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Biomedical subjects

M Ohara

Publications and source records attributed to M Ohara.

At least 91 records · Page 5Linked to original sources

Upregulation of endothelial and neuronal constitutive nitric oxide synthase in pregnant rats.

Pregnancy is characterized by hemodynamic and body fluid alterations. Increased nitric oxide (NO) production has been suggested to play a role in the hemodynamic alterations of pregnancy and has also been reported to increase arginine vasopressin (AVP) release. We therefore hypothesized that gestation could increase both NO synthase (NOS) constitutive isoforms, neuronal NOS and endothelial NOS, and thereby contribute to the hyposmolality and peripheral arterial vasodilation of pregnancy, respectively. The present study was therefore undertaken to examine the constitutive NOS isoforms in aortas, mesenteric arteries, and hypothalami of pregnant rats on day 20 of gestation compared with age-matched nonpregnant rats. Plasma AVP was determined by radioimmunoassay and hypothalamic mRNA AVP by solution hybridization assay. Hypothalamic neuronal NOS was assessed by Northern blot and Western blot; endothelial NOS was assessed by Western blot in arteries and hypothalamus. The results demonstrated that 1) plasma AVP and hypothalamic AVP mRNA are increased in pregnant rats (n = 8), 2) neuronal NOS protein and mRNA are increased in hypothalamus of pregnant rats (n = 4), and 3) endothelial NOS expression, as assessed by Western blot analysis, is increased in both conductance (aorta) as well as resistance (mesenteric) arteries of pregnant rats (n = 4). We conclude that both of the constitutive NOS isoforms are increased in pregnant rats, suggesting that the peripheral arterial vasodilation and hyposmolality of pregnancy could be mediated by these isoforms.

Animals↗

[Responses of ankle plantar-flexors to various inhibitions of muscular activities in rats].

Effects of hindlimb suspension, tenotomy, denervation, and/or the combination of these models on plantar-flexors were studied in adult rats. Suspension-induced atrophy was not promoted by addition of tenotomy. But the magnitude of the atrophy was advanced if denervation or both denervation and tenotomy were combined with 5-day hindlimb suspension. Similar effects were noted in the cross-sectional area of single muscle fibers, especially of slow-twitch fibers. A shift of muscle fiber type from slow- to fast-twitch type was also induced mainly in soleus. The atrophy and fiber transformation were closely associated with a passive shortening of muscle due to the plantar-flexion of ankle and/or tenotomy and a disappeared electrical activity caused by denervation. The fiber atrophy, but not the shift of fiber type, was further advanced by the combination of tenotomy and denervation. It is suggested that muscle atrophy is caused by the decreased fiber size and protein content. The water content was also reduced proportionally.

Animals↗

Enhancement of lymphokine-activated killer cell cytotoxicity implicated in the increased expression of surface adhesion molecules on tumor cells treated with anticancer agents.

We investigated mechanisms underlying lymphokine-activated killer (LAK) cell cytotoxicity in terms of intensity of expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte-function-associated antigen-3 (LFA-3) on Daudi and KATO-III cells treated with cis-diamminedichloroplatinum (II) (CDDP) and mitomycin-C (MMC). Enhancement (mean, 49.8%) of ICAM-1 or LFA-3 in mRNA and protein expression on treated tumor cells was found by flow cytometry, slot-blot RNA analysis, and reverse transcription-polymerase chain reaction (RT-PCR). Increases in adhesion and cytotoxicity of LAK cells to treated tumor cells were 10.1% and 17.7%, respectively. Results suggested that increased ICAM-1 or LFA-3 expression by low-dose CDDP or MMC binds LAK cells to tumor cells, helping to kill tumor cells. Thus, LAK cell therapy with anticancer agent pretreatment could be useful for treatment of cancer patients.

Antibodies, Monoclonal↗

[Clinical evaluation of hepatic arterial infusion chemotherapy in patients with liver metastases from colorectal cancer].

Seventy-four cases of hepatic metastasis of colorectal cancer experienced in our hospital from January 1988 to February 1996 were examined for hepatic arterial infusion chemotherapy induced macrobiotic effect. A group (21 cases of hepatectomy and hepatic arterial infusion chemotherapy), B group (31 cases of hepatic arterial infusion chemotherapy only) and C group (22 cases of iv and po systemic chemotherapy) were comparatively examined for survival rate using Kaplan-Meier method. Single administration of adriamycin, epirubicin, cisplatin (CDDP) and 5-FU, along with CDDP-5-FU combined therapy and 5-FU 1,000 mg/5 hr intermittent continuous infusion therapy, were used. Mean survival period was 719 +/- 369, 426 +/- 417, 158 +/- 125 days for groups A, B and C, respectively. One-year survival rate by degrees of H factor was comparatively examined because of different H factor rates for these 3 groups. As a result, it proved to be 83 and 40% for groups A and B, respectively, in H1,2 cases and 32 and 11% for groups B and C, respectively, in H3 cases, with their respective significant differences (p < 0.05). Positive treatment, including hepatectomy, hepatic arterial infusion chemotherapy and the like, was suggested to contribute to patient macrobiosis.

Aged↗

How safe are the xenogeneic hemostats?--Report of a case of severe systemic allergic reaction.

We report herein the unusual case of a 55-year-old woman who developed a severe systemic allergy to Avitene (microfibrillar collagen hydrochloride), a xenogeneic agent sometimes used for topical hemostasis in laparoscopic cholecystectomy. The patient developed fever, general fatigue, mild liver dysfunction, and prominent eosinophilia postoperatively. A skin allergy test confirmed that these abnormal findings were attributable to an allergic reaction to Avitene.

Abdominal Abscess↗

Conformational changes of alpha-lactalbumin induced by the stepwise reduction of its disulfide bridges: the effect of the disulfide bridges on the structural stability of the protein in sodium dodecyl sulfate solution.

Four disulfide bridges of bovine alpha-lactalbumin (alpha-lact) were selectively reduced to obtain its derivatives with three, two, and zero disulfide bridges (designated as 3SS, 2SS, and 0SS alpha-lact, respectively). The original helicity was almost maintained in 3SS alpha-lact missing only the Cys6-Cys120 bridge. Upon the reduction of both Cys28-Cys111 and Cys6-Cys120 bridges, various changes occurred in the protein. In particular, the maximum fluorescence of 1-anilinonaphthalene-8-sulfonic acid was observed in this stage. Upon the reduction of all disulfide bridges, the hydrophobic box of the protein, formed by Trp60, Ile95, Tyr103, and Trp104, was disrupted and an internal helical structure was destroyed. The conformation of each derivative was examined mainly in a solution of sodium dodecyl sulfate. In the surfactant solution, the helicity increased from 33% to 37% in 3SS alpha-lact, from 26% to 31% in 2SS alpha-lact, and from 18% to 37% in 0SS alpha-lact, as against from 34% to 44% in intact alpha-lact. On the other hand, the tryptophan fluorescence of each derivative was affected in very low surfactant concentrations, suggesting that the tertiary structure considerably changed prior to the secondary structural change in the surfactant solution.

Anilino Naphthalenesulfonates↗

A case of Werner's syndrome associated with systemic lupus erythematosus.

The case of a 40-year-old woman with Werner's syndrome associated with systemic lupus erythematosus (SLE) is reported. The patient exhibited short stature, slender extremities, thinned hair, high-pitched voice, cataracts, ulceration of the fingers, and mental retardation. Malar erythema, photosensitivity, and proteinuria had been noted since age 34. The serum contained high titers of antibodies to dsDNA, Sm, nRNP, and SS-A/Ro. The simultaneous presence of Werner's syndrome and SLE could be a coincidental occurrence of the two diseases, although it might be due to an abnormality in replication or degeneration of DNA leading to the development of both diseases.

Adult↗

Gold sodium thiomalate selectivity inhibits interleukin-5-mediated eosinophil survival.

Gold sodium thiomalate (GST) has been used for treatment of patients with bronchial asthma. In this study we investigated the effects of GST on interleukin (IL)-5-mediated eosinophil survival in vitro. Blood cells were obtained from patients with bronchial asthma (n = 18). Eosinophils were purified from the blood samples by a Percoll discontinuous method and negative selection of neutrophils. Eosinophils (10(6) cells/ml) were incubated for 96 hours in 10% fetal bovine serum-RPMI 1640 (Nissui Pharmaceutical Co. Ltd., Tokyo, Japan) with various concentrations of recombinant human IL-5 (2 x 10(-9) to 2 x 10(-5) mmol/L) and with GST (0.01 to 100 mumol/L) in 96-well, flat-bottomed microtiter plates at 37 degrees C in a humidified 5% carbon dioxide atmosphere. Eosinophil viability was determined by trypan blue exclusion. IL-5 enhanced eosinophil survival in a dose-dependent manner. Higher concentrations of GST inhibited IL-5-mediated eosinophil survival. Moreover, GST induced apoptosis of eosinophils by antagonizing the effects of IL-5. However, GST did not inhibit IL-3- or granulocyte-macrophage colony stimulating factor-mediated eosinophil survival, suggesting that GST selectivity inhibits IL-5-mediated eosinophil survival. These results suggest that IL-5-mediated eosinophil survival is inhibited by GST and that GST blocks eosinophil apoptosis by IL-5. It is possible that GST may be capable of controlling eosinophil functions regulated by IL-5 in patients with bronchial asthma.

Apoptosis↗

Insulin nonattenuation of vasoactive agent-induced responses in mesangial cells from spontaneously hypertensive rats.

We recently found that insulin attenuates intracellular calcium transients and cell contraction caused by vasoactive agents in cultured rat mesangial cells. Because altered glomerular function may be causally related to the evolution of hypertension, we examined in the present study the effects of insulin on the functions of mesangial cells derived from spontaneously hypertensive rats (SHR) of 4- and 8-weeks of age. Age-matched Wistar Kyoto rats (WKY) were used as controls. Intracellular calcium concentration ([Ca2+]i) was measured with Fura-2 method in suspended mesangial cells. Pretreatment of mesangial cells with 5 micrograms/ml insulin for 120 minutes did not affect basal [Ca2+]i in either WKY or SHR mesangial cells. However, insulin pretreatment significantly attenuated [Ca2+]i transients to vasoactive agents in WKY mesangial cells. In contrast, [Ca2+]i transients to these agents were not attenuated by insulin in SHR mesangial cells. Additionally, SHR mesangial cell contraction in response to angiotensin II (Ang II) was not altered by insulin, while WKY mesangial cell contraction to Ang II was, as in normal Wistar rats, significantly reduced by insulin. Since we previously showed the possibility that the attenuation of calcium signal by insulin is via insulin-like growth factor I (IGF-I) receptor, we also examined the effect of IGF-I. In contrast to WKY mesangial cells, IGF-I-induced attenuation of [Ca2+]i responses to platelet activating factor was absent in SHR mesangial cells. [125I]-IGF-I binding in SHR mesangial cells was not significantly different from that in WKY mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Elevated serum levels of 3-deoxyglucosone, a potent protein-cross-linking intermediate of the Maillard reaction, in uremic patients.

3-Deoxyglucosone (3-DG) has been identified as an intermediate of the Maillard reaction in vitro. We measured serum 3-DG levels using gas chromatography/mass spectrometry and found a marked elevation in serum 3-DG levels in uremic patients compared with healthy subjects. The uremic patients with diabetes showed significantly higher serum concentrations of 3-DG than those without diabetes. 3-DG was demonstrated to be a potent protein-cross-linking agent in the reaction with lysozyme, leading to browning, fluorescence formation and polymerization of the protein by formation of advanced glycation end products (AGE). The increase in serum 3-DG levels in the uremic patients suggests that 3-DG may be responsible for the development of uremic complications by promoting the formation of AGE.

Adult↗

[Histological effect and prognosis after preoperative chemotherapy in esophageal cancer].

Preoperative chemotherapy for esophageal cancer was performed and the toxic effects, post-operative complications, histological effects and survival time were evaluated. Toxic effects and post-operative complications were rare. The histological effect was evaluated according to the Guidelines for Clinical and pathologic studies on carcinoma of the esophagus by the Japanese Society for Esophageal Disease. A histological effect of more than Grade II was seen from 25 to 42.1%. A significant difference was seen in the Kaplan-Meier survival curves between the response group and the no response group (p < 0.05). If we perform preoperative chemotherapy for esophageal cancer only to responsive cases determined by chemosensitivity tests, the prognosis of advanced esophageal cancer may be improved.

Adult↗

[Clinical experiences with the insertion of Dumon-type endotracheal stent tube for the patients with tracheal stenosis due to advanced esophageal carcinoma].

To relieve tracheal stenosis due to esophageal carcinoma, we have inserted Dumon-type endotracheal stent tube to 2 patients with stenosis of the left main bronchus and a patient with tracheal stenosis. Severe dyspnea and stridor found in these patients was much improved in all three cases. After insertion of the stent tube to 2 patients with stenosis of the left main bronchus, radiation therapy with the dose of 65 Gy to main esophageal lesion was undergone, which resulted in the partial remission. These management allowed the patients to discharge. The last case with tracheal stenosis was due to recurrence of the esophageal carcinoma, which required additional insertion of the stent tube at the proximal site after initial insertion in a short period. We conclude that the quality of life and prognosis of patients with tracheal stenosis due to advanced esophageal carcinoma may be improved by the insertion of Dumon-type endotracheal stent tube.

Aged↗

Supplementation of an elemental enteral diet with alanyl-glutamine decreases bacterial translocation in burned mice.

Although there are many reports of the importance of early enteral feeding in maintaining gastrointestinal integrity and preventing bacterial translocation (BT) following burn injury, no diet has been shown clinically to protect the GI tract postburn. Several studies suggest that glutamine (GLN) may benefit gut integrity following injury, shock and other stress. Unfortunately, the free amino acid GLN is unstable in solution. Alanyl-glutamine (ALA-GLN), a soluble form of GLN, maintains long-term stability in solution and could be supplemented to conventional liquid enteral diets. We studied the effects of ALA-GLN supplementation of the elemental diet Vivonex TEN on effecting BT in mice following 32 per cent TBSA full skin thickness burns. Groups A-D were burned. Group A (30 mice) was fed standard rodent chow, which contains extremely high (clinically non-useable) levels of protein. Group B (51 mice) was fasted 24 h, then fed chow 24 h. Group C (64 mice) was fed Vivonex TEN, and Group D (65 mice) received Vivonex TEN plus ALA-GLN (GLN equivalent, 14 g/l). A control group (Group E) consisted of 22 normal mice (no burn injury, chow diet). Mice were assessed for BT by sterile harvesting and plating of mesenteric lymph node tissue, 48 h postburn. Plates were considered positive if any bacterial growth was noted. Non-burned mice exhibited no BT, while burn-fasted mice showed a 64.3 per cent incidence of BT (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Enzyme linked immunosorbent assay (ELISA) and immunoprecipitation studies on anti-goblet cell antibody using a mucin producing cell line in patients with inflammatory bowel disease.

Circulating anti-goblet cell antibody and its corresponding antigen in patients with inflammatory bowel disease were investigated. Anti-goblet cell antibody in the serum was examined by immunocytochemistry and enzyme linked immunosorbent assay (ELISA), using a colonic cancer cell line, HT29-18-N2, which differentiates into intestinal goblet cells. The frequencies of anti-goblet cell antibody detected by immunocytochemistry were 14 in 48 patients with ulcerative colitis (29%) and five in 15 patients with Crohn's disease (33%). By ELISA, the frequencies of anti-goblet cell antibody were 38% in ulcerative colitis and 33% in Crohn's disease. This antibody did not relate directly to anti-neutrophil cytoplasmic antibodies (ANCA), although the serum samples positive for anti-goblet cell antibody were commonly positive for ANCA in ulcerative colitis. Immunoprecipitation and SDS polyacrylamide gel electrophoresis (PAGE) study showed that the antibody in the ELISA positive serum samples recognised a > 200 kD goblet cell antigen, which remained unchanged after reduction, indicating that it consists of single chain polypeptides. These results suggest that there is a subgroup of inflammatory bowel disease that has circulating anti-goblet cell antibody reactive with a > 200 kD antigen. The antibody detected by newly established ELISA will be a disease marker for this group and the identification of the corresponding antigens may be important for the understanding of the underlying immune abnormalities.

Adolescent↗

Modification of mesangial cell function by chloride is attenuated in spontaneously hypertensive rats.

The effects of extracellular Cl- concentration ([Cl-]o) on cultured mesangial cells from spontaneously hypertensive rats (SHR) were examined. Angiotensin II (ANG II)- and vasopressin (VP)-induced cell contraction and Ca2+ transients of SHR mesangial cells were unaffected when the cells were preincubated with 10 mM [Cl-]o, while obvious suppression of the responses to these agents was observed in Wistar-Kyoto (WKY) mesangial cells. Enhanced prostaglandin E2 (PGE2) production was elicited by a decrease in [Cl-]o in WKY mesangial cells. In contrast, PGE2 synthesis by SHR mesangial cells was not enhanced by low [Cl-]o. However, ANG II-stimulated PGE2 production and the attenuation of ANG II-induced cell contraction and Ca2+ transients by the addition of exogenous PGE2 were present equally in both WKY and SHR mesangial cells. Based on these findings, we conclude that the absence of modification of mesangial cell function by [Cl-]o in SHR is due to the inability of low [Cl-]o to enhance PGE2 production. Insensitivity of SHR mesangial cells to changes in [Cl-]o might underlie the dysregulation of renal function in SHR.

Angiotensin II↗

[Three cases of respiratory failure of collagen diseases accompanied by syndrome of inappropriate secretion of antidiuretic hormone (SIADH)].

We experienced three patients who have collagen diseases with respiratory failure accompanied by hyponatremia. They were one systemic lupus erythematosus patient with interstitial pneumonia, one rheumatoid arthritis patient with acute pneumonitis, and one dermatomyositis patient with pulmonary fibrosis and organizing pneumonia. In all 3 patients, hyponatremia appeared along with a decrease in arterial O2 partial pressure (PaO2) and the hyponatremia tended to improve when the PaO2 increased after inhalation of oxygen, even though their respiratory failure were not improved. In dermatomyositis patient, serum Na levels were over-corrected after increase in PaO2. The serum and urine osmolality, serum antidiuretic hormone (ADH) levels and clinical pictures demonstrated a presence of inappropriate secretion of ADH (SIADH) in all 3 cases when hyponatremia and hypoxia appeared. A close association between hyponatremia and hypoxia observed in 3 patients strongly suggested that their SIADH were associated with hypoxia since SIADH could be demonstrated by hypoxia. Therefore, it is important to realize that hypoxia-induced hyponatremia will be promptly corrected to hypernatremia by an oxygen inhalation, which could cause a lethal central pontine myelinolysis.

Adult↗