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Biomedical subjects

S Machida

Publications and source records attributed to S Machida.

At least 37 records · Page 2Linked to original sources
PubMed2000

Lack of effect of running training at two intensities on cardiac myosin isozyme composition in rats.

Little information is available regarding the influence of the intensity of endurance training over biochemical profiles in cardiac muscle. We assessed the effect of running training at two different intensities on cardiac myosin isozyme composition in rats. Male Sprague-Dawley rats (4 weeks old) were divided into four groups: sedentary control (SC), trained at 20 m/min (T20), trained at 40 m/min (T40), and weight-matched sedentary control (WMSC) groups. The T20 and T40 group rats were trained by treadmill running for 60 min/d, 5 d/week at 20 or 40 m/min, respectively, for 11 to 12 weeks. In both groups the left ventricle was significantly heavier than in WMSC animals. The ratio of left ventricle weight to body weight was significantly greater in T40 rats than in either the untrained (SC and WMSC) or trained T20 rats. Thus the extent of exercise-induced cardiac hypertrophy appears to be influenced by the intensity of running training. However, neither of the training programs (1) induced a change in cardiac myosin isozyme composition or (2) had any effect on myocardial succinate dehydrogenase or citrate synthase activity. These results suggest that although the intensity of running training may play an important role in cardiac morphological adaptation, it does not modulate the cardiac biochemical adaptation to running training.

Animals↗
PubMed2000

The effect of calcium channel blocker diltiazem on photoreceptor degeneration in the rhodopsin Pro213His rat.

PURPOSE: To determine whether the calcium channel blocker D-cis-diltiazem promotes photoreceptor survival in rats with the Pro23His rhodopsin mutation. METHODS: Heterozygous Pro23His rhodopsin line 1 rats (n = 11) were treated daily, according to a protocol applied successfully in rd mice, with D-cis-diltiazem hydrochloride increased incrementally from 21 to 54 mg/kg in a divided dose (8 AM and 8 PM) administered by intraperitoneal (i.p.) injection for 21 days, beginning on days of age 10 through 12. Saline-treated line 1 rats (n = 6) received i.p. injections of an equal volume of 0.9% saline. Analysis on day 35 of age included dark-adapted corneal electroretinogram (ERG) b- and a-waves recorded from threshold to 0.63 log candela-seconds [cd-s]/m2, saturated a-waves elicited with a 2.1 log cd-s/m2 flash, and morphometry of the outer nuclear layer (ONL) and rod outer segments (ROS). RESULTS: ONL width and cell counts of diltiazem-treated and saline-treated animals at 35 days were reduced to 64%-68% of 15-day-old untreated P23H line 1 retinas. No photoreceptor rescue was found by measuring ONL width (P = 0.84), cell count (P = 0.42), or ROS length (P = 0.85). Functional assays by ERG b-wave threshold (P = 0.57), b-wave maximum amplitude (P = 0.46), and saturated a-wave amplitude (P = 0.59) also showed no rescue. CONCLUSIONS: D-cis-Diltiazem did not rescue photoreceptors of Pro23His rhodopsin mutation line 1 rats treated according to the protocol used in rd mouse.

Animals↗
PubMed2000

P23H rhodopsin transgenic rat: correlation of retinal function with histopathology.

PURPOSE: To correlate retinal functional changes with structural changes in P23H rhodopsin transgenic rats as a model of autosomal dominant retinitis pigmentosa. METHODS: P23H heterozygote (lines 1 and 3) and Sprague-Dawley control rats were studied at 4 to 29 weeks by retinal histology, electroretinogram (ERG), and a-wave transduction modeling. RESULTS: Both line 1 (faster degeneration) and line 3 (slower degeneration) showed progressive rod outer segment (ROS) shortening and outer nuclear layer (ONL) cell loss with age. ERG b-wave maximum amplitude (Vb(max)) decreased with age, but b-wave threshold remained constant within each line despite progressive ONL thinning and ROS shortening. The only exception was in line 1 at 29 weeks, which showed a slight threshold change relative to earlier ages. Va(max) and a-wave threshold changed more rapidly and were more sensitive than the b-wave in reflecting histologic degeneration. Va(max) was linearly proportional to the product of (ROS x ONL) across a two log unit range of data combined from both lines. The photopic b-wave was normal for both lines until the ONL thinned beyond 50%. Phototransduction sensitivity was normal for both lines, and dark-adaptation recovery after bleaching rhodopsin was normal. CONCLUSIONS: The P23H transgenic rat has a slow rod degeneration with initially normal cone function, consistent with clinical findings of P23H patients. However, the normal bleach recovery and the normal phototransduction sensitivity in this rat model are different from human P23H disease. a-Wave measures were more sensitive than the b-wave for tracking changes. b-Wave threshold was inexplicably poor for tracking degeneration. Although line 1 degenerated faster than line 3, the functional-structural correlates were the same. The tight linear relationship between saturated a-wave amplitude and the product of (ROS x ONL) indicates that the density of cGMP-gated channels per unit ROS plasma membrane area remains constant over a wide range of degenerations.

Animals↗
PubMed1999

An investigation of the nature and function of module 10 in a family F/10 xylanase FXYN of Streptomyces olivaceoviridis E-86 by module shuffling with the Cex of Cellulomonas fimi and by site-directed mutagenesis.

Although the amino acid homology in the catalytic domain of FXYN xylanase from Streptomyces olivaceoviridis E-86 and Cex xylanase from Cellulomonas fimi is only 50%, an active chimeric enzyme was obtained by replacing module 10 in FXYN with module 10 from Cex. In the family F/10 xylanases, module 10 is an important region as it includes an acid/base catalyst and a substrate binding residue. In FXYN, module 10 consists of 15 amino acid residues, while in Cex it consists of 14 amino acid residues. The Km and kcat values of the chimeric xylanase FCF-C10 for PNP-xylobioside (PNP-X2) were 10-fold less than those for FXYN. CD spectral data indicated that the structure of the chimeric enzyme was similar to that of FXYN. Based on the comparison of the amino acid sequences of FXYN and Cex in module 10, we constructed four mutants of FXYN. When D133 or S135 of FXYN was deleted, the kinetic properties were not changed from those of FXYN. By deletion of both D133 and S135, the Km value for PNP-X2 decreased from the 2.0 mM of FXYN to 0.6 mM and the kcat value decreased from the 20 s(-1) of FXYN to 8.7 s(-1). Insertion of Q140 into the doubly deleted mutant further reduced the Km value to 0.3 mM and the kcat value to 3.8 s(-1). These values are close to those for the chimeric enzyme FCF-C10. These results indicate that module 10 itself is able to accommodate changes in the sequence position of amino acids which are critical for enzyme function. Since changes of the spatial position of these amino acids would be expected to result in enzyme inactivation, module 10 must have some flexibility in its tertiary structure. The structure of module 10 itself also affects the substrate specificity of the enzyme.

Amino Acid Sequence↗
PubMed1999

Molecular analyses of five new chimpanzee MHC class I alleles: implications for differences between evolutional mechanisms of HLA-A, -B, and -C loci.

In order to study the origin of the polymorphism of MHC class I molecules, we have cloned and sequenced five new Patr-A, -B, and -C loci alleles from two chimpanzees. Previous studies of sequence comparison between Patr and HLA class I alleles revealed that many of the sequence motifs were shared and the origin of class I molecules predated the divergence of chimpanzees and humans. These findings are confirmed by our current study. Additionally, our data suggest significant differences between mechanisms of evolution of the A, B, and C loci: (1) The B locus is characterized by frequent nucleotide substitutions, whereas the A and C loci are relatively more conserved; (2) However, unlike the A locus, the alpha2 domains of the C locus sequenced appear to produce MHC polymorphism between these species. These differences might imply the distinctive contributions of each locus during the evolutionary history.

Alleles↗
PubMed1999

A phase II study of irinotecan and infusional cisplatin with recombinant human granulocyte colony-stimulating factor support for advanced non-small-cell lung cancer.

PURPOSE: We administered chemotherapy consisting of a combination of 5-day continuous infusion of cisplatin (20 mg/m2 per day) plus irinotecan (160 mg/m2 per day, as a bolus, on day 1) with recombinant human granulocyte colony-stimulating factor (rG-CSF) support to previously untreated advanced non-small-cell lung cancer (NSCLC) patients, and evaluated the effectiveness and safety of this therapy. PATIENTS: Enrolled in the study were 41 NSCLC patients. RESULTS: Of the 41 patients, 24 achieved a partial response. The response rate was 58.5% (95% confidence interval, 42.2% to 74.8%), with a median response duration of 32.1 weeks. The median survival time was 44.8 weeks and the 1-year survival rate was 44%. A total of 100 courses of therapy were given. The major toxic effects were grade 3 or 4 diarrhea (23%), granulocytopenia (20%), thrombocytopenia (15%) and anemia (15%). There were no treatment-related deaths. CONCLUSIONS: Combination chemotherapy with irinotecan plus infusional cisplatin with rG-CSF support was well tolerated and effective in patients with advanced NSCLC.

Adult↗
PubMed1999

High prevalence of Borna disease virus in domestic cats with neurological disorders in Japan.

A total of 15 (T-1-T-15) domestic cats with neurological disorders in Tokyo area were examined for association with Borna disease virus (BDV). None had detectable antibodies to feline immunodeficiency virus (FIV), feline leukemia virus, feline infectious peritonitis virus and Toxoplasma gondii, and only cat T-8 had detectable antibody to FIV. Serological and molecular epidemiological studies revealed a significantly high prevalence of BDV infection in these cats: antibodies against BDV p24 and/or p40 proteins in 10/15 (66.7%) and p24 and/or p40 RNA in peripheral blood mononuclear cells in 8/15 (53.3%). Further, in situ hybridization and immunohistochemistry analyses of the autopsied brain samples derived from one of the cats (T-15) revealed BDV RNA predominantly in neuronal cells in restricted regions, such as olfactory bulb and medulla of cerebrum. Thus, BDV is present in Japanese domestic cats with neurological disorders at a high prevalence.

Animals↗
PubMed1999

Lung cancer in patients under 50 years old.

A long-term retrospective study was carried out on 790 cases of lung cancer to determine if the clinicopathologic characteristics and survival rates of lung cancer patients under the age of 50 differ from those of patients 50 years of age or older at diagnosis by analyzing data on patients registered at Tochigi Cancer Center Hospital. Of the 790 patients, 77 (9.7%) were under the age of 50 at diagnosis. The percentage of women in the younger patient group was significantly higher than that in the older patient group (39.0% vs. 27.5%; P = 0.034). Tumor histology revealed a significant preponderance of adenocarcinomas (60 patients, 77.9%) and a paucity of squamous cell carcinomas (8 patients, 10.4%) in the younger age group (P<0.001). The preponderance of adenocarcinoma was significant in both males and females (male: P = 0.004, female: P = 0.004). Smoking rates and rate of detection by cancer screening did not differ between the two age groups. Because of the paucity of smokers among the younger female patients, causes of lung cancer other than smoking should be sought in younger patients. No difference was found in the stage of the disease at presentation, treatment methods and survival rates between the two age groups. It is suggested that the prognosis for patients with lung cancer under the age of 50 is not significantly worse than for those aged 50 years or older, as has been shown by several investigators.

Adult↗
PubMed1999

Detection of brain metastasis in potentially operable non-small cell lung cancer: a comparison of CT and MRI.

STUDY OBJECTIVE: To compare the usefulness of MRI and CT in the detection of brain metastases during preoperative evaluation and postoperative follow-up. DESIGN: A prospective and sequential comparison. PATIENTS AND METHODS: Of 332 patients with potentially operable non-small cell lung cancer who were free of neurologic signs and symptoms, brain CT was performed preoperatively on 155 patients (CT group) and brain MRI on 177 patients (MRI group). Patient characteristics in both groups were comparable. In 279 patients with complete resection of the primary lung tumor, intensive follow-up with CT and MRI was performed in the respective groups. The preoperative detection of brain metastases, postoperative intracranial recurrence rates, and characteristics of detected brain tumors were compared between the two groups. The survival of patients with brain metastases was also compared. RESULTS: From the first evaluation to 12 months after surgery for primary lung cancer, brain metastases were observed in 11 patients (7.1%) from the CT group and 12 patients (6.8%) from the MRI group. MRI detected brain metastases preoperatively in 6 of the 12 patients (3.4% of the total MRI group), whereas CT detected brain metastases preoperatively in 1 of the 11 patients (0.6% of the total CT group). MRI showed a tendency toward a higher preoperative detection rate of brain metastases than CT (p = 0.069). Furthermore, the mean (+/- SD) maximal diameter of the brain metastases was significantly smaller in the MRI group (12.8+/-9.1 mm) than in the CT group (20.3+/-7.0 mm) (p = 0.041). However, the median survival time and 2-year survival rate after treatment of detected brain metastases, respectively, were 10 months and 27% in the CT group and 17 months and 28% in the MRI group. There was no significant difference between the groups in survival time. CONCLUSIONS: Preoperative evaluation and intensive follow-up with MRI could facilitate early detection of brain metastases in patients with potentially operable lung cancer. However, further studies on detection and treatment of the metastatic tumors are considered necessary.

Adenocarcinoma↗
PubMed1998

Overproduction of beta-glucosidase in active form by an Escherichia coli system coexpressing the chaperonin GroEL/ES.

beta-Glucosidase from Cellvibrio gilvus was successfully overproduced in soluble form in Escherichia coli, with the coexpression of GroEL/ES. Without the GroEL/ES protein, the beta-glucosidase overexpressed in E. coli constituted a huge amount (80%) of the total cellular protein, but was localized in the insoluble fraction, and little activity was detected in the soluble fraction. Coexpression of the E. coli GroEL/ES had a drastic impact on the proper folding of the beta-glucosidase; 20% of the overexpressed enzyme was recovered in the soluble fraction in active form. In addition, the synergistic effect of GroEL/ES and the low induction temperature led to 70% solubilization of the total expressed target protein and more than a 20-fold increase in activity. Similar effects of GroEL/ES were also observed on the overexpressed beta-glucosidase from Agrobacterium tumefaciens.

Chaperonin 60↗
PubMed1998

Helical computed tomography diagnosis of pleural dissemination in lung cancer: comparison of thick-section and thin-section helical computed tomography.

Pleural dissemination in lung cancer was prospectively evaluated by helical computed tomography (CT), and the usefulness of thick-section CT (10-mm collimation; pitch 1) and thin-section CT (2-mm collimation; pitch 1) were compared. The study included 54 patients with pulmonary adenocarcinoma in whom plain chest radiographs showed no evidence of pleural effusion and in whom the primary lesion was seen to be contiguous with the pleural surface on thick-section CT. Thin-section CT was performed for evaluation of the costal, mediastinal, interlobar, and diaphragmatic pleural surfaces. Pathologic examination revealed pleural dissemination in 20 patients (8 resected, 12 nonresected). Pleural dissemination was diagnosed in 12 patients on thick-section CT, and in 20 patients on thin-section CT. False negatives occurred in ten and two patients, respectively. The same two patients were false positives by both methods. Accuracy was 78% for thick-section CT and 93% for thin-section CT, and sensitivity was 50% and 90%, respectively. Thin-section CT provided more useful information than thick-section CT for the evaluation of pleural dissemination in lung cancer.

Adenocarcinoma↗
PubMed1998

The complete sequence and expression patterns of the atrial myosin heavy chain in the developing chick.

We have earlier reported partial cloning of a cDNA of a chick atrial myosin heavy chain (MHC) gene, CCSV2 and its expression pattern in embryonic chick hearts (Oana et al (1995) Eur J Cell Biol 67, 42-49). In this study, five overlapping cDNA clones (including CCSV2) which together encode the entire open reading frame of the chick atrial MHC gene were characterized, and both the entire nucleotide sequence consisting of 5825 bases and the deduced amino acid sequence consisting of 1931 amino acids determined. Reinvestigation of the nucleotide sequence of the previously reported and presumably different chick atrial specific MHC cDNA clone, AMHC1 (Yutzey et al (1994) Development 120, 871-883), revealed that our clone and AMHC1 encoded the same MHC. The chick atrial MHC gene was strongly expressed in developing chick atria from a very early stage (Hamburger and Hamilton stage 9, 29-33 h) to the adult stage. This gene was also expressed, although weakly, in the ventricle, somite (the precursor to skeletal muscle) and skeletal muscle during embryonic stages but not in adults.

Amino Acid Sequence↗
PubMed1998

[HLA antigens are associated in seronegativity to cytomegalovirus(CMV)].

Cytomegalovirus(CMV) is ubiquitous in the world, but the rate of CMV antibody positivity (seropositivity) in adults varies geographically. In Japan, CMV seropositivity in adults in 90% and we perceived seronegative adults tend to remain seronegative in 10 years follow up study. We have performed HLA typing 125 seronegative healthy donors of 28 years and up (28-57, Ave.35), and the results were compared with those of healthy donors in same area and whole Japan (data from 10th HLA workshop). Incidence of HLA-A33 and HLA-Cw4 were significantly higher in seronegatives than control groups. This report suggests possible involvement of HLA type in CMV negativity.

Adult↗
PubMed1998

[Kampo medicines for the prevention of irinotecan-induced diarrhea in advanced non-small cell lung cancer].

A combination of irinotecan hydrochloride (CPT-11; 160 mg/m2, intravenous infusion, day 1) and cisplatin (5-day continuous intravenous infusion; 20 mg/m2/day) was administrated to advanced non-small cell lung cancer patients. They were given Hangeshashin-to (TJ-14), a Kampo medicine, to prevent the occurrence of irinotecan-induced diarrhea. The authors studied the Kampo medicine's clinical usefulness in a randomised comparative trial. Subjects in the study comprised 41 non-resectable and untreated non-small cell lung cancer patients. A daily dosage of 7.5 g Hange shashin-to was divided into three portions, each of which was given to the subjects orally before each meal. The subjects began taking the medicine three or more days before the start of chemotherapy, and continued taking it more than 21 days after starting chemotherapy. A total of 18 patients received TJ-14, and 23 did not. Compared with the latter, those given the Kampo medicine reported a significant (p = 0.044) improvement in the grade of diarrhea, and had a lower incidence of diarrhea grade 3 and above (p = 0.018). However, no differences were seen among the two groups in terms of the frequency of diarrhea and the duration of the diarrhea. As side effects, two patients developed grade 1 constipation. These findings showed that TJ-14 was effective in preventing and alleviating the incidence of diarrhea induced by CPT-11.

Adult↗
PubMed1997

Ykt6p, a prenylated SNARE essential for endoplasmic reticulum-Golgi transport.

Vesicular transport between secretory compartments requires specific recognition molecules called SNAREs. Here we report the identification of three putative SNAREs, p14 (Sft1p), p28 (Gos1p), and a detailed characterization of p26 (Ykt6p). All three were originally isolated as interacting partners of the cis Golgi target membrane-associated SNARE Sed5p, when Sec18p (yeast NSF) was inactivated. YKT6 is an essential gene that codes for a novel vesicle-associated SNARE functioning at the endoplasmic reticulum-Golgi transport step in the yeast secretory pathway. Depletion of Ykt6p results in the accumulation of the p1 precursor (endoplasmic reticulum form) of the vacuolar enzyme carboxypeptidase Y and morphological abnormalities consistent with a defect in secretion. Membrane localization of Ykt6p is essential for protein function and is normally mediated by isoprenylation. However, replacement of the isoprenylation motif with a bona fide transmembrane anchor results in a functional protein confirming that membrane localization, but not isoprenylation per se, is required for function. Ykt6p and its homologues are highly conserved from yeast to human as demonstrated by the functional complementation of the loss of Ykt6p by its human counterpart. This is the first example of a human SNARE protein functionally replacing a yeast SNARE. This observation implies that the specific details of the vesicle targeting code, like the genetic code, are conserved in evolution.

Amino Acid Sequence↗
PubMed1997

A phase I study of irinotecan and infusional cisplatin with recombinant human granulocyte colony-stimulating factor support in the treatment of advanced non-small cell lung cancer.

We conducted a phase I study to examine whether support with recombinant human granulocyte colony-stimulating factor (rG-CSF) would permit dose intensification of irinotecan (CPT-11) in combination with cisplatin (20 mg/m2 x 5 days) in non-small cell lung cancer (NSCLC) patients. CPT-11 was administered by bolus infusion at a starting dose of 100 mg/m2 on day 1, followed by serial increments at 20 mg/m2, given every 4 weeks. The major toxic effects were granulocytopenia and diarrhoea. The response rate was 55% (11/20). The optimum dose for phase II studies appears to be 20 mg/m2/day (5-day continuous infusion) for cisplatin and 160 mg/m2 (day 1) for CPT-11 with rG-CSF support in NSCLC.

Aged↗
PubMed1997

[Choroidal lesions and surgical treatment of bullous retinal detachment].

To define choroidal lesions of bullous retinal detachment, we performed indocyanine green angiography (IA) on 20 eyes of 10 patients with bullous retinal detachment. Four of these eyes were treated with sclerectomy and sclerostomy (Gass), and the benefit was evaluated. IA showed the following choroidal abnormalities: choroidal filling delay in the macular region (6 of 18 eyes, 33%) and underneath the leaking sites (9 of 18 eyes, 50%), localized (1 eye, 5%) and extended (18 eyes, 90%) choroidal venous dilatation, and intrachoroidal hyperfluorescence (all eyes, 100%). After the surgical treatment, retinal detachments resolved within 9 weeks (mean 5.3 weeks). Since choroidal filling delay, choroidal venous dilatation and intrachoroidal hyperfluorescence were observed, it is suggested that choroidal congestion plays a causative role in bullous retinal detachment. Sclerectomy and sclerostomy seemed to be beneficial in treatment of this condition.

Adult↗