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Biomedical subjects

T Kubota

Publications and source records attributed to T Kubota.

At least 163 records · Page 9Linked to original sources
PubMed2001

Laparoscopic detection of sentinel lymph nodes in gastrointestinal cancer: a novel and minimally invasive approach.

Although the sentinel node (SN) concept has been validated in malignant melanoma and breast cancer, the application of this concept for other solid tumors, including gastrointestinal (GI) cancer, is still controversial. We have demonstrated the feasibility of radioguided SN mapping during laparotomy in patients with esophageal, gastric, and colorectal cancers. In 188 patients, the SNs identified by this technique had an overall diagnostic accuracy of 96% for regional lymph node metastasis. Aberrant drainage sites that have been called skip metastasis from the primary lesion were detectable using this method. More recently, we have undertaken SN mapping during laparoscopic surgery. A combination of radiotracer and blue dye optimized the identification of SNs that drained GI cancers. Our preliminary data indicate that laparoscopic mapping of the SN is a sensitive intraoperative technique for identifying lymph node micrometastasis, and we believe that it will become an important component of a minimally invasive approach to early-stage GI cancers.

Colonic Neoplasms↗
PubMed2001

[Clinical significance of sentinel node navigation surgery in the treatment of early gastric cancer].

Radical lymphadenectomy is the standard surgical approach even for early-stage gastric cancer with a relatively low incidence of lymph node metastasis because of the limited sensitivity of diagnostic imaging to detect micrometastasis in regional lymph nodes. The sentinel node (SN) concept is one topic among novel diagnostic procedures for micrometastasis. The SN is defined as the first draining node from the primary lesion and it would be the first site of micrometastasis. SN biopsy has been clinically validated and applied for the surgical treatment of malignant melanoma and breast cancer. Although the feasibility of this technique in other solid tumors including gastric cancer is still controversial, there are several reports demonstrating the diagnostic significance of SN mapping in early gastric cancer. We have established radio-guided SN mapping for early gastric cancer, and the diagnostic accuracy using this procedure in cT1N0 cases reached 98%. The radio-guided method allows us to detect the SN in endoscopic surgery quantitatively and reproducibly. Validation of the SN concept in gastric cancer in a multi-centric clinical trial is essential for clinical application of this procedure, including the establishment of a novel, minimally invasive approach for early-stage gastric cancer.

Humans↗
PubMed2001

Pregabalin enhances nonrapid eye movement sleep.

Pregabalin, an analog of gamma-aminobutyric acid (GABA) that does not interact with GABA receptors, is in development as an analgesic, an anticonvulsant, and an anxiolytic. We evaluated the potential somnogenic actions of pregabalin in rats and compared it to those of triazolam, a widely used hypnotic. Pregabalin increased the duration of nonrapid eye movement sleep (NREMS) and decreased rapid eye movement sleep (REMS) after either dark onset or light onset administration. Triazolam increased duration of NREMS and had no effect on duration of REMS. Pregabalin markedly increased the duration of NREMS episodes and decreased the number of NREMS episodes. Power spectrum analysis revealed pregabalin-induced dose-dependent increases in relative delta power after administration. In contrast, triazolam decreased electroencephalographic power density in low frequency bands. Results suggest that pregabalin is a potential sleep modulating agent.

Animals↗
PubMed2001

Lack of association between smoking and CYP2A6 gene polymorphisms in A Japanese population.

This study determined the genotypes of the CYP2A6 gene in 96 smokers and 141 non-smokers in a Japanese population. The frequencies of wild-type of the CYP2A6* 1 and those with a whole deletion of the CYP2A6 gene were 93 (96.9%) and 3 (3.1%) in 96 smokers, and 134 (95.0%) and 7 (5.0%) in non-smokers, respectively. In addition, neither the CYP2A6* 2 nor CYP2A6* 3 alleles were observed in the population studied. There were no significant differences in the CYP2A6 genotype frequencies between smokers and non-smokers, as well as in the number of cigarettes smoked and the nicotine amounts inhaled per day between the CYP2A6* 1 and the deletion of CYP2A6. These results suggest that either the deletion or non-deletion of the CYP2A6 gene shows no significant effect on smoking behavior for the Japanese population examined.

Adult↗
PubMed2001

Macrophage infiltration-associated thymidine phosphorylase expression correlates with increased microvessel density and poor prognosis in astrocytic tumors.

PURPOSE AND EXPERIMENTAL DESIGN: To clarify the significance of thymidine phosphorylase (TP)/platelet-derived endothelial cell growth factor/gliostatin in human glioma, we examined TP expression immunohistochemically in a series of 50 astrocytic tumors and correlated its expression with tumor angiogenesis and apoptosis, as well as prognosis. RESULTS: The majority of TP-positive cells were of macrophage origin, which was confirmed by immunostaining TP and CD68 on mirror sections. TP expression was significantly associated with glioma malignancy grading, intratumoral microvessel density, and VEGF expression but showed no relationship with apoptotic index or P53 expression. Regardless of glioma grading, patients with TP-positive tumors had a significantly shorter mean survival time than those with TP-negative tumors. CONCLUSIONS: These findings suggest that TP might play a crucial role in angiogenesis during glioma development, and immunodetection of TP is useful for clinical prediction. Further studies are necessary to better elucidate the role of TP in glioma, which may provide insights into adequate TP-targeted therapy.

Antigens, CD↗
PubMed2001

Tracer accumulation in femoral head during early phase of bone scintigraphy after renal transplantation.

UNLABELLED: Nontraumatic osteonecrosis of the femoral head (ONF) is a complication of renal transplantation. The pathogenic mechanism of ONF is thought to be an ischemic event. The purpose of this study was to investigate whether 3-phase bone scintigraphy can reveal early hemodynamic changes associated with ONF after renal transplantation. METHODS: We performed 3-phase bone scintigraphy on 19 renal allograft recipients between 3 and 9 wk after they underwent renal transplantation. Regions of interest (ROI) were assigned bilaterally in the femoral heads, diaphyses, and soft tissue. The head-to-diaphysis ratio (HD) in each phase was then calculated. RESULTS: ONF occurred in 8 femoral heads of 4 patients. Three of the 4 ONF patients had no abnormal MRI findings at the time of bone scintigraphy. In phase 1, no significant difference in HDs was observed between the ONF patients (mean HD +/- SD, 0.62 +/- 0.44) and the non-ONF patients (0.31 +/- 1.40). The difference between the mean counts for bone and soft tissue was small in both instances, and the HD had a large dispersion. In phase 2, the HDs for the ONF patients (0.70 +/- 0.27) and the non-ONF patients (1.31 +/- 0.43) were significantly different (P = 0.0005). The HD was <1.00 in all femoral heads of the ONF patients, whereas 9 non-ONF heads had an HD that was <1.00. In phase 3, the HD of the ONF patients was significantly lower than that of the non-ONF patients (ONF patients, 0.92 +/- 0.17; non-ONF patients, 1.62 +/- 0.46; P = 0.0002). CONCLUSION: All ONF patients were in the group with a low HD in phase 2, suggesting a reduction in blood flow or blood pool. Phase 2 accumulation in 3-phase bone scintigraphy can be used to estimate early hemodynamic changes in patients with ONF after renal transplantation.

Adult↗
PubMed2001

[A case of granulomatous angiitis of the central nervous system presented with subacute mental deterioration resembling diffuse white matter disease].

We reported a 60-year-old man with granulomatous angiitis of the central nervous system (GACNS) manifesting as subacute mental deterioration. His first symptoms were nausea and vomiting which brought him to a hospital, where no abnormality was found except for gastritis. One month later, he began to feel dizziness and brain tumor was suspected by a neurosurgeon with the MRI findings such as abnormal T2 signal and swelling in his brainstem. While he was followed up, he gradually presented mental change, disorientation and dysmnesia with the abnormal T2 signal spreading over the cerebral white matter bilaterally. Corticosteroid therapy was started based on the suspicion of a lymphoproliferative disease, and his symptoms and the abnormal MRI findings improved. Then he was referred to our department for further evaluation. Because we could not find any evidence of systemic diseases and he had been almost fully recovered, we discontinued the therapy. Soon after that, his mental deterioration as well as the abnormal T2 signal lesions on MRI relapsed. By open brain biopsy, the diagnosis of GACNS was established, and steroid pulse therapy was started. His symptoms and the abnormal T2 signal lesions improved gradually and the steroid was tapered to the maintenance dose without remission. Since the laboratory and imaging findings are not specific for the diagnosis of the angiitis confined to the central nervous system, brain biopsy is recommended for these disorders.

Acute Disease↗
PubMed2000

Representational difference analysis using myeloid cells from C/EBP epsilon deletional mice.

C/EBP epsilon is a recently cloned member of the C/EBP family of transcriptional factors. Previous studies demonstrated that the expression of this gene is tightly regulated in a tissue specific manner; it is expressed exclusively in myeloid cells. C/EBP epsilon-deficient mice developed normally but failed to generate functional neutrophils and eosinophils, and these mice died of opportunistic infections suggesting that C/EBP epsilon may play a central role in myeloid differentiation. To identify myelomonocytic genes regulated by the C/EBP epsilon gene, we performed representational difference analysis (RDA), a polymerase chain reaction (PCR)-based subtractive hybridization using neutrophils and macrophages from wild-type and C/EBP epsilon knockout mice. We identified a set of differentially expressed genes, including chemokines specific to myelomonocytic cells. Several novel genes were identified that were differentially expressed in normal myelomonocytic cells. Taken together, we have found several genes whose expression might be enhanced by C/EBP epsilon. (Blood. 2000;96:3953-3957)

Animals↗
PubMed2000

Expression and localization of heme oxygenase in human placental villi.

The aim of the present study was to investigate the expression and distribution patterns of heme oxygenase (HO)-1 and HO-2 in human placental villi at term and in the first trimester of pregnancy using reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemistry. RT-PCR detected mRNA for HO-1 and HO-2 in human placental villi during gestation. Western blotting also revealed the expression of the two distinct HO proteins throughout gestation. HO-1 was constitutively expressed, while HO-2 expression was apparently greater at term than in early pregnancy. Immunohistochemistry showed that distribution of the two HO isoforms had distinct topographic patterns: HO-1 was observed in villous trophoblastic cells, while HO-2 was found in endothelial cells and smooth muscle cells of blood vessels of placental villi. These results may provide a microtopographic basis for elucidating the mechanism of carbon monoxide (CO)-mediated vasodilatation, and it is suggested that the CO/HO system may be involved in the control of placental vascular function and may protect the syncytiotrophoblast and endothelium against oxidative injury.

Antibodies↗
PubMed2000

Molecular genetic study of japanese patients with X-linked alpha-thalassemia/mental retardation syndrome (ATR-X).

X-linked alpha-thalassemia/mental retardation syndrome (ATR-X) is one of the many known X-linked mental retardation syndromes. Mutations in the ATR-X gene (ATRX) that encodes a putative global transcription factor have been identified in patients with ATR-X as well as those with other forms of X-linked mental retardation syndrome. To better understand the genetic basis of ATR-X, we investigated nine patients with the ATR-X phenotype from eight independent Japanese families for mutations in ATRX. We identified seven missense mutations, including six novel mutations, all of which were located either in the N-terminal region corresponding to the putative zinc finger domain (N179S, P190L, V194I, and R246C) or in the C-terminal region corresponding to the helicase domain (V1552F, L1645S, and Y1847C). R246C was found in two independent patients. Furthermore, we investigated the origin of the mutations in seven mothers. Five mothers were found to be carriers, and two were not, indicating de novo origin of the mutations. When we compared clinical manifestations with respective mutations, we could not find apparent phenotype-genotype correlation. Therefore, the putative zinc finger domain and the helicase domains may have similar functional significance for the function of ATRX.

Adult↗
PubMed2000

Hypothalamo-pituitary-adrenal axis activation by administration of cyanamide: a potent inhibitor of aldehyde dehydrogenase.

In this report, we investigated the effects of cyanamide (a potent inhibitor of aldehyde dehydrogenase (ALDH: EC 1.2.1.3)) on hypothalamo-pituitary adrenal (HPA)-axis using in situ hybridization histochemistry and radioimmunoassay. Cyanamide administration resulted in a dose-dependent increase in plasma corticosterone concentrations, significant increases in not only corticotrophin releasing factor (CRF) mRNA, but also arginine vasopressin (AVP) mRNA in the paraventricular nucleus (PVN) and proopiomelanocortin (POMC) mRNA in the anterior pituitary. These results suggest that cyanamide is able to activate the HPA axis at all levels of the axis.

Aldehyde Dehydrogenase↗
PubMed2000

Genotype analysis of the CYP2C19 gene in HCV-seropositive patients with cirrhosis and hepatocellular carcinoma.

This study was conducted to assess whether the genotypic frequency of Smephenytoin 4'-hydroxylase CYP2C19 gene differs in Japanese cirrhotic patients who developed hepatocellular carcinoma. Thirty-eight patients with cirrhosis were studied. The wild-type allele CYP2C19*1 and the two mutated alleles, CYP2C19*2 and CYP2C19*3, were identified by PCR-RFLP method. Individuals with homozygous CYP2C19*2 or CYP2C19*3 mutation and those with CYP2C19*2 and CYP2C19*3 heterozygous mutation were predicted to be the poor metabolizer (PM) phenotype. The overall frequency of PM predicted from the genotyping analysis was 29% (11 of the 38 patients), consisting of 5 patients homozygous for CYP2C19*2, two homozygous for CYP2C19*3 and four heterozygous for the two defects. Among 24 HCV-seropositive patients with cirrhosis and hepatocellular carcinoma, the frequency of PM was 41.7% and significantly higher than that observed in 186 healthy controls. We postulate that the PM phenotype caused by the mutation of CYP2C19 gene in cirrhotic patients with HCV infection is associated with a high risk for developing hepatocellular carcinoma.

Alleles↗
PubMed2000

Soluble tumor necrosis factor receptor abrogates myocardial inflammation but not hypertrophy in cytokine-induced cardiomyopathy.

BACKGROUND: Transgenic mice with cardiac-specific overexpression of tumor necrosis factor (TNF)-alpha develop dilated cardiomyopathy. The present study was designed to evaluate therapeutic effects of adenovirus-mediated neutralization of TNF-alpha on this model. METHODS AND RESULTS: An adenovirus encoding the 55-kDa TNF receptor-IgG fusion protein (AdTNFRI) was injected intravenously into 6-week-old transgenic mice, which resulted in high levels of TNFRI in both plasma and myocardium. AdTNFRI did not reverse cardiomegaly but abrogated myocardial inflammation. Furthermore, AdTNFRI blocked the myocardial expression of intercellular adhesion molecule-1 and downstream cytokines, including interleukin-1beta and monocyte chemotactic protein-1. Downregulation of alpha-myosin heavy chain was restored by the treatment, whereas upregulation of beta-myosin heavy chain was not reversed. In contrast, the downregulation of sarcoplasmic reticulum Ca(2+)-ATPase and phospholamban was normalized by AdTNFRI. Echocardiographic measurements showed that left ventricular end-systolic diameter was significantly larger in transgenic mice than in control mice, and this increase was reversed by the AdTNFRI treatment. However, left ventricular wall thickening was not reversed. CONCLUSIONS: These results suggest that anti-TNF therapy may hold promise in the treatment of end-stage heart failure.

Adenoviridae↗
PubMed2000

An alternative method of arterial reconstruction after hepatic arterial thrombosis following living-related liver transplantation.

BACKGROUND: Hepatic artery thrombosis (HAT) remains an important cause of graft loss after liver transplantation. Emergency rearterialization methods are limited in cases of living-related liver transplantation in which the graft hepatic artery is thin and short. CASE: A 19-year-old woman who underwent living-related liver transplantation for biliary atresia developed HAT on the 4th postoperative day. During the emergency laparotomy the recipient hepatic artery was found to be too short to anastomose, so the recipient's right gastroepiploic artery was anastomosed to the graft hepatic artery. The patient is now alive and well 6 months after reoperation, and she has experienced no further episode of HAT. CONCLUSION: The right gastroepiploic artery can be used easily and safely for hepatic graft revascularization without causing ischemia of the stomach. An additional skin incision is not required, and the artery is long enough to anastomose to the graft artery directly. The method of hepatic graft rearterialization described here is an important option for patients who undergo living-related or split liver transplantation.

Adult↗
PubMed2000

Effects of MK-801 on clozapine-induced potentiation of excitatory synaptic responses in the perforant path-dentate gyrus pathway in chronically prepared rabbits.

We previously found that the atypical antipsychotic drug, clozapine, when intraperitoneally (i.p.) injected, long-lastingly potentiated excitatory synaptic responses elicited in the dentate gyrus by single electrical stimulations to the perforant path in chronically prepared rabbits, and called this phenomenon 'clozapine-induced potentiation'. In the present study, we likewise examined whether clozapine-induced potentiation is caused by NMDA receptor-mediated neurotransmission in the perforant path-dentate gyrus pathway of chronically prepared rabbits. The non-competitive NMDA receptor antagonist - 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imino hydrogen maleate (MK-801; 1.0 mg/kg, i.p.) - completely prevented the potentiation of synaptic responses induced by subsequent administration of 20 mg/kg clozapine, whereas the 0.5 mg/kg dose had virtually no effect on the potentiation. These results suggest that the effect of clozapine requires NMDA receptor activation.

Analysis of Variance↗
PubMed2000

The role of tumor necrosis factor in the pathophysiology of heart failure.

Recent studies have focused their attention on the role of the proinflammatory cytokine tumor necrosis factor (TNF) in the development of heart failure. First recognized as an endotoxin-induced serum factor that caused necrosis of tumors and cachexia, it is now recognized that TNF participates in the pathophysiology of a group of inflammatory diseases including rheumatoid arthritis and Crohn's disease. The normal heart does not express TNF; however, the failing heart produces robust quantities. Furthermore, there is a direct relationship between the level of TNF expression and the severity of disease. In addition, both in vivo and in vitro studies demonstrate that TNF effects cellular and biochemical changes that mirror those seen in patients with congestive heart failure. Furthermore, in animal models, the development of the heart failure phenotype can be abrogated at least in part by anticytokine therapy. Based on information from experimental studies, investigators are now evaluating the clinical efficacy of novel anticytokine and anti-TNF strategies in patients with heart failure; one such strategy is the use of a recombinantly produced chimeric TNF alpha soluble receptor. Thus, in view of the emerging importance of proinflammatory cytokines in the pathogenesis of heart disease, we review the biology of TNF, its role in inflammatory diseases, the effects of TNF on the physiology of the heart and the development of clinical strategies that target the cytokine pathways.

Animals↗