Search PubMed⌕ Search

Biomedical subjects

H Sakai

Publications and source records attributed to H Sakai.

At least 667 records · Page 37Linked to original sources
PubMed1994

Nontoxic intravitreal dose of ofloxacin for rabbit retina.

We studied the nontoxic intravitreal concentration of ofloxacin, a new quinolone antibacterial agent, by evaluating its effects on in vitro and in vivo electroretinograms (ERGs) in albino and pigmented rabbits. After perfusion with a 36 micrograms/ml solution of ofloxacin, the in vitro ERG remained unchanged. The in vivo ERG and the visually evoked potential remained unchanged 4 weeks after vitrectomy with 50 micrograms/ml ofloxacin, and the retina was within normal limits both ophthalmoscopically and histologically. Therefore, the retinal toxicity of ofloxacin is low and within safe limits at clinical dosage.

Animals↗
PubMed1994

GDP inhibits the activity of the centrosome to nucleate microtubules.

Microtubule-nucleating ability of the centrosome in the isolated mitotic apparatus was investigated under the condition that the centrosomal fragment was preincubated with guanine nucleotides or its derivatives. GTP and non-hydrolyzable GTP analogues such as GTP-gamma S or GMP-PNP consistently supported high activity of the centrosome to nucleate microtubules. On the other hand, GDP substantially suppressed the microtubule-nucleating activity of the centrosomes. Evidence has been presented that this is not simply due to the inhibitory effect of GDP on microtubule assembly. This result is consistent with the idea that GTP binding proteins such as 51 kDa protein and gamma-tubulin localized to the pericentriolar materials in the centrosome are competent for the nucleation of microtubules when it is saturated with GTP.

Animals↗
PubMed1994

Studies on cerebral protective agents. VI. Synthesis of novel 4-(4-nitrobenzoyl)pyrimidine and related compounds with anti-anoxic activity.

Novel pyrimidine derivatives, possessing linkages between the aryl group and the pyrimidine nucleus at the C-4 position, were prepared and tested for anti-anoxic (AA) activity in mice. Among them, 5-(4-methylpiperazin-1-ylcarbonyl)-4-(4-nitrobenzoyl)-2-p henylpyrimidine (2f, FR76659) possessed significant AA activity (10-100 mg/kg, i.p.) with low acute toxicity (LD50 > 1000 mg/kg, i.p.). Structure-activity relationships in regard to AA activity of this series of compounds were examined.

Animals↗
PubMed1994

Studies on anti-platelet agents. V. Synthesis and structure-activity relationship of 3-substituted 5,6-bis(4-methoxyphenyl)-1,2,4-triazines.

The syntheses and structure-activity relationships of a series of 3-substituted 5,6-bis(4-methoxyphenyl)-1,2,4-triazines as anti-platelet agents based on cyclooxygenase (CO) inhibition are described. Of these compounds, 1-[5,6-bis(4-methoxyphenyl)-1,2,4-triazin-3-yl]carbonyl-4-methylpi perazine (10) exhibited potent CO inhibition in vitro (IC50 = 2.8 x 10(-7) M) with vasodilatory activity (ED50 = 4.5 x 10(-5) M). Compound 10 also showed potent ex vivo activities, completely preventing platelet aggregation induced by arachidonic acid and collagen at 6 h after oral administration of 3.2 and 1.0 mg/kg. The ex vivo potency of 10 is more than three times that of aspirin. Moreover, 10 demonstrated no gastrointestinal side effect in rats even at 100 mg/kg in spite of its potent CO inhibition activity, while aspirin, the most widely-used anti-platelet drug, showed gastrointestinal side effects in a dose-dependent manner (32, 100, and 320 mg/kg) in our study. These results suggested that 10 is a very attractive candidate for development as an anti-platelet drug since an aspirin-like anti-platelet agent, based on CO inhibition and being free from gastrointestinal side effects, is a major goal of thromboembolic research.

Animals↗
PubMed1994

A sensitive method of non-radioactive in situ hybridization for mRNA localization within human renal biopsy specimens: use of digoxigenin labeled oligonucleotides.

A sensitive method of non-radioactive in situ hybridization using digoxigenin-labeled oligonucleotides is described for the detection of mRNA within human renal biopsy specimens. Although non-radioactive in situ hybridization typically has the drawback of low sensitivity, we increased the sensitivity of this method, providing a practical alternative to the use of radiolabelled probes. The four main points are: 1) assessment of the efficiency of labeling, 2) optimization of the probe concentration for hybridization, 3) requirement of deproteinization of tissues with HCl and proteinase K, and 4) the use of a four-layer immunoperoxidase staining system. This technique was found to clearly localize individual mRNA positive cells within cryostat tissue sections. A variety of controls including sense probes, excess unlabeled anti-sense probes, and RNase-treatment demonstrated the specificity of the technique. This improved method is a powerful technique for detecting mRNA within human renal tissue and will be most useful in the study of gene expression in the pathogenesis of renal diseases.

Actins↗
PubMed1994

Diagnosis of inflammatory pseudotumor of the liver: value of CT.

OBJECTIVE: Inflammatory pseudotumor of the liver is a localized mass consisting of a fibrous stroma and chronic inflammatory infiltrate without anaplasia. Diagnosis of this rare disease is important to avoid surgery. The purpose of this study was to determine if CT is useful in the diagnosis of this lesion. SUBJECTS AND METHODS: CT scans of nine patients with a proved diagnosis of inflammatory pseudotumor of the liver were reviewed. Diagnosis was made by the surgical resection in three patients and by percutaneous biopsy in six patients. Six patients had symptoms and laboratory data suggesting active inflammation caused by the pseudotumor. The remaining three patients were asymptomatic. CT scans were performed with IV administration of the contrast material; scans were obtained in the portal venous and delayed phases in six patients and in the delayed phase in three patients. CT scans were analyzed for the number and size of the hepatic masses, and the degree and pattern of contrast enhancement on portal venous phase and delayed-phase images. RESULTS: Eight patients had a solitary hepatic mass, and one patient had two masses on the CT scan. The average size of the masses in the symptomatic patients (8.3 cm) was larger than that in the asymptomatic group (3.6 cm). CT scans in the portal venous phase showed a variable degree of contrast enhancement (seven masses). At least a part of seven masses, six of which were in symptomatic patients, showed greater contrast enhancement on delayed-phase CT scans than on the normal liver parenchyma. No constant pattern of enhancement was observed on delayed-phase CT scans in asymptomatic patients. CONCLUSION: Inflammatory pseudotumor of the liver should be included in a differential diagnosis in patients with a hepatic mass on a CT scan, especially when patients are symptomatic and the mass is fairly large and solitary showing contrast enhancement greater than that of liver parenchyma on delayed-phase CT scans. Percutaneous biopsy should be performed to obtain a histologic confirmation.

Adolescent↗
PubMed1994

Convenient method to purify hemoglobin.

A convenient method to purify Hb solution from outdated RBC has been established for the starting material of Hb-based blood substitutes. To prevent MetHb formation during the procedure, Hb in RBC was carbonylated in advance. Then RBC was mixed with organic solvent for hemolysis and centrifuged for removal of stroma. The resulting SFHb solution was heated at 60 degrees C and generated precipitates were removed out by centrifugation. The purity of Hb (25 g/dl) was confirmed by SDS-PAGE. IEF and oxygen binding property of the Hb solution also guaranteed its purity and no denaturation of Hb. This method is applicable to large scale production of the purified Hb for the starting material of Hb-based blood substitutes.

Blood Substitutes↗
PubMed1994

Characteristics of Hb-vesicles and encapsulation procedure.

The performance of Hb-vesicles depends on the weight ratio of Hb to lipid ([Hb]/[Lipid]). This value is improved by lowering the number of bilayer membrane of the vesicle and raising the concentration of Hb in the interior of the vesicle. Maximum [Hb]/[Lipid] ratio was obtained at ca. pH 7, that would relate to the isoelectric point (pI) of Hb at 25 degrees C. On the other hand, the [Hb]/[Lipid] ratio decreased with ionic strength and increased with lowering temperature. The Hb-vesicles encapsulating 40 g/dl Hb with only one bilayer membrane were isolated by using the difference in the density of the vesicles.

Blood Substitutes↗
PubMed1994

[The clinical significance of interleukin-6 as an inflammatory marker (the studies in patients with open heart surgery)].

We analyzed serum levels of interleukin-6 (IL-6) and seven acute phase proteins in CRP positive samples and in patients with open heart surgery. The concentrations of serum IL-6 were not correlated with other acute phase proteins in CRP positive samples. However, IL-6 were in inverse correlation with CRP, AAG, AAT and CER in patients with open heart surgery. These discrepancies were due to the differences in response time of each acute phase protein after the start of inflammation. Responses of acute phase proteins after open heart surgery were investigated from hour to hour. IL-6 increased rather rapidly than other acute phase proteins, and increases of CRP, TRF, AAT, AAG, CER, HAP and AMG followed. The time reached the peak were IL-6, CRP, TRF, AAT, AMG, AAG, HAP reached the peak in that order. IL-6 constantly increased seven hours earlier, and reached at maximum values forty three hours earlier than CRP in each case. The measurement of serum concentration of IL-6 may be useful for early detection of acute inflammation.

Acute Disease↗
PubMed1994

Nephrotic syndrome associated with subacute bacterial endocarditis (SBE): a case report.

We experienced a female nephrotic patient associated with subacute bacterial endocarditis. Her proteinuria was completely normalized after antibiotic therapy and valve replacement. Immunofluorescence and an electron microscopic study of a renal biopsy specimen showed little evidence of immune complex in the glomeruli. Marked deposition of properdin in the glomeruli and the reduced level of serum complement may indicate involvement of the complement system in the pathogenic mechanism of massive proteinuria in this case.

Adult↗
PubMed1994

A novel GTP gamma S-dependent regulatory mechanism in the basolateral Cl- channel of gastric parietal cells.

A housekeeping basolateral Cl- channel in rabbit gastric parietal cells (0.3-0.4 pS) is closed by an intracellular application of GTP gamma S. Here, we found a novel GTP gamma S-dependent regulatory mechanism, in which GTP gamma S stimulates intracellular superoxide (O2-) production and the O2- acts as a messenger in the closure of the Cl- channel. Other oxygen species such as .OH and H2O2 were not involved in the closing mechanism.

Animals↗
PubMed1994

[An autopsy case of AIDS with hemophilia A who died of DIC and gastrointestinal bleeding associated with gastric carcinoma (signet ring cell carcinoma)].

We describe a 39 years-old male hemophilia A patient with acquired immunodeficiency syndrome (AIDS) developing to disseminated intravascular coagulation (DIC) due to gastric carcinoma. He had been diagnosed as human immunodeficiency virus (HIV) sero-positive in 1990. Since then, he has been treated by the oral administration of zidovudine (AZT), dideoxyinosine (ddI) and intravenous administration of glycyrrhizin. In September 1990, he suddenly complained abdominal pain with bloody stool. His condition deteriorated in spite of our intensive treatment for DIC. He died of multiple organ failure (MOF) due to DIC. The autopsy findings showed gastric carcinoma, defined of signet ring cell carcinoma histopathologically. But neither opportunistic infection nor other cause of DIC were observed.

Acquired Immunodeficiency Syndrome↗
PubMed1994

[Studies of comparison with fluorescent bioparticles and microspheres for phagocytosis by flow cytometric assay in polymorphonuclear leukocytes].

We have determined the conditions for quantitative phagocytosis assay in human polymorphonuclear leukocytes by flow cytometry using fluorescent bioparticles (Zymosan A, S. aureus, E. coli). The changes in the phagocytic index after an exogenous stimulation and after addition of monoclonal antibodies against receptor antigens on polymorphonuclear leukocytes were examined by using fluorescent microspheres (FM particles) and bioparticles. When bioparticles were used, the phagocytic index decreased after an exogenous stimulation with phorbol myristate acetate (PMA). The phagocytic index obtained with the FM particles increased by the addition of PMA and the supernatant of E. coli, but decreased by the addition of the supernatant of S. aureus. After the addition of the monoclonal antibodies the phagocytosis for the S. aureus and E. coli particles was blocked by anti-CR3, that for the Zymosan A particles was blocked by anti-CR3 and IgGFcR2, and that for the PM particles was blocked by anti-CR1, CR3, and LFA-1 beta, partially. These findings implied the involvement of a complement receptor. However, the degree of its involvement varied with the target particle.

Adult↗
PubMed1994

A point mutation in the bile acid biosynthetic enzyme sterol 27-hydroxylase in a family with cerebrotendinous xanthomatosis.

Cerebrotendinous xanthomatosis (CTX) is a rare familial disorder characterized by progressive neurological dysfunction, atherosclerosis, and xanthomas with sterol storage in the nervous system, vessels, and tendons. Increased serum cholestanol, derived from intermediates of cholesterol catabolism, may possibly be a major cause of the disease. An examination was made of the cDNA encoding cytochrome P450 sterol 27-hydroxylase (CYP27) in hepatic mitochondria, considered a defective enzyme inducing CTX, in a Japanese housewife afflicted with CTX and her family. The proposita and one of her brothers, who also had CTX symptoms and hypercholestanolemia, were found to be homozygotic, carrying a point mutation in the CYP27 gene at Arg104 (CGG) to Trp104 (TGG). The mutant position has a 100% conserved positive charge in all known vertebrate cytochrome P450s and even in bacterial cytochrome P450cam. The mother of the proposita and another brother were both free of CTX symptoms and were heterozygotic for the mutation, although their plasma cholesterol increased moderately. An increase in plasma cholestanol alone would, thus, not appear to be a direct cause of sterol storage in CTX, while CTX is strongly suggested to be caused by defects in both alleles of the CYP27 gene.

Aged↗