Search PubMed⌕ Search

Biomedical subjects

K Hatakeyama

Publications and source records attributed to K Hatakeyama.

At least 217 records · Page 12Linked to original sources
PubMed1997

Human small Maf proteins form heterodimers with CNC family transcription factors and recognize the NF-E2 motif.

The transcription factor NF-E2, a heterodimeric protein complex composed of p45 and small Maf family proteins, is considered crucial for the regulation of erythroid gene expression and platelet formation. To facilitate the characterization of NF-E2 functions in human cells, we isolated cDNAs encoding two members of the small Maf family, MafK and MafG. The human mafK and mafG genes encode proteins of 156 and 162 amino acid residues, respectively, whose deduced amino acid sequences show approximately 95% identity to their respective chicken counterparts. Expression of mafK mRNA is high in heart, skeletal muscle and placenta, whereas mafG mRNA is abundant in skeletal muscle and is moderately expressed in heart and brain. Both are expressed in all hematopoietic cell lines, including those of erythroid and megakaryocytic lineages. In electrophoretic gel mobility shift assays binding to NF-E2 sites was found to depend on formation of homodimers or heterodimers with p45 and p45-related CNC family proteins. The results suggest that the small Maf family proteins function in human cells through interaction with various basic-leucine zipper-type transcription factors.

Amino Acid Sequence↗
PubMed1997

GTP cyclohydrolase I feedback regulatory protein is a pentamer of identical subunits. Purification, cDNA cloning, and bacterial expression.

GTP cyclohydrolase I feedback regulatory protein (GFRP) mediates feedback inhibition of GTP cyclohydrolase I activity by tetrahydrobiopterin and also mediates the stimulatory effect of phenylalanine on the enzyme activity. To characterize the molecular structure of GFRP, we have purified it from rat liver using an efficient step of affinity chromatography and isolated cDNA clones, based on partial amino acid sequences of peptides derived from purified GFRP. Comparison between the amino acid sequence deduced from the cDNA and the N-terminal amino acid sequence of purified GFRP showed that the mature form of GFRP consists of 83 amino acid residues with a calculated Mr of 9,542. The isolated GFRP cDNA was expressed in Escherichia coli as a fusion protein with six consecutive histidine residues at its N terminus. The fusion protein was affinity-purified and digested with thrombin to remove the histidine tag. The resulting recombinant GFRP showed kinetic properties similar to those of GFRP purified from rat liver. Cross-linking experiments using dimethyl suberimidate indicated that GFRP was a pentamer of 52 kDa. Sedimentation equilibrium measurements confirmed the pentameric structure of GFRP by giving an average Mr of 49,734, which is 5 times the calculated molecular weight of the recombinant GFRP polypeptide. Based on the pentameric structure of GFRP, we have proposed a model for the quaternary structure of GFRP and GTP cyclohydrolase I complexes.

Amino Acid Sequence↗
PubMed1997

Tumor spread and outcome of treatment in primary esophageal small cell carcinoma.

BACKGROUND: The most effective treatment for patients with esophageal small cell carcinoma has not yet been established because of the overall extremely poor prognosis regardless of the mode of treatment. The role of esophagectomy has been controversial in the management of patients with this disease. METHODS: The clinicopathologic characteristics of 13 patients with primary esophageal small cell carcinoma were retrospectively studied and the prognostic significance of various factors with respect to esophagectomy were evaluated. RESULTS: Lymph node metastases and distant metastases were found at the time of presentation in 92.3 and 46.2%, respectively. Two of nine patients treated by surgical resection for local-regional disease survived >5 years after radical esophagectomy with a projected 5-year survival rate of 22.2%. The remaining 4/13 patients were treated by nonsurgical modalities, but died of the disease within 10 months. A significant difference (P < 0.05) was detected between the survival curves of the two groups of patients. CONCLUSION: Radical esophagectomy may be an effective treatment modality in improving survival and the odds of a cure in patients with local-regional small cell carcinoma of the esophagus.

Aged↗
PubMed1997

Synchronous primary tumors of the extrahepatic bile duct and gallbladder.

BACKGROUND AND OBJECTIVES: This study aims to clarify clinicopathologic characteristics of synchronous primaries of the extrahepatic bile duct and gallbladder. Understanding multiplicity and its histologic confirmation is an important step for successful surgical management. METHODS: Of the 190 cases of resection of biliary tract neoplasms in this study, 10 had two separate tumors in the extrahepatic bile duct and gallbladder, which were investigated by the microscopic mapping technique for tumor extent using serial stepwise sectioning of specimens. RESULTS: Clinical diagnosis was made successfully in only two cases. Detailed histologic examination revealed seven cases with synchronous primaries and three cases with metastatic tumors. Several microscopic parameters had additional diagnostic value. The presence of synchronous primaries is not necessarily associated with a poor prognosis, since we had four long-term survivors. CONCLUSIONS: Diagnosis of synchronous extrahepatic biliary neoplasms is rarely made preoperatively. However, aggressive resection and careful microscopic examination are essential for the successful management and diagnosis of these special cases.

Aged↗
PubMed1997

Patterns of lymphatic spread of carcinoma of the ampulla of Vater.

BACKGROUND: The pattern of lymphatic spread of ampullary cancer is poorly documented. This pattern was clarified in order to define the rational extent of radical lymphadenectomy. METHOD: Thirty-nine consecutive patients who underwent pancreaticoduodenectomy with radical lymphadenectomy were included in the study. A total of 1447 lymph nodes dissected from the resected specimens was examined to detect the presence of metastatic foci. RESULTS: Twenty-one of the 39 patients had a total of 97 positive nodes. The sites of nodal involvement were the posterior pancreaticoduodenal (20 of 21 patients), inferior pancreaticoduodenal artery (IPDA; 12 of 21), anterior pancreaticoduodenal (three of 21), trunk of the superior mesenteric artery (three of 20), pericholedochal (three of 21), retroportal (two of 21), and para-aortic (three of five) regions. No metastases were found in the hepatic artery, cystic duct, perigastric, right coeliac, middle colic artery or right caval node groups. CONCLUSION: Ampullary cancer mainly spreads to the posterior pancreaticoduodenal node group, then to the IPDA node group, and finally to the para-aortic area. The rational extent of radical lymphadenectomy should include the pancreaticoduodenal, superior mesenteric, pericholedochal, retroportal and para-aortic nodes.

Ampulla of Vater↗
PubMed1997

Absolute dependence of T cell receptor(hi) cell generation and relative dependence of T cell receptor(int) cell generation on the thymus.

Recent evidence indicates that conventional T cells are generated by the mainstream of T cell differentiation in the thymus and acquire a high density of T cell receptor expression (i.e. TCRhi). In contrast, primordial T cells (or NK1.1+ T cells) are generated by the extrathymic pathways or an alternative intrathymic pathway and express an intermediate density of TCR (i.e. TCRint). To obtain further evidence, it was examined how thymus grafting influenced the distribution of T cell populations in athymic nude mice. When BALB/c nu/nu mice were engrafted with thymocyte-depleted BALB/c+/+ fetal thymi, two changes emerged after grafting: nude mice generated TCRhi cells de novo in the periphery as well as in the grafted thymi, and the absolute number of interleukin-2 receptor beta chain+ TCRint cells increased prominently in number in the periphery. Among thymic hormones tested, the administration of thymosin alpha induced a slight expansion of CD3int cells in nude mice. To examine a possible interaction of TCRint cells with TCRhi cells in the periphery, B6 nu/nu mice (Ly5.2+) were injected with TCRhi cells purified from the spleen of B6 Ly5.1 congenic mice. In this case, TCRint (Ly5.2+) cells expanded well in all tested organs of nude mice. These results suggest that the generation of TCRhi cells is absolutely dependent on the thymus and that TCRint cells expand under the influence of the thymus (humoral) and due to interaction with thymus-derived conventional T cells.

Animals↗
PubMed1997

Mouse liver T cells: their change with aging and in comparison with peripheral T cells.

Mouse liver contains both IL-2Rbeta- (or low positive) high T-cell receptor (TCR(hi)) cells and IL-2Rbeta+ intermediate TCR (TCR(int)) cells. TCR(int) cells consist of natural killer 1.1 (NK1)+ and NK1- subsets. NK1- TCR(int) cells increase constantly with age whereas TCR(hi) cells decrease. NK1+ TCR(int) cell proportions in the liver increase until middle age and decrease thereafter. Although NK1+ TCR(int) cells in other organs are few regardless of age, NK1- TCR(int) cells gradually appear in other lymphoid organs with aging. Skewed usage of Vbeta7 and Vbeta8 TCR was observed in NK1+ TCR(int) cells in the liver but the predominance was less obvious in NK1- TCR(int) and TCR(hi) cells in the liver and other organs. TCR V alpha14 messenger RNA (mRNA) was detected in NK1+ TCR(int) cells but not in the other two populations. In contrast, although NK1+ TCR(int) cells contain virtually no V alpha11+ T cells, NK1- TCR(int) cells contain a much higher proportion (approximately 12%) of V alpha11+ T cells, whereas approximately 4% of TCR(hi) cells are V alpha11+. NK activities of liver mononuclear cells (MNC) and splenocytes decrease with aging, although the former is always greater than the latter. NK activity of liver MNC is a function of NK cells, partly NK1+ TCR(int) cells but not NK1- TCR(int) cells or TCR(hi) cells. These results suggest that lymphocytes of liver and other organs at old age are no longer occupied solely by conventional thymus-derived T cells, and the increase of extrathymic IL-2Rbeta+ NK1- TCR(int) cells in liver and periphery could be closely related to immunological changes with aging.

Aging↗
PubMed1997

Dedifferentiated human ventricular cardiac myocytes express inducible nitric oxide synthase mRNA but not protein in response to IL-1, TNF, IFNgamma, and LPS.

There is evidence that nitric oxide (NO) may mediate some of the functional myocardial changes caused by bacterial LPS and inflammatory cytokines. The expression of the inflammatory or inducible NO synthase (iNOS) in human cardiac myocytes, however, has not been well characterized. Therefore, we treated cultured, dedifferentiated human ventricular cardiac myocytes with the combination of TNF-alpha (500 U/ml), IL-1beta (30U/ml), IFNgamma (100 U/ml), and LPS (E.coli 0111:B4, 10 microg/ml). Northern blot analysis revealed a approximately 4.5 kb transcript for inducible NOS (iNOS) in the stimulated human heart cells but not in untreated cells. RT-PCR confirmed that iNOS mRNA was only present in stimulated cells. However, treatment of the myocytes for up to 96 h with cytokines and LPS did not result in NO synthesis as measured by nitrite + nitrate accumulation in the culture medium, and no iNOS enzymatic activity could be detected in the cell lysates. Western blot analysis failed to detect iNOS protein. Thus, despite high and persistent levels of iNOS mRNA in cytokine-treated cells, iNOS protein was absent in this experimental model. GTP-cyclohydrolase I was induced both at the mRNA and protein levels and resulted in increased biopterin levels, indicating sufficient amounts of the cofactor tetrahydrobiopterin (BH4) were present, and that the failure to express an inducible protein was specific to iNOS. To determine if the absence of iNOS protein was due to a novel cardiac iNOS gene or modified iNOS transcript in human myocytes, we cloned an iNOS cDNA from cytokine-treated myocytes. Sequencing and expression of the clone revealed a functional iNOS cDNA with >99% identity to other human iNOS cDNA clones. When human cardiac cells were transduced with a retroviral vector carrying only the coding region of the human hepatocyte iNOS cDNA, both iNOS mRNA and protein could be detected. In conclusion, these cells derived from cultured human cardiac myocytes lacked the capacity to express an endogenous iNOS protein, the basis of which appears to be a cell-specific suppression or failure of iNOS translation.

Argininosuccinate Synthase↗
PubMed1997

Ischemic stricture of the rectosigmoid colon caused by division of the superior rectal artery below Sudeck's point during sigmoidectomy: report of a case.

Despite Sudeck's cautionary report regarding the risk of colon necrosis following a pull-through procedure, published in 1907, most colorectal surgeons do not pay close attention to Sudeck's critical point when operating in the rectosigmoid region. We report herein the case of a patient who developed an ischemic stricture, 6 cm in length, in the rectosigmoid colon distal to the anastomosis following a radical sigmoidectomy with division of the superior rectal artery immediately distal to Sudeck's point. This is the first documentation of a patient developing an ischemic stricture attributable to sigmoidectomy. Division of the artery distal to Sudeck's point most probably impaired the blood supply to the rectosigmoid colon, which subsequently resulted in occlusive ischemic colitis. Thus, there is a risk that division of the superior rectal artery distal to Sudeck's point may lead to colonic ischemia in the remaining rectosigmoid region following sigmoidectomy.

Aged↗
PubMed1997

Early gastric cancer manifested as brain metastasis: report of a case.

A case of early gastric cancer, limited to submucosal layer, which was manifested as cerebral metastasis is presented herein. A 47-year-old man was admitted to Nagaoka Chuo General Hospital with convulsions and a disturbance in consciousness, where a computed tomography (CT) scan revealed a cerebral tumor in the left temporal lobe. The resected tumor was identified as a metastatic adenocarcinoma. Further investigation revealed gastric cancer involving the posterior wall of the cardia. At laparotomy, multiple and small metastases of the liver and a jejunal metastasis were found and a palliative total gastrectomy was performed. The surgical specimen revealed a protruding, poorly differentiated medullary adenocarcinoma, with invasion of the submucosal layer. The patient died 4 months after undergoing the laparotomy. This case report is presented to make clinicians aware of the possibility that early gastric cancers may present as brain metastasis.

Brain Neoplasms↗
PubMed1997

Right hepatectomy for pyogenic liver abscesses with true multiloculation.

We report the case of 61-year-old woman with cryptogenic liver abscesses who had been profoundly ill with severe upper abdominal pain, impaired consciousness, prostration, continuous high fever secondary to sepsis, and thrombocytopenia (platelets, 1-5 x 10(4)/mm3) since admission. Ultrasonograms and computed tomograms revealed two separate multiloculated lesions in the right lobe of the liver, consistent with the liver abscesses. Immediately after diagnosis, percutaneous abscess drainage was performed under ultrasonographic guidance; however, only a small amount of pus was drained, prompting continuous irrigation of the abscess cavity. Four days later, transcatheter hepatic arterial infusion of antibiotics was attempted. However, the abscesses had enlarged and her general condition had worsened. On hospital day 8, she underwent right hepatectomy because the multiloculated lesions were refractory to drainage. The operation was successful in terms of hepatectomy, although she continued to suffer from sepsis, secondary right subphrenic abscess formation, and prolonged thrombocytopenia with associated coagulation disorders for two months. Examination of multiple cross sections of the resected specimen disclosed that the lesions consisted of aggregations of multiple small locules. There was no communication between the locules and there were true septations, rather than multiloculated lesions with pseudoseptations. The patient has been well for 2 years without recurrent abscess of the liver or any infectious disease.

Drainage↗
PubMed1997

Evaluating the rational extent of dissection in radical esophagectomy for invasive carcinoma of the thoracic esophagus.

To define the rational extent of dissection in radical esophagectomy for esophageal cancer, survival was studied according to nodal status in 154 patients undergoing extended radical esophagectomy. The incidence of cervical metastasis in patients with upper or middle esophageal tumors did not differ between those with favorable (grade N < or = 4) or unfavorable (grade N > or = 5) lymph node status, at 28.6% vs 20%, respectively. On the other hand, in patients with lower esophageal tumors, the incidence of cervical metastasis was significantly lower in those with favorable grade (grade N < or = 4) node status than in those with unfavorable grade (grade N > or = 5) node status, at 6.5% vs 46.7%, respectively. Survival did not differ in patients with upper or middle esophageal tumors according to whether they had regional (n = 42) or distant (n = 15) lymph node metastases, the 5-year survival rates being 11.6% vs 25%, respectively. However, in patients with lower esophageal tumors, none of 10 patients with distant node metastases survived for more than 4 years, whereas the survival rate was 43.7% at 5 years for 36 patients with regional node metastases. These results show that cervical lymphadenectomy should only be performed as part of radical esophagectomy in those patients with upper or middle esophageal cancer.

Adult↗
PubMed1997

What is the risk factor for metachronous colorectal carcinoma?

PURPOSE: The purpose of this study was to determine the risk factors for developing metachronous colorectal carcinoma and to determine an adequate postoperative colonoscopic surveillance. METHODS: Two hundred eighty-four patients, examined by routine colonoscopy after resection for colorectal carcinoma, were reviewed. Clinical and pathologic factors were assessed by multiple logistic regression analysis. RESULTS: One hundred eighty-three patients with synchronous adenoma or carcinoma at the initial operation had a significantly higher incidence of both metachronous adenoma and carcinoma than the 101 patients without a synchronous lesion. Other clinical factors including age, gender, tumor stage, tumor site, and tumor grade were not significant for an increased incidence of metachronous carcinoma. The presence of synchronous lesions proved to be the only risk factor (relative risk, 3.293; P = 0.0155) for developing metachronous carcinoma. Metachronous carcinoma was detected in 30 patients (10.6 percent) and completely removed from all patients. Mucosal carcinoma was found in 25 patients (8.8 percent) and invasive carcinoma in 5 patients (1.8 percent). All five invasive carcinomas were detected in asymptomatic patients having synchronous lesion. Four patients required a second operation for metachronous carcinoma more than 13 months following the first. CONCLUSION: The risk factor for developing metachronous carcinoma is the presence of synchronous adenoma or carcinoma at the initial operation. To detect metachronous carcinoma at a curable stage, annual colonoscopic surveillance should be performed for high-risk patients.

Adenoma↗
PubMed1997

Ischemic colitis arising in watershed areas of the colonic blood supply: a report of two cases.

There are several weak points in the colonic blood supply, known as watershed areas, which result from incomplete anastomoses of the marginal arteries. These watershed areas are more vulnerable to ischemic injury than other parts of the colon. We report herein the cases of two patients who developed ischemic colitis well localized in the cecum, and in the rectosigmoid region at Sudeck's point, respectively. This report and our review of the literature suggest that watershed areas, including the splenic flexure, or Griffith's point, Sudeck's point, and the ileocecal region, are high-risk regions for the development of ischemic colitis.

Colectomy↗
PubMed1997

Omental delivery of prostaglandin E1 effectively increases portal venous blood flow in 66%-hepatectomized rats.

Changes in portal venous blood flow (PVF) and systemic arterial blood pressure (SAP) were examined following prostaglandin E1 (PGE) application to the greater omentum and femoral vein in 66%-hepatectomized rats. PVF increased when PGE was administered to the omentum and femoral vein at 7.5 micrograms/kg per min for 2 min. The magnitude of PVF response due to both administrations was dose-dependent, but the duration of the PVF response in the omental application was longer than that in the femoral administration. SAP was unchanged after omental application, while femoral administration reduced SAP concomitant with an increase in PVF. These results suggest that, in this hepatectomized model, the omentum is a better site for PGE administration than the vein, and that omental PGE delivery is also effective for enhancing PVF without inducing any changes in SAP.

Alprostadil↗
PubMed1997

Acute portal hypertension reflecting shear stress as a trigger of liver regeneration following partial hepatectomy.

The concept of injury in liver regeneration after partial hepatectomy (PHx), and the reason hepatocytes that have not been directly injured regenerate, remain unclear. It is known that shear stress resulting from blood flow plays an important role in the mechanism of remodeling blood vessels, and portal pressure reflects shear stress. This study was conducted to determine whether acute portal hypertension (APH) can become a trigger of liver regeneration as shear stress following PHx in a rat model. Portal pressures became elevated immediately after 70% and 90% PHx, peaking on postoperative day (POD) 3, and thereafter decreasing in proportion to the diminution of liver regeneration. The portal pressures after 90% PHx were significantly higher than those after 70% PHx even on POD 7, while those of the portocaval (PC) shunt groups decreased following PC shunting both with and without 70% PHx. The liver/body weight (LW/BW) ratio also decreased in the PC shunt both with and even without 70% PHx. The gradient expressions of class I antigen on sinusoidal endothelial cells (SEC) were found only in the periportal area, which has the highest portal pressure in the healthy rat liver. However, after hepatectomy these expressions were detected from the periportal area to the central venous area. These results suggest that APH as shear stress following PHx may not only become a trigger of hepatocyte regeneration, but also of SEC regeneration, and that surplus APH induces liver dysfunction.

Animals↗
PubMed1997

Occult lymph node metastases detected by cytokeratin immunohistochemistry predict recurrence in "node-negative" colorectal cancer.

There is controversy about the prognostic significance of occult lymph node metastases detected by immunohistochemistry with the anti-cytokeratin antibody CAM 5.2. The aim of this study was to characterize occult lymph node metastases in colorectal carcinomas that might be associated with a higher risk of recurrence. Three hundred fifty-eight lymph nodes from 10 recurrent and 9 nonrecurrent cases of colorectal carcinoma were examined. All these patients had been reported originally as having no lymph node metastases by routine hematoxylin and eosin staining. Three 10-micron sections or ten 3-micron sections (30-micron total thickness) from each lymph node were stained with CAM 5.2 and examined for the presence of occult lymph node metastases. Occult metastases were detected in 67 of 175 lymph nodes from the recurrent cases, and in 23 of 183 lymph nodes from the nonrecurrent cases. The frequency of positive nodes was significantly higher in the recurrent cases. The recurrent cases had metastases in nodes more distant from the main tumor than did the nonrecurrent cases. Detection of occult lymph node metastases with cytokeratin immunohistochemistry may make it possible to identify patients with a higher risk of recurrence after the removal of a primary colorectal tumor.

Adult↗