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Biomedical subjects

H Sakai

Publications and source records attributed to H Sakai.

At least 721 records · Page 40Linked to original sources
PubMed1993

Cell-dependent requirement of human immunodeficiency virus type 1 Vif protein for maturation of virus particles.

A highly sensitive single-round infection assay using a bacterial chloramphenicol acetyltransferase was developed to analyze an early stage of human immunodeficiency virus type 1 replication. By a combination of transfection and single-round infection assay, a virus with a vif mutation, depending on host cells from which the virus was derived, was demonstrated to be defective at the early phase of infection cycle. Analysis of viral proteins synthesized in cells indicated that incorporation of the Env surface protein into virions of the vif mutant, again in a cell-dependent way, was greatly restricted. Taken together, it is concluded that the Vif protein acts through modulation of the Env protein in the virions, directly or indirectly, to enhance viral infectivity in a certain cell type.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Peritubular endothelial cell proliferation in mice during compensatory renal growth after unilateral nephrectomy.

The proliferation of peritubular endothelial cells during compensatory renal growth (CRG) following unilateral nephrectomy in mice was investigated using a labeling index. The labeling index of peritubular endothelial cells increased 6 h after uninephrectomy and decreased to the normal level within 72 h. Immunohistochemical study revealed that c-myc protein was expressed in the nuclei of both cortical tubular cells and peritubular endothelial cells. Furthermore, intravenous injection of anti-basic fibroblast growth factor (bFGF) neutralizing antibody just after uninephrectomy led to significant inhibition of proliferation of peritubular endothelial cells, but not tubular cells. These results indicate that peritubular endothelial cells proliferate transiently during CRG and that bFGF plays an important role for the growth regulation of that cell in the kidney.

Animals↗
PubMed1993

Microtubule nucleating activity of centrosomes in cell-free extracts from Xenopus eggs: involvement of phosphorylation and accumulation of pericentriolar material.

We have studied the regulation of microtubule nucleating activity of the centrosome using cell-free extracts from Xenopus eggs. We found that the number of microtubules per centrosome increases dramatically with time during incubation of isolated centrosomes in interphasic egg extracts prepared 20-30 minutes after electric activation of cytostatic factor (CSF)-arrested eggs. The increase in microtubule nucleation was still conspicuous even when KCl-treated centrosomes (centrosomes stripped of their microtubule nucleating activity by 1 M KCl treatment) were incubated in interphasic extracts. Electron microscopy and immunostaining by anti-gamma-tubulin and 5051 human anti-centrosome antibodies revealed that pericentriolar material (PCM) was accumulated during the increase in microtubule nucleation from centrosomes in interphasic extracts, suggesting regulation of centrosomal activity by PCM accumulation. The ability of egg extracts to activate microtubule nucleation from centrosomes was also assumed to be regulated by phosphorylation, since addition of protein kinase inhibitors into interphasic extracts totally blocked the increase in microtubule nucleation from the KCl-treated centrosome. The ability of CSF-arrested mitotic extracts to increase microtubule nucleation from KCl-treated centrosomes was 3.5- to 5-fold higher than that of interphasic extracts, while PCM accumulation in mitotic extracts seemed to be similar to that in interphasic extracts. The increase in microtubule nucleation from KCl-treated centrosomes was strikingly enhanced by the addition of purified p34cdc2/cyclin B complex to interphasic extracts, but not by MAP kinase, which is activated downstream of p34cdc2/cyclin B. These results suggest two pathways activating centrosomal activity in egg extracts: accumulation of PCM and phosphorylation mediated by p34cdc2/cyclin B.

Alkaloids↗
PubMed1993

Studies on cerebral protective agents. III. Novel 4-arylpyrimidine derivatives with anti-anoxic and anti-lipid peroxidation activities. (3).

Novel 4-arylpyrimidine derivatives, bearing an amino moiety in the C-5 or C-6 position of the pyrimidine ring, were synthesized and tested for anti-anoxic (AA) activity in mice. Among them, 6,7-dihydro-6-[2-(dimethylamino)-ethyl]-4-(3-nitrophenyl)-2-phenyl-5H- pyrrolo[3,4-d]pyrimidine-5-one (2a, FR 75469) and 6-methyl-5-(4-methyl-piperazin-1-ylmethyl)-4-(3-nitrophenyl) - 2-phenylpyrimidine (4c, FR 72707) had comparable potency 10-100 mg/kg, i.p. and p.o.) to that of 6-methyl-5-(4-methylpiperazin-1-ylcarbonyl)-4-(3-nitrophenyl )-2-phenylpyrimidine (FK 360). These were also effective on anti-lipid peroxidation (ALP) assay and arachidonate-induced cerebral edema in rats. Structure-activity relationship in regard to AA activity of this series of compounds are discussed. Three-dimensional molecular electrostatic potentials (3D-MEP) around the nitrogenous basic moiety of FK 360 and 5-acetyl-6-(2-dimethylaminoethyl)-4-(3-nitrophenyl)-2- phenylpyrimidine (5f) were compared, and both electrostatic potential maps were similar.

Animals↗
PubMed1993

Studies on cerebral protective agents. IV. Synthesis of novel 4-arylpyridine and 4-arylpyridazine derivatives with anti-anoxic activity.

In a search for new cerebral protective agents, a series of 4-(3- or 4-nitrophenyl)-6-phenylpyridines (or pyridazines) and 2-(3-nitrophenyl)-6-phenylpyridines, possessing an amino moiety at the C-3 position of the pyridine (or pyridazine) ring, were synthesized through the corresponding novel 1,4-dihydro derivatives and tested for anti-anoxic (AA) activity in mice. Four compounds (2c, 2f, 3a, 4a) possessed significant AA activity at a dose of 32 mg/kg, i.p. These results suggest that four-atom linkages between the C-3 position of the pyridine (or pyridazine) ring and the nitrogenous basic moiety also seems to be a prerequisite for the expression of AA activity.

Animals↗
PubMed1993

Studies on cerebral protective agents. V. Novel 4-(3-nitrophenyl)pyridine and 4-(3-nitrophenyl)pyrimidine derivatives with anti-anoxic activity.

Novel 4-(3-nitrophenyl)pyridine and 4-(3-nitrophenyl)pyrimidine derivatives, possessing three-atom linkages between basic nitrogen and at the C-5 (or C-3) position of the pyrimidine (or pyridine) ring, were synthesized and tested for anti-anoxic (AA) activity in mice. Among them, 6-methyl-4-(3-nitrophenyl)-2-phenyl-5-(pyrrolidinomethylcarbonylamino )pyrimidin e (10f) had the most potent AA activity (3.2 mg/kg, i.p.). Three-dimensional molecular electrostatic potentials (3D-MEP0 around the nitrogenous basic moiety of 6-methyl-5-(4-methylpiperazin-1-ylcarbonyl)-4-(3-nitrophenyl )-2-phenylpyrimidin e (FK 360) and 10f were compared. The negative zone of 10f is broader and deeper and positioned somewhat differently to that of FK 360, although there is a co-occupied spacial area in part.

Animals↗
PubMed1993

Altohyrtins B and C and 5-desacetylaltohyrtin A, potent cytotoxic macrolide congeners of altohyrtin A, from the Okinawan marine sponge Hyrtios altum.

Following the characterization of altohyrtin A (1), altohyrtins B (2) and C (3) and 5-desacetylaltohyrtin A (4) have been isolated from the Okinawan marine sponge Hyrtios altum and their plane structures and parts of their relative configurations elucidated. Three congeneric macrolides (2, 3, and 4) exhibit extremely potent cytotoxicities similar to those of 1 against KB cells with IC50 values of 0.02, 0.4, and 0.3 ng/ml, respectively.

Animals↗
PubMed1993

A neopullulanase-type alpha-amylase gene from Thermoactinomyces vulgaris R-47.

Shimizu et al. and ourselves have reported some enzymatic properties of an alpha-amylase from Thermoactinomyces vulgaris R-47 that hydrolyzed pullulan to produce panose [M. Shimizu et al., Agric. Biol. Chem., 42, 1681-1688 (1978); Y. Sakano et al., Agric. Biol. Chem., 46, 1121-1129 (1982)]. In this study, we cloned a gene for an alpha-amylase, which was different from the one mentioned above but also hydrolyzed pullulan to produce panose, from T. vulgaris R-47, and analyzed the entire primary structure of the gene. We designated the previously reported enzyme as T. vulgaris alpha-amylase I (TVA I), and this novel enzyme as T. vulgaris alpha-amylase II (TVA II). The nucleotide sequence had an open reading frame of 1755 base pairs corresponding to a protein of 585 amino acid residues. Although this novel alpha-amylase, TVA II, hydrolyzed both pullulan and starch, the ratio of pullulan-hydrolyzing activity to starch-hydrolyzing activity of the enzyme was higher than that of TVA I, and the primary structure of the enzyme resembled neopullulanase, which scarcely hydrolyzed starch, rather than that of TVA I.

Amino Acid Sequence↗
PubMed1993

Importance of the central region of 130-kDa insecticidal proteins of Bacillus thuringiensis var. israelensis for their activity in vivo and in vitro.

To delineate the mosquitocidal regions of the ISRH3 (CryIVB) and ISRH4 (CryIVA) proteins, which are two of the mosquitocidal 130-kDa proteins contained in the crystalline protein bodies (CPBs) of Bacillus thuringiensis var. israelensis (BTI), a deletion analysis of these protein genes has been done. Based on the evidence that each 130-kDa protein had two mosquitocidal regions, N-terminal and C-terminal ones, and these two regions shared a common part in the center of the 130-kDa proteins, deleted genes on this region were constructed. As the protein products which lacked the central region had reduced activities, the central region could be important for the mosquitocidal activity. The mosquitocidal and non-mosquitocidal truncated gene products of 130-kDa protein genes were also applied to a cultured lepidopteran cell line, TN-368. The mosquitocidal proteins caused the swelling and disruption of the cells in spite of the insecticidal specificity of CPBs of BTI, but the non-mosquitocidal proteins did not. Therefore, TN-368 cells were sensitive to the mosquitocidal fragments of 130-kDa proteins of BTI under the assay conditions used.

Animals↗
PubMed1993

Disseminated pancreatic polypeptidioma.

Pancreatic polypeptidioma, a pancreatic endocrine tumor, is an extremely uncommon disease and its clinical features and responses to therapy are not well known. We present a 33-year-old woman with disseminated pancreatic polypeptidioma, who subsequently showed various signs and symptoms of metastases, including bone pain, cranial nerve palsy, spinal block, and hematuria, and died 22 months after the presentation. Responses to various therapeutic regimens including hepatic arterial embolization, radiation therapy, systemic chemotherapy, and administration of interferon-alpha or somatostatin analogue, are discussed. Particular note in this case is a prompt response of bone metastases to the radiotherapy.

Adult↗
PubMed1993

Glomerulocystic kidney--report of an adult case.

A 32-year-old adult case of glomerulocystic kidney disease (GCK) is reported. He had brain and muscle atrophy, probably due to congenital malformation. Progressive renal failure developed and he died. Autopsy disclosed multiple tiny cysts exclusively in the renal cortices. Microscopic study revealed that the cysts were dilated Bowman's spaces. This case is the 12th adult case reported in the world.

Adult↗
PubMed1993

[High-dose busulfan, VP-16 and ACNU therapy with stem cell transplantation for the treatment of children with acute leukemia].

In order to strengthen the anti-leukemia effect, we developed a new conditioning regimen with high dose busulfan, VP-16 and ACNU (BVA) for cytoreduction before stem cell transplantation. Fourteen patients with refractory acute leukemia received allogeneic bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT) after conditioning with the BVA regimen, 7; allogeneic BMT, 1; syngeneic BMT, 6; PBSCT. # Seven patients were transplanted in the first complete remission, and 8 patients were in their second or third remission. Although total body irradiation or cyclophosphamide was not included in this regimen, engraftment was obtained in all cases. Two patients suffered relapse, and one patient died of cytomegalovirus interstitial pneumonitis (IP) 64 days after PBSCT. The other 11 patients are alive and free of disease at a median follow up time of 647 days (98-1235 days). Major regimen-related toxicity was pulmonary complications such as IP (3 cases) and pulmonary edema (2 cases). However, all patients recovered rapidly following steroid therapy. The results indicate that this conditioning regimen is highly effective for the treatment of childhood acute leukemia.

Acute Disease↗
PubMed1993

[An autopsied case of type 2 Machado-Joseph's disease or spino-pontine degeneration].

The authors present the clinico-pathological findings in a member of a family residing in Akita Prefecture located in the north-eastern region of Japan. Four members in three generations of the family developed ataxia. The autopsied patient was a 42-year-old woman, who, at the age of 25, had developed progressive cerebellar ataxia with pyramidal spasticity and increased deep tendon reflexes predominant in the lower extremities. However, she retained fine movement of the hands and fingers and showed no dysarthria until the age of 35. She could no longer walk unassisted at 38 years old. She showed cerebellar ataxia in both hands and legs, dysarthria, bulging eyes, progressive extraoculomotor palsy with nystagmus, bradykinesia, sensory disturbance, and dystonia in the face, upper extremities, and fingers. Deep tendon reflexes were decreased, especially in the lower extremities. Subacute generalized muscular atrophy developed at the age of 39. She became bedridden and died of pneumonia. The clinical diagnosis was Type-2 of the entity known in Japan as Machado-Joseph disease. At neuropathological examination, the brain weight was 1,250 g. The spinocerebellar system including Clarke's column and the spinocerebellar tracts were degenerated, but the cerebellar cortex and inferior olivary nucleus were spared. Slight-to-moderate degeneration was observed in the pontocerebellar system. In the dentate nucleus, most of the neurons showed what is known in Japan as "grumose degeneration", but there was no neuronal loss or gliosis. The hilus of the dentate nucleus and the superior cerebellar peduncle were intact.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

[A modified composite graft: glutaraldehyde treatment of the vein and impervious covering on the composite site--an experimental and clinical study].

Composite grafts have a tendency to develop intimal hyperplasia (IH) at the anastomosis between the different graft materials. The author developed a new prosthesis, modified composite graft (MCG) to control this problem. Experimental study: MCG consists of proximal 3cm of Dardik Biograft and a distal 3cm of autogenous vein (AV). Proximal segment of AV, which is anastomosed to the Biograft, was treated with 1% glutaraldehyde during operation. Then MCG was implanted in the canine infrarenal abdominal aorta. The anastomosis between Biograft and AV was wrapped with a strip of Biograft to prevent the invasion from the surrounding tissue that may also cause IH. The patency rate at 33 months was 75% (9/12). No IH was observed at Biograft-AV anastomosis. Clinical study: Thirty MCG's were implanted in patients with chronic obstructive arterial disease. None of the patients had enough autogenous vein for a complete graft. Cumulative patency rates were 67.3% at 1 year and 31.6% at 5 years. Over-all limb salvage rate was 75%. All graft failure was caused by IH at the site of proximal anastomosis between the femoral artery and Biograft or graft thrombosis probably due to low blood flow. In conclusion, IH was successfully prevented at the site of Biograft-AV anastomosis in MCG.

Aged↗