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J Takeda

Publications and source records attributed to J Takeda.

At least 55 records · Page 3Linked to original sources
PubMed2001

Advanced gastric cancer effectively treated by neoadjuvant continuous low-dosage 5-fluorouracil and cisplatin (FP regimen): a case report.

We have experienced a case of advanced gastric cancer with para-aortic lymph node metastasis effectively treated by neoadjuvant continuous low dosage 5-fluorouracil and cisplatin (FP regimen). The patient was a 67-year-old man diagnosed as having advanced gastric cancer type 4 with para-aortic lymph node metastasis. This patient was treated by continuous infusion of 5-fluorouracil (5-FU) 500 mg/day, for 28 days, and infusion of cisplatin 10 mg/day over 1 hr on days 1-5, 8-12, 15-19, and 22-26. At 4 weeks later, a CT revealed that swelling in the para-aortic lymph node had disappeared, and the thickening in the stomach wall had diminished. This patient underwent a curative operation, and both the serum level of carcinoembryonal antigen (CEA) and carbohydrate antigen (CA 19-9) decreased to normal. These results suggested that the FP regimen was an effective neoadjuvant treatment for advanced gastric cancer with para-aortic lymph node metastasis.

Aged↗
PubMed2001

Long-term survival after gastric cancer with liver metastasis: a report of two cases.

We have experienced two cases of long-term survival after surgery for gastric cancer case with liver metastasis. One case was of a 66-year-old male patient diagnosed as having type 1 advanced gastric cancer located in the posterior wall of the lower body with liver metastasis. The stage of this case was P0H1N1T2M0 stage IV. This patient underwent distal gastrectomy with D2 lymph node resection, partial hepatectomy of the S3 region including the metastatic liver tumor and coagulation of metastatic liver tumors in the S6 and S7 regions. This patient was treated by intra-hepatic arterial infusion of 5-FU, CDDP and peroral administration of UFT after surgery. This patient has died at 3 years and 7 months after surgery. The other case was of a 55-year-old male patient diagnosed as having type 2 advanced gastric cancer located in the lesser curvature of the cardia with liver metastasis. The stage of this case was P0H1N1T3 M0 stage IV. This patient underwent total gastrectomy with D2 lymph node dissection, wedge resection of the S8 region including the metastatic liver tumor and coagulation of a metastatic liver tumor in the S4 region. This patient was treated by obstruction of the hepatic artery using coils, peroral administration of UFT, lentinan, MMC, and continuous low-dosage 5-FU and CDDP after surgery. This patient has died at 3 years and 6 months after surgery. These results suggest that for long-term survival in cases of gastric cancer with liver metastasis, hepatectomy or coagulation of the metastatic tumor with postoperative chemotherapy are indicated in cases that have no non-curative factors and only a few metastatic tumors.

Aged↗
PubMed2001

Beta-catenin expression as a prognostic indicator in cervical adenocarcinoma.

The purpose of this study was to assess the prognostic influence of beta-catenin expression by immunohistochemistry in patients with cervical adenocarcinomas. The study group comprised of 51 patients who underwent total hysterectomy for cervical cancer. The median follow-up was 39 months (range 1-138 months). beta-catenin was expressed strongly on the membranes of normal cervical epithelial and glandular cells. Uniform membranous beta-catenin staining localized to intercellular borders was observed in 35% of tumors, whereas 65% of tumors demonstrated an abnormal pattern of reduced or aberrant beta-catenin expression (i.e., cytoplasmic and/or nuclear staining patterns). Abnormal beta-catenin immunoreactivity was associated statistically with advanced pathologic stage (p=0.018). The 10-year disease-free survival was 51.0% in patients with preserved expression of beta-catenin. On the other hand, a poorer prognosis was noted in the group with abnormal expression of beta-catenin with a 10-year disease-free survival of 43.4%. By multivariate analysis, low pathologic stage (stages I and II, p=0.001) and preservation of beta-catenin expression (p=0.012) were independently favorable prognostic factors. Our results indicate that changes in beta-catenin expression occur during the progression of cervical adenocarcinoma to an invasive phenotype. These results suggest that beta-catenin is an important intercellular adhesion molecule. Assessment of beta-catenin immunoreactivity may be a useful prognostic tool in cervical adenocarcinoma complementary to established prognostic factors. Furthermore, we developed a strategy for choosing biomarkers representing the steps in malignant progression in an effort to identify patients with occult metastases who will need adjuvant therapy and spare women from unnecessary interventions.

Adenocarcinoma↗
PubMed2000

Two distinct signaling pathways in hair cycle induction: Stat3-dependent and -independent pathways.

The hair follicle is an epidermal derivative that undergoes cycles of growth, involution, and rest. The hair cycle has well-orchestrated kinetics regulated by interactions between mesenchymal and epithelial cells, although the intracellular signals remain unclear. We previously established keratinocyte-specific Stat3-disrupted mice, by which we demonstrated that signal transducer and activator of transcription 3 (Stat3) is required for wound healing and anagen progression in the hair cycle. Growth factor-dependent migration of Stat3-disrupted keratinocytes was severely impaired, suggesting that not only wound healing but also telogen-to-anagen progression required organized keratinocyte migration in response to mesenchymal stimuli. In the present study, to examine whether Stat3 activation in keratinocytes is a prerequisite for hair cycle progression, we applied methods for experimental anagen induction to Stat3-disrupted mice. It was demonstrated that anagen was successfully induced in Stat3-disrupted as well as wild-type mice by chemical or mechanical stimulation, i.e. , by topical application of phorbol 12-myristate 13-acetate (PMA) or by hair plucking, respectively. This result indicated that anagen in these methods occurred in the absence of Stat3. Furthermore, PMA stimulated the migration of Stat3-disrupted keratinocytes in vitro, supporting a hypothesis that the protein kinase C (PKC) and Stat3 pathways occur independently in the postnatal anagen induction. Both Stat3-dependent and -independent migration of keratinocytes was inhibited by a phosphoinositide 3-kinase (PI3K) inhibitor, wortmannin. Therefore, we infer that entry into anagen is mediated by at least two distinct signaling pathways: Stat3-dependent pathway for spontaneous hair cycling and Stat3-independent (probably PKC-dependent) pathway for exogenously induced hair cycling, whereas both pathways require PI3K activation.

Animals↗
PubMed2000

Regional expression of a gene encoding a neuron-specific Na(+)-dependent inorganic phosphate cotransporter (DNPI) in the rat forebrain.

We have analyzed expression of a gene encoding a brain-specific Na(+)-dependent inorganic phosphate cotransporter (DNPI), which was recently cloned from human brain, in rat forebrain using in situ hybridization. The expression of DNPI mRNA showed a widespread but highly heterogeneous pattern of distribution in the forebrain, where hybridization signals were observed in neurons but not in any other types of cells. Neurons expressing the mRNA were far more numerous in the diencephalon than in the telencephalon. In the thalamus, a number of neurons with high levels of signals were localized to all nuclei of the dorsal thalamus, habenular nuclei and subthalamic nucleus, but not the reticular nucleus and zona incerta. Moderate signal levels were seen in many neurons throughout the hypothalamus, particularly the ventromedial, paraventricular, supraoptic and arcuate nuclei, lateral hypothalamic area and mammillary complex. In contrast, expression of DNPI mRNA in the telencephalon was generally at a low level and occurred locally in some restricted regions within the neocortex, retrosplenial cortex, piriform cortex, olfactory regions, hippocampal formation and medial amygdaloid nucleus. The present results suggest that DNPI functions in heterogeneous neuron populations as a neuron-specific Na(+)-dependent inorganic phosphate cotransport system predominantly expressed in the diencephalon of the rat.

Animals↗
PubMed2000

Anti-tumor immunity against CT26 colon tumor in mice immunized with plasmid DNA encoding beta-galactosidase fused to an envelope protein of endogenous retrovirus.

Endogenous retroviral gene products have been recognized as being expressed in human cancerous tissues. However, these products have not been shown to be antigenic targets for T-cells, possibly due to immune tolerance. Since carcinogen-induced colon tumor CT26 expresses an envelope protein, gp70, of an endogenous ecotropic murine leukemia virus that is comparable to human tumor-associated antigens, we examined whether a DNA vaccine containing the gp70 gene induces protective immunity against CT26 cells. Injection of mice with plasmid DNA (pDNA) encoding gp70 alone failed to induce anti-gp70 antibody (Ab) or anti-CT26 cytotoxic T lymphocyte (CTL) responses. However, immunization with pDNA encoding the beta-galactosidase (beta-gal)/gp70 fusion protein induced anti-gp70 Ab and anti-CT26 CTL responses and conferred protective immunity against CT26 cells. These results indicate that beta-gal acts as an immunogenic carrier protein that helps in the induction of immune responses against the poorly immunogenic gp70. Considering these results, it is possible that potential tolerance to the endogenous retroviral gene products expressed by human tumors may be overcome by DNA vaccines that contain an endogenous retroviral gene fused to genes encoding immunogenic carrier proteins.

Animals↗
PubMed2000

A novel reporter mouse strain that expresses enhanced green fluorescent protein upon Cre-mediated recombination.

The success of Cre-mediated conditional gene targeting depends on the specificity of Cre recombinase expression in Cre-transgenic mouse lines. As a tool to evaluate the specificity of Cre expression, we developed a reporter transgenic mouse strain that expresses enhanced green fluorescent protein (EGFP) upon Cre-mediated recombination. We demonstrate that the progeny resulting from a cross between this reporter strain and a transgenic strain expressing Cre in zygotes show ubiquitous EGFP fluorescence. This reporter strain should be useful to monitor the Cre expression directed by various promoters in transgenic mice, including mice in which Cre is expressed transiently during embryogenesis under a developmentally regulated promoter.

Alleles↗
PubMed2000

Cloning of cDNA and the gene encoding human hepatocyte nuclear factor (HNF)-3 beta and mutation screening in Japanese subjects with maturity-onset diabetes of the young.

AIMS/HYPOTHESIS: Molecular defects of the genes for transcription factors, hepatocyte nuclear factor (HNF)-4 alpha, HNF-1 alpha, HNF-1 beta and insulin promoter factor-1 cause maturity-onset diabetes of the young (MODY1, 3, 5, and 4, respectively). This suggests the HNF-related transcription cascade is important in insulin secretion which is induced by glucose. These genes and the gene encoding glycolytic enzyme glucokinase (MODY2) are, however, responsible for only 15-20% of cases of MODY in the Japanese. Searching for a novel form of MODY in this population, we cloned a new candidate gene encoding human HNF-3 beta, a winged helix transcription factor, which also belongs to the same HNF-transcription cascade. METHODS: The cDNA clone for human HNF-3 beta was isolated from a liver cDNA library. The gene was also cloned from a genomic library and its organization and chromosomal localization were determined. We screened 68 Japanese subjects with MODY/early-onset diabetes for mutations in this gene. RESULTS: Human HNF-3 beta is composed of 457 amino acids. The human gene, which was mapped to the segment 30 cR from SHGC-37039 on chromosome 20p by radiation hybrid mapping, spans approximately 4.5 kb and consists of three exons. Direct sequencing of the exons and flanking regions identified one missense mutation A328 V and seven polymorphisms, although the functional significance of the mutation in the pathogenesis of diabetes is not known. CONCLUSION/INTERPRETATION: The characterization of the structure of the HNF-3 beta gene and its mapping in the framework of markers will be helpful in genetic studies of the various forms of diabetes mellitus.

Amino Acid Sequence↗
PubMed2000

Identification of missense mutations in the hepatocyte nuclear factor-3beta gene in Japanese subjects with late-onset Type II diabetes mellitus.

AIMS/HYPOTHESIS: Hepatocyte nuclear factor (HNF)-3beta, a transcription factor expressed in pancreatic beta cells, is an upstream regulator of HNF-1alpha/MODY3, HNF-4alpha/MODY1 and IPF1/MODY5 genes. Our previous screening of MODY subjects showed that mutations in the HNF-3beta gene are not a common cause of this form of diabetes in the Japanese. We tested the hypothesis that mutations in the HNF-3beta gene cause late-onset Type II (non-insulin-dependent) diabetes mellitus in this population. METHODS: Genotyping of the polymorphic TCC repeat in the HNF-3beta gene was done in 112 Japanese subjects with Type II diabetes (age at diagnosis > 35 and family history of Type II diabetes among their second-degree relatives) and 96 Japanese control subjects. Furthermore, we screened 57 Type II diabetic patients for mutations of the HNF-3beta gene. Transactivation activity of variant HNF-3beta was investigated by transfection assay. RESULTS: The distribution of alleles of the TCC repeat was similar between diabetic and control groups. Mutation screening identified two missense mutations, A86T and G114E. Neither mutation was observed in 225 control subjects. The transactivation activity of G114E-HNF-3beta was similar to that of wild typeHNF-3beta. In contrast, the activity of A86T-HNF-3beta was statistically significantly reduced to 83-86 % of that of wild type. CONCLUSIONS/INTERPRETATION: The A86T mutation in the HNF-3beta gene might be involved in the development of late-onset Type II diabetes in a small group of Japanese people.

Adult↗
PubMed2000

Conditional gene targeting and its application in the skin.

The knockout mouse is one of the most useful experimental animal systems in which to clarify functions of identified genes in vivo. Numerous knockout mice have been produced, and studies in these models have revealed new aspects in various biological fields. In fair cases, however, mice died during embryogenesis due to complete gene disruption, making it difficult to elucidate functions of given genes in adulthood. To avoid this, conditional gene targeting has been performed and shown to be effective on numerous cases. Here, we will overview established strategies for conditional gene targeting and present the results of our recent studies using the Cre/loxP system in the skin.

Animals↗
PubMed2000

Hypermagnesemia-induced cardiopulmonary arrest before induction of anesthesia for emergency cesarean section.

We describe a 42-yr-old woman scheduled for emergency cesarean section who had sudden cardiopulmonary arrest just before induction of general anesthesia. Hypermagnesemia, caused by accidental overdose of magnesium sulfate during transportation to the operating room, was the primary cause of this life-threatening event. Anesthetic management after such events and a brief summary of the literature regarding iatrogenic hypermagnesemia in obsteric patients are provided.

Adult↗
PubMed2000

Additional droperidol, not butorphanol, augments epidural fentanyl analgesia following anorectal surgery.

STUDY OBJECTIVE: To examine the effects of additional droperidol or butorphanol to epidural fentanyl infusion on postsurgical analgesia. DESIGN: Prospective, randomized, single blinded clinical study. SETTING: University-affiliated medical center. PATIENTS: 60 ASA physical status I and II patients undergoing anorectal surgery by one surgeon. INTERVENTIONS: Patients were randomly allocated to the following groups according to the medication that was continuously administered into the epidural space: 1) Group C (n = 20) received 0.4 mg fentanyl in 40 ml of 0.125% bupivacaine; 2) Group D (n = 20) received 2.5 mg droperidol and 0.4 mg fentanyl in 40 ml of 0.125% bupivacaine; and 3) Group B (n = 20) received 2 mg butorphanol and 0.4 mg fentanyl in 40 ml of 0.125% bupivacaine over 24 hours postoperatively. MEASUREMENTS AND MAIN RESULT: Postsurgical analgesia and the incidence of fentanyl-related complications, such as nausea/vomiting, somnolence, pruritus, and respiratory depression, were assessed for 24 hours postoperatively. At 16 and 24 hours after surgery, 75% of patients in Group D reported no pain versus 35% in Group C (p < 0.05). In addition, the overall visual analogue scale examined at 24 hours was significantly lower in Group D than that in Group C (22 +/- 17 mm vs. 44 +/- 22 mm, respectively; p < 0.05). Simultaneously, the incidence of postoperative nausea/vomiting was lower in Group D compared with Group C (20% vs. 60%; p < 0.05). On the other hand, butorphanol did not modify the analgesic effects or complications of epidural fentanyl infusion. CONCLUSION: In this study population, additional droperidol, not butorphanol, improved postsurgical analgesia accompanied by less incidence of nausea/vomiting during epidural fentanyl administration.

Adjuvants, Anesthesia↗
PubMed2000

Glioma/glioblastoma-specific adenoviral gene expression using the nestin gene regulator.

For glioma- and glioblastoma-specific gene expression, we utilized a nestin regulatory element whose activity was evaluated by the reporter gene lacZ. Nestin is a 38-kDa intermediate filament protein, and is expressed specifically in the neuroepithelial stem cells. Nestin is detected in gliomas and glioblastomas, but not in normal brain tissue. We constructed a nestin gene regulator by placing nestin's second intron before the 5' upstream region (2iNP). To obtain enhanced expression of this tissue-specific regulator, we utilized the adenovirus double-infection method with a Cre-loxP on/off switching system. We constructed a 'regulator' vector, Ax2iNPNCre, which expresses Cre recombinase under the control of the nestin regulatory element, 2iNP. A 'reporter' vector, AxCALNLNZK, expresses lacZ under the control of a strong CAG promoter when the stuffer sequence has been removed by Cre recombinase at a pair of loxP sites. We used seven human glioma/glioblastoma cell lines: U251, KG-1C, NGM5, U87 MG, LN-Z308, NP-2 and T98G. Of these, nestin was expressed highly in U251 and KG-1C, less in NGM5, and undetectably in the other four lines. With the use of the two adenovirus vectors, we found X-gal staining and high nestin regulator-promoted beta-galactosidase activities in four of the seven glioma/glioblastoma cell lines. Staining was strong in U251, KG-1C and NGM5, and less in U87 MG. LacZ expression was nearly undetectable in the non-glioma cell line, HeLa, but a little in COS-7. The adenovirus double-infection method, which uses a nestin regulator, is applicable for glioma/glioblastoma-specific expression.

Adenoviridae↗
PubMed2000

Molecular cloning of a novel brain-type Na(+)-dependent inorganic phosphate cotransporter.

We have isolated a human cDNA encoding a protein, designated DNPI, that shows 82% amino acid identity and 92% similarity to the human brain-specific Na(+)-dependent inorganic phosphate (Na(+)/P(i)) cotransporter (BNPI), which is localized exclusively to neuron-rich regions. Expression of DNPI mRNA in Xenopus oocytes resulted in a significant increase in Na(+)-dependent P(i) transport, indicating that DNPI is a novel Na(+)/P(i) cotransporter. Northern blot analysis shows that DNPI mRNA is expressed predominantly in brain, where the highest levels are observed in medulla, substantia nigra, subthalamic nucleus, and thalamus, all of which express BNPI mRNA at low levels. In contrast, DNPI mRNA is expressed at low levels in cerebellum and hippocampus, where BNPI mRNA is expressed at high levels. No hybridizing signal for DNPI mRNA is observed in the glia-rich region of corpus callosum. In other regions examined, both mRNAs are moderately or highly expressed. These results indicate that BNPI and DNPI, which coordinate Na(+)-dependent P(i) transport in the neuron-rich regions of the brain, may form a new class within the Na(+)/P(i) cotransporter family.

Animals↗
PubMed2000

Hemodynamic effects of milrinone during weaning from cardiopulmonary bypass: comparison of patients with a low and high prebypass cardiac index.

OBJECTIVE: To compare the hemodynamic effects of milrinone during weaning from cardiopulmonary bypass (CPB) in patients with a low pre-CPB cardiac index (CI) <2.5 L/min/m2) and in patients with a high pre-CPB CI (> or =2.5 L/min/m2). DESIGN: Prospective, randomized, double-blind study. SETTING: University hospital. PARTICIPANTS: Forty-eight patients scheduled for elective coronary artery bypass graft surgery. INTERVENTION: Patients were divided into 4 groups: (1) low pre-CPB CI/placebo, (2) low pre-CPB CI/milrinone, (3) high pre-CPB CI/placebo, and (4) high pre-CPB CI/milrinone. Patients received a loading dose of 20 microg/kg of milrinone followed by an infusion of 0.2 microg/kg/min or placebo 15 minutes before the anticipated weaning time. MEASUREMENTS AND MAIN RESULTS: In the low pre-CPB CI/ placebo group, low CIs and high systemic vascular resistances (SVRs) were observed after CPB. High doses of dopamine and dobutamine were needed, and infusion of epinephrine was used in 5 of the 12 patients for hemodynamic support. Milrinone improved CI and reduced SVR in the low pre-CPB CI/milrinone group. Norepinephrine was needed to maintain an adequate systemic blood pressure in 6 of the 12 patients, however. In the high pre-CPB CI/placebo group, satisfactory CIs and SVRs were observed during weaning from CPB with low doses of dopamine and dobutamine. Milrinone significantly increased CI and decreased SVR in the high pre-CPB CI/milrinone group: 10 of the 12 patients had CIs above the upper limit of normal, and 7 patients had SVRs below the lower limit of normal. CONCLUSION: Milrinone was effective during weaning from CPB in patients with a low pre-CPB CI. Milrinone in combination with norepinephrine was a good alternative to epinephrine for the treatment of myocardial dysfunction after CPB.

Aged↗