Biomedical subjects

Y Sakai

Publications and source records attributed to Y Sakai.

At least 289 records · Page 16Linked to original sources

PubMed1998

Quantitative light microscopic study on the heterogeneity in the superficial pineal gland of the rat.

BACKGROUND: The previous results regarding regional and day-night differences in pinealocyte size in rats are conflicting. The relationships between these differences and the vascularity and sympathetic innervation have scarcely been investigated. METHODS: Wistar-King rats, kept under light/dark 12:12, were killed at midday or midnight in October. The nuclear density of pinealocytes in the superficial pineal was measured on the dorsoperipheral, dorsocentral, ventroperipheral, and ventrocentral regions at distal, middle, and proximal levels at daytime and nighttime. The total area of blood vessels per unit area at daytime and nighttime and total length of tyrosine hydroxylase (TH)-immunoreactive fibers per unit area at daytime were determined on the same regions at the same levels. RESULTS: Pinealocyte size was larger toward the distal levels and in the periphery than in the center at any level. The area of blood vessels and length of TH fibers were also larger toward the distal levels; the former in the ventral region and the latter in the dorsal and ventral regions were larger in the periphery than in the center. Ventral pinealocytes, but not dorsal ones, showed day-night changes in size. Prominent day-night rhythms in area of blood vessels occurred in the ventral region, where TH fibers were more abundant than in the dorsal region. CONCLUSIONS: Pinealocyte size shows the distal to proximal and peripheral to central gradients, which may be related to the differential distribution of blood vessels and sympathetic fibers. Since pinealocytes and blood vessels, showing prominent day-night changes in size, are localized in the more richly innervated regions, sympathetic fibers may play an important role in controlling these rhythms.

Analysis of Variance↗

PubMed1998

Anaesthetic management of a patient with Williams syndrome undergoing aortoplasty for supravalvular aortic stenosis.

PURPOSE: A case of a patient associated with Williams syndrome undergoing aortoplasty for supravalvular aortic stenosis is presented. CLINICAL FEATURES: Williams syndrome is a rare disease associated with a characteristic facies, supravalvular aortic stenosis, and mental retardation. A 15-yr-old girl with Williams syndrome underwent aortoplasty for supravalvular aortic stenosis. Anaesthesia was induced with fentanyl and thiamylal, and maintained with nitrous oxide, oxygen, sevoflurane, and continuous intravenous infusion of fentanyl. Supravalvular aortic stenosis was evaluated using a multiplane transesophageal echocardiography (TEE) probe before and after repair. CONCLUSION: Multiplane TEE was found to be very useful for anaesthetic management in a patient with Williams syndrome undergoing aortoplasty for supravalvular aortic stenosis.

Adolescent↗

PubMed1998

Nine-year survivor after resection of cholangiocellular carcinoma with tumor thrombi in the main portal trunk.

We report a patient with cholangiocellular carcinoma with tumor thrombi in the main portal trunk who has survived for 9.5 years after hepatic resection. A 57-year-old woman underwent an extended left lobectomy, and resection of the caudate lobe plus the main portal trunk for a liver tumor that had a portal tumor thrombus in the main portal trunk. The portal vein was reconstructed with an autologous vein graft obtained from the external iliac vein. Histological examination of the resected specimen revealed moderately differentiated tubular adenocarcinoma compatible with cholangiocellular carcinoma. Factors contributing to the patient's long-term survival are discussed. Aggressive surgical resection can be effective even for such an advanced case of cholangiocellular carcinoma.

Bile Duct Neoplasms↗

PubMed1998

Dissociation of ligand-induced internalization of CXCR-4 from its co-receptor activity for HIV-1 Env-mediated membrane fusion.

The C-terminal cytoplasmic tail of chemokine receptors is important for their internalization upon ligand binding. We generated several deletion mutants of the C-terminal cytoplasmic tail of CXCR-4, a co-receptor for T cell line tropic strains of human immunodeficiency virus type 1 (HIV-1), to know whether or not co-receptor internalization is associated with HIV-1 entry. Our data showed that the removal of C-terminal 15 amino acid residues of the cytoplasmic tail from CXCR-4 completely abolished its internalization, but did not affect the co-receptor activity at all. Co-receptor activity was fully retained even when all 45 amino acid residues in the C-terminal cytoplasmic tail had been deleted. These data indicated that no cytoplasmic tail nor internalization of CXCR-4 is required for its co-receptor activity for HIV-1 entry.

Animals↗

PubMed1998

Alternations of diacylglycerol kinase in streptozotocin-induced diabetic rats.

Dysfunction of organs has been reported in diabetic rats, suggesting an association with changes in intracellular signal transduction pathways including phosphatidylinositol (PI) turnover. Diacylglycerol (DG) kinase catalyses the phosphorylation of DG, which is considered to play a major physiological role in the metabolism of the intracellular messenger DG. However, no relation between DG kinase activity and any disease in mammalian tissue has been reported to date. In the present study, we investigated whether the changes in DG kinase activity are related to diabetes. Basal resting level of DG kinase activity changed in tissue isolated from diabetic rats. Decreases in resting activity detected in aorta and kidney and agonist-induced responses differed between these tissues. Submaximal increases in basal activity also were detected in vas deferens and hepatocytes. These changes in DG kinase activity resemble the functional changes associated with complications of diabetes, suggesting that changes in PI turnover followed by DG kinase activity are a key element in the complications. It is the first study about the changes in DG kinase activity in mammalian disease.

Animals↗

PubMed1998

New orally active enkephalinase inhibitors: their synthesis, biological activity, and analgesic properties.

A series of (4S)-4-[(2S)-benzyl-3-mercaptopropionylamino]-4-(N-phenylcarbamoyl )-butyric acids has been identified as potent systemically active enkephalinase inhibitors. Structure-activity relationships (SAR) are discussed. Further chemical modification of the inhibitors was carried out in order to identify the inhibitors which are orally active in an animal model. Compounds of particular interest are the prodrug-like analogues, including 5b (ONO-9902). Their analgesic effects after oral administration were evaluated.

Administration, Oral↗

PubMed1998

Sendai virus C proteins are categorically nonessential gene products but silencing their expression severely impairs viral replication and pathogenesis.

BACKGROUND: The P/C mRNA of Sendai virus (SeV), a prototypic member of the family Paramyxoviridae in the Mononegavirales superfamily comprising a large number of nonsegmented negative strand RNA viruses, encodes a nested set of accessory proteins, C', C, Y1 and Y2, referred to collectively as C proteins, initiating, respectively, at ACG/81 and AUGs/114, 183, 201 in the +1 frame relative to the ORF of phospho (P) protein, the smaller subunit of RNA polymerase. Among them, C is the major species expressed in infected cells at a molar ratio which is several-fold higher than the other three. However, their function has remained an enigma. It has not even been established whether or not the C proteins are essential for viral replication. Many other viruses in Mononegavirales encode C-like proteins, but their roles also remain to be defined. RESULTS: By taking advantage of a recently developed reverse genetics system to recover infectious SeV from cDNA, we created mutants in which C protein frames were variously silenced. C/C'(-) viruses which did not express C and C', but did express Y1 and Y2, were severely attenuated in replication in tissue culture cells of various species and tissues, as well as in embryonated chicken eggs. More notably, they were almost totally incapable of growing productively in--and hence nonpathogenic for mice--the natural host. Both gene expression and genome replication appeared to be impaired in C/C'(-) viruses. Additionally silencing the Y1 and Y2 expression was also possible, and a critically impaired but viable clone, the 4C(-) virus, was isolated which expressed none of the four C proteins. CONCLUSION: SeV C proteins are categorically nonessential gene products, but greatly contribute to full replication capability in vitro and are indispensable for in vivo multiplication and pathogenesis. This study represents the first comprehensive functional assessment of the accessary C protein for Mononegavirales.

Animals↗

PubMed1998

Efficacy of a bioreactor filled with porcine hepatocytes immobilized on nonwoven fabric for ex vivo direct hemoperfusion treatment of liver failure in pigs.

We developed a new bioreactor for a bioartificial liver filled with porcine hepatocytes immobilized on polyester nonwoven fabric (NWF) and in our previous study showed that this NWF bioreactor has promising in vitro efficiency. In the present study, we investigated the efficacy of the NWF bioreactor in a direct hemoperfusion experiment conducted to treat pigs with liver failure. Porcine hepatocytes were isolated from the whole liver of a Sangen strain pig. They were immobilized in a 200 ml column containing NWF via perfusion in a closed circuit for 24 h to prepare a NWF bioreactor. The following day an operative liver failure model was produced by creating a portocaval shunt and ligating the entire hepatoduodenal ligament in the porta hepatis. Perfusion treatment was initiated 4 h after operative induction of liver failure and continued for about 1 h. The pigs which underwent perfusion treatment showed significant improvements in survival and blood data, including ammonia, total bile acid, glucose, and prothrombin time, attributed to significant improvements in the post- as compared to the prebioreactor levels in the perfused blood of the treated pigs. These beneficial effects of the NWF bioreactor were based on its excellent composition which allows the accommodation of adequate numbers of hepatocytes and direct contact between hepatocytes and perfused blood.

Ammonia↗

PubMed1998

Effect of ultrafiltration during cardiopulmonary bypass for pediatric cardiac surgery.

The effect of ultrafiltration during cardiopulmonary bypass (CPB) was evaluated for correcting ventricular septal defects with associated pulmonary hypertension in patients less than 18 months old. Interleukin (IL)-6 and IL-8 concentrations in the blood, ultrafiltrate, and urine were measured. The blood IL-6 concentration increased to 128.4+/-20.2 pg/ml by the end of surgery, which is lower than the concentration seen in adult patients (273.1+/-48.2 pg/ml, p < 0.02). The blood IL-8 concentration was not significantly different than that of adults. The total amounts of excreted IL-6 in the ultrafiltrate and urine during CPB were 11.5+/-0.32 pg/kg and 0.32+/-0.07 pg/kg, respectively (p < 0.05). The total amounts of excreted IL-8 in the ultrafiltrate and urine were 4.64+/-0.69 pg/kg and 1.92+/-0.56 pg/kg, respectively (p < 0.05). No differences were seen in these values for excretion between children and adults. We conclude that ultrafiltration during CPB in pediatric patients is more effective in removing proinflammatory cytokines than in adults and more effective than renal filtration alone.

Cardiopulmonary Bypass↗

PubMed1998

Limitations of percutaneous transhepatic cholangioscopy for the diagnosis of the intramural extension of bile duct carcinoma.

BACKGROUND AND STUDY AIMS: Vascular dilatation seen on percutaneous transhepatic cholangioscopy (PTCS) is diagnostic of intramural invasive carcinoma of the bile duct, but the limitations of the technique, including biopsy, for the diagnosis of intramural extension of bile duct carcinoma have not to our knowledge been investigated before. The aims of the present study were to estimate the thickness of the specimens of bile duct wall taken by biopsy, to assess the sensitivity of PTCS for detecting intramural invasive carcinoma, and to identify the characteristics of the intramural extension of bile duct carcinoma associated with vascular dilatation. PATIENTS AND METHODS: A total of 135 biopsy, and 16 surgical specimens obtained from 25 bile duct carcinomas were examined for: the thickness of the biopsy specimens and of the mucosa and combined mucosal-fibromuscular layers in the resected common bile ducts and common hepatic ducts; the presence of muscular and neural bundles in the biopsy specimens; the number of invasive carcinomas in the biopsy specimens that had been taken from stenosed regions; and the relation between intramural extension of invasive carcinoma and vascular dilatation. RESULTS: The mean thickness of the biopsy specimens did not differ from the mean thickness of the mucosa in the resected specimens, but was significantly lower than that of the combined mucosa and fibromuscular layer. Muscular bundles were included in only 13 (14%) of the biopsy specimens, and there were no neural bundles. Carcinomas and invasive carcinomas were diagnosed histologically from the biopsy specimen in 96% and 91% of the cases, respectively. The sensitivity of a single biopsy for diagnosis for invasive carcinoma in stenosed regions was 62%, almost the same as the sensitivity in non-stenosed regions with vascular dilatation (68%). On histologic examination of 16 resected specimens, the sensitivity and specificity of vascular dilatation as a marker of the intramural extension of an invasive carcinoma were 39% and 100%, respectively, and this was significantly more common in invasive carcinomas that were invading the mucosa beyond the adventitia than in those limited to the adventitia. CONCLUSION: Histologic examinations of specimens obtained by PTCS-guided biopsy can detect invasive carcinoma in only the superficial layers of the bile duct, such as the mucosa and the shallowest fibromuscular layer. Multiple specimens are needed for the diagnosis of invasive carcinoma because the sensitivity of examination of a single specimen for detecting invasive carcinoma is low. Vascular dilatation is characteristic of carcinoma that is invading the mucosa beyond the adventitia, so the diagnosis of intramural extension of bile duct carcinoma limited to the adventitia, particularly if it has spread to the deeper fibromuscular layer and the adventitia, is difficult to make by PTCS.

Adult↗

PubMed1998

Everting closure for interrupted aortic arch, ventricular septal defect, and severe subaortic stenosis.

Interrupted aortic arch with ventricular septal defect in the neonate is sometimes complicated by severe subaortic stenosis from posterior deviation of the infundibular septum. We have developed a novel approach to the treatment of this condition. The infundibular septum is penetrated from the right-ventricular side to the left-ventricular outflow tract. It is compressed with patch fixation. The lower margin of the infundibular septum is everted. Three consecutive neonates were treated. The smallest diameters of the left-ventricular outflow tract were 3,4, and 2.5 mm. All patients survived the operation and were discharged from the hospital. They remained well 2 to 7 years after the repair and were in normal sinus rhythm without a left bundle branch block or any significant pressure gradient between the upper and lower extremities. Follow-up two-dimensional and Doppler echocardiography demonstrated no residual shunt, no left-ventricular outflow-tract pressure gradient, and no aortic regurgitation. This technique provides effective widening of the left-ventricular outflow tract, and is more safely and easily performed than conventional methods.

Aorta↗

PubMed1998

Surgical intervention for patients with stage IV-A hepatocellular carcinoma without lymph node metastasis: proposal as a standard therapy.

OBJECTIVE: The aim of this study was to evaluate the effects of surgical treatments for patients with stage IV-A hepatocellular carcinoma (HCC) without lymph node metastasis. SUMMARY BACKGROUND DATA: Nonsurgical therapy for highly advanced HCC patients has yielded poor long-term survival. Surgical intervention has been initiated in an effort to improve survival. METHODS: The outcome of 150 patients who underwent hepatic resection was studied. Survival analysis was made by stratifying stage IV-A HCC patients into two groups-those with and those without involvement of a major branch of the portal or hepatic veins. Those with involvement were further divided into subgroups according to major vascular invasions. RESULTS: Patients who had multiple tumors in more than one lobe without vascular invasion had a significantly better 5-year survival rate (20%) than those with vascular invasion (8%) (p < 0.01). The survival rate of patients with hepatic vein tumor thrombi (10%) was better than the rate for those with tumor thrombi in the inferior vena cava (0%), in whom no patients survived more than 2 years, although the survival rate for those with portal vein tumor thrombi in the first branch (11%) was no different from the rate for that in the portal trunk (4%). The operative mortality decreased from 14.3% in the first 6 years to 1.4% in the following 5 years. CONCLUSIONS: Surgical intervention for stage IV-A HCC patients brought longer survival rates for some patients. We recommend surgical intervention as an effective therapeutic modality for patients with advanced HCC.

Adolescent↗

PubMed1998

First report of Trichosporon ovoides isolated from the home of a summer-type hypersensitivity pneumonitis patient.

Trichosporon species have been known to cause summer-type hypersensitivity pneumonitis (SHP). During the isolation of yeasts from an SHP patient's house, we recovered a strain belonging to the genus Trichosporon. Morphologically, the isolate produced rectangular arthroconidia when grown on corn meal agar. DNA-DNA hybridization experiments identified the isolate as T. ovoides. A slide agglutination test using specific factor sera demonstrated that the serotype of the strain was type II. Previously, T. asahii, a serotype II species, was considered to be the major antigen of SHP, but it is possible that T. ovoides may also be responsible for SHP. This is the first report of T. ovoides isolated from an SHP patient's home environment.

Aged↗

PubMed1998

An outbreak of hepatitis A in a day-care center: immunoprophylaxis with human immunoglobulin.

BACKGROUND: An outbreak of seven cases of hepatitis A (HA) occurred in a day-care center. Five of the cases were children attending the center, one was a nurse and one was the mother of a child. It is probable that the first case with HA was a male child infected by an unknown source. METHODS AND RESULTS: Human immunoglobulin (HIG) was administered to both children and staff at the center following which there were no new cases of infection among in-center contacts. However, a new case of HA among household contacts developed 3 weeks following the treatment of in-center contacts. CONCLUSIONS: The outbreak may have been prevented if the sibling (case 2) of the source case of infection (case 1) had been given HIG as soon as infection had been confirmed. Additionally, the data suggest that HIG for prevention of HA should be given not only to children but also to their parents.

Adult↗

PubMed1998

Regulation and physiological role of the DAS1 gene, encoding dihydroxyacetone synthase, in the methylotrophic yeast Candida boidinii.

The physiological role of dihydroxyacetone synthase (DHAS) in Candida boidinii was evaluated at the molecular level. The DAS1 gene, encoding DHAS, was cloned from the host genome, and regulation of its expression by various carbon and nitrogen sources was analyzed. Western and Northern analyses revealed that DAS1 expression was regulated mainly at the mRNA level. The regulatory pattern of DHAS was similar to that of alcohol oxidase but distinct from that of two other enzymes in the formaldehyde dissimilation pathway, glutathione-dependent formaldehyde dehydrogenase and formate dehydrogenase. The DAS1 gene was disrupted in one step in the host genome (das1Delta strain), and the growth of the das1Delta strain in various carbon and nitrogen sources was compared with that of the wild-type strain. The das1Delta strain had completely lost the ability to grow on methanol, while the strain with a disruption of the formate dehydrogenase gene could survive (Y. Sakai et al., J. Bacteriol. 179:4480-4485, 1997). These and other experiments (e.g., those to determine the expression of the gene and the growth ability of the das1Delta strain on media containing methylamine or choline as a nitrogen source) suggested that DAS1 is involved in assimilation rather than dissimilation or detoxification of formaldehyde in the cells.

Aldehyde-Ketone Transferases↗

PubMed1998

Measles virus attenuation associated with transcriptional impediment and a few amino acid changes in the polymerase and accessory proteins.

Measles virus (MV) isolated in B95a cells, a marmoset B-cell line, retains full pathogenicity for cynomolgus monkeys, while its derivative obtained by adaptation to the growth in Vero cells, a monkey kidney cell line, loses the pathogenic potential (F. Kobune, H. Sakata, and A. Sugiura, J. Virol. 64:700-705, 1990). Here, we show with a pair of strains, a fresh isolate (9301B) in B95a cells and its Vero cell-adapted form (9301V), that the in vivo attenuation parallels the decrease of replication and syncytium-inducing capabilities in the original B95a cells and that these in vitro phenotypes are attributable to impediment of transcription, which is already obvious at the level of primary transcription catalyzed by the virion-associated RNA polymerase. On the other hand, cell fusion assays detected no functional difference between the glycoproteins of the two viruses. Essentially the same transcriptional impediment with reduced syncytium induction following Vero cell adaptation was found with two other pairs of strains that had been similarly prepared. Nucleotide sequence comparison between the 9301B and 9301V viruses revealed that a few (at most five) amino acid changes, which sporadically took place in the polymerase (L and P proteins) and/or accessory V and C proteins, were responsible for the in vitro and in vivo attenuation through adaptation to growth in Vero cells.

Adaptation, Physiological↗

PubMed1998

Interferon therapy for chronic hepatitis C in hemodialysis patients: increased serum levels of interferon.

BACKGROUND/AIMS: The efficacy and side effects of interferon (IFN) therapy have not been well clarified in hemodialysis patients with chronic hepatitis C. METHODS: In 6 of 9 hemodialysis patients with chronic hepatitis C, 3 million units (MU) or 6 MU of recombinant IFN-alpha2b or natural IFN-alpha were administered intramuscularly daily for the first 2 weeks, followed by three times a week for 22 weeks. In the remaining 3 patients, 3 MU of IFN-alpha2b were given three times a week for 24 weeks. Serum concentrations of IFN-alpha2b were measured sequentially after the injection of interferon. Responders were defined as the patients with normal serum aminotransferase and negative serum HCV RNA 6 months after the cessation of IFN therapy. RESULTS: Three of the 6 patients who were administered IFN daily in the first 2 weeks were responders, while the other 3 withdrew from the therapy due to serious adverse events such as depression, loss of consciousness and persistence of high-grade fever. Serious adverse events were not observed in the 3 patients without daily administration. Half-lives of IFN-alpha2b in hemodialysis patients were significantly longer than those in nonuremic patients (10.0 vs. 6.0 h, p < 0.05). Moreover, the areas under the serum concentration curve of the hemodialysis patients were significantly larger than those of nonuremic patients (756 +/- 223 vs. 324 +/- 223 IU.h/ml, p < 0.05), despite the fact that the dose of IFN-alpha administered to hemodialysis patients was half that administered to nonuremic patients. CONCLUSIONS: In hemodialysis patients with chronic hepatitis C, pharmacokinetic parameters of IFN may be different from those in nonuremic patients, and daily or high-dose administration of IFN may lead to serious adverse events in those patients.

Adult↗

PubMed1998

Effects of Cu, Zn-superoxide dismutase delivered by genetically modified skin fibroblasts on cold-induced skin edema in rats.

The effects of Cu, Zn-superoxide disumutase (SOD) delivered by genetically modified skin fibroblasts on cold-induced skin edema were studied in rats. Cold-induced skin edema was induced on the dorsal skin following transplantation of ILSOD cells, genetically modified skin fibroblasts which release secretable SOD protein into the extracellular space. The degree of skin edema induced by cold injury was estimated by measuring the amounts of Evans' blue (EB) leaking into the injured skin following intravenously administration. The amounts of EB leakage were significantly reduced by transplantation of ILSOD cells relative to that observed following transplantation of host cells as a control. The degrees and durability of these effects of ILSOD cells were dependent on the number of cells transplanted. Also, the increases of lipid peroxidation following cold injury were significantly reduced by transplantation of ILSOD cells but not of host cells. These findings suggested that transplantation of ILSOD cells was a suitable delivery system for obtaining efficient and continuous effects of SOD. This strategy using genetically modified skin fibroblasts may also be useful as a drug delivery system for other therapeutic proteins.

Animals↗