Biomedical subjects

Y Kobari

Publications and source records attributed to Y Kobari.

7 recordsLinked to original sources

PubMed1996

Induction of vascular cell adhesion molecule-1 by low-density lipoprotein.

Low-density lipoprotein (LDL) is a well-established risk factor for atherosclerosis. When endothelial cells are incubated with this lipoprotein in pathophysiologic amounts, the cells are activated. Among the documented cellular responses to LDL is increased recruitment of monocytes, which are believed to play a major role in promoting intimal plaque formation. The findings presented here link an atheogenic lipoprotein, LDL, with the induction of an adhesion molecule important in atherogenesis Human LDL induces the vascular cell adhesion molecule-1 (VCAM-1) transcriptionally with an increase in mRNA levels through activation of the VCAM promoter. This effect is blocked by anti-VCAM antibodies. After a 2-day incubation in LDL, the binding of NF-kappa B, which is believed to be a key oxidative-stress sensor for VCAM regulation, remains at basal level. In contrast, the binding activities of AP-1 and GATA, on the other hand, are increased by LDL. Thus, a component of LDL-enhanced endothelial recruitment of monocytes is attributed to VCAM-1 expression, which appears to be mediated through AP-1 and GATA. These data identify LDL as a VCAM-inducer possibly distinct from cytokines and endotoxin.

Arteriosclerosis↗

PubMed1996

Native LDL increases endothelial cell adhesiveness by inducing intercellular adhesion molecule-1.

Native LDL (n-LDL) increased human umbilical vein endothelial cell (EC) adherence of mononuclear cells. Such phenotypic changes suggest that n-LDL alters the usual expression of cell adhesion molecules to enhance the adhesive properties of the endothelium. To investigate n-LDL mechanisms governing adherence, ECs were exposed to n-LDL in concentrations up to 240 mg/dL for 2 and 4 days. n-LDL-treated ECs bound nearly threefold more phorbol myristate acetate (PMA)-stimulated U937 cells than control ECs but did not bind unstimulated U937 cells. Anti-cellular adhesion molecule-1 (ICAM-1) antibodies blocked PMA-stimulated U937 cell binding to control and n-LDL-treated ECs by more than 80%, suggesting that increases in ICAM-1 may be involved in this increased adherence. Although increases in PMA-stimulated U937 cell binding developed with respect to time and concentration, statistically significant increases were achieved only when n-LDL concentrations exceeded 180 mg cholesterol/dL at day 4. n-LDL increased endothelial adherence of freshly isolated human monocytes more than twofold and neutrophils by almost twofold. Fluorescent-linked immunoassays revealed that n-LDL increased ICAM-1 protein expression by twofold, which corresponded with increased ICAM-1 message levels. n-LDL also appeared to increase E-selectin and vascular cell adhesion molecule-1 message levels, but these changes did not translate into statistically significant differences in protein levels. Taken together, these data indicate that n-LDL increases ICAM-1 expression to enhance the adhesive properties of the endothelium. Such perturbations in EC function likely represent a proinflammatory response to protracted n-LDL exposure and one of the early steps in atherogenesis.

Base Sequence↗

PubMed1996

Reduced gene expression of vascular endothelial NO synthase and cyclooxygenase-1 in heart failure.

Endothelium-dependent responses are depressed in coronary and peripheral blood vessels after the onset of pacing-induced heart failure in dogs and heart failure of various etiologies in humans. The present study was designed to examine whether these responses were due to decreases in the expression of endothelial cell NO synthase (ecNOS) and cyclooxygenase-1 (COX-1). After 1 month of left ventricular pacing, 8 mongrel dogs were monitored for heart failure as defined by clinical signs and left ventricular end diastolic pressures > 25 mm Hg. Total RNA and protein were isolated from endothelial cells scraped from the thoracic aorta and analyzed by Northern and Western blotting, respectively. Blots probed with 32P-labeled cDNAs for ecNOS and COX-1 were quantified densitometrically, and results were normalized against GAPDH or von Willebrand factor (vWF). In arbitrary units, the ratios of ecNOS to GAPDH were 2.66 +/- 0.77 (mean +/- SEM, n = 17) and 1.12 +/- 0.37 (n = 6 and the ratios of COX-1 to GAPDH were 1.52 +/- 0.52 and 0.56 +/- 0.15 before and after heart failure, respectively. These represent 56% to 64% (P < .05) reductions in ecNOS and COX-1 gene expression. There was no change in the ratios of either COX-1 or ecNOS to vWF. There was also a marked reduction in ecNOS protein after heart failure, estimated at 70%. A marked reduction in nitrite production, a measure of enzyme activity, from thoracic aortas in response to stimulation by either acetylcholine or bradykinin also occurred. To determine whether ecNOS and COX-1 could be independently regulated, an orally active NO-releasing agent, CAS 936, was given to 7 normal dogs for 7 days, and aortic ecNOS and COX-1 mRNAs were analyzed. The ratio of ecNOS to GAPDH was depressed by 52% (P < .05) in aortas from these dogs, whereas the ratio of COX-1 to GAPDH was unchanged. Similar results were found when data were normalized to vWF. These results suggest that at least two endothelial vasodilator gene products are reduced in heart failure, as opposed to a selective defect in NO synthase gene expression.

Animals↗

PubMed1995

[Two patients with far advanced gastric cancer responding to combination chemotherapy with 5-FU and CDDP].

Combination chemotherapy with 5-FU and CDDP was given to two patients with far advanced gastric cancer. One patient was associated with metastases of lung, liver, pancreas and Virchow and periaortic lymph nodes, and the other was associated with metastases of periaortic lymph nodes and malignant ascitis. The regimen consisted of 5-FU 1,000 mg/m2 (day 1-5, continuous infusion) and CDDP 100 mg/m2 (day 3, 1 hr drip infusion). The interval was from the 6th to the 21st day. The response to chemotherapy showed shrinking of primary gastric lesions and metastases of liver, pancreas and periaortic lymph nodes, and disappearance of Virchow lymph nodes and malignant ascitis. Adverse reactions were thrombocytopenia (Grade 4), leukocytopenia (Grade 3), stomatitis (Grade 1, 3), vomiting (Grade 1, 2) and peripheral neuropathy (Grade 3). This therapy is thought to be effective against far advanced gastric cancer.

Adenocarcinoma↗

PubMed1991

Regression of diet-induced atherosclerosis in Göttingen miniature swine.

The regression of diet-induced atherosclerosis in Göttingen Miniature Swine was investigated after a 6-month induction period. At 1 month after feeding a high-cholesterol and high-fat diet, levels of beta-lipoprotein, total cholesterol, free fatty acids and phospholipid had increased rapidly and the high levels were maintained throughout the 6 month induction period. Morphological features at 6 months showed fatty streaks in the thoracic aorta and fibrous plaques in the abdominal aorta. After return to the conventional diet at 6 months, serum lipids decreased rapidly and maintained the baseline level throughout the 9 month regression period. Histopathological findings showed the regression of fatty streaks but the fibrous plaques did not regress. The present study therefore confirms the regression of fatty streaks in the aorta of Göttingen Miniature Swine by the administration of a cholesterol lowering diet.

Animals↗

PubMedDate not supplied

Ocular fixation using a baseball catcher's mask for postoperative prone positioning.

1. The optimal ocular position after vitreoretinal surgery with intravitreous gas tamponade is with the axis of the eye pointed downward. 2. Careless prone fixation may cause accidents of eyeball depression. 3. To help patients keep the proper prone facial and ocular positions, a modified catcher's mask was developed for use as a facial support.

Fixation, Ocular↗

PubMedDate not supplied

An eye on comfort: positioning a patient for ophthalmic surgery.

1. Because precise microsurgical procedures must be done within an extremely small surgical field, securing the patient's head during such surgery becomes imperative. 2. While the patient is placed in a position convenient for the surgeon, the position must also be comfortable for the patient; a compromise has to be made. 3. The successful outcome of surgery is the goal desired by both the surgeon and the patient. To achieve this, various surgical systems have received attention. Some of these systems attempt to minimize patient discomfort, such as using an air pillow to easily adjust the patient's head into the correct position.

Eye Diseases↗