The effects of inhalation of nebulized nitroglycerin on dogs with experimental pulmonary hypertension induced by U46619

Ｔｏｆｉｎｄａｓａｆｅ,ｓｉｍｐｌｅ,ｅｆｆｅｃｔｉｖｅａｎｄｓｅｌｅｃｔｉｖｅｐｕｌｍｏｎａｒｙｖａｓｏｄｉｌａｔｏｒ,ｗｅｔｅｓｔｅｄｔｈｅｅｆｆｅｃｔｉｖｅｎｅｓｓａｎｄｓａｆｅｔｙｏｆｉｎｈａｌｅｄｎｅｂｕｌｉｚｅｄｎｉｔｒｏｇｌｙｃｅｒｉｎ(ＮｅｂＮＴＧ)ｉｎｄｏｇｓｗｉｔｈｅｘｐｅｒｉｍｅｎｔａｌｐｕｌｍｏｎａｒｙｈｙｐｅｒｔｅｎｓｉｏｎ(ＰＨ)ｉｎｄｕｃｅｄｂｙｃｏｎｔｉｎｕｏｕｓｉｎｆｕｓｉｏｎｏｆａｔｈｒｏｍｂｏｘａｎｅａｎａｌｏｇｕｅ(Ｕ46619)ＴｈｅｕｓｅｏｆｉｎｔｒａｖｅｎｏｕｓＮ…     

Cytosol and serum concentration of cytokeratin subunit-19 fragment (cyfra-21-1) in breast-cancer

Cytokeratin 19 is a subunit of cytokeratin intermediate filament. CYFRA 21-1 is a new tumor marker using monoclonal antibodies which recognize a fragment of cytokeratin 19. CYFRA 21-1 was measured in cytosol of breast cancer tissues or in sera of patients with breast cancer or benign breast diseases to study the significance of this protein as a tumor marker. The cytosol concentration of CYFRA 21-1 was elevated in cancerous tissue compared to that in adjacent noncancerous tissue, and correlated with the tumor stage or the estrogen receptor status. In the serum, the mean value and positive rate for CYFRA 21-1 (assuming 2.2 ng/ml as the cut-off value) were 0.61 ng/ml (0%) in benign breast diseases, 0.98 ng/ml (6.7%) in stage I/II primary breast cancer, 75.67 ng/ml (60.0%) in stage III/IV primary breast cancer, 45.28 ng/ml (60.0%) in recurrent breast cancer, and 0.64 ng/ml (2.6%) in those with no evidence of recurrence. From the above, we concluded that CYFRA 21-1 could be a tumor marker with high specificity in breast cancer.     

Lipid alterations in the liver and serum of rats in histidine-excess and copper deficiency

To obtain further information on lipid metabolism in the histidine-excess and copper-deficiency, rats were fed basal, histidine-excess (the addition of 50 g L-histidine/kg diet) or copper-deficient diets for 0, 7, 21 and 42 d ad libitum. Liver triacylglycerol accumulated and the serum triacylglycerol level decreased after feeding of the histidine-excess diet for 21 or 42 d, but not after feeding of the copper-deficient diet. Serum cholesterol level increased in rats fed the histidine-excess diet for 7, 21 and 42 d, but not in rats fed the copper-deficient diet. Copper content in the liver and serum significantly decreased in rats fed the histidine-excess diet. Copper content in the liver and serum was markedly decreased in rats fed the copper-deficient diet. Liver zinc content was constant, but the serum zinc level decreased in rats fed the histidine-excess diet. Feeding of the copper-deficient diet hardly affected zinc content in the liver and serum. Urinary copper and zinc increased in rats fed the histidine-excess diet, and decreased or showed a decreasing tendency in rats fed the copper-deficient diet. Overall results indicated that feeding the histidine-excess diet caused copper deficiency, whereas hypercholesterolemia was not shown in rats fed the copper-deficient diet although the livers of rats fed the copper-deficient diet contained less copper than those of rats fed the histidine-excess diet. Thus, the responses on liver triacylglycerol and serum cholesterol to copper deficiency induced by the feeding of a histidine-excess diet are different from those to copper deficiency induced by feeding of a copper-deficient diet.     

Changes in immune function following surgery for esophageal carcinoma.

Changes in immune function due to surgical injury have been well-documented. Immunosuppression is one of the causes of infectious complications leading to organ dysfunction in critical illness. It is not known what kind of surgery in the daily clinical practice causes immunosuppression. Stress response and immune function following surgery for esophageal carcinoma, assuming a highly-stressed operation, were studied and then compared with the stress response and immune function following gastric surgery, a moderately-stressed procedure. Forty patients who underwent esophagectomy and 39 patients receiving gastric operation were studied. The concentrations of serum interleukin-6 (IL-6) were measured preoperatively, at 1, 2, and 6 h, and at 1, 3, and 10 d after operation. Total protein, serum albumin, rapid turnover protein, serum CRP, and cortisol were measured before operation and at 1, 3, 7, and 21 d after operation. ConA- and PHA-stimulated lymphocyte proliferation, IgA, IgG, and IgM were also measured preoperatively, and on 7 and 21 d following surgery. The patients were fed exclusively by total parenteral nutrition (TPN). A striking rise of IL-6 was observed, with a peak in both groups at 1 to 6 h following operation. The peak values were 419+/-30 pg/mL, which was approximately twice as high in the esophagectomy patients as in the gastrectomy patients (195+/-40 pg/mL). CRP and cortisol also increased after operation, and these increases were also significantly greater in the esophagectomy patients. ConA- and PHA-stimulated lymphocyte proliferation decreased significantly 7 d after esophagectomy (P<0.05), but was unchanged in the patients receiving gastrectomy. Suppression of cellular immunity correlated significantly with serum cortisol, and was preceded by a rise in serum IL-6. The IgA, IgG, and IgM levels, however, remained unchanged from their preoperative values throughout the study in both groups. Nutritional status in terms of serum protein, albumin, and rapid turnover protein, decreased postoperatively, but there was no difference between the two groups. It is, therefore, concluded that cell-mediated immunosuppression, preceded by a hyperinflammatory response, is an observable reaction in patients following esophageal surgery, but not in patients undergoing gastric surgery.     

17 Beta-estradiol increases VEGF receptor-2 and promotes DNA synthesis in retinal microvascular endothelial cells.

PURPOSE: Estrogen is known to promote angiogenesis in gonads. The presence of estrogen receptors in the vascular endothelium of organs other than gonads has been reported. The goal of this study was to determine whether estrogen promotes the proliferation of retinal microvascular endothelial cells and to explore the mechanism of it. METHODS: DNA was quantitated using primary cultures of bovine retinal endothelial cells that were incubated with different doses of 17 beta-estradiol (E2), VEGF, or both. The changes in expression level of VEGF and VEGF receptor-2 (VEGFR2) were measured using northern blot analysis after treatment with E2. The presence of estrogen receptors in the endothelial cells was studied by immunohistochemistry and western blot analysis. RESULTS: 17 Beta-estradiol (E2) increased the DNA level in bovine retinal capillary endothelial cells (BRECs) by 177% at 1 nM (P < 0.05) and 150% at 10 nM (P < 0.05) by comparison with unstimulated BREC. One hundred nanomole tamoxifen completely blocked the E2-induced DNA synthesis in BRECs. Ten nanomole E2 augmented vascular endothelial growth factor (VEGF)-induced DNA synthesis in BRECs significantly (160%, P < 0.01). Ten nanomole E2 also increased VEGF mRNA expression, which peaked after 24 hours (6.7 times, P < 0.05), and VEGF receptor-2 (VEGFR2) mRNA expression, which peaked after 9 hours (2.4 times, P < 0.05). The mRNA expression level of VEGFR2 peaked with 10 nM E2 (P < 0.05) and that of VEGF reached maximum with 1 nM E2 (15 times, P < 0.001). VEGFR2 and VEGF proteins increased in parallel with their mRNA levels. Immunocytochemistry showed estrogen receptor expression in BRECs, and western blot analysis indicated the presence of a 67-kDa protein that was compatible with the estrogen receptor. CONCLUSIONS: These findings suggest that E2 may stimulate BREC growth by the receptor-mediated pathway and that E2 may augment the VEGF-dependent angiogenesis partly through the upregulation of VEGFR2.     

Adhesion molecules involved in pleural dissemination of esophageal cancer cells

Pleural dissemination is a common cause of recurrence after surgery of patients with esophageal cancer. Very little is known about the biochemical processes involved in the initial attachment of cancer cells to pleural mesothelial cells. The authors conducted in vitro and in vivo studies to assess the role of adhesion molecules in this process, using 2 cell lines derived from human esophageal cancer. TE-1 cells, which pronouncedly express CD44H, adhered to the monolayers of mesothelial cells more firmly than T.Tn cells. On the other hand, the adhesion of TE-I cells to mesothelial cells was markedly inhibited by antibodies to CD44H or the beta(1) integrin subunit, and more strongly blocked by using a combination of the two antibodies. These antibodies inhibited the dissemination of TE-1 cells in the pleural cavity of nude mice. The findings suggest that CD44 and integrin play important roles in the initial attachment of esophageal cancer cells to mesothelial cells.     

Studies on Iridoid-related Compounds III: Gentiopicral, the Aglucone of Gentiopicroside

Enzymatic hydrolysis of gentiopicroside ( 1) provided the new aglucone, gentiopicral ( 2), the structure of which was firmly elucidated by means of spectroscopic methods.     

The significance of HLA-DRB1 matching in clinical renal transplantation.

We analyzed the genotype for HLA-DRB1 alleles by digestion of polymerase chain reaction-amplified genes with the restriction endonucleases (PCR-RFLP) method to investigate the influence of HLA-DR antigen "splits" at the DRB1 gene level on the incidence of acute graft rejection in the renal transplant. For all patients, the incidence of acute rejection was proportional to the number of the serological HLA mismatch (0% in patients with two-haplotype match; 18% with HLA-A, -B, and -DR zero mismatch; 33% with HLA-DR zero mismatch; and 48% with HLA-DR one mismatch). For the patients with serological HLA-DR zero mismatch, the incidence of acute rejection in patients with HLA-DRB1 one mismatch (10/13: 77%) was significantly higher than that in those with zero mismatch (2/27: 7%). It was concluded that genotyping for HLA-DRB1 alleles would be beneficial in predicting acute rejection in patients with serological HLA-DR zero mismatch, although no difference was noted in the graft survivals.