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Biomedical subjects

K Hatakeyama

Publications and source records attributed to K Hatakeyama.

At least 127 records · Page 7Linked to original sources
PubMed2000

The differential effect of stress on natural killer T (NKT) and NK cell function.

When C57Bl/6 mice were exposed to restraint stress for 12 h or 24 h, lymphocytopenia was induced in the liver, spleen, and thymus. We examined which types of lymphocytes were sensitive or resistant to such stress by a immunofluorescence test. T cells of thymic origin were sensitive while NKT and NK cells were resistant. In contrast to the increase in the proportion of NK cells, NK activity of liver lymphocytes against YAC-1 targets decreased at 24 h after stress. On the other hand, their NKT cytotoxicity against syngeneic thymocytes increased in parallel with an increase in their proportion. In perforin -/- B6 mice and B6-gld/gld (Fas ligand-) mice, NK cells were found to mediate cytotoxicity through perforin while NKT cells mediated self-reactive cytotoxicity through Fas ligand. These results suggest that stress increases the proportion of both NK and NKT cells, but that NK cytotoxicity is suppressed while self-reactive NKT cytotoxicity is not, due to a diversity of their functional mechanisms.

Animals↗
PubMed2000

Disparate effect of beige mutation on cytotoxic function between natural killer and natural killer T cells.

Beige mice lack natural killer (NK) cytotoxicity, although NK cells are normally present. In recent studies, NK T cells have been newly identified. We therefore examined the number and function of NK T cells in beige mice. The number of NK T cells was at a normal level in the liver of beige mice. NK cytotoxicity was decreased in the liver of these mice, whereas NK T cytotoxicity was intact. When immunochemical staining for perforin was conducted, the majority of NK cells and the minority of NK T cells in beige mice carried a giant granule, containing perforin, in the cytoplasm. In the case of control B6 mice, the majority of NK cells and the minority of NK T cells had multiple, dispersed granules containing perforin. These results suggest that NK T cytotoxicity is unaffected by the beige mutation, owing to their cytotoxicity being mediated without the secretion system of perforin.

Animals↗
PubMed2000

Resistance of extrathymic T cells to stress and the role of endogenous glucocorticoids in stress associated immunosuppression.

When mice were exposed to restraint stress for 12 or 24 h, severe lymphopenia was induced in all immune system organs, including the liver and the thymus. However, in adrenalectomized mice, this response was completely absent. Phenotypic characterization revealed that interleukin (IL)-2Rbeta+CD3int cells (i.e. extrathymic T cells) with CD4+ phenotype and the NK1.1+ subset of CD3int cells (i.e. NKT cells) in the liver as well as the mature conventional T cells in the thymus were resistant to such stress. In adrenalectomized mice, there was no significant change in the distribution of lymphocyte subsets in all tested organs before stress. Interestingly, the number of lymphocytes in the liver and spleen and the proportion of NKT cells in the liver rather increased after stress in these adrenalectomized mice. Therefore, endogenous steroid hormones were indicated to be important in the induction of immunosuppressive states after stress. Among stress associated cytokines, the secretion of tumour necrosis factor (TNF)-alpha was completely suppressed while that of IL-6 was partially suppressed in adrenalectomized mice. These results suggest that endogenous steroid hormones are important for the induction of the stress associated immunosuppression and that NKT cells are resistant to stress, namely, resistant to exposure to endogenous steroid hormones.

Adrenalectomy↗
PubMed2000

Intensive expansion of natural killer T cells in the early phase of hepatocyte regeneration after partial hepatectomy in mice and its association with sympathetic nerve activation.

When C57BL/6 mice were partially hepatectomized (PHx), severe lymphocytosis was induced in the liver in the early phase of hepatocyte regeneration (4 to 12 hours after PHx). A major lymphocyte subset expanding in this organ was estimated to be natural killer 1.1(+) (NK1.1(+)) intermediate CD3 (CD3(int)) cells (i.e., NKT cells). CD3(int) cells are extrathymic T cells generated in situ in the liver. These changes were suppressed when mice with PHx were pretreated with a beta-adrenergicD antagonist (i.e., beta-blocker), propranolol (PPL). This might have been caused by sympathetic nerve stimulation during hepatocyte regeneration. An alpha-blocker showed a similar effect, although the magnitude of suppression was lower than that of the beta-blocker. We previously showed that NK and NKT cells express surface beta-adrenergic receptors and are activated in number by sympathetic nerve stimulation. In the present study, NK cytotoxicity mediated by liver lymphocytes obtained from mice with PHx decreased, whereas NKT cytotoxicity against syngeneic thymocytes increased. Purified CD3(int) cells were also found to be able to mediate NKT cytotoxicity against regenerating hepatocytes. These results suggest that sympathetic nerve stimulation after PHx results in subsequent activation of NKT cells and that these NKT cells might be associated with immunologic surveillance during hepatocyte regeneration.

Adrenergic alpha-Antagonists↗
PubMed2000

Significance of immunohistochemically demonstrated micrometastases to lymph nodes in esophageal cancer with histologically negative nodes.

BACKGROUND: We examined the prevalence, patterns, and clinical significance of nodal micrometastases in patients with esophageal cancer. METHODS: Cervical, mediastinal, and abdominal lymph nodes systematically removed from 37 patients without conventional histologic evidence of lymph node metastasis from esophageal squamous cell carcinoma were immunohistochemically examined to detect cells that were stained for cytokeratins by the monoclonal antibody cocktail AE1/AE3. Postoperative care and survival were compared in cases with and without such micrometastases. RESULTS: Nodal micrometastases were found in 14 of 37 patients (38%). Among these patients, 9, 7, and 4 had micrometastases to abdominal, mediastinal, and cervical lymph nodes, respectively. Postoperative tumor recurrence was significantly more frequent in patients with micrometastases (50%) than in those without (9%, P = .008). Overall and relapse-free survival in the former group was significantly worse than in the latter group (P = .042 and P = .002, respectively). Nodal micrometastases had an independent prognostic importance for relapse-free survival as determined by multivariate analysis. CONCLUSIONS: Metastatic tumor cells are frequently present in lymph nodes, even in patients without histologic evidence of nodal metastasis from esophageal cancer. Nodal micrometastases indicates a poorer prognosis after a curative esophagectomy procedure in histologically node-negative cases.

Aged↗
PubMed2000

Firm adherence of Staphylococcus aureus and Staphylococcus epidermidis to human hair and effect of detergent treatment.

Staphylococcus aureus and S. epidermidis are common pathogens in hospitals, and care should be taken not to disseminate these organisms among patients. We have focused on human hair as a source of bacterial contamination. We treated hair with culture solutions of S. aureus and S. epidermidis, and then performed scanning electron microscopy. Bacteria were detected on the surface of the cuticles of the hair, and the attached bacteria were not completely removed even by repeated washing with detergents. These results suggested that hair could be a source of bacterial contamination and indicated the importance of decontamination of hair.

Bacterial Adhesion↗
PubMed2000

Pseudo-Meigs' syndrome caused by secondary ovarian tumors from gastrointestinal cancer. A case report and review of the literature.

BACKGROUND: Pseudo-Meigs' syndrome is a condition characterized by nonmalignant ascites and/or pleural effusion caused by pelvic tumors other than solid benign ovarian tumors. This syndrome has only rarely occurred in association with gastrointestinal cancers. METHOD: We treated a 53-year-old woman who developed this syndrome due to ovarian metastasis from colon cancer. Diagnostic work-up for abdominal distension disclosed a sigmoid colon cancer and bilateral ovarian masses. Ultrasonography demonstrated massive ascites and a right pleural effusion. Repeated cytologic examinations of both effusions revealed no malignant cells. Laparotomy disclosed no peritoneal dissemination. A radical sigmoidectomy and hysterectomy with bilateral salpingo-oophorectomy were performed. RESULTS: Histologic examination confirmed ovarian metastases from the colonic primary tumor. After resection, both effusions disappeared promptly, confirming a diagnosis of pseudo-Meigs' syndrome caused by sigmoid colon cancer. The patient remains alive with disease after 52 months. CONCLUSION: Among 6 reported occurrences with gastrointestinal tumors including our case, the primary site was the colon or rectum in 5 and the stomach in 1. Two cases were due to Krukenberg tumors. Three patients with documented outcomes were alive 108, 52, and 12 months after resection. Clinicians should note that gastrointestinal cancers, especially colorectal tumors, rarely may cause pseudo-Meigs' syndrome and resection may provide long-term palliation.

Adenocarcinoma↗
PubMed2000

Evaluation of splenic circulation after spleen-preserving distal pancreatectomy by dividing the splenic artery and vein.

BACKGROUND/AIM: In the present study, we investigated the acute and late phases of splenic circulation after spleen-preserving distal pancreatectomy (SPDP) involving the division of splenic vessels. METHODS: An acute phase of splenic circulation was evaluated by laser flow meter and the late phase was estimated by (99m)Tc-galactosyl human serum albumin spleen scintigraphy. RESULTS: Splenic blood supply, evaluated by laser flow meter immediately after SPDP, dropped to one half of the prior blood supply. However, blood supply recovered 10 days after SPDP, as estimated by (99m)Tc-galactosyl human serum albumin spleen scintigraphy. CONCLUSION: There are two variations of SPDP: SPDP without preservation of the splenic artery and vein, and SPDP with preservation of the splenic artery and vein. The disadvantage of the former is the resulting decrease in splenic blood supply. The present findings may help to make up for this disadvantage.

Humans↗
PubMed2000

Endothelialization of the coils used to occlude a persistent ductus arteriosus: an angiographic study.

To assess the endothelialization of the coils used to close a persistent ductus arteriosus (PDA), the present study comprised a review of the follow-up aortograms and pulmonary angiograms in 25 patients who underwent coil occlusion. The minimal diameter and the length of the PDA were measured prior to the procedure, and the shortest distance between the aortic end of the deployed coil and the aortic end of the PDA was measured after coil deployment. Evidence of endothelial coverage of the coil was sought on follow-up angiograms performed 6-24 (15+/-5) months later and the factors that determined the thickness of the endothelial coverage on the aortic end were investigated. Separation of the coil and the contrast column were detected at the aortic end in all cases and at the pulmonary end in 18 of 25 cases. The thickness of the separation ranged from 0.4 to 1.3 (0.7+/-0.2) mm at the aortic end and 0.3 to 0.8 (0.6+/-0.2) mm at the pulmonary end. The length of the ductus and of the ampulla had a significant positive correlation with the thickness of the aortic end separation. Apparent endothelial coverage of the coil was completed by 6 months after coil occlusion. Infective endocarditis or thromboembolism is an unlikely complication once endothelium covers the implanted coil.

Angiography↗
PubMed2000

Analysis of oxidation sensitivity of maleate cis-trans isomerase from Serratia marcescens.

The maleate cis-trans isomerase gene (maiA) from Serratia marcescens IFO3736 was cloned and sequenced. Serratia MaiA has 62.4% amino acid identity with Alcaligenes faecalis IFO13111 MaiA and 64.9% with Bacillus stearothermophilus MI-102 MaiA. All known ten amino acid sequences of MaiA had significant conserved regions containing cysteine residues, which were previously suggested to be involved in an active site of the enzyme. The maiA gene was expressed in Escherichia coli, and expressed products MaiA was purified and characterized. The purified enzyme of strain IFO3736 showed high activity at room temperature and high heat stability. It also showed higher activity in the presence of high concentration of aspartic acid than the enzyme of A. faecalis IFO13111, but it was also sensitive to chemical oxidation. By amino acid composition analysis, cysteine, methionine, and tyrosine residues were suggested to be oxidized to inactivate the enzyme by chemical oxidation. To investigate the mechanism of chemical oxidation of the enzyme, six methionine residues in the conserved regions of S. marcescens MaiA were replaced with cysteine residues by site-directed mutagenesis. The analysis of the constructed mutants suggested that the Met201 residue near the Cys198 residue is involved in the sensitivity of the enzyme to chemical oxidation.

Amino Acid Sequence↗
PubMed2000

Molecular analysis of maleate cis-trans isomerase from thermophilic bacteria.

Several strains of thermophilic bacteria containing maleate cis-trans isomerase were isolated from soil samples and identified as Bacillus stearothermophilus, Bacillus circulans, Bacillus brevis, and Deleya halophila. The maleate cis-trans isomerase was purified and characterized from one of the isolated strains, B. stearothermophilus MI-102. The purified enzyme of strain MI-102 showed higher thermal stability than the enzyme of a mesophile, Alcaligenes faecalis IFO13111. The seven maleate cis-trans isomerase genes (maiA) of thermophile were cloned and sequenced. B. stearothemophilus MI-102 MaiA has 67% amino acid identity with A. faecalis MaiA. All eight amino acid sequences of maiA gene products had significant conserved regions containing cysteine residues, which were previously suggested to be involved in an active site of the enzyme. To probe the catalytic mechanism, three cysteine residues in the conserved regions of A. faecalis MaiA were replaced with serine by site-directed mutagenesis. The results suggest that Cys80 and Cys198 play important roles in the enzyme activity.

Alcaligenes↗
PubMed1999

Mechanisms underlying immunologic states during pregnancy: possible association of the sympathetic nervous system.

NK and extrathymic T cells are abundant in the decidua of the pregnant uterus. To determine how this unique pattern is induced, overall populations of leukocytes were examined in the blood and other tissues in pregnant women. Time-kinetic studies showed that a basal change of leukocytes during pregnancy was granulocytosis and lymphocytopenia in the blood. This change might be due to sympathetic nerve activation during pregnancy, because the administration of catecholamine is known to activate myelopoiesis in the bone marrow. In addition to the numerical change, the functional activation of NK and extrathymic T cells also seemed to be present. This might be due to NK cells and extrathymic T cells (as well as granulocytes), which carry a high density of surface adrenergic receptors. Such functional activation of NK and extrathymic T cells was more prominent in the blood and urine in patients with preeclampsia and hyperemesis gravidarum than in normal pregnant women. The present results suggest that the activation of granulocytes, NK cells, and extrathymic T cells is essential for the maintenance of pregnancy but that overactivation thereof may be responsible for the onset of pregnancy disorders.

Adult↗
PubMed1999

Administration of glucocorticoids markedly increases the numbers of granulocytes and extrathymic T cells in the bone marrow.

Glucocorticoids, steroid hormones, are widely used as an anti-inflammatory drug. However, clinicians have sometimes encountered adverse drug reactions such as ulcers and tissue damage. In this study, we investigated how such adverse reactions of glucocorticoids are evoked, using an experimental mice model. When hydrocortisone (0.5 or 1.0 mg/day/mouse) was administered daily for 2 weeks, severe leukocytopenia was induced in all immune system organs. However, granulocytes (Gr-1(+)Mac-1(+)) were increased in number in the bone marrow and peripheral blood. This seemed to be due to an elevated level of myelopoiesis in the bone marrow. As well as increasing in number, granulocytes were functionally activated as estimated by the Ca2+ influx and superoxide production. The proportion of primordial T cells (CD3(int)IL-2Rbeta+) in the thymus and the number of primordial T cells in the bone marrow also increased. Mice administered hydrocortisone became susceptible to stress. Thus, these mice showed gastric ulcers when they were exposed to restraint stress for 12 h. These results suggest that activated granulocytes and primordial T cells might provide a mechanism involved in steroid ulcers and tissue damage, possibly through the superoxide production of granulocytes and the autoreactivity of primordial T cells.

Animals↗
PubMed1999

Immunohistochemical detection of lymph node micrometastases from gallbladder carcinoma using monoclonal anticytokeratin antibody.

BACKGROUND: The objective of this study was to define the sensitivity and clinical implications of the immunohistochemical detection of lymph node micrometastases in patients with gallbladder carcinoma (GBC). METHODS: The authors examined a total of 385 regional lymph nodes taken from 26 consecutive patients with GBC who had undergone a radical resection. Histologic sections of the primary tumor and regional lymph nodes in each case were stained with both hematoxylin and eosin and an antibody against cytokeratins 8 and 18 (CAM5.2). A "micrometastasis" was defined as a metastasis missed on routine histologic examination with hematoxylin and eosin but detected by immunohistochemical examination with CAM5.2. Survival rates were calculated only in patients with Stage II or more advanced stage disease. RESULTS: All primary tumors were positive for CAM5.2. Routine histologic examination revealed 53 positive lymph nodes that were stained consistently with CAM5.2. Another seven lymph nodes had micrometastases. Patients with micrometastases showed a significantly worse survival rate than those without micrometastases (P = 0.037, log rank test). Among patients with no lymph node disease on routine histologic examination, there was a trend toward a worse survival rate in those with lymph node micrometastases (P = 0.10, log rank test). The paraaortic lymph nodes were involved more frequently in patients with lymph node micrometastases than those without (P = 0.009, Fisher exact test). CONCLUSIONS: The immunohistochemical detection of lymph node micrometastases using CAM5.2 is feasible in GBC patients and is useful in predicting survival in patients undergoing radical resection. Lymph node micrometastases may be an indicator of widespread lymph node disease in patients with GBC.

Aged↗
PubMed1999

Mutations in the p53 and scid genes do not cooperate in lymphomagenesis in doubly heterozygous mice.

Analysis of double mutant mice of the p53 and scid genes, which have a combination of cell cycle checkpoint/apoptosis and DNA repair defects, shows that the latter defect synergistically enhances lymphoma development with loss of the former function. These mice lack the ability to eliminate lymphocytes predisposed to neoplastic transformation resulting from faulty antigen receptor gene rearrangement. Here we examine the cooperativity in double heterozygotes of p53 and scid in which normal development of lymphocytes is not impaired. MSM mice carrying a p53-knockout allele were crossed with BALB/c mice heterozygous for the scid locus and 129 offspring were obtained. They were subjected to gamma-ray irradiation, 84 thymic lymphomas being generated. The tumors and host mice were genotyped of p53 and scid. Among 42 mice developing p53-deficient lymphomas, scid/+ and +/+ genotypes did not provide difference in onset and latency. Besides, allelic loss of the Scid gene occurred at a high frequency in those lymphomas but the loss exhibited no allelic bias. The results suggest that the scid/+ genotype is not a modifier of loss of p53 function in the double heterozygotes.

Alleles↗
PubMed1999

Esophageal mucoepidermoid carcinoma containing signet-ring cells: three case reports and a literature review.

We report 3 cases of esophageal signet-ring cell carcinoma which were found in a set of 505 resected esophageal tumors. The incidence of esophageal signet-ring cell carcinoma was 0.6%. All of the signet-ring cell carcinomas were histologically mixed with squamous cell carcinoma (mucoepidermoid carcinoma). The signet-ring cells had intracellular mucin, which was positive for both periodic acid-Schiff (PAS) and alcian blue at pH 2.5. At the time of presentation, extensive extraesophageal tumor spread and local extension were found in all cases. All of the patients died within 2 years after the esophagectomy irrespective of whether they received chemotherapy or radiotherapy. Our results, and those previously reported, suggest that most esophageal carcinomas containing signet-ring cell carcinoma are aggressive neoplasms associated with a poor prognosis after esophagectomy.

Aged↗
PubMed1999

Liver fatty acid-binding protein is a new prognostic factor for hepatic resection of colorectal cancer metastases.

BACKGROUND AND OBJECTIVES: Liver fatty acid-binding protein (L-FABP) is reported as a biological marker for enterocytic differentiation. We evaluated the prognostic value of L-FABP expression for patients undergoing hepatic resection of colorectal cancer metastases. METHODS: The study group comprised 68 patients who underwent hepatic resection for colorectal cancer metastases between 1982 and 1996 at Niigata University Medical Hospital, Niigata, Japan. L-FABP expression was immunohistochemically studied in metastatic liver tumors and their primary colorectal cancers. The relationship between L-FABP expression and patient prognoses was statistically analyzed. RESULTS: L-FABP was positively stained in 56% (38/68) of liver metastases from colorectal cancers and in 56% (38/68) of their primary tumors. Of 68 cases, 54 (79%) showed similar immunohistochemical findings between primary and metastatic tumors. Patients with L-FABP-positive liver metastases showed better prognosis than patients with L-FABP-negative metastases (P = 0.046). L-FABP expression in primary colorectal cancers more significantly (P = 0.009) affected long-term survival after hepatic surgery. Multivariate analysis revealed that the prognostic effect of L-FABP expression in primary colorectal cancers was exerted independently and that its impact was larger than conventional pathological prognosticators. CONCLUSIONS: L-FABP expression is suitable for use as a new presurgical prognostic factor for patients undergoing hepatic surgery for colorectal cancer metastases.

Adult↗