Biomedical subjects

K Miyake

Publications and source records attributed to K Miyake.

At least 379 records · Page 21Linked to original sources

PubMed1992

Enantioselective pharmacokinetics of homochlorcyclizine. II: Disposition and metabolism of (+)-, (-)- and racemic homochlorcyclizine after oral administration to man.

The pharmacokinetics of a single oral dose of 20 mg (+)-, (-)- and racemic homochlorcyclizine (HCZ) have been studied in humans. The formation of the quarternary ammonium-linked glucuronide was an important metabolic pathway, and the metabolic process was enantioselective as a result of differing urinary excretion rates of (+)-, (-)- and racemic glucuronide. There were significant differences between (+)-, (-)- and racemic HCZ in AUC (0-14 h) and plasma protein binding, but all HCZ enantiomers were slowly absorbed and eliminated (elimination half-lives about 11 h). The results shows help to establish a more efficient dosage regimen for HCZ therapy.

Administration, Oral↗

PubMed1992

Superficial bladder cancer treated by total cystectomy: tumour characteristics and patient survival.

Of 113 patients with bladder cancer who underwent total cystectomy from January 1980 to December 1990, 30 (27%) had superficial tumours (pTa, pTis, and pT1). Nineteen of these 30 patients (63%) were primarily treated by total cystectomy and the remaining 11 (37%) had a past history of treatment for bladder cancer. Major reasons for choice of total cystectomy were multifocal tumours, frequent recurrence, and diffuse carcinoma in situ. Histologically stage pT1, grade 3 tumours were frequently accompanied by carcinoma in situ and often by lymphatic invasion. None of the 24 patients undergoing pelvic lymphadenectomy had lymph node metastasis. Of 25 male patients 15 (60%) underwent simultaneous prophylactic urethrectomy. Two of the remaining 10 males (20%) not undergoing this additional operation died of subsequent urethral recurrence. The 5-year actuarial survival rate was 80% for the 30 patients when all causes of death were considered. It was concluded that patients with superficial bladder cancer who undergo total cystectomy without prophylactic urethrectomy require close follow-up with urethral washings for cytology to detect early urethral recurrence, an important determinant for survival.

Adult↗

PubMed1992

Emperipolesis of lymphoid cells by human follicular dendritic cells in vitro.

Isolated follicular dendritic cells (FDCs) showed true and pseudoemperipolesis of fresh tonsillar lymphocytes, even after long-term (50-day) cultivation. Emperipolesis by FDCs was not restricted by allotype specificity, nor was it inhibited by the addition of antibodies against MHC-I & II antigens. Follicular dendritic cells predominantly engulfed B-cells; monocytes and macrophages were not found between FDC cytoplasmic extensions. When highly purified T-cell populations were added to FDC cultures emperipolesis of T-cells occurred, particularly those of the CD4-positive phenotype. Mitoses appeared within 6 h in the emperipolesed lymphocytes and, after an additional 18 h, some lymphocytes exhibited apoptosis.

Antigens, Differentiation↗

PubMed1992

Relationship of the type of bcr-abl hybrid mRNA to clinical course and transforming activity in Philadelphia-positive chronic myelogenous leukemia.

We studied the type of bcr-abl mRNA for 34 patients with chronic myelogenous leukemia and analyzed for correlations among the mRNA type, the clinical outcome and the transforming activity using the tumorigenicity assay. There was no difference in the distribution of the mRNA-types (b2-a2 and b3-a2) between clinical phases. We found no correlation between the two types of bcr-abl mRNA and the chronic phase duration or survival. The DNA from 12 of 20 chronic phase patients and all five blastic phase patients showed transforming activity. Although there was no difference in the positive rate of transforming activity among the two mRNA-type groups, the blastic phase patients showed a tendency to have higher transforming activity.

3T3 Cells↗

PubMed1992

Role of the endothelial adhesion molecule VCAM in murine cardiac allograft rejection.

Murine heterotopic cardiac isografts (C57B1/6----C57B1/6) undergo transient, non-destructive inflammation that is characterized by the acquisition of microvascular endothelial reactivity with the antibody MECA 32. Cardiac allografts (C57B1/6----DBA/2) undergo destructive inflammation that is characterized by the acquisition of reactivity with the antibody M/K-2, in addition to MECA 32. M/K-2 recognizes the murine endothelial adhesion molecule, VCAM-1. Hence, there appear to be antigen-dependent and antigen-independent forms of graft inflammation. Treatment of cardiac allograft recipients with 200 micrograms/day M/K-2 antibody retarded graft loss by only a few days, and did not interfere significantly with leukocytic infiltration, as detected by limiting dilution analysis of graft-reactive CTL, despite the fact that large amounts of M/K-2 could be detected on graft microvascular endothelia and in the peripheral blood as rejection progressed. These data indicate that VCAM is apparently not essential for the leukocytic infiltration and subsequent rejection of cardiac allografts, and is not involved in leukocytic infiltration of murine cardiac isografts.

Animals↗

PubMed1992

Blood-aqueous barrier in eyes with retinal vein occlusion.

PURPOSE: The purpose of this study is to examine the changes of blood-aqueous barrier function in cases of central or branch retinal vein occlusion. METHODS: In addition to fluorophotometry of the aqueous humor and posterior vitreous, the authors used a method that quantifies protein in the aqueous (aqueous flare) by measuring the intensity of scattered laser light. RESULTS: Aqueous and posterior vitreous fluorescein concentrations and aqueous flare were significantly higher than in unaffected fellow eyes or eyes of visually normal age-matched controls both in central and branch retinal vein occlusions. They also were significantly higher in eyes with central vein occlusion than in those with branch vein occlusion. Among those eyes with central vein occlusion, aqueous and posterior vitreous fluorescein concentrations and aqueous flare were significantly higher in the hemorrhagic than in the venous stasis type of disease. Among eyes with branch vein occlusion, cases at the acute stage showed significantly higher amounts of aqueous and posterior vitreous fluorescein concentrations and aqueous flare than did those with chronic occlusion. CONCLUSION: The authors believe that increased amounts mainly reflect blood-ocular barrier disruption. Not only the blood-retinal barrier but also the blood-aqueous barrier disruption is a common sequela in the disorder.

Aged↗

PubMed1992

Active transport system of prostaglandins: clinical implications and considerations.

We hypothesize that two factors are essential in the development of epinephrine-induced cystoid macular edema (CME): (1) the stimulation of prostaglandin synthesis by some tissues, presumably the anterior uvea by epinephrine; (2) the dysfunction of the active transport (Bito's pump) which is responsible for the removal of prostaglandins from intraocular fluids. We conducted several experimental studies to confirm these hypotheses. The results strongly suggest that epinephrine maculopathy is induced by a mechanism involving prostaglandins or, possibly, other related eicosanoids and not simply by epinephrine itself, as has been postulated. This suggests the existence of some common factors in the pathogenesis of epinephrine maculopathy and aphakic or pseudophakic CME.

Animals↗

PubMed1992

Requirement for VLA-4 and VLA-5 integrins in lymphoma cells binding to and migration beneath stromal cells in culture.

Physical interaction between human lymphomas and murine bone marrow derived stromal cells were studied. Nalm-6 pre-B cells adhered to BMS2 stromal cells and subsequently migrated beneath them, while Ramos Burkitt lymphoma cells, adhered but did not migrate. Four mAbs were established against Nalm-6 cells, which were able to block initial adhesion of Nalm-6 cells. Two of them were directed against the alpha 4 chain of VLA-4, and other two recognized the beta 1 chain of VLA integrins. Therefore, the initial adhesion of Ramos and Nalm-6 cells to BMS2 was largely mediated by the VLA-4 integrin expressed on lymphocytes. The corresponding ligand on stromal cells appears to be VCAM-1, because antibodies against murine VCAM-1 blocked the adhesion. However, antibodies against the alpha chain of VLA-4 were not capable of blocking subsequent migration beneath stromal cells. In contrast, antibodies against the beta chain of VLA integrins blocked the migration beneath stromal cells as well as the initial adhesion. Because a common beta chain can be shared among integrins, the role of other VLA integrins in Nalm-6 cells migration was investigated. VLA-5 and VLA-6 as well as VLA-4 were expressed on Nalm-6 cells, but not on Ramos cells. Additional blocking experiments revealed that VLA-4 and VLA-5 are likely to work in concert to mediate the migration of Nalm-6 cells beneath stromal cells. Thus, particular VLA integrins appear to be responsible not only for lymphocyte adhesion but also for migration with respect to stromal cells. These findings may have implications for cell-cell interactions and directed migration of lymphocytes in bone marrow and other tissues.

Animals↗

PubMed1992

Treatment of Langerhans cell histiocytosis in children with etoposide.

Ten children with Langerhans cell histiocytosis (LCH) were treated with etoposide. For five patients, this was the initial diagnosis. The other five had failed to respond to previous therapies. Etoposide (100 mg/m2) was given intravenously twice a week for 4 weeks, followed by maintenance therapy every 2 to 4 weeks for 2 years. All 10 patients responded to etoposide, and 6 of them (60%) have been in complete remission for 3 to 36 months without any side effects. One patient relapsed with diabetes insipidus, one with a soft tissue mass, and two others developed multiple bone lesions. Chemotherapy with etoposide appears to be effective and safe for the treatment of children with systemic LCH.

Adolescent↗

PubMed1992

Immunohistochemical localization of calmodulin in the human testis [corrected].

The localization of calmodulin in the normal human testis was studied by the indirect immunoperoxidase method. Three different types of fixative were used: phosphate-buffered formalin, Bouin's solution or Carnoy's solution. Immunoreactivity specific for calmodulin was not detectable in the testis fixed in Carnoy's solution. The specimens fixed in phosphate-buffered formalin and in Bouin's solution were stained. The immunostaining for calmodulin was observed in pachytene spermatocytes, secondary spermatocytes and round spermatids but not in spermatogonia, or in pre-leptotene, leptotene and zygotene spermatocytes, elongated spermatids, spermatozoa or Leydig cells. Sertoli cells were not stained or were stained slightly. Among pachytene spermatocytes, the cells at the early stage were barely stained but those at the middle and late stages were slightly and intensely stained, respectively. The present report provides the first confirmation of the localization of calmodulin in the human testis.

Adult↗

PubMed1992

Diffusion of cefmenoxime and latamoxef into prostatic fluid in the patients with acute bacterial prostatitis.

Twenty-two patients with acute bacterial prostatitis were treated with cefmenoxime (CMX) or latamoxef (LMOX), which have susceptibilities against various gram-negative bacteria. First 11 patients received a 5- to 12-day course of cefmenoxime and the next 11 received a 6- to 13-day course of latamoxef. All patients were treated successfully except 1 patient with a drug allergy. Diffusion of CMX or LMOX into prostatic fluid in these patients and healthy controls were evaluated. The mean value of CMX in the expressed prostatic fluid was 12.8 micrograms/ml in the patients receiving 2 g of CMX intravenously and 0.7 micrograms/ml in the controls. The mean value of LMOX was 14.0 micrograms/ml in the patients receiving 2 g of LMOX intravenously and 1.2 micrograms/ml in the controls. The diffusion of CMX and LMOX into prostatic fluid in the patients with acute bacterial prostatitis was strikingly higher than that of controls.

Body Fluids↗

PubMed1992

Effect of extracorporeal shockwave lithotripsy for urolithiasis on concentrations of creatine kinase isozymes in patient serum and urine.

To determine whether extracorporeal shockwave lithotripsy (ESWL) for urolithiasis causes renal injury, we immunoassayed creatine kinase isozymes (CK-B and CK-M) in serum and urine from patients with renal stone (n = 21) and ureteral stone (n = 18) before and after (0, 2, and 24 h) ESWL. CK-B is generally present in renal tissue at relatively high concentrations, whereas CK-M is found at low concentrations. CK-B and CK-M levels were enhanced both in the serum and urine samples after ESWL in both groups of patients but CK-B levels return to almost normal very rapidly. Because CK-M, which is mainly localized in muscle tissue, also increased in both groups, the increased CK-B in serum after ESWL might be derived not only from kidney but also from muscle tissues which also contain a significant level of CK-B. These results suggest that significant tissue injury, including kidney and muscles, might be caused by ESWL treatment for urolithiasis but there is no long-term renal adverse effect, and that creatine kinase isozymes in serum and urine might be useful markers of tissue injury by such treatment.

Adult↗

PubMed1992

Small hyperechoic renal tumors displaying no fat content on CT.

We report two cases of small renal adenocarcinoma and one case of small angiomyolipoma, which were identified as hyperechoic tumors by ultrasonography. None of the three tumors displayed fat content on plain CT. Since CT cannot reliably identify the intratumoral structure of small hyperechoic renal tumors, we recommend intraoperative pathological examination when CT findings do not correspond with the results of ultrasonography.

Adult↗

PubMed1992

Sustained damage to energy metabolism of brain regions after microsphere embolism in rats.

BACKGROUND AND PURPOSE: Information on sustained damage to cerebral function and metabolism after cerebral ischemia is useful for prophylaxis and therapeutics of cerebral infarction. The purpose of the present study was to induce sustained damage to brain regions after cerebral ischemia in experimental animals. For this purpose, we examined animal behavior and cerebral energy metabolism following microsphere embolism in rats. METHODS: We injected 900 microspheres (48 microns in diameter) into the right internal carotid artery of 110 rats and determined the time course of changes in the rats' behavior and the energy metabolism of the cortex, striatum, and hippocampus of both hemispheres. We injected the same volume of vehicle, without microspheres, into 28 sham-operated rats; there were 14 nonoperated control rats. RESULTS: Peak increase in lactate content and decrease in adenosine triphosphate and creatine phosphate of these brain regions of the right hemisphere were seen on the first day after microsphere embolism, whereas peak increases in glucose and glycogen contents of these regions were observed on the third day. Most of the metabolic alterations in all these regions continued for up to 28 days after operation, although they recovered toward control levels with time after the operation. The extent and trend of metabolite changes of the right hemisphere after microsphere embolism were similar in the three brain regions. In the left hemisphere, similar metabolic changes were observed, but to a lesser degree. The time course of changes in behavioral scores following microsphere embolism revealed marked stroke-like symptoms on the first day and relatively rapid disappearance of the symptoms with time after embolism. CONCLUSIONS: Microsphere embolism is capable of inducing widespread, sustained damage to energy metabolism of brain regions.

Adenosine Triphosphate↗

PubMed1992

Dangerous mixture of household detergents in an old-style toilet: a case report with simulation experiments of the working environment and warning of potential hazard relevant to the general environment.

A housewife cleaned toilet porcelain connected directly to a sewage storage tank with a mixture of cleaning agents; sodium hypochlorite (NaOCl) and hydrochloric acid (HCl) solutions. She complained of insomnia on the night after cleaning and suffered from severe metabolic acidosis with extremely low blood pH, PCO2 and bicarbonate values. She recovered from the acidosis after bicarbonate transfusion, plasmapheresis and plasma exchange. Permanent blindness ensued, however, from the third day after the event. These clinical symptoms suggested that the toxic substances responsible were chloramine and methyl chloride. Their generation was confirmed by in-vitro experiments, mixing NaOCl, HCl and pooled urine from normal people. In the simulation, the methyl chloride level far exceeded (100,000 ppm) the maximal allowable concentration recommended (ca 400 ppm) by the American Conference of Governmental Industrial Hygienists (ACGIH). Chloramine's toxic actions were confirmed using purified enzyme assay, and the inhibition of carbonic anhydrase and aldehyde dehydrogenase and the enhancement of superoxide dismutase activity were confirmed in neutral pH. The patient's clinical symptoms suggested that insomnia and permanent blindness seemed to be partly ascribable to chronic repetitive exposure to methyl chloride; catching a cold, drug intake and alcohol intake, in addition, precipitated the patient's visual loss. The possibility of this kind of intoxication with such a mixture of agents may lie latent in any situation where sewage or garbage are exposed to the open air.

Acidosis↗

PubMed1992

Pharmacokinetic analysis of amitriptyline and its demethylated metabolite in serum and brain of rats after acute and chronic oral administration of amitriptyline.

The compartmental model analysis by use of simultaneous curve fitting was carried out to ascertain the pharmacokinetic relationship between amitriptyline (AMT) and nortriptyline (NRT) in the serum and brain after acute or chronic oral administration of AMT. The estimated F value, a fraction of dose reached at systemic circulation, and the MD value, a fraction metabolized to NRT, were 0.044 and 0.020, respectively, after acute administration, indicating first-pass metabolism of AMT. The estimated parameters kin and kout, the transfer rate constants to and from the brain, showed no marked difference between AMT and NRT. These findings indicate equivalent ability of AMT and NRT to penetrate into the brain. The area under the concentration curve (AUC) values of AMT and NRT in the serum increased 1.4 and 8.2 times, respectively, with the increase of NRT being greater after chronic administration. The MD value was increased from 0.020 to 0.096, whereas the estimated F value showed no marked change. These results indicate the enhanced first-pass metabolism. The estimated transfer rate constants kin and kout of AMT were close to those of NRT. In addition, the transfer rate constants after chronic administration were similar to those after acute administration, indicating no marked change in penetration into the brain by multiple dosing.

Administration, Oral↗

PubMed1992

Pharmacokinetic interaction of zonisamide in rats. Effect of other antiepileptics on zonisamide.

The pharmacokinetics of zonisamide (ZNS) and the effects of phenobarbital (PB), valproic acid (VPA), carbamazepine (CBZ) and phenytoin (PHT) on ZNS kinetics were investigated in rats. The effects of other antiepileptics on the serum protein binding, erythrocyte distribution and metabolism of ZNS were also studied in vitro to elucidate the mechanism of pharmacokinetic interaction of ZNS. ZNS showed a linear disposition kinetics after oral administration of ZNS within the dose examined. Moreover, the pharmacokinetic behaviors of ZNS were not altered after multiple dosing. The decreased t1/2 value of ZNS by PB or CBZ pretreatment and the increased Vd/F value of ZNS by VPA pretreatment were observed, although it showed no marked effect of PHT on ZNS kinetics. The enhanced metabolism of ZNS was observed by PB or CBZ pretreatment from an in vitro metabolism study. The serum protein binding and erythrocyte distribution of ZNS showed no significant change in the presence of other antiepileptics in vitro. These results indicate that the decreased t1/2 value of ZNS is attributable to the enzyme inducing effect of PB or CBZ, and that neither protein binding nor erythrocyte distribution of ZNS could be the reason for the increased Vd/F value of ZNS by VPA coadministration.

Administration, Oral↗

PubMed1992

Method for optical resolution of racemic homochlorcyclizine and comparison of optical isomers in antihistamine activity and pharmacokinetics.

A method was developed for semi-preparative scale enantioseparation of racemic homochlorcyclizine (HCZ) by high performance liquid chromatography (HPLC) on Chiralcel OD column. The best resolution was achieved using an eluent composed of n-hexane plus 0.2 M isopropylamine. By this method, about 5.0 mg of racemic HCZ could be resolved completely in one run. The optical purity of the enantiomers were both greater than 99.9%. The studies of antihistamine activity on guinea pig ileum demonstrated that l-HCZ is significantly more potent than d- and racemic HCZ. The pharmacokinetics of d- and l-HCZ after oral administration to rats also differed. The successful resolution of racemic HCZ permits comparison of the pharmacokinetics and antihistamine activity of the enantiomers.

Animals↗