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Biomedical subjects

S Hino

Publications and source records attributed to S Hino.

At least 55 records · Page 3Linked to original sources
PubMed1999

Balance between activated-STAT and MAP kinase regulates the growth of human bladder cell lines after treatment with epidermal growth factor.

Epidermal growth factor (EGF) is a potent mitogen, and its action is mediated by MAP kinase (MAPK). Reportedly EGF activates STAT, induces the expression of p21waf1, and subsequently inhibits the growth of several types of cancer cells. In this study, we used human bladder cancer cells (T24 and RT4), immortalized non-tumorigenic human urothelial cells (1T-1, 1T-2, and 1T-3), and epidermal carcinoma cells (A431). EGF inhibited the growth of T24 and A431, and stimulated the growth of 1T-1, 1T-3 and 1T-2, but did not affect the growth of RT4. EGF activated MAPK strongly in 1T-1, and slightly in A431, T24, 1T-2, and 1T-3 but marginally in RT4. We detected the activation of STAT in T24, 1T-3 and A431 after EGF treatment. EGF enhanced the expression of p21waf1 mRNA in T24, 1T-2, 1T-3 and A431, and activated the p21waf1 promoter in T24 cells. These results suggest that i) EGF inhibits the growth of T24 cells via induction of p21waf1 mediated by STAT, and ii) the balance between the STAT-induced p21waf1 and MAPK activities regulates the growth of human bladder cells after EGF treatment.

Blotting, Northern↗
PubMed1998

Aberrant expression of double-stranded RNA-dependent protein kinase in hepatocytes of chronic hepatitis and differentiated hepatocellular carcinoma.

We immunohistochemically analyzed the expression of double-stranded RNA-dependent protein kinase (PKR) using a monoclonal antibody, 71/10. Test samples included 64 human liver biopsies and 25 liver sections of rats inoculated with diethylnitrosamine. The PKR signals in human fatty livers and normal rat livers were minimum. Scoring signal intensity from 0-4, the average scores of chronic active (14 cases) and chronic persistent (6 cases) hepatitis associated with hepatitis virus C (HCV) were 2.8 and 2.0, respectively (P = 0.038). The stained cells were significantly more abundant in the periportal than centrilobular regions for both chronic active and persistent hepatitis (P < 0.001 each). The average score of liver cirrhosis associated with HCV was 1.9. Those scores of well-, moderately, and poorly differentiated hepatocellular carcinomas associated with HCV were 3.4, 2.1, and 0.3, respectively (P < 0.001 for each pair). Those scores of well- and poorly differentiated carcinomas associated with hepatitis virus B were 2.3 and 0.0, respectively (P < 0.001). The average score of rat carcinomas induced by diethylnitrosamine was 1.9. Morphologically, nuclei of the vast majority of PKR-positive cells looked not apoptotic. The ratio of PKR-positive cells to apoptotic cells by terminal transferase-mediated dUTP nick end labeling method was approximately 20 in hepatitis, and over 100 in well-differentiated carcinoma.

Animals↗
PubMed1998

Deleted HTLV-1 provirus in cord-blood samples of babies born to HTLV-1-carrier mothers.

We screened 596 cord-blood samples by nested short PCRs for the gag and pX regions of HTLV-1 which are capable of detecting a single copy. The samples were derived from 449 and 147 babies born to seropositive and seronegative mothers respectively. Of these, 20 samples were positive in at least one of the PCRs: 9 (45%) were positive in both PCRs, but 10 and 1 samples in either the pX or the gag PCR respectively. These samples were tested further in nested long PCRs directed for gag-pX, gag-pol and pol-pX regions capable of detecting 8, 1 and 2 copies respectively. Of 9 dually positive samples, 7 (77%) showed the predicted 6.2-kbp band in the gag-pX PCR; only 2 of them had the predicted band alone; 7 samples had discrete bands shorter than the predicted size. In the gag-pol PCR, all 9 samples showed the predicted 2.2-kbp band alone. In the pol-pX PCR, 819 samples showed the predicted 4.2-kbp band, including one with an additional 2.1-kbp band, and the last a 1.0-kbp band alone. Thus, all of the dually positive samples had proviruses harboring gag, pol and pX priming sites. In contrast, none of the 11 singly positive samples showed the predicted band in the gag-pX PCR: 5 had no visible band, and the other 6 had shorter bands only. None of these 11 samples showed any positive signal in either gag-pol or pol-pX PCR. Our results suggest that HTLV-1 proviruses in the cord blood are frequently defective.

Base Sequence↗
PubMed1998

Down-regulation of TSC-22 (transforming growth factor beta-stimulated clone 22) markedly enhances the growth of a human salivary gland cancer cell line in vitro and in vivo.

We have recently isolated TSC-22 (transforming growth factor beta-stimulated clone 22) cDNA as a new anticancer drug (Vesnarinone)-inducible gene in a human salivary gland cancer cell line, TYS. We conducted the present study to examine whether up-regulation or down-regulation of TSC-22 can affect the growth of TYS cells in vitro and in vivo. We constructed an expression vector containing sense- or antisense-oriented human TSC-22 cDNA under the transcriptional control of the SR alpha promoter. We cotransfected TYS cells with the sense or antisense expression vector and pSV2neo and obtained more than 200 G418-resistant colonies in each sense or antisense transfectant. Approximately 80% of representative G418-resistant clones expressed the transcripts from transfected sense or antisense TSC-22 cDNA. To avoid the clonal heterogeneity of the cells, we mixed all of the G418-resistant colonies together in each sense or antisense transfectant and examined the expression of TSC-22 protein, in vitro growth, and the tumorigenicity in nude mice. The expression of TSC-22 protein was examined by solid-phase ELISA using a specific antibody against recombinant TSC-22 protein. The expression of TSC-22 protein was up-regulated in the sense transfectants and down-regulated in the antisense transfectants. Contrary to our expectation, up-regulation of TSC-22 protein did not affect both in vitro and in vivo growth of TYS cells. However, down-regulation of TSC-22 markedly enhanced the growth of TYS cells in vitro and in vivo. Furthermore, we examined the expression of TSC-22 mRNA in several human salivary gland tumors. The mRNA expression of TSC-22 in benign and malignant salivary gland tumors was significantly decreased when compared to that in tumor-free salivary glands (P < 0.05; one-way ANOVA), and in some salivary gland tumors, the expression of TSC-22 mRNA was not detectable by reverse transcription-PCR. These results suggest that down-regulation of TSC-22 may play a major role on salivary gland tumorigenesis.

Animals↗
PubMed1998

Induction of TSC-22 by treatment with a new anti-cancer drug, vesnarinone, in a human salivary gland cancer cell.

We undertook the present study to clarify the molecular mechanism of the effect of a new anti-cancer drug, vesnarinone, on a human salivary gland cancer cell line, TYS. We isolated TSC-22cDNA as avesnarinone-inducible gene from a cDNA library constructed from vesnarinone-treated TYS cells. TSC-22 was originally reported as a transforming growth factor (TGF)-beta-inducible gene. The expression of TSC-22 was up-regulated within a few hours after treatment with vesnarinone and was continued for 3 days. The level of TSC-22 mRNA in TYS cells was continuously increased until the cells reached confluency. Furthermore, the induction of TSC-22 by vesnarinone was inhibited by treatment with cycloheximide. When we treated the cells with an antisense oligonucleotide against TSC-22 mRNA under quiescent conditions, the antisense oligonucleotide stimulated the growth of TYS cells; however, under growing conditions the antisense oligonucleotide did not affect cell growth. Furthermore, the antisense oligonucleotide suppressed the antiproliferative effect of vesnarinone. These results suggest that TSC-22 may be a negative growth regulator and may play an important role in the antiproliferative effect of vesnarinone.

Antineoplastic Agents↗
PubMed1998

Follow-up study of children with nephrotic syndrome treated with a long-term moderate dose of cyclosporine.

Because of its potential for chronic nephrotoxicity, the long-term use of cyclosporine A (CsA) as treatment for nephrotic syndrome (NS) is controversial. The clinical outcome of patients with NS treated with CsA is unclear. We retrospectively evaluated 35 children with idiopathic NS, 24 with steroid-dependent NS (SDNS), and 11 with steroid-resistant NS (SRNS), who received CsA therapy for more than 12 months (median, 23 months) at the dosage maintaining 50 to 120 ng/mL in trough level. For SDNS patients, CsA was added to prednisolone after complete remission was achieved. For SRNS patients, CsA was used in combination with alternate-day prednisolone. Initial renal histology showed minimal changes (MC) in 28 patients (including all of the patients with SDNS) and focal segmental glomerulosclerosis (FSGS) in seven patients. The patients were followed up for 2 to 10.5 years (median, 6.5 years) after the termination of the CsA therapy. In SDNS patients, the relapse rate, dosage of prednisolone, standard deviation score for height, and body mass index significantly improved during CsA treatment. The follow-up study showed the proportion of SDNS decreased to 13 of 24 (54%) patients. In SRNS patients, CsA therapy induced remission in 8 of 11 patients (73%) (complete remission in seven and incomplete remission in one). Six of 11 patients (55%) then became steroid sensitive. Post-therapy biopsies, performed in 13 patients (10 with SDNS and three with SRNS), showed mild stripped interstitial fibrosis in two SDNS patients (15%). Long-term CsA therapy in moderate doses was effective to the patients with SDNS and SRNS and low in incidence of nephrotoxicity. The long-term use of CsA appears to result in a decrease in the proportion of SDNS and acquisition of subsequent steroid responsiveness in SRNS.

Adolescent↗
PubMed1998

Population dynamics of phenol-degrading bacteria in activated sludge determined by gyrB-targeted quantitative PCR.

A method for quantifying bacterial populations introduced into an activated-sludge microbial community is described. The method involves extraction of DNA from activated sludge, appropriate dilution of the extracted DNA with DNA extracted from nonintroduced activated sludge, PCR amplification of a gyrB gene fragment from the introduced strain with a set of strain-specific primers, and quantification of the electrophoresed PCR product by densitometry. The adequacy of the method was examined by analyzing the population dynamics of two phenol-degrading bacteria, Pseudomonas putida BH and Comamonas sp. strain E6, that had been introduced into phenol-digesting activated sludge. The density of each of the two populations determined by the PCR method immediately after the introduction was consistent with the density estimated from a plate count of the inoculum. This quantitative PCR method revealed different population dynamics for the two strains in the activated sludge under different phenol-loading conditions. The behavior of both of these strains in the activated sludge reflected the growth kinetics of the strains determined in laboratory axenic cultures.

Base Sequence↗
PubMed1998

Active-MMP2 in cancer cell nests of oral cancer patients: correlation with lymph node metastasis.

We examined the gelatinolytic activity in human oral squamous-cell carcinoma tissues in order to evaluate the capability of intravasation and extravasation of cancer cells. By a microdissection-zymography, we demonstrated separately the gelatinolytic activities in cancer cell nests and stroma adjacent to the cancer cells. The gelatinolytic activities, such as pro-matrix metalloproteinase (MMP)9 and active-MMP2 in most of cancer cell nests were much higher than those of normal gingival epithelium. Moreover, the activities of active-MMP2 in cancer cell nests of metastatic cancers were significantly higher than those of non-metastatic cancers (p<0.05). These results suggest that active-MMP2 in cancer cells can be a predictive marker for metastasis formation in oral squamous-cell carcinoma patients.

Carcinoma, Squamous Cell↗
PubMed1997

Urinary transforming growth factor-beta in patients with glomerular diseases.

We measured the urinary levels of active transforming growth factor-beta (TGF-beta) by enzyme-linked immunosorbent assay in 12 healthy controls and 42 patients with various glomerular diseases, including mesangial proliferative (IgA nephritis, Henoch-Schönlein purpura nephritis, and IgA-negative mesangial proliferative glomerulonephritis) and non-proliferative (minimal change nephrotic syndrome and focal glomerulosclerosis) types. Urinary TGF-beta, expressed as a ratio to urinary creatinine (ng/mg creatinine), was elevated in patients with IgA nephritis and focal glomerulosclerosis, and was significantly higher than in patients with other types of glomerular diseases and healthy controls. There was a significant correlation between urinary TGF-beta levels and the grade of interstitial fibrosis. Among patients with proliferative-type disease, urinary TGF-beta was significantly correlated with the grade of mesangial matrix increase and the magnitude of proteinuria. The relationship between urinary TGF-beta levels and the immunostaining intensity of TGF-beta in the glomeruli was not significant. These results indicated that urinary TGF-beta reflects the grade of interstitial fibrosis in glomerular diseases and also the mesangial matrix increase in proliferative-type glomerulonephritis. Measuring TGF-beta levels in the urine might be helpful in monitoring patients with some types of glomerular disease.

Enzyme-Linked Immunosorbent Assay↗
PubMed1997

Primary prevention of HTLV-1 in Japan.

The Nagasaki Prefecture, Japan (population: 1.5 million), is one of the hot endemic foci of Human T-lymphotropic virus type 1 (HTLV-1). Prevalence of HTLV-1 carriers are approximately 10% in the age group over 40 years old (40,000 individuals), approximately 10 times of the national average. Annual registry of adult T-cell leukemia (ATL) in the Prefecture is approximately 60 cases (estimated incidence: 100 cases), or a half percent of total deaths. A effective measure to control the endemic cycle of HTLV-1 has been imperative, since practical ways to prevent or control ATL are not available. A prefecture wide intervention at Nagasaki by refrain from breast-feeding blocked approximately 80% of mother-to-child transmission of HTLV-1.

Adult↗
PubMed1996

Proto-oncogene expression in human glomerular diseases.

The expression of the protein products and mRNA of c-fos, c-myc, p53, and c-raf was examined in normal renal tissues and biopsy specimens from 73 patients with various glomerular diseases. Immunofluorescent staining showed that there were cell nuclei stained for c-Fos, c-Myc, and p53, and cytoplasm positive for c-Raf, in the glomeruli of patients with proliferative types of glomerulonephritis, including IgA nephritis and lupus nephritis, and in patients with focal glomerular sclerosis. Glomerular expression of c-fos and c-myc mRNA was detected by in situ hybridization. The number of proto-oncogene-positive glomerular cells was significantly higher in lupus nephritis, IgA nephritis, and focal segmental sclerosis, as compared with minimal change nephrotic syndrome and normal specimens. In IgA nephritis, the population of glomerular cells positive for c-Fos and c-Myc and the grade of c-Raf immunoreactivity were significantly correlated with the proportion of proliferating cell nuclear antigen (PCNA)-positive glomerular cells, with histological grading of mesangial hypercellularity and matrix increase, and with the magnitude of proteinuria. These data indicate that proto-oncogene expression is associated with mesangial proliferation and matrix expansion in proliferative types of glomerulonephritis and in focal glomerular sclerosis.

Cell Nucleus↗
PubMed1996

Absence of alpha 6(IV) collagen in kidney and skin of X-linked Alport syndrome patients.

To identify the abnormalities of the type IV collagen alpha 6 chain, alpha 6(IV), in Alport syndrome, we examined renal and skin tissue using rat monoclonal antibodies against non-consensus amino acid sequences of alpha 6(IV). Immunofluorescence of normal human kidney and skin tissue revealed linear alpha 6(IV) staining in the basement membrane (BM) of Bowman's capsule, in some tubules, and also in the epidermal BM. Renal specimens from five male patients of four families with X-linked Alport syndrome showed no reactivity for alpha 6(IV) in Bowman's capsules and tubules. In these patients, alpha 1(IV) and alpha 2(IV) were normal, whereas alpha 3(IV), alpha 4(IV), and alpha 5(IV) were absent from the BMs of the kidney. In skin tissue of male patients, neither alpha 5(IV) nor alpha 6(IV) were detected. The epidermal BM of female heterozygotes with X-linked Alport syndrome showed a mosaic staining for alpha 5(IV) and alpha 6(IV). These findings indicate that, in addition to a disturbed alpha 3(IV)-alpha 4(IV)-alpha 5(IV) network, patients with X-linked Alport syndrome have abnormalities in alpha 6(IV) of the renal and epidermal BMs at the protein level.

Amino Acid Sequence↗
PubMed1996

Primary prevention of HTLV-I in Japan.

The ATL prevention program (AAP) in the Nagasaki Prefecture since 1987 consists of screening of pregnant women and asking the seropositives to refrain from breast-feeding. We screened approximately 90% of gravidas in the Prefecture and > 90% of the seropositive women agreed not to breast-feed. The maternal transmission rate dropped from approximately 20% to approximately 3%. PCR of cord bloods showed that 2.5% were PCR-positive. However, among formula-fed children, none of the cord-positives seroconverted, and none of the seropositives tested had been cord-positive. Breast-feeding for less than six months decreased the transmission rate significantly, but may have a higher transmission rate than the formula feeding.

Adolescent↗
PubMed1996

Identification of a functionally important population in phenol-digesting activated sludge with antisera raised against isolated bacterial strains.

Antisera were raised against nine strains which had been isolated from phenol-acclimated oil refinery activated sludge. Although several antisera reacted significantly with the activated sludge during a period of adaptation to phenol, only an antiserum against one of the isolates, Alcaligenes sp. E2, reacted with the activated sludge after the adaptation period. A kinetic pattern of phenol-oxygenating activity of the activated sludge after the adaptation period was similar to that of strain E2. These results suggest that a functionally important population in the phenol-digesting activated sludge was serologically identified.

Animals↗
PubMed1996

Expression of tenascin in normal and diseased human kidneys.

Expression of tenascin was studied in normal human adult and fetal kidney specimens, and in renal tissues biopsied from patients with several types of glomerulonephritis. Immunofluorescent staining of the normal kidneys showed that tenascin was present weakly in the mesangial area and interstitium, but was absent from the glomerular capillaries. In the fetal kidney, tenascin was detected in the interstitium, but not in the immature glomeruli. In kidney tissues biopsied from patients with various renal diseases, expression of tenascin was associated with increased mesangial expansion and tubulointerstitial changes. In situ hybridization showed that tenascin mRNA was expressed in the renal tissues, but tenascin mRNA and tenascin protein were occasionally dissociated. These findings indicate that expression of tenascin is associated with mesangial expansion and also with tubulointerstitial changes in human glomerulonephritis. Tenascin expression may contribute to repair of injured glomeruli and interstitium.

Adult↗
PubMed1996

[Present status of endoscopic therapy for esophageal varices--endoscopic variceal ligation (EVL)].

Recently, EVL was developed to provide the endoscopist a safer method for the treatment of esophageal varices. The purpose of this report is to reveal our data and the present status. From 1989 to 1995, we performed EVL with EIS using Aethoxysklerol in a total of 214 patients who had bleeding and/or risky esophageal varices. Our technique of EVL is as follows; For prophylactic and elective patients, a spiral ligation method was employed and followed by EIS to obtain the complete eradication. When active bleeding was observed, direct ligation was performed onto the bleeding point and if the bleeding point was not found, spiral ligation method was done. Eradicating effect was observed in 97% of the entire patients and 29 active/spurting bleedings were well controlled by this technique. Complications were experienced in 12 cases (2 stenosis and 10 post EVL ulcedr bleeding), however, there were no patients who could not be managed by endoscopic treatment. Variceal recurrence after EVL/EIS were occurred in 36 of 214 patients (16.8%). Recurrent period was ranged from 1 month to 24 months and mean period was 10 months. We conclude that EVL/EIS is safe, easy and effective mean for the treatment of esophageal varices.

Combined Modality Therapy↗