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Biomedical subjects

Y Jo

Publications and source records attributed to Y Jo.

At least 19 recordsLinked to original sources
PubMed2006

Induction of steroidogenesis in immature rat Leydig cells by interleukin-1alpha is dependent on extracellular signal-regulated kinases.

Interleukin-1alpha (IL-1alpha) plays an important role in the regulation of immune responses as well as in non-inflammatory events in different types of cells. Here we have investigated the involvement of the extracellular signal-regulated kinase (ERK) cascade in IL-1alpha-induced steroidogenesis by primary cultures of immature rat Leydig cells. Our findings indicate that protein kinase C functions as an upstream component of signal transduction from the IL-1 receptor type I (IL-1RI) to the ERK cascade. It was observed that IL-1alpha upregulated both steroidogenic acute regulatory (StAR) protein expression and its phosphorylation when compared with controls. Selective inhibition of these mitogen-activated protein kinases (MAPKs) by UO126 enhanced both the expression and phosphorylation of the StAR protein, but suppressed androgen production by the immature Leydig cells as well as dissipating the mitochondrial electrochemical potential (Psim) in these cells. The evidence that water-soluble cholesterol but not 22R-hydroxycholesterol-stimulated steroidogenesis was inhibited by UO126 suggested that an intact Psim across the inner mitochondrial membrane is required for cholesterol translocation and is positively regulated by the ERK cascade. We propose that activation of ERKs by IL-1alpha plays a dual role in the regulation of steroidogenesis in immature Leydig cells: these MAPKs downregulate StAR expression and phosphorylation, while at the same time they support an intact Psim across the inner mitochondrial membrane, thereby promoting translocation of cholesterol into the mitochondria of the Leydig cell.

Animals↗
PubMed2005

Mucosal proinflammatory cytokine and chemokine expression of gastroduodenal lesions in Crohn's disease.

BACKGROUND: The stomach and the duodenum are frequent sites of involvement by diminutive lesions in Crohn's disease (CD). AIM: To assess mucosal proinflammatory cytokines and chemokines in gastroduodenal lesions of CD. METHODS: 13C-Urea breath test and upper endoscopy were performed in 29 CD patients and seven control subjects, and biopsy specimens were obtained from the gastric cardia and the duodenum. Histology and mucosal levels of IL-1beta, IL-8/CXCL8 and RANTES/CCL5 were assessed and compared according to the presence of gastric cardial lesion [bamboo joint-like appearance (BJA)] and duodenal lesion (notched appearance, aphthous erosion and polypoid lesion). In 11 CD patients, these procedures were repeatedly performed after administration of famotidine. RESULTS: H. pylori was less frequently positive in CD patients than in controls (10% vs. 71%, P = 0.003). Prevalence of cardial and duodenal lesion was significantly higher in CD than in controls (59% vs. 0%, P = 0.008 for gastric lesion; 45% vs. 0%, P = 0.034 for duodenal lesion). There were no differences in IL-1beta, IL-8 and RANTES between CD and controls. Duodenal mucosal IL-1beta and IL-8 were significantly higher in positive duodenal lesion than in negative duodenal lesion. However, there were no such differences with respect to cardial lesions. Endoscopic findings remained unchanged after administration of famotidine, while there was a trend towards decreases in IL-1beta and IL-8 in the gastric cardia. CONCLUSIONS: The pathogenesis of diminutive lesions of CD may be different between the stomach and the duodenum. Famotidine may not have a therapeutic effect on duodenal lesion in CD.

Adolescent↗
PubMed2004

Oxysterols regulate expression of the steroidogenic acute regulatory protein.

The steroidogenic acute regulatory (StAR) protein promotes intramitochondrial delivery of cholesterol to the cholesterol side-chain cleavage system, which catalyzes the first enzymatic step in all steroid synthesis. Intriguingly, substrate cholesterol derived from lipoprotein can upregulate StAR gene expression. Moreover, substrate oxysterols have been suggested to also play a role. To investigate whether oxysterols can regulate StAR expression, two steroidogenic cell lines, mouse Y1 adrenocortical and MA-10 Leydig tumor cells, were treated with various oxysterols and steroids, including 25-hydroxycholesterol (25 OHC), 22(R)OHC and 20alphaOHC. The majority of these compounds rapidly increased StAR protein levels within as little as 1 h. The most potent oxysterols were 20alphaOHC for Y1 and 25 OHC for MA-10 cells. After 8 h, StAR mRNA abundance also increased whereas there were no detected changes in promoter activity. Thus, in contrast to lipoprotein, oxysterols acutely increase StAR protein levels independently of mRNA abundance, and later increase mRNA levels independently of new gene transcription. Therefore, we propose that oxysterols modulate steroidogenesis at two levels. First, oxysterols may be important in post-transcriptional regulation of StAR activity and production of steroids for paracrine action. Secondly, through direct conversion to steroid, oxysterols may account in part for StAR-independent steroid production in the body.

Adrenal Cortex Neoplasms↗
PubMed2003

CCR4 is an up-regulated chemokine receptor of peripheral blood memory CD4+ T cells in Crohn's disease.

Several chemokine receptors are expressed selectively on the surface of T cells depending on their polarization. The aim of this study was to characterize chemokine receptor expression in peripheral blood memory T cells in Crohn's disease (CD) and ulcerative colitis (UC), and to correlate the expression with disease activity. Peripheral blood mononuclear cells (PBMCs) were obtained from 24 patients with CD, 30 patients with UC, 24 normal controls and 10 disease controls. PBMCs were stained by anti-CCR3, CCR4, CCR5, CXCR3, CD4, CD8, CD45RO and beta 7 integrin, and the expression of the chemokine receptors were determined by flow cytometry. CCR4 expression on memory T cells was significantly lower in UC than in CD or normal controls, and that of memory CD4+ T and beta 7(high) memory CD4+ T cells was significantly higher in CD than in UC or normal controls. CCR4 expression on memory CD4+ T cells exhibited significant positive correlation with disease activity in CD, and this decreased significantly after treatment. Such a decrease was not found in the disease controls. CCR5 and CXCR3 expression on memory CD8+ T cells was significantly lower in CD than in normal controls. CXCR3 expression on beta 7(high) memory CD4+ T and CXCR3 expression on memory CD8+ T cells were lower in UC than in normal controls. These findings suggest that in peripheral blood memory T cells, chemokine receptor expression is different between CD and UC. Enhancement of CCR4 and suppression of CCR5 and CXCR3 seem to be the characteristic chemokine receptor profile in peripheral blood memory T cells of CD.

Acute Disease↗
PubMed2003

Chromosomal translocation t(11;18)(q21;q21) in gastrointestinal mucosa associated lymphoid tissue lymphoma.

AIMS: To evaluate the chromosomal translocation t(11;18)(q21;q21) in gastrointestinal lymphomas. METHODS: A possible API2-MLT fusion transcript specific to t(11;18)(q21;q21) was examined by means of reverse transcription-polymerase chain reaction (RT-PCR) in tumours from 47 cases of primary gastrointestinal lymphoma (28 low grade mucosa associated lymphoid tissue (MALT) lymphomas, four low grade MALT lymphomas with a high grade component, nine secondary diffuse large B cell lymphomas, four primary diffuse large B cell lymphomas, and two T cell lymphomas). RESULTS: API2-MLT fusion was seen in four of 28 cases of low grade MALT lymphoma, but it was not seen in other types of lymphoma. Among the low grade MALT lymphomas, the fusion transcript was seen more frequently in colonic tumours than in gastric tumours (two of three compared with two of 24) and in tumours with submucosal invasion than in those confined to the mucosa (four of 13 compared with 0 of 15). Helicobacter pylori negative tumours tended to show a higher positive rate than H pylori positive tumours (three of six compared with one of 21). None of the gastric tumours that responded to H pylori eradication expressed the API2-MLT fusion transcript. CONCLUSIONS: t(11;18)(q21;q21) seems to be one of the genetic alterations related to the development of gastrointestinal low grade MALT lymphoma. Such translocations may be predominantly associated with the development of intestinal MALT lymphoma.

Adult↗
PubMed2003

Multiple microcarcinoids in a patient with long standing ulcerative colitis.

A male patient with a 17 year history of intractable ulcerative colitis of the entire type was treated by total proctocolectomy. Colonoscopy before surgery did not identify dysplasia. Histological examination of the resected colorectum revealed that, in addition to chronic inflammatory infiltrates, there were 21 areas of microcarcinoids located in the muscularis propria and in the superficial layer of the submucosa. Carcinoids may be more common than previously thought, and they may be a reactive phenomenon to a variety of factors in ulcerative colitis.

Adult↗
PubMed2001

Inhibition of Kv1.3 channels by H-89 (N--[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide) independent of protein kinase A.

The effects of H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide), a potent and selective inhibitor of protein kinase A (PKA), were examined on Kv1.3 channels stably expressed in Chinese hamster ovary (CHO) cells using the patch clamp technique. In whole-cell recordings, H-89 decreased Kv1.3 currents and accelerated the decay rate of current inactivation in a concentration-dependent manner with an IC(50) value of 1.70 microM. These effects were completely reversible after washout. Intracellular infusion with PKA inhibitors, adenosine 3', 5'-cyclic phosphorothioate-Rp (Rp-cAMPS) or protein kinase A inhibitor 5-24 (PKI 5-24) had no effect on Kv1.3 currents and did not prevent the inhibitory action of H-89 on the current. H-89 applied to the cytoplasmic surface also inhibited Kv1.3 currents in excised inside-out patches. These findings suggest that H-89 inhibits Kv1.3 currents independently of PKA.

Animals↗
PubMed2001

Biochemical markers for the detection of bone metastasis in patients with prostate cancer: diagnostic efficacy and the effect of hormonal therapy.

In the present study, we investigated the diagnostic effectiveness of biochemical markers of bone turnover for the detection of bone metastasis from prostate cancer and changes in the levels of these markers caused by hormonal therapy. Ninety-five patients with prostate cancer were divided into one of three groups: 26 patients with bone metastasis (BM(+)), 35 patients without bone metastasis on nonhormonal therapy (BM(-)HT(-)) and 34 patients without bone metastasis on hormonal therapy (BM(-)HT(+)). All patients in the BM(+) group had received hormonal therapy. Serum or urinary levels of the following biochemical markers of bone turnover were examined: bone-specific alkaline phosphatase (B-ALP), osteocalcin (OC), type I procoIlagen C-propeptide (PICP), type I collagen cross-linked C-telopeptide (ICTP), C-telopeptide fragment (CTx), N-telopeptide fragment (NTx), total pyridinoline (T-Pyr), total deoxypyridinoline (T-D-Pyr) and free deoxypyridinoline (F-D-Pyr). The BM(+) group showed significantly higher values than the BM(-)HT(-) group for B-ALP, PICP, NTx, CTx, T-Pyr, T-D-Pyr, and F-D-Pyr. Compared with the BM(-)HT(+) group, the BM(-) group showed significantly higher values for B-ALP, ICTP, NTx, T-Pyr and T-D-Pyr. The levels of B-ALP, NTx, CTx, T-D-Pyr and F-D-Pyr were significantly different between the BM(-)HT(-) and BM(-)HT(+) groups. All markers, except OC and CTx, significantly were correlated with the extent of bone metastasis on bone scintigraphy. Of all markers, receiver operating characteristic (ROC) analyses revealed B-ALP and F-D-Pyr to be the most sensitive and specific for differentiation between the BM(+) and BM(-)HT(-) groups with regard to bone formation and resorption. respectively. In contrast, B-ALP and ICTP were most sensitive and specific for differentiation between the BM(+) and BM(-)HT(+) groups. The results suggest that hormonal therapy greatly affects the efficacy of PICP, CTx and F-D-Pyr in the diagnosis of bone metastasis, whereas its effects on ICTP are small. Although bone metabolic markers would be useful in the diagnosis of bone metastasis from prostate cancer, the effects of hormonal therapy on bone metabolism should be kept in mind in their evaluation.

Aged↗
PubMed2001

Prognostic factors for survival and bladder recurrence in transitional cell carcinoma of the upper urinary tract.

BACKGROUND: Prognostic factors for survival in transitional cell carcinoma of the upper urinary tract have been extensively evaluated, but detailed analyses of patterns of bladder recurrence after surgery have been rare. METHODS: The outcome and tumor recurrence of 93 patients with transitional cell carcinoma of the upper urinary tract surgically treated between 1975 and 1999 were reviewed, retrospectively. Disease-specific survival by pathologic stage and grade were analyzed by the Kaplan-Meier METHOD: Prognostic factors for survival and bladder recurrence were examined by univariate and multivariate analysis. RESULTS: The 5-year disease-specific survival rates of the patients with pTa, T1 and T2 were 92.9%, 100% and 88.9%, respectively. However, that of the pT3 patients was 61.9% and the median survival of the pT4 cases was only 7 months. Bladder recurrence was seen in 40 cases and recurrences occurred within 1 year in 32 of these patients. The stage and grade of metachronous bladder tumors usually resembled those of primary tumors, but invasive recurrences were seen in 19% of recurrent cases with primary pTa, pT1 tumors. The significant prognostic factor for survival was pathologic stage (pT3, pT4), but no significant variables were detected for bladder recurrence by multivariate analysis. CONCLUSIONS: The prognosis of pT3, pT4 patients is poor and effective systemic adjuvant therapy is necessary. Invasive bladder recurrence occurred in 19% of patients with superficial primary tumors. As no significant prognostic variables for bladder recurrence were identified, careful follow up for bladder recurrence is important even if the primary tumors are non-invasive.

Administration, Intravesical↗
PubMed2000

Immunohistochemical localization of phospholipase D1 in rat central nervous system.

Phospholipase D (PLD) is one of the intracellular signal transduction enzymes and plays an important role in a variety of cellular functions. We investigated the distribution of PLD isozyme, PLD1 in the rat brain and spinal cord using an immunological approach. Western blot analysis showed the presence of PLD1 protein in all tissues studied, with significantly higher levels in the brainstem and spinal cord, which was correlated with the results obtained from PLD activity assay. Prominent and specific signals of PLD1 were observed in many functionally diverse brain areas, including the olfactory bulb, medial septum-diagonal band complex, cerebral cortex, brainstem, cerebellum, and spinal cord. In the brainstem, the red nucleus, substantia nigra, interpeduncular nucleus, cranial motor nuclei (trigeminal motor, abducent, facial, and hypoglossal), sensory cranial nerve nuclei (spinal trigeminal, vestibular, and cochlear), as well as nuclei of the reticular formation, all showed intense immunoreactivity. Purkinje cells and deep cerebellar nuclei of the cerebellum were also labeled intensely. However, no significant labeling was found in the thalamus, epithalamus, and basal ganglia. Although many of the PLD1 immunoreactive cells were neurons, PLD1 was also expressed in glial cells such as presumed astrocytes and tanycytes. These findings suggest that PLD1 may play an important role in the central nervous system of the adult rat.

Animals↗
PubMed2000

Analysis of tissue inhibitor of metalloproteinases-2 effect on pro-matrix metalloproteinase-2 activation by membrane-type 1 matrix metalloproteinase using baculovirus/insect-cell expression system.

Membrane-type 1 matrix metalloproteinase (MT1-MMP; MMP14) is known to activate pro-matrix metalloproteinase-2 (pro-MMP-2; progelatinase A) on the cell surface. To analyse the tissue inhibitor of metalloproteinases-2 (TIMP-2) effect on activation of pro-MMP-2 by MT1-MMP, we have expressed the full-size MT1-MMP (fMT1-MMP) and a transmembrane (TM)-domain-deleted soluble MT1-MMP (sMT1-MMP) in the baculovirus/Sf9 (Spodoptera frugiperda 9) insect-cell system, where neither endogenous gelatinolytic MMPs nor TIMP-2 are expressed. Both fMT1-MMP and sMT1-MMP expressed in the expression system were found not to contain the pro-domain and were able to activate the TIMP-2-free pro-MMP-2. Both in the insect cells and in vitro, activation of pro-MMP-2 by fMT1-MMP was enhanced at low concentrations of TIMP-2 and inhibited by its higher concentrations. The maximal enhancing effect was detected at 0.05 molar fraction of TIMP-2/fMT1-MMP. In contrast, activation of pro-MMP-2 by sMT1-MMP was dose-dependently inhibited by TIMP-2. These results demonstrate that the TM domain of MT1-MMP is not required for the ability to activate pro-MMP-2, but is required for the enhancing effect of TIMP-2 on pro-MMP-2 activation by recruiting pro-MMP-2 to the MT1-MMP-TIMP-2 complex as a cell-surface pro-MMP-2 receptor. Moreover, our data strongly suggest that the pro-domain of MT1-MMP is not required for the TIMP-2-mediated enhancing effect on pro-MMP-2 activation. In addition, the pro-MMP-2 in the MT1-MMP-TIMP-2-pro-MMP-2 ternary complex was not activated without external activator, but readily by addition of sMT1-MMP. This result demonstrates that MT1-MMP free of TIMP-2 would be the enzyme responsible for activation of the pro-MMP-2 in the ternary complex under physiological conditions.

Animals↗
PubMed2000

Preclinical Cushing's syndrome: report of seven cases and a review of the literature.

BACKGROUND: Adrenal adenomas showing autonomous cortisol secretion without specific endocrine symptoms are sometimes discovered in patients with adrenal incidentalomas. This entity has been described as subclinical or preclinical Cushing's syndrome (PCS), but the endocrine data of reported cases have varied and the diagnostic criteria of PCS have been uncertain. METHODS: We report seven Japanese cases of PCS due to a unilateral, solitary adrenal adenoma with examination of the endocrine data of these patients. The diagnostic parameters of subtle hypercortisolism and the risk of postoperative adrenal insufficiency and surgical indications are discussed and reviewed. RESULTS: In the present cases, the most frequently found biochemical parameters of autonomous cortisol secretion were a low adrenocorticotropic hormone (ACTH) level (100%) and insufficient suppression of cortisol by low-dose dexamethasone (85.7%). Unilateral accumulation of radiopharmaceuticals in tumors was also frequently observed (100%). A postoperative hydrocortisone supplement was given to six of the seven patients for 5-122 days. It was not given to case 4, because a moderate response of 11-deoxycortisol to metyrapone was identified. Plasma ACTH levels and the diurnal rhythm of plasma cortisol rapidly recovered within 3 weeks postoperatively in six of the seven cases. CONCLUSION: This entity is heterogeneous and various degrees of cortisol excess have been observed. It should be diagnosed in the wide spectrum and the risk of adrenal insufficiency after surgery should be evaluated by dynamic tests such as the corticotropin-releasing hormone (CRH) test. Based on the results of the present study and a review of the literature, PCS patients may not require hydrocortisone supplement therapy for a long period.

Aged↗
PubMed2000

[Familial isolated hyperparathyroidism: a report of two cases].

A family (a brother and a sister) of the familidal isolated hyperparathyroidism (FIH) was reported. The older brother with age of 58 year-old was pointed out hypercalcemic while examining his hypertension and proteinuria. He had high levels of serum total and ionized calcium, intact-PTH and gastrin, and hypophosphatemia. His neck CT scan revealed swelling of the two parathyroid glands in each side. He underwent resection of the tumors and the auto-implantation of the glands under diagnosis of primary hyper parathyroidism. Histopathology was diagnosed to be hyperplasia of the parathyroid glands. The younger sister with age of 52 year-old was referred to our clinic because she was suffering from recurrent urolithiasis. Biochemical examination of her blood sampling resulted in very resemble values of her brother mentioned above. Her neck CT scan showed three tumors consisting of each one at the bilateral parathyroid glands and one in the thymic region. She underwent resection of the tumors and the auto-implantation of the glands and histopathological diagnosis was hyperplasia as same as her brother's one. The postoperative courses of these cases have been uneventful for four years. FIH is a low significant disease of which ten lineages have been reported in Japanese literature although it should be differentiate with such a disease of multiple endocrine neoplasms.

Biomarkers↗
PubMed2000

[Clinical evaluation of low dose glucocorticoid therapy for hormone-refractory prostate cancer].

Fifteen cases with hormone-refractory metastatic carcinoma of the prostate were treated by the combination therapy of LH-RH analogue and low-dose glucocorticoid. Prior treatments of the patients were composed of maximum androgen blockade (MAB) therapy (14 cases) and bilateral orichiectomy (1 case). Nine of 15 cases underwent estramustine based treatment or anti-cancer chemotherapy as the second-line therapy. As a glucocorticoid (steroid) therapy, 1.5 or 2.0 mg of dexamethasone or 10 mg of predonisolone were given for a median period of nine months. Clinical responses were evaluated by the determination of serum PSA, EOD score and QOL scales. PSA responses were classified as CR, PR and PD according to the following categories; CR : PSA level decreased to less than 2 ng/ml, PR : PSA level decreased to less than half values of pretreatment level, PD: 20% or more increased to pretreatment level. PSA responses (CR + PR) were observed in eight of 15 patients for a median period of six months. Responses are seemed to be correlated with the Gleason scores. No apparent improvement on EOD scores by bone scintigraphy was seen, however, definite improvement of bone pain was identified in eight of 11 cases. The steroid therapy was considered as one of the useful treatment choice for patients with hormone-refractory prostate cancer.

Aged↗