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Biomedical subjects

S Hori

Publications and source records attributed to S Hori.

At least 163 records · Page 9Linked to original sources

Pharmacokinetics of anticancer drugs in cerebrospinal fluid.

OBJECTIVE: To examine the pharmacokinetics of anticancer drugs in the cerebrospinal fluid (CSF) during chemotherapy by the lumbar-ventricular (LV) and ventricular-lumbar (VL) routes. CASE SUMMARY: A 69-year-old Japanese woman with disseminated glioblastoma received two LV and four VL courses of CSF perfusion chemotherapy with methotrexate, nimustine, and cytarabine hydrochloride. Samples of CSF from the ventricles and lumbar spinal canal were obtained via Ommaya reservoirs during one LV and one VL course. Drug concentrations in the CSF were measured by fluorescence polarization immunoassay or HPLC. RESULTS: During LV CSF perfusion, the highest CSF drug concentrations in both the ventricles and the lumbar spinal canal were observed at the end of perfusion. During treatment, the concentrations of all three drugs in the lumbar spinal canal were higher than those in the ventricles. The CSF AUC of methotrexate in the ventricles was 16.1% of that in the lumbar spinal canal. During VL CSF perfusion, the highest drug concentrations were also observed at the end of perfusion. The drug concentrations in the lumbar spinal canal were initially lower than those in the ventricles. However, the concentrations of methotrexate and cytarabine in the lumbar spinal canal exceeded those in the ventricles 3 hours after perfusion. The AUC of methotrexate in the lumbar spinal canal was 174.9% of that in the ventricles. CONCLUSIONS: The pharmacokinetics of anticancer drugs in ventricular CSF differ from those in lumbar CSF during LV and VL perfusion chemotherapy.

Aged↗

Adaptive changes in the thermogenesis of rats by cold acclimation and deacclimation.

Male Wistar rats, aged 6 weeks, were maintained at 25 degreesC for 9 to 11 weeks (W group), at 10 degreesC for 9 to 11 weeks (C group), and at 25 degreesC for 2 weeks after exposure to 10 degreesC for 9 weeks (D group). Thermogenesis at 10 degreesC was significantly greater than at 25 degreesC. Thermogenesis per body mass in the C group was greater than in the W and D groups. The RQ value at 10 degreesC was greater than at 25 degreesC in the W group, whereas the opposite was observed in the C and D groups. It is suggested that a large part of enhanced thermogenesis, caused by cold acclimation for 9 weeks, is lost because of a decreased secretion of calorigenic hormones, in spite of a slight decrease in BAT mass, during deacclimation for 2 weeks.

Adaptation, Physiological↗

Third ventricular neuroepithelial cyst originating from the massa intermedia--case report.

A 47-year-old female presented with a 3-year history of progressive emotional disturbance. Computed tomography and magnetic resonance imaging revealed a cyst in the third ventricle causing hydrocephalus. Endoscopic surgery found the cyst originated at the massa intermedia. Histological examination confirmed the diagnosis of neuroepithelial cyst. Neuroepithelial cyst originating from the massa intermedia may be due to persistence of neuroepithelial crest at this location.

Cerebral Ventricles↗

[Evaluation of a new anti-cancer drug regimen for endometrial cancer].

BACKGROUND: The purpose of this study was to describe a new anti-cancer drug regimen for endometrial cancer. METHODS: The cytotoxicities of some anti-cancer drugs regimens against human endometrial cancer xenografted into nude mice (TEI, TET, TEU, TEN) have been studied. The activities of ADM, CDDP, CPM, CPT-11, TXL, CDDP + ADM, CDDP + CPM, CDDP + CPT-11, CDDP + TXL, CPT-11 + TXL were evaluated in comparison with a control group using saline. Three mice were used for each group, and when xenografted tumor reached 6 mm of its diameter, 1/5 LD50 of these drugs was administered into the periotoneal cavity mice once a week for three weeks. RESULTS: The effective regimens were CPT-11 + TXL, CDDP + CPT-11, CDDP + CPM, CDDP + TXL for the endometrial cancer. CONCLUSIONS: It is suggested that these new drugs regimens should be tested in clinical studies.

Animals↗

[The present status of ophthalmological management for diabetics].

A questionnaire regarding management of patients with diabetes was mailed to 315 ophthalmologists. The status of ophthalmological management at the hospitals and clinics was investigated. The return rate of questionnaires was 73%. The problems at the clinics were 1. many cases have ophthalmological symptoms at the first ophthalmological examination (longer time from the onset of diabetes to the first ophthalmological examination), 2. appropriate cooperation between ophthalmology and internal medicine is lacking, 3. the collection of information on blood glucose control level is difficult, and 4. there is not enough consultation by appointment. The common problems to both hospitals and clinics were 1. satisfactory measures are not taken regarding dropout ophthalmology patients, and 2. a system of patient education does not exist. There is a pressing need for comprehensive measures to be taken by medical association leaders and medical administrators to settle these problems.

Adult↗

[Evaluation of a new anti-cancer drug regimen for surface epithelial-stromal ovarian cancer].

BACKGROUND: The purpose of this study was to describe a new anti-cancer drug regimen for epithelial ovarian cancer. METHODS: The cytotoxicities of some anti-cancer drugs regimens against human epithelial ovarian cancer xenografted into nude mice (TOM, TOH, TON) have been studied. The activities of CDDP, CPT-11, TXL, CDDP + CPM, CDDP + CPT-11, CDDP + TXL, CPT-11 + CPM, CPT-11 + TXL, and TXL + CPM were evaluated comparing with a control group using saline. Three mice were used for each group, and when the xenografted tumor reached 6 mm in diameter, 1/5 LD50 of these drugs was administered into the peritoneal cavity of mice once a week for three weeks. RESULTS: The three most effective regimens were CPT-11 + TXL, CDDP + CPM, and CDDP + CPT-11 for epithelial ovarian cancer.

Adenoma↗

Dietary balance chart for an on-line computerized graphical support system in MHTS.

Dietary habits are believed to play an important role in the etiology of adult disease. For this reason, it is necessary to include effective dietary guidance in multiphasic health testing and services (MHTS) programmes for primary disease prevention. We have developed such a programme of simple dietary advice, using a computer system for the MHTS. Examinees' dietary habits are checked using optical character record (OCR) questionnaire forms, and the results are displayed on the screen of a colour display terminal. They are required to prepare a menu of their usual daily dietary intake in terms of quantity and type of food. Thus the data collected relate to the nutritional composition of the examinee's usual diet. Nutritional requirements of the Japanese according to sex, height, and level of physical activity, in accordance with criteria set by the Japanese Ministry of Health and Welfare, are fed into the computer in advance. For each examinee, these criteria and the results of the assessment of the diet are displayed together on the screen in the form of colour graphs for comparison.

Adult↗

Coexistence of proguanylin (1-15) and somatostatin in the gastrointestinal tract.

In order to identify proguanylin-secreting cells, we have raised an antiserum against the synthetic fragment of human proguanylin (1-15) and have examined the proguanylin-positive cells in the human and rat gastrointestinal tract by immunohistochemical methods. Numerous proguanylin (1-15)-immunoreactive cells were found in the gastrointestinal tract. They were either pyramidal or spindle shaped in the stomach. Spindle-shaped cells, frequently possessing long slender processes, were located at the base of the pyloric epithelium and did not extend to the lumen. In the duodenum and jejunum, these cells were mostly pyramidal in shape and often had a slender process towards the lumen. The immunostaining was completely blocked by the human proguanylin (1-15) fragment. Paneth and goblet cells were negative against this antiserum. The number of serotonin-positive cells was much larger than that of proguanylin-positive cells in all the segments tested. The number of proguanylin-positive cells decreased from the jejunum to the ileum and very few cells were observed in the colon. In contrast to serotonin-positive cells, most somatostatin-positive cells were also positive for proguanylin. Thus, proguanylin (1-15) or its related protein appears to coexist with somatostatin in intestinal endocrine D cells which may be a source of circulating proguanylin. Proguanylin, like somatostatin, may also regulate intestinal function as a local regulator.

Animals↗

Dissemination in Japanese hospitals of strains of Staphylococcus aureus heterogeneously resistant to vancomycin.

BACKGROUND: Since the discovery of the vancomycin-resistant Staphylococcus aureus (VRSA) strain Mu50 (minimum inhibitory concentration [MIC] 8 mg/L), there has been concern about the potential spread of such strains throughout Japanese hospitals. Two important questions need to be answered: (1) what is the prevalence of VRSA, and (2) by what mechanism does vancomycin resistance occur. METHODS: The vancomycin susceptibilities of three methicillin-resistant S aureus (MRSA) strains (Mu50, Mu3, and H1) and the methicillin-susceptible S aureus type strain FDA209P were compared by MIC determinations and population analysis. Mu3 (MIC 3 mg/L) was isolated from the sputum of a patient with pneumonia after surgery who had failed vancomycin therapy. H1 (MIC 2 mg/L), which is a representative vancomycin-susceptible MRSA strain, was isolated from a patient with pneumonia who responded favourably to vancomycin therapy. Subclones of Mu3 with increased resistance against vancomycin were selected with serial concentrations of vancomycin and their MICs were determined. The prevalence of VRSA and Mu3-like strains in Japanese hospitals was estimated by population analysis from 1149 clinical MRSA isolates obtained from 203 hospitals throughout Japan. The genetic traits of the Mu3 and Mu50 strains were compared with clonotypes of MRSA from around the world. FINDINGS: Mu3 and Mu50 had an identical pulsed-field gel electrophoresis banding pattern. When grown in a drug-free medium, Mu3 produced subpopulation of cells with varying degrees of vancomycin resistance, thus demonstrating natural heterogeneity, or variability, in susceptibility to vancomycin. In the presence of vancomycin, Mu3 produced subclones with resistance roughly proportional to the concentrations of vancomycin used. Selection of Mu3 with 8 mg/L or more of vancomycin gave rise to subclones with vancomycin resistance equal to that of Mu50 (MIC 8 mg/L) at a frequency of 1/1,000,000. During screening of Japanese MRSA strains, no strain of VRSA additional to Mu50 was found. The prevalence of MRSA isolates heterogeneously resistant to vancomycin was 20% in Juntendo University Hospital, 9.3% in the other seven university hospitals, and 1.3% in non-university hospitals or clinics. INTERPRETATION: Heterogeneously resistant VRSA is a preliminary stage that allows development into VRSA upon exposure to vancomycin. Heterogeneously resistant VRSA was found in hospitals throughout Japan. This finding could explain, at least partly, the frequent therapeutic failure of MRSA infection with vancomycin in Japan.

Aged↗

Monoclonal antibodies against pupa-specific surface antigens of Sarcophaga peregrina (flesh fly) hemocytes.

Monoclonal antibodies were raised against pupal hemocytes of Sarcophaga peregrina. Four of the antibodies tested bound specifically to the surface of live pupal hemocytes, and these hemocytes appeared to be granulocytes from their morphology. The antigen recognized by one of the antibodies, MAb 9C8, was considered to be a membrane protein with a molecular mass of 120-kDa. Another antibody, MAb 9F3, was found to recognize possibly the same 120-kDa protein and two cytoplasmic proteins commonly present in both pupal and larval hemocytes.

Animals↗

Hepatoprotective effect of a nonselective endothelin receptor antagonist (TAK-044) in the transplanted liver.

This study was designed to investigate whether or not a novel nonselective endothelin A/B (ETA/ETB) receptor antagonist (TAK-044) provides hepatoprotection during porcine liver transplantation. The grafts were stored in chilled Euro-Collins solution and recirculated following reflush with lactated Ringer's with (TAK group) or without (control group) TAK-044 (10 mg/kg). Intracellular (cytoplasma, mitochondria, and nucleus) calcium (Ca) concentrations were measured in the hepatic biopsy materials obtained serially at varying time point from donor laparotomy to recipient closure using an electron probe X-ray microanalyzer. Liver function tests also were determined. The cold and warm ischemia times of the grafts were comparable between the two groups. The peak endothelin-1 T-1) concentration after recirculation was significantly higher in the TAK group than in the control group (129 +/- 30 pg/ml vs 26 +/- 6.5 pg/ml). However, release of liver enzymes, increases in total bile acid, and deterioration of indocyanine green retention rate were significantly suppressed in the TAK group. In the control group, the intracellular Ca concentrations, especially in the mitochondrial fraction, were elevated markedly following recirculation of the hepatic arterial flow. In the TAK group, this effect was suppressed. Thus, the supplementary use of the nonselective ETA/ETB receptor antagonist TAK-044 via a rinse route may alleviate an early postreperfusion microcirculatory disturbance of the liver grafts without adverse effects by the increased ET-1 on the systemic circulation.

Animals↗

Effect of graft preservation and IgM depletion on guinea pig to rat cardiac xenograft survival.

BACKGROUND: Heterotopic guinea pig (GP) cardiac xenografts (XG) are hyperacutely rejected within minutes when transplanted into rats. METHODS: In this GP to rat cardiac XG model, we studied the effect on graft survival of a short cold preservation time (1 hr at 4 degrees C) in the presence or absence of rat anti-GP IgM preformed antibodies. The complete depletion of circulating IgM was obtained by two intraperitoneal injections of anti-rat IgM monoclonal antibody (MARM-4) on preoperative days -3 and -1. RESULTS: When the GP cardiac XG was cold preserved for 1 hr before transplantation, the mean graft survival time (MST) was 13.5+/-2.8 min, whereas without previous cold preservation, the MST was significantly prolonged to 51.5+/-12.3 min (P<0.001). Interestingly, the complete depletion of preformed circulating IgM before grafting significantly prolonged the MST of a cold-preserved XG to 37.1+/-11.3 min in comparison with a nondepleted recipient of a cold-preserved XG (P<0.02), but did not prolong the graft survival of a XG that was not cold preserved (42.5+/-14.1 min). To assess the effect of cold preservation and/or ischemia reperfusion, we intravenously injected a superoxide-dismutase mimetic (EUK-134) just before transplantation of a cold-preserved XG. This antioxidant regimen improved the MST from 13.5+/-2.8 min to 35.3+/-7.3 min (P<0.001). These results clearly suggested that either preservation lesions or preformed IgM are capable of accelerating the loss of the cardiac graft function, but also that the presence of preformed IgM seems to be especially deleterious when the cardiac XG has previously been ischemically injured. Analyzing the histological data, we also observed that the prompt cessation of cardiac function seen in cold-preserved grafts was uniformly associated with massive interstitial hemorrhage, thereby suggesting a particular susceptibility of the GP cardiac XG to cold preservation. To assess the effect of preservation on the GP cardiac function in a nonimmunological model, we performed syngeneic GP cardiac grafts and found that 1 hr of cold preservation provoked massive interstitial hemorrhage capable of promptly inducing the cessation of the heartbeat. CONCLUSIONS: Overall, this study demonstrated that both ischemic lesions and immunological processes might induce the cessation of cardiac graft function in the GP to rat model and this cessation of graft function is probably often misinterpreted as a XG rejection only.

Animals↗

Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1.

Extracellular levels of the excitatory neurotransmitter glutamate in the nervous system are maintained by transporters that actively remove glutamate from the extracellular space. Homozygous mice deficient in GLT-1, a widely distributed astrocytic glutamate transporter, show lethal spontaneous seizures and increased susceptibility to acute cortical injury. These effects can be attributed to elevated levels of residual glutamate in the brains of these mice.

ATP-Binding Cassette Transporters↗