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Biomedical subjects

T Shinagawa

Publications and source records attributed to T Shinagawa.

At least 73 records · Page 4Linked to original sources
PubMed1992

Cellular immune responses of peripheral blood mononuclear cells to HBV antigens during chronic and acute HBV infection.

Patients with acute self-limited and chronic HBV infection were studied to determine their in vitro cellular immune response to HBV antigens. In interferon-gamma production cultures which were evaluated as an indicator of cellular immune response, peripheral blood mononuclear cells from patients with HBeAg-positive chronic hepatitis showed elevated response to HBcAg, while those from HBeAg-positive asymptomatic carriers revealed no response to either HBcAg or HBeAg. HBeAg-stimulated interferon-gamma production was higher in anti-HBe-positive chronic hepatitis and asymptomatic carriers than that in HBeAg-positive patients. Interferon-gamma production against HBcAg was shown to be HLA class II restricted by blocking assay using monoclonal antibodies. HBsAg with or without pre-S2 did not amplify interferon-gamma production of patients with chronic hepatitis. In acute hepatitis B, both envelope and nucleocapsid antigens induced greater interferon-gamma production than in chronic HBV carriers. These results indicate that the patients with acute hepatitis responded more to HBV antigens compared with chronic HBV carriers. Furthermore, enhanced cellular immune responses, particularly to HBeAg, were observed in anti-HBe-positive patients compared to HBeAg-positive patients during chronic HBV infection, suggesting that the poor response to HBeAg in HBeAg-positive patients may account for the failure to clear HBV.

Adult↗
PubMed1992

[Quantitative X-ray CT analysis of calcification of the abdominal aorta and its relationship to obesity].

Quantitative analysis of abdominal aorta calcification by X-ray CT is a useful method for non-invasive diagnosis of atherosclerosis. We recently examined the relationship between the X-ray CT measurement of abdominal aorta calcification and the degree of obesity. For this purpose, the body mass index (BMI) and the subcutaneous fat thickness (determined by X-ray CT at the umbilical level) were analyzed in relation to the abdominal aorta calcification index (ACI) in 845 patients (453 males and 392 females aged 40-79 years). Patients with BMI under 20 were classified as "lean", those with BMI between 20-26 as "normal" and those with BMI over 26 as "obese". 1. Among males, the ACI was highest in lean individuals and lowest in obese individuals. The difference in ACI between lean and obese males was significant in the middle aged group (40-65 years). Among females, no relationship was observed between the degree of obesity and ACI. 2. Among males, ACI was higher in individuals with low subcutaneous fat thickness and lower in individuals with greater subcutaneous fat thickness. The difference was significant in the middle aged group. Among females, no relationship was observed between the two parameters. 3. When the visceral fat to subcutaneous fat ratio (V/S) in 85 males and females aged 60-69 years was analyzed in relation to ACI, ACI tended to decrease as the V/S increased, in both males and females. 4. Relationships between BMI and subcutaneous fat thickness, between BMI and lipids and between lipids and ACI were also analyzed.

Adipose Tissue↗
PubMed1991

Identification of renal cathepsin B as a human prorenin-processing enzyme.

Prorenin, the inactive biosynthetic precursor of renin, is proteolytically cleaved in the renal juxtaglomerular cells to renin. The activity of renin is rate-limiting for generation of angiotensin II in the circulation. We identified a renal thiol protease which activates and accurately cleaves the 43-amino acid prosegment of human recombinant prorenin. In the current studies, 6.5 mg of this protease was purified from human renal cortex using a three-step procedure dependent upon Leu-Leu-arginyl affinity chromatography. This represented an overall 766-fold purification and resulted in three protein bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis of molecular weights 30,000, 25,000, and 24,000. All three bands cross-reacted with an anti-human liver cathepsin B antibody upon immunoblot analysis; electrolution of each band and amino-terminal sequence analysis confirmed that the Mr 30,000 protein was mature cathepsin B and the Mr 25,000 and 24,000 bands were cathepsin B subunits. The pH optimum for the hydrolysis of pure human recombinant prorenin by pure renal cathepsin B was 6, and the Michaelis-Menten constant, Km, of the reaction was 1.4 x 10(-9) M. Immunostaining of human kidney using a sheep anti-human cathepsin B antibody demonstrated the presence of cathepsin B in the juxtaglomerular areas of the kidney, as well as in the renal proximal tubules. Electron microscopic immunohistochemistry using the same antibody demonstrated cathepsin B in dense secretory granules of the juxtaglomerular cells. Renin was also shown to be present in these granules. This study provides both biochemical and morphological evidence that renal cathepsin B is a human prorenin-processing enzyme.

Amino Acid Sequence↗
PubMed1991

Apoptosis in cultured rat hepatocytes: the effects of tumour necrosis factor alpha and interferon gamma.

We investigated the cytotoxic effects of tumour necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma) on rat hepatocytes in culture. Under phase contrast microscopy, we found a small number of dying hepatocytes in control cultures, each having been transformed into a cluster of small spheres. Under transmission electron microscopy, these cells showed the characteristics of apoptosis. TNF alpha and a combination of TNF alpha and IFN gamma exerted a cytotoxic effect, whereas IFN gamma showed no significant cytotoxicity when assessed by neutral red assay and by measuring LDH activity in culture medium. Under phase contrast microscopy, the number of apoptotic cells increased with the addition of either TNF alpha or IFN gamma, and markedly with the addition of both. DNA extracted from apoptotic cells cultured with TNF alpha and IFN gamma was fragmented, and a set of bands of the '200 bp ladder', which is characteristic of the DNA of apoptotic cells, was observed in agarose gel electrophoresis. These findings indicate that cultured hepatocytes die from apoptosis. TNF alpha killed cultured rat hepatocytes by increasing apoptosis, and this effect was potentiated by the addition of IFN gamma, which by itself was also weakly cytotoxic.

Animals↗
PubMed1991

Activity of antibodies to hepatitis C virus of patients with chronic non-A, non-B hepatitis decreases during interferon alpha therapy.

The activity of antibodies to hepatitis C virus (anti-HCV) was investigated in 80 patients with chronic non-A, non-B liver diseases. Anti-HCV antibodies were positive in 82.5% (66/80), and the titers were 1 for 18 patients, 2 for 40 and 3 for 8, respectively. The frequency of anti-HCV was significantly lower in patients with chronic persistent hepatitis (8/13, 61.5%) than in those with chronic active hepatitis (42/49, 85.7%) (P less than 0.05). There was no significant difference in the distribution of anti-HCV titers among the different stages of hepatitis. There was no correlation between anti-HCV titer and histology activity index score in chronic hepatitis. Activity of anti-HCV decreased more frequently in the patients who responded to interferon alpha (IFN alpha) therapy (8/22, 36.4%) than in those who did not (0/9, 0%) (P less than 0.05). These results indicate that anti-HCV activity does not correlate with the activity or disease stage of chronic hepatitis, but that anti-HCV activity decrease more frequently during IFN alpha treatment in patients who responded to IFN alpha therapy.

Adult↗
PubMed1991

Effect of sizofiran, a polysaccharide, on interferon gamma, antibody production and lymphocyte proliferation specific for hepatitis B virus antigen in patients with chronic hepatitis B.

To examine whether sizofiran (SPG), a polysaccharide isolated from Schizophyllum commune Fries, could modulate the immune response of immunocompetent cells to hepatitis B virus (HBV) nucleocapsid antigens, we investigated in vitro the production of interferon-gamma (IFN-gamma) and antibody (antibody to HB core and e antigens; anti-HBc and anti-HBe), and proliferation by peripheral blood mononuclear cells (PBMC) from six patients with chronic hepatitis B and four control individuals in the presence of recombinant HBcAg and purified HBeAg. Sizofiran alone in culture and in combination with HBV Ag was found to enhance IFN-gamma production and the proliferative response of PBMC from the patients compared with corresponding medium or HBV Ag alone culture. In contrast, antibody production was not elicited by SPG alone, but amplified by the drug in HBcAg-stimulated culture. In vitro leukocyte IFN-alpha addition increased IFN-gamma production, but suppressed the proliferation of PBMC from both controls and patients in the presence or absence of SPG and HBV Ag. These results indicate that SPG is able to modulate both cellular and humoral immune responses specific for nucleocapsid antigens in patients with chronic hepatitis B.

Hepatitis B↗
PubMed1991

Myxoid variant of epithelioid leiomyosarcoma of the uterus.

A rare case of myxoid variant of epithelioid leiomyosarcoma of the uterus in a 76-year-old woman is reported. Palpation and computed tomography revealed an enlarged uterus. Total hysterectomy and bilateral salpingo-oophorectomy were performed, and a hemispheric tumor, measuring 2.7 x 2.5 x 1.8 cm, was found protruding into the uterine cavity of the upper uterine segment. The tumor contained a prominent myxoid stroma and epithelioid tumor cells, which were round and polygonal in shape and showed positive immunoreactivity for desmin and vimentin. High mitotic activity was observed in the tumor cells. Electron microscopic examination revealed bundles of filaments in the cytoplasm and fine reticular material in the extracellular matrix. Histochemically, the myxoid stroma contained abundant acid mucopolysaccharide. The tumor cells were considered to originate from smooth muscle cells, while the myxoid stroma expressed varying differentiation of uterine mesenchymal cells. The patient is currently well with no evidence of recurrence or metastasis one year after the operation.

Aged↗
PubMed1991

Detection of pre-C and core region mutants of hepatitis B virus in chronic hepatitis B virus carriers.

We analyzed the pre-C and core region of hepatitis B virus (HBV) DNA by a polymerase chain reaction in 22 chronic carriers. In 9 hepatitis B e antigen-positive asymptomatic carriers, a single DNA band was detected at the expected size, whereas additional shorter DNA bands were observed in 7 out of 11 patients with chronic hepatitis. The smaller-sized DNAs from one chronic hepatitis patient had various lengths of deletions spanning from 105 to 183 bp in the middle of the core gene, and all deletions included common nucleotide sequences. All of the smaller-sized DNAs from the other patients proved to be variant core genes. They were deleted in similar regions by Southern analysis using oligonucleotide probes. A follow-up study revealed that four out of seven chronic hepatitis patients with a short core gene seroconverted to antibody to hepatitis B e antigen, but those with only a "wild type" did not. In another set of sequence studies, clones isolated from two chronic carriers displayed heterogeneity of the pre-C and core gene which was more often present in sera with normal alanine aminotransferase levels than with abnormal levels. These results suggest that mutant HBV alters the host immune response, and may modulate the clinical course of HBV infection. An alternative possibility is that chronic hepatitis selects for mutant forms.

Adolescent↗
PubMed1991

T cell lines reactive with hepatitis B core and E antigens in patients with chronic hepatitis B.

Hepatitis B virus (HBV)-associated nucleocapsid antigen (HB core and HB e) is believed to be a major target for T cell-mediated hepatocellular damage in chronic HBV carriers. Studies were undertaken to determine whether both nucleocapsid Ag could be recognized by T cell lines from peripheral blood mononuclear cells (PBMC) from patients with chronic hepatitis B. After cultivation in the presence of rHBcAg or purified HBeAg, growing cells were cloned by limiting dilution in the presence of PHA, IL-2 and allogenic feeder cells. Four HBcAg-reactive and three HBeAg-reactive T cell lines from two patients were generated by proliferation assays. None of the cell lines responded to HB surface Ag or PPD. Four lines were of the CD8+ CD11b- cytotoxic phenotype, two of the CD4+ Leu8- helper phenotype, and the remaining one consisted of mixed populations of CD4+ Leu8+ and CD4+ Leu8- cells. Cross-reactivity study showed that a HBcAg-induced CD4+ T cell line responded to HBeAg, and similarly a HBeAg-induced CD8+ T cell line responded to HBcAg. The reactions were inhibited by HLA class II antibody, but not by class I Ab.

Adult↗
PubMed1991

Intratesticular leiomyoma: a case report.

A case of leiomyoma of the testis is reported. The origin of the intratesticular leiomyoma is controversial, but recently it is thought to arise from the contractile cells in the tunica propria of the seminiferous tubules. This is the first case reported in Japan and the fifth in the world literature.

Adult↗
PubMed1991

Anti-hepatitis C antibodies in patients with chronic non-A, non-B hepatitis: relation to disease progression and effect of interferon alpha.

The activity of antibodies to hepatitis C virus (anti-HCV) was investigated in 80 patients with chronic non-A, non-B liver diseases. Serum anti-HCV titer was determined by the "Ortho-HCV" enzyme-linked immunosorbent assay with some modifications to quantify the activity. Anti-HCV was positive in 82.5% of cases (66/80). Anti-HCV occurred significantly less often in the patients with chronic persistent hepatitis (8/13, 61.5%) than in those with chronic active hepatitis (42/49, 85.7%) (p less than 0.05). Anti-HCV titer of the patients with chronic persistent hepatitis and that with chronic active hepatitis was significantly higher than that with liver cirrhosis (p less than 0.01 and p less than 0.05). There was no correlation between anti-HCV titer and histology activity index in chronic hepatitis. Serial study demonstrated that anti-HCV titer decreased more frequently in the patients who responded to IFN alpha therapy (11/22, 50.0%) than in those who did not respond to IFN alpha therapy (0/10, 0%) (p less than 0.01). These results indicate that anti-HCV level does not correlate with the activity of hepatitis, but that it decreases in accordance with the disease progression to liver cirrhosis or with the response to IFN alpha therapy.

Adult↗
PubMed1991

Serum interleukin 6 levels in patients with chronic hepatitis B.

Studies were undertaken to evaluate the role of interleukin 6 (IL-6) in the pathogenesis of chronic hepatitis B. Using recently developed sensitive and specific enzyme-linked immunosorbent assay, we determined serum levels of IL-6 in patients with chronic active hepatitis B (B-CAH), chronic persistent hepatitis B (B-CPH), and primary biliary cirrhosis (PBC). Serum IL-6 activity tended to increase in patients with B-CAH (38.4 +/- 68.0 pg/ml) (+/- SD), compared with controls (9.7 +/- 6.8 pg/ml), although the difference was not significant because of the wide scatter in values. IL-6 levels in B-CPH and PBC were similar to those of controls. There was a significant correlation between the levels of IL-6 and aminotransferase in B-CAH. In addition, IL-6 activity was significantly enhanced during acute exacerbation of the illness, accompanied by clearance of HBeAg. Patients who received IFN-alpha and IL-2 therapy showed depressed IL-6 activity during treatment, and a rebound beyond pretreatment values after cessation of therapy. These findings suggest that IL-6 plays a role in the development of chronic hepatitis B, and it may contribute, at least in part, to the elimination of HB virus.

Adult↗
PubMed1990

Identification of an enzyme in human kidney that correctly processes prorenin.

Using pure recombinant human prorenin as a substrate, we have identified an enzyme in human kidney that accurately processes prorenin to active renin (EC 3.4.23.15). In the crude homogenate, the predominant activity of this potential renin-processing enzyme (RPE) converted the Mr 47,000 inactive prorenin to Mr 44,000 active renin and had a pH optimum of approximately 6. The activity was blocked by cysteine protease inhibitors, but not by pepstatin, EDTA, or serine protease inhibitors. This RPE activity was not detected in a similarly prepared homogenate of human chorion decidua tissue, which produces primarily prorenin, or in human plasma. The activity was purified 100-fold by ammonium sulfate precipitation, p-chloromercuribenzoate affinity chromatography, and chromatofocusing. The partially purified enzyme has a Mr of approximately 27,000 and an isoelectric point in the pH 4.8-5.6 range. The activity in the purified RPE preparation had the same pH optimum as that in crude homogenate, cleaved the prosegment at the same site used by the kidney in vivo based on amino-terminal sequencing of the processed renin, and did not degrade prorenin or renin. These data suggest that the cysteine protease we have isolated is a candidate for authentic renal RPE.

Amino Acid Sequence↗
PubMed1990

[Metastatic penile tumor from lower pharynx: a case report].

Metastatic tumor of the penis is uncommon and only 95 cases have been reported in Japan. A 70-year-old man, who had squamous cell carcinoma of the lower pharynx, complained of urethral induration. Biopsy was performed and pathological diagnosis was metastatic tumor of penis originating from the lower pharynx. Although partial response in tumor size was noted by irradiation therapy, the patient died of multiple metastases in the 4th month after the diagnosis. This case is the first report of metastatic penile tumor originating from the lower pharynx.

Aged↗
PubMed1990

[Two cases of ureteral tumors occurring after operation on bladder tumors].

Among 116 patients with bladder tumors treated during a 17-year period, 2 patients were found to have ureteral tumors (1.7%). The first case was found 8 years after transurethral resection (T.U.R.) and the second case was diagnosed as multiple ureteral tumors 3 years after six T.U.R.s. Long term follow-up by urinary cytology should be performed for patients with bladder tumors to find upper urinary tract tumors, especially for the patient with multiple bladder tumors.

Aged↗
PubMed1989

Extrarenal renin-secreting tumors: insights into hypertension and ovarian renin production.

Although renin-secreting tumors are rare, they must be considered in the differential diagnosis of hypertension associated with hypokalemia, which occurs commonly in the hypertensive population. The finding of an ovarian renin-secreting tumor emphasizes the potential importance of the ovary as an extrarenal source of renin; the local ovarian renin-angiotensin system may play a key role in reproductive function by regulating vascular reactivity, local blood flow, steroidogenesis and other physiologic effects. In the illustrative case presented, a renin-secreting ovarian leiomyosarcoma was obtained from a women who presented with hypertension and hypokalemia. Plasma prorenin levels were markedly elevated. Tumor excision was quickly followed by a fall in prorenin levels and tumor recurrence was accompanied by an increase in prorenin levels. Active renin concentration in the tumor homogenates was similar to that found in kidney homogenates while the tissue prorenin concentration was approximately 20 times that found in kidney tissue. When cultured for up to 4 weeks, ovarian tumor cells secreted greater than 95% prorenin. Immunoblot analysis demonstrated that tumor renin had a molecular weight of 47,000, similar to that of human recombinant prorenin. Immunohistochemical staining of tumor tissue with antibodies against human renal renin at the electron microscopic level demonstrated the presence of renin primarily in membrane-bound vesicles and rarely in dense-core secretory granules. These findings suggest that prorenin in this ovarian tumor was secreted by the constitutive pathway, which is mediated by these amorphous vesicles.

Aged↗
PubMed1989

Human decidua is a major source of renin.

Plasma prorenin levels are elevated in normal pregnant women. Current evidence suggests renin production by tissues of the uteroplacental unit contribute to this elevation. The purpose of this investigation was to define the source of renin biosynthesis within the human uteroplacental unit and to characterize the renin produced. RNA extraction and Northern blot analysis consistently demonstrated renin mRNA expression in uterine lining both in the pregnant (decidua) and nonpregnant states (endometrium) and in fetal chorion laeve, which is inseparable from the decidua. In contrast, renin mRNA expression was not detected in basal plate and intertwin chorion (which is separate from decidua), amnion, myometrium, or placental villi. The total renin content in decidual homogenates was two- to threefold greater than in endometrial homogenates, and cultured human decidual cells produced significantly more total renin than cultured human endometrial cells, suggesting that pregnancy enhanced renin production by the cells lining the uterus. Immunoblot analysis and [3H]leucine incorporation identified 47,000-mol wt prorenin as the major form of renin produced by cultured human decidual cells. These studies indicate that maternal decidua is the major source of prorenin in the uteroplacental unit.

Adult↗