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Biomedical subjects

H Yamazaki

Publications and source records attributed to H Yamazaki.

At least 289 records · Page 16Linked to original sources
PubMed1997

Relationship between glucocorticoid receptor and response to glucocorticoid therapy in ulcerative colitis.

PURPOSE: To clarify the relationship between the glucocorticoid receptor and the effectiveness of glucocorticoid therapy in patients with ulcerative colitis, we investigated the number and apparent dissociation constant of glucocorticoid receptor in peripheral blood mononuclear leukocytes of patients with ulcerative colitis. MATERIALS AND METHODS: Eleven patients with ulcerative colitis (5 who responded to intravenous glucocorticoids and 6 who did not) and ten control subjects were studied. The number and apparent dissociation constant of glucocorticoid receptor were measured using a whole-cell binding assay. Results were expressed as a median (interquartile range). RESULTS: The number of glucocorticoid receptors from the six nonresponders, five responders, and ten healthy controls were 4922 (range, 4484-5643), 3413 (range, 3183-4450), and 3610 (range, 2594-3979) binding sites/cell, respectively. The apparent dissociation constant of the glucocorticoid receptors from the nonresponders, responders, and healthy controls were 7.03 (range, 5.66-10), 4.27 (range, 4-5.13), and 6.18 (range, 5.86-6.74) nM, respectively. Nonresponders had a significant increase both in the number of binding sites and in the apparent dissociation constant compared with responders (P = 0.045; P = 0.029). CONCLUSIONS: The increased number and apparent dissociation constant of glucocorticoid receptor are closely associated with the effectiveness of glucocorticoid therapy. The measurement of the number and apparent dissociation constant of glucocorticoid receptor may be useful in predicting response to glucocorticoids.

Adult↗
PubMed1997

HDR and MDR intracavitary treatment for carcinoma of the uterine cervix. A prospective randomized study.

AIM: Treatment of carcinoma of the uterine cervix by remote afterloading brachytherapy has been accompanied with new isotopes having dose rates different from the classical low-dose rate (LDR) radium source. The dose rate conversion factor from LDR to high-dose rate (HDR) found to be around 0.54 in most studies. As regards medium-dose rate (MDR) brachytherapy, the published data are very few and the experience is still short. In this study the experience of Osaka University Hospital with micro-HDR-Selectron and Selectron-MDR, as a preliminary report of the clinical trial, is presented. PATIENTS AND METHOD: From August 1991 through April 1993, a total of 45 patients with carcinoma of the uterine cervix were randomly allocated to either microSelectron-HDR or Selectron-MDR at the Osaka University Hospital. As regards HDR, dose to point A was adjusted to 32 Gy (for stages I and II). 30 Gy/4 fractions, and 22.5 Gy/3 fractions, for stages III, and IV, respectively. The corresponding values in case of MDR were 35.6, 34 Gy/4 fractions, and 25.5 Gy/3 fractions. External irradiation, according to the stage, was the same in the 2 groups. Nucletron Planning System (NPS) was used for pre-treatment dose calculation at point A, rectal and bladder wall. The dose rate at point A ranged from 24 to 75.6 cGy/min for the HDR group, while for the MDR group ranged among 174.8 to 229.6 cGy/h. RESULTS: The 3-year survival and loco-regional control rates for both modalities were nearly equivalent (62% and 67% for HDR and 68% and 74% for MDR). The cumulative rectal and bladder complication rates were the same in both groups (29% at 3 years), with only 1 patient (MDR-group) developed grade 3 rectal and bladder complication. In this study, point A dose rate correction factor from LDR to HDR was 0.53 and 0.6 from LDR to MDR. CONCLUSIONS: From the previous reports from Osaka University Medical School, as well as others, HDR was proposed as an alternative to LDR brachytherapy for treatment of carcinoma of the uterine cervix. In this report, Selectron-MDR was nearly equivalent to the microSelectron-HDR as regards survival and loco-regional control rates as well as radiation-induced complication. This is a preliminary report, and the study still needs larger number of patients, and longer follow-up period.

Brachytherapy↗
PubMed1997

Cytochrome P450-dependent drug oxidation activities in liver microsomes of various animal species including rats, guinea pigs, dogs, monkeys, and humans.

Levels of cytochrome P450 (P450 or CYP) proteins immunoreactive to antibodies raised against human CYP1A2, 2A6, 2C9, 2E1, and 3A4, monkey CYP2B17, and rat CYP2D1 were determined in liver microsomes of rats, guinea pigs, dogs, monkeys, and humans. We also examined several drug oxidation activities catalyzed by liver microsomes of these animal species using eleven P450 substrates such as phenacetin, coumarin, pentoxyresorufin, phenytoin, S-mephenytoin, bufuralol, aniline, benzphetamine, ethylmorphine, erythromycin, and nifedipine; the activities were compared with the levels of individual P450 enzymes. Monkey liver P450 proteins were found to have relatively similar immunochemical properties by immunoblotting analysis to the human enzymes, which belong to the same P450 gene families. Mean catalytic activities (on basis of mg microsomal protein) of P450-dependent drug oxidations with eleven substrates were higher in liver microsomes of monkeys than of humans, except that humans showed much higher activities for aniline p-hydroxylation than those catalyzed by monkeys. However, when the catalytic activities of liver microsomes of monkeys and humans were compared on the basis of nmol of P450, both species gave relatively similar rates towards the oxidation of phenacetin, coumarin, pentoxyresorufin, phenytoin, mephenytoin, benzphetamine, ethylmorphine, erythromycin, and nifedipine, while the aniline p-hydroxylation was higher and bufuralol 1'-hydroxylation was lower in humans than monkeys. On the other hand, the immunochemical properties of P450 proteins and the activities of P450-dependent drug oxidation reactions in dogs, guinea pigs, and rats were somewhat different from those of monkeys and humans; the differences in these animal species varied with the P450 enzymes examined and the substrates used. The results presented in this study provide useful information towards species-related differences in susceptibilities of various animal species regarding actions and toxicities of drugs and xenobiotic chemicals.

Adrenergic beta-Antagonists↗
PubMed1997

Lack of correlation between gallbladder opacification in delayed CT and contrast-associated nephropathy.

The objective of our study was to determine the correlation between gallbladder opacification by delayed CT and contrast-associated nephropathy (CAN). Delayed CT after angiography was performed in 269 patients. Gallbladder opacification was defined when the CT value in gallbladder was more than 30 HU. Positive renal dysfunction was recognized as CAN which defined as an increase in serum creatinine level > 0.3 mg/dl and > 20 % on days 1, 3, or 7. Gallbladder opacification appeared in 154 of 269 (57 %) patients and CAN in 35 (13 %) patients. Of 117 patients without gallbladder opacification, 17 CAN (14 %) were recognized, and of 152 patients with gallbladder opacification, 18 CAN (12 %) were recognized. No significant correlation existed between delayed gallbladder opacification and CAN.

Angiography↗
PubMed1997

Induction of autocytotoxic T cells with cyclosporine and interferon-gamma for patients with non-Hodgkin's lymphoma after transplantation of peripheral blood stem cells.

BACKGROUND: Autologous graft-versus-host disease is inducible after autologous bone marrow transplantation by means of administration of cyclosporine. OBJECTIVE: This study was performed to investigate the inducibility of autologous graft-versus-host disease after transplantation of peripheral blood stem cells (PBSCs). METHODS: Two patients with non-Hodgkin's lymphoma in remission underwent PBSC transplantation followed by administration of cyclosporine and low-dose interferon-gamma. RESULTS: Although autologous graft-versus-host disease did not develop in either patient, T lymphocytes with cytotoxic activity against autologous lymphocytes appeared transiently in the early posttransplant period. Such autocytotoxic lymphocytes were not detectable in another patient who underwent PBSC transplantation who did not receive cyclosporine and interferon-gamma. When CD4+ and CD8+ cells were sorted from the peripheral blood mononuclear cells of one of the two patients and tested for cytotoxicity against autologous lymphocytes, only CD8+ cells exhibited cytotoxic activity. CONCLUSIONS: The results indicate that administration of cyclosporine and interferon-gamma after PBSC transplantation can induce autocytotoxic CD8+ T cells, even though it may not produce autologous graft-versus-host disease. It is unclear whether induction of such autocytotoxic T cells among patients with non-Hodgkin's lymphoma who undergo PBSC transplantation has any antilymphoma effect.

Adult↗
PubMed1997

Progressive effect of alpha-phenyl-N-tert-butyl nitrone (PBN) on rat embryo development in vitro.

In the present study we demonstrated the effects of the spin-trapping agent alpha-phenyl-N-tert-butylnitrone (PBN) on the in vitro development of rat embryos at the early stage. In rat embryos, PBN increased the speed of the first cleavage and had no toxicity during pregnancy after embryo culture. These results showed that reactive oxygen species (ROIs) that were formed by activating molecular oxygens through redox reactions regulated the speed of development for early-stage embryos. Thus, PBN caused a decrease in the level of ROIs and toxicity and an in increase in the level of the development of rat embryos. On the other hand, PBN could not decrease the 2-cell block in vitro nor increase the blastulation rate, in contrast to the fact that a scavenger of superoxide anions, SOD, is effective in doing so for mouse embryos. From these results it was concluded that free radicals play an important role in the in vitro development of rat embryos at the early stage, but play no role in the decrease of the 2-cell block or their blastulation rate. It should be noted that PBN had no toxicity for embryonic development at the 2-cell stage.

Animals↗
PubMed1997

Aflatoxin B1 8,9-epoxide hydrolysis in the presence of rat and human epoxide hydrolase.

Aflatoxin B1 (AFB1) must be activated to the electrophilic AFB1 exo-8,9-epoxide to be genotoxic and carcinogenic. A role for epoxide hydrolase in detoxication has been suggested but never directly addressed. In light of recent studies determining the instability of AFB1 exo-8,9-epoxide in H2O, a role for epoxide hydrolase appears dubious. Rat liver or recombinant rat epoxide hydrolase provided an enhancement to the already fast hydrolysis rate of up to 22%. Purified human epoxide hydrolase provided no detectable enhancement to the rate of chemical hydrolysis. Some reduction in the genotoxicity of AFB1 was observed when the ratio of rat epoxide hydrolase to cytochrome P450 was high (approximately 50-fold). An 80-fold excess of human epoxide hydrolase over cytochrome P450 only produced an effect of approximately 25% inhibition. It appears, therefore, that there is little evidence to support a role for epoxide hydrolase in the detoxication of AFB1.

Aflatoxin B1↗
PubMed1997

Comparison of radiobiological effective depths in 65-MeV modulated proton beams.

To assess the achievement of uniformity of radiobiological effectiveness at different depths in the proton spread-out Bragg peak (SOBP), Chinese hamster ovary (CHO) cells were exposed to 65-MeV modulated proton beams at the Research Center for Nuclear Physics (RCNP) of Osaka University. We selected four different irradiation positions: 2 mm depth, corresponding to the entrance, and 10, 18 and 23 mm depths, corresponding to different positions in the SOBP. Cell survival curves were generated with the in vitro colony formation method and fitted to the linear-quadratic model. With 137Cs gamma-rays as the reference irradiation, the relative biological effectiveness (RBE) values for a surviving fraction (SF) level of 0.1 are 1.05, 1.10, 1.12 and 1.19 for depths of 2, 10, 18 and 23 mm respectively. A significant difference was found between the survival curves at 10 and 23 mm (P < 0.05), but not between 18 and 10 mm or between 18 and 23 mm. There was a significant dependence of RBE on depths in modulated proton beams at the 0.1 surviving fraction level (P < 0.05). Moreover, the rise of RBEs significantly depended on increasing SF level or decreased approximately in correspondence with irradiation dose (P = 0.0001). To maintain uniformity of radiobiological effectiveness for the target volume, careful attention should be paid to the influence of depth of beam and irradiation dose.

Animals↗
PubMed1997

Murine P-glycoprotein on stromal vessels mediates multidrug resistance in intracerebral human glioma xenografts.

Human glioma usually shows intrinsic multidrug resistance because of the blood-brain barrier (BBB), in which membrane-associated P-glycoprotein (P-gp), encoded by the human multidrug resistance gene MDR1, plays a role. We studied drug sensitivity to vincristine (VCR), doxorubicin (DOX) and nimustine (ACNU) in both intracerebrally and subcutaneously xenotransplanted human glioma. We examined the levels of MDR1 and murine mdr3 gene expression in the xenografts by reverse transcriptase polymerase chain reaction and the localization of P-gp by immunohistochemistry. Six of seven subcutaneously transplanted xenografts (scX) were sensitive to the above three drugs. In contrast, all three intracerebrally transplanted human glioma xenografts (icX) were resistant to P-gp-mediated drugs VCR and DOX, but were sensitive to the non-P-gp-mediated drug ACNU. Neither icX nor scX showed any MDR1 expression. Intracerebrally transplanted human glioma xenografts showed an increased level of murine mdr3 gene expression, whereas scX showed only faint expression. The localization of P-gp was limited to the stromal vessels in icX by immunohistochemistry, whereas scX expressed no P-gp. Our findings suggest that the P-gp expressed on the stromal vessels in icX is a major contributing factor to multidrug resistance in human glioma in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

A wide spectrum of collagen vascular and autoimmune diseases in transgenic rats carrying the env-pX gene of human T lymphocyte virus type I.

To investigate the pathogenesis of human T lymphocyte virus type I (HTLV-I)- related diseases, the env-pX gene of HTLV-I was introduced into the germline of inbred Wistar-King-Aptekman-Hokudai rats. A wide spectrum of collagen vascular diseases was evident in the transgenic rats, including chronic destructive arthritis similar to rheumatoid arthritis, necrotizing arteritis mimicking polyarteritis nodosa, polymyositis, myocarditis, dermatitis, and chronic sialoadenitis and dacryoadenitis resembling Sjögren's syndrome in humans. Thymic atrophy with the depletion of CD4 and CD8 double-positive thymocytes was also observed. In these animals, a number of autoantibodies, including high titers of rheumatoid factor, were present in the serum. We propose that the HTLV-I env-pX gene region may play a pathogenetic role in the development of collagen vascular and autoimmune diseases associated with autoimmune phenomenon.

Animals↗
PubMed1997

Postural and gait disturbance correlated with decreased frontal cerebral blood flow in Alzheimer disease.

In a group of 45 patients with Alzheimer disease (AD) and 15 control subjects, we studied the relationship between parameters showing postural and gait disturbance and regional cerebral blood flow (rCBF) measured with N-isopropyl-p-[123I]iodoam-phetamine single photon emission computed tomography at different clinical stages. Patients with AD with mild dementia exhibited only increased postural sway associated with a reduced mean value of rCBF in the cortex. At a moderate stage, the reduced mean values of rCBF in the cortex and in the frontal lobe were associated with increased postural sway and stride length variability and with decreased stride length. At a severe stage, reduced rCBF in the basal ganglia and in the frontal lobe additionally were associated with increased postural sway, double support time, and stride length variability, and with decreased walking speed and stride length. In multiple regression analysis, there was a high contribution by rCBF in the frontal lobe to account for postural and gait disturbance in AD. We propose that impaired frontal lobe circulation is an important factor causing postural and gait disturbance as AD progresses.

Aged↗
PubMed1997

Arthroplasty for rheumatoid forefoot deformities by a shortening oblique osteotomy.

Seventy-five feet in 47 patients (46 women, 1 man) who had rheumatoid arthritis were observed for an average of 6 years (range, 4-11 years) after an operation on the forefoot that included a shortening oblique osteotomy of the metatarsal neck of the lateral toes. In addition, patients underwent either flexible hinge toe implant arthroplasty or Mitchell's osteotomy in the first metatarsophalangeal joint. Forty-two feet (56%) looked normal with no valgus or dorsal displacement of the toes. Recurrence of callosities occurred in 9 feet (12%) with moderate pain in 3 feet. Thirty-nine (83%) patients were satisfied with the outcome after surgery. Resection arthroplasty often is recommended for management of forefoot deformities. However, as shown in this series, the improvement in deformities, function, and cosmesis of metatarsophalangeal joint preservation may be better with an osteotomy of the metatarsal neck than with a resection arthroplasty. Because of the development of combined drug therapy, the benefits of synovectomy, osteotomy, and shortening in length should be reconsidered. The authors' studies suggest that the shortening oblique osteotomy should be considered 1 of the surgical reconstruction options for patients with rheumatoid arthritis who have forefoot deformities.

Adult↗
PubMed1997

Autonomic differences between athletes and nonathletes: spectral analysis approach.

The purpose of this study was to assess the adaptive effects of endurance training on autonomic function in athletes with spectral analysis of cardiovascular variability signals. Continuous ECG, arterial blood pressure (ABP), and respiratory signals were recorded from 15 athletes (VO2max > 55 mL.min-1.kg-1) and 15 nonathletes (VO2max < 45 mL.min-1.kg-1) during 10 min at sitting position. Autonomic function was assessed by low frequency power (LF power: 0.06-0.14 Hz) and high frequency power (HF power: the region of the respiratory frequency based on respiratory spectrum) obtained from the autospectra of RR interval, systolic arterial pressure (SAP), and diastolic arterial pressure (DAP) variability signals. The spontaneous baroreflex sensitivity was evaluated by the moduli, BRSLF and BRSHF, of the transfer function between RR interval and SAP variability in LF and HF bands. The resting HR in athletes was significantly lower than that in nonathletes. The HF power, an index of parasympathetic activity, in RR interval spectra were significantly higher in athletes than in nonathletes. Meanwhile, the LF power (an indicator of sympathetic activities contributing to RR interval and of ABP variabilities) showed no significant difference between both groups, although that of athletes was slightly less than that of nonathletes. Also, BRSLF and BRSHF were not significantly different between athletes and nonathletes. These results indicate that endurance training results in the enhanced vagal activities in athletes, which may contribute in part to the resting bradycardia.

Adult↗
PubMed1997

Relationship between CYP2C9 and 2C19 genotypes and tolbutamide methyl hydroxylation and S-mephenytoin 4'-hydroxylation activities in livers of Japanese and Caucasian populations.

Genomic DNA was isolated from livers of 39 Japanese and 45 Caucasians and the genotypes of CYP2C9 and 2C19 genes were determined with PCR methods using synthetic oligonucleotide primers. Liver microsomes were also prepared from these human samples and activities for tolbutamide methyl hydroxylation and S-mephenytoin 4'-hydroxylation were determined. The single base mutation of C416T (Arg144Cys) in CYP2C9 was detected in 22% of Caucasians but not in Japanese samples. Another single base mutation at A1061C (Ile359Leu) in the CYP2C9 gene was found with frequencies of about 8% in both races. We did not detect any individuals who have either homozygous Cys144/Cys144 or Leu359/Leu359 CYP2C9 variant nor both heterozygous Cys144-Ile359 and Arg144-Leu359 CYP2C9 variant in the human samples examined. The CYP2C19m2 genetic polymorphism was found only in Japanese people, while CYP2C19m1 type was determined in both races, with higher incidence in Japanese than in Caucasian population. Immunoblotting analysis of human liver microsomes suggested that CYP2C9 is a major component of the human CYP2C enzyme pool; it accounted for approximately 20% of total P450 in liver microsomes of both human populations. The levels of CYP2C19 protein were determined to be about 0.8% and 1.4% of total P450 (mean) in Japanese and Caucasians, respectively. We did not detect CYP2C19 protein in liver microsomes of humans who were genotyped for CYP2C19 gene as m1/m1, m1/m2, and m2/m2 variants but detected CYP2C9 protein in all of the samples examined. Good correlations were found between levels of CYP2C9 and activities of tolbutamide methyl hydroxylation (r = 0.77) and between levels of CYP2C19 and activities of S-mephenytoin 4'-hydroxylation (r = 0.86) in liver microsomes of the human samples examined. Tolbutamide methyl hydroxylation activities were lower in human samples with the Leu359 allele of CYP2C9 than those with the Cys144 allele and wild-type (Arg144-Ile359); the former type showed slightly higher K(m) values. When calculated on P450 basis, liver microsomes of individuals having m1/m1, m1/m2, and m2/m2 types of CYP2C19 had very low catalytic activities for S-mephenytoin 4'-hydroxylation. These results provide useful comparisons for pharmacokinetic and toxicokinetic models of some of the clinically used drugs that are oxidized by CYP2C proteins in humans.

Aryl Hydrocarbon Hydroxylases↗
PubMed1997

Effect of weight loss on body fat distribution in obese children.

The intra-abdominal visceral fat to subcutaneous fat ratio (V/S ratio) has been reported to be strongly related to disorders of glucose and lipid metabolism, and hypertension. It is a matter of concern as to whether weight loss causes an improvement of the V/S ratio or not in obese children. Changes in body fat distribution during weight loss in 23 obese children were quantified by weight, bioelectrical impedance analysis (BIA) and computed tomography (CT scan of the abdomen). Twenty-three patients were divided into two groups; six were in the inpatient group and 17 were in the outpatient group. Bodyweight, body fat percentage, subcutaneous fat and visceral fat were significantly higher in the inpatient group than in the outpatient group before weight loss. Whereas the V/S ratio was almost equal between the two groups before weight loss. Bodyweight, body fat percentage, subcutaneous fat and visceral fat were found to decrease significantly during weight loss in the two groups. The V/S ratio of the outpatient group did not change after weight loss. In contrast, the V/S ratio of the inpatient group decreased significantly during weight loss. These preliminary findings suggest that a large amount of body fat and a high obesity rate are not always accompanied by a high V/S ratio in obese children. The fat pattern changes during weight loss with strict dietary therapy and therapeutic exercise. A larger sample of obese children should be studied to test this conjecture.

Abdomen↗
PubMed1997

Magnetic resonance imaging of the cauda equina in two patients with Guillain-Barré syndrome.

The results are presented of magnetic resonance imaging (MRI) of the spine in two cases of childhood Guillain-Barré syndrome. After injection of gadolinium-diethylenetriamine pentaacetic acid, MRI showed enhancement of the cauda equina in these patients. These MRI observations may help confirm the diagnosis of Guillain-Barré syndrome. The nerve root enhancement resolved as the clinical symptoms improved. Serial imaging may be useful in monitoring the response to therapy and assessing new treatment regimens. It may also yield a better understanding of the disease process.

Cauda Equina↗
PubMed1997

A xenograft line of human teratocarcinoma established by serial transplantation in severe combined immunodeficient (SCID) mice.

We established a xenograft line of human teratocarcinoma (TC-1) and characterized the pluripotency of differentiation of the neoplastic cells. A teratocarcinoma specimen obtained from a primary mediastinal lesion (22-year-old male patient) was inoculated subcutaneously into severe combined immunodeficient (SCID) mice. The carcinoma formed tumors in the mice. We established a xenograft line by serial passage of the tumor in vivo. The primary tumor was composed of papillary and pseudoglandular nests of highly atypical epithelial cells with foci of glomeruloid structures. The metastatic cells showed apparent production of mucin and differentiation to striated muscle. The xenograft line TC-1 retained the basic histopathological features seen in the primary and metastatic cells. The xenograft line showed focal differentiation to cartilage through serial passages. Immunohistochemical studies with anti-alpha-fetoprotein (AFP) demonstrated positive immunoreactivity on the TC-1 cells. Serum AFP levels were also elevated in the TC-1-bearing SCID mice. The human teratocarcinoma xenograft line TC-1 will be useful for studying the differentiation mechanism in human totipotent stem cells.

Adult↗