Search PubMed⌕ Search

Biomedical subjects

H Ohta

Publications and source records attributed to H Ohta.

At least 181 records · Page 10Linked to original sources

Activation of phospholipase C-Ca2+ system by sphingosine 1-phosphate in CHO cells transfected with Edg-3, a putative lipid receptor.

Sphingosine 1-phosphate (S1P) induces phospholipase C (PLC) activation and Ca2+ mobilization in many types of cells. We examined the possible involvement of Edg-3, one of the putative S1P receptors, in the phospholipase C (PLC)-Ca2+ system. S1P increased the cytoplasmic free Ca2+ concentration without detectable inositol phosphate production in vector-transfected CHO cells. In the Edg-3-transfected cells, however, the S1P-induced Ca2+ response was clearly enhanced, which was associated with a significant production of inositol phosphate. These S1P-induced responses in the Edg-3-transfected cells were inhibited by U73122, a potent PLC inhibitor. We conclude that Edg-3 may be one of the S1P receptors participating in the activation of the PLC-Ca2+ system.

Animals↗

CD28-deficient mice are highly resistant to collagen-induced arthritis.

CD28 provides a critical costimulatory signal in Ag-specific T cell activation. Recent studies have revealed an important role for CD28 in the development of autoimmune diseases. We have examined the role of CD28 in collagen-induced arthritis (CIA) by inducing CIA in CD28-deficient DBA/1 mice. CD28-deficient mice never developed arthritis and showed markedly decreased levels of IgG and IgM anti-type II collagen (CII) Abs. In addition, the CD28+/- mice had similar levels of IgG1 and IgG2a anti-CII Abs, whereas in the CD28-deficient mice the level of IgG1 anti-CII Abs was decreased compared with that of IgG2a. IFN-gamma production by lymph node cells in response to CII was also reduced. CD28-deficient mice were either immunized four times with CII in CFA to augment Ag loading or given low doses of IL-12 to enhance Thl type responses. Both treatments resulted in a very low incidence of CIA development and minimal disease. CD28-deficient mice developed arthritis from injection of lymph node cells from CII-immunized wild-type mice, followed by immunization with CII in CFA. Taken together, these results indicate that costimulation of CD28 cannot be replaced by repeated activation through TCR or other costimulatory molecules. Thus, CD28 plays a critical role in both cellular and humoral immunity against CII and is indispensable for the development of CIA.

Adoptive Transfer↗

Volumetric comparisons on some nuclei in the cerebellar complex of prosimians.

Seven measurements were performed on the cerebellar complex of 30 specimens, covering three species each of Cheirogaleidae, Lemuridae and Indriidae, and Daubentonia, and three each of Lorisinae, Galaginae, and Tarsius. The items measured were the volume of the medial (CM), interposed (CI), and lateral (CL) cerebellar nuclei, ventral pons (VPo), inferior olivary principal (OLIPr) and accessory (OLIAc) nuclei, and the vestibular nuclear complex (VES). The raw data for these measurements were previously reported [Matano et al., Folia Primatol 44:171-181, 182-203, 1985; 47:189-203, 1986; Matano, Anthropol Soc Nippon 100:69-82, 1992]. For this paper, the relative size of each nucleus was expressed in terms of size indices based upon the allometric line obtained by reduced major axis analysis and comparisons between species within family or subfamily were made. Lemur showed one of the highest cerebellar complex indices and Lepilemur one of the lowest. Generally, the three cerebellar nuclei (CM, CI, and CL) were enlarged to the same extent in each species. Only Daubentonia showed higher size indices of CL, VPo, and OLIPr than of CM and OLIAc. Characteristics of the cerebellar complex enlargement of Tarsius were comparable to those of prosimians. The VES indices for non-leaping Lorisinae were markedly lower than those for the actively leaping Galago and Tarsius.

Animals↗

Biocatalytic asymmetric decarboxylation.

Biocatalytic decarboxylation is a unique reaction, in the sense that it can be considered to be a protonation reaction to a "carbanion equivalent" intermediate in aqueous medium. Thus, if optically active compounds can be prepared via this type of reaction, it would be a very characteristic biotransformation, as compared to ordinary organic reactions. An enzyme isolated from a specific strain of Alcaligenes bronchisepticus catalyzes the asymmetric decarboxylation of alpha-aryl-alpha-methylmalonic acid to give optically active alpha-arylpropionic acids. The effect of additives revealed that this enzyme requires no biotin, no co-enzyme A, and no ATP, as ordinary decarboxylases and transcarboxylases do. Studies on inhibitors of this enzyme and spectroscopic analysis made it clear that the Cys residue plays an essential role in the present reaction. The unique reaction mechanism based on these results and kinetic data in its support are presented.

Alcaligenes↗

Hepatic lymph node involvement in resected cases of liver metastases from colorectal cancer.

PURPOSE: Lymph node metastasis in the hepatoduodenal ligament is known as one of the most significant prognostic factors after liver resection for colorectal metastasis. However, there have been very few articles on the clinical features of node-positive patients and on detailed distribution of positive nodes. Further, there has been no established strategy on how to handle hepatic lymph nodes during liver resection. To address these subjects, a retrospective study was conducted. METHODS: During the period of 1980 through April 1998, 182 hepatic resections were performed for metastatic colorectal carcinoma. Of these, 78 cases had hepatic lymph node sampling during the operation. Distribution of positive nodes, location of liver metastasis, stage of the primary lesion, and outcome after liver resection were analyzed. RESULTS: Nine cases (12 percent) had secondary lymph node metastases in the hepatoduodenal ligament. The incidence was slightly higher (13.5 percent) in the most recent 44 consecutive cases. There was a tendency for liver metastases in the right lobe to metastasize to No. 12b (or node of the foramen of Winslow, lymph nodes along the common bile duct) and liver metastases in the left lobe to metastasize to No. 8a (anterosuperior group of the lymph nodes along the common hepatic artery). Outcome of node-positive patients (n = 9) was extremely poor (P < 0.001) compared with that of node-negative patients (n = 66), and the most common site of recurrence in the node-positive patients was remnant liver and hepatic lymph nodes. Preoperatively, there were no significant predicting factors for positive hepatic lymph nodes. CONCLUSIONS: No. 8a and No. 12b nodes are principal nodes that should be palpated and sampled during liver resection to check the secondary lymphatic spread from liver metastases. Hepatic nodal involvement indicates the progression of disease beyond simple liver metastases and may not be the indication for simple surgical removal. Further study, including hepatoduodenal dissection and systemic adjuvant chemotherapy, may elucidate the survival benefit, if any, of liver resection in node-positive patients.

Case-Control Studies↗

MR and Tc-99m HMPAO SPECT images in a case of unusual widening of perivascular spaces (Virchow-Robin spaces).

We report a rare case of unusual widening of perivascular spaces (Virchow-Robin spaces). MR images showed multiple small round cystic areas along the perforating medullary arteries with signal intensity identical to the cerebrospinal fluid predominantly in the right cerebral white matter. Tc-99m HMPAO SPECT images showed no remarkable laterality and no definite ischemic lesion, and the neurological status of the patient was not remarkable. MR was a diagnostic examination and Tc-99m HMPAO SPECT was a useful supplementary examination in the evaluation of this case of unusual widening of Virchow-Robin spaces.

Aged↗

Zinc accumulation and metallothionein gene expression in the proliferating epidermis during wound healing in mouse skin.

Metallothionein (MT), a low molecular weight metal-binding protein, has been related to zinc and copper metabolism, the acute-phase response, and cellular proliferation. In this study, we investigated changes in zinc metabolism and MT gene expression occurring in tissue damage and repair during wound healing in mouse skin. Northern blot analysis revealed that a significant increase of MT mRNA was observed in the liver for 18 h after wounding, and serum zinc downfall and hepatic zinc uptake were observed. In situ hybridization analysis showed that no significant expression of MT mRNA was detected within the first 9 h after wounding. However, it was expressed restrictively in the proliferating epidermis of the wound margin after 12 h. Zinc began to accumulate in wounded skin after MT gene expressed. Northern blotting and immunocytochemical staining revealed that MT has been synthesized actively during the growth phase compared with the stationary phase in normal human epidermal keratinocytes in vitro. Intracellular zinc accumulation was observed in the proliferating cells. We concluded that hepatic MT plays an important role as an acute phase protein against host damage, and epidermal MT contributes in the supply of zinc to wounded tissue and activates proliferation for the regeneration of epidermis.

Animals↗

Mucin-producing biliary papillomatosis associated with gastrobiliary fistula.

We report a case of mucin-producing biliary papillomatosis in a 78-year-old woman. Abdominal ultrasound (US) and computed tomography (CT) showed wall thickening and dilatation of the intrahepatic bile duct (IHBD), as well as a nodular lesion, 1.2 cm in diameter, in the left branch of the IHBD. Gastric endoscopy revealed excretion of bile-containing mucin on the anterior wall of the body of the stomach. Endoscopic ultrasonography (EUS) showed gastrobiliary fistula and discharge of mucin into the stomach. Needle biopsy of the biliary tumor revealed papillary proliferation, but no malignant cells were recognized histologically. Therefore this patient was diagnosed as having mucin-producing biliary papillomatosis forming gastrobiliary fistula. She did not present with obstructive jaundice, probably because of the fistula. She is alive, without obstructive jaundice, 16 months after the diagnosis without having had surgery. This is, to our knowledge, the first reported case of biliary papillomatosis forming gastrobiliary fistula and with the patient free of obstructive jaundice.

Aged↗

Cardiac tamponade originating from primary gastric signet ring cell carcinoma.

A 45-year-old man with dry cough and dyspnea was referred by a medical practitioner for evaluation of heart failure on February 10, 1996. Chest X-ray revealed increased cardiothoracic ratio, and ultrasonographic echocardiography disclosed massive pericardial effusion with right ventricular collapse. Cardiac tamponade was diagnosed and pericardiocentesis was performed. Ten days after admission, the pleural effusion had become more pronounced, and thoracocentesis was performed. Carcinoembryonic antigen level was elevated in both the pericardial and pleural effusion, and cytology implicated adenocarcinoma, which suggested malignant effusion. Endoscopic study disclosed gastric cancer in the posterior wall of the upper body, and the histopathological diagnosis was signet-ring cell carcinoma. The patient died of respiratory failure on May 2, 1996, and autopsy was performed. The final diagnosis was gastric cancer with pulmonary lymphangitis, pericarditis, and pleuritis carcinomatosa, accompanied by enlargement of mediastinal and paraaortic lymph nodes. Interestingly, the primary signet-ring cell carcinoma of the stomach was situated mostly in the mucosa. Deep in the submucosal region, there was prominent invasion of the intralymphatic vessels, without direct destruction of the mucosa muscularis.

Carcinoma, Signet Ring Cell↗

A simple immunoradiometric assay for measuring the entire molecules of adrenomedullin in human plasma.

We developed a one-step two-site immunoradiometric assay (IRMA) using two kinds of monoclonal antibodies, which enables us to directly measure the entire molecules of adrenomedullin (AM) (the sum of mature-type AM (abbreviated, m-AM) amidated at the C-terminus and Gly-extended non-amidated AM) in human plasma using a small amount of sample (100 microl) without prior extraction. The detection limit of this assay was 0.5 pmol/l for a 100-microl sample. Intra- and inter-assay precisions were 3.4-7.3% and 5.8-7.6%, respectively. The dilution curves of plasma samples showed good linearity and analytical recovery was 89-118%. The mean total AM in plasma of healthy subjects was 9.00+/-2.13 pmol/l, whereas m-AM was 1.05+/-0.24 pmol/l. This method, together with our previously reported simplified method to specifically measure m-AM (Ohta et al., Clin Chem 1999;45:244-251), allows facile estimation of the plasma concentration of AM-Gly by subtracting m-AM from the total AM measured by the procedure described in this paper. We were able to show that the concentration of total AM in patients with sepsis was markedly higher than that in the healthy controls and that the ratios of m-AM/total AM were significantly different between the controls and patients.

Adrenomedullin↗

Rheologic analysis of gastric mucosal hemodynamics in patients with cirrhosis.

BACKGROUND: Portal hypertensive gastropathy causes some gastric mucosal microcirculatory disorders in cirrhotic patients, but the nature of the rheologic dysfunction in the gastric microcirculation remains to be clarified. METHODS: To examine the rheologic properties of the gastric microcirculation, we subjected 112 cirrhotic patients and 51 control subjects to endoscopic laser Doppler flowmetry and measured multiple variables of flow, red blood cell volume, and velocity. Furthermore, based on these results, we analyzed the shear rate which reflects the status of the microcirculatory system. To validate the laser Doppler flowmetry, we derived the relationship between red blood cell volume and cross-sectional areas of submucosal collecting venules; near-infrared endoscopy was used to evaluate this relationship. RESULTS: Analysis of shear rate according to the severity of portal hypertensive gastropathy showed that the mucosa was exposed to strong hemokinetic stress in severe cases, characterized by a higher shear rate than in control subjects or in mild cases. Nitroglycerin, administered by intravenous infusion (1.0 microg/kg/min), reduced blood flow and restored shear rate to control levels in patients with severe portal hypertensive gastropathy. CONCLUSION: This rheologic study of the gastric mucosa suggests that a disorder of the shear rate control mechanism in the microcirculation is associated with severe portal hypertensive gastropathy.

Endoscopy, Digestive System↗

Titres of biogenic amines and ecdysteroids: effect of octopamine on the production of ecdysteroids in the silkworm Bombyx mori.

At day two, a sharp peak of octopamine (OA) was observed in last instar female Bombyx mori larvae. This peak also appeared in male larvae a day later than in females at day three. An OA peak was also observed before the 3rd ecdysis. However, no OA peaks were observed in 4th instar larvae. At day eight and nine of the 5th instar, another OA peak was observed for male and female, respectively. A peak of tyramine (TA) was found at day one followed by a peak of OA at day two in 3rd instar larvae. At day two, a day before OA peak, a peak of TA was observed for male insects and before the 2nd peak of OA, TA titre was also high in 5th instar larvae. Immediately after 3rd ecdysis, a high titre of DL-beta-(3,4-dihydroxyphenyl)alanine (DOPA) was observed, followed by a peak of dopamine (DA) at day five. A peak of DOPA was found at day one followed by a peak of DA at day two in 3rd instar larvae. Similarly, a small peak of DOPA was observed at day two, followed by an increase of DA at days eight and nine after the 4th ecdysis. Ecdysteroid peaks were observed just before the 3rd and 4th ecdysis and an ecdysteroid titre increased after the start of spinning. The effects of OA and JH on production of ecdysteroids by prothoracic glands (PGs) were examined in order to identify neuromediators responsible for triggering pupation in B. mori larvae. Exogeneous OA (10-100 mM) reduced and 10 &mgr;M OA stimulated the production of ecdysteroids in the presence and absence of brain extracts by PGs in the final instar (day five) of B. mori in vitro. Meanwhile, exogeneous JHI (10 &mgr;g/ml) stimulated and at 5 &mgr;g/ml it reduced production of ecdysteroids in the presence of brain extracts. Gramine, an OA antagonist, delayed pupation when applied in the diet. Thus, OA may produce some biological effects on the programming of larval-pupal development.

Journal Article↗

Cryopreservation of sperm from the endangered formosan landlocked salmon (Oncorhynchus masou formosanus).

The Formosan landlocked salmon (Oncorhynchus masou formosanus) are at a high risk of extinction, and the sustained maintenance of the population will soon depend on aquaculture systems, which use cryopreservation of spermatozoa to increase genetic diversity. We investigated the effectiveness of dimethyl sulfoxide (DMSO), dimethyl-acetamide (DMA), and methanol as cryoprotectants in combination with 300 mM glucose as extender on the freezing of Formosan landlocked salmon spermatozoa. We also evaluated the morphological changes of Formosan landlocked salmon spermatozoa after their immediate dilution in the 300 mM glucose-DMSO extender and after freeze-thawing. The spermatozoa frozen with DMSO as a cryoprotectant showed significantly higher post-thaw motility and fertility than spermatozoa frozen with DMA or methanol. The fertilization capacity of frozen-thawed Formosan landlocked salmon was comparable to that of fresh spermatozoa. Intersubspecies fertilization trials between cryopreserved Formosan landlocked salmon spermatozoa and Amago salmon eggs showed high fertilization rates. Based on the findings, the potential value of using sperm bank to safeguard this endangered species is discussed.

Animals↗

Lineage switch in childhood leukemia with monosomy 7 and reverse of lineage switch in severe combined immunodeficient mice.

Morphophenotypic lineage switches occur in a small percentage of those with acute leukemia, and the underlying mechanisms are not clear. In this study, we attempted to induce a lineage switch in acute myelocytic leukemia (AML) with monosomy 7, whose lineage had switched from acute T-lymphocytic leukemia (T-ALL) during chemotherapy, in severe combined immunodeficient (SCID) mice. Although the transplanted myeloid cells were engrafted in SCID mice without cytokine administration, T-ALL developed in SCID mice treated with recombinant human granulocyte-macrophage colony-stimulating factor or recombinant human interleukin 3. Analysis of the nucleotide sequences of the rearranged T-cell receptor gamma-chain (TCR-gamma) gene revealed that this lineage switch resulted from the selection of the T-lineage subclone in SCID mice, which had expanded at onset. In addition, we found that the T-lineage and myeloid cells belonged to the distinct subclones, which were different in TCR-gamma gene rearrangements, but were derived from a common clone with an identical N-ras gene mutation for both subclones. In in vitro cultures, only the myeloid subclone grew; the T-lineage subclone failed to grow even in the presence of recombinant human granulocyte-macrophage colony-stimulating factor or recombinant human interleukin 3. These results suggested that the initial diagnostic T-lymphoid subclone, whose growth was dependent on these cytokines and the hematopoietic microenvironment, emerged from a bipotential T-lymphoid/myeloid leukemic stem cell, and further genetic event(s) induced the myeloid subclone, which grew independently of these cytokines and the microenvironment.

Acute Disease↗

Optical resolution of racemic citronellol via a double coupling system in an interface bioreactor.

A double coupling system consisting of acetyl coenzyme A [acetyl-CoA] formation via the metabolism of glucose and the subsequent acetylation of a primary alcohol by acetyl-CoA with the aid of alcohol acetyltransferase [AATFase], was applied for the optical resolution of racemic citronellol. Pichia kluyveri IFO 1165 was superior for the optical resolution of racemic citronellol and provided (S)-citronellyl acetate and (R)-citronellol with high enantioselectivity and yield. The strain also exhibited excellent resistance to high concentrations of citronellol, i.e., it could maintain metabolism and enantioselective acetylation even in the presence of 30% citronellol. The coupling system using P. kluyveri IFO 1165 was applied to two new types of interface bioreactors, tentatively referred to as bead-packed and multistory interface bioreactors. Using the latter bioreactor, (S)-citronellyl acetate and (R)-citronellol were produced in large amounts at high enantioselectivity and yield.

Journal Article↗

Histocompatibility antigens and alleles in Japanese haemophilia A patients with or without factor VIII antibodies.

We carried out human leukocyte antigen (HLA)-A, B, Cw, DR and DQ serological typing and HLA-DQA1, DQB1, DRB1 and DPB1 genetic typing for 46 Japanese haemophilia A patients, including 20 who had developed an antibody to factor VIII. It appears that anti FVIII inhibitor formation is associated with the major histocompatibility complex in Japanese haemophilia A patients. Absence of HLA-A24 is a principal risk factor for inhibitor formation in Japanese haemophilia A patients. As supplemental risk factors, HLA-DR4.1, DQ4 and DQA1*0301=2 are positively associated with patients exhibiting inhibitor compared with normal subjects. This and previous studies show that the association between HLA antigens and the formation of inhibitor depends on race. Data of HLA typing may be useful for the recognition of groups at high risk for the possible formation of inhibitor among Japanese haemophilia A patients.

Alleles↗

Thrombotic microangiopathy associated with reactivation of human herpesvirus-6 following high-dose chemotherapy with autologous bone marrow transplantation in young children.

Thrombotic microangiopathy (TMA) is a serious complication of BMT. Several factors are important in the etiology of TMA, such as cyclosporin A, GVHD, irradiation, intensive conditioning chemotherapy and infection, which cause damage to vascular endothelial cells leading to activation of these cells. We describe two young children with TMA following high-dose chemotherapy with autologous BMT. Development of TMA was accompanied by reactivation of HHV-6, which was identified by both an increase in the copy number of HHV-6 DNA in the peripheral blood and a significant increase in antibody titers to HHV-6. Thus, it was suggested that reactivation of HHV-6 together with high-dose chemotherapy played an important role in the pathogenesis of TMA in these patients. Since HHV-6 is known to infect vascular endothelial cells, and CMV which is virologically closely related to HHV-6, has been reported to be a pathogen that causes TMA, infection with HHV-6 of vascular endothelial cells may induce TMA via damage and activation of these cells.

Bone Marrow Transplantation↗