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Biomedical subjects

A Nohara

Publications and source records attributed to A Nohara.

At least 19 recordsLinked to original sources

Plasma homocysteine level and development of coronary artery disease.

BACKGROUND: The plasma level of homocysteine is an independent risk factor for atherosclerotic vascular disease. The relationship between plasma homocysteine level and the onset of coronary artery disease (CAD) has not been established. OBJECTIVE: To investigate the relationship between plasma homocysteine level and the age at which CAD was diagnosed. METHODS: Fifty-seven male patients aged < or = 65 years (mean age 53 years) with angiographically proven symptomatic CAD seen consecutively and 138 age-matched male control subjects (mean age 52 years) free from atherosclerotic vascular disease were studied. They were divided into two subgroups, a group of younger subjects (aged < or = 55 years) and a group of older subjects (aged 56-65 years). RESULTS: Plasma homocysteine levels in CAD patients significantly exceeded those of control subjects (means 13.4 versus 10.6 nmol/ml, P = 0.0002). Plasma homocysteine level of subjects in younger CAD group was significantly higher than that of subjects in older CAD group (15.0 versus 11.3 nmol/ml, P = 0.03), and age and logarithmically transformed plasma homocysteine level exhibited a significant negative correlation (r = -0.28, P = 0.03) for subjects in CAD group. Among control subjects, members of our two age subgroups had similar plasma homocysteine levels. Younger CAD patients had significantly higher plasma homocysteine levels than did younger controls (15.0 versus 10.4 nmol/ml, P < 0.0001). However, for older groups there was no significant difference between plasma homocysteine levels in CAD patients and controls (11.3 versus 10.9 nmol/ml). Multiple regression analysis showed that only logarithmically transformed plasma homocysteine level was a significant predictor for age of onset of CAD. CONCLUSION: An elevated level of plasma homocysteine is more important in the development of premature CAD than it is in that of late-onset CAD among men.

Adult

Prolactin stimulates mitogen-activated protein kinase in human leiomyoma cells.

The effects of prolactin (PRL) on proliferation of cultured human uterine leiomyoma-derived smooth muscle cells (SMC) and its mechanism of action were investigated. PRL stimulated DNA synthesis and the expression of PRL receptor was identified by ribonuclease protection assay. Moreover, the regulation of mitogen-activated protein (MAP) kinase by PRL in leiomyoma-derived SMC was investigated. PRL stimulated MAP kinase activity, as detected by 32P incorporation into MAP-2, in a dose-dependent manner. PRL also rapidly stimulated MAP kinase phosphorylation as detected by in vivo phosphorylation using 32P labeling and phosphotyrosine immunoblotting. These results suggest that PRL stimulates the proliferation of human leiomyoma cells via the MAP kinase cascade.

Calcium-Calmodulin-Dependent Protein Kinases

Reversibility in blood-brain barrier, microcirculation, and histology in rat brain after decompression.

To examine the changes in blood-brain barrier (BBB), cerebral microcirculation, and histology from 15 min to 72 h after decompression, 90 rats were exposed to experimental compression to 6 atm abs air for 90 min and subsequent rapid decompression. The disruption of BBB was examined by Evans blue extravasation. The cerebral microcirculation was demonstrated by perfusion with India ink. The area stained with Evans blue and the regions of defective filling with India ink, observed immediately after decompression decreased in size with time and were undetectable 3-24 h after decompression. The edematous brain tissue with enlarged perivascular space and darkly stained nerve cells also decreased to the uncompressed control level 1-24 h after decompression. These reversible dysbaric changes, however, reappeared 48-72 h after decompression. The different mechanisms, the physicochemical effects of microbubbles, and the maturation phenomenon after temporary brain ischemia induced by dysbaric microbubbles may be involved in the brain damage after decompression sickness.

Animals

The role of mitogen-activated protein kinase in oxytocin-induced contraction of uterine smooth muscle in pregnant rat.

Oxytocin causes the rapid tyrosine phosphorylation of mitogen-activated protein (MAP) kinase in both human and rat puerperal uterine myometrial cultured cells. The potential role of the MAP kinase pathway in oxytocin action was investigated with the specific MAP kinase kinase (MEK) inhibitor, PD98059. Oxytocin stimulation of the tyrosine phosphorylation of MAP kinase in both human and rat cultured puerperal uterine cells was abolished by pretreatment of the cells with MEK inhibitor in a dose-dependent manner. Although MEK inhibitor had no effect on oxytocin-induced intracellular Ca2+ mobilization in either pregnant human or pregnant rat uterine cells, it partly inhibited oxytocin-induced pregnant rat uterine contraction in a dose-dependent manner. These results suggest that MAP kinase pathway may have some important roles in oxytocin-induced uterine contraction.

Animals

Oxytocin stimulates mitogen-activated protein kinase activity in cultured human puerperal uterine myometrial cells.

The regulation of mitogen-activated protein (MAP) kinase by oxytocin in cultured human uterine myometrial cells was investigated. Oxytocin caused the rapid stimulation of MAP kinase activity detected in 32P incorporation of MAP-2. Oxytocin also stimulated the phosphorylation of MAP kinase detected in incorporation of [32P]orthophosphate into MAP kinase. Furthermore, oxytocin induced the tyrosine phosphorylation of MAP kinase. The oxytocin-dependent increase in the tyrosine phosphorylation of MAP kinase displayed a transient time course and was dependent on the concentration of oxytocin applied to the cells. Furthermore, we examined the mechanism by which oxytocin induced MAP kinase phosphorylation. Islet-activating protein (100 ng/ml), which inactivates Gi/Go proteins, blocked the oxytocin-induced phosphorylation of MAP kinase. Moreover, 1 microM ritodrine, which is known to relax uterine muscle contraction, attenuated oxytocin-induced MAP kinase activity and phosphorylation. These results provide evidence that oxytocin acutely activates MAP kinase through an islet-activating protein-sensitive G-protein in human uterine myometrial cells, suggesting that this new pathway may play an important role in the biological action of oxytocin on these cells.

Calcium-Calmodulin-Dependent Protein Kinases

In vitro effects of CINC/gro, a member of the interleukin-8 family, on hormone secretion by rat anterior pituitary cells.

We investigated the effects of CINC/gro on hormone secretion using normal rat anterior pituitary cells. In normal anterior pituitary cells, 10-100 ng/ml of CINC/gro significantly increased the secretion of PRL within 3 h of incubation, and two-fold enhancement of PRL secretion was induced by 100 ng/ml of CINC/gro within 24-h incubation, while the response of GH and ACTH secretions to CINC/gro was weak. On the other hand, CINC/gro suppressed basal LH and FSH secretions in a concentration-dependent manner. The percent inhibition of basal secretion by CINC/gro (50 ng/ml) within 24-h incubation was 70% for LH and 43% for FSH. Twenty-four-hour incubation with 100 ng/ml of IAP completely blocked the CINC/gro-stimulated PRL and GH secretions and CINC/gro's suppression of both basal LH and FSH secretions. These data demonstrate a new biological activity for CINC/gro and provide evidence for immune system regulation of anterior pituitary hormone secretion.

Analysis of Variance

The production of CINC/gro, a member of the interleukin-8 family, in rat anterior pituitary gland.

We investigated the possibility of detection of CINC/gro, which is a IL-8-like neutrophil chemoattractant, immunoreactivity in rat normal anterior pituitary gland by immunohistochemistry, western blot analysis and an ELISA. We first ascertained the possibility of detection of CINC/gro immunoreactivity in the anterior pituitary gland by immunocytochemistry. In the anterior lobe of the pituitary gland, a few CINC/gro-like immunoreactive cells were observed (1-3% of all cells in the anterior pituitary). The positive cells were middle or large in size and looked angular in shape. Intense immunoreactivity was observed in the cytoplasm but not in the nucleus. Analysis by immunoblotting with anti-CINC/gro antiserum gave a characteristic single CINC/gro band with a molecular weight of 6.3 kDa. CINC/gro immunoreactivity was also detected in 3-h conditioned medium of normal anterior pituitary cells by an ELISA, and that immunoreactivity increased significantly in a time-dependent manner during 24-h incubation. This immunoreactivity could be induced by TNF-alpha in a dose-dependent manner. These findings indicate that CINC/gro is produced in pituitary gland and also suggests the possibility that CINC/gro may play some role asa modulator of anterior pituitary function, especially in the cross-talk mechanism between the immune and neuroendocrine systems.

Analysis of Variance

Dopamine inhibits TRH-induced MAP kinase activation in dispersed rat anterior pituitary cells.

We recently reported the existence of two separate pathways for thyrotropin-releasing hormone (TRH)-induced mitogen-activated protein (MAP) kinase activation in GH3 pituitary tumor cells. To test the role of MAP kinase in TRH action, we examined the effect of dopamine (DA) on TRH-induced MAP kinase in primary cultures of rat anterior pituitary cells. 1 microM of DA attenuated 1 microM TRH-induced MAP kinase activity and phosphorylation. 100 ng/ml of islet-activating protein (IAP) blocked these inhibitory effects of DA. These results suggest that crosstalk exists between the DA signaling pathway and the TRH-stimulated MAP kinase activating pathway in rat anterior pituitary cells.

Adenosine Triphosphate

In vitro effects of CINC/gro, a member of the interleukin-8 family, on interleukin-6 secretion by rat posterior pituitary cells.

We investigated the effects of CINC/gro on IL-6 secretion by rat posterior pituitary cells. CINC/gro immunoreactivity was already detected in 1-h conditioned medium of normal posterior pituitary cells, and it increased significantly in a time-dependent manner during the first 24 h of culture. This immunoreactivity could be induced by TNF-alpha in a dose-dependent manner. On the other hand, CINC/gro stimulated IL-6 secretion by posterior pituitary monolayer cultures in a concentration dependent manner. Thus, CINC/gro significantly (P < 0.01) increased the secretion of IL-6 within 13 h of incubation, and this effect continued throughout 24 h of incubation. The stimulatory effect of 100 ng/ml CINC/gro on IL-6 secretion was completely blocked by 24-h incubation with 100 ng/ml IAP. These data demonstrate a new biological activity for CINC/gro in the posterior pituitary system.

Animals

[Effect of intraoperative stored blood transfusion on plasma neutrophil elastase and its modification by ulinastatin].

The effect of intraoperative stored blood transfusion on the changes in plasma neutrophil elastase (PMN-E) was studied in packed red cell, and in the patients transfused with stored blood (400-1000 ml) during surgery (n = 22), compared with the control in patients who had not received transfusion (n = 6). PMN-E was measured as elastase.alpha 1-antitrypsin complex (EAC) and the effect of ulinastatin (UTI) treatment on EAC was also evaluated. There was a significant correlation between transfusion volume and EAC or EAC/WBC (r2 = 0.65, P < 0.05 and r2 = 0.51, P < 0.05; respectively). There was no significant correlation between transfusion volume and EAC (r2 = 0.44, P > 0.05) in patients with UTI treatment during blood transfusion. These results and increased H2O2 concentration of expired breath in the patient whose plasma EAC exceeded 1,000 micrograms.l-1, suggested PMN-E is released from triggered neutrophil by increased EAC.

Blood Preservation

[The influence of the alcohol and the low protein diet on rat pancreas].

We investigated the influence of alcohol and the low protein diet upon rat pancreas. Rats were separated in four groups, 1) Control diet group (Cont), 2) Alcohol diet group (Al), 3) Low protein diet group (Lp), 4) Low protein and alcohol diet group (Lp+Al). They were fed on isocaloric liquid diet compulsorily through the gastric tube. They were sacrificed 3, 6, 12 weeks after. By the light microscopic observation on the rat pancreas which were fed for 12 weeks, lipid droplets in the acinar cells were observed in all groups other than Cont. Apoptosis was founded in Lp and Lp+Al groups. Protein plugs were observed in all groups, and no relation was found between the plugs and the location of the injured acinar cells. By the electromicroscopic observation, in Lp+Al group, acinar cells were typically injured (ER dilation, atrophic nuclei, mitochondria degeneration, etc.) and mesenchymal cells appeared among acinar cells. These results suggest that alcohol causes pancreatic acinar cell injury directly, and relative low protein diet helps to turn it worse.

Animals

[Chronic fatigue syndrome--51 cases in the Jikei University School of Medicine].

Between April 1991 and August 1992, we diagnosed 51 cases of CFS who met definition of CFS designated by CDC, 1988. They are 41 female and 11 male, and 78% are women. At first visit, their ages are ranged from 16 to 64 years old, and approximately 45% is 20 to 30 years old. In periods of illness from onset, 39.2% of the patients are in period of 6 month to 1 year, 19.6% within 2 years, and 15.6% within 3 years, respectively. The sufferer who have symptoms of CFS over 10 years long are in 6 cases. Most of patients have already been examined by many other clinics and hospitals. They have been told as no abnormal medical condition, or often as neurosis, depressive state and autonomous imbalance etc. Interesting things are trigger of CFS. 77.5% of patients have onset of flu-like symptom, including 5 cases of acute infectious mononucleosis. In many female patients, symptoms of CFS begun after hand work in addition to psychological factors. Specific laboratory results are not shown in CBC, urinalysis, biochemical studies and inflammatory marhers. 6 cases hare positive Rheumatoid factor and positive ANF are shown in 16 cases (31.3%). Specific patterns of anti EBV antibodies are not shown. Lymphocyte subsets used by monoclonal antibodies are not specific. At the present, prognosis is good and 56.8% of CFS patients are generally improved. For severe cases, NSAID, Sulpiride, Amitryptiline and minor tranquilizer are used.

Adolescent

Effects of the enantiomers of lansoprazole (AG-1749) on (H+ + K+)-ATPase activity in canine gastric microsomes and acid formation in isolated canine parietal cells.

The effects of the enantiomers of 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]-sulfinyl ]- 1H-benzimidazole (lansoprazole, AG-1749) on acid formation in isolated canine parietal cells and (H+ + K+)-ATPase activity in canine gastric microsomes were investigated. Both the (+)-and the (-)-enantiomer of lansoprazole inhibited the acid formation stimulated by dibutyryl cyclic AMP (db-cAMP) in isolated canine parietal cells in a concentration-dependent manner with IC50 values of 59 and 82 nM, respectively. The enantiomers showed concentration-dependent inhibition of (H+ + K+)-ATPase with IC50 values of 4.2 and 5.2 microM, respectively. On the other hand, the IC50 values of lansoprazole for db-cAMP-stimulated acid formation and (H+ + K+)-ATPase were 59 nM and 2.1 microM, respectively. These results suggest that the two enantiomers of lansoprazole have antisecretory action due to inhibition of (H+ + K+)-ATPase.

2-Pyridinylmethylsulfinylbenzimidazoles