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S Saitoh

Publications and source records attributed to S Saitoh.

At least 235 records · Page 13Linked to original sources

Refined crystal structure of recombinant murine interferon-beta at 2.15 A resolution.

The crystal structure of recombinant murine interferon-beta (reMuIFN-beta) has been refined at 2.15 A resolution using newly collected synchrotron data. Based on 11,228 reflections (8.0 to 2.15 A), a final R-factor of 19.1% (with a free R-factor of 25.8%) was obtained with a model obeying standard geometry within 0.013 A in bond lengths and 1.4 degrees in bond angles. Compared with the previously reported model, several amino acid residues in helix A are frame-shifted, the conformations are changed for parts of loops AB and BC, helix C is extended and a new short helix exists in loop CD. Evolutionary considerations taken together, the type I interferons appear to share common structural features with respect to the chain-folding topology and the hydrogen-bond networks between various polypeptide segments. Specifically, the disposition of the C-terminal segment of loop AB (after Arg33), known to be an important receptor-binding site, seems to be strictly maintained among the type I interferons. The exposed amino acid residues on helices A and C, which have recently been implicated as the binding site for another receptor molecule, are less well conserved. This may be responsible for varied cellular effects among the subtypes of type I interferons.

Amino Acid Sequence↗

Diagnosis of hepatocellular carcinoma by concanavalin A affinity electrophoresis of serum alpha-fetoprotein.

BACKGROUND: Concanavalin A (Con A) affinity electrophoresis of serum alpha-fetoprotein (AFP) can distinguish hepatocellular carcinoma (HCC) from other malignancies when the serum AFP concentration is elevated. However, Con A has not been able to distinguish HCC from benign chronic liver disease such as cirrhosis or chronic hepatitis. METHODS: The Con A affinity electrophoresis of serum AFP was analyzed in patients with a serum AFP concentration greater than 50 ng/mL by antibody affinity electrophoresis and Western blotting in an attempt to distinguish hepatocellular carcinoma from benign chronic liver disease. Before the assay, the serum AFP concentrations were adjusted between 100 ng/ml and 300 ng/ml by concentrating or diluting the samples. RESULTS: Of 180 patients with HCC, 44 (24%) had a single band and 91 (51%), 35 (19%), and 10 (6%) had 2, 3, and 4 bands, respectively. All 35 patients with chronic hepatitis had a single band. All but 1 of 72 patients with cirrhosis had a single band. Multiple AFP bands on Con A affinity electrophoresis appear to be diagnostic of HCC. This method has a sensitivity of 76%, a specificity of 99%, a positive predictive value of 99%, and a negative predictive value of 71% for detecting HCC. The number of AFP bands correlated with serum AFP concentration and tumor size in patients with HCC. CONCLUSIONS: This assay is useful for distinguishing HCC from benign chronic liver diseases.

Adult↗

Comparison of the telescoping anastomotic technique with the end-to-end technique utilizing vein grafts for venous defects: short- and long-term results.

The telescoping anastomotic technique was used for both anastomoses of vein grafts placed in the rat left epigastric vein in an effort to make the anastomosis easier and faster. Vein grafting in the right epigastric vein was completed using the conventional technique. The 20 rats with 20 left and 13 right vein grafts, which were patent at 3 weeks, were seen again 3 months postoperatively to compare the two techniques with regard to long-term stenosis and histological changes. Patency of the grafts 2 hr postoperatively was also compared between the two techniques in another 25 rats to eliminate the influence of recanalization on patency. All the vein grafts, which had been patent 3 weeks postoperatively, remained patent after 3 months and no statistically significant difference was found between the telescoping and conventional technique in the degree of stenosis. The vein grafts 2 hr postoperatively were all patent in both groups.

Anastomosis, Surgical↗

Sympathetic activity is lower in rats fed a beef tallow diet than in rats fed a safflower oil diet.

Effects of dietary fats consisting of different fatty acids on sympathetic activity and body fat accumulation were studied in rats. Rats were meal-fed an isoenergetic diet based on either beef tallow or safflower oil for 8 weeks. Carcass fat content was greater (P < .05) in rats fed the beef tallow diet than in rats fed the safflower oil diet. Norepinephrine (NE) turnover rate was significantly lower (P < .05) in interscapular brown adipose tissue (IBAT) and pancreas in rats fed the beef tallow diet than in rats fed the safflower oil diet, resulting in a decreased (P < .05) diet-induced thermogenesis (DIT) and an increased (P < .05) serum insulin concentration in the former. To confirm the effects of dietary fats on sympathetic activity in relation to body fat accumulation, rats were chemically sympathectomized. Sympathectomy abolished the differences in body fat accumulation, DIT, and serum insulin concentration between the two dietary groups. These results suggest that the beef tallow diet promotes body fat accumulation by reducing sympathetic activity as compared with intake of the safflower oil diet.

Adipose Tissue↗

The development of neural visinin-like Ca(2+)-binding protein 2 immunoreactivity in the rat neocortex and hippocampus.

Neural visinin-like Ca(2+)-binding protein 2 (NVP2) immunoreactivity in the rat neocortex and hippocampus was barely detectable by immunoblot analysis on postnatal day 1 (P1), but increased during postnatal weeks 2-3, reaching a plateau on P28. Immunohistochemical analysis revealed moderate immunoreactivity firstly on P7 in some subsets of the hippocampal interneurons and in the hippocampal pyramidal cells and dentate granule cells. Immunoreactivity of the interneurons decreased during postnatal weeks 2-3 and disappeared by P28. In contrast, immunoreactivity of the cortical and hippocampal pyramidal cells and dentate granule cells abruptly increased during postnatal week 2. The distinctly immunoreactive cells were distributed throughout the neocortex, especially in the cortical plate, and the stratum pyramidale of Ammon's horn and granular layer of the dentate gyrus on P14. Immunoreactivity was homogeneously concentrated in the cell bodies and proximal dendrites at this stage, whereas thereafter immunoreactivity in the neuropil gradually increased, and underwent a relative decrease in the cell bodies. By P28, the higher and granular immunoreactivity in the neuropil covered whole layers of the neocortex, Ammon's horn and the dentate gyrus, the same as in adults. Differential expression of NVP2 in different neuron populations may reflect the differential functional consequences for neuronal development.

Animals↗

Genotype, slow decrease in virus titer during interferon treatment and high degree of sequence variability of hypervariable region are indicative of poor response to interferon treatment in patients with chronic hepatitis type C.

In a study assessing factors associated with a good or a poor response to interferon treatment in patients with chronic hepatitis type C, we analyzed serum samples taken from 26 interferon-treated patients and found further evidence that infection with genotype II is associated with a poor response. Whereas all seven patients with group III genotype tested showed a good response (normalization of alanine aminotransferase level for more than 6 months), only 10 of 19 (53%) patients infected with group II genotype showed a good response. We also observed that 16 of 17 (94%) patients who exhibited a rapid virus titer decrease during the first 2 weeks of treatment later showed a good response. In contrast, only three of nine (33%) patients with an initially slow viral decrease eventually showed a good response (p<0.04). None of the 26 control patients exhibited a marked virus decrease or normalization of serum alanine aminotransferase level. Interestingly, high degrees of sequence variability were seen in three patients with group II hepatitis C virus who responded poorly to the therapy. All three showed slow decreases in virus titer during the first 2 weeks of treatment. In contrast, patients with genotype II who showed a good response to treatment were seen to have very few mutations. In three patients with genotype III who had responded well to interferon treatment, all showed very little amino acid sequence variability in the hypervariable region compared with patients with genotype II who had responded poorly to interferon treatment. These data suggest that a slow decrease in virus titer during the beginning of interferon treatment and a high degree of sequence variability, both of which are often seen in patients with group II genotype, are associated with poor response to interferon treatment.

Adult↗

Molecular analysis of intraspousal transmission of hepatitis C virus.

BACKGROUND/AIMS: Although intraspousal transmission of hepatitis C virus (HCV) has been speculated, there is no direct evidence. METHODS: To investigate whether transmission of HCV occurs by this route, 295 spouses of persons diagnosed with HCV were studied. Of these, 25 (8.8%) tested positive for anti-HCV. Next, the HCV genotype was determined by polymerase chain reaction using a mixed primer set, and cDNA was obtained in 17 of the 25 couples for comparison of the genotypes. RESULTS: Of these 17, 14 (82.4%) spouses were shown to be infected with HCV of the same genotype. Analysis of the nucleotide sequences of putative E1 gene of eight couples having the same HCV genotype revealed that five couples had remarkably high nucleotide sequence homologies (> 97%), whereas samples obtained from the remaining three couples showed relatively low homology (91-92%). Nucleotide sequence homologies were significantly higher between spouses than between non-spouse pairs of isolates. Phylogenetic analysis using the neighbor-joining method suggests that infection in these five couples probably occurred after marriage. Furthermore, none of the five couples had shared other possible transmission routes such as intravenous drug use, dental treatment or acupuncture. CONCLUSION: These data strongly suggest the occurrence of intraspousal transmission of HCV.

Adult↗

Conservative treatment of thoracic outlet syndrome using an orthosis.

We describe a strapping device for elevation of the shoulder in patients with thoracic outlet syndrome (TOS). The device was used by 86 patients with TOS whose symptoms had been alleviated by passively raising the shoulder. Symptoms of TOS were classified as proximal, including pain in the shoulder girdle, and distal, in which there were neurological deficits related to the brachial plexus. The device was more effective in patients with distal symptoms: pain disappeared or improved in 67% of patients; numbness in 85%; sensory disturbance in 84%; and motor disturbance in 80%. However, proximal symptoms were relieved in only 65% of the patients. The ability to perform activities of daily living was rated as excellent in 33% of patients, good in 44%, fair in 12%, and poor in 9%. The shoulder orthosis described in this report can counterbalance downward traction on the brachial plexus and reduce the tension on it, thereby relieving symptoms of TOS.

Activities of Daily Living↗

Inherited microdeletions in the Angelman and Prader-Willi syndromes define an imprinting centre on human chromosome 15.

A subset of patients with Angelman and Prader-Willi syndrome have apparently normal chromosomes of biparental origin, but abnormal DNA methylation at several loci within chromosome 15q11-13, and probably have a defect in imprinting. Using probes from a newly established 160-kb contig including D15S63 (PW71) and SNRPN, we have identified inherited microdeletions in two AS families and three PWS families. The deletions probably affect a single genetic element that we term the 15q11-13 imprinting centre (IC). In our model, the IC regulates the chromatin structure, DNA methylation and gene expression in cis throughout 15q11-13. Mutations of the imprinting centre can be transmitted silently through the germline of one sex, but appear to block the resetting of the imprint in the germline of the opposite sex.

Angelman Syndrome↗

Tissue-type transglutaminase is not a tumor-related marker.

The level of transglutaminase (TGase) expressed in various tumor cell lines was investigated. We found that each cell line could be categorized into three distinct groups, that is, (i) cell lines with low or negligible TGase activity, (ii) cell lines with significant or high TGase activity and immunoreactive to a monoclonal antibody against tissue type TGase, and (iii) cell lines with significant or high TGase activity but not immunoreactive to the antibody. Results reported here argue against the former proposal that tissue-type TGase is expressed at a lower level in malignant cells compared to the level in normal cells.

3T3 Cells↗

A prospective randomized evaluation of a compound of tegafur and uracil as an adjuvant chemotherapy for hepatocellular carcinoma treated with transcatheter arterial chemoembolization.

A prospective randomized trial was conducted to evaluate the efficacy of long-term oral administration of low-dose tegafur combined with uracil as an adjuvant chemotherapy, following transcatheter arterial embolization (TAE) in 40 patients with hepatocellular carcinoma (HCC). Forty eligible patients were randomized into two groups: 20 with TAE plus UFT (a compound of tegafur 200 mg and uracil 448 mg per day) and 20 with TAE alone. A good necrosis rate or decrease in size of more than 70% of the original tumor mass was attained in 10 by TAE plus UFT arm and in 12 by TAE arm alone. As for the "responded" patients, there was no significant difference in the time from tumor response to tumor regrowth between the two groups. The appearance rate of ascites and/or encephalopathy in patients with chemotherapy was slightly higher than that in control patients. The median survival time was 22.7 months for TAE plus UFT arm and 28.2 months for TAE arm alone. There was no significant difference in the cumulative survival curves. In conclusion, these results indicated no substantial benefit for this chemotherapy regimen, as an adjuvant therapy for patients with HCC during repeated TAE.

Adult↗

Telescoping and glue technique in vein grafts for arterial defects.

Fibrin glue was applied at the anastomotic site of the vein graft that was placed in rat femoral artery defects by the telescoping anastomotic technique at both proximal and distal anastomoses. All 35 vein grafts thus placed were patent, yielding a statistically higher patency rate than those placed in the same femoral artery by the same telescoping anastomotic technique but without fibrin glue. The telescoping anastomotic technique assisted by fibrin glue appears to give as reliable a patency rate as the conventional method even if it is used twice, both at the proximal and distal anastomoses, in autogenous vein grafting for arterial defects. Deformities of the inserted vessel should be minimized for patency by some means such as an application of fibrin glue so that the inserted vessel does not bulge under high arterial pressure.

Animals↗

In vivo administration of IL-1 beta accelerates silk ligature-induced alveolar bone resorption in rats.

The effects of recombinant human interleukin-1 beta (rhIL-1 beta) on alveolar bone resorptive activity in rats were examined. Continuous administration of rhIL-1 beta or phosphate-buffered saline (PBS) was given via osmotic pumps for 3, 7 and 14 days to rats with silk ligatures around second maxillary molars. Other animals without ligatures received insertion of pumps containing rhIL-1 beta or remained untreated. Sections were subject to three different stains:--hematoxylin and eosin (H-E) for histology, acid phosphatase (ACPase) activity for osteoclast detection, and immunohistochemistry using anti-rat monocyte/macrophage monoclonal antibody (ED 1). In addition, body weight, plasma calcium and phosphorus levels were monitored. The mean body weight of rats receiving rhIL-1 beta was significantly lower (P < 0.05 to P < 0.01) compared with untreated rats throughout the experimental period. On Day 7, plasma calcium and phosphorus levels were significantly lower in rats receiving rhIL-1 beta than in rats receiving PBS only (P < 0.05). Sections revealed a moderate inflammatory cell infiltrate reaching near the alveolar crest in both groups with ligatures on Day 3. Only rats receiving rhIL-1 beta exhibited enhancement of inflammatory cell invasion on Days 7 and 14. In rats receiving rhIL-1 beta with ligatures, numerous resorption lacunae containing ACPase-positive multinucleated giant cells (MNGCs), coinciding with ED1-positive cells, were located on the mesial side of the septum where extensive bone resorption had occurred throughout the experimental period. In animals receiving rhIL-1 beta without ligatures, compared with untreated rats, increased ACPase-positive cells were observed on the mesial side of the septum on Day 3. In animals receiving PBS only, a few ACPase-positive cells were observed confined to the mesial regions where slight bone resorption occurred on Days 7 and 14. These results indicate that the administration of rhIL-1 beta accelerated alveolar bone destruction in ligature-induced periodontal tissue inflammation over a two-week period.

Acid Phosphatase↗

Hemodynamic effects and pharmacokinetics of oral milrinone for short-term support in acute heart failure.

The present study evaluated the acute hemodynamic response, effects on subjective symptoms and physical findings, and the pharmacokinetics of a single oral dose (2.5, 5, or 10 mg) of milrinone in 31 patients with acute or decompensated heart failure. We found a significant increase in cardiac index (29, 31, and 29%, respectively, p < 0.01) and a significant decrease in pulmonary capillary wedge pressure (39, 43, and 47%, respectively, p < 0.01) accompanied with improvement in subjective symptoms and physical findings. These hemodynamic effects persisted for 4-8 h after each dosage of milrinone. Dose-dependent hemodynamic response was observed between the drug concentration and percent maximum changes in pulmonary capillary wedge pressure (peak milrinone concentration, 2.5 mg: 99.99 +/- 57.49, 5 mg: 187.11 +/- 71.37, and 10 mg: 300.94 +/- 158.5 ng/ml). The finding, together with results of the Prospective Randomized Milrinone Survival Evaluation (PROMISE) study, suggests lower dose of milrinone will be useful for the short-term inodilator support in patients with acute or decompensated heart failure.

Acute Disease↗

Effect of inhibiting renal kallikrein on prostaglandin E2, water, and sodium excretion.

To test the hypothesis that renal kinins act as natriuretic and diuretic hormones, we examined the effect of inhibiting glandular kallikrein on renal function in normotensive unanesthetized rats during normal sodium intake. To inhibit kallikrein at both the luminal and basolateral sides of the distal nephron, we used Fab fragments of monoclonal antibodies to rat urinary kallikrein (Fab-kallikrein). Fab fragments have advantages over intact IgG: they are filtered through the glomerulus and reach the lumen of the distal nephron, where kallikrein is localized and urinary kinins are released. Furthermore, the Fab fragment-antigen complex does not activate the complement system, avoiding the side effects associated with intact antibodies. Fab-kallikrein effectively blocked generation of kinins in the nephron lumen, decreasing urinary kininogenase activity (kallikrein) by 74% to 85% and kinin excretion by 76% to 79%. Fab-kallikrein induced a 30% decrease in urine volume and a 20% to 40% decrease in urinary sodium excretion but did not alter blood pressure, glomerular filtration rate, or renal blood flow. Although urinary prostaglandin E2 excretion also tended to decrease, this change was slower and of lesser magnitude than those of kinin and kininogenase excretion and did not attain statistical significance after Bonferroni's correction. In controls injected with either vehicle or Fab fragments of monoclonal antibodies to ricin (a vegetable protein not present in mammals), none of these parameters decreased significantly. We conclude that renal kinins participate in the short-term regulation of water and sodium excretion in normotensive unanesthetized rats, acting as diuretic and natriuretic hormones.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A mechanism of resistance to partial macrolide and streptogramin B antibiotics in Staphylococcus aureus clinically isolated in Hungary.

A plasmid pEP2104 originated from Staphylococcus aureus was clinically isolated in Hungary during 1977. The plasmid mediates inducible resistance to PMS-antibiotics; partial macrolide [the 14-membered macrolides, erythromycin (EM) and oleandomycin and the 16-membered macrolides mycinamicin I (MCM I) and mycinamicin II (MCM II)and type B streptogramin (MKM-B) antibiotics. The sequence of 31 amino acid residues obtained by N-terminal analysis of the 63kDa protein (MsrSA) present in the membrane from 8325(pEP2104) cells whose PMS-resistance was induced by a concentration of 1.35 micrograms EM/ml [EM-induced 8325(pEP2104)], was identical to the corresponding sequence in a membrane protein MsrA related to promoting efflux of [14C]EM [Ross J.I., et al., Mol. Microbiol., 4, 1207 (1990)]. A constitutive PMS-resistant strain 8325(pMC38) was obtained from the 8325( pEP2104) strain in the presence of 1 microgram MCMI/ml. No inactivation of EM in EM-induced 8325(pEP2104) was observed. Moreover, poly (A)-directed polylysine synthesis by a cell-free system containing ribosomes from EM-induced 8325 (pEP2104) cells and S100 from Escherichia coli was inhibited by not only EM but spiramycin and MKM-B [Matsuoka M., et al., Biol. Pharm. Bull., 16, 1288 (1993)]. In addition, ribosomes from both EM-induced 8325 (pEP2104) and 8325(pMC38) strains showed about the same affinity as those from the host stain. NCTC8325. These results suggest, that like MsrA protein, active drug-efflux due to MsrSA protein may be responsible for PMS-resistance. How can the 8325 (pMC38) strain discriminate PMS-antibiotics from most of 16-membered macrolides and lincosamides? A possible explanation is discussed in terms of the pKa-value related to the physicochemical nature of the antibiotics.

Amino Acid Sequence↗

Specific detection of Campylobacter jejuni by means of polymerase chain reaction in chicken litter.

A routine detection assay of Campylobacter jejuni was developed with the polymerase chain reaction (PCR). A pair of oligonucleotide primers from the flaA of C. jejuni were used in detection by PCR. Although the primer pair specifically detected C. jejuni strains, they did not detect strains of C. coli, C. fetus, Salmonella spp. or Escherichia coli. In litter inoculated with C. jejuni, specific detection of C. jejuni was obtained by PCR with this primer pair.

Animals↗