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Biomedical subjects

K Shirota

Publications and source records attributed to K Shirota.

At least 73 records · Page 4Linked to original sources

Effect of trapidil on serum lipid and apolipoprotein levels in patients with ischemic heart disease.

1. Serum total cholesterol (TCH), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein (LDL-C), atherosclerotic index (AI) and apolipoprotein (apo A-I, A-II, B, C-II, C-III and E) levels were investigated in patients with ischemic heart disease before and after medication of trapidil. 2. Twenty-one patients were orally given 100 mg of trapidil, three times daily (300 mg/day). After 8 weeks' administration, serum HDL-C level increased (P < 0.01) and AI decreased (P < 0.02) significantly, whereas TCH, TG and LDL-C levels tended to decrease but not significantly. 3. Among the parameters of apolipoproteins, apo A-I, a main protein of HDL-C, was significantly increased (P < 0.05) by trapidil. 4. These results indicate that trapidil has a beneficial effect on the coronary risk profile as reflected by lipid measurements.

Aged↗

Serological evidence of Coxiella burnetii infection in wild animals in Japan.

One hundred and thirty-four (26%) of 511 sera from 11 wild animal species in eight prefectures in Japan had antibody titers to Coxiella burnetii by the enzyme-linked immunosorbent assay. High prevalences were observed in Japanese black bears (Ursus thibetanus) (78%), Hokkaido deer (Cervus nippon yesoensis) (69%), Japanese hares (Lepus brachyurus) (63%), Japanese deer (Cervus nippon centralis) (56%), and to some extent in Japanese monkeys (Macaca fuscata) (28%). A low prevalence (13%) was observed in nutrias (Myocastor coypus). Japanese serows (Capricornis crispus), wild rats (Muroides sp.), raccoon dogs (Nyctereutes procyonoides viverrinus), wild pigs (Sus scrofa leucomystax), and masked palm civets (Paguma larvata) had no detectable antibodies to C. burnetii. Thus, six of 11 wild animal species in Japan were exposed to C. burnetii. Based on the high prevalences in some species, they may be a potential source of infection to both domestic animal and human populations.

Animals↗

Transcription of carcinoembryonic antigen in normal colon and colon carcinoma. In situ hybridization study and implication for a new in vivo functional model.

Recently carcinoembryonic antigen (CEA) has been functionally identified in vitro as a cell adhesion protein. Identification of its function in vivo requires knowing how CEA mRNA is transcribed in intact tissues. For this purpose, 16 cases of colon adenocarcinomas and autologous normal colon were studied by quantitative in situ hybridization for the expression of CEA mRNA. Normal colonic crypts displayed an upward gradient of mRNA expression. In colon carcinoma, tumor cells at the deep invading front of the tumor contain 2.6 times more CEA mRNA than tumor cells near the luminal surface. Immunoelectron microscopy showed intercellular CEA. In normal colon and colonic carcinoma, changes in CEA mRNA were paralleled by similar gradients in CEA protein, consistent with a transcriptional regulation of CEA expression. A new in vivo model of CEA function is presented to account for this overexpression of CEA occurring at sites characterized by changes in cell adhesion. The model requires that secreted CEA inhibits cell adhesion mediated by cell-bound CEA.

Aged↗

Comparison of coronary responses to intracoronary and intraaortic ergonovine and isosorbide dinitrate in patients with atypical chest pain.

Fifty patients with atypical chest pain were studied to compare coronary responses to intracoronary and intraaortic ergonovine. The diameters of the proximal, middle (1) and (2) (proximal segments of segments 2 and 3 [AHA classification], respectively), and distal segments of the right coronary artery were measured before and after intracoronary ergonovine (4 micrograms/minute over 4 minutes) and isosorbide dinitrate (ISDN) (2 mg) in 24 patients, and before and after intraaortic ergonovine (0.2 mg) and ISDN (5 mg) in 26. Mean vasoconstriction by intracoronary and intraaortic ergonovine were 13 +/- 1.5% and 9 +/- 0.8%, respectively (p < 0.02). Irrespective of the methods of administration, the responses to ergonovine were similar in the 4 segments. Mean vasodilation by intracoronary and intraaortic ISDN, which were used to quantify the degree of basal coronary tone, were 25 +/- 2.2% and 27 +/- 1.5%, respectively (p = not significant [NS]). There were significant negative linear correlations between the responses to ergonovine and ISDN in the middle (2) (r = -0.51; p < 0.05) and distal (r = -0.53; p < 0.01) segments in patients with intracoronary injection, and the proximal (r = -0.41; p < 0.05), middle (1) (r = -0.66; p < 0.01) and middle (2) (r = -0.69; p < 0.01) segments in patients with intraaortic injection. These observations indicate that low-dose administration of intracoronary ergonovine produces sufficient coronary vasoconstriction, similar to or slightly greater than that of intraaortic ergonovine in patients with atypical chest pain, but basal coronary tone may influence the vasoreactivity to ergonovine.

Aorta↗

Development of nitrate tolerance and usefulness of pulse therapy in a patient with vasospastic angina.

In a 58-year-old man with vasospastic angina, we investigated the relationship between the antianginal effects of isosorbide dinitrate (ISDN) and plasma ISDN concentration. Despite adequate plasma ISDN levels, sustained therapy using ISDN tapes and oral ISDN (transcutaneously 160 mg and orally 100 mg ISDN day-1) failed to exhibit antianginal effects. However, pulse therapy using sublingual short-acting ISDN prevented anginal episodes, although the plasma ISDN levels were less than those of sustained therapy. Nitrate tolerance of the antianginal effects was avoided by creating an abrupt plasma ISDN concentration gradient using sublingual ISDN.

Administration, Oral↗

Relation between serum uric acid and angiographically defined coronary artery disease in postmenopausal women.

Serum uric acid (UA) levels were studied in 40 postmenopausal women and 57 men, almost matched for age and body mass index (BMI) and undergoing coronary angiography. For women, the mean value of UA increased as the number of coronary arteries with > or = 50% stenosis increased. Its value was significantly higher (p < 0.05) in a three-vessel disease group than that of a group without stenosis. No significant changes were seen in men. However, the increase in UA for postmenopausal women was statistically (p < 0.05) correlated with serum triglyceride levels. Possibly, UA is not an independent coronary risk factor. However, elevated UA levels may suggest the prevalence of severe coronary artery stenosis for postmenopausal women.

Aged↗

Antiserum against tumor necrosis factor-alpha and a protease inhibitor reduce immune glomerular injury.

Previous studies in this laboratory have documented tumor necrosis factor alpha (TNF) release by macrophage laden glomeruli in the accelerated autologous form of nephrotoxic serum nephritis (AA-NTSN). We now report that the administration of anti-TNF antiserum to rats with the AA-NTSN reduces albuminuria in a dose related manner (day 8 postinduction) and limits glomerular necrosis (P less than 0.05) without affecting the endogenous creatinine clearance (CCr). Protease inhibitors block cytolytic activity of TNF in vitro and reduce glomerular necrosis in experimental nephritis in vivo. The combined administration of anti-TNF antiserum and an amidine-type protease inhibitor (BABIM) to rats with the AA-NTSN caused a greater diminution of albuminuria and histopathology than observed in rats treated with either agent alone, and also prevented the fall in CCr otherwise observed in this model system. Since, in our studies, BABIM did not inhibit cytolytic TNF activity in vitro, we conclude that the effects of combined administration of these two agents are mediated by independent mechanisms. Our results highlight the pathogenic significance of local TNF release in immune renal disease accompanied by prominent glomerular macrophage accumulation.

Albuminuria↗

Onset of subacute aggravation of chronic thyroiditis followed immediately by transient hypothyroidism during antithyroid drug therapy for Graves' hyperthyroidism.

A 56-year-old man presented with clinical and biochemical hyperthyroidism with high thyroid 99mTc uptake, positive result for antimicrosomal antibody (MCHA; 1:8,100) and markedly high activities of thyrotropin-binding inhibitory immunoglobulin (TBII; 90.0%) and thyroid-stimulating antibody (TSAb; 2,400%). Fifty days after the initiation of antithyroid drug therapy, he developed a painful tender enlarged thyroid and an accelerated erythrocyte sedimentation rate (ESR), which were followed immediately by hypothyroidism with a transient increase in MCHA titer (peak; 1:218,700) despite of maintenance of high TBII and TSAb activities. Two and a half months after the recovery from hypothyroidism, recurrent hyperfunction was observed with further elevation of TSAb activity (4,643%). After about 2 weeks, recurrences of a painful tender enlarged thyroid and an accelerated ESR, which were followed by abrupt progression to hypothyroidism, were found. Specimens obtained when he had still slightly tender goiter after the first and second episodes of neck pain showed microscopically extremely extended interstitial fibrosis with collapsed follicles and moderate lymphocytic infiltration. Thyroid-stimulation-blocking antibody was not detected at either onset of hypothyroidism. Thus, it is possible that Graves' disease, subacute aggravation of chronic thyroiditis and hypothyroidism coexist in the same individual. In such patients, thyroid status may be determined by the degree of each of the stimulating factors (TSH, TSAb and/or unknown factors) and suppressive or destructive factors (humoral and/or cellular) and may be changed in a very short interval.

Autoantibodies↗

Binding characteristics of [3H]ketanserin for serotonin-2 receptor in the rabbit platelet.

The present study was designed to examine 1) the properties of [3H]ketanserin binding to serotonin-2 (5HT2)-serotonergic receptors in the rabbit platelet membranes, 2) displacement affinities of various chemicals and 3) difference of the affinities between their chemicals and new agents, MCI-9042 and M-1. The plots of specific binding obtained from the Scatchard analysis using [3H]ketanserin for the platelet membranes were monophasic when the non-specific binding was determined by the use of 0.1 mM serotonin (5HT), and the Kd and Bmax values were 3.93 +/- 0.41 nM and 1.19 +/- 0.20 pmol/mg protein, respectively. The displacement potencies of chemicals which were serotonin receptor-, dopamine receptor-, histamine receptor-, and alpha-adrenoceptor-related agents were characterized by [3H]ketanserin binding to 5HT2-serotonergic receptor. The pKi values of a new antiplatelet agent, MCI-9042, and its metabolite, M-1, were 7.19 and 7.59, respectively and these values were lower than those of ketanserin and pirenperone but higher than those of methysergide, cinanserin and cyproheptadine. The affinities of ketanserin for 5HT2-receptors in the rabbit platelet were similar to those for 5HT2-receptors previously identified in the rat frontal lobe and in canine aorta, but cinancerin was selective to 5HT2-receptors in the rat frontal lobe and in canine aorta, prazosin was selective to 5HT2-receptor in the rabbit platelet, and MCI-9042 and M-1 had the same affinities to the receptors in the rat frontal lobe and in the rabbit platelet.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Distributional change of achromatic epithelial cells of the intestine in the fetuses and young of rats.

The achromatic epithelial cells (AEC), whose cellular materials remain unstained by several stains, e. g., H.E, PAS, Alcian blue, Orange G Anilin blue and Mucicarmin, are detected in the intestinal mucous epithelium of the Iar: Wistar Imamichi rat from the 19th day of gestation to the 21st day after birth. The results of light microscopic and transmission electron microscopic observations suggest that the rats AEC are equivalent to the previously reported vacuolar cells (VC) in cattle and in mice. The present paper describes that rat intestinal AEC appear first in the small intestine, and spread progressively toward the anal direction, while they disappear first in the cecum, and finally disappear at the ileum and the colon 22 days after birth.

Alcian Blue↗

Interleukin-6 and its receptor are expressed in human intestinal epithelial cells.

Recent studies have suggested that intestinal epithelial cells demonstrate some of the functions associated with immune competent cells. Based on these observations, we investigated whether gastrointestinal epithelial cells express Interleukin-6 (IL-6). The presence of this cytokine was tested in 53 normal and pathological tissue specimens of the human gastrointestinal tract using an immunohistochemical technique with anti-IL-6 monoclonal and polyclonal antibodies. Immunostaining shows that IL-6 is expressed in gastric and small intestinal epithelial cells. The tumor cells from a large subset (11 of 15) of colon cancer specimens were strongly immunostained. IL-6 immunostaining was less conspicuous and less frequent in the epithelial cells of normal colonic mucosa. Northern blot experiments indicated that the expression of IL-6 in colonic mucosa correlates quantitatively with the presence of its m-RNA. Furthermore, IL-6 receptor (IL-6R) m-RNA was also detected and was twice as abundant in colonic carcinoma as in normal colon. It is concluded that mucosal epithelial cells of the gastrointestinal system express IL-6 and that in the case of the colon, malignancy is accompanied by a higher expression. In addition, the presence of IL-6R transcript suggests that normal and neoplastic colonic epithelial cells might be autocrinally regulated by IL-6.

Antibodies, Monoclonal↗

Mammary carcinoma with pulmonary metastasis in a sow.

Mammary adenocarcinoma was diagnosed in a 3-year-old Landrace sow with prolonged infertility, anorexia and progressive emaciation after parturition. Gross examination confirmed a large tumour in the left anterior mammary gland with metastatic nodules on the pleura and in the parenchyma of lung. Microscopically, the tumour consisted mainly of solid adenomatous proliferations with numerous mitotic figures. Irregular glandular structures, solid nests of polygonal tumour cells without polarity and nests consisting of glandular, cribriform and solid portions were evident in dense fibrous stroma. Immunostaining revealed keratin in the tumour cells.

Animals↗

Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule.

Carcinoembryonic antigen (CEA) is a member of a family of cell surface glycoproteins that are produced in excess in essentially all human colon carcinomas and in a high proportion of carcinomas at many other sites. The function of this widely used tumor marker and its relevance to malignant transformation is therefore of considerable interest. We demonstrate here that CEA mediates Ca2+-independent, homotypic aggregation of cultured human colon adenocarcinoma cells (LS-180) and rodent cells transfected with functional CEA cDNA. Furthermore, CEA can effect the homotypic sorting of cells in heterogeneous populations of aggregating cells. CEA can thus be considered a new addition to the family of intercellular adhesion molecules. We also show that, whereas CEA is localized mainly to epithelial cell membranes facing the lumen in normal adult intestine, it is found on adjacent cell membranes in both embryonic intestine and colonic tumors. A model for the role of CEA in the tissue architecture of adult, embryonic, and aberrant tumor intestinal epithelium is presented.

Biomarkers, Tumor↗

Natural infection with canine distemper virus in a Japanese monkey (Macaca fuscata).

A case of encephalitis in a Japanese monkey (Macaca fuscata) was examined histopathologically and serologically. The animal had brain lesions consisting of perivascular cuffs, malacia, inclusion bodies and giant cells. Monoclonal antibody to the nucleoprotein of canine distemper virus (CDV) stained the inclusions, and the distribution of the virus antigen was closely associated with that of the histological lesions. Serologically, all the 22 monkeys in the same group as the diseased monkey had relatively high titers of neutralizing antibody to CDV, but not to measles virus (MV). The pattern of the antibody titers to CDV and MV closely resembled that of cynomolgus monkeys experimentally inoculated with CDV, but differed from that of monkeys inoculated with MV. These findings suggest that an epidemic of CDV occurred in these Japanese monkeys, associated with one case of fatal viral encephalitis. This is believed to be the first report of a natural infection by CDV in non-human primates.

Animals↗

Protein G-gold immunoelectron microscopy of colon carcinoma: the effect of tumor differentiation on carcinoembryonic antigen immunostaining.

The distribution of carcinoembryonic antigen (CEA) in human colonic cancer cells was compared to normal colonic epithelial cells by the recently introduced protein G-gold immunoelectron microscopy method. Immunostaining for CEA was obtained in glutaraldehyde-fixed tissues, but tissues fixed in osmium tetroxide failed to retain CEA immunoreactivity. In normal colonic mucosa CEA was found on the brush border and in the apical vesicles of the absorptive cells. The labeling was most intense in the cells lining the upper crypts and luminal surfaces. Mucin granules of goblet cells were also labeled. Well-differentiated adenocarcinoma cells showed cytoplasmic and apical labeling sites similar to those of normal colonic epithelial cells and in addition labeling of the basolateral membranes. The latter sites were more intensely labeled in poorly differentiated cancer cells whereas the intracytoplasmic reactivity was less intense compared to well-differentiated tumor cells. One case of poorly differentiated adenocarcinoma showed no labeling. These results indicate that the cellular site and intensity of CEA expression are closely associated with cellular differentiation in colonic cancer cells. The findings are consistent with the hypothesis that the biosynthesis and processing of CEA are different in colonic cancer cells as compared to normal colonic epithelial cells.

Carcinoembryonic Antigen↗