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Biomedical subjects

T Okazaki

Publications and source records attributed to T Okazaki.

At least 91 records · Page 5Linked to original sources
PubMed1999

Ceramide generation in nitric oxide-induced apoptosis. Activation of magnesium-dependent neutral sphingomyelinase via caspase-3.

Sodium nitroprusside (SNP), a NO donor, has been recognized as an inducer of apoptosis in various cell lines. Here, we demonstrated the intracellular formation of ceramide, a lipid signal mediator, in SNP-induced apoptosis in human leukemia HL-60 cells and investigated the mechanisms of ceramide generation. The levels of intracellular ceramide increased to, at most, 160% of the control level in a time- and dose-dependent manner when the cells were treated with 1 mM SNP. SNP also decreased the sphingomyelin level to approximately 70% of the control level and increased magnesium-dependent neutral sphingomyelinase (N-SMase) activity to 160% of the control activity 2 h after treatment. Neither acid SMase nor magnesium-independent N-SMase was affected by SNP. Caspases are thought to be key enzymes in apoptotic cell death. Acetyl-Asp-Glu-Val-Asp-aldehyde, a synthetic tetrapeptide inhibitor of caspases, inhibited magnesiumdependent N-SMase, ceramide generation, and apoptosis. Moreover, recombinant purified caspase-3 increased magnesium-dependent N-SMase in a cell-free system. These results suggest that the findings that SNP increased ceramide generation and magnesium-dependent N-SMase activity via caspase-3 are interesting to future study to determine the relation between caspases and sphingolipid metabolites in NO-mediated signaling.

Apoptosis↗
PubMed1999

Molecular cloning and characterization of two sets of alpha-theta genes in the rat alpha-like globin gene cluster.

The highly heterogeneous rat hemoglobin system was investigated at the gene level. Two regions of the alpha-like globin gene cluster from a Wistar rat were isolated. Four lambda Dash recombinant clones carrying rat alpha-like globin genes were localized on two distinct gene regions. A region of approximately 16kb was found to contain the 5'-IIalpha1-psi theta 1-3' loci, and another of approximately 24kb the 5'-IIalpha2-psi theta2-psiI alpha3-3' loci. Both IIalpha1 and IIalpha2 are considered to be active, coding the IIalpha-globin chain. The nt sequences of IIalpha1 and IIalpha2 are identical except for six nt in the non-coding region. The psiI alpha3 locus is a truncated pseudogene. The putative promoter region of an alpha-like globin gene is joined directly to the third exon, homologous to that of Ialpha-globin cDNA. psi theta1 and psi theta2 are also pseudogenes, as evidenced by several deletions located in the protein-coding regions of these loci. The psi theta1 and psi theta2 loci exhibit extensive homology, but the restriction maps of these genes and their flanking regions differ considerably. Genomic Southern blot analyses of the total liver DNA from six rats showed the existence of three theta-globin-related genes, including psi theta1 and psi theta2. These results indicate that the two gene regions investigated are not allelic variants, but may be generated by block duplication. This is the first report of the existence of rodent theta-globin genes.

Animals↗
PubMed1999

Supplement of liver enzyme by intestinal and kidney transplants in congenitally enzyme-deficient rat.

Gunn rats have a congenital deficiency of bilirubin-uridine diphosphate glucuronyltransferase (B-UDP-GT) activity and are unable to glucuronidate bilirubin in the bile, resulting in unconjugated hyperbilirubinemia. Other than the liver, several organs, including small bowel and kidneys, are known to have B-UDP-GT activity in normal rats. We performed total- or partial-small-bowel transplantation as well as kidney transplantation for Gunn rats in congenic combination and compared the effects of these procedures. Serum total bilirubin (TBil) levels significantly decreased from 7.84 +/- 0.24 mg/dl to 2.19 +/- 0.43 mg/dl 2 weeks after total-small-bowel transplantation (n = 12). Correlation of hyperbilirubinemia was roughly proportional to the length of the transplanted small bowel. There were no difference in metabolic correction between jejunal and ileal transplantation. Serum TBil levels significantly decreased from 7.83 +/- 0.21 mg/dl to 2.24 +/- 0.98 mg/dl 2 weeks after kidney transplantation (n = 5). In conclusion, small-bowel and kidney transplantation were effective in correcting metabolic abnormality in Gunn rats for the period of 4-6 months. Estimated total B-UDP-GT activity supplemented by small-bowel or kidney transplantation was about 1/5-1/4 of the minimal requirement for the complete normalization of serum total bilirubin levels.

Animals↗
PubMed1999

Organization, structure, and evolution of the nonadult rat beta-globin gene cluster.

The beta-globin gene cluster of Wistar rat was extensively cloned and the embryonic genes were mapped and sequenced. Four overlapping lambda Dash recombinant clones cover about 31 kb and contain four nonadult beta-globin genes, 5'-epsilon1-gamma1-gamma2-psigamma3-3'. The epsilon1 and gamma2 are active genes, since their protein products were detected in the fetal stage of the rat (Iwahara et al., J Biochem 119:360-366, 1996). The gamma1 locus might be a pseudogene, since the ATA box in the promoter region is mutated to GTA; however, no other defect is observed. The psigamma3 locus is a truncated pseudogene because a 19-base deletion, which causes a shift of the reading frame, is observed between the second nucleotide of the putative codon 68 and codon 76. A sequence comparison suggests that the psigamma3 might be produced by a gene conversion event of the proto-gamma-globin gene set. Possible histories of the evolution of rat nonadult beta-globin genes are discussed.

Amino Acid Sequence↗
PubMed1999

Long-term postsurgical outcome of biliary atresia.

BACKGROUND/PURPOSE: A successful Kasai procedure is effective in creating biliary drainage and radically altering the natural history of infants with biliary atresia (BA). Since its introduction in the 1950s, long-term follow-up would appear to show that only 30% to 50% of patients have a good long-term prognosis despite initially good surgical outcome. The authors reviewed their experience in treating BA from 1968 to 1997 to assess long-term outcome. MATERIALS AND METHODS: The records of 163 patients treated surgically for BA from 1968 to 1997 were reviewed. Forty-eight (29%) were alive at the end of 1997, of whom, 14 had received liver transplants (LT). Surviving patients who had not undergone transplantation were divided into two groups according to clinical condition: group A, normal liver function without cholangitis (CG) and portal hypertension (PH) and group B, liver dysfunction with CG or PH. The study period was divided arbitrarily into three periods, 1968 to 1975 (period I, n = 34); 1976 to 1985 (period II, n = 81); 1986 to 1997 (period III, n = 48). RESULTS: Thirty-four patients were alive without LT at the end of 1997. There were eight patients (mean age, 16.3+/-4.8 years) in group A, and 26 patients (mean age, 14.3+/-7.6 years) in group B. Recently, four group A patients (mean age, 19.3+/-1.9 years) shifted to group B because of sudden deterioration in condition involving severe CG with multiple bile lakes (n = 2), uncontrollable intestinal bleeding (n = 1), and liver atrophy (n = 1). Survival deteriorated with length of follow-up. There were three survivors from 34 patients treated in period I, 16 survivors from 81 patients treated in period II (three had LT), and 29 survivors from 48 patients treated in period III (11 had LT). CONCLUSIONS: Although satisfactory bile drainage can be obtained with portoenterostomy, our data suggest that liver function can deteriorate progressively, with a possible turning point in late adolescence, indicating that as the length of follow-up increases, clinical assessment should be regular and comprehensive. The timing of LT in postoperative BA patients with deteriorating liver function is a vital management issue.

Adolescent↗
PubMed1999

Hyaluronic acid: a specific prognostic indicator of hepatic damage in biliary atresia.

BACKGROUND/PURPOSE: Hepatic fibrosis can progress in biliary atresia (BA) and is associated with capillarization of hepatic sinusoids. The significance of serum hyaluronic acid (HA) as a noninvasive indicator of histological sinusoidal endothelial cell (SEC) damage and hepatic fibrosis in BA, is investigated. METHODS: A total of 28 postoperative BA patients (mean age, 11.0+/-3.7 years) and 20 normal controls (mean age, 10.5+/-2.8 years) were studied. BA patients were divided into group I, good liver function (n = 8); group II, moderate liver dysfunction (n = 10); and group III, severe liver dysfunction (n = 10). Serum HA was determined using a one-step sandwich enzyme immunoassay, and liver histological damage was confirmed immunohistochemically using an antibody against factor VIII-related antigen (FVIIIRAg), which is specific for detecting damaged SEC. RESULTS: Serum HA was significantly higher (P < .0001) in group III (84.6+/-36.5 ng/mL) than in group I (15.9+/-6.9 ng/mL) or group 11 (28.7+/-10.7 ng/mL). Although immunoreactive products of FVIIIRAg were abundant in group III, they were not detected in SEC from group II. CONCLUSION: Serum HA may be of value for monitoring postoperative BA patients as a noninvasive indicator of SEC damage and progressive hepatic fibrosis.

Adolescent↗
PubMed1999

Acute myeloid leukemia with hypergranular cytoplasm accompanied by t(X;11)(q24;q23) and rearrangement of the MLL gene.

This report describes a unique case of acute myeloid leukemia with hypergranular cytoplasm and t(X;11)(q24;q23). The breakpoint on 11q23 was identified within the MLL gene. The hypergranular cytoplasm of leukemic cells and the associated coagulopathy resembled a characteristic of acute promyelocytic leukemia, despite the absence of RARalpha gene rearrangement in this case. The Xq24 site possibly played a role in this atypical blast phenotype.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Acute myeloid leukemia with t(5;11): two case reports.

A case of acute monocytic leukemia (AMoL) with t(5;11)(q31;q23) and a case of acute myelomonocytic leukemia (AMMoL) with t(5;11)(q35;q13.1) are reported. The translocation between the long arm of chromosome 11q and that of chromosome 5q with leukemia have been rarely reported. Though breakpoint of both cases were subtlety different, they had morphologically monocytic character and showed hyperleukocytosis and chemoresistance.

Adult↗
PubMed1999

A weight reduction and weight maintenance program with long-lasting improvement in left ventricular mass and blood pressure.

Obesity is a major risk factor for cardiovascular disease and is associated with hypertension and increased left ventricular mass (LVM). Maintenance of reduced weight has been a matter of recent concerns in the treatment of obese subjects. This study was conducted to confirm the effect of the addition of exercise to diet on maintenance of body weight in a weight reduction program. In addition, this study was conducted to estimate whether LVM changes in parallel with a change in body weight during a long-term follow-up after a weight-reduction program. Twenty-two normotensive (NT) obese subjects and 14 mild hypertensive (HT) obese subjects ranging in age from 22 to 51 years participated in a 12-week supervised weight-reduction program involving mild exercise and a mild hypocaloric diet. After this 12-week intervention, they were advised to maintain their modified lifestyle during a 1-year follow-up period. After the 12-week intervention, the mean reductions in body weight (BW) in the NT and HT groups were 4.1 kg (P < .0001) and 5.8 kg (P < .0001), respectively. LVM in the NT and HT groups was significantly reduced from 154 g to 136 g (P < .005) and from 169 g to 152 g (P < .002), respectively. One year after intervention, the mean gains in BW in the NT and HT groups were 2.3 kg (not significant, NS) and 0.4 kg (NS), respectively. The mean gains in LVM in the NT and HT groups were 8 g (NS) and 7 g (NS), respectively. It was also shown that blood pressures in the HT group were significantly decreased after the 12-week intervention and there was no significant change in blood pressure in the HT group 1 year after intervention. In conclusion, reduced body weight was maintained for 1 year after a 12-week supervised weight-reduction program in both normotensive and mild hypertensive obese subjects. Reduced left ventricular mass was maintained for a long period in both normotensive and mild hypertensive obese subjects and lowered blood pressure was maintained in the mild hypertensive obese subjects.

Adult↗
PubMed1999

Health status and satisfaction of asymptomatic HIV-positive haemophiliacs in Kyushu, Japan.

The purpose of this study was to elucidate the effects of human immunodeficiency virus (HIV) on haemophiliacs with physical functional disabilities induced by haemophilia in Kyushu, Japan. The subjects were 38 adult haemophiliacs who were selected from 129 patients registered with the North Kyushu Haemophilia Centre. They were divided into 21 asymptomatic HIV-positive and 17 HIV-negative adult haemophiliacs. Coagulation factor levels, modified DePalma classification, Arthritis Impact Measurement Scale 2 (AIMS 2), and a satisfaction in daily life (SDL) questionnaire were used to investigate the clinical severity of their haemophilia and arthropathy, physical functional disabilities, and satisfaction. Although there were no significant differences in the objective assessments of health status between the HIV-positive and -negative haemophiliacs, the HIV-positive haemophiliacs were significantly more dissatisfied with their social activities and mood, according to AIMS 2, and with social intercourse, job, self-development, and social security and pension according to SDL assessment. These dissatisfactions were due to the effects of HIV, in addition to the physical functional disabilities that were caused by haemophilia. Dissatisfaction with social security and pension may be a specific feature in HIV-positive haemophiliacs in Japan resulting from the origin of HIV infection.

Adult↗
PubMed1999

The lower entrainable limit of rat circadian rhythm to sinusoidal light intensity cycles: a preliminary study.

The lower entrainable limit of the circadian behavioral rhythm was examined in rats exposed to sinusoidal light intensity cycles with maximum illuminance of 20 lux and the minimum of 0.01 lux. The period (T) of the light intensity cycle was initially kept at 23.5 h for 20 cycles, and then shortened to 23 h for 33 cycles. Thereafter the rats were released into constant darkness. Five out of 10 rats entrained their circadian rhythms to T = 23.5-h cycle, and they also entrained to the T = 23-h cycle. The phase angle of entrainment was almost unchanged when T was shortened from 23.5 h to 23 h. These results suggest that the T = 23-h cycle was close to the lower limit of entrainment.

Animals↗
PubMed1999

Reconstruction of full-thickness lower eyelid defects using a blepharoplasty technique with a hard palate mucosal graft.

The authors report a method of reconstruction of a full-thickness lower eyelid defect using a blepharoplasty technique utilizing excess skin of the lower eyelid with a hard palate mucosal graft. In all patients the hard palate mucosa took well, and good functional and aesthetic results were obtained. The most suitable indication of this technique might be for the defect occurring horizontally (for which direct closure is difficult to apply) and located in the lateral side of the lower eyelid (when a large amount of excess skin can be utilized). The authors conclude that although the shape and size of the defect to which this method can be applied is restricted, this is a useful option in the reconstructive methods of a full-thickness lower eyelid defect.

Aged↗
PubMed1999

Enhanced expression of vascular endothelial growth factor in lungs of newborn infants with congenital diaphragmatic hernia and pulmonary hypertension.

BACKGROUND: Pulmonary hypoplasia accompanied by pulmonary hypertension resistant to treatment is an important feature of congenital diaphragmatic hernia (CDH). The pathogenesis of the pulmonary vascular abnormalities in CDH remains to be elucidated at the molecular level. Vascular endothelial growth factor (VEGF), an endothelial cell specific mitogen, is known to play a role in pulmonary angiogenesis and vascular remodelling but there are no data on VEGF expression in patients with CDH. METHODS: Necroscopic lung specimens from 21 patients with CDH with lung hypoplasia and from seven age matched control newborn infants without lung hypoplasia were processed for immunohistochemical analysis using affinity purified anti-human VEGF antibodies. All the cases of CDH had pulmonary hypoplasia, indicated by a lung/body weight index of </=0.012, and pulmonary hypertension indicated by repeated cardiac ultrasonography. Cellular localisation of VEGF was semiquantitatively analysed using a staining score ranging from 0 (no staining) to 4 (very strong staining). RESULTS: Significantly raised levels of VEGF immunoreactivity were observed in lung specimens from cases of CDH compared with controls. VEGF was detected mainly in the bronchial epithelium and the medial smooth muscle cells of large (>200 microm) and small (<200 microm) pulmonary arteries, the most intense staining being in the medial smooth muscle cells of the small pulmonary arteries. Endothelial cells were positive for VEGF staining in patients with CDH but not in controls. CONCLUSIONS: This is the first study of VEGF expression in newborn infants with CDH. Increased levels of VEGF, especially in the small, pressure regulating pulmonary arteries, point to a potential role in vascular remodelling. This may reflect an unsuccessful attempt by the developing fetus to increase the pulmonary vascular bed in the hypoplastic lungs to alleviate the associated pulmonary hypertension.

Case-Control Studies↗
PubMed1999

Isolated primary chylopericardium.

A 16-year-old man was found to have an enlarged cardiac silhouette. Primary chylopericardium was diagnosed when pericardiocentesis yielded the characteristic milky-white fluid. The thoracic duct was easily identified by giving milk and butter and an injection of ethylene blue immediately before the operation. Intraoperative thoracic ductography showed no abnormal findings. Mass ligation of the thoracic duct above the diaphragm and partial pericardiectomy were successfully performed through a right thoracotomy approach. In addition, many of the lymphatics were ligated above the diaphragm. The right thoracotomy approach was a useful method for resection and ligation of the thoracic duct just above the diaphragm. Follow-up showed no accumulation of pericardial fluid or pleural effusion.

Adolescent↗
PubMed1999

An experience of pubic hair reconstruction using free temporoparietal fasciocutaneous flap with needle epilation.

Lack of pubic hair may cause suffering for pubescent and adult patients; thus, rapid and precise reconstruction is required for their mental health. We reported pubic hair reconstruction for burn alopecia using a free temporoparietal fasciocutaneous flap transfer with needle epilation. Fourteen months after the reconstruction, an acceptable aesthetic result was obtained, and our patient is satisfied with her reconstructed pubic hair. We conclude that reconstruction using a free temporoparietal fasciocutaneous flap with needle epilation is a useful method for selected patients.

Adult↗
PubMed1998

Association of autonomous replication activity with replication origins in a human chromosome.

A systematic analysis of the correlation of autonomous replication activity with initiation of replication in a human chromosome was performed. The temporal order of replication of segments in a pericentric 320-kb MEN203 locus on human chromosome 10 (10q11.2) was determined by pulse-labeling of cells with 5-bromodeoxyuridine after synchronization with aphidicolin. The entire MEN203 locus replicated during the late S phase. Two distinct segments replicated earlier than the others in the locus, indicating that replication was initiated within or near these segments. Two other segments also showed an earlier response than the respective neighboring regions. These results suggest that the MEN203 locus contains two distinct replication origins and two possible origins that may be used less frequently. The results were essentially confirmed by synchronization of the cell cycle with mimosine. Analysis of autonomous replication activity of 10-kb long chromosome fragments covering the 320-kb region showed that certain fragments replicated two or three times more efficiently than others. The results are consistent with our previous observations with randomly cloned human chromosome fragments. The replication origins colocalized with fragments exhibiting relatively high autonomous replication activity. Thus, the capacity for autonomous replication of chromosome fragments might be prerequisite for the initiation of chromosomal replication.

Aphidicolin↗