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Biomedical subjects

T Migita

Publications and source records attributed to T Migita.

At least 19 recordsLinked to original sources

Effect of different pedal rates on oxygen uptake slow component during constant-load cycling exercise.

AIM: We hypothesized that an extremely high pedal rate would induce much more type II muscle fibers recruitment even at an early phase of the same absolute work rate compared with normal pedal rates, and would result in changed amplitude of the pulmonary oxygen uptake slow component (VO(2)SC) during heavy constant-load exercise. METHODS: Two square-wave transitions of constant-load exercise were carried out at an exercise intensity corresponding to a VO(2) of 130% of the ventilatory threshold. The amplitude of the VO(2)SC in phase III during heavy constant-load exercise was determined at normal (60 rpm) and extremely high pedal rates (110 rpm). The VO(2) kinetics were analyzed by nonlinear regression. RESULTS: Although the absolute work rates were almost identical in the two pedal rates cycling exercise, the amplitude of the VO(2) in phase II (phase II amplitude), end-exercise VO(2) (EEVO(2)) and blood lactate accumulation ([La]) were significantly greater at 110 rpm than at 60 rpm (2 260+/-242 vs 1.830+/-304 mL.min(-1) for phase II amplitude; P<0.01, 2 350+/-265 vs 1 709+/-342 mL.min(-1) for EEVO(2); P<0.01, 6.4+/-1.3 vs 3.2+/-1.3 mmol.L(-1) for [La]; P<0.01, respectively). The amplitude of the VO(2)SC in phase III also revealed a significantly higher value at 110 rpm compared with 60 rpm (416+/-73 vs 201+/-89 mL.min(-1), P<0.01). In spite of the appearance of greater VO(2)SC at 110 rpm, no corresponding changes in integrals of the electromyography (EMG) signal and mean power frequency were observed. CONCLUSIONS: The results of this study indicate that the amplitude of the VO(2)SC was greater in higher pedal rate during the same work rate constant-load cycling exercise, which might be associated with a progressive increase in the adenosine triphosphate requirement of already recruited muscle fibers in exercising muscle.

Adult↗

Haplotype analysis of a 100 kb region spanning TNF-LTA identifies a polymorphism in the LTA promoter region that is associated with atopic asthma susceptibility in Japan.

BACKGROUND: The tumour necrosis factor (TNF) gene family, which includes TNF, LTA, and LTB, is located consecutively on human chromosome 6p21 region, which has been linked to asthma by several genome-wide screens. (LTA, lymphotoxin-alpha; LTB, lymphotoxin-beta). OBJECTIVE: The aim of the present study was to determine whether genes on 6q21 are related to development of atopic asthma. Methods We screened for mutations in the coding and promoter regions of genes in the TNF-LTA region, including BAT1, NFKBIL1, LTA, TNF, LTB, AIF, and BAT2, and conducted a transmission disequilibrium test of 41 polymorphisms in 137 families identified through pro-bands with childhood-onset atopic asthma. (BAT1, HLA-B-associated transcript 1; NFKBIL1, nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor-like 1; AIF, allograft inflammatory factor 1). RESULTS: Haplotypes of the LTA/TNF linkage disequilibrium block were associated significantly with asthma (global P=0.0097). Transmission patterns of the common haplotypes to asthmatic offspring were predicted by a single-nucleotide polymorphism in the LTA promoter region. The G allele of the LTA-753G/A polymorphism was transmitted preferentially to asthma-affected individuals (P=0.001). Luciferase reporter assays with constructs containing the 5' and 3' flanking regions of the LTA gene showed 30-50% lower transcriptional activity when the -753A allele was present than that of other haplotypes. CONCLUSION: Our results suggest that LTA is one of the genes that contributes to susceptibility to atopic asthma, and that the association of the TNF/LTA haplotypes to asthma may be defined by the polymorphism in the LTA promoter region in the Japanese population.

Adolescent↗

A case of bladder pheochromocytoma.

The clinical picture of bladder pheochromocytoma is usually typical; however, the diagnosis is occasionally delayed because of the rarity of this neoplasm. We report a case of unsuspected bladder pheochromocytoma in which the patient had a hypertensive episode during transurethral resection. A 67-year-old male presented with the chief complaint of painless macrohematuria. Cystoscopy revealed a submucosal tumor on the right lateral wall of the bladder. The tumor was operated on transurethrally, followed by partial cystectomy. The pathological diagnosis was pheochromocytoma, primarily occurring in the bladder. Treatment of this lesion requires a high degree of clinical suspicion based on the patient's symptom complex in order to enable adequate preparation prior to surgical manipulation.

Aged↗

High expression of the Cap43 gene in infiltrating macrophages of human renal cell carcinomas.

We used suppression subtractive hybridization to identify highly expressed genes in the cancerous region of human renal cell carcinoma (RCC) compared with noncancerous tissue. Nine genes were identified to show increased expression in the cancerous region compared with the noncancerous region. The nine genes included thymosin beta4, secreted protein acidic and rich in cysteine (SPARC), Cap43, ceruloplasmin, serum amyloid A, osteopontin, heat shock protein 90 (HSP90), LOT1, and casein kinase I. Of these 9 genes, in situ hybridization with 10 clinical samples consistently showed a strong expression of Cap43 mRNA in infiltrating macrophages in RCCs, but not in cancer cells proliferating in an alveolar pattern. However, Cap43 mRNA was also apparently detected in epithelial cells of the renal proximal tubuli in noncancerous tissue. The higher expression of the Cap43 gene in the cancerous region of RCCs appears to depend on macrophage infiltration. Moreover, treatment with phorbol ester resulted in enhanced expression of the Cap43 gene in human monocytic cells in vitro. The expression of the Cap43 gene in infiltrating macrophages is discussed in association with the differentiated or activated status of monocyte/macrophage.

Adult↗

The accumulation of angiostatin-like fragments in human prostate carcinoma.

PURPOSE: Angiostatin, a potent inhibitor of angiogenesis and, hence, the growth of tumor cell metastasis, is generated by a proteolytic enzyme from plasminogen. However, its localization and specific enzymes have yet to be ascertained in human tissue. EXPERIMENTAL DESIGN: To elucidate the generation and the localization of angiostatin in prostate carcinoma, we examined angiostatin generation in a panel of human prostate cancer cell lines and performed immunohistochemistry with the antibodies to angiostatin and prostate-specific antigen (PSA), a potent proteolytic enzyme of angiostatin in 55 cases of prostate carcinoma. RESULTS: We demonstrated that the lysates of human prostate carcinoma cell lines could generate angiostatin-like fragments from purified human plasminogen but could not generate angiostatin in the absence of exogenous plasminogen. The fragmented proteins were reacted with the monoclonal antibody specific for plasminogen lysine-binding site 1 (LBS-1). Immunohistochemically, the intracytoplasmic immunostaining of LBS-1 was positive in 87.3% (48 of 55) of prostate carcinoma cases, and the immunostaining of miniplasminogen was negative in all cases. There was a significant relationship between the positive immunostaining of LBS-1 and Gleason score (P = 0.0007). The intracytoplasmic immunostaining of PSA was positive in 37.0% (20 of 54) of prostate carcinoma cases, but there was no significant relationship between the expression of PSA and Gleason score, or between the positive immunostaining of LBS-1 and PSA. CONCLUSIONS: These findings suggest that angiostatin is generated by prostate carcinoma cells and is accumulated within the cytoplasm. In addition, the generation of angiostatin-like fragments was correlated with tumor grade; however, PSA may not be the only enzyme for angiostatin generation in human prostate carcinoma.

Aged↗

Significant evidence for linkage of febrile seizures to chromosome 5q14-q15.

Febrile seizures (FSs) represent the most common form of childhood seizure. In the Japanese population, the incidence rate is as high as 7%. It has been recognized that there is a significant genetic component for susceptibility to this type of seizure. Two putative FS loci, FEB1 (chromosome 8q13-q21) and FEB2 (chromosome 19p), have been mapped. Furthermore, a mutation in the voltage-gated sodium (Na(+))-channel beta1 subunit gene ( SCN1B ) at chromosome 19q13.1 was identified in a family with a clinical subset, termed generalized epilepsy with febrile seizures plus (GEFS(+)). These loci are linked to some large families. In this study, we conducted a genome-wide linkage search for FS in one large family with subsequent linkage confirmation in 39 nuclear families. Significant linkage was found at D5S644 by multipoint non-parametric analysis using GENEHUNTER ( P = 5.4 x 10(-6)). Estimated lambda(s)at D5S644 was 2.5 according to maximum likelihood analysis. Significant linkage disequilibria with FS were observed at the markers D5S644, D5S652 and D5S2079 in 47 families by transmission disequilibrium tests. These findings indicate that there is a gene on chromosome 5q14-q15 that confers susceptibility to FSs and we call this gene FEB4.

Child, Preschool↗

Inhibitory effects of flavonoids on rabbit heart carbonyl reductase.

The inhibitory effects of flavonoids (galangin, kaempferol, quercetin, myricetin, morin, and taxifolin) on rabbit heart carbonyl reductase (RHCR) were investigated using 4-benzoylpyridine (4BP) as the substrate. The stereochemical characteristics of the flavonoids were found to be a factor determining their inhibitory potencies toward RHCR. Furthermore, the lipophilicity, and the scavenging or antioxidative effects of the flavonoids were likely to complicate the structure-activity relationship of their inhibitory effects on RHCR. Quercetin inhibited RHCR uncompetitively with respect to NADPH and competitively with respect to 4BP, suggesting that it competes with 4BP at the substrate-binding site of RHCR. RHCR efficiently reduced benzoquinones (1,4-benzoquinone and 2-methyl-1, 4-benzoquinone) and naphthoquinones (1,4-naphthoquinone and menadione). Galangin was a potent inhibitor of RHCR when menadione was used as the substrate, and prevented the formation of the superoxide anion radical in the presence of RHCR, NADPH, and menadione. Flavonoids may be useful compounds for suppressing the cardiotoxicity of quinones by inhibiting RHCR.

Alcohol Oxidoreductases↗

Differing expression of MMPs-1 and -9 and urokinase receptor between diffuse- and intestinal-type gastric carcinoma.

Gastric cancer is classified into intestinal and diffuse types, which exhibit different biological behavior. Urokinase-type plasminogen activator (uPA), its receptor (uPAR) and matrix metalloproteinases (MMPs)-1 and -9 are considered to play important roles in cancer invasion and metastasis. We have already suggested a functional duality of these matrix-degrading enzymes/factors; they may also be involved in the matrix turnover (remodeling) or host immune/inflammatory reactions as far as they are expressed by host cells. We performed a retrospective study on the immuno-histochemical expression of these enzymes/factors in surgical specimens from patients with gastric cancer, including 26 with the diffuse and 78 with the intestinal type. We also evaluated macrophages since they are major sources of uPAR. The positivity rate for uPA in cancer cells was significantly lower in diffuse-type than in intestinal-type. Stromal expression was seen mainly along the invasive margin (tumor-host interface). The degree of stromal expression of uPAR and MMP-9 and the macrophage number were markedly decreased in diffuse-type compared with intestinal-type. Stromal expression of uPAR and macrophage number in intestinal-type were higher in patients without liver metastasis than in patients with liver metastasis, while uPA expression in cancer cells was more pronounced in patients with liver metastasis. Studies using frozen sections revealed that the expression of MMP-1, restricted to the stromal area, was more decreased in diffuse-type (18 patients) than in intestinal-type (21 patients). Our results show that the in situ expression of matrix-degrading enzymes/factors in gastric cancer is significantly more diminished in diffuse-type than in intestinal-type, suggesting a multifunctional aspect of the matrix-degradation process in cancer tissue.

Antigens, CD↗

Another observation of microphthalmia in an XX male: microphthalmia with linear skin defects syndrome without linear skin lesions.

A case of microphthalmia with Xp microdeletion is reported. The patient was a boy who showed bilateral microphthalmia with corneal opacities, hypospadias without evidence of hypogonadism, and a conduction disturbance of the heart (Wenckebach conduction). No skin lesion was discerned. High-resolution chromosome analysis revealed the karyotype of 46,X,del(X)(p22). The phenotype was considered to be microphthalmia with linear skin defects (MLS) syndrome without skin lesions. Polymerase chain reaction and fluorescence in-situ hybridization analyses revealed that the chromosome aberration resulted from an X;Y translocation: the presence of pseudoautosomal boundary Y and the sex-determining region of Y was confirmed, while Xp deletion involving the region distal to DXS1129 was ascertained. Thus the chromosome designation using the ISCN 1995 nomenclature is 46,X,der(X),t(X;Y)(p22.13;q11.2). Despite the absence of skin lesions, the Xp deletion of our patient corresponded to those of previously reported typical cases of MLS syndrome. Our observation further supports the current hypothesis that the phenotypic variation of MLS syndrome represents tissue-different X inactivation rather than different genetic effects of two contiguous genes.

Chromosome Deletion↗

Negative C-reactive protein in children with bacterial infection.

PURPOSE: To evaluate the practical value of initial C-reactive protein (CRP) in the diagnosis of bacterial infection in children. METHODS: The subjects comprised 11 children, six boys and five girls, aged 3 months through to 3 years (median age 16 months), whose initial CRP levels were < 1.0 mg/dL despite bacterial infection. C-reactive protein was quantitated at the first medical examination by nephelometry. RESULTS: The diagnosis was urinary tract infection (n = 4), bacterial meningitis (n = 2), sepsis (n = 2), pneumonia (n = 2) and arthritis of the hip joint (n = 1). The CRP levels were significantly elevated during the course of infection, ranging from 7.6 to 28.5 mg/dL. The bacterial etiology was non-specific. Eight patients were examined within 12 h of onset, three exhibited negative CRP values despite the duration of the insult over 12 h. Six patients were tentatively diagnosed as having a bacterial infection, but the other five were not. Each patient was treated, leading to a favorable outcome without any serious complications. CONCLUSIONS: Low levels of CRP do not rule out the possibility of bacterial infection in children. The initial value of CRP may be negative, even in patients with severe bacterial infection or even after 12 h from onset. The data suggest that pediatricians should consistently be aware of the possibility of bacterial infection even if the initial CRP test result is negative and that serial CRP measurements appear to be practical.

Bacterial Infections↗

Purification and catalytic properties of a tetrameric carbonyl reductase from rabbit heart.

An enzyme responsible for the ketone-reduction of 4-benzoylpyridine (4BP) was purified 350-fold to homogeneity from the cytosolic fraction of rabbit heart. The purified enzyme exhibited a molecular mass of 110 kDa on gel filtration, and 27 kDa on SDS-PAGE, indicating that it is a tetrameric protein composed of four identical-size subunits. Aromatic aldehydes, ketones, and menadione were effective substrates for the enzyme. Flavonoids were potent inhibitors of the enzyme, but barbiturates or pyrazole was not. Based on this substrate specificity and inhibitor sensitivity, the enzyme was taken to be a carbonyl reductase. Kinetic studies led us to conclude that the reduction of 4BP by the enzyme follows an ordered Bi Bi mechanism. The enzyme also appeared to catalyze the redox (oxidation-reduction) cycling of menadione to produce the superoxide radical. Furthermore, we provide evidence that a hydrophobic pocket, which corresponds to a straight-chain alkyl group of five carbon atoms in length, is located in the substrate-binding site of the enzyme.

Alcohol Oxidoreductases↗

Inhibition of rabbit heart carbonyl reductase by fatty acids.

The inhibition of rabbit heart carbonyl reductase (RHCR) by fatty acids was examined using 4-benzoylpyridine (4BP) as a substrate. The inhibitory potency of saturated fatty acids increased with elongation in the carbon chain from caprylic acid to myristic acid, but decreased with further elongation. Myristic acid with 14 carbon atoms most strongly inhibited RHCR. All of the unsaturated fatty acids tested strongly inhibited RHCR; the cis-isomers were more potent inhibitors than the corresponding trans-isomers. The methyl esters and alcohols, which lack a carboxyl group, derived from fatty acids did not exert a significant inhibitory effect on RHCR. These results indicate that the existence of a proper length of carbon chain, double bond(s), and a carboxyl group in a fatty acid molecule is important for RHCR inhibition. We also propose the possibility that myristic acid at low concentrations inhibits the reduction of 4BP by interacting with a binding site other than the coenzyme- and substrate-binding sites of RHCR.

Alcohol Oxidoreductases↗

[A case of prostate cancer associated with osteolytic bone metastases].

It is well known that prostate cancer metastasizes bone with osteoblastic change and that osteolytic change is rare. We report a case of prostate cancer that had bone metastases which were all osteolytic. A 62-year-old man was referred to our department because of abnormal prostatic acid phosphatase and pain in his right upper arm. Digital examination revealed an enlarged and hard prostate. A computed tomographic scan revealed multiple osteolytic changes and a bone scintigraphy was positive at these sites. Histopathology of both prostate and humerus showed poorly differentiated adenocarcinoma. He received castration and antiandrogen as hormonal therapy, but the patient's prostate specific antigen did not normalize. Therefore this case was suspected to be hormone-refractory prostate cancer.

Adenocarcinoma↗

[Interstitial cystitis in case of primary Sjögren's syndrome].

A 53-year-old woman who had xerostomia for ten years was admitted to our hospital because of refractory lower abdominal pain and pollakisuria of five years duration. Although she had undergone surgical treatments including cholecystectomy, ovarian cystectomy and groin hemiorrhaphy, she still suffered from abdominal symptoms. A diagnosis of interstitial cystitis was confirmed by hydraulic distention during a cystoscopic examination and by histopathological examination of the bladder. Her symptoms disappeared soon after the cystoscopic procedure, which also had a therapeutic effect of interstitial cystitis. Laboratory findings revealed hypergammaglobulinemia, a high titer of rheumatoid factor, positive anti-nuclear antibody, and positive anti-SS-A/Ro antibody. She was diagnosed as having primary Sjögren's syndrome based on the results of a gum test (8.5 ml/ 10 min), sialography (Stage II), and a positive minor salivary gland biopsy. Starting one month after the hydraulic distention, her abdominal symptoms gradually reappeared along with elevation of her serum IgG level. These features were markedly improved with 30 mg/day of oral prednisolone, which was then successfully tapered. These results suggested that interstitial cystitis in this case was caused by immunological abnormalities associated with Sjögren's syndrome.

Cystitis, Interstitial↗

Characterization of acetohexamide reductases purified from rabbit liver, kidney, and heart: structural requirements for substrates and inhibitors.

The structural requirements of acetohexamide reductases purified from rabbit liver, kidney, and heart for substrates and inhibitors were examined. Acetohexamide, an oral antidiabetic drug with a ketone group, and analogs of it with various alkyl groups instead of the cyclohexyl group were used as substrates for these three enzymes. The results obtained as to substrate specificity suggested that the nature of the substrate-binding region of the heart enzyme is markedly different from those of the substrate-binding regions of the liver and kidney enzymes. Tolbutamide, which has no ketone group within its chemical structure, strongly inhibited the heart enzyme, whereas it had little ability to inhibit the liver or kidney enzyme. The inhibition of the heart enzyme by tolbutamide was competitive with respect to acetohexamide and uncompetitive with respect to NADPH. Furthermore, tolbutamide analogs with n-pentyl and n-hexyl groups instead of the n-butyl group exhibited very pronounced inhibition of only the heart enzyme. Therefore, it is reasonable to postulate that the heart enzyme, unlike the liver and kidney ones, has a cleft of a strongly hydrophobic nature near its substrate-binding region, and that this hydrophobic cleft plays a critical role in the interaction of the heart enzyme with the cyclohexyl group of acetohexamide.

Acetohexamide↗

Effect of repeated exercise on urinary 8-hydroxy-deoxyguanosine excretion in humans.

The purpose of this study was to investigate the effect of repeated exercise on oxidative damage to DNA in 10 well trained long distance runners who participated in an 8-day training camp. The average running distance during the camp was 30 +/- 3 km/day. The amount of urinary 8-hydroxy-deoxyguanosine (8-OHdG) excretion was used to estimate the oxidative DNA damage. Urine samples were collected for both a 3-day control period as well as throughout the camp. Blood samples were drawn after overnight fasting both before and after the camp. Urinary 8-OHdG excretion was significantly increased during the camp compared to the control period (265.7 +/- 75.5 vs. 335.6 +/- 107.4 pmol/kg/day, P < 0.05). The content of 8-OHdG in the lymphocyte DNA on the day after finishing the camp did not differ from that before the camp. Plasma TBARS, LDH, CK, CK-MB, and myoglobin significantly rose after the camp (P < 0.05). The plasma beta-carotene levels tended to rise after the camp, while the plasma alpha-tocopherol levels increased significantly after the camp (P < 0.05). These results indicate that repeated exercise augments oxidative stress and the DNA is also injured by exercise-induced reactive oxygen species. However, the oxidative damage to DNA is not accumulated by consecutive exercise, although it is sustained as long as the exercise is repeated.

8-Hydroxy-2'-Deoxyguanosine↗

Basement membrane abnormality in merosin-negative congenital muscular dystrophy.

In muscle biopsy specimens from three patients with merosin-negative congenital muscular dystrophy (CMD), there was marked variation in fiber size with evidence of necrotic and regenerating processes and with marked interstitial fibrosis. No muscle fibers or intramuscular nerves stained with merosin antibody. On electron microscopy, the basement membrane of all the muscle fibers was very poorly discernible and there were occasional disruptions, while the basement membrane of the Schwann cells was well preserved. On the other hand, the sarcolemmal basement membrane in merosin-positive CMD was well preserved even in patient with severe interstitial fibrosis. It remains to be determined how the defective basement membrane in merosin-negative CMD induces defective sarcolemma and eventual fiber necrosis.

Basement Membrane↗