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Biomedical subjects

Y Deguchi

Publications and source records attributed to Y Deguchi.

At least 127 records · Page 7Linked to original sources
PubMed1988

Kinetics of peritoneal drug transport in rats: an application of the pore theory of transcapillary exchange.

In order to quantitatively describe the peritoneal transport of drugs, this paper proposes a kinetic model that is based on the hydrodynamic pore theory of transcapillary exchange, and incorporates an explicit description of volume and osmolality changes in the dialysate. Sulfisoxazole (SIX) and benzoic acid (BA) were used as model compounds. Following intraperitoneal administration of dialysate in rats, the osmolality, volume, and drug concentration in the dialysate were measured with respect to time. The obtained data were analyzed to give hydrodynamic parameters for solvent and a solute (including drug) by a computer-aided curve-fitting procedure according to the differential equations derived from the model. The present method, requiring no approximation of the changes in dialysate volume, made it possible to predict the concentration profiles of BA under different initial conditions of dialysate (i.e., different osmolality and volume). Solvent drag effect contributed little to the peritoneal transport of SIX and slightly to that of BA. It was also found that the peritoneal transport of BA is blood-flow limited while that of SIX is diffusion limited.

Animals↗
PubMed1988

Peritoneal transport of beta-lactam antibiotics: effects of plasma protein binding and the interspecies relationship.

In order to examine quantitatively the effect of plasma protein binding on the peritoneal transport of beta-lactam antibiotics, we employed a kinetic model based on the pore theory of transcapillary exchange. This model incorporates the changes in the volume, osmolality, and antibiotic concentration in the dialysate, so that the apparent capillary membrane permeability (Pd) and the reflection coefficient (sigma d) of an antibiotic could be assessed. Six cephalosporins (cefatrizine, cefazolin, cefpiramide, ceftazidime, ceftriaxone, cephaloridine) were used as model compounds. While the unbound fractions of these antibiotics ranged widely from 0.08 to 0.57, including linear and nonlinear protein binding, the concentration-time profiles in plasma and the peritoneal dialysate after intravenous administration in rats could be interpreted well by our model, assuming that only the unbound antibiotic is available for the peritoneal transport. The estimated Pd values were almost the same among the drugs examined. Moreover, the Pd values of cefazolin in mice, rats, and rabbits exhibited a 0.83-power dependency on the animal body weight, indicating that Pd is significantly related to the peritoneal surface area. On the other hand, the sigma d values of cefazolin were found to be almost the same among the animal species examined. Finally, the concentration-time profile of cefazolin in the dialysate after intravenous administration in a patient with end-stage renal failure was successfully predicted using the Pd value extrapolated from those of the experimental animals.

Aged↗
PubMed1988

Interindividual changes in volume of distribution of cefazolin in newborn infants and its prediction based on physiological pharmacokinetic concepts.

The purpose of this study was to investigate factors affecting the volume of distribution of cefazolin (a beta-lactam antibiotic) in newborn infants with bacterial infections, and to propose a method for predicting the volume of distribution at steady state per body weight (Vdss/BW). Cefazolin and tobramycin (an aminoglycoside) were simultaneously given to newborn infants (aged 2 to 28 d), and plasma concentration-time data were analyzed on the basis of model-independent moment analysis. The Vdss/BW values ranged from 0.212 to 0.373 L/kg for cefazolin and from 0.384 to 0.541 L/kg for tobramycin. The unbound fraction of cefazolin in plasma (fp) fluctuated widely, from 0.22 to 0.83, among patients. The Vdss/BW value for cefazolin was characterized by both large extracellular water volume and a remarkable change in fp, and could be predicted as a function of fp using physiological pharmacokinetic concepts. Moreover, interindividual changes in the unconjugated bilirubin:albumin molar ratio were predominantly responsible for the individual variation in the fp values of cefazolin in newborn infants.

Blood Proteins↗
PubMed1988

Age-related changes of proliferative response, kinetics of expression of protooncogenes after the mitogenic stimulation and methylation level of the protooncogene in purified human lymphocyte subsets.

Proliferative responses of highly purified T and B cells from aged persons to the combined stimulation with ionomycin and PMA were more significantly reduced than that from young ones although the degree of the age-related reduction was more significant in T cells than in B cells. In B cells, the levels and kinetics of c-myc gene expression after the stimulation were comparable between aged and young groups. In T cells, the maximum level of c-myc gene expression after the stimulation was comparable between the two age groups but the rate of reduction of c-myc mRNA was significantly retarded in the aged. The results of nuclear run on transcription assay showed the reduction of the rate of c-myc mRNA degradation seemed to be the cause. The levels and kinetics of c-myb gene expression in either T or B cells were comparable between the two age groups. We further examined the level of methylation of Xho I site of c-myc gene. The level of the methylation was significantly lower in the aged T cells and more significant in aged CD 8 positive T cells although that in aged B cells was comparable to that in young ones. The relation between a reduced proliferation, a retarded rate of c-myc mRNA degradation and reduction of methylation level of c-myc gene was discussed.

Aging↗
PubMed1988

Cellular oncogene expression in the idiopathic cardiomyopathic hamster heart during the growing process.

The expression of various proto-oncogenes was evaluated in the Syrian hamster with hereditary idiopathic cardiomyopathy. mRNA from the heart and aorta of controls (BIO-RB) and cardiomyopathic hamsters (UM-X7.1 strain, BIO 14.6 line) was tested using RNA hybridization techniques. Of the 19 different v-oncogene probes used in the study, only the v-myc probe revealed a substantially greater expression of oncogene in the 30th day of cardiomyopathic hamster heart than in control hamster heart. The amplified expression of c-myc was also observed in the heart of 1-year-old, but not of 7-day-old cardiomyopathic hamster. Overexpression of c-myc, otherwise associated with the regulation of cell differentiation or rapid growth, may relate to the pathological state or pathogenesis of the hereditary cardiomyopathy.

Age Factors↗
PubMed1988

Autoantibody to human c-myc oncogene product in autoimmune patients' sera.

Sera from autoimmune diseases including systemic lupus erythematosus, dermatomyositis, progressive systemic sclerosis and Sjögren's disease, were examined for reactivity against human c-myc oncogene product. We first found the presence of the autoantibody to human c-myc oncogene product in sera from autoimmune diseases. No significant correlation between the presence of the anti-c-myc product antibody and disease activity, clinical disease types and other autoantibodies such as antinuclear factor, anti-DNA antibody, anti-RNP antibody and anti-Sm antibody were shown in this study.

Autoantibodies↗
PubMed1988

Blockade of the development of analgesic tolerance to morphine by concurrent treatment with opioid- but not non-opioid-mediated stress in mice.

Studies have been carried out to determine how the analgesic effect of morphine and the development of tolerance to the effect would be influenced by concurrent exposure to stresses in mice. Application of footshock (FS) stress, which produces analgesia mediated by opioid mu-receptors, or psychological (PSY) stress, which produces analgesia in a manner more closely related to opioid kappa-receptors, did not affect the analgesic effect of morphine, but completely blocked the development of tolerance during 5 daily concomitant treatments. On the other hand, forced swimming (SW) stress induced analgesia (SIA), which was not antagonized by naloxone, suppressed morphine analgesia, but failed to block the tolerance development. The blockade of the development of tolerance to morphine analgesia by stresses may not be attributed to the analgesic effect induced by the stresses because a combination of weak FS stress, which induces no analgesia, also effectively suppressed the development of morphine tolerance. In addition to the opioid mechanism, an adrenergic mechanism can not be excluded because of the reserpine antagonism of these SIAs.

Animals↗
PubMed1988

Proto-oncogene expression and nuclear factor specifically bound to c-myc gene in peripheral blood mononuclear cells from progressive systemic sclerosis patients as the indicator of clinical activity.

In the present study, we examined the expression of various protooncogenes and the specific binding of nuclear factor to c-myc gene in peripheral blood mononuclear cells (PBMC) from progressive systemic sclerosis (PSS) patients. We demonstrated first amplified expression of c-myc and c-myb gene and the existence of a nuclear protein specifically bound to 5'-non-coding fragment of c-myc gene. We then found a positive correlation between the degree of expression and/or affinity for the c-myc gene fragment of the nuclear protein and clinical disease activity. The amount of the factor was significantly reduced along with or prior to the amelioration of clinical symptoms and laboratory abnormalities with treatment. The significance of c-myc and c-myb proto-oncogene expression and nuclear factor specifically bound to c-myc gene is discussed.

Binding, Competitive↗
PubMed1987

c-fos expression in human skin fibroblasts by reperfusion after oxygen deficiency: a recovery change of human skin fibroblasts after oxygen deficiency stress.

A dramatic and specific induction of c-fos mRNA was observed in human skin fibroblasts in vitro culture by oxygen reperfusion after oxygen deficiency treatment. C-fos mRNA reached a maximum about 30-60 min after oxygen reperfusion and declined to basal level after 120 min. And this phenomenon was duration of oxygen deficiency-dependent, and remarkably observed for 0.5-2 hr of oxygen deficiency. More long duration of oxygen deficiency induced a decreasing tendency of c-fos mRNA overexpression due to essential and irreversible cellular damage. Thus increased c-fos gene expression might be an early event in cellular recovery process in particularly human skin fibroblasts with oxygen deficiency.

Cells, Cultured↗
PubMed1987

Heat-shock protein synthesis by human peripheral mononuclear cells from SLE patients.

Peripheral blood mononuclear cells (PBMC) from systemic lupus erythematosus (SLE) patients have heat shock protein (hsp) 70 and hsp 85 as well as the response to various temperatures of normal PBMC and are inducible for these proteins over about 5-8 levels with heat exposure in short-term culture. Synthesis of hsp 70 and hsp 85 as well as the response to various temperatures and the time course of induction were typical for mammalian cell systems. This enhancement with heat-shock treatment was blocked by actinomycin D added before heat exposure. This demonstration that hsp genes are activated in PBMC from active SLE patients without heat exposure supports the hypothesis that gene activation can serve some roles in these cells and be related to the PBMC function in SLE patients. These observations are at least correlative and consistent with a possible homeostatic function for hsps in this system.

Dactinomycin↗
PubMed1987

Methylation of c-myc gene changes in human lymphoproliferative diseases.

The degree of methylation at the c-myc proto-oncogene was found to change in human lymphoproliferative diseases, when examined using a methylation-sensitive restriction enzyme. In peripheral blood mononuclear cells (PBMC) c-myc DNA showed hypomethylation in human lymphoproliferative diseases, in comparison to normal subjects matched in age and sex. In cases of chronic lymphocytic leukemia (CLL), the change was amplified in the crisis. When the DNA was examined at the actin gene, no significant change was observed. The results suggest that the change in c-myc protooncogene methylation might become an important clue in understanding the relationship between levels of gene expression and methylation in human lymphoproliferative diseases.

DNA↗
PubMed1987

Protooncogene expression in peripheral blood mononuclear cells from patients with systemic lupus erythematosus as an indicator of the disease activity.

In the present study, we examined the various protooncogene expressions in PBMC (peripheral blood mononuclear cell) of systemic lupus erythematosus (SLE) patients to determine if they could be an indicator for the disease activity. We divided SLE patients into "very active," "active," and "remitting" states according to the clinical symptoms in addition to the laboratory data peculiar to SLE. In addition, we determined the amount of circulating immune complex (IC) as one of the representative laboratory indicators for the disease activity. We found a positive correlation with either c-myc or c-myb expression and the amounts of IC and clinical disease activity. The degree of c-myc and c-myb expression was significantly reduced along with or prior to the amelioration of clinical symptoms and improvement as determined by laboratory data under treatment with prednisolone and/or azathioprine administration. The degree of c-myc and c-myb gene expression had no direct relation to the presence of particular clinical sign(s) or autoantibody. The expression of the c-raf gene was found in SLE and other systemic autoallergic patients although it showed no correlation with the disease activity. No significant expression of c-src, c-ras, c-fos, c-fgr, c-fps, c-fes, c-fms, c-yes, c-rel, c-abl, c-mos, c-sis, and c-erb B genes was found in the patients. c-myc and c-myb expression as having pathogenic and clinical significance is discussed.

Antigen-Antibody Complex↗
PubMed1986

Occurrence of tetrodotoxin and anhydrotetrodotoxin in Vibrio sp. isolated from the intestines of a xanthid crab, Atergatis floridus.

Vibrio sp. isolated from a xanthid crab, Atergatis floridus, was cultured, and tetrodotoxin (TTX) and anhydroTTX were indicated to be present in several fractions of the cell extract and the culture medium by reverse phase HPLC. The presence of the C9-base in alkaline hydrolyzates of these fractions was confirmed by GC-MS and UV spectrometry. These results showed the production of TTX and anhydroTTX in the Vibrio sp., thus indicating one of the origins of TTX in nature.

Animals↗