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Biomedical subjects

C Shimizu

Publications and source records attributed to C Shimizu.

At least 19 recordsLinked to original sources
PubMed2006

Solvent effect on intramolecular electron transfer rates of mixed-valence biferrocene monocation derivatives.

Intramolecular electron transfer (ET) rates in various solvents of mixed-valence biferrocene monocation (Fe(II), Fe(III)) and the 1',1' ''-diiodo and 1',1' ''-diethyl derivatives (respectively abbreviated as BFC(+), I(2)BFC(+), and Et(2)BFC(+)) were determined by means of the spin-lattice relaxation times of the protons, taking into account the local magnetic field fluctuation caused by the electron hopping between the two ferrocene units. We also determined the ET rates of a mixed-valence diferrocenylacetylene monocation (DFA(+)) in order to examine the effect of the insertion of an acetylene bridge between the two ferrocene units. The insertion of the bridge decreased the ET rate, while the effect of substitution on the cyclopentadienyl rings on the rate was minor. The observed rates for each mixed-valence monocation in various solvents did not correlate with the reorganization energies, but we did find a significant contribution of the solvent dynamics. The observed rates were considerably higher than those expected on the basis of the Sumi-Marcus-Nalder model in which the solvents were regarded as dielectric continua. The slope of the logarithm plot of the pre-exponential factors in various solvents for each mixed-valence monocation versus the inverse of the longitudinal dielectric relaxation times of the solvents was significantly smaller than unity, and the slope for DFA(+) was larger than those for BFC(+), I(2)BFC(+), and Et(2)BFC(+). These results were ascribed to a partial contribution of the dielectric friction to the dynamics along the solvent coordinate; the extent of the contribution decreased with a reduction in the ET distance. For the dynamics along the solvent coordinate of the ET reactions in methanol, the observed rates indicated an important contribution by the minor dielectric relaxation components with faster relaxation times, rather than the major component with an extraordinarily long relaxation time.

Journal Article↗
PubMed2006

A case of reversed pituitary dysfunction with intrasellar mass.

Hypopituitarism can be caused by tumor, inflammation, granuloma and injuries. Once pituitary function is disturbed, hormone replacement therapy is necessary for the remaining life span in most cases. We have experienced a rare case of a unique intrasellar mass associated with pituitary dysfunction in which both spontaneously reversed. A 61-yr-old woman developed hypoadrenalism and central diabetes insipidus (cDI). Magnetic resonance (MR) imaging revealed a lobular, strong hypointense lesion with spotty signal in the middle of the hypophysis. This spotty lesion showed isointensity on T1- and high-intensity on T2-weighted MR images. The spotty signal as well as the normal pituitary lobe were enhanced by the administration of gadolinium. As replacement therapies for hypoadrenalism and cDI, 10 mg of hydrocortisone and 2.5 microg of desmopressin acetate were prescribed. Three months later, slight shrinkage of intrasellar mass and spontaneous improvement of pituitary functions were found. Hydrocortisone was then discontinued. Furthermore, because polyuria and polydipsia were improved nine months later, desmopressin acetate was stopped. Currently, the intrasellar mass continues to shrink, and the patient shows no symptoms without medication. Based upon the unique features of MR images, we suspect that the origin of the mass is an intrasellar hemangioma.

Diabetes Insipidus, Neurogenic↗
PubMed2005

A rare case of Gitelman's syndrome presenting with hypocalcemia and osteopenia.

Gitelman's syndrome (GS), an autosomal recessive disorder caused by a defect of the thiazide-sensitive Na-Cl cotransporter (TSC) at the distal tubule, is characterized by hyperreninemic hyperaldosteronism with normal or low blood pressure, hypokalemia, metabolic alkalosis, hypomagnesemia and hypocalciuria. An 18-yr-old Japanese man was admitted to our hospital with a history of muscle weakness and transient tetanic episodes. He showed hypocalcemia in addition to hypokalemia, severe hypomagnesemia, hypocalciuria and hyperreninemic hyperaldosteronism with normal blood pressure. Furthermore, bone mineral density at the lumbar spine revealed osteopenia. A diagnosis of GS was made on the basis of clinical features, laboratory data and renal function test. The electrolyte imbalance was corrected and bone mineral density was slightly increased with chronic treatment of magnesium and potassium salts. Genetic analysis revealed that TSC gene of the patient has a heterozygous C to A nucleotide substitution at position 545 in exon 4, which causes a threonine (Thr) to lysine (Lys) substitution at position 180. This is a rare case of GS with hypocalcemia and osteopenia which could be caused by severe hypomagnesemia.

Adolescent↗
PubMed2005

Family-based association analysis implicates IL-4 in susceptibility to Kawasaki disease.

Several compelling lines of evidence suggest an important influence of genetic variation in susceptibility to Kawasaki disease (KD), an acute vasculitis that causes coronary artery aneurysms in children. We performed a family-based genotyping study to test for association between KD and 58 genes involved in cardiovascular disease and inflammation. By analysis of a cohort of 209 KD trios using the transmission disequilibrium test, we documented the asymmetric transmission of five alleles including the interleukin-4 (IL-4) C(-589)T allele (P=0.03). Asymmetric transmission of the IL-4 C(-589)T was replicated in a second, independent cohort of 60 trios (P=0.05, combined P=0.002). Haplotypes of alleles in IL-4, colony-stimulating factor 2 (CSF2), IL-13, and transcription factor 7 (TCF7), all located in the interleukin gene cluster on 5q31, were also asymmetrically transmitted. The reported associations of KD with atopic dermatitis and allergy, elevated serum IgE levels, eosinophilia, and increased circulating numbers of monocyte/macrophages expressing the low-affinity IgE receptor (FCepsilonR2) may be related to effects of IL-4. Thus, the largest family-based genotyping study of KD patients to date suggests that genetic variation in the IL-4 gene, or regions linked to IL-4, plays an important role in KD pathogenesis and disease susceptibility.

Child↗
PubMed2004

Effects of hypophysectomy and in vivo administration of ACTH or dexamethasone on the level of ACTH receptor mRNA in adrenal glands and adipose tissues of mice.

OBJECTIVE: In rodents, ACTH induces steroidogenesis in the adrenal cortex and also lipolysis in adipose tissues via the sole specific receptor for ACTH. Up-regulation of the ACTH receptor (ACTH-R) mRNA by ACTH was found to be evident in adrenocortical cells. However, a role of in vivo ACTH on ACTH-R mRNA expression in the adrenal cortex is not well understood. In addition, so far less attention has been also paid to the regulation of ACTH-R expression in adipose tissues. We investigated the effects of hypophysectomy and in vivo administration of ACTH or dexamethasone on the level of ACTH-R mRNA in the adrenal gland and adipose tissues of mice. METHODS: ACTH mRNA in the adrenal glands and epididymal adipose tissues of mice sacrificed 10 days after hypophysectomy or sham operation, and 24 hours after ACTH-Z (2 IU i.m.) or physiological saline solution (PSS) injection, and also 3-days after dexamethasone (300 microg/day i.m.) or PSS administration was analysed by Northern blot, and intensities of autoradiographic bands were quantified. RESULTS: In the adrenal gland, in vivo administration of ACTH-Z significantly increased the level of ACTH-R mRNA to 342% of control values, but in vivo administration of dexamethasone or hypophysectomy induced no significant alteration of ACTH-R mRNA. In adipose tissues, these conditions did not significantly alter the level of ACTH-R mRNA. CONCLUSION: Low circulating ACTH may not be a substantial factor for ACTH-R gene expression in the adrenal gland, but a high level of in vivo ACTH dose up-regulated the expression. A different regulation of ACTH-R gene expression exists in the adrenal cortex and adipose tissues of mice.

Adipose Tissue↗
PubMed2001

Transcriptional regulation of human 3'-phosphoadenosine 5'-phosphosulfate synthase 1.

Sulfonation, which is essential for normal growth, development and maintenance of the internal milieu, requires the universal sulfonate donor molecule 3'-phosphoadenosine 5'-phosphosulfate (PAPS) produced from ATP and inorganic sulfate by two bifunctional PAPS synthase isozymes. The gene for PAPS synthase 1 containing neither a TATA nor a CCAAT box was found to be under the influence of the Sp1 family of transcription factors. Multiple GC/GT boxes are present in the proximal promoter region and deletion analysis implicated their involvement in transcription, a finding supported by mutational analysis of specific GC/GT boxes. Nuclear extract of SW13 cells, which highly express PAPS synthase 1, contains proteins that bind to probes possessing specific GC/GT boxes; furthermore, the presence of Sp1, Sp2, and Sp3 proteins in nuclear extracts was confirmed by supershift analysis. Cotransfection experiments using SL2 cells yielded additional support for the involvement of Sp1 in transcriptional regulation of the PAPS synthase 1 gene; the involvement of Sp2 and/or Sp3 is presently unclear.

Animals↗
PubMed2001

Inhibition of tumor metastasis by adoptive transfer of IL-12-activated Valpha14 NKT cells.

A unique lymphocyte lineage, the Valpha14 NKT cells, expresses both NK1.1 and an invariant antigen receptor encoded by Valpha14 and Jalpha281 gene segments. Valpha14 NKT cells play crucial roles in various immune responses, including autoimmune diseases, allergic reactions and anti-tumor immunity. Valpha14 NKT cells were demonstrated to be essential for anti-tumor effect of IL-12 in vivo. Here, we report that adoptive transfer of IL-12-activated Valpha14 NKT cells prevents hepatic metastasis of B16 melanoma. The injection of large amounts of IL-2, IL-4, and IFN-gamma, which are cytokines produced by activated Valpha14 NKT cells, exhibited no significant inhibition of the metastasis of this melanoma. The cells prepared from the liver of IL-12-injected mice expressed a potent cytotoxic activity on B16 melanoma cells in vitro. Although the adoptive transfer of IL-12-activated Valpha14 NKT cells prevents hepatic metastasis of B16 melanoma, activated NK cells from IL-12-injected RAG-1-/- mice failed to inhibit the metastasis of this melanoma. Thus, the anti-tumor effect of IL-12 can be replaced by adoptive transfer of IL-12-activated Valpha14 NKT cells but not by IL-12-activated NK cells, suggesting a minor role of NK cells for the IL-12-mediated anti-tumor effect in this experimental system. Moreover, our studies have suggested the involvement of direct cytotoxic mechanisms rather than cytokine-mediated immune responses at the effector phase of the Valpha14 NKT cell-mediated anti-tumor activity.

Adoptive Transfer↗
PubMed2001

Differences in estrogen receptor status, HER2, and p53 comparing metachronous bilateral breast carcinoma.

BACKGROUND AND OBJECTIVES: We analyzed the clinicopathologic characteristics and tumor biology of metachronous bilateral breast carcinoma with regard to p53, HER2 and hormone receptor status. METHODS: A consecutive series of 54 female metachronous bilateral breast carcinoma patients treated at the National Cancer Center Hospital between 1980 and 1997 were the primary source of these retrospective data. Clinicopathologic background factors were analyzed, and immunohistochemical staining for p53, HER2, and hormone receptor status was carried out on paraffin-embedded specimens. RESULTS: There were no significant differences in clinical stage, p53 and HER2 expression levels between the first and second primary tumors. The positive rates for ER and PR were 48% (25 of 52) and 46% (25 of 54) for the first tumors, but only 19% (10 of 52) and 32% (17 of 54) for the second tumors (P = 0.004 for ER, P = 0.16 for PR), showing a significant loss of ER. CONCLUSIONS: Our findings indicate that p53 and HER2 expression levels in the second tumors might be the same as those of the first tumors in metachronous bilateral breast carcinoma; however, loss of ER was more frequently observed in the second primary tumors than in the first tumors.

Adult↗
PubMed2001

Hemolymph analysis and evaluation of newly formulated media for culture of shrimp cells (Penaeus stylirostris).

Creation of a shrimp cell line has been an elusive goal. This failure may be due to the composition of the cell culture medium, which may be inadequate to support primary cultured cells. Shrimp hemolymph should contain the nutritional components needed to support cell growth and division. We report here the comprehensive biochemical analysis of hemolymph from the blue shrimp, Penaeus stylirostris (Litopenaeus stylirostris) (see Holthuis, L. B. Shrimps and prawns of the world, in: FAO species catalog. Vol. 1. Rome: Food and Agriculture Organization of the United Nations; 1980), for free amino acids (FAAs), carbohydrates, electrolytes, metals, pH, and osmolality. Levels of hemolymph components were compared to 2xL-15 with 20% fetal bovine serum, a commonly used culture medium for crustacean cells. The FAAs, taurine and proline, and the metals, strontium and zinc, were significantly higher in hemolymph than in the 2 x L-15 medium. In contrast, other FAAs were up to 50 times higher in the 2 x L-15 medium than in the hemolymph. To mimic more closely the hemolymph composition, we created two new media based on either the 0.2 x L-15 or the M199 medium. We compared the microscopic appearance of cells cultured in these media and evaluated deoxyribonucleic acid (DNA) and protein synthesis by 3H-thymidine uptake and 35S-methionine uptake assays. The ovary cells of P. stylirostris cultured in either of the new media formed monolayers, while the cells cultured in 2 x L-15 medium did not. Despite these differences, there was no evidence of sustained DNA or protein synthesis with any of the media. Future studies to establish a shrimp cell line should focus on analysis of the cell cycle and on overcoming the molecular blocks to cell division.

Animals↗
PubMed2001

Multicentricity and histopathological background features of familial breast cancers stratified by menopausal status.

BACKGROUND: We investigated histopathological background and multicentricity in patients with familial breast cancers (FBCs) in comparison with these features in patients with sporadic breast cancers (SBCs), stratifying patients by menopausal status. METHODS: We collected a consecutive series of 469 FBC patients and 3334 SBC patients treated at our hospital between 1965 and 1995. The following criteria were used to define FBC, regardless of the presence or absence of a family history of other cancer or the patient's past history of malignancies: (1) Three or more second-degree relatives had been affected by breast cancer; (2) two first-degree relatives had been affected by breast cancer, and either one of them was under 40 years of age and/or had had bilateral breast cancers. The presence or absence of background proliferative lesions (PL; ductal/lobular hyperplasia and/or adenosis) and the multicentricity of breast carcinomas in FBCs and SBCs were analyzed for each group. RESULTS: In premenopausal FBC patients, there was a non-significant trend towards a high frequency of multicentricity compared with findings in patients with SBCs overall (P = 0.087; odds ratio [OR], 1.43; 95% confidence interval [CI], 0.96-2.13). In premenopausal FBC patients, the frequency of background proliferative lesions with/or without fibroadenomas (FA) in the resected specimen was significantly higher than that in SBC patients overall (P = 0.001 for PL; OR, 1.47; 95% CI, 1.18-1.83; P < 0.001 for PL +/- FA; OR, 6.84; 95% CI, 4.93-9.49). With regard to the other clinicopathological factors examined, there were no significant differences between the two groups, except for the higher frequency of premenopausal patients among the FBC patients. CONCLUSION: These results indicate that premenopausal patients with FBCs had more proliferative lesions in the histopathological background and more multicentric breast cancers than premenopausal patients with SBCs.

Adult↗
PubMed2001

Regulation of Th2 cell differentiation by mel-18, a mammalian polycomb group gene.

Polycomb group (PcG) gene products regulate homeobox gene expression in Drosophila and vertebrates and also cell cycle progression of immature lymphocytes. In a gene-disrupted mouse for polycomb group gene mel-18, mature peripheral T cells exhibited normal anti-TCR-induced proliferation; however, the production of Th2 cytokines (IL-4, IL-5, and IL-13) was significantly reduced, whereas production of IFNgamma was modestly enhanced. Th2 cell differentiation was impaired, and the defect was associated with decreased levels in demethylation of the IL-4 gene. Significantly, reduced GATA3 induction was demonstrated. In vivo antigen-induced IgG1 production and Nippostrongylus brasiliensis-induced eosinophilia were significantly affected, reflecting the deficit in Th2 cell differentiation. Thus, the PcG gene products play a critical role in the control of Th2 cell differentiation and Th2-dependent immune responses.

Animals↗
PubMed2001

Interleukin-6 (IL-6) producing phaeochromocytoma: direct IL-6 suppression by non-steroidal anti-inflammatory drugs.

A 35-year-old Japanese woman presented with a phaeochromocytoma and demonstrated marked inflammatory reactions and pyrexia as a result of excessive production of interleukin-6 (IL-6) by the tumour. Serum IL-6 level was 262 ng/l (normal; < 4.0 ng/l). Fever and inflammatory markers were largely overcome by the administration of the nonsteroidal anti-inflammatory drug, naproxen, and all symptoms disappeared soon after the tumour was excised. Immunohistochemical study revealed positive staining using an antihuman IL-6 antibody and Northern analysis showed increased IL-6 mRNA levels in the tumour. Cultured tumour cells showed IL-6 protein synthesis, and nonsteroidal anti-inflammatory drugs such as naproxen and indomethacin directly inhibited IL-6 release. These results indicate that the effects of naproxen in vivo were due, at least in part, to direct suppression of IL-6 secretion from the tumour.

Adrenal Gland Neoplasms↗
PubMed2001

Progression of T cell lineage restriction in the earliest subpopulation of murine adult thymus visualized by the expression of lck proximal promoter activity.

The proximal promoter of lck directs gene expression exclusively in T cells. To investigate the developmental regulation of the lck proximal promoter activity and its relationship to T cell lineage commitment, a green fluorescence protein (GFP) transgenic (Tg) mouse in which the GFP expression is under the control of the proximal promoter of lck was created. In the adult GFP-Tg mice, >90% of CD4(+)CD8(+) and CD4(+)CD8(-) thymocytes, and the majority of CD4(-)CD8(+) and CD4(-)CD8(-) [double-negative (DN)] thymocytes were highly positive for GFP. Slightly lower but substantial levels of expression of GFP was also observed in mature splenic T cells. No GFP(+) cells was detected in non-T lineage subsets, including mature and immature B cells, CD5(+) B cells, and NK cells, indicating a preserved tissue specificity of the promoter. The earliest GFP(+) cells detected were found in the CD44(+)CD25(-) DN thymocyte subpopulation. The developmental potential of GFP(-) and GFP(+) cells in the CD44(+)CD25(-) DN fraction was examined using in vitro culture systems. The generation of substantial numbers of alphabeta and gammadelta T cells as well as NK cells was demonstrated from both GFP(-) and GFP(+) cells. However, no development of B cells or dendritic cells was detected from GFP(+) CD44(+)CD25(-) DN thymocytes. These results suggest that the progenitors expressing lck proximal promoter activity in the CD44(+)CD25(-) DN thymocyte subset have lost most of the progenitor potential for the B and dendritic cell lineage. Thus, progression of T cell lineage restriction in the earliest thymic population can be visualized by lck proximal promoter activity, suggesting a potential role of Lck in the T cell lineage commitment.

Animals↗
PubMed2001

Acute hepatitis C among Japanese hemodialysis patients: a prospective 9-year study.

OBJECTIVES: The aims of this prospective survey were to determine the incidence and clinical characteristics of newly acquired hepatitis C virus (HCV) infection in hemodialysis patients after the start of antibody to HCV (anti-HCV) screening for blood products in Japan in 1989. METHODS: In serial serum samples from 269 hemodialysis patients who were followed over a mean period of 6.6 yr (+/- 2.1 yr) from 1990 to 1998, HCV RNA and anti-HCV were detected by reverse transcription-polymerase chain reaction and second generation ELISA, respectively. RESULTS: During the observation period, newly acquired HCV infection was found in 26 (15.4%) of the 169 hemodialysis patients without anti-HCV or HCV RNA at entry, an annual incidence rate of 2.59%. Of these 26, only four had a history of blood transfusion, one of whom had received the blood transfusion after 1992, the year in which screening of blood products for anti-HCV by second-generation ELISA was introduced in Japan. Persistent HCV viremia was found in 17 (65.4%) of the 26 patients; the other nine (34.6%) had transient HCV infection. The mean period of continuous ALT abnormality was significantly longer in the former (12.4+/-13.6 months) than in the latter (1.9+/-3.5 months) (p = 0.0067). However, only three (17.6%) of 17 patients with chronic HCV viremia had continuous ALT abnormality for more than 24 months; in all of them, ALT eventually normalized. CONCLUSIONS: These findings indicate that newly acquired HCV infection has continued to occur in hemodialysis patients after the initiation of anti-HCV screening of blood products and that the abnormal ALT found in these patients is related to HCV chronicity.

Acute Disease↗
PubMed2001

Cholesterol and hydroxycholesterol sulfotransferases: identification, distinction from dehydroepiandrosterone sulfotransferase, and differential tissue expression.

In humans, the biotransformation of cholesterol and its hydroxylated metabolites (oxysterols) by sulfonation is a fundamental process of great importance. Nevertheless, the sulfotransferase enzyme(s) that carries out this function has never been clearly identified. Cholesterol is a relatively poor substrate for the previously cloned hydroxysteroid sulfotransferase (HST), i.e. dehydroepiandrosterone (DHEA) sulfotransferase (HST1). Recently, cloning of a single human gene that encodes for two proteins related to HST1 was reported. These newly cloned sulfotransferases (HST2a and HST2b), while exhibiting sequence similarity to other members of the soluble sulfotransferase superfamily, also contain unique structural features. This latter aspect prompted an examination of their substrate specificity for comparison with HST1. Thus, HST1, HST2a, and HST2b were overexpressed as fusion proteins and purified. Furthermore, a novel procedure for the isolation of cholesterol and oxysterol sulfonates was developed that was used in association with HPLC to resolve specific sterol sulfonates. HST1 preferentially sulfonated DHEA and, to a lesser extent, oxysterols; whereas cholesterol was a negligible substrate. The reverse, however, was the case for the HST2 isoforms, particularly HST2b, which preferentially sulfonated cholesterol and oxysterols, in contrast to DHEA, which served as a poor substrate for this enzyme. RT-PCR analysis revealed distinct patterns of HST1, HST2a, and HST2b expression. It was particularly notable that both HST2 isoforms, but not HST1, were expressed in skin, a tissue where cholesterol sulfonation plays an important role in normal development of the skin barrier. In conclusion, substrate specificity and tissue distribution studies strongly suggest that HST2a and HST2b, in contrast to HST1, represent normal human cholesterol and oxysterol sulfotransferases. Furthermore, this study represents the first example of the sulfonation of oxysterols by a specific human HST.

Amino Acid Sequence↗
PubMed2001

Involvement of the cholinergic pathway in the pathogenesis of pituitary Cushing's syndrome.

Transsphenoidal adenomectomy is currently the first choice for treatment of patients with pituitary ACTH-dependent Cushing's syndrome. However, pharmacotherapy is prescribed for some patients, e.g., unsuccessful surgery. We treated a woman in whom pituitary Cushing's syndrome was improved while she was on antimuscarinic cholinergic agents, atropine sulphate and pirenzepine hydrochloride. The diminished effect of anticholinergics on ACTH and cortisol was incidentally identified in an inferior petrosal sinus sampling procedure. A single intramuscular injection of atropine significantly decreased both ACTH (43.9 pg/ml to less than 12.0; normal, 12.0-40.0 pg/ml) and cortisol (29.9 microg/dl to 13.6; normal, 7.6-23.6 microg/dl). An M1-muscarinic receptor specific antagonist, pirenzepine hydrochloride, also had a diminishing effect on these hormones and this inhibiting effect was partially blocked by the simultaneous administration of an anticholinesterase agent, pyridostigmine bromide. Chronic oral ingestion of these agents led to improvement in clinical symptoms, and urinary 17-hydroxycorticosteroid and 17-ketosteroid levels were at normal to upper-normal levels. This is the first documentation of involvement of the cholinergic system in the pathogenesis of pituitary Cushing's syndrome.

17-Hydroxycorticosteroids↗