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Biomedical subjects

T Baba

Publications and source records attributed to T Baba.

At least 19 recordsLinked to original sources
PubMed2006

A successful IVF-pregnancy in a patient who underwent conservative surgery followed by a regimen of cisplatin, vinblastine and peplomycin to treat an advanced ovarian mixed germ cell tumour: a case report.

Mixed germ cell tumours of the ovary, one type of malignant ovarian germ cell tumours (MOGCTs), are rare gynaecologic cancers usually affecting young women. We report the case of a patient with an advanced ovarian mixed germ cell tumour who underwent fertility-saving surgery followed by a chemotherapy regimen of cisplatin, vinblastine and peplomycin. The patient was disease-free 8 years after initial presentation. She conceived and gestated dichorionic twins after IVF-embryo transfer. To the best of our knowledge, the patient is the first to be treated successfully with the combination chemotherapy regimen and then conceive safely using assisted reproductive technology (ART).

Adult↗
PubMed2006

Application of in vivo cryotechnique to the examination of cells and tissues in living animal organs.

When all biological materials in cells and tissues of living animal organs are quickly and promptly frozen, immunolocalization of their components and structural features in situ is necessary to understand their in vivo functioning states. However, these direct morphological analyses were difficult to achieve by conventional chemical fixation methods during the last century. A new cryofixation method, named the "in vivo cryotechnique", in which the normal blood circulation in living animals is always retained at the moment of freezing, has become a powerful tool to visualize the real native morphology of cells and tissues with functional meaning. The "in vivo cryotechnique" can usually be combined with a wide range of subsequent preparation techniques, and can thereby enable us to perform various direct analyses on biological samples, reflecting the physiological functions of living animal organs.

Animals↗
PubMed2006

Immunohistochemical study of serum albumin in normal and cadmium-treated mouse testis organs by "in vivo cryotechnique".

The in vivo injection of cadmium (Cd) was reported to induce blood-testis barrier disruption, and assumed to be an experimental model to examine junctional structures in seminiferous tubules. The purpose of this study is to investigate time-dependent changes of albumin permeability in the normal or Cd-treated mouse testis by our "in vivo cryotechnique" with immunohistochemistry, reflecting tight junctional (TJ) barriers of Sertoli cells. The albumin in the seminiferous tubules was firstly immobilized by the cryotechnique, in which normal blood circulation was always kept. The cryofixed testicular tissues were then processed for freeze-substitution, and embedded in the paraffin wax. Serial sections were immunostained by anti-mouse albumin antibody with peroxidase immunostaining, and also stained with hematoxylin-eosine (HE) for morphological observation. In normal seminiferous tubules, the immunoreaction products were localized around peritubular myoid cells and between Leydig cells, as well as in blood vessels. They were also localized as arch-like patterns around some spermatogonia in basal compartments of seminiferous tubules. Twenty-four and 48 hrs after Cd-treatment, some enlarged spaces and vesicular formations in the seminiferous epithelium were observed on the HE-stained sections. The albumin immunolocalization was detected not only in the basal compartments, but also in the adluminal compartments between Sertoli cells and germ cells. Thus, the structural disruptions of inter-Sertoli TJ barriers could be clearly demonstrated by the "in vivo cryotechnique".

Animals↗
PubMed2005

Gene expression in spermiogenesis.

Germ cells convey parental genes to the next generation, and only germ cells perform meiosis, which is a mechanism that preserves the parental genes. The fusion of the products of germ cell meiosis, the haploid sperm and egg, creates the next generation. Sperm are the haploid germ cells that contribute genes to the egg. In preparation for this, the haploid round spermatids produced by meiosis undergo drastic morphological changes to become sperm. During this process of spermiogenesis, the nuclear form of the haploid germ cell takes shape, the mitochondria are rearranged in a specific manner, the flagellum develops and the acrosome forms. Spermatogenesis is supported by precise and orderly regulation of gene expression during the changes in chromatin structure, when protamine replaces histone. In this report, we summarize the molecular mechanisms involved in spermiogenesis.

Animals↗
PubMed2005

Interleukin-4 gene transduced tumor cells promote a potent tumor-specific Th1-type response in cooperation with interferon-alpha transduction.

To investigate antitumor mechanisms in interleukin (IL)-4 therapy, we established an IL-4-overexpressing MC38 murine colorectal cancer cell line (MC38-IL4). As a therapy against established tumors, MC38-IL4 cells were inoculated contralaterally 7 days after wild-type (MC38-WT) cells had been injected, significantly reducing growth of wild-type tumors (P=0.030). Immunohistochemical analysis showed numerous granulocytes infiltrating wild-type tumors of MC38-IL4-inoculated mice. Injection of MC38-IL4 cells in leukocyte-depleted mice confirmed that granulocytes were involved in IL-4-related primary antitumor effects. Inoculation of MC38-WT in leukocyte-depleted mice initially injected with MC38-IL4 suggested that T cells contributed to the antitumor effects. To investigate tumor-specific responses, we stimulated splenocytes of MC38-immune mice with MC38-IL4 cells in vitro, resulting in MC38-specific lysis (57.5+/-7.2%, effector to target ratio=20). Treatment of established wild-type tumors with MC38-IL4 in combination with interferon (IFN)-alpha-overexpressing MC38 cells (MC38-IFNalpha) significantly reduced the growth of wild-type tumors (P=0.009). In vitro IFN-gamma production by splenocytes from mice injected with both MC38-IL4 and -IFNalpha was greatly enhanced in comparison with MC38-IL4 alone, while IL-10 production was not increased. Thus, granulocytes concern early antitumor effects of IL-4 therapy. Subsequently, IL-4 induces long-lasting, tumor-specific immune responses. IL-4 appears to promote a T-helper 1-type antitumor immune response, which is enhanced in cooperation with IFN-alpha.

Animals↗
PubMed2004

Effects of anoxia on serum immunoglobulin and albumin leakage through blood-brain barrier in mouse cerebellum as revealed by cryotechniques.

The purpose of this study was to examine time-dependent topographical changes of leaking proteins from blood vessels in the mouse cerebellum to assess the effect of normal blood circulation on the blood-brain barrier (BBB). The distribution of leaking serum proteins was immunohistochemically examined by various cryotechniques including our "in vivo cryotechnique". The cryofixed cerebellar tissues were processed for the freeze-substitution method, and finally embedded in the common paraffin wax. Serial de-paraffinized sections were immunostained by anti-mouse immunoglobulin-G (IgG) or albumin antibody. By combination of the "in vivo cryotechnique", in which normal blood flow into the cerebellum was always kept in vivo, with the freeze-substitution method, serum IgG and albumin were clearly localized inside of cerebellar blood vessels. To examine abnormal leakage of blood vessels as a model of anoxia, some cerebellar tissues were partially removed from brains in the mouse skull and quickly frozen in the isopentane-propane within a minute. In such resected cerebellar tissues, serum IgG and albumin were diffusely immunostained in large areas around the blood capillaries, probably because of easy leakage of the serum components through the immediately changed BBB. To the contrary, no serum protein could be identified outside blood capillaries under living conditions of the anesthetized mice. The present combination method, both "in vivo cryotechnique" and freeze-substitution, for immunohistochemistry enabled us to examine the in vivo localization of serum components in mouse brains due to alteration of the BBB.

Animals↗
PubMed2004

Theoretical study on the excited states of psoralen compounds bonded to a thymine residue.

Time-dependent density functional theory calculations have been performed for the excited states of psoralen, 5-methoxypsoralen, and 8-methoxypsoralen in systems and furan and pyrone monoadducts bonded to a thymine residue. The theoretical assignments to ultraviolet (UV) absorption spectra of isolated systems have been performed. The present calculations have clarified that the excitation energies of the first singlet excited (S1) state of monoadducts are blue-shifted compared with the isolated systems. It is shown that, in particular, the S1 excitation energy of the pyrone monoadduct is significantly blue-shifted and, therefore, the pyrone monoadduct is not excited by UV-A light (300-400 nm), which is used in the photochemotherapy.

Furocoumarins↗
PubMed2004

Model for the drug-drug interaction responsible for CYP3A enzyme inhibition. II: establishment and evaluation of dexamethasone-pretreated female rats.

1. Cytochrome P450 (CYP) 3A catalysis of testosterone 6beta-hydroxylation in female rat liver microsomes was significantly induced, then reached a plateau level after pretreatment with 80 mg kg(-1) day(-1) dexamethasone (DEX) for 3 days. 2. Midazolam was mainly metabolized by CYP3A in DEX-treated female rat liver microsomes from an immuno-inhibition study, and the apparent K(m) was 1.8 microM, similar to that in human microsomes. 3. Ketoconazole and erythromycin, typical CYP3A inhibitors, demonstrated extensive inhibition of midazolam metabolism in DEX-treated female rat liver microsomes, and the apparent K(i) values were 0.088 and 91.2 microM, respectively. The values were similar to those in humans, suggesting that DEX-treated female rat liver microsomes have properties similar to those of humans. 4. After oral administration of midazolam, the plasma midazolam concentration in DEX-treated female rats significantly decreased compared with control female rats. The area under the plasma concentration curve (AUC) and elimination half-life were one-11th and one-20th of those of control female rats, respectively. 5. Using DEX-treated female rats, the effect of CYP3A inhibitors on midazolam pharmacokinetics was evaluated. The AUC and maximum concentration in plasma (C(max)) increased when ketoconazole was co-administered with midazolam. 6. It was shown that the drug-drug interaction that occurs in vitro is also observed in vivo after oral administration of midazolam. In conclusion, the DEX-treated female rat could be a useful model for evaluating drug-drug interactions based on CYP3A enzyme inhibition.

Administration, Oral↗
PubMed2004

Model for the drug-drug interaction responsible for CYP3A enzyme inhibition. I: evaluation of cynomolgus monkeys as surrogates for humans.

1. Anti-human cytochrome P450 (CYP) 3A4 antiserum completely inhibited midazolam metabolism in monkey liver microsomes, suggesting that midazolam was mainly metabolized by CYP3A enzyme(s) in monkey liver microsomes. 2. Midazolam metabolism was also inhibited in vitro by typical chemical inhibitors of CYP3A, such as ketoconazole, erythromycin and diltiazem, and the apparent K(i) values for ketoconazole, erythromycin and diltiazem were 0.127, 94.2 and 29.6 microM, respectively. 3. CYP3A inhibitors increased plasma midazolam concentrations when midazolam and CYP3A inhibitors were co-administered orally. However, the pharmacokinetic parameters of midazolam were not changed by treatment with CYP3A inhibitors when midazolam was given intravenously. This suggests that CYP3A inhibitors modified the first-pass metabolism in the liver and/or intestine, but not systemic metabolism. 4. The drug-drug interaction responsible for CYP3A enzyme(s) inhibition was observed when midazolam and inhibitors were co-administrated orally. Therefore, it was concluded that monkeys given midazolam orally could be useful models for predicting drug-drug interactions in man based on CYP3A enzyme inhibition.

Administration, Oral↗
PubMed2004

No nephropathy in Type 2 diabetic patient with POEMS syndrome with an elevated plasma VEGF.

Vascular endothelial growth factor (VEGF) is considered to have a role in the pathogenesis of diabetic retinopathy. Recent experimental observations that anti-VEGF neutralizing antibody fully abolished the hyperfiltration and the increase in urinary albumin excretion suggested the contribution of VEGF to the development of diabetic nephropathy, as well. Here, we present a case of POEMS (Crow-Fukase) syndrome with Type 2 diabetes, which was associated with elevated plasma VEGF level, but no sign of diabetic nephropathy. The findings obtained from this case did not support the hypothesis that VEGF may enhance the development of diabetic nephropathy.

Diabetes Mellitus, Type 2↗
PubMed2003

Global metabolic response of Escherichia coli to gnd or zwf gene-knockout, based on 13C-labeling experiments and the measurement of enzyme activities.

An integrated study on cell growth, enzyme activities and carbon flux redistribution was made to investigate how the central metabolism of Escherichia coli changes with the knockout of genes in the oxidative pentose phosphate pathway (PPP). Mutants deficient in glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were constructed by disrupting the zwf and gnd genes and were grown in minimal media with two different carbon sources, such as glucose or pyruvate. It was shown that the knockout of either gnd or zwf gene did not affect the cell growth rate significantly, but the cellular metabolism was changed. While the specific substrate uptake rate and the specific carbon dioxide evolution rate for either mutant grown on glucose were higher than those obtained for the parent strain, these two rates were markedly decreased in mutants grown on pyruvate. The measurement of enzyme activities implied a significant change in metabolism, when alternative pathways such as the Entner-Doudoroff pathway (EDP) and the malic enzyme pathway were activated in the gnd mutant grown on glucose. As compared with the parent strain, the activities of phosphoglucose isomerase were increased in mutants grown on glucose but decreased in mutants grown on pyruvate. The metabolic flux redistribution obtained based on 13C-labeling experiments further indicated that the direction of the flux through the non-oxidative PPP was reversed in response to the gene knockout. Moreover, the knockout of genes caused an increased flux through the tricarboxlic acid cycle in mutants grown on glucose but caused a decrease in the case of using pyruvate. There was also a negative correlation between the fluxes through malic enzyme and isocitrate dehydrogenase in the mutants; and a positive correlation was found between the fluxes through malic enzyme and phosphoenolpyruvate carboxylase.

Carbohydrate Metabolism↗
PubMed2003

Primary motor cortex stimulation within the central sulcus for treating deafferentation pain.

Nine patients with post-stroke pain, six with brachial plexus injuries, two with phantom limb pain, one with spinal cord injury, and one with brain stem injury were treated with a modified motor cortex stimulation (MCS) protocol. Preoperative pharmacological tests were performed with phentolamine, lidocaine, ketamine, thiopental, morphine, and placebo. We placed a grid electrode in the subdural space to decide upon the best stimulation point for pain relief over a few weeks with the purpose of determining the placement of a Resume electrode. In five patients, Resumes were implanted in the interhemispheric fissure to reduce lower extremity pain. In five other patients, Resumes were placed within the central sulcus to stimulate area 4 and area 3b. In addition, electrodes were also placed on the surface of the precentral gyrus. Fourteen of the 19 patients showed pain reduction (6 excellent, 3 good, and 5 fair) using the MCS with our results indicating area 4 within the central sulcus to be the optimal stimulation point for pain relief. We speculate that conventional method may sometimes fail to stimulate area 4 and that focal stimulation of the primary motor cortex within the central sulcus may improve the efficacy of this treatment. Our pharmacological tests show that patients with ketamine sensitivity seem to be good candidates for MCS. Test stimulation with a subdural multi-grid electrode and Resumes in the cetral sulcus were helpful in locating the best stimulation point for pain relief.

Adult↗
PubMed2003

Effects of 3,3',4,4',5-pentachlorobiphenyl, a coplanar polychlorinated biphenyl congener, on cultured neonatal mouse testis.

3,3',4,4',5-Pentachlorobiphenyl (PCB126), a congener with a planar configuration, has been established to have relatively strong toxicities similar to those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) via aryl hydrocarbon receptors. We investigated the effects of this coplanar PCB on mammalian early spermatogenesis and steroidogenesis in a mouse neonatal testicular organ culture system. Testes collected from newborn mice were subjected to organ culture in medium containing 0, 10, 100 or 1000 nM PCB126. Histochemical analysis revealed that the BrdU-labeling indices of both spermatogenic cells and Sertoli cells were unchanged in all testis specimens exposed to the coplanar PCB. CYP1A1 and steroidogenic enzymes (P450scc, P450c17, 3beta-HSD and 17beta-HSD) mRNA levels were determined by semiquantitative RT-PCR. The CYP1A1 mRNA level in cultured testis was significantly increased by PCB126 in a dose-dependent manner. Although mRNA levels of 3beta-HSD and 17beta-HSD were unchanged, the P450scc mRNA level was significantly down-regulated by PCB126 in a dose-dependent manner. In contrast, the P450c17 mRNA level was significantly higher in 1000 nM PCB126-exposed testis than in control testis. These results suggest that the coplanar PCB does not alter the proliferative activity of spermatogenic cells and Sertoli cells in neonatal testis, but that it directly affects the expression of steroidogenic enzyme genes.

Animals↗
PubMed2003

Alkylphenol and bisphenol A levels in rubber products.

Levels of p-t-butylphenol (PTBP), p-t-octylphenol (PTOP), p-nonylphenol (NP) and bisphenol A (BPA) in rubber products in food-contact use, infant-related use and other uses are reported. Of 60 rubber products tested, PTOP was found in three in a concentration range of 2.2-37 microgram g(-1), and NP in 15 in a concentration range of 2.6-513 microgram g(-1). PTBP and BPA were not found in any sample. PTOP and NP were not detected in any infant-related sample, regardless of the material type. In contrast, among the samples with food contact and with other uses, the percentages containing PTOP or NP were 33 and 43%, respectively. A migration test was performed on eight samples containing NP and used in food-contact environments. The migration level of NP from spatulas to n-heptane was 0.83-1.52 microgram ml(-1). The average migration rates to water, 20% ethanol and n-heptane were 0.03, 0.7 and 6.6%, respectively.

Benzhydryl Compounds↗
PubMed2002

Total plasma homocysteine is associated with hypertension in Type I diabetic patients.

AIMS/HYPOTHESIS: Although hyperhomocysteinaemia and methylenetetrahydrofolate reductase gene polymorphism are accepted risk factors for cardiovascular disease, their association with micro angiopathy or blood pressure in diabetic patients is still being debated. This study explores the relation between plasma homocysteine concentrations, methylenetetrahydrofolate reductase gene polymorphism, hypertension, diabetic microvascular and macrovascular complications associated with kidney function. METHODS: Vascular complications, hypertension, methylenetetrahydrofolate reductase genotype (RFLP with Hinf I digestion), and total plasma homocysteine (HPLC) were investigated in 389 well-characterized Type I (insulin-dependent) diabetic patients with normal (GFR> or=75 ml x min(-1) x (1.73 m(2))(-1); n=273), or impaired renal function (GFR <75 ml x min(-1) x (1.73 m(2))(-1); n=116). RESULTS: Patients with microvascular and macrovascular complications showed higher total plasma homocysteine concentrations than those without complications. However, after the data for GFR (main determinant for plasma homocysteine) was adjusted we observed that plasma homocysteine concentrations greater than 8.6 micro mol/l in patients with normal GFR are not related to vascular complications, but to hypertension (8.6-11.3 micro mol/l: OR 1.9; >11.3 micro mol/l: OR 3.7). The risk for coronary heart disease (CHD) was also enhanced by a plasma homocysteine concentration greater than 11.3 micro mol/l (OR 5.9). Although the T allele was an independent determinant of plasma homocysteine, the methylenetetrahydrofolate reductase gene polymorphism was neither associated with diabetic vascular complications nor with hypertension. CONCLUSION/INTERPRETATION: Increased plasma homocysteine concentrations but not the T allele per se, enhance the risk of hypertension and of CHD in Danish Type I diabetic patients with normal renal function.

Adult↗
PubMed2002

An evaluation of chest X-ray screening for lung cancer in gunma prefecture, Japan: a population-based case-control study.

In order to evaluate the efficacy of annual chest X-ray screening for lung cancer, a case-control study was conducted in Gunma Prefecture, Japan. Population-based annual lung cancer screening programmes have been conducted by the local government in Gunma Prefecture since the mid-1970s. A total of 121 case subjects, including 91 high-risk males and 30 non-high-risk females between the ages of 40 and 79 years who died of lung cancer from 1992 to 1997 were evaluated. A total of 536 controls (3-5 controls for each case) were matched to case subjects by gender, year of birth, address and smoking habits. Controls were selected from screening programme lists provided by the local governments. All case subjects were also included on these lists. The smoking-adjusted odds ratio (OR) of lung cancer death for those subjects screened within 12 months prior to diagnosis versus those not screened was 0.68 (95% confidence interval (CI): 0.44-1.05; P=0.084). When the analysis was conducted without matching case and control subjects by smoking habits, the OR was 0.79 (95% CI: 0.53-1.18). When stratified by histological type, the OR was 0.62 (95% CI: 0.31-1.24) for adenocarcinoma, and 1.01 (95% CI: 0.44-2.31) for squamous cell carcinoma. The results of this study suggest 20-30% of deaths attributable to lung cancer, especially adenocarcinoma, might be prevented by annual chest X-rays.

Adenocarcinoma↗
PubMed2002

Long-term effect on optic nerve of silicone oil tamponade in rabbits: histological and EDXA findings.

PURPOSE: Side-effects after intravitreal use of silicone oil (SO) are not well defined and elucidated. The object of this study was to examine the influence and toxicity of SO on the optic nerve after vitrectomy with SO tamponade. METHODS: We injected medical grade SO and emulsified SO into rabbit eyes after gas-mediated vitreous compression and examined the eyes by light microscopy (LM), transmission electron microscopy (TEM) and energy dispersive X-ray analysis (EDXA) (point analysis and area analysis) 6 months after injection. We compared the findings in the non-treated eyes and eyes with only gas-mediated vitreous compression with those in SO-injected eyes. RESULTS: Vacuole-like structures were seen in the optic nerve posterior to the lamina cribrosa. In the group treated with only gas-mediated vitreous compression, the myelin structures were shown by TEM to be destroyed and replaced by glial tissue, while in groups injected with medical grade or emulsified SO severe destruction of the myelin sheath (myelinolysis) was observed. Silicone was identified at the electron-dense edges of the vacuoles by EDXA point analysis, but not in the vacuoles without electron-dense deposits. Dots of Si K alpha were not seen in the control groups, and dense dots were observed in SO-injected groups, by EDXA area analysis. CONCLUSIONS: Some of the vacuoles might be artefacts caused by insufficient fixation or the operative procedure, but TEM showed almost no artefacts in the control optic nerve. Thus, most vacuoles may be SO storage sites. SO uptake into the optic nerve might play a role in the pathogenesis of optic nerve atrophy after SO injection.

Animals↗