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Biomedical subjects

K Shimizu

Publications and source records attributed to K Shimizu.

At least 217 records · Page 12Linked to original sources
PubMed2001

[Clinical efficacy of treatment with low-dose flutamide in maximum androgen blockade therapy].

To prevent treatment withdrawal due to flutamide-induced liver dysfunction, we performed maximum androgen blockade (MAB) therapy by combining a luteinizing hormone-releasing hormone agonist or orchiectomy with low-dose flutamide (125 mg x 2/day) in patients with prostate cancer. In this study, the efficacy, adverse effects such as hepatotoxicity, and compliance were compared retrospectively between 35 patients who received low-dose flutamide therapy (1995-1999) and 27 patients who received flutamide at its ordinary dose (125 mg x 3/day). No significant difference was observed in the response rate (> or = PR) as determined from the prostate-specific antigen parameter (p = 0.6211) or the incidence of hepatotoxicity based on the aspartate aminotransferase and alanine aminotransferase levels. However, flutamide withdrawal due to liver dysfunction was less frequent in the low-dose group (2.9%) than in the ordinary dose group (18.5%) (p = 0.0386). MAB therapy using low-dose flutamide is expected to prevent the reduction in the compliance due to side effects and to improve the long-term prognosis in patients with prostate cancer, who are mostly elderly individuals.

Aged↗
PubMed2001

Treatment of glioblastoma by direct inoculation of concentrated high titer-recombinant retrovirus carrying the herpes simplex virus thymidine kinase gene.

We prepared retroviruses carrying the lacZ gene or herpes simplex virus thymidine kinase (HTK) gene with titers of 1.4-2.5 x 10(11) colony-forming units (cfu)/ml, and stereotaxically inoculated only 3 microliters of the retroviruses into a mouse glioma model. This resulted in highly efficient transduction in vivo. The transduced glioma cells migrated far from the implantation site, potentiating the induction of the remarkable bystander effect. Following repetitive ganciclovir (GCV) intraperitoneal injection, effective killing of glioma cells in the mouse brain was observed. The transduction efficiency was nearly as high as that observed for the implantation of high-titer retrovirus-producing fibroblasts. Eighty per cent of brain tumor-bearing mice were completely cured by our treatment protocol using concentrated HTK-harboring retroviruses. Our results suggest that repeated inoculations of high-titer retroviruses carrying the HTK gene followed by GCV treatment may be a promising strategy for the clinical treatment of malignant gliomas. To achieve further safety in the gene therapy of glioma, genes abundantly expressed in human glioblastoma were searched by the Serial Analysis of Gene Expression (SAGE) technique. Among the top-147 most expressed tags in glioblastoma, we found a tag, TTTTGGGTAT, originated from an unidentified gene, which was not detected in human astrocyte cultures. Real-time quantitative RT-PCR showed that MAGE-E1 expression was 2.6-15 fold enriched in glioblastoma relative to human astrocytes. Expressed Sequence Tags (ESTs) containing this tag were homologous to melanoma-associated antigen gene (MAGE) family, and this new cDNA, named MAGE-E1, was cloned by 5'-rapid amplification of cDNA ends (RACE) technique. MAGE-E1 expression was enriched in glioblastoma and low in other cancers, and MAGE-E1 expression was detected only in brain and ovary among normal tissues. These results indicate that MAGE-E1 is a novel and glioma-specific member of MAGE family, which can be applied to glioma-specific gene transduction.

Animals↗
PubMed2001

[Examination of serum nitric oxide in Yusho patients].

In order to evaluate the influence of oxidative stress by PCB, we measured serum nitric oxide (NO) in Yusho patients by the Griess method, which detected nitrite (NO2-) formed by the oxidization of NO. Serum NO2- concentrations were significantly increased in Yusho patients as compared to healthy controls, but no correlation was detected between serum NO2- concentration and PCB or PCQ level in Yusho patients. The relationship was analyzed between serum NO2- concentration and certain parameters such as clinical symptoms, habits and clinical data. Serum NO2- level had a positive correlation with CPK in male patients, but not in female and all Yusho patients. Furthermore, no mutual relation was detected between serum NO2- concentration and the other parameters such as blood pressure, smoking and each laboratory data. Therefore, the possibility is considered that Yusho is one of the diseases which show the increase of serum NO.

Female↗
PubMed2001

[A case of acute pulmonary embolism associated with squatting].

The patient was a 69-year-old man with a 3-year history of diabetes mellitus accompanied by cerebral infarction and arteriosclerosis obliterans of the lower extremities. After squatting to clean a car, the patient began to experience dyspnea. A blood gas analysis was performed upon admission, and the patient's PaCO2 and PaO2 levels were found to be low. Examination of a blood sample revealed elevated FDP, FDP-D dimer and platelet factor 4 levels. A perfusion lung scan showed multiple defects in both lungs, but no abnormal findings were detected on a ventilation scan. A pulmonary angiogram showed an interrupted blood flow in branches A9 + 10 of the left pulmonary artery. Accordingly, a pulmonary embolism was diagnosed. Squatting may have caused a partial obstruction of the venous return from the lower extremities by compression of the inguinal region and may have been a predisposing cause of the thrombosis. To our knowledge, such cases of pulmonary embolism triggered by the act of squatting are very rare.

Acute Disease↗
PubMed2001

[A case report of rectal cancer with liver and pulmonary metastases responding to TS-1].

TS-1 is an oral anticancer drug that produces biochemical modulation. TS-1 is composed of FT (tegafur), CDHP (gimestat), and Oxo (ostat potassium), in a molar ratio of 1:0.4:1. We administered TS-1 to a patient with liver and pulmonary metastasis of rectal cancer (phase II study). Each treatment course consisted of a four-week administration followed by two drug-free weeks. The daily dose was 120-150 mg/day. Before the administration, hepatic metastasis was 30 x 20 mm. After 2 courses, it was reduced to 20 x 15 mm (reduction rate: 50%). Three pulmonary metastases that were recognized in chest radiographs before the administration tended to reduction after 3 courses. The reduction rate after 4 courses was 42.5%. The reduction was judged PR for the hepatic metastasis and MR for pulmonary metastases. There was no side effect and hospitalization was not required during the treatment. Thus, the administration of TS-1 enhanced the quality of life of this patient.

Adenocarcinoma↗
PubMed2001

[Dynamic variance of intracellular metabolic energies under rhythmical control for dissolved oxygen in PHB mixed cultivation].

The mixed cultivation using cheaper carbon source-wasted food material contained glucose and lactate at the same time was conducted in 5L fermentor, within which glucose was converted to lactate by L. delbrueckii in anaerobic condition and the lactate was converted to PHB by R. eutropha in aerobic condition. Considering dissolved oxygen concentration may affect the level of intracellular ATP and NADPH of the metabolic pathways for R. eutropha in lactate under autotrophy or heterotrophy, rhythmical oscillated control for DO based on chaos control method was consequently presented. This method was employed to satisfy two strains for opposite oxygen preferences, moreover, excite the intracellular metabolic energy simultaneously. The values examined through spectrophotofluorimetry represented that both ATP and NADPH exhibited fluctuations in accordance with the DO rhythm. By means of this control design, the concentration of PHB can be doubled than the usual under stable DO control.

3-Hydroxybutyric Acid↗
PubMed2001

Antitumor efficacy in vitro and in vivo of falconensones, a new type of polyene.

Falconensones A and B are new type of yellow pigment isolated from the mycelial extract of ascomycetous fungi, Emericella falconensis. To date, these falconensones and their derivatives, falconensone A p-bromophenylhydrazone and falconensone A dioxime are known to exhibit biological activities, which include growth inhibition and both induction of differentiation and apoptosis of HL60 human leukemia cells. The synthetic derivatives have been shown to be more potent than natural falconensone A and B in eliciting these activities. Herein, we investigate whether falconensones inhibit growth of other cancer cell lines in vitro, and we evaluate their ability to modify survival in C57 BL/6J mice using M5076 murine reticulosarcoma in vivo, which is established as the metastasis model. Falconensone A, falconensone A p-bromophenylhydrazone, and falconensone A dioxime inhibit growth of human myeloid leukemia cell lines, HL60 and HL60R, human hepatoma cell line HepG2, human prostate cancer cell line DU-145, and human breast cancer cell line MCF-7/Adr(R), whereas falconensone B, the 4'-nor-methyl derivative of falconensone A, shows extremely low or no activity. In contrast, all of the falconensones are active in growth inhibition of human breast cancer cell line MCF-7. Survival time of M5076-implanted mice was prolonged by treatment with falconensones, particularly falconensone A dioxime. These results indicate that falconensone A and its derivatives exhibit anticancer efficacy in a broad spectrum of cancer cell lines. These agents may have great potential for clinical use in the treatment of various cancers.

Animals↗
PubMed2001

[Chemotherapy (low-dose CDDP + UFT) to advanced pancreatic cancer in an ambulatory setting improved survival and quality of life].

The prognosis of pancreatic cancer is very poor. Past attempts to treat advanced pancreatic cancer with single agent or combination chemotherapy have yielded low response rates and little reproducible impact on patient survival or quality of life. We performed systemic chemotherapy in case of unresectable or recurrent pancreatic cancer with CDDP 25 mg/body intravenous weekly or biweekly and oral administration of UFT (300-400 mg/day) as an outpatient treatment. Tumor markers were well controlled for about over one year or more. This ambulatory combination is a well-tolerated regimen that results in improved survival and quality of life.

Ambulatory Care↗
PubMed2001

[Four cases of multiple liver metastasis of colorectal cancer treated with hepatic resection after chemotherapy].

Four cases of multiple liver metastasis of colorectal cancer treated with hepatic resection after chemotherapy were investigated. The 4 patients consisted of 3 males and 1 female with a mean age of 67.8 years. Two patients underwent systemic chemotherapy, and the other 2 received hepatic arterial infusion chemotherapy. The effect was PR in all patients, and mean duration until resection was 8.5 months. One patient had lung metastasis and one had recurrence in a local lesion and residual liver after hepatic resection, but all patients remain alive. The longest survival periods in 4 patients who underwent hepatic resection and 13 who did not were 32 and 24 months, respectively. It is suggested that hepatic resection after chemotherapy for multiple liver metastasis of colorectal cancer may be useful for improvement of outcome.

Aged↗
PubMed2001

[Underestimation of intraocular pressure after laser in situ keratomileusis].

PURPOSE: We reviewed 115 eyes of 65 patients regarding the intraocular pressure(IOP) following laser in situ keratomileusis(LASIK). PATIENTS AND METHODS: The ages averaged 31.2 +/- 10.5(mean +/- standard deviation) years. The preoperative spherical equivalent averaged -6.85 +/- 2.54 (mean +/- standard deviation) D. A noncontact pneumatic tonometer and Goldmann applanation tonometer were used in measuring the IOP. RESULTS: The IOP difference before and after surgery was statistically significant(Mann-Whitney U test). The IOP was significantly corrected with the corrected diopter value, corneal thickness, and corneal curvature(Spearman coefficient by rank). CONCLUSION: The findings show that postoperative IOP may be underestimated due to decreased corneal thickness and curvature. Due attention has to be paid to this feature in evaluating IOP after LASIK.

Adult↗
PubMed2001

[The role of MN/CA IX antigen in carcinogenesis and metastasis of renal cell carcinoma].

MN/CA IX is a carbonic anhydrase (CA) isoenzyme expressed in normal alimentary tract in a tissue-specific manner. This antigen is activated in the majority of renal cell carcinomas (RCC) but not in normal kidney tissues. Although the exact role of CA activity in carcinogenesis and metastasis has not been established, MN/CA9 has been suggested to be implicated in acidification of extracellular milieu surrounding the cancer cells and thus create a microenvironment conductive to tumor growth and spread. Mutations in the von Hippel-Lindau (VHL) gene cause the familial syndrome and are also found in the majority of sporadic RCC. Wild-type VHL was recently described to down-regulate MN/CA9 in RCC cell lines, and the molecular mechanism of MN/CA9 and VHL in renal carcinogenesis is of interest. To investigate the mechanism of MN/CA9 activation in RCC, we examined the methylation status of this gene in RCC cell lines and human tissue samples and found that hypomethylation in the promoter region may play an important role in the expression of MN/CA9. RT-PCR analysis of blood samples from RCC patients revealed the presence of circulating MN-positive cells in the blood. This antigen may be a potential therapeutic target as well as diagnostic marker for RCC. Therefore, we are currently investigating whether or not MN/CA IX peptide could be an appropriate molecule for use antigen specific immunotherapy on RCC patients.

Antigens, Neoplasm↗
PubMed2001

Estimation of bidirectional metabolic fluxes from MS and NMR data using positional representations.

It is quite important to estimate the metabolic flux distribution (MFD) vectors in vivo, and to investigate the effect of culture environments on the flux distributions to uncover the metabolic regulation mechanism of microbial cells. The conventional approach is to compute the MFD using the stoichiometric equations and the measured specific rates (input and output variables). However, this method cannot give the MFD for the complex metabolic network which includes cyclic pathways. In the present investigation, we considered the method of analysing the metabolic fluxes based on 13C tracer experiments. In particular, we compared the different techniques of estimating the bidirectional fluxes in the metabolic networks, studying their applicability with respect to the different types of data formats obtained through GC-MS (gas chromatography-mass spectrometry) and NMR (nuclear magnetic resonance) measurements in labeling experiments. It was found that some techniques cannot be applied for GC-MS and NMR data. In the present research, therefore, a new preprocessing method for MS and NMR data was developed, to solve some of the problems encountered in the conventional approaches.

Carbon Isotopes↗
PubMed2001

[Effect of ATP-sensitive K+ channel blocker (quinine) on the dopamine decrease induced by selective D3 agonist (7-OH-DPAT) in the rat striatum].

In vivo brain microdialysis was used to investigate the role of D3 receptors relating to dopamine auto-regulated systems in the rat. A local infusion of the dopamine D3 selective agonist, 7-OH-DPAT (100 nM), into the striatum through the dialysis membrane produced a significant decrease in extracellular concentrations of dopamine. A local application of ATP-sensitive K+ (KATP) channel blocker, quinine (10 microM, 100 microM, 1 mM), produced dose-dependent increases in extracellular concentrations of dopamine. Quinine (100 microM, 1 mM) significantly blocked a 7-OH-DPAT-induced decrease in the striatal dopamine levels in the dose-dependent manner. Because of many previous reports, the autoregulated functions of dopamine release by D3 receptors in the striatum can be regarded mainly as nerve terminal autoreceptors and/or a short-loop negative feedback system. Therefore these results suggest that KATP channels may be present in nigrostriatal dopaminergic terminals and that in the striatum, presynaptic dopamine D3 autoreceptors and/or a post-synaptic D3 related short-loop negative feedback system inhibit dopamine release tonically by the activation of KATP channels.

Adenosine Triphosphate↗
PubMed2001

Lipid extracted freeze-dried bank bone sterilized with low temperature plasma.

Ethylene oxide gas (EOG) is widely used for sterilization of freeze-dried bone. Recently EOG is regulated for clinical use because of cytotoxicity and environmental pollution concerns. Low Temperature Plasma Sterilization (LTPS) has no toxicity and mutagenicity working with a hydrogen peroxide gas plasma at 45 degrees centigrade. We have now used this method experimentally and clinically to sterilize freeze-dried bone. Cortical bone with a thickness of 5 mm and cancellous bone with a 10 mm cubic size were prepared, washed, defatted, dehydrated by freeze drying and finally sterilized by LTPS. As a Microbiological test, defatted freeze-dried bone was contaminated with B. subtilis, and after then the contaminated bone was treated with LTPS and the bacteria was proven inactive. Mechanical testing on rabbit cortical bone was investigated by compression testing using a mechanical testing machine. No differences between EOG treated and LTPS treated bone were found. From December 1996, 52 patients who had small and middle bone defects were treated with defatted, freeze-dried and LTPS sterilized bone. Clinical result was good. No deep infections, no transmission of virus infections or severe graft absorption were noted. The LTPS bank bone is safe and useful to reconstruction to small bone defects.

Bone Banks↗