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91.
To assess the pathophysiological role of atrial natriuretic factors in the regulation of blood pressure, we studied the effect of chronic infusion of a synthetic atrial natriuretic factor of 25 amino-acid residues on blood pressure and sodium-water excretion. Experimental subjects were rats with hypertension made by chronic infusion of vasopressin on regular intakes of sodium or on sodium loading with 1% NaCl as drinking water. When a subdepressor dose (150 micrograms/kg/day) of synthetic atrial natriuretic factor was delivered via an osmotic minipump into the jugular vein simultaneously with 7.2 U/kg/day of vasopressin infused intraperitoneally by another osmotic minipump, the expected elevation of systolic blood pressure was completely inhibited. This was not accompanied by any changes in urine volume and urinary sodium excretion. The antihypertensive effect was sustained throughout the experimental period lasting 3 days in rats on regular sodium intake (p less than 0.01) or on sodium loading with 1% NaCl as drinking water (p less than 0.01). These results indicate that a subdepressor dose of synthetic atrial natriuretic factor can modulate the vasopressor effect of vasopressin. Therefore it is suggested that an atrial natriuretic factor may be involved in the regulation of blood pressure via its antagonizing effect to vasopressin.  相似文献   
92.
93.
Protein kinase C (PKC) has been implicated in enhancing cellular sensitivity to cis-diamminedichloroplatinum(II) (CP). We have synthesized a series of novel analogues of lyngbyatoxin A (7-linalylindolactam V), a natural tumor promoter and a potent activator of PKC, and investigated the effects of these synthetic compounds on PKC activity and the antiproliferative activity of CP. Lyngbyatoxin A was as effective as phorbol esters, such as 12-O-tetradecanoylphorbol-13-acetate, in enhancing the sensitivity of HeLa cells to CP. A 24-h pretreatment of HeLa cells with 1 to 100 nM lyngbyatoxin A caused an approximately 9-fold sensitization to CP. All analogues of lyngbyatoxin A that retained the lactam ring portion of the molecule but contained different hydrophobic substituents at C-7 including indolactam V (ILV), tert-butyl-ILV, or n-hexyl-ILV increased cellular sensitivity to CP in a concentration-dependent manner. Maximum cellular sensitization to CP (9-fold) was seen with 10 nM n-hexyl or tert-butyl compounds, and ILV devoid of any C-7 substitution required higher concentrations (1 microM) for equivalent sensitization. The ability of lyngbyatoxin A analogues to sensitize cells to CP correlated directly with their ability to activate PKC in vitro. Synthetic analogues that lacked the lactam ring structure neither activated PKC nor sensitized cells to CP. The C-9 epi analogue of n-hexyl-ILV was less effective than the corresponding natural stereoisomer in activating PKC as well as sensitizing cells to CP. Exposure of HeLa cells to 100 nM lyngbyatoxin A for 24 h caused a substantial decrease in cellular PKC activity to 20% of the untreated control value, but a similar treatment of cells with n-hexyl- or tert-butyl-ILV led to only a 25% reduction in PKC activity. Concentrations of ILV (e.g. 1 microM) that sensitized HeLa cells to CP caused no down-regulation of PKC. Thus, on the basis of results with these novel lyngbyatoxin A analogues, we conclude that activation but not down-regulation of PKC is necessary for sensitization of HeLa cells to CP.  相似文献   
94.
95.
Background: Ketamine has been shown to suppress platelet aggregation, but its mechanisms of action have not been defined. The purpose of the current study is to clarify the effects of ketamine on human platelet aggregation and to elucidate the underlying mechanisms of its action.

Methods: Platelet aggregation was measured using an eight-channel aggregometer, and cytosolic free calcium concentration was measured in Fura-2/AM-loaded platelets using a fluorometer. Inositol 1,4,5-triphosphate (IP3) was measured with use of a commercially available IP3 assay kit. To estimate thromboxane A2 (TXA2) receptor binding affinity and expression, Scatchard analysis was performed using [3H]S145, a specific TXA2 receptor antagonist. TXA2 agonist binding assay was also performed. The membrane-bound guanosine 5'-triphosphatase activity was determined using [[gamma]-32P]guanosine triphosphate by liquid scintillation analyzer.

Results: Ketamine (500 [mu]m) suppressed aggregation induced by adenosine diphosphate (0.5 [mu]m), epinephrine (1 [mu]m), (+)-9,11-epithia-11,12-methano-TXA2 (STA2) (0.5 [mu]m), and thrombin (0.02 U/ml) to 39.1 +/- 30.9, 46.3 +/- 4.3, -2.0 +/- 16.8, and 86.6 +/- 1.4% of zero-control, respectively. Ketamine (250 [mu]m-1 mm) also suppressed thrombin- and STA2-induced cytosolic free calcium concentration increase dose dependently. Although ketamine (2 mm) had no effect on TXA2 receptor expression and its binding affinity, it (1 mm) suppressed intracellular peak IP3 concentrations induced by thrombin and STA2 from 6.60 +/- 1.82 and 4.39 +/- 2.41 to 2.41 +/- 0.98 and 1.90 +/- 0.86 pmol/109 platelets, respectively, and it suppressed guanosine triphosphate hydrolysis induced by thrombin (0.02 units/ml) and STA2 (0.5 [mu]m) to 50.3 +/- 3.2 and 67.5 +/- 5.5%versus zero-control, respectively.  相似文献   

96.
The postnatal ontogeny of neurons containing different GABAA receptor beta (beta 1, beta 2 and beta 3) subunit mRNAs were examined in the rat thalamus using in situ hybridization histochemistry. Neurons containing beta 1 or beta 2 subunit mRNA developed remarkably postnatally, while most neurons were already strongly labeled with beta 3 probe at birth. However, beta 3 subunit mRNA decreased rapidly after birth, few cells being labeled with this probe at day 35 and thereafter.  相似文献   
97.
Recently, we found CD3-CD4(bright) cells with comparative specificity for normal rat liver. In the current study, we investigated the type and form of both CD3-CD4(bright) cells and CD3-CD4(dull) cells in the rat liver. The surface phenotype of hepatic mononuclear cells in Lewis rats was identified by using monoclonal antibodies including anti-CD4, anti-CD3, and antimacrophage in conjunction with two- or three-color immunofluorescence analysis. CD3-CD4(bright) cells and CD3-CD4(dull) cells were examined morphologically using May-Giemsa staining and scanning electron microscopy. The distribution of CD3-CD4(bright) cells and CD3-CD4(dull) cells 48 hours after intravenous administration of liposome-encapsulated dichloromethylene diphosphate was also investigated. In comparison to CD3-CD4(dull) cells, CD3-CD4(bright) cells were slightly larger macrophages with abundant cytoplasmic granules, being present with comparative specificity for normal rat liver and showing negligible effects by intravenous liposome-encapsulated dichloromethylene diphosphate administration. These data suggest that in normal young rat liver these CD3-CD4(dull) and CD3-CD4(bright) cells may be dendritic cells and Kupffer cells that shift from the liver to the spleen or vice versa. These cells may also be able to locally proliferate in liver or spleen due to changes in the developing liver.  相似文献   
98.
Summary Haemorrhage in regions remote from the site of following intracranial operations is rare, but they do occur. We performed supratentorial craniotomy on 639 patients between the time of introduction of computed tomography (CT) for clinical use in 1983 and June 1992; subarachnoid haemorrhage (SAH) in the posterior fossa occurred postoperatively in six of these cases. These included four patients with tumours in the sellar region, one with an arteriovenous malformation (AVM) and one who underwent superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis. The ages of the six patients ranged from 17–72 years.Haemorrhage occurred on the day of operation in one case and was detected on CT examination on the day following surgery in the remaining five cases. Of three patients with disturbance of consciousness, two underwent suboccipital craniectomy for reduction of intracranial pressure, while one received barbiturate therapy and later underwent cerebrospinal fluid (CSF) shunt surgery. No special treatment was necessary for the remaining three patients with less serious lesions. Five of the six patients ultimately recovered their pre-operative neurological status apart from the primary diseases.Factors inducing such haemorrhages seem likely to include displacement of the cerebellum by reduced CSF pressure during and after operations, and stretching and tearing of the veins and venules in the sulci of the tentorial surface of the cerebellum. Consideration should therefore be given to the maintenance of an appropriate CSF pressure during operation; this is particularly important in elderly patients and those with an atrophied cerebral cortex.  相似文献   
99.
100.
An elderly case of systemic lupus erythematosus (SLE) with suspected hemolytic anemia was experienced. A 70 year-old female was admitted to our hospital on December 31 with complaints of herpetic eruption. She complained of arthralgia since 3 month prior to her admission. The positive findings on examination were skin eruption in the left chest, a systolic heart murmur and a palpable elastic hard liver. Laboratory data showed raised erythrocyte sedimentation rate of 149 mm per hour, decreased Hb (10.1 g/dl), decreased hematocrit (30.0%), increased reticulocytes (33%1000), decreased thrombocytes (73,000/mm3), increased gamma-globulin (33%) and positive rheumatoid factor. During admission, she developed anemia. A stool test for occult blood was negative. The haptoglobin was 38.8 mg/dl and bone marrow aspiration showed increased erythropoiesis, suggesting features of immune hemolytic anemia, except she was negative on Coomb'test. Eye fundi were similar to case of typical bleeding observed in SLE. Concerning immunological findings, the antinuclear factor was x 1280 and the anti-dsDNA antibody was x 80, on which a diagnosis of SLE was based. She experienced numbness of the left arm and developed left hemiparesis 2 days later. Therapy with 15 mg/day prednisone obtained a good response and anemia, abnormal immunological findings and hemiparesis disappeared.  相似文献   
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