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Biomedical subjects

K Miyake

Publications and source records attributed to K Miyake.

At least 307 records · Page 17Linked to original sources
PubMed1994

In vivo induction of IgG anti-DNA antibody by autoreactive mixed haplotype A beta z/A alpha d MHC class II molecule-specific CD4+ T-cell clones.

We characterized autoreactive T-cell clones derived from (NZB x NZW)F1 (B/WF1) mice. These autoreactive T-cell clones are shown to be CD4+ by immunofluorescence staining and to belong to Th2 type by cytokine release assay. Specificity analysis revealed the existence of mixed haplotype A beta z/A alpha d major histocompatibility complex (MHC) class II molecule-specific T-cell clones as well as A beta z/A alpha z- or A beta d/A alpha d-specific T-cell clones. Some but not all of the mixed haplotype A beta z/A alpha d-specific autoreactive T-cell clones showed strong activity to induce IgG anti-DNA antibody production upon transfer to young (4-month-old) B/WF1 mice, indicating that T cells with these specificities might be involved in B/WF1 autoimmunity.

Animals↗
PubMed1994

Pharmacokinetic behavior of cyclosporine A in liver dysfunction.

The pharmacokinetic behavior of cyclosporine A (CyA), known as a potential immunosuppressive agent to prevent graft rejection in transplantation, was studied in patients with acute hepatitis and primary biliary cirrhosis (PBC). The ratios of blood concentration of total CyA (CyA and its metabolites), CyA, and CyA metabolites to dose/kg body weight, (t-CyA/dose, CyA/dose, and CyA-Met/dose, respectively) were significantly higher in patients with hepatitis than those in renal transplantation. In PBC patients these ratios showed a tendency to be smaller than those in renal transplantation, but were not significant. The ratio of CyA-Met/CyA was higher in the patients with hepatitis and PBC than that in renal transplantation. It was highest in the patients with PBC. The ratio of CyA-Met/CyA was significantly increased with a decrease of liver functions evaluated by serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and total serum bilirubin (t-Bil). These results indicate that hepatic function affects the pharmacokinetic behavior of CyA and the increased ratio of CyA-Met/dose could be caused by a possible increased efflux of metabolites into the blood circulation due to impaired bile excretion. These results also indicate the importance of therapeutic drug monitoring (TDM) in the use of CyA with patients with hepatic dysfunction.

Acute Disease↗
PubMed1994

Intraluminal content is required for the maintenance of antigrade proluminal movement of 3H-androgens into rat caput epididymal tubules.

The present study was undertaken to determine whether or not antigrade, proluminal 3H-androgen movement in the caput epididymis occurs in the absence of native lumen content. A single tubule was perfused with artificial caput fluid containing no androgen-binding protein for 30 min and subsequently tubules were perifused with Minimum Essential Medium perifusion fluid containing 26.7 microCi/ml 3H-testosterone and 1.3 microCi/ml 14C-polyethyleneglycol for 1 h. Radioactivity of isotopes in perifusion and intraluminal fluids was determined at 1 h after sustaining perifusion, and the percentage of peritubular isotopes appearing in the intraluminal fluid was determined. Net entry of 3H-androgen into the epididymal tubules in the presence of native intraluminal content was approximately 323%. In contrast, intraluminal 3H-androgen concentrations in the epididymal fluid in the absence of native lumen content were significantly reduced, to 100% of those in the peritubular fluid. Antigrade, proluminal movement of 3H-androgen in the caput epididymis does not occur in the absence of native lumen content. Androgen-binding protein in the epididymal lumen may be required to maintain uphill proluminal movement of 3H-androgen into the tubules.

Androgens↗
PubMed1994

Effects of protein synthesis inhibitor and antimicrotubular agent on transepithelial movement of 3H-androgens in the rat caput epididymis.

The effects of protein synthesis inhibition and disassembly of microtubules in the epididymal epithelia on proluminal movement of 3H-androgens were investigated by using in vivo microperifusion of 3H-testosterone and subsequent micropuncture to obtain peritubular and intraluminal fluids of caput epididymal tubules. Cycloheximide (100 micrograms/ml) was used as protein synthesis inhibitor. Nocodazole (3 micrograms/ml) was used to depolymerize microtubules in the cell. The perifusion fluid was Minimum Essential Medium containing 26.7 microCi/ml 3H-testosterone and 1.3 microCi/ml 14C-polyethyleneglycol (14C-PEG), or the same fluid supplemented with cycloheximide or nocodazole. Radioactivity of 3H-androgen and 14C-PEG in perifusion and intraluminal fluids was determined at one hour after initiation of the sustaining perifusion, and the percentage of radioactivity of 3H-androgen and 14C-PEG appearing in the intraluminal fluid to that in the peritubular fluid was determined. Proluminal movement of 3H-androgens into the caput epididymal tubules in the control rats was 323.4 +/- 73.2%. This value was significantly reduced to 121.8 +/- 13% by addition of cycloheximide to the perifusion fluid (p < 0.01). Transepithelial movement of 3H-androgen in the caput epididymis was significantly decreased to 86.6 +/- 5.3% by exposure of the epididymal tubules to nocodazole (p < 0.01). Inhibition of protein synthesis and disassembly of microtubules in the epididymal epithelial cells completely eliminated antigrade proluminal movement of 3H-androgen into the tubules. Study of the incorporation of 35S-Methionine into epididymal tissue protein revealed significant reduction of the quantity of radiolabeled proteins in the perifused tissue with fluid containing cycloheximide (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effect of albumin on proluminal movement of 3H-androgen into seminiferous and epididymal tubules and androgen binding in the interstitium of the testis and epididymis after perifusion with fluid containing albumin.

Effect of albumin on proluminal androgen movement from the peritubular space to the intratubular fluids of the adult rat testis and epididymis was examined by using in vivo microperifusion and subsequent micro-puncture of the seminiferous tubules and caput epididymal tubules. Tubules were perfused with four different fluids: (1) Minimum Essential Medium (MEM) containing 3H-testosterone and 14C-polyethyleneglycol (PEG) alone; (2) MEM + 8 mg/ml Bovine Serum Albumin (BSA) containing the same radiolabeled compounds as above; (3) MEM + 80 mg/ml albumin containing the same radiolabeled compounds as above; and (4) Testosterone-free rat serum containing the same radiolabeled compounds as above. Bound 3H-androgens in the interstitial fluids of the testis and epididymis after one-hour perifusion with the four different fluids above were measured by charcoal assay. In the testis, proluminal 3H-androgen movement was not significantly altered by addition of albumin to the perifusion fluid (p = 0.08). Bound 3H-androgens in the interstitial fluid after perifusion were significantly increased with increasing albumin concentrations in the perifusion fluid. In the caput epididymis, proluminal 3H-androgen movement was significantly decreased with increasing albumin concentration in the perifusion fluid. Bound 3H-androgens in the interstitial fluid after perifusion were significantly increased with increasing albumin concentrations in the perifusion fluid (p < 0.05). These findings suggest that proluminal transepithelial movement of 3H-androgens in the reproductive tract could be influenced by the presence of albumin, androgen-binding protein or some other binding protein in the peritubular space.

Animals↗
PubMed1994

The effect of varicocele ligation on oocyte fertilization and pregnancy after failure of fertilization in in vitro fertilization-embryo transfer.

Although varicocelectomy is generally believed to improve semen quality and the hamster egg penetration assay, these parameters do not correlate well with in vitro fertilization (IVF) success. The effect of varicocelectomy on IVF of human oocytes was examined on thirteen couples with normal female fertility, but severe oligozoospermia and the presence varicocele in the males with failure of fertilization preoperatively in in vitro fertilization-embryo of transfer (IVF-ET) attempts. The couples were readmitted for the IVF-ET procedure following varicocelectomy. A 31% pregnancy rate was achieved after the operation, while no pregnancies occurred before surgery. Sperm density and motility improved significantly after operation, resulting in a coinciding improved fertilization and pregnancy rates.

Embryo Transfer↗
PubMed1994

[Clinical trial of protocol-AL851 for children with high-risk acute lymphoblastic leukemia. Kyushu Yamaguchi Children's Cancer Study Group (KYCCSG)].

Fifty five children diagnosed as having high-risk acute lymphoblastic leukemia (ALL) between 1985 and 1988 were treated with protocol AL851. The agents used in the protocol were as follows: induction therapy: vincristine (VCR), prednisolone, daunorubicin (DNR) and l-asparaginase, consolidation therapy: an intermediate-dose methotrexate (MTX), central nervous system (CNS) leukemia prophylaxis: intrathecal MTX and 24Gy cranial irradiation, reinduction therapy: VCR, adriamycin, dexamethasone and high dose cytarabine (AraC), maintenance therapy: 6-mercaptopurine, cyclophosphamide, MTX, DNR, VCR and AraC. Patients received chemotherapy for 3 years after achieving complete remission (CR). CR was obtained in 51 patients (92.7%). Twenty-four of them relapsed after achieving CR (bone marrow 16, CNS 3 and testis 5). At median follow-up of 79 (range 64-102) months, the estimated 8-year disease free survival rate was 49.1 +/- 6.7%. Four patients relapsed at bone marrow during the first 6 months of the treatment, indicating that more intensive combination chemotherapy should be included in earlier stage of the protocol. The high incidence of testicular relapse (14.3% in boys) suggests that high-dose MTX or AraC should be needed for improvement of the prognosis of high-risk ALL patients.

Age Factors↗
PubMed1994

[Persistent müllerian duct syndrome: report of two cases].

Persistent Mullerian duct syndrome is characterized by the retention of mullerian derivatives in patients otherwise normally virilized. Clinically, the persistence of uterus and tubes leads either to cryptorchidism or inguinal hernia. The condition is usually discovered at surgery. We report two boys with this anomaly. In each case, hysterectomy and orchidopexy were carried out. The gonads were testes and the karyotype was 46, XY. Long-term follow up for these patients is necessary because of an increased risk of testicular tumors and infertility which will develop in future.

Cryptorchidism↗
PubMed1994

[Liver cirrhosis associated with alpha 1-antitrypsin deficiency].

alpha 1-antitrypsin (alpha 1-AT) is a glycoprotein called an acute phase reactant, which increases in blood in a variety of inflammations. alpha 1-AT deficiency with an inherited remarkable reduction of alpha 1-AT in blood has two major disorders, pulmonary emphysema and liver diseases, particularly an infantile cirrhosis. It is of great interest that each disorder has peculiar mechanisms based on an imbalance between proteases and protease inhibitors. alpha 1-AT constitutes genetic polymorphism of which alpha 1-AT deficiency presents rare PiZ or PiZ-like variants. alpha 1-AT deficiency is an inherited metabolic disorder associated with not only a severe reduction of alpha 1-AT in blood, but also amino acid substitutions of alpha 1-AT due to gene variations.

Adult↗
PubMed1994

[Corneal autofluorescence in eyes with branch retinal vein occlusion].

Basic studies have suggested that corneal autofluorescence, originating from flavoprotein and pyridine nucleotides, is caused by metabolically impaired corneal mitochondrial respiration. In this study, we used corneal autofluorescence as a parameter for evaluating the pathology at the corneal cell level in eyes with branch retinal vein occlusion. Unilateral branch retinal vein occlusion cases with durations of 2 months to 7 years since the onset and age-matched normal eyes were used for the study. The corneal autofluorescence was measured with a Fluorotron Master, with a special device attached to measure the anterior segment at the corneal peak. The autofluorescence was 15.6 +/- 5.8 (n = 68), 13.8 +/- 4.0 (n = 68), 14.2 +/- 3.7 (n = 14), and 14.0 +/- 3.6 (n = 14) (ng Eq/ml, mean +/- SD), respectively, in eyes with branch retinal vein occlusion, their fellow eyes, normal controls, and their fellow eyes. The affected eyes showed statistically significantly higher autofluorescence than the fellow eyes; there was no essential difference among the fellow eyes of those with branch retinal occlusion, normal controls, and their fellow eyes. The eyes with branch retinal vein occlusion, which is a focal retinal lesion, commonly exhibit corneal cellular pathologies.

Aged↗
PubMed1993

Classification of aphakic cystoid macular edema with focal macular electroretinograms.

We compared the amplitude and implicit times of the a-waves, b-waves, and oscillatory potentials of the focal macular electroretinograms of 30 eyes with aphakic cystoid macular edema and the healthy fellow eyes. Ten affected eyes were characterized by reduced amplitudes of the oscillatory potentials with normal a-wave and b-wave responses (type 1). Nine affected eyes had both reduced amplitudes of the oscillatory potentials and the b-waves (type 2). Ten affected eyes were characterized by reduced amplitude of the oscillatory potentials, the a-waves, and the b-waves (type 3). One eye could not be classified. Visual acuities were as follows: type 1, 0.55 (20/36.4); type 2, 0.31 (20/64.5); and type 3, 0.12 (20/166.7). The mean time between cataract surgery and the electroretinographic testing was significantly longer for type 2 and 3 eyes than for type 1 eyes. The differences in the electroretinographic responses between the affected eye and the normal fellow eye suggested either an increased severity or the stage of the cystoid macular edema.

Aged↗
PubMed1993

Alterations in the deleted in colorectal carcinoma gene in human primary leukemia.

To evaluate the role of the deleted in colorectal carcinoma (DCC) gene in leukemogenesis, we examined loss of heterozygosity (LOH) in the DCC gene in 64 primary human leukemias using Southern blot analysis and examined the expression of the DCC gene using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Allelic loss in the DCC gene was observed in two patients (6%, 2 of 35 informative cases), and expression of the DCC gene was reduced or absent in 8 of 26 (31%) patients with acute myelogenous leukemia (AML), 3 of 9 (33%) patients with acute lymphocytic leukemia (ALL), and 7 of 29 (24%) patients with chronic myelogenous leukemia (CML). Moreover, in one ALL patient with absent DCC expression at diagnosis, its expression became normal after performing chemotherapy and achieving remission. These findings suggest that inactivation of the DCC gene contributes to some instances of leukemogenesis.

Alleles↗
PubMed1993

Effects of naftidrofuryl oxalate on microsphere embolism-induced changes in tricarboxylic acid cycle intermediates of rats.

The present study was undertaken to determine whether naftidrofuryl oxalate, a cerebral vasodilator, may improve or attenuate microsphere embolism-induced damage to the mitochondrial tricarboxylic acid cycle. For this purpose, the intermediates in the tricarboxylic acid cycle were determined using cerebral cortex isolated from microsphere-injected rats with and without naftidrofuryl oxalate treatment. Seven-hundred microspheres, with a diameter of 48 microns were injected into the right hemisphere through the right common carotid artery. The presence of cerebral infarction on the 3rd day after the operation was confirmed by the development of triphenyltetrazolium chloride-unstained areas in brain sections. Succinate, fumarate, malate, citrate and alpha-ketoglutarate, but not oxaloacetate, contents were significantly decreased in the right hemisphere of rats on the 3rd day following microsphere embolism. In the left hemisphere, a similar but smaller decrease in these intermediates was seen. The rats, which showed typical stroke-like symptoms, were treated with 15 mg/kg naftidrofuryl oxalate i.p., twice daily for 2.5 days, resulting in a significant reversal of the intermediate content of both hemispheres toward the control and an increased in the triphenyltetrazolium-stained area of a coronal section of the right hemisphere relative to the untreated animals. The results suggest that naftidrofuryl oxalate attenuates the development of microsphere embolism-induced cerebral infarction and improves microsphere-induced impairment of the mitochondrial tricarboxylic acid cycle. The observed effects provided evidence for a possible site of action of the agent on ischemic brain energy metabolism.

Animals↗
PubMed1993

Inhibitory action of chloramine on formate-metabolizing system. Studies suggested by an unusual case record.

We previously reported on a patient exposed simultaneously to methyl chloride and chloramine gas who developed metabolic acidosis and permanent blindness [M. Minami et al., Hum Exp Toxicol 11: 27-34, 1992]. The case report suggested the possibility of potentiation of methyl chloride toxicity by chloramine. The potentiating mechanism was investigated by exposing mice to methyl chloride followed by ammonia chloramine, and then the level of formate in urine samples was measured with an enzyme coupling method to detect disturbance of formate metabolism. Mice dosed with 0.05 mL 1.0 mM chloramine after methyl chloride exposure excreted a significantly larger amount of urinary formate than mice treated with only methyl chloride. There was no difference in urinary formate levels between mice treated with only 0.05 mL 1.0 mM chloramine and those given only the vehicle (0.1 M phosphate buffer pH 6.0) for chloramine. The underlying biochemical mechanism of deterioration of formate metabolism was found to be the inhibition of the enzyme, N10-formyl tetrahydrofolate (N10-f-THF) dehydrogenase by 0.56-3.35 microM chloramine in the in vitro experiment using the purified enzyme. Positive control mice, given orally 0.1 mL 10% methanol in 0.1 M phosphate buffer (pH 6.0) excreted the same amount of urinary formate as those receiving 0.05 mL 1.0 mM chloramine after methanol administration. This was ascribed to the inhibitory effect of chloramine on formaldehyde dehydrogenase and depletion of substrate for further metabolism. The inhibition of the enzyme by chloramine (2.7-100.8 microM) was confirmed by in vitro experiments, using the purified enzyme, formaldehyde dehydrogenase.

Aldehyde Oxidoreductases↗
PubMed1993

Enantioselective pharmacokinetics of homochlorcyclizine. III. Simultaneous determination of (+)- and (-)- homochlorcyclizine in human urine by high-performance liquid chromatography.

A method is described for the simultaneous determination of (+)- and (-)-homochlorcyclizine (HCZ) in human urine by high-performance liquid chromatography on a chiral stationary phase of ovomucoid-bonded silica. The pH of the buffer and organic modifier in the mobile phase markedly affected the chromatographic separation. A mobile phase of methanol-0.02 M acetate buffer (pH 4.7) (25:75,v/v) at a flow-rate of 1.0 ml/min was used for the urine assays. The ultraviolet absorption was monitored at 240 nm, and diphenhydramine was employed as the internal standard for the quantitation. (+)-HCZ, (-)-HCZ and the internal standard were eluted at retention times of 15, 25 and 8 min, respectively. The limit of determination for HCZ enantiomers was ca. 50 ng/ml of urine. One of the metabolites in human urine, which was a quaternary ammonium-linked glucuronide, could also be determined in a manner similar to unchanged HCZ after beta-glucuronidase hydrolysis. A pharmacokinetic study was conducted with three healthy volunteers, who each received a single oral dose of racemic HCZ (20 mg). Distinct differences were found between the two enantiomers, particularly in the metabolic process, that is, the urinary excretion as (-)-HCZ-glucuronide within 48 h was ca. four times higher than that of the (+)-isomer. This method should be very useful for enantioselective pharmacokinetic studies of HCZ.

Adult↗