemotherapy.

Antigens, CD↗

Identification of Aeromonas species isolated from freshwater fish with the microplate hybridization method.

Aeromonas isolates were obtained from the intestinal tracts of six species of cultured freshwater fish and identified on the basis of their genotypic and phenotypic characters. The microplate hybridization method could differentiate type strains of Aeromonas species and related bacteria. DNA-DNA hybridization analysis showed that 65 aeromonad isolates were 72 to 100% related with either Aeromonas caviae, Aeromonas hydrophila, Aeromonas jandaei, Aeromonas sobria, or Aeromonas veronii. As many as 48% of the genotypically identified A. caviae, A. hydrophila, and A. sobria isolates differed from the type strains of corresponding species in one to three phenotypic characters. These results strongly suggest that not all aeromonad isolates from freshwater fish could be identified correctly on the basis of only the phenotypic characters, indicating the usefulness of the microplate hybridization method for the identification of aeromonads.

Journal Article↗

[Antinociceptive effects of counterirritants].

Counterirritants such as l-menthol, methyl salicylate, camphor, thymol and capsaicin are widely used in the treatment of mild pains and itches by topical application. However, little experimental research on counterirritants has been reported. In the present study, we investigated the antinociceptive effects and mechanisms of topically applied counterirritants, especially those of l-menthol. From the formalin test in mice, l-menthol (at a concentration of 1-30% in ethanol) showed a major effect in the early phase of pain response (0-5 min). In contrast, the antinociceptive effects of indomethacin (10 mg/kg, p.o.) were found only in the late phase of pain response (15-25 min). Furthermore, morphine (0.75-6 mg/kg, s.c.) dose-dependently inhibited both phases. l-Menthol-induced analgesia during the early phase was significantly blocked by naloxone and potentiated by bestatin. The antinociceptive effects of l-menthol were furthermore examined in dexamethasone-treated mice. l-Menthol also produced antinociceptive effects in the hot plate test of mice and hind paw pressure test of rats. l-Menthol showed mild surface and infiltrating anesthetic effects in guinea pigs. l-Menthol did not inhibit both carrageenin-induced paw edema of rats and the synthesis of prostaglandin E2 in vitro. Based on these findings, we proposed that l-menthol produces antinociceptive effects by activation of the endogenous opioid system and/or partially by local anesthetic actions without anti-inflammatory effects.

Administration, Topical↗

[Bone mineral density of the lumbar spine and its relation to biological and lifestyle factors in middle-aged and aged Japanese women (Part 1). Relationship of age and menopause to bone mineral density of the lumbar spine measured by dual-energy X-ray absorptiometry].

Bone mineral density (BMD) of the lumbar spine in 198 community-dwelling Japanese women aged 35 years and over was measured by dual-energy X-ray absorptiometry to investigate the effects of aging and menopause on BMD. A highly significant negative correlation between age and BMD was observed in postmenopausal women as widely accepted. We found a weak but statistically significant negative correlation between age and BMD in even premenopausal women, suggesting that their bone loss had commenced before menopause. Marked decrement in BMD was seen during the first ten years after menopause. Menopause clearly accelerated bone loss in the lumbar spine. Two-way analysis of variance of BMD on age and menopausal status showed that these explanatory variables had a significantly decreasing effect on BMD independently of each other. Menopausal status had a greater sum of squares than age, which suggested that menopause played a greater role in bone loss than did aging. Early menopause has been implied as one of the risk factors for bone loss. The women aged 50 to 59 having encountered menopause before 49 years old exhibited significantly lower BMD than those of similar age who experienced menopause at age 49 and older. This difference in BMD was not observed in the women aged 60 and over. Early menopause was no more likely to be a risk factor for bone loss in the elderly women. We conclude that bone loss in the lumbar spine begins before menopause and is accelerated markedly by menopause for about ten years, and that menopause has a greater decreasing effect on the bone mass than does chronological age while each of them has an independent effect on the bone mass decrement.

Absorptiometry, Photon↗

Pharmacokinetics of amlodipine and its occupancy of calcium antagonist receptors.

We characterized the occupancy of dihydropyridine (DHP) calcium antagonist receptors by amlodipine in spontaneously hypertensive rats (SHR) in relation to its pharmacokinetics. Oral administration of amlodipine (10 mg/kg) in SHR produced a significant (20-70%) decrease in the number of specific (+)[3H]PN 200-110 binding sites in cardiac tissues 0.5-18 h later, and the effect was greatest 3 h later. In these rats, there was little change in cerebral cortical (+)[3H]PN 200-110 binding. Occupancy of cardiac calcium antagonist receptors after oral administration of amlodipine correlated well with its plasma concentration. In vitro blockade of cardiac (+)[3H]PN 200-110 binding sites induced by amlodipine also persisted after the tissues were washed by centrifugation and suspension, whereas that induced by nifedipine was reversible under these conditions. Thus, our results suggest that the gradual onset and long-lasting pharmacologic effect of amlodipine are due to its slow binding kinetics (association and dissociation) of cardiovascular receptor sites in addition to its slow pharmacokinetics.

Amlodipine↗

A human homeobox gene, HB24, inhibits development of CD4+ T cells and impairs thymic involution in transgenic mice.

The HB24 gene encodes a diverged human homeodomain-containing protein known to be expressed in hematopoietic progenitors and activated lymphocytes. We have generated transgenic mice that express HB24 under the control of the T cell receptor beta chain promoter/enhancer. Analysis of T cells and thymocytes from the transgenic mice revealed a marked increase in activated cells as assessed by cell size profiles and interleukin-2 receptor expression. Within the thymus these changes were most pronounced in the CD4+CD8- subset. Strikingly, the normal development of CD4+ T cells in the transgenic mice was impaired. Single positive CD4 cells were reduced 35% in the thymus, and CD4+ T cells were reduced 90% in the spleen and lymph nodes compared to the controls. Similar findings were found both in young mice (6 weeks old) and in more elderly mice (1 y old). However, the thymuses of the elderly mice failed to undergo normal involution. Sera from HB24 transgenic mice had levels of IgG1 10-100-fold lower than sera from matched controls, most likely as a consequence of the decrease in CD4+ T cells. These transgenic mice provide a useful model for studying the role of HB24 in lymphocyte activation as well as for understanding the effects of abnormal T cell activation on thymic and T cell development.

Animals↗