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Biomedical subjects

Y Matsubara

Publications and source records attributed to Y Matsubara.

At least 145 records · Page 8Linked to original sources

Stage-specific elevated expression of the genes for hepatocyte growth factor, keratinocyte growth factor, and their receptors during the morphogenesis and differentiation of rat stomach mucosa.

Hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) are two factors considered to be involved in the morphogenesis of several organs. To understand the role of HGF and KGF in the stomach development, we analyzed changes in the levels of expression of the genes for the two growth factors and their receptors in the fetal rat stomach by competitive RT-PCR. Resembling our previous results for HGF, the expression of the genes for KGF and its receptor was observed in the mesenchyme and epithelium of 16.5 day fetal stomach, respectively, indicating the possibility that KGF mediates the epithelial-mesenchymal interaction in the early stage of stomach development. The developmental profile of the expression of the genes for the two growth factors and their receptors were different, indicating a difference in their roles; the genes for HGF and c-met, the receptor for HGF, are expressed mainly during the morphogenetic period, while the genes for KGF and its receptor mainly after the morphogenetic period. Thus, it is probable that HGF controls the proliferation of epithelial cells during the morphogenetic process. The expression of the genes for KGF and its receptor is not correlated with epithelial proliferation during morphogenesis, but it does appear to be linked with epithelial differentiation. These results, together with the absence of significant mitogenic effect of KGF on the epithelial cells of the fetal rat glandular stomach in vitro, suggest a role for KGF as a differentiation factor. In addition, the expression profile of the genes for KGF and its receptor towards the end of fetal period appears to be closely correlated with that of mesenchymal cell proliferation, suggesting another role for the growth factor that is not regulated by the epithelial-mesenchymal interaction.

Animals↗

Complementary DNA cloning and sequencing of rat enteropeptidase and tissue distribution of its mRNA.

A cDNA clone encoding enteropeptidase (EC 3.4.21.9), a key enzyme for the conversion of trypsinogen to trypsin, was isolated from a rat duodenal mucosa cDNA library. Sequences of the 3585 base pair clone predicted that enteropeptidase is synthesized as a single-chain precursor form, proenteropeptidase, consisting of 1058 amino acid residues with an internal signal sequence (51 residues) and is then processed into the mature enzyme consisting of three different peptide chains, i.e., mini, light and heavy chains, not the previously reported two-chain enzyme. The structure of enteropeptidase is relatively conserved among different species and the rat enteropeptidase is 24 and 39 amino acids longer than the porcine and human ones, respectively. Northern blot analysis of rNAs from normal rat tissues revealed that the enteropeptidase mRNA of around 4.4 kb in size was expressed only in the duodenal mucosa, and high proteolytic activity of the enzyme was detected in the proximal small intestine. Additional analysis of the RNAs by RT-PCR revealed that a low level of the mRNA was also expressed in the other parts of the small intestine, i.e., jejunum and ileum. These results indicate that the biosynthesis of enteropeptidase takes place mainly in the proximal small intestine, the duodenum, and the importance of the region in the physiology of intestinal protein digestion regulated by the enzyme is suggested. Furthermore a faint signal of the mRNA was also detected in the stomach, colon and brain in which the existence of trypsin-like serine proteases were reported. The significance of the low level expression of the gene is unclear, but the potential peptide-processing function of the enzyme in these tissues is also suggested.

Amino Acid Sequence↗

Effect of the oral administration of Lactobacillus brevis subsp. coagulans on interferon-alpha producing capacity in humans.

OBJECTIVE: This study was designed to determine whether the oral administration of Lactobacillus brevis subsp. coagulans modulates immunological responses in human subjects, and whether there are differences in response between live and heat-treated preparations. METHODS: The effect of the oral administration of Lactobacillus brevis subsp. coagulans (Labre) for 4 weeks on the interferon-alpha (IFN-alpha) producing capacity of apparently healthy subjects was evaluated. Sixty volunteers were divided into five groups for the determination of virus-induced IFN-alpha production in response to various doses of live and to heat-killed Labre. 2-5A synthetase activity was measured to detect trace amounts of IFN production. Routine blood tests were also performed to determine the state of health of the subjects involved in this study and to test any side effects of Labre treatment. RESULTS: The oral administration of live Labre showed a statistically significant increase in IFN-alpha production at 2 weeks (p < 0.05) and at 4 weeks (p < 0.05) in the group receiving 600 million bacteria/day and at 4 weeks (p < 0.05) in the group receiving 300 million bacteria/day. In particular, IFN-alpha production in those with initially low levels rose significantly when either 300 million or 600 million bacteria/day were ingested. Consumption of heat-killed Labre 300 million bacteria/day did not result in a statistically significant change in IFN-alpha production. The level of 2-5A synthetase activity remained the same in the control and experimental groups. CONCLUSIONS: Oral administration of live Labre significantly increased IFN-alpha production in a dose-dependent manner. Labre intake tended to be most beneficial in subjects with initially low levels of IFN-alpha production. Heat-treated Labre did not elicit a response similar to that of the live bacteria.

2',5'-Oligoadenylate Synthetase↗

Significance of IL-1beta and IL-1 receptor antagonist (IL-1Ra) in bronchoalveolar lavage fluid (BALF) in patients with diffuse panbronchiolitis (DPB).

We evaluated the effect of erythromycin therapy on pulmonary function tests and the airway inflammatory response of patients with DPB. The number of neutrophils in BALF obtained from DPB patients was significantly higher than that of healthy volunteers. Treatment with erythromycin (600 mg/day for 12.9+/-9.5 months (mean +/- s.d.)) significantly reduced the total number of cells and neutrophils in the airway, and significantly improved pulmonary function tests. The levels of IL-1beta and IL-8 were significantly higher in DPB compared with healthy volunteers (P<0.05, P<0.05, respectively). IL-1Ra in patients is considered to have a weak inhibitory activity for IL-1beta, with approximately five-fold concentration of IL-1beta compared with that in healthy volunteers (approx. nine-fold concentration of IL-1beta). Erythromycin therapy significantly reduced these cytokines to levels comparable to those of healthy volunteers, and produced a trend toward reduction in the level of IL-1Ra in BALF. The level of IL-1beta correlated significantly with the concentration of neutrophils in BALF (r=0.72, P<0.01), as well as with the level of IL-1Ra (r=0.688, P<0.05) and IL-8 (r=0.653, P<0.05). A nearly significant or significant correlation was observed between the concentration of neutrophils and levels of IL-1Ra or IL-8 in BALF (r=0.526, P=0.053 or r=0.776, P<0.01, respectively). There was also a significant relationship between FEV(1) and the concentration of neutrophils in BALF (r=0.524, P<0.05). Our results suggest that the relative amounts of IL-1beta and IL-1Ra or IL-8 may contribute, at least in part, to the neutrophil-mediated chronic airway inflammation in patients with chronic airway disease, and long-term erythromycin therapy may down-regulate the vigorous cycle between the cytokine network and neutrophil accumulation, with resultant reduction of neutrophil-mediated inflammatory response.

Adult↗

Inhibitory effect of erythromycin on interleukin 8 production by 1 alpha,25-dihydroxyvitamin D3-stimulated THP-1 cells.

We have recently reported that long-term administration of erythromycin at a low dose reduced the number of neutrophils and concentrations of interleukin 8 (IL-8) in bronchoalveolar lavage fluid in patients with chronic lower respiratory tract disease. To investigate the mechanism of action of erythromycin, we evaluated its effect on IL-8 production in the 1 alpha,25-dihydroxyvitamin D3-stimulated human monocytic cell line THP-1. Erythromycin at a concentration of 10 micrograms/ml significantly reduced IL-8 production by THP-1 cells stimulated with lipopolysaccharide (10 ng/ml) and 1% normal human serum compared with the amount produced by untreated cells (untreated cells, 2,448 pg/ml; erythromycin-treated cells, 872 pg/ml). Our results suggest that erythromycin may impair IL-8 production by alveolar macrophages, ultimately reducing neutrophil accumulation in the airspace.

Anti-Bacterial Agents↗

Penetration by field vole spermatozoa of mouse and hamster zonae pellucidae without acrosome reaction.

Spermatozoa of the field vole (Microtus montebelli) that bound to the zona pellucida of field vole oocytes underwent the acrosome reaction before passing through it. In contrast, vole spermatozoa that bound to the zonae of mouse and hamster oocytes penetrated the zonae without any sign of the acrosome reaction. The presence or absence of proteinase/hyaluronidase inhibitors in the medium did not make any difference to zona penetration by acrosome-intact vole spermatozoa. These observations suggest that field vole spermatozoa can cross mouse and hamster zonae mechanically without assistance from zona-hydrolysing enzymes.

Acrosome↗

[Chest wall reconstruction using polyester mesh].

From January 1987 through December 1994, we performed chest wall reconstruction using the polyester mesh in 15 patients with lung cancer, 11 with empyema after open drainage, 8 with chest wall tumor and 1 with radiation dermatitis and costal chondritis. Twenty five patients were resected 3 or more ribs. Chest wall defects were reconstructed with the polyester mesh covered with Gore-Tex soft tissue patch. Twenty two cases passed more than a year without signs of infection and follow-up averaged 27.6 months. Polyester mesh was removed due to bronchial fistula (3 cases), deformities (3 cases) and abscess formation (1 case). In these cases, polyester mesh was well incorporated and had no foreign body change. In conclusion, the polyester mesh seems to be a dependable prosthetic material for chest wall reconstruction.

Adult↗

[Flow cytometric analysis of the DNA content of resected non-small cell lung cancer with reference to long-term follow-up].

We measured the cellular DNA content of paraffin-embedded tumor specimens by flow cytometry from 340 cases of resected non-small cell lung cancer, and investigated the correlation of DNA content and prognosis of these cases with long-term follow-up. These 340 cases were divided into some populations according to pathological stage, histologic type, surgical curativity and N factor, and we compared the prognosis of DNA diploidy cases and DNA aneuploidy cases in each population. DNA aneuploidy cases had a significantly less favorable prognosis than DNA diploidy cases in population of stage I adenocarcinoma, stage IIIA non-small cell lung cancer and N2 cases among stage IIIA non-small cell lung cancer, all after curative operation. But in other populations, there was no significant difference in prognosis between DNA diploidy cases and DNA aneuploidy cases. In conclusion, DNA ploidy pattern is a prognostic factor for survival in patients with stage I adenocarcinoma and N2 cases of stage IIIA non-small cell lung cancer.

Adenocarcinoma↗

[T cell lymphoma presenting as recurrent bilateral pulmonary infiltrates over five years].

A 52-year-old man presented with BOOP-like recurrent bilateral pulmonary infiltrates. In 1989 a chest X-ray film showed an infiltrative shadow in the right S6 region which disappeared after administration of prednisolone. Thereafter, bilateral patchy infiltrates recurred many times, and each time they resolved rapidly with steroid therapy. Skin eruptions on the face recurred. In October 1994 the patient underwent an open-lung biopsy of the infiltrate in the left S6 region. The pathological findings were consistent with BOOP, except for the moderate-to marked infiltration of lymphocytes. A lymphoproliferative disorder was suspected, and Southern blot analysis of the specimen revealed a rearrangement of the TCR-beta gene, which led to the diagnosis of T cell lymphoma. Ten months after the diagnosis, no recurrence of the lymphoma had been detected. In this case a gene analysis of the biopsy specimen was very useful for the diagnosis of T cell lymphoma.

Cryptogenic Organizing Pneumonia↗

Serial magnetic resonance imaging follow-up study of lumbar disc herniation conservatively treated for average 30 months: relation between reduction of herniation and degeneration of disc.

The natural history of lumbar disc herniation in conservatively treated patients is not entirely clear. This study was undertaken to clarify the relation between morphologic changes in the herniation and the clinical course. Serial magnetic resonance imaging studies were performed an average of 4.4 times in 30 patients in a 30-month-average period. The Japanese Orthopaedic Association (JOA) score and straight leg raising (SLR) test were improved, with the average reduction ratio of the herniation 15 and 18% on the sagittal and axial images, respectively. The JOA score and SLR test showed the most improvement within 1 year, with little change noted thereafter. In contrast, the disc herniation continued to reduce not only within 1 year, but also thereafter. Patients with progression of disc degeneration showed more marked regression of herniation than those in whom progression was not observed.

Adolescent↗

Variance of age at onset in a Japanese family with amyotrophic lateral sclerosis associated with a novel Cu/Zn superoxide dismutase mutation.

Although about 5 to 10% of amyotrophic lateral sclerosis (ALS) cases are familial, the pathophysiology of ALS remains unknown. A new point mutation in exon 4 of the Cu/Zn superoxide dismutase (SOD) gene, resulting in an amino acid substitution of leucine84 by valine (L84V), in a Japanese patient with familial ALS (FALS) was identified. This L84V substitution was not observed in 57 normal Japanese control subjects. The enzymatic activities of Cu/Zn SOD of skin fibroblasts were significantly reduced to 75% of the control level in the affected patient. The progression of the disease with this mutation is very rapid, but the age at onset varies with sex or generation within a family.

Adult↗

Serial changes on MRI in lumbar disc herniations treated conservatively.

Using serial MRI, we studied 32 patients with herniated lumbar discs, treated conservatively, to clarify the natural history of this condition. MRI was performed in the acute stage, then 6 months and 1 year later. On axial images, the proportion of the cross-sectional area of the spinal canal occupied by the herniated disc was 31.9% on the average on the initial scan, 28.7% 6 months and 25.3% 1 year later. The size of the herniation decreased by more than 20% in 11 patients (34%), by 10-20% in 8 (28%) and was unchanged in 12 (38%). The height of the disc slightly decreased with time, but there was no significant change in the angle of lordosis in the affected segment. The initial MRI revealed degeneration of all affected discs, and progressive degeneration was observed in 9 patients. The more degenerate the disc and the larger the initial herniation the more the size of the herniated fragment decreased.

Adolescent↗

Granulomatous lesions caused by Pseudomonas aeruginosa in the ostrich (Struthio camelus).

Granulomatous lesions were observed in imported ostriches aged 3 months. Clinically, the birds showed lassitude, incoordination, and inappetence. At necropsy, yellowish white nodules often accompanied by a pseudodiphtheritic membrane were found in the oral, pharyngeal, tracheal and air sac mucosae, the lungs, oesophageal serosa, and abdominal peritoneum. Histopathological examination revealed purulent granulomatous lesions containing central bacterial colonies with an outer shell and club formation. The bacteria were small Gram-negative bacilli, which showed positive immunohistochemical staining for Pseudomonas aeruginosa. The bacterial colonies were positive for chicken IgM. Clubs around the colonies were negative for P. aeruginosa and chicken IgM. Such findings have not previously been reported in the ostrich.

Animals↗

Placental Na+, K+ activated ATP-ase activity in SHRSP in connection with pregnancy induced hypertension and intra-uterine growth retardation.

1. Placental Na+, K+ -ATPase activities were measured in connection with the active transport of amino acid, intra-uterine growth retardation (IUGR) or small for date infants (SFD) in salt-loaded pregnant SHRSP. 2. All parameters such as fetal weight, placental weight and Na+, K+ -ATPase activity in the placental tissue were significantly depressed in SHRSP, especially in the salt-loaded SHRSP compared with WKY. 3. Besides a decrease of blood flow, a decline of Na+, K+ -ATPase activity associated with an active transport of amino acid in the placenta would cause IUGR and SFD in the salt-loaded pregnant SHRSP. 4. Pregnant SHRSP given water containing salt would be a good model for pregnancy induced hypertension in humans.

Animals↗

Studies on pregnancy hypertension and IUGR-SFD: effects of drugs on the blood vessels in the placenta of pregnant SHRSP.

1. Based upon our previous work, we came to the conclusion that a decrease in placental blood volume was a possible factor behind intrauterine growth retardation (IUGR) in pregnancy-induced hypertension. 2. In a second study, we used an image analysis system to measure cross-sectional areas and wall thicknesses of central blood vessels of the spiral artery, the so-called 'central artery'. 3. It was thought that one of the more basic factors behind IUGR in pregnancy-induced hypertension might possibly be narrowings and spasms of the maternal placental blood vessels. 4. In this study, we found that the three drugs we used (MgSO4 center dot 7H2O, Solcoseryl and KCl) all resulted in an enlargement of the cross-sectional areas of the maternal blood vessels, and that MgSO4 center dot 7H2O, in particular, also relaxed maternal blood vessel spasms in SHRSP placenta.

Animals↗

Molecular cloning and sequence analysis of the gene encoding the collagenase from Cytophaga sp. L43-1 strain.

Cytophaga sp. strain L43-1 secretes a collagenase [Y. Sasagawa et al., Biosci. Biotech. Biochem., 57, 1894-1898 (1993)]. A cog gene encoding the collagenase from this strain was cloned, and the nucleotides were sequenced. The structural gene of cog consisted of 3846 base pairs, which encoded a polypeptide consisting of 1282 amino acid residues with a predicted molecular mass of 130 kDa which was synthesized as a pre-matured enzyme. The deduced N-terminal 14 amino acids sequence, molecular mass of 120 kDa, and pI of 4.96 of the predicted matured enzyme were consistent with those previously found for the collagenase purified from the strain. The cog gene was expressed in Escherichia coli using the lac promoter and ribosomal binding sequence in plasmid vector pUC119 or pKK223-3, but not its own putative promoter and Shine-Dalgarno sequence. The consensus amino acid sequence (His-Glu-Xaa-Xaa-His) of an active site of the metal proteases including the collagenase from Vibrio arginolyticus and a series of human MMPs was found in the Cog protein of the strain.

Amino Acid Sequence↗

Effects of repeated doses of compound E for 4 and 9 weeks on the male reproductive organs.

Results of two toxicity studies of Compound E, which is an anticancer drug, on male reproductive organs and fertility by oral repeated dosing at dose levels of 12.5, 25 and 50 mg/kg/day for 4 and 9 weeks in rats were compared. After repeated dosing, the male fertility was studied by mating with untreated female animals. At the dose of 50 mg/kg/day in the 4-week study, Compound E significantly decreased testes weight and number of epididymal sperm, caused histopathological changes in the testis and epididymis characterized by decreased germ cells, but did not affect fertility. The dose of 25 mg/kg/day in the 9-week study caused reduction in epididymal weight and number of epididymal sperm and histopathological changes in the testis. The dose of 50 mg/kg/day in the 9-week study was lethal and caused more prominent toxic effects in the reproductive organs and loss of fertility. The present studies suggest that the order of sensitivity of parameters on male reproductive organs is as follows; histopathological examination = organ weight > number of sperm in epididymis > pregnancy index> copulation index. Further, 4-weeks repeated dosing is of sufficient duration to predict adverse effects of test compounds.

Animals↗