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Biomedical subjects

H Sakai

Publications and source records attributed to H Sakai.

At least 577 records · Page 32Linked to original sources
PubMed1995

Inhibition of nitric oxide production increases dimethylnitrosamine-induced liver injury in rats.

Intravascular coagulation is involved in the development of certain types of liver injury, including that induced by dimethylnitrosamine. Nitric oxide inhibits platelet aggregation and adhesion; however, its role in protecting against intravascular coagulation has not been clarified. We therefore investigated the effect of blocking the production of NO in a dimethylnitrosamine-induced liver injury model. Wistar male rats received dimethylnitrosamine (50 micrograms/kg) intraperitoneally, and were treated with N omega-nitro-L-arginine, an inhibitor of nitric oxide synthase, or N omega-nitro-D-arginine, an inactive isomer. Each arginine derivative (40 mg/kg) was injected intraperitoneally every 6 h. Twenty-four hours after dimethyl-nitrosamine administration, we observed a significant increase in the serum level of alanine aminotransferase in the N omega-nitro-L-arginine group compared with the N omega-nitro-D-arginine group. The N omega-nitro-L-arginine-treated group also exhibited a significant reduction in platelet count, a prolongation of prothrombin time, and an elevation of plasma soluble fibrin monomer complex levels. Sinusoidal congestion, intravascular coagulation, and coagulation necrosis around the central veins were prominent in the N omega-nitro-L-arginine group. In conclusion, the inhibition of nitric oxide production exacerbated the hepatic damage induced by dimethylnitrosamine, mediated by the acceleration of intravascular coagulation.

Animals↗
PubMed1995

Serum 7 alpha-hydroxycholesterol as a new parameter of liver function in patients with chronic liver diseases.

To examine bile acid synthesis in chronic liver diseases, serum total 7 alpha-hydroxycholesterol level was measured by gas-liquid chromatography-mass spectrometry in patients with cirrhosis (n = 23), patients with chronic hepatitis (n = 21), and control subjects (n = 18). The serum 7 alpha-hydroxycholesterol levels were significantly lower in patients with cirrhosis than the controls (78 +/- 59 pmol/mL vs. 237 +/- 97 pmol/mL; mean +/- SD). However, in patients with chronic hepatitis, the level was fully retained (262 +/- 102 pmol/mL). Serum 7 alpha-hydroxycholesterol levels of 17 patients with cirrhosis classified as Child B and C ranged from 33 to 69 pmol/mL, and all were less than the normal range (between 104 and 466 pmol/mL), however, those levels of some patients classified as Child A were within the normal range. Serum 7 alpha-hydroxycholesterol levels significantly correlated with serum albumin, cholinesterase, total bile acid, direct bilirubin, alkaline phosphatase, indocyanine green (ICG) retention rate, hepaplastin test, and lecithin-cholesterol acyltransferase activities. We conclude that bile acid synthesis is well preserved in patients with chronic hepatitis and that it is decreased in most patients with cirrhosis. Serum 7 alpha-hydroxycholesterol may be a new parameter of liver function testing to assess hepatic bile acid synthesis in patients with chronic liver diseases.

Adult↗
PubMed1995

NAC covers ribosome-associated nascent chains thereby forming a protective environment for regions of nascent chains just emerging from the peptidyl transferase center.

We demonstrate that nascent polypeptide-associated complex (NAC) is one of the first cytosolic factors that newly synthesized nascent chains encounter. When NAC is present, nascent chains are segregated from the cytosol until approximately 30 amino acids in length, a finding consistent with the well-documented protease resistance of short ribosome-associated nascent chains. When NAC is removed, the normally protected nascent chains are susceptible to proteolysis. Therefore NAC, by covering COOH-terminal segments of nascent chains on the ribosome, perhaps together with ribosomal proteins, forms a protective environment for regions of nascent chains just emerging from the peptidyl transferase center. Since NAC is not a core ribosomal protein, the emergence of nascent chains from the ribosome may be more dynamic than previously thought.

Amino Acid Sequence↗
PubMed1995

Function of human immunodeficiency virus type 1 Vpu protein in various cell types.

We evaluated the function of human immunodeficiency virus type 1 vpu gene in various cell lines. We established a highly sensitive system consisting of chloramphenicol acetyltransferase and reverse transcriptase assays and used it to monitor the effects of mutation of the vpu gene. In some cell lines, Vpu protein was not required at the early phase of viral replication but was important for efficient virion production. In these cells, the Vpu protein functioned effectively irrespective of the presence of intact env gene products. Likewise, CD4 gene expression had no effects on Vpu function. In the other cell lines tested, Vpu protein was not important for virion release, and the vpu mutant clone generated a normal level of progeny virions upon transfection.

3T3 Cells↗
PubMed1995

Early replication block of human immunodeficiency virus type 1 in monkey cells.

The genetic and functional basis of the replication-defective nature of human immunodeficiency virus type 1 (HIV-1) in monkey cells was studied. By the generation and characterization of chimeras between HIV-1 and simian immunodeficiency virus, the sequence encompassing the 3' half of the long terminal repeat, gag and pol genes of HIV-1 was found to be responsible for the growth restriction. Early and late phases of HIV-1 replication in monkey cells were analysed in detail using several assay systems: transfection/coculture, transcomplementation between various proviral clones carrying the CAT gene and effector clones and evaluation of transcription and reverse transcription. All the data were consistent with the notion that HIV-1 replication is blocked at a very early stage(s) such as uncoating and/or reverse transcription in monkey cells.

Animals↗
PubMed1995

Inhaled nitric oxide and extracorporeal membrane oxygenation in persistent pulmonary hypertension of the newborn.

Persistent pulmonary hypertension of the newborn (PPHN) may occasionally require an invasive treatment with extracorporeal membrane oxygenation (ECMO). Inhaled nitric oxide (NO) has recently been introduced as a selective pulmonary vasodilator for treatment of PPHN. We describe a case of PPHN in which neither inhaled NO nor ECMO was effective in reversing pulmonary hypertension. The clinical course of the patient suggested a potential role of NO inhalation in predicting the outcome of ECMO treatment for PPHN.

Administration, Inhalation↗
PubMed1995

Proliferating cell nuclear antigen in ACTH-independent bilateral macronodular adrenal hyperplasia.

ACTH-independent bilateral macronodular adrenal hyperplasia (AIMAH) has been recently described as a rare cause of Cushing's syndrome and it is an unusual process of unknown etiology. This report describes a case of a 59-year-old man with AIMAH. The proliferating cell nuclear antigen (PCNA) has been implicated in the process of cell proliferation and is detectable throughout most of the cell cycle. This report also describes the expression of PCNA in AIMAH by immunohistochemical staining. Most of the positive expression was seen in the greater part of the epithelial cells of the cortical lesion, but not in the interstitial cells. These data suggest that some effective factor, specific for adrenal cortical cell growth, might be produced in AIMAH.

Adrenal Glands↗
PubMed1995

Effects of translation initiation factor eIF-5A on the functioning of human T-cell leukemia virus type I Rex and human immunodeficiency virus Rev inhibited trans dominantly by a Rex mutant deficient in RNA binding.

The viral transactivator proteins Rex and Rev are necessary for the expression of structural proteins of human T-cell leukemia virus type I and human immunodeficiency virus type 1, respectively. Although the interaction of Rex/Rev with a cellular cofactor(s) has been thought to be required for Rex/Rev action, there is no suitable system to search for the cofactor(s) in mammalian cells. We found that a Rex mutant, TAgRex, which contains a simian virus 40 nuclear localization signal in place of the N-terminal 19 amino acids of Rex, could dominantly inhibit wild-type Rex/Rev functions. The inhibition did not require either Rev response element/Rex response element binding or the oligomerization ability of the mutant, but it did require a region around amino acid 90 of the Rex protein, suggesting that TAgRex sequestered the cellular cofactor. Complementation with the eukaryotic translation initiation factor 5A (eIF-5A) in this system could restore the impaired Rex function. These results indicate that eIF-5A is the cofactor indispensable for Rex function. Additionally, by using a two-hybrid system, the homo-oligomer formation of Rex was found to be mediated by the region around amino acid 90 in addition to Tyr-64 and Trp-65 of Rex protein. Thus, eIF-5A may play a part in the formation of the Rex homo-oligomer.

Animals↗
PubMed1995

Differential distribution of type IV collagen chains in patients with diabetic nephropathy in non-insulin-dependent diabetes mellitus.

Thickening of the glomerular basement membrane (GBM) and expansion of the mesangial matrix are hallmarks of human diabetic nephropathy. Renal tissues from 15 patients with type II (non-insulin-dependent) diabetes (NIDDM) were studied by immunofluorescence (IF) and immunogold electron microscopy (IEM) for the distribution of 2 type IV collagen peptides [alpha 3(IV) noncollagenous (NC) domain and alpha 4(IV) NC domain] and 2 classical type IV collagen chains [alpha 1(IV) NC domain and alpha 2(IV) domain]. There was intense staining for alpha 3(IV) NC and alpha 4(IV) NC domain in the GBM but not in the mesangial matrix of patients with overt diabetic nephropathy. In contrast, staining with antibodies to alpha 1(IV) NC and alpha 2(IV) NC domain reacted with mesangial matrix but was significantly decreased in the GBM in the patients with overt diabetic nephropathy. IEM confirmed the IF findings. These data suggest that expansion of the mesangial matrix and thickening of GBM in NIDDM involves separate and distinct type IV collagen components and that the site-specific matrix alterations in NIDDM and type I (insulin-dependent) diabetes are parallel.

Adult↗
PubMed1995

Lyme disease in Japan. Analysis of Borrelia species using rRNA gene restriction fragment length polymorphism.

BACKGROUND: Lyme disease is sporadically observed in Japan since the first report in 1987. We have experienced 19 cases of Lyme disease. In 12 out of 13 trials we succeeded in isolating Borrelia strains (JEM1-12) from erythema migrans (EM) lesions. Recently, Borrelia burgdorferi sensu lato was classified into at least three distinct subgroups, B. burgdorferi sensu stricto, B. garinii and B. afzelii. OBJECTIVE: In order to characterize Lyme disease in Japan, we summarized the clinical features of our cases and investigated the nature of the isolated Borrelia strains. METHODS: The 12 Borrelia strains were analyzed by restriction fragment length polymorphism (RFLP) of ribosomal RNA gene. RESULTS: Most of our 19 patients were in stage I with EM as the main clinical manifestation. RFLP analysis using 12 strains isolated from the patients indicated that 8 strains (group IV, V) were different from the three aforementioned genospecies. CONCLUSION: Clinical data from the present study substantiate the view that Japanese Lyme disease has a relatively milder course. We speculate that this may be related to the specific Borrelia strains in Japan.

Adult↗
PubMed1995

Development of electroretinographic alterations in streptozotocin-induced diabetes in rats.

Development of electroretinographic alterations in 9-week-old experimental diabetic rats was studied for up to 6 weeks after a single intraperitoneal injection of streptozotocin (STZ, 60 mg/kg). The amplitudes and the peak latencies of the a and b waves in the diabetic rats did not differ significantly from those in the control rats. In contrast, the diabetic rats showed a significantly smaller amplitude of the second oscillatory potential (OP) 6 weeks after STZ treatment, and furthermore significantly delayed OP peaks as early as 2-3 weeks after STZ treatment. Vitreous fluorophotometric abnormality developed 6 weeks after STZ treatment. None of the diabetic rats had fundus angiographic changes. These results suggest that hyperglycemia or its related changes rapidly affects the light-induced electrical activities of the retina.

Animals↗
PubMed1995

Studies on cerebral protective agents. VII. Synthesis of novel 4-arylazole derivatives with anti-anoxic activity.

Novel 4-arylazole (i.e. thiazole, oxazole, and imidazole) derivatives, possessing an amino moiety at the C-5 position of the azole ring, were prepared and tested for anti-anoxic (AA) activity in mice. Among them, 5-(4-methylpiperazin-1-yl)methyl-4-(3-nitrophenyl)-2-phenylthia zole (3b, FR75094) possessed significant AA activity (10 mg/kg, i.p. and 100 mg/kg, p.o., respectively), and was also effective on anti-lipid peroxidation (ALP) assay and inhibited arachidonate-induced cerebral edema in rats. Structure-activity relationships in regard to AA activity of this series of compounds are discussed.

Animals↗
PubMed1995

The effect of left ventricular chamber compliance on early diastolic filling during coronary reperfusion.

This study was designed to assess the changes in left ventricular (LV) diastolic filling and to evaluate the dynamic determinants of LV diastolic filling during coronary reperfusion after acute myocardial ischemia. We examined LV diastolic pressure-volume relations (D-PVRs) using the conductance catheter technique with a high-fidelity micromanometer, and the transmitral flow using transesophageal pulsed Doppler echocardiography in 9 open-chest anesthetized dogs with the pericardium opened. We measured early diastolic peak flow velocity (E), late diastolic peak flow velocity (A), the ratio of peak E to peak A (E/A), operational chamber compliance at the minimum LV pressure [(dV/VdP) nadir], and the time constant of LV relaxation (TC). Acute regional myocardial ischemia was produced by occluding the proximal portion of the left anterior descending coronary artery. Data were acquired at baseline, 10 min after acute myocardial ischemia, and after 15 and 90 min of reperfusion under left atrial pacing at 100 beats/min. During myocardial ischemia, D-PVRs shifted upward and rightward on the same curvilinear relationship compared with that at baseline (LV end-diastolic pressure (LVEDP) from 7.3 to 10.5 mmHg, LVEDV from 25 to 31 ml, both p < 0.01), accompanied by a decrease in peak E and E/A (E from 41 to 25 cm/sec, E/A from 1.7 to 1.1, both p < 0.01) and a prolongation of TC (from 25.4 to 30.3 msec, p < 0.01). After coronary reperfusion, D-PVRs returned to baseline accompanied by an improvement in the peak E and E/A ratio. No significant changes in peak A were observed in any of the stages. There was no correlation between peak E and TC, however, a significant positive correlation was observed between peak E and (dV/VdP) nadir (r = 0.76, p < 0.01). In conclusion, this study demonstrated that, using pulsed Doppler echocardiography, the improvement of diastolic filling after coronary reperfusion was based mainly on changes in early diastolic filling, and that LV operational chamber compliance at early diastole, rather than a LV relaxation property, might play an important role in determining early diastolic filling during coronary reperfusion.

Analysis of Variance↗
PubMed1995

Molecular cloning of the genes for pyruvate kinase of two bacilli, Bacillus psychrophilus and Bacillus licheniformis, and comparison of the properties of the enzymes produced in Escherichia coli.

The genes for the pyruvate kinases of a psychrophile, Bacillus psychrophilus, and a mesophile, Bacillus licheniformis, have been cloned in Escherichia coli, and all their nucleotides were sequenced. The two bacterial enzymes each had an extra C-terminal sequence consisting of about 110 amino acid residues, which has been found in the B. stearothermophilus enzyme. Both enzymes were overexpressed in E. coli and the properties of the purified enzymes were compared to those of the B. stearothermophilus enzyme. Both enzymes were less stable than the B. stearothermophilus one. The B. psychrophilus enzyme was more stable than the B. licheniformis one. Similarly to the B. licheniformis and B. stearothermophilus pyruvate kinases, the B. psychrophilus enzyme was activated by AMP or ribose 5-phosphate, and inhibited by ATP or fructose 1,6-bisphosphate. Thus, these enzymes were very similar in the sigmoidal saturation curve for phosphoenolpyruvate and allosteric effectors, but their optimum temperatures and thermostabilities were very different.

Amino Acid Sequence↗