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Biomedical subjects

K Uchida

Publications and source records attributed to K Uchida.

At least 595 records · Page 33Linked to original sources
PubMed1997

[Mechanism mediating hypertension induced by chronic inhibition of nitric oxide synthesis].

Although the inhibition of nitric oxide (NO) synthesis is known to induce systemic hypertension, the underlying mechanisms mediating this type of hypertension are incompletely understood. In the present study we investigated the influence of sodium intake on the pressor effect of long-term administration of the NO synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 16 mg/dl in drinking fluid for 8 weeks), in conscious Sprague-Dawley rats. Urinary excretion rates of catecholamine during NO synthesis inhibition were also examined. Long-term administration of L-NAME produced a sustained elevation in tail-cuff pressure without altering urine flow, or sodium excretion rate. L-NAME-induced hypertension was accompanied by a decreased urinary excretion of the stable NO metabolites, NO2- and NO3-, and was aggravated when rats drank 0.9% saline in place of tap water. Thus, inhibition of NO synthesis resulted in a rightward shift of the pressure natriuresis relationship and a significant decrease in the slope of this relationship. Urinary excretion of epinephrine and norepinephrine, but not that of dopamine, in L-NAME-treated rats significantly increased within the first week of the study when compared with those observed in control rats. A natriuretic index of the sympathetic nervous system, the ratio of dopamine to norepinephrine excretion, was significantly less in L-NAME-treated rats than in control rats. After 8-week treatment with L-NAME, renal morphologic evaluation revealed significant narrowing and obliteration of the arterioles. L-arginine (2 g/dl in drinking fluid) completely reversed the elevation of blood pressure as well as the decrease in urinary NO2- and NO3- excretion and the increased urinary excretion of catecholamines associated with L-NAME treatment after 3 weeks of concomitant administration. These results suggest that the inhibition of chronic NO synthesis produces sodium-sensitive hypertension and that changes in sympathetic nerve activity may, at least in part, contribute to the sodium sensitivity in this type of hypertension.

Animals↗
PubMed1997

[Selective transcatheter embolization for renal artery aneurysms: report of three cases].

Selective transcatheter embolization using an interlocking detachable coil (IDC) or detachable balloon was performed in three patients with renal artery aneurysms. All aneurysms were of the saccular type, located on segmental branches of the renal artery. After the embolization procedures, the levels of LDH, GOT, WBC and the body temperature were transitionally elevated in all patients. Complete occlusion of the aneurysms were achieved in all cases. Good clinical results were achieved in two of these patients without any renal dysfunction. However, local infarction of ipsilateral renal parenchyma occurred in one patient immediately after the embolization and a Tc-99m-DMSA renal scintigraphy study suggested renal dysfunction after infarction, and the level of serum renin activity was slightly elevated. Selective transcatheter embolization may constitute an acceptable therapeutic approach for renal artery aneurysms because beside avoiding surgery, it has a low risk of complications.

Aged↗
PubMed1997

Correlation between antifungal activity and hydrophobicity of imidazole antifungal agents.

To examine the effects of the affinity of antifungal imidazole agents to cell membranes on the in vitro antifungal activity, the correlation between antifungal activity and hydrophobicity of these drugs was investigated. The capacity factor (k') in HPLC was used as a parameter of hydrophobicity, and the minimum inhibitory concentration (MIC) as a parameter of antifungal activity. Consequently, a significant portion correlation was noted in the case of Candida albicans. However, no obvious correlation was noted for Trichophyton mentagrophytes and Trichophyton rubrum. Therefore, the mechanism of action of imidazole derivatives for Candida albicans was considered to mainly consist in the membrane action.

Antifungal Agents↗
PubMed1997

[Measurement of fecal lactoferrin for diagnosis on pediatric gastrointestinal disease].

The fecal proteins in blood and granules related with inflammation have been measured to examine the conditions of inflammation in inflammatory bowel disease (IBD). To noninvasively examine the conditions in pediatric patients with various gastrointestinal diseases, we evaluated the usefulness of measuring the concentration of fecal lactoferrin (Lf), which is the specific granule component in neutrophils. Lf was measured by ELISA in patients with infectious enteritis (E), Henoch Schönlein purpura (HSP), and ulcerative colitis (UC), and in control subjects. The fecal Lf levels were significantly higher in patients with E, HSP, and UC than in control subjects. The fecal Lf levels were significantly increased in not only patients with bacterial but also those with viral gastroenteritis. These findings suggest that the measurement of fecal Lf concentration is useful for noninvasive monitoring of the disease activity in pediatric patients with gastrointestinal disease and the activities of neutrophils elevate in patients with viral infectious enteritis.

Child↗
PubMed1997

[Effects of recombinant human erythropoietin (rHuEpo) on the interactions between glomerular endothelial cells and mesangial cells: regulation of cell proliferation via endothelin (ET)-1].

To elucidate the effects of recombinant human erythropoietin (rHuEpo) on the interactions between glomerular endothelial cells (GENs) and mesangial cells (GMCs), we investigated whether or not cultured bovine GENs alter endothelin (ET)-1 secretion from bovine MCs and MC proliferate under basal or rHuEpo-stimulated conditions. Incubation for 24 hours with synthetic ET-1 stimulated MC in a dose-dependent manner. In addition, 100 pg/ml of ET-1 significantly stimulated MC proliferation after more than 12 hours incubation. Moreover, rHuEpo stimulated ET-1 secretion from GENs in a dose-dependent manner and showed less stimulation of ET-1 secretion from GMCs than GENs. DNA synthesis in both GENs and GMCs was significantly stimulated with more than 5 U/ml of rHuEpo. ET-1 secretion from GENs co-cultured with GMCs was higher than that from cultured GENs only. Conditioned medium, obtained from co-culture of GENs and GMCs, stimulated the proliferation of GMCs that were significantly inhibited with 10(-6) M approximately 10(-5) M BQ-123, a ETA receptor antagonist. These results suggest that rHuEpo directly stimulates the proliferation of GENs and GMCs, and this stimulatory effect is in part due to ET-1 secreted from these cells, especially GENs.

Animals↗
PubMed1997

[A case of asynchronous quadruple cancer arising from the prostate, stomach, rectum and urinary bladder].

Herein, we report a case of quadruple cancer arising from the prostate, stomach, rectum and urinary bladder. A 92-year-old man was admitted to our hospital on March, 1996, with complaints of macroscopic hematuria and micturition pain. He had a history of prostate cancer (no details) at the age of 67, and subtotal gastrectomy for gastric cancer (tubular adenocarcinoma, conclusive stage Ia) at the age of 89. He underwent a polypectomy for rectal cancer (well-differentiated adenocarcinoma)2 at the age of 90. There was no evidence of local recurrence or metastasis of these three carcinomas. Cystoscopy revealed multiple papillary tumors which were resected transurethrally. At the same time transrectal needle biopsy of prostate was performed. Pathology revealed transitional cell carcinoma G2 of urinary bladder and well differentiated adenocarcinoma of prostate. The postoperative course was uneventful and the patient has been doing well without recurrence of bladder cancer during the follow-up period of six months.

Adenocarcinoma↗
PubMed1997

Herniated cervical intervertebral discs: histological and immunohistochemical characteristics.

We examined the histological and immunohistochemical changes within and around herniated cervical intervertebral discs. A total of 28 herniated discs were harvested en bloc during anterior decompressive surgeries and examined together with the surrounding tissues. The presence of herniated discs correlated with the degeneration of cartilaginous endplate and torn annulus fibrosus. Formation of new blood vessels around the herniated discs was detected, using von Willebrand factor antibody, in seven (25% of all) uncontained hernias and eight (38%) contained hernias. Immunohistochemical studies using specific antibodies showed the presence of cells positive for matrix metalloproteinase-3 (chondrocytes), CD68 (macrophages and monocytes), and interleukin-1 beta (endothelial cells), in cervical disc hernias. Our results suggested that the magnitude and degree of immunohistochemical tissue reaction in cervical disc herniation correlate with the extent as well as location of herniated disc material.

Adult↗
PubMed1997

PARP cleavage in the apoptotic pathway in S2 cells from Drosophila melanogaster.

Caspase activities and two cDNA sequences have been identified in Drosophila melanogaster. To study the molecular events following the activation of the apoptotic pathway in D. melanogaster, S2 cells were treated with etoposide and the timing of the apoptotic events, such as caspase activation, mitochondrial pore opening, and loss of membrane asymmetry, was determined. Poly(ADP-ribose) polymerase (PARP) is known to be cleaved in the early phase of apoptosis in vertebrate systems. Little is known about the involvement of PARP cleavage in apoptosis in invertebrates. If PARP inactivation is a general event, this could mean that DNA repair enzymes need to be cleaved for the death pathway to be completed. We have found that in etoposide-treated cells, PARP protein is processed, but the nature of the cleavage is not known. Further experiments must be conducted and the peptide fragments must be sequenced to relate protease activities with PARP cleavage.

Animals↗
PubMed1996

Inactivation of p16/CDKN2 and p15/MTS2 genes in different histological types and clinical stages of primary ovarian tumors.

To define the involvement of p16/CDKN2 and p15/MTS2 inactivation in ovarian tumorigenesis and the association of these inactivation events with histological types and clinical stages of ovarian tumors, we analyzed homozygous deletion and somatic mutation of p16/CDKN2 and p15/MTS2 genes, as well as hypermethylation of the 5'-CpG island of the p16/CDKN2 gene, in 49 primary ovarian tumors and 6 ovarian carcinoma cell lines. We found homozygous deletions of p16/CDKN2 and p15/MTS2 in 6 (12%) and 5 (10%) primary tumors, respectively. Somatic mutation of p16/CDKN2 was found in only 1 primary tumor, but mutation of p15/MTS2 was not detected in any sample. None of the 28 primary tumors or 6 cell lines was hypermethylated at the 5'-CpG island of p16/CDKN2. The incidence of inactivation of p16/CDKN2 in primary tumors was significantly higher in the advanced stages (7 of 29) than in the early stages (0 of 14). Seven of 9 alterations in p16/CDKN2 and p15/MTS2 were observed in serous (3 of 12), endometrioid (3 of 9) and clear-cell (1 of 4) carcinomas. However, only normal sequences of these genes were detected in mucinous carcinomas. Loss of heterozygosity (LOH) at the IFNA locus was detected in 1 of 19 (5%) tumors, but no change at the D9S171 locus was observed in 17 tumors. These results suggest that: (i) homozygous deletion is the main mechanism of inactivation of p16/CDKN2 and p15/MTS2 in ovarian tumorigenesis; (ii) inactivation of p16/CDKN2 and p15/MTS2 may be the histological type-specific events involved in ovarian tumorigenesis; and (iii) inactivation of p16/CDKN2 is potentially involved in the progression of ovarian tumors in advanced stages.

Carcinoma↗
PubMed1996

Molecular analysis of the FHIT gene at 3p14.2 in lung cancer cell lines.

Chromosome 3p is frequently deleted in various cancers including examples in the lung. A novel gene, termed FHIT, was recently isolated from the fragile site at 3p14.2, with aberrant transcripts being reported in lung cancer tumor specimens. To avoid overlooking tumor-specific altered transcripts due to contaminating normal cells in primary tumors, FHIT alterations were examined in 41 lung cancer cell lines in the present study. Lack of detectable expression or exclusive expression of aberrantly spliced transcripts, often accompanied by intragenic homozygous deletions, were observed in 7 of 24 non-small cell lung cancers (29%) but in 0 of 17 small cell lung cancers (0%). Extensive reverse transcription-PCR-single-strand conformation polymorphism analysis revealed polymorphisms and alternative splicing but failed to identify point mutations. These results suggest distinct mechanisms for FHIT alterations in lung tumorigenesis and that further studies of this interesting gene are warranted.

Acid Anhydride Hydrolases↗
PubMed1996

Somatic in vivo alterations of the JV18-1 gene at 18q21 in human lung cancers.

The chromosome region 18q21 is frequently deleted in lung cancers. Recent identification of JV18-1 at this locus led us to examine whether or not it might also be altered in lung cancers, as is the case for the closely related DPC4 tumor suppressor gene. A missense somatic mutation and a 9-bp in-frame deletion were detected in the highly conserved region of JV18-1 among 57 lung cancer specimens taken directly from patients. The total alterations in JV18-1 and DPC4, however, are not sufficient to account for all 18q21 deletions in lung cancers. These findings suggest that although JV18-1 and DPC4 may play roles in a limited fraction of lung cancers, another tumor suppressor gene may also exist in this chromosome region.

Carcinoma, Non-Small-Cell Lung↗
PubMed1996

Subcellular localization and protein interaction of the human LIMK2 gene expressing alternative transcripts with tissue-specific regulation.

In our efforts to explore possible roles of proteins with a LIM domain, which is a cysteine-rich Zinc-binding motif, in differentiation and oncogenesis in the lung, we have cloned a human LIMK2 gene and identified two alternative transcripts, LIMK2a and LIMK2b, which are probably due to variation in transcriptional initiation. The former encodes a protein containing two LIM domains, a PDZ domain, and a kinase domain, while the latter has only one and half LIM domains. The predominance of the two transcripts appears to be regulated in a tissue-specific manner. Alteration of the regulation is also observed in some cancer cell lines. Transfection studies have shown an association of 63-kDa and 58-kDa proteins with the LIMK2a and LIMK2b protein; the former is distributed in the cytoplasm and nucleus and the latter occurs mainly in the cytoplasm and is scarcely translocated to the nucleus. In contrast, a truncated LIMK2-Kinase has a nuclear location, not showing the protein association.

Alternative Splicing↗
PubMed1996

Neural toxicity of retroviruses.

Recombinant retroviruses containing the cDNA for human tyrosine hydroxylase-1 and Escherichia coli lacZ gene were used to infect primary foetal ventral mesencephalon and cortical cultures from rat brain. Severe neuronal toxicity resulted 3-4 days after infection, glial cells seemed to be much more resistant. The toxicity was likely to have resulted from an agent present within the virus-containing medium itself, rather than from the retrovirus itself. The results of this study indicate that retroviruses are not suitable vectors for the introduction of tyrosine hydroxylase into primary neuronal cultures.

Animals↗
PubMed1996

The hepatic vagal nerve is receptive to incretin hormone glucagon-like peptide-1, but not to glucose-dependent insulinotropic polypeptide, in the portal vein.

To examine whether incretin hormones, truncated glucagon-like peptide-1 (tGLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are recognized by the hepatic vagal nerve, changes of the impulse discharge rate in the afferent vagus upon their intraportal administrations were measured in situ in rats anesthetized with urethan and chloralose. One-min injection of tGLP-1 at a periphysiological dose of 0.2 pmol or a pharmacological dose of 4.0 pmol, but not of the vehicle, significantly facilitated the hepatic vagal afferents. However, the injection of GIP at either a physiological dose of 0.2 pmol, a periphysiological dose of 4.0 pmol, or an even much larger dose of 40.0 pmol did not change the afferents at all. The present results indicate that the hepatic vagus specifically recognizes an intraportal appearance of tGLP-1 in the hepatoportal area, suggesting that the vagal monitoring system for intraportal levels of the incretin hormone operates on ingestion of a mixed meal.

Afferent Pathways↗
PubMed1996

4-Hydroxy-2-nonenal cytotoxicity in renal proximal tubular cells: protein modification and redox alteration.

4-Hydroxy-2-nonenal (HNE), one of the major products of membrane lipid peroxidation, has been shown recently to be present in a form covalently attached to proteins in the renal proximal tubules of rats treated with a renal carcinogen, ferric nitrilotriacetate (Toyokuni, S., et al. (1994) Proc. Natl. Acad. Sci. USA 91, 2616-2620; Uchida, K., et al. (1995) Arch. Biochem. Biophys. 317, 405-411). In the present study, the mechanism of HNE cytotoxicity was studied using the renal tubular epithelial cells (LLC-PK1), focusing on the protein modification and alteration of cellular redox status induced by HNE. Upon treatment with HNE for 2 h, the LLC-PK1 cells were found to be resistant to the low concentration (10 microM) of HNE, while HNE at higher concentrations (> or = 50 microM) mediated cell death. The cytotoxicity of HNE appeared to be correlated with the HNE modification of cellular proteins. Among a number of proteins modified by HNE, a glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase was detected as one of the major targets of HNE in the cells. On the other hand, exposure of LLC-PK1 cells to HNE resulted in rapid reduction of cellular glutathione (GSH) levels, suggesting that HNE influenced primarily the redox status of the cells. Depletion of GSH with buthionine sulfoximine, a potent suppressor of GSH biosynthesis, before HNE treatment caused the cells to be sensitive to HNE cytotoxicity and to HNE modification of cellular proteins, whereas the increase in intracellular GSH levels by treatment with N-acetylcysteine before HNE treatment resulted in a dose-dependent inhibition of HNE-mediated protein modification. These results suggest that intracellular GSH is a determinant on cellular resistance against the HNE-mediated cytotoxicity.

Acetylcysteine↗
PubMed1996

Production of 1,5-anhydroglucitol from 1,5-anhydrofructose in erythroleukemia cells.

The pyranoid polyol 1,5-anhydroglucitol (1,5AnGlc-ol) occurs in a wide variety of organisms. In humans, it is present as one of the major monosaccharide components in body fluids and serves as an indicator for glycemic control in diabetic care. However, its metabolic origin and fate have been poorly understood. Here we demonstrate that 1,5AnGlc-ol is produced from glucose in erythroleukemia cells, K-562. We show the occurrence of 1,5-anhydrofructose (1,5AnFru), a derivative of 1,5AnGlc-ol oxidized at the C2 position, in K-562 cells. In addition, several pieces of evidence indicated that 1,5AnFru, rather than glucose, was the immediate precursor in 1,5AnGlc-ol production in erythroleukemia cells: exogenous 1,5AnFru was readily taken up into the cells and reduced to 1,5AnGlc-ol, but the reverse reaction, oxidation of 1,5AnGlc-ol to 1,5AnFru, was scarcely observed. The apparent K(m) of the overall cellular reduction for 1,5AnFru was estimated as 70 mg/l. This reduction was markedly inhibited by glucose in the culture medium but not by 1,5AnGlc-ol or glucitol. Since 1,5AnFru arises from alpha-1,4-glucans through lyase reactions in fungi and algae, we suggest the possibilities that glycogen in the precursor of 1,5AnFru and, therefore, 1,5AnGlc-ol originates from glycogen in mammals.

Animals↗
PubMed1996

Gene regulation of senescence marker protein-30 (SMP30): coordinated up-regulation with tissue maturation and gradual down-regulation with aging.

Senescence marker protein-30 (SMP30) is a calcium binding protein also called regucalcin. The amounts of SMP30 decrease androgen-independently with aging in the livers of rats. We have studied the expression of SMP30 in livers and kidneys of rats from the embryonic to the senescent stages of life. No transcript was detected in livers or kidneys in day 18 embryos. However, Northern blot analysis showed a marked increase of SMP30 mRNA in livers of neonatal and young rats. The first peak of SMP30 transcript was found in a 5-day-old neonate, in which the amount of mRNA was threefold higher in comparison with 3- to 6.5-month-old adults. The expression of SMP30 protein started to increase from day 7 and rapidly reached a plateau at day 10. The substantial amounts of protein and transcript were maintained in adults up to 3-6.5 months of age. In the kidney, SMP30 mRNA and protein started to increase at day 21 and reached near-maximal levels at day 35. The levels of transcript and protein remained high in adults up to 3 months of age. As the aging process progressed to senescent stages, the levels of transcript and protein decreased significantly in the liver and kidney of aged rats. Therefore, the age-associated decrease of SMP30 in the liver and kidney may be, in a large part, controlled at transcriptional levels. Furthermore, immunohistochemical analysis showed a similar pattern of changes in SMP30 protein expression during neonate, adult and senescent stages in hepatocytes and renal proximal tubular epithelia. The high expression of SMP30 in the tissue-maturing process and adulthood suggests that SMP30 may be required for the maintenance of highly differentiated hepatic and renal functions.

Aging↗