Biomedical subjects

S Saitoh

Publications and source records attributed to S Saitoh.

At least 109 records · Page 6Linked to original sources

PubMed1999

Proper metaphase spindle length is determined by centromere proteins Mis12 and Mis6 required for faithful chromosome segregation.

High-fidelity chromosome transmission is fundamental in controlling the quality of the cell division cycle. The spindle pole-to-pole distance remains constant from metaphase to anaphase A. We show that fission yeast sister centromere-connecting proteins, Mis6 and Mis12, are required for correct spindle morphogenesis, determining metaphase spindle length. Thirty-five to sixty percent extension of metaphase spindle length takes place in mis6 and mis12 mutants. This may be due to incorrect spindle morphogenesis containing impaired sister centromeres or force unbalance between pulling by the linked sister kinetochores and kinetochore-independent pushing. The mutant spindle fully extends in anaphase, although it is accompanied by drastic missegregation by aberrant sister centromere separation. Hence, metaphase spindle length may be crucial for segregation fidelity. Suppressors of mis12 partly restore normal metaphase spindle length. In mis4 that is defective in sister chromatid cohesion, metaphase spindle length is also long, but anaphase spindle extension is blocked, probably due to the activated spindle checkpoint. Extensive missegregation is caused in mis12 only when Mis12 is inactivated from the previous M through to the following M, an effective way to avoid missegregation in the cell cycle. Mis12 has conserved homologs in budding yeast and filamentous fungi.

Amino Acid Sequence↗

PubMed1999

An imprinted, mammalian bicistronic transcript encodes two independent proteins.

Polycistronic transcripts are common in prokaryotes but rare in eukaryotes. Phylogenetic analysis of the SNRPN (SmN) mRNA in five eutherian mammals reveals a second highly conserved coding sequence, termed SNURF (SNRPN upstream reading frame). The vast majority of nucleotide substitutions in SNURF occur in the wobble codon position, providing strong evolutionary evidence for selection for protein-coding function. Because SNURF-SNRPN maps to human chromosome 15q11-q13 and is paternally expressed, each cistron is a candidate for a role in the imprinted Prader-Willi syndrome (PWS) and PWS mouse models. SNURF encodes a highly basic 71-aa protein that is nuclear-localized (as is SmN). Because SNURF is the only protein-coding sequence within the imprinting regulatory region in 15q11-q13, it may have provided the original selection for imprinting in this domain. Whereas some human tissues express a minor SNURF-only transcript, mouse tissues express only the bicistronic Snurf-Snrpn transcript. We show that both SNURF and SNRPN are translated in normal, but not PWS, human, and mouse tissues and cell lines. These findings identify SNURF as a protein that is produced along with SmN from a bicistronic transcript; polycistronic mRNAs therefore are encoded in mammalian genomes where they may form functional operons.

Amino Acid Sequence↗

PubMed1999

Specific IgG to gelatin in children with systemic immediate- and nonimmediate-type reactions to measles, mumps and rubella vaccines.

We examined anti-gelatin IgG in sera of children who suffered from systemic adverse reactions upon immunization with gelatin-containing live virus vaccines. In the group of 30 children who had immediate-type reactions and anti-gelatin IgE, 30 (100%) had anti-gelatin IgG and 29 (96%) had anti-gelatin IgG4. In another group of 75 children who had nonimmediate-type reactions and no anti-gelatin IgE, 22 (29%) had anti-gelatin IgG and six (8%) had IgG4. The IgG positivity well correlated with the lymphocyte proliferation assay positivity. In contrast, as a negative control, all 24 children who had no allergic reaction to live virus vaccines had no anti-gelatin IgG and IgG4. The results suggest that immune-response to gelatin may play a role in the pathogenesis of systemic nonimmediate-type reactions to the live virus vaccines.

Animals↗

PubMed1999

Anti-tumor activity of interleukin-2-producing tumor cells and recombinant interleukin 12 against mouse glioma cells located in the central nervous system.

Interleukin 12 (IL-12) exhibits anti-tumor activity in a variety of laboratory models. Although IL-12 itself activates strong anti-tumor activity, the combination of vaccine therapy with IL-2-transduced tumor cells and systemic rIL-12 has been shown to cure tumor-bearing mice more effectively than either rIL-12 or IL-2-transduced tumor vaccines alone. In the present study, regression of brain tumors established in naive mice was obtained by combined administration of an intratumoral injection of a single dose of IL-2-producing glioma cells (SR/IL-2 cells) and recombinant IL-12. Intraperitoneal rIL-12 administration substantially delayed the growth of s.c. inoculated gliomas, but not of gliomas located in the brain. Although vaccination with SR/IL-2 cells alone was not effective against s.c. inoculated gliomas, the combination therapy of vaccination with irradiated SR/IL-2 cells and systemic rIL-12 was more effective than rIL-12 alone. In our brain-tumor model, intratumoral administration of irradiated SR/IL-2 cells and of rIL-12 remarkably prolonged survival as compared with untreated mice. Efficacy was reduced when studies were performed in mice depleted of CD8+ cells or NK cells. Mice cured of their intracerebral tumors by combined administration of SR/IL-2 cells and rIL-12 demonstrated protective immunity upon rechallenge. In summary, the therapeutic potential for control of tumor growth by intratumoral administration of IL-2-producing glioma cells and rIL-12 may be useful in the development of treatment for patients with glioma.

Animals↗

PubMed1999

Fluctuations of hepatitis C virus load are not related to amino acid substitutions in hypervariable region 1 and interferon sensitivity determining region.

Hepatitis C virus (HCV) load is one of the most important predictive factors of response to interferon treatment. However, little is known about the mode and determinants of viremia. The mode of viremia was investigated in 78 patients with chronic HCV genotype 1b infection during 1-2 years follow up. Virus load, determined by a branched chain DNA amplification assay, was stable in 73 of 78 (93.6%) patients, whereas 5 (6.4%) showed marked fluctuation (from undetectable level to more than 10 Meq/ml) in viral titer. To study the mechanisms mediating fluctuations in viral titer, amino acid sequences of two regions were examined; hypervariable region (HVR) 1 and the interferon sensitivity determining region (ISDR). Multiple amino acid substitutions were observed in HVR 1 but no relationship was evident between substitutions and virus titers. In contrast, no amino acid substitutions were observed in the ISDR in any patients with stable virus titer during a follow-up period of 12-24 months (7-24 samples) or in one patient who was observed for 15 years. Interestingly, multiple amino acid substitutions in the ISDR appeared in only two of the five patients with marked titer fluctuation, when the virus decreased markedly. Alanine aminotransferase levels in these five patients correlated with viral load. The data suggest that amino acid substitutions in HVR1 and ISDR are not essential for changes in viral titer. Possible mechanisms of fluctuations of viral titer and amino acid substitutions in the ISDR accompanying marked reductions in viral load are discussed.

Alanine Transaminase↗

PubMed1999

Long-term result of arterial grafts interposed for arterial defects using the telescoping anastomotic technique: histological and angiographic study.

The arterial grafting model for arterial defects provides an ideal environment for the microvascular telescoping anastomosis because tension of the repaired vessel is maintained low and deformities of the inserted vessel end is minimal due to the thick arterial wall. The left femoral artery was grafted in 46 rats into the defect created in the right femoral artery using the telescoping anastomotic technique at both the proximal and distal anastomoses. The grafts were seen histologically and angiographically 3 to 4 months postoperatively in order to fairly evaluate the telescoping anastomosis in terms of long-term patency, stenosis, and changes in the outer and inner walls at the anastomosis. All arterial grafts were patent 3 to 4 months postoperatively and there were no aneurysms at the anastomoses. Enlargement of the graft diameter was minimal. The rate of stenosis at the anastomosis was smaller than that 1-day postoperatively. Even though the thick arterial wall was initially inserted and the intimal hyperplasia was still present at the anastomosis 3 to 4 months postoperatively, the long-term stenosis was relatively mild due to the atrophy in the overlapped walls.

Anastomosis, Surgical↗

PubMed1999

Multicenter study of paroxysmal dyskinesias in Japan--clinical and pedigree analysis.

To investigate the clinical features of paroxysmal dyskinesias and carry out a pedigree analysis, we conducted a multicenter survey in Japan. A questionnaire was mailed to 229 medical institutions. A total of 150 patients with paroxysmal kinesigenic choreoathetosis (PKC), including 53 sporadic cases and 97 affected individuals from 32 pedigrees, were identified. The mean age of onset of PKC was 8.8 years, and 80% of the cases were men. Of the 32 pedigrees with familial occurrence, 18 (56%) were compatible with an autosomal-dominant inheritance (AD) with complete penetrance, and seven (22%) had AD with incomplete penetrance; the remaining seven were sibling recurrence cases with apparently healthy parents. In six of seven familial cases with incomplete penetrance, the disease gene was thought to be transmitted by clinically unaffected females. Paroxysmal dystonic choreoathetosis (PDC) was found in five cases, including two sporadic cases and three affected individuals from two pedigrees; the mean age of onset was 0.6 years, and a male predominance was noted (male:female = 4:1). There was one case of paroxysmal hypnogenic dyskinesia and one case of paroxysmal exertion-induced dyskinesia. There is an unexplained male predominance for paroxysmal dyskinesias. When the genetic defect of patients with paroxysmal dyskinesias is identified, the pathophysiology of the disease will become more clear.

Adolescent↗

PubMed1999

Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: A long-term observation study of 1,643 patients using statistical bias correction with proportional hazard analysis.

The activity of interferon (IFN) is not elucidated from the viewpoint of cancer prevention in chronic hepatitis C patients en masse. The hepatocellular carcinogenesis rate was analyzed statistically in 1,643 patients with chronic hepatitis C: 1,191 patients with IFN therapy and 452 without IFN therapy. Hepatocellular carcinogenesis rates in the treated and untreated groups were 2.1% and 4.8% at the end of the 5th year, and 7.6% and 12.4% at the 10th year, respectively (P =.0036). Multivariate analysis showed that IFN slightly decreased the risk of carcinogenesis by 33%, compared with that of untreated patients (P =. 14), adjusting for the confounding effects of age, fibrotic stage, gender, and gamma-glutamyl transpeptidase (GGTP) value. Among 1,191 patients with IFN, 461 patients attained persistent loss of hepatitis C virus (HCV) RNA, and the other 145 patients retained normal alanine transaminase (ALT) values without loss of HCV RNA. The hazard of carcinogenesis in these 606 patients with persistent normal ALT with or without HCV-RNA clearance was significantly lower than that of untreated patients (hazard ratio: 0.32; P =.012) and that of the abnormal aminotransferase group. Among patients with chronic hepatitis C, IFN significantly decreased the hepatocellular carcinogenesis rate in those patients with normal or persistent low ALT values.

Adolescent↗

PubMed1999

Peroneal nerve palsy caused by intraneural ganglion.

A case of peroneal nerve palsy caused by an intraneural ganglion is presented. The cystic mass was located posterolateral to the lateral femoral condyle and extended along the common peroneal nerve distal to the origin of the peroneus longus muscle. The nerve was compressed in the narrow fibro-osseous tunnel against the fibula neck and the tight origin of the peroneus longus muscle. The nerve was decompressed by complete tumor excision and transection of the origin of the peroneus longus muscle. Full recovery of nerve function was obtained in 6 months.

Cysts↗

PubMed1999

Acute arterial occlusion associated with total knee arthroplasty.

Acute arterial occlusion is a rare but limb-threatening complication in total knee arthroplasty. Most of the previously reported cases of this complication required surgical intervention. This report illustrates an unusual case of this complication that was managed conservatively with an acceptable outcome. The case is also indicative of the etiology and the optimal prevention of this complication. In a patient with advanced arteriosclerosis, as indicated by vascular calcification around the knee or in the abdomen, knee arthroplasty should be performed without a tourniquet, and intra-operative manipulation should be done cautiously because of the potential for intimal disruption.

Acute Disease↗

PubMed1999

Adenoma arising from the cystic duct and extending to the confluence of the extrahepatic biliary tract.

We describe a rare case of adenoma with a few foci of severe atypia arising from the cystic duct in a 68-year-old woman, initially diagnosed by the presence of intracholecystic tumefactive sludge on abdominal ultrasonography. Endoscopic retrograde cholangiography (ERC) disclosed a tuberous filling defect at the orifice of the cystic duct. Pathology examination of the biopsied specimen obtained from ERC disclosed not a cancerous but an adenomatous lesion. Macroscopically, the resected specimen showed a superficially spreading and shallowly elevated lesion extending from the cystic duct to the common bile duct. Although a few sporadic foci of severe atypia were observed, microscopy did not reveal any cancer findings, but confirmed the tumorous lesion as benign adenoma, showing mild-to-moderate atypia. Postoperative immunohistochemistry revealed no expression of p53 protein. We briefly refer to the rarity of adenoma in the biliary tract and discuss the difficulty of differential diagnosis of neoplastic lesions in the extrahepatic biliary tract.

Aged↗

PubMed1999

Predictive value of different hepatitis C serological assays in the treatment of chronic hepatitis C with interferon alpha.

In order to predict the complete response rate of natural interferon-alpha (nIFN-alpha) treatment in patients with chronic active hepatitis C, we examined the predictive value (PV) of different hepatitis C serological assays. We performed first generation (ver.1) and second generation (ver.2) hepatitis C virus (HCV) branched DNA-probe assays (bDNA-probe), HCV core protein assay (core protein), HCV Amplicor Monitor assay (amplicor monitor), and HCV competitive polymerase chain reaction (competitive PCR) assay, using serum samples collected immediately before initiation of treatment. For each marker, we studied, in patients stratified by serological group (Gr), which predictive value (PV) of the HCV titers showed association with the therapeutic effect. In 59 Gr 1 patients, complete response to nIFN-alpha treatment was predicted from the following PVs for each marker: 0.5 Meq/ml or less (odds ratio 11.7: P = 0.0010) with ver.1, 1.0 Meq/ml or less (odds ratio 5.3; P = 0.0119) with ver.2 of the bDNA-probe, 50 pg/ml or less (odds ratio 10.3; P = 0.0062) with core protein, 200 x 10(3) copy/ml or less (odds ratio 7.8; P = 0.0031) with amplicor monitor, and 10(4) copy/ml or less (odds ratio 6.2; p = 0.8395) with competitive PCR. In 27 Gr 2 patients, the PV for each marker indicating complete response was as follows: There was no relationship between PV and therapeutic effect with ver.1 of the bDNA-probe, while the PVs for the other markers were 0.2 Meq/ml or less (odds ratio 2.2; P = 0.3788) with ver.2, 20 pg/ml or less (odds ratio 5.6; P = 0.0597) with core protein, 400 x 10(3) copy/ml or less (odds ratio 4.0; P = 0.2965) with amplicor monitor, and 10(5.5) copy/ml or less (odds ratio 29.2; P = 0.0096) with competitive PCR. Our findings showed that complete response to the treatment may be predicted using the appropriate PV for each marker.

Adult↗

PubMed1999

Enzyme-linked immunosorbent assay to detect hepatitis C virus serological groups 1 to 6.

By conventional serological grouping methods, it is possible to determine hepatitis C virus (HCV) serological groups for genotypes 1a, and 1b, and genotypes 2a, and 2b, but not for other genotypes, i.e., 3a, 3b, 4a, 5a, and 6a. In this study, we attempted to serologically group HCV with the Murex HCV serotyping 1 to 6 assay (Murex Diagnostics, Kent, UK), using an enzyme-linked immunosorbent assay (ELISA) based on genotype-specific peptides from the NS4 region. The subjects of this study were 365 patients infected with HCV of genotype 1a, 1b, 2a, 2b, 3a, or 3b. The sensitivity of the assay was 100% in patients with genotype 1a, 82.7% in those with 1b, 68.5% in those with 2a, 84.2% in those with 2b, 50.0% in those with 3a, and 76.5% in those with genotype 3b. The overall sensitivity was 78.4%. The specificity of the assay was 100% in the subjects with genotype 1a, 98.8% in those with 1b, 98.4% in those with 2a, 96.9% in those with 2b, 100% in those with 3a, and 100% in those with genotype 3b. The overall specificity was 98.6%. The concordance of the assay was 100% in subjects with genotype la, 81.7% in those with 1b, 67.4% in those with 2a, 81.6% in those with 2b, 50.0% in those with 3a, and 76.5% in those with genotype 3b. The overall concordance was 77.5%. We believe it would be better to serotype with the Murex HCV serotyping 1 to 6 assay, if other than serological group (Gr) 1 or Gr 2 is suspected in particular ethnic groups or in subjects with an indeterminate result with the Immucheck HCV Gr assay (Kokusai, Kobe, Japan), assuming that the genotype must be other than 1a, 1b, 2a, or 2b.

Enzyme-Linked Immunosorbent Assay↗

PubMed1999

Hypertension as a paraneoplastic syndrome in hepatocellular carcinoma.

We report a 66-year-old man with hepatocellular carcinoma who was positive for hepatitis B surface antigen, and was hospitalized because of hypoglycemia and hypertension. His plasma renin activity was normal (2.3 ng/ml per h), but concentrations of angiotensin I (>2500 pg/ml) and II (86 pg/ml) were high. Increased angiotensin I level at sites proximal and distal from the confluence of the hepatic vein and the inferior vena cava indicated that the hypertension was provoked by overproduction of angiotensin I from the hepatocellular carcinoma. Previous reports of patients with hepatocellular carcinoma with hypertension due to abnormality of renin-angiotensin system are reviewed.

Aged↗

PubMed1999

Clinical and virological features of chronic hepatitis C carriers with normal alanine aminotransferase levels despite positive serum HCV-RNA after interferon therapy.

Interferon (IFN) is the only drug that induces viral clearance, but in patients with chronic hepatitis C, HCV-RNA clearance is achieved in only 20%-40% of patients treated with IFN for 6 months. The remaining patients have positive serum HCV-RNA, but about 5%-15% of the patients with positive serum HCV-RNA after IFN therapy showed normal alanine animotransferase (ALT) levels (incomplete response; ICR). In these patients, IFN therapy is thought to be related to the suppression of necroinflammatory reaction in the liver. The aim of this study was to evaluate the demographic, clinical, histological, and virological characteristics of patients with an ICR. In this study, ICR was defined as normalization of serum ALT, but positive HCV-RNA by reverse-transcription (RT) nested PCR at two points, 3 and 6 months after cessation of IFN therapy. By multiple logistic regression analysis, the risk ratio for ICR appearance in patients treated with IFN for more than 12 months was 3.06 compared with patients treated with IFN for less than 12 months. In patients with ICR after IFN therapy, serum ALT was often reelevated during the follow-up period. The incidence of ALT re-elevation was about 10% per year in the patients treated with IFN for less than 12 months, while the incidence of ALT reelevation in the patients treated with IFN for 12 months and more was significantly lower (P = 0.0176) by the log rank test.

Adolescent↗

PubMed1999

Prader-Willi syndrome in a child with XYY.

We report a 26-month-old boy with XYY syndrome, with the complication of Prader-Willi syndrome (PWS) due to uniparental maternal disomy of chromosome 15. To our knowledge, this is the first case of XYY syndrome and PWS. Clinical findings were fully compatible with the diagnostic criteria for PWS. Molecular analysis revealed a maternal heterodisomy of chromosome 15, indicating that non-disjunction of chromosome 15 had occurred at maternal meiosis I, and that the non-disjunction of chromosome Y and of chromosome 15 had occurred independently.

Child, Preschool↗

PubMed1999

Effects of the menstrual cycle on excess postexercise oxygen consumption in healthy young women.

The effects of the menstrual cycle on excess postexercise oxygen consumption (EPOC) were studied in seven healthy young women aged 18 to 20 years. EPOC, resting metabolic rate (RMR), and energy expenditure during exercise (EEDE) in the fasting state were measured in the follicular and luteal phases. On the experimental days, subjects exercised for 60 minutes on a bicycle ergometer at an intensity of 60% maximal oxygen consumption (VO2max) followed by rest for 6 hours. The EPOC and RMR were significantly higher (P < .05) and the postexercise respiratory exchange ratio (RER) was significantly lower (P < .05) in the luteal phase versus the follicular phase, whereas differences in the EEDE and basal and exercise RER were negligible in both phases. Fat oxidation during the experimental period was significantly greater in the luteal phase (P < .05). These results suggest that exercise in the luteal phase results in greater postexercise energy expenditure and fat utilization than in the follicular phase.

Adolescent↗

PubMed1999

Histological changes in liver biopsies after one year of lamivudine treatment in patients with chronic hepatitis B infection.

BACKGROUND/AIMS: The aim of this study was to examine the histological changes in liver biopsies induced by 52 weeks of lamivudine therapy in patients with e-antigen positive and e-antigen negative chronic hepatitis B infection. METHODS: Twenty patients were enrolled into this open-label study. All patients had a liver biopsy within the 4 weeks before starting lamivudine therapy. Lamivudine was given orally at a dose of 100 mg OD for 52 weeks. A second liver biopsy was taken for comparison at the end of week 52. Blinded biopsies were evaluated by a histopathologist and scored according to Knodell's histology activity index (HAI). RESULTS: Ninety-five percent (19/20) patients had a reduction of their hepatic necroinflammatory HAI score (components 1 through 3) by > or =2 points at the end of 52 weeks of lamivudine therapy compared to their pretreatment values. Not only were improvements in necroinflammatory activity observed, but 7/20 (35%) of patients had improvement in fibrosis. This histologic improvement was independent of the presence or absence of e-antigen. CONCLUSIONS: Significant improvements in liver histology can be obtained in the majority of patients when they are treated with lamivudine for 1 year.

Adult↗