Biomedical subjects

Y Katoh

Publications and source records attributed to Y Katoh.

At least 37 records · Page 2Linked to original sources

PubMed2001

Salt-inducible kinase is involved in the ACTH/cAMP-dependent protein kinase signaling in Y1 mouse adrenocortical tumor cells.

The involvement of salt-inducible kinase, a recently cloned protein serine/threonine kinase, in adrenal steroidogenesis was investigated. When Y1 mouse adrenocortical tumor cells were stimulated by ACTH, the cellular content of salt-inducible kinase mRNA, protein, and enzyme activity changed rapidly. Its level reached the highest point in 1-2 h and returned to the initial level after 8 h. The mRNA levels of cholesterol side-chain cleavage cytochrome P450 and steroidogenic acute regulatory protein, on the other hand, began to rise after a few hours, reaching the highest levels after 8 h. The salt-inducible kinase mRNA level in ACTH-, forskolin-, or 8-bromo-cAMP-treated Kin-7 cells, mutant Y1 with less cAMP-dependent PKA activity, remained low. However, Kin-7 cells, when transfected with a PKA expression vector, expressed salt-inducible kinase mRNA. Y1 cells that overexpressed salt-inducible kinase were isolated, and the mRNA levels of steroidogenic genes in these cells were compared with those in the parent Y1. The level of cholesterol side-chain cleavage cytochrome P450 mRNA in the salt-inducible kinase-overexpressing cells was markedly low compared with that in the parent, while the levels of Ad4BP/steroidogenic factor-1-, ACTH receptor-, and steroidogenic acute regulatory protein-mRNAs in the former were similar to those in the latter. The ACTH-dependent expression of cholesterol side-chain cleavage cytochrome P450- and steroidogenic acute regulatory protein-mRNAs in the salt-inducible kinase-overexpressing cells was significantly repressed. The promoter activity of the cholesterol side-chain cleavage cytochrome P450 gene was assayed by using Y1 cells transfected with a human cholesterol side-chain cleavage cytochrome P450 promoter-linked reporter gene. Addition of forskolin to the culture medium enhanced the cholesterol side-chain cleavage cytochrome P450 promoter activity, but the forskolin-dependently activated promoter activity was inhibited when the cells were transfected with a salt-inducible kinase expression vector. This inhibition did not occur when the cells were transfected with a salt-inducible kinase (K56M) vector that encoded an inactive kinase. The salt-inducible kinase's inhibitory effect was also observed when nonsteroidogenic, nonAd4BP/steroidogenic factor-1 -expressing, NIH3T3 cells were used for the promoter assays. These results suggested that salt-inducible kinase might play an important role(s) in the cAMP-dependent, but Ad4BP/steroidogenic factor-1-independent, gene expression of cholesterol side-chain cleavage cytochrome P450 in adrenocortical cells.

Adrenal Cortex Neoplasms↗

PubMed2001

[A case of tumor-forming chronic pyelonephritis that was difficult to be differentiated from renal cell carcinoma].

We experienced a rare case of tumor-forming type of chronic pyelonephritis that could hardly be differentiated from renal cell carcinoma. A 62-year-old man was admitted to our department with right renal tumor which was discovered when he underwent examination for gastric cancer. Abdominal ultrasound sonography and computed tomography revealed a mass in the middle portion of the right kidney, measuring 3.8 x 3.5 cm in diameter, with irregular surface and isoechoic and isodense inner mass. Renal angiography demonstrated a hypervascular area in the middle portion. Radical nephrectomy and subtotal gastrectomy were performed under a tentative diagnosis of right renal cell carcinoma and early gastric cancer. The excised specimen macroscopically demonstrated a yellowish mass in the middle portion and microscopically revealed many lymphocytes and few neutrophils, macrophages or foam cells. The patient was diagnosed as tumor-forming type of chronic pyelonephritis. Such obvious inflammatory findings very rarely exist in the tumor-forming type of chronic pyelonephritis. Therefore, caution should be exercised in the differential diagnosis between this disease and renal cell carcinoma.

Carcinoma, Renal Cell↗

PubMed2001

[A case of intratubular germ cell tumor giving rise to seminoma in a subfertile man].

A 34-year-old man visited our hospital with the complaint of right scrotal swelling. Right high orchiectomy was performed under the diagnosis of testicular tumor. Pathological examination was seminoma, pT2pN0pM0 and 3 courses of chemotherapy (cisplatin, vinblastine, bleomycin) were performed. The patient had undergone testicular biopsy for infertility at another hospital 6 years before this visit. Re-examination of the biopsy specimen revealed a intratubular germ cell tumor. No evidence of recurrence or metastasis was found 2 years after surgery.

Adult↗

PubMed2000

Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages.

Electrophiles and reactive oxygen species have been implicated in the pathogenesis of many diseases. Transcription factor Nrf2 was recently identified as a general regulator of one defense mechanism against such havoc. Nrf2 regulates the inducible expression of a group of detoxication enzymes, such as glutathione S-transferase and NAD(P)H:quinone oxidoreductase, via antioxidant response elements. Using peritoneal macrophages from Nrf2-deficient mice, we show here that Nrf2 also controls the expression of a group of electrophile- and oxidative stress-inducible proteins and activities, which includes heme oxygenase-1, A170, peroxiredoxin MSP23, and cystine membrane transport (system x(c)(-)) activity. The response to electrophilic and reactive oxygen species-producing agents was profoundly impaired in Nrf2-deficient cells. The lack of induction of system x(c)(-) activity resulted in the minimum level of intracellular glutathione, and Nrf2-deficient cells were more sensitive to toxic electrophiles. Several stress agents induced the DNA binding activity of Nrf2 in the nucleus without increasing its mRNA level. Thus Nrf2 regulates a wide-ranging metabolic response to oxidative stress.

Adaptor Proteins, Signal Transducing↗

PubMed2000

The regulation of prostaglandin and arachidonoyl-CoA formation from arachidonic acid in rabbit kidney medulla microsomes by palmitoyl-CoA.

Under physiological conditions, small amounts of free arachidonic acid (AA) are released from membrane phospholipids, and cyclooxygenase (COX) and acyl-CoA synthetase (ACS) competitively act on this fatty acid to form prostaglandins (PGs) and arachidonoyl-CoA (AA-CoA). In the present study, we investigated the effects of palmitic acid (PA) and palmitoyl-CoA (PA-CoA) on the PG and AA-CoA formation from high and low concentrations of AA (60 and 5 microM) in rabbit kidney medulla microsomes. The kidney medulla microsomes were incubated with 60 or 5 microM [14C]-AA in 0.1 M-Tris/HCl buffer (pH 8.0) containing cofactors of COX (reduced glutathione and hydroquinone) and cofactors of ACS (ATP, MgCl2 and CoA). After incubation, PG (as total PGs), AA-CoA and residual AA were separated by selective extraction using petroleum ether and ethyl acetate. PA (10-100 microM) had no effect on the PG and AA-CoA formation from either 60 or 5 microM AA. PA-CoA (10-100 microM) was without effect on the PG and AA-CoA formation from 60 microM AA, whereas it markedly decreased the PG formation (6-40%) and increased the AA-CoA formation (1.1-2.3-fold) from 5 microM AA, showing that the effects of PA-CoA on the PG and AA-CoA formation change depending on the AA concentration. These results suggest that PA-CoA, but not PA, may regulate the PG and AA-CoA formation at low substrate concentrations (close to the physiological concentration of AA), and that this in-vitro method using 5 microM AA may be useful for clarifying the homeostatic control of the metabolic fate of AA into these two enzymatic pathways.

Acyl Coenzyme A↗

PubMed2000

Abnormal structure and expression of PTEN/MMAC1 gene in human uterine cancers.

The PTEN/MMAC1 gene, located on human chromosome 10q23, has recently been implicated as a candidate tumor suppressor gene in human cancers. In the present study, 12 uterine cancer cell lines and 87 uterine cancers of various grades and histological type were analyzed for PTEN/MMAC1 gene. Three of 44 endometrial carcinoma (7%) showed no PTEN/MMAC1 mRNA expression by RT-PCR analysis. Sequencing analysis of entire coding region of PTEN/MMAC1 gene revealed mutations in three of six endometrial cancer cell lines (50%) and 17 of 44 endometrial cancer tissues (39%). In contrast, for cervical cancers, only one of six cancer cell lines (2%) showed mutation, and one of 43 cancer tissues (2%) had an abnormality. Overall, 36% of the abnormal spots were located in exon 5, 24% were in exon 8, 16% were in exon 3, and 8% were in exon 6, and single cases of abnormality were found in exons 1, 4, and 7. Our results revealed that, in total, 60% of abnormalities were clustered in exons 5 and 8. Exon 5 is a functional domain of the PEN/MMAC1 gene, and therefore, abnormalities in this region may be important for loss of PTEN/MMAC1 gene function. Finally, we found a high frequency of PTEN/MMAC1 gene abnormalities in endometrial carcinomas but a low frequency in cervical carcinomas. These findings suggest that disruption of PTEN/MMAC1 by mutation or absence of expression may contribute to the pathogenesis or neoplastic evolution in a large proportion of endometrial carcinomas but in a small proportion of cervical carcinomas.

DNA, Complementary↗

PubMed2000

Factors influencing mortality in the rat elastase-induced-aneurysm model.

BACKGROUND: Intraarterial infusion of elastase has been used to create an experimental model of aortic aneurysm in rats. Unfortunately, the utility of this model is limited by a high mortality rate among experimental animals. This study examined the factors influencing mortality to help refine this model. MATERIALS AND METHODS: A total of 126 Wistar rats were divided into six groups. A 1.0-cm segment of infra-renal abdominal aorta was clamped (n = 21), clamped and cannulated via the femoral artery (n = 21), infused with saline (n = 21), or infused with solution containing 25 U of elastase from three different lots (each group, n = 21). Clamping or infusion was performed for 30 (n = 7), 60 (n = 7), and 120 min (n = 7). The mortality rates were calculated at 7 days. RESULTS: There were no deaths in the clamp group, but 29% of the rats that underwent cannulation with clamping or saline infusion for 2 h died. The mortality rate for a 30-min elastase infusion ranged from 0 to 71%. Mortality for a 60-min infusion ranged from 14 to 100%. Mortality for a 2-h infusion ranged from 43 to 100%. The mortality rate was dependent on the treatment time and the elastase lot number. CONCLUSIONS: Aortic cannulation, elastase infusion, and prolonged infusion times all increase the mortality rate in the elastase-induced rat aortic aneurysm model. Mortality is also dependent on the elastase lot number.

Animals↗

PubMed2000

The effect of immunosuppression on aortic dilatation in a rat aneurysm model.

This study was conducted to investigate whether systemic immunosuppression attenuated aortic dilatation in a rat aneurysm model. Sprague-Dawley rats were subjected to elastase infusion of the infrarenal aorta and divided into two groups of 12 rats each. The immunosuppression group (group 1) was given subcutaneous injections of cyclosporine A (5 mg/kg per day), azathioprine (2 mg/kg per day), and methylprednisolone (2 mg/kg per day) from the operative day until postoperative day (POD) 6. An additional subcutaneus injection of cyclophosphamide 30 mg/kg was also given on the operative day. The control group (group 2) was given subcutaneous injections of saline. Relaparotomy was performed on POD 7. After measurement of the aortic diameter, aortography and ultrasonography were performed in three rats from each group, following which the aortas were excised for histologic examination. The aortic diameter was significantly smaller in group 1 (2.58 +/- 0.37 mm) than in group 2 (6.21 +/- 1.74 mm) (P < 0.01) and the aortic lumen was slightly dilated in group 1, whereas it was spherically dilated in group 2. Total loss of elastic tissue was seen in both groups. Inflammatory cell infiltration and collagen fiber fragmentation were noted in group 2, whereas very little inflammatory cell infiltration and well-preserved collagen fibers were seen in group 1. These findings showed that immunosuppression attenuates aortic dilatation, partly by preserving the collagen fibers, in this rat aneurysm model.

Animals↗

PubMed2000

The time course of elastin fiber degeneration in a rat aneurysm model.

Previous findings vary regarding the timing and cause of elastin fiber degeneration in the elastase-induced rat abdominal aortic aneurysm model. We examined the timing and cause of elastin fiber degeneration after elastase infusion using two different elastase infusion times. Twenty-four Sprague-Dawley rats were divided into two groups. The infrarenal abdominal aorta was infused with 15 U of elastase for 15 min (n = 12, 15-min infusion group) or 30 min (n = 12, 30-min infusion group). In each group, three rats were killed immediately and 1, 3, and 7 days after infusion, and then the aortas were excised for a histologic examination. Elastin fibers did not stain, even immediately after elastase infusion, in the 30-min infusion group. The degeneration of elastin fibers did not progress in the 15-min infusion group during the period of observation. Inflammatory cells infiltrated mainly to the adventitia near regions where the degeneration of elastin fibers spread totally through the aortic media. Elastin fibers degenerate immediately after elastase infusion and thus seem to degenerate not due to endogenous proteinases that are produced by the infiltrating cells, but due to the exogenously infused elastase itself. Inflammatory cell infiltration was thus found to be a result of the degeneration of elastin fibers in this model.

Animals↗

PubMed2000

Association of Helicobacter pylori-dependent gastritis with gastric carcinomas in young Japanese patients: histopathological comparison of diffuse and intestinal type cancer cases.

AIMS: The causal relationship of H. pylori gastric colonization with gastric cancer development has not as yet been fully elucidated. The prevalence of H. pylori infection increases with age in the asymptomatic population in Japan, and reaches a high plateau in those older than 40 years. The objective of this study was to assess the link between H. pylori and gastric carcinomas in patients younger than 40 years. METHODS AND RESULTS: Detection of H. pylori and assessment of background mucosa based on the Sydney system was performed histopathologically for 40 Japanese gastric cancer cases younger than 40 years and compared with 40 age- and sex-matched controls. H. pylori infection in gastric mucosa was detected significantly more frequently (P < 0.001) in patients with cancer (29/40; 72.5%) than in controls (11/40; 27.5%). Additionally, by histopathological comparison between intestinal (18 cases) and diffuse (70 cases) types of young gastric cancer patients, mucosal atrophy and intestinal metaplasia were found to coexist with acute and chronic inflammation in the background mucosa of both intestinal and diffuse types, being significantly more prevalent than in young controls. CONCLUSIONS: As well as the high prevalence of H. pylori in young subjects with gastric cancer, it is clear that persistent infection induces mucosal damage, resulting in atrophy and intestinal metaplasia. Thus, acute/chronic gastritis could play an essential role in the early development of neoplasia in the stomach.

Adult↗

PubMed2000

Hepatitis C virus quasispecies and response to interferon therapy in patients with chronic hepatitis C: a prospective study.

We prospectively examined whether the complexity of hepatitis C virus (HCV) quasispecies is related to the response to interferon (IFN) therapy. Among 64 patients who had histologically proven chronic hepatitis and were treated with natural IFN-alpha, 53 patients were analysed. The other 11 patients discontinued therapy because of adverse effects of IFN. The complexity of the hypervariable region 1 (HVR 1) in quasispecies was determined using both clone number determined by fluorescence single-strand conformation polymorphism (SSCP) and nucleotide diversity determined by direct sequencing. These parameters were measured not only before treatment but also at completion and 6 months after therapy, if serum HCV RNA was detectable. This population of patients was different from the general Japanese population with regard to the high prevalence of patients infected with genotype 2a or 2b (49%), who had a higher viral load than those with genotype 1b (P = 0.021). Twenty-two patients (41.5%) were sustained responders. Genotype non-1b (P = 0.0009) and a smaller clone number (P = 0.008) were significantly associated with a sustained response. In multivariate analysis, these variables were independently associated with a sustained response (i.e. genotype: odds ratio 6.84, 95% CI 1.84-30. 12; and clone number: odds ratio 1.26, 95% CI 0.99-1.68). The clone number and nucleotide diversity did not change significantly between pretreatment and at completion or 6 months after therapy. These results suggest that lower complexity of HVR 1 quasispecies predicts a preferable response to IFN therapy that is independent of viral load, especially in the population of the relatively high prevalence of patients infected with genotype 2.

Adolescent↗

PubMed2000

GB virus C/hepatitis G viremia and antibody response to the E2 protein of hepatitis G virus in hemodialysis patients.

The aim of this study was to assess the relationship between the prevalence of GB virus C/hepatitis G virus (GBV-C/HGV) RNA and that of antibody to the putative E2 protein (anti-E2) in hemodialysis patients. GBV-C/HGV RNA in serum was detected by a reverse transcription polymerase chain reaction (RT-PCR) assay, and anti-E2 was measured in 244 hemodialysis patients by enzyme-linked immunosorbent assay using recombinant E2 protein. The GBV-C/HGV RNA level was determined by competitive RT-PCR with an interval of 1 year. GBV-C/HGV RNA, anti-E2. and both together were detected in 11 (4.5%), in 19 (7.8%), and in 3 patients (1.2%), respectively. Comparison of clinical characteristics between GBV-C/HGV RNA-positive patients and negative patients revealed the longer duration of hemodialysis (9.8 years vs. 6.0 years; p < 0.05), and the greater frequency of anti-hepatitis C virus (HCV) (63.6% vs. 20.3%; p < 0.05) and HCV RNA (36.4% vs. 12.9%; p < 0.05) in GBV-C/HGV RNA-positive patients. The GBV-C/HGV RNA levels of patients who were positive for anti-E2 remained under detection limit (< 10(2) copies/mL), whereas only one of eight patients who were negative for anti-E2 showed a GBV-C/HGV RNA level under detection limit (p < 0.05). The presence of anti-E2 in serum was associated with loss of detectable GBV-C/HGV RNA or with a very small amount of HCV RNA in hemodialysis patients.

Antibodies, Viral↗

PubMed2000

Significant increase in prostaglandin E-main urinary metabolite by laxative administration: comparison with ulcerative colitis.

OBJECTIVE: To assess the production of prostaglandin E(2), an important chemical mediator in diarrhea induced by laxative administration, a prostaglandin E-main urinary metabolite (7alpha-hydroxy-5,11-diketotetranor-prosta-1,16-dioic acid, PGE-MUM) was measured in healthy volunteers and compared with the values of patients with ulcerative colitis. METHODS: PGE-MUM was determined by a simplified immunoassay of bicyclic PGE-MUM and analyzed for the influence of laxative administration and active/remission phases of ulcerative colitis. RESULTS: Administration of laxatives induced a significant increase in PGE-MUM in healthy volunteers. A significant elevation was also found in the active as compared with the remission phase of ulcerative colitis. The PGE-MUM levels were significantly correlated with our modified Talstad scores, clinical disease activity indices in ulcerative colitis. It was confirmed by time course studies of individual patients that changes in PGE-MUM correlated well with colitis activity. CONCLUSION: Laxative administration induces production of prostaglandin E(2) as one of the chemical mediators, although its production grade is relatively low as compared with ulcerative colitis in the active phase.

Aged↗

PubMed2000

RT-PCR suggests human skeletal muscle origin of alveolar soft-part sarcoma.

In 1952, Christopherson et al. proposed that alveolar soft-part sarcoma (ASPS) was a distinct entity with unique clinical and pathological features. Since their report, its histogenesis has not been determined. In order to clarify the histogenesis of ASPS, a study using reverse transcription polymerase chain reaction using cDNAs from MyoD1 and myogenin, and the actin filament from human-skeletal-muscle-related mRNAs has been performed in 5 cases of ASPS. The expression of MyoD1 and myogenin was determined in 5 and 2 cases of the 5 cases, respectively. Moreover, expression of the many mRNAs from the actin filament of skeletal muscle was also found in ASPS. According to these findings, it is now postulated that ASPS is of skeletal muscle origin.

Actins↗

PubMed2000

Inhibitory action of troglitazone, an insulin-sensitizing agent, on the calcium current in cardiac ventricular cells of guinea pig.

We investigated the effects of troglitazone, a new orally active hypoglycemic agent, on the voltage-dependent L-type Ca2+ current in single cardiac ventricular myocytes of guinea pigs by the whole-cell voltage clamp technique. Troglitazone blocked the Ca2+ currents in a concentration-dependent manner. The inhibitory effect was more potent at the holding potential (HP) of - 50 mV than at - 80 mV. The half-maximum inhibiting concentration (IC50) of troglitazone was 0.8 microM with the Hill coefficient of 0.84 at -50 mV HP. In contrast, the IC50 value was higher than 10 microM at -80 mV HP. These results suggest that troglitazone at therapeutic concentrations inhibit the Ca2+ channels and may exert cardioprotective effects in diabetic conditions.

Animals↗

PubMed2000

Serum concentrations of 20K human growth hormone in normal adults and patients with various endocrine disorders. Study Group of 20K hGH.

The 20K hGH isoform is produced by alternative splicing of GH mRNA, and comprises approximately 10% of all GH in the pituitary. The physiological role of 20K hGH remains to be determined partly because of the lack of a simple and specific assay. We have established sensitive enzyme-linked immunoadsorbent assays (ELISAs) specific to 20K and 22K hGH. The serum levels of 20K hGH after overnight fasting was 118 +/- 178 pg/mL (N=282) in normal women, significantly higher than in normal men (64 +/- 170 pg/mL, N=226). However, there was no difference in the proportion of 20K hGH to 20K plus 22K hGH between men (6.3 +/- 2.6%, N=176) and women (6.3 +/- 2.1%, N = 263). No correlation was detected between the ratio of 20K hGH and age, body height, body weight or body fat mass in normal subjects. The proportion of 20K hGH was significantly (P < 0.001) higher in patients with active acromegaly (9.2 +/- 2.2%, N=33) and in patients with anorexia nervosa (9.0 +/- 1.9, N=8), both of which are characterized by chronic elevation of circulating GH levels. The proportion of the 20K hGH in successfully treated acromegalic patients did not differ from that in normal subjects, suggesting that GH-producing pituitary tumors secrete a higher proportion of 20K hGH, or chronic excess of 22K hGH altering the metabolic clearance rate of 20K hGH. The values in patients with adult growth hormone deficiency (GHD), hyperthyroidism, primary hypothyroidism, or GH-independent short stature did not differ from those in normal subjects. The 20K ratio did not change after acute GH provocative tests such as insulin tolerance test and GRH test. These results suggest that secretion of 20K hGH from the pituitary is under the same control as that of 22K hGH.

Acromegaly↗

PubMed2000

SIK (Salt-inducible kinase): regulation of ACTH-mediated steroidogenic gene expression and nuclear/cytosol redistribution.

Possible involvement of salt-inducible kinase (SIK), a serine/threonine protein kinase first cloned from high K+-diet treated rat adrenal glands, in the regulation of steroidogenesis was investigated. Y-1 cells, when treated with ACTH, underwent a rapid change in SIK's mRNA content. It reached the maximum within a few hours and returned to the base after 8 h. In contrast, the levels of mRNAs for CYP11A and StAR protein reached the maxima after 8 h. The SIK's mRNA induction failed to occur in ACTH-, forskolin- or 8-Br-cAMP-treated Kin-7 cells, a mutant cell line of Y-1 with defective cAMP-dependent protein kinase A (PKA). Y-1 cells that overexpress SIK, when treated with ACTH, had significantly repressed levels of mRNAs for CYP11A and StAR protein. Therefore, SIK might have a negative effect on the CYP11A- and StAR protein-gene expression in the early phase of ACTH-mediated steroidogenesis. To further explore the mechanisms underlying this phenomenon, we examined intracellular distribution of the green fluorescence protein (GFP)-tagged SIK. When GFP-SIK was introduced into HeLa cells, the fluorescent signals were detected in the nucleus. In Y-1 cells GFP-SIK was detected both in the nucleus and cytosol, and the signal in the former moved to the latter after ACTH-treatment. The nuclear/cytosol re-distribution of GFP-SIK was also observed in forskolin- or 8-Br-cAMP-treated Y-1 cells, but not in Kin-7 cells. These results suggest that the intracellular re-distribution of SIK in Y-1 cells may depend on the cAMP/PKA signaling pathway and has an important regulatory role in the ACTH-mediated steroidogenic gene expression.

Adrenal Cortex↗

PubMed2000

[A case of testicular tumor in a patient with Down's syndrome: a case report].

A 40-year-old man with Down's syndrome was admitted to our hospital for complaint of painless, swollen right scrotum. Computed tomography revealed a right testicular tumor and mass of iliac fossa. Right high orchiectomy and extirpation of mass were performed. Histological diagnosis of right testicular tumor was seminoma and the mass was an external iliac lymph node metastasis of seminoma. After operation, radiation therapy was performed.

Adult↗