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Biomedical subjects

H Miyake

Publications and source records attributed to H Miyake.

At least 145 records · Page 8Linked to original sources

Relationship between suicide and holidays.

Employing the vital statistics from January 1, 1979 to December 31, 1994 in Hokkaido Prefecture, Japan, we investigated the relationship between suicide (ICD 9 code, El15) and days of the week. In one day 1.97 males and 0.98 females committed suicide on average. On Saturdays the number of suicides per day was the smallest. On Mondays it was the highest. When the days were classified into (1) a holiday, (2) the day before a holiday, (3) the day after a holiday (4) the day both before and after a holiday and (5) others, the rate of suicide was the lowest in the days before a holiday. In the days after a holiday, however, the rate was the highest. The same tendency was also noted when the subjects were classified into several subgroups from the viewpoint of ages, seasons or calendar years. The time relation of holidays seemed to have something to do with the intention to commit suicide.

Chi-Square Distribution↗

New concept for the pressure setting of a programmable pressure valve and measurement of in vivo shunt flow performed using a microflowmeter. Technical note.

The aim of this study was to establish a standard method for determining the pressure setting of the Codman Hakim valve (CHV) in patients with hydrocephalus. The authors' investigation was twofold. It focused on: 1) the relationships among CHV setting, intracranial pressure (ICP), intraabdominal pressure (IAP), hydrostatic pressure (HP), and perfusion pressure (PP); and 2) the shunt flow in 18 patients with normal-pressure hydrocephalus. With the patient in a sitting position, the pressure environment around the ventriculoperitoneal shunt stabilized when PP became equal to the CHV setting. The lower the CHV setting, the lower the ICP obtained in patients in a sitting position (ICPsit) settled. This indicated the possibility of calculating the CHV setting by the equation CHV setting = HP + ideal ICPsit - IAP, where the ideal ICPsit was estimated to be between -70 and -140 mm H2O. The CHV setting was individually determined for 18 patients by using this method. The ICPsit, was controlled at a level equal to the estimated ICPsit in most cases, which supported the rationality of our concept. Shunt flow was intermittent or very low when the patient assumed a supine position and between 200 and 600 microl/minute when the patient was seated. Determining the CHV setting by using the equation CHV setting = HP + ideal ICPsit - IAP was found to be useful when directly measuring HP and IAP in patients and estimating the ideal ICPsit to be between -70 and -140 mm H2O. Postoperative shunt control performed using this method was satisfactory, and shunt complications and the number of CHV resettings were lower than in those published in previous reports. Shunt-flow measurement performed in vivo and in real time by using a microflowmeter should be useful not only in testing the functioning of shunt systems, but also in clarifying the pathophysiology of hydrocephalus.

Abdomen↗

Modification of a nasal speculum for transsphenoidal surgery. Technical note.

The authors modified a Hardy nasal speculum to improve the access to surgical fields and the handling of various instruments during transsphenoidal surgery. A section of the inferior edge of the speculum was cut out 2 cm from its orifice on both sides. The thickness of the tip of the speculum was also reduced. The authors are prepared to operate using a variety of speculum lengths (the distance between the tip and the cutting level), and this length is selected depending on the distance between the anterior wall of the sphenoid sinus and the surface of the gingiva in the individual patient. A modified nasal speculum was used in transsphenoidal surgery for a pituitary adenoma. With use of this device, the protrusion of the speculum above the gingiva was markedly decreased. Because most instruments are inserted into the inferior portion of the speculum orifice, this approach facilitated the handling of all surgical instruments through the modified nasal speculum. The actual surgical field became shallow and wide, and the long surgical instruments that are generally used for transsphenoidal surgery were unnecessary in most cases.

Adenoma↗

Posture-related changes in the pressure environment of the ventriculoperitoneal shunt system.

OBJECT: The purpose of this study is to clarify the whole pressure environment of the ventriculoperitoneal (VP) shunt system in patients with successfully treated hydrocephalus and to determine which factor of the pressure environment has a preventive effect on overdrainage. METHODS: Thirteen patients with hydrocephalus who had been treated with VP shunt therapy by using a Codman-Hakim programmable valve without incidence of overdrainage were examined. The authors evaluated intracranial pressure (ICP), intraabdominal pressure (IAP), hydrostatic pressure (HP), and the perfusion pressure (PP) of the shunt system with the patients both supine and sitting. With patients supine, ICP, IAP, and HP were 4.6 +/- 3 mm Hg, 5.7 +/- 3.3 mm Hg, and 3.3 +/- 1 mm Hg, respectively. As a result, the PP was only 2.2 +/- 4.9 mm Hg. When the patients sat up, the IAP increased to 14.7 +/- 4.8 mm Hg, and ICP decreased to-- 14.2 +/- 4.5 mm Hg. The increased IAP and decreased ICP offset 67% of the HP (42.9 +/- 3.5 mm Hg), and consequently the PP (14 +/- 6.3 mm Hg) corresponded to only 33% of HP. CONCLUSIONS: The results observed in patients indicated that IAP as well as ICP play an important role in VP shunt therapy and that the increased IAP and the decreased ICP in patients placed in the upright position allow them to adapt to the siphoning effect and for overdrainage thereby to be avoided.

Aged↗

Sodium butyrate induces apoptosis in human renal cell carcinoma cells and synergistically enhances their sensitivity to anti-Fas-mediated cytotoxicity.

Sodium butyrate (NaBt), one of the short chain fatty acids naturally formed in the gastrointestinal tract, induces differentiation as well as apoptosis in numerous cell types. The objectives of this study were to characterize the effects of NaBt on the growth, cell cycle, and apoptosis of human renal cell carcinoma (RCC) cells, and to determine whether NaBt enhances the Fas-mediated cytotoxicity in these cells. NaBt reduced the in vitro growth rate of human RCC ACHN cells in a time- and dose-dependent manner. Treatment of ACHN cells with 1 mM NaBt resulted in G1 cell cycle arrest, accompanied by up-regulation of p21 (waf1/cip1) and down-regulation of cyclin D1. In contrast, 5 mM NaBt-induced apoptotic cell death in ACHN cells, accompanied by up-regulation of BaK and down-regulation of Bcl-2. Furthermore, NaBt synergistically enhanced the growth-inhibitory effect of anti-Fas monoclonal antibody, CH11 on CH11-sensitive ACHN cells, and apoptotic cell death was induced by the combination of sublethal doses of NaBt and CH11, but not by either agent alone. Similar synergy was also observed in CH11-resistant human RCC KN39 cells. These findings suggest that NaBt could be a novel attractive approach for patients with RCC, and that the efficacy of NaBt may be enhanced by the combined use of Fas-mediated therapy.

Antibodies, Monoclonal↗

Thrombopoietin stimulates murine lineage negative, Sca-1+, C-Kit+, CD34- cells: comparative study with stem cell factor or interleukin-3.

It has recently been reported that human thrombopoietin (TPO) acts on early hematopoietic progenitor cells. Consequently, we investigated the effects of TPO on murine hematopoietic progenitor cells using lineage negative (Lin-), Sca-1+, c-Kit+ marrow cells from 5-fluorouracil-treated mice. One hundred enriched cells were cultured in suspension with various single cytokines for 5 days. When cultured with the single cytokines as stem cell factor (SCF), TPO, or interleukin (IL)-3, these cells were maintained or had increased by day 5, whereas only a few cells survived in cultures with granulocyte colony stimulating factor, IL-11, or IL-6. We extended the study in serum-free or serum-containing suspension cultures with SCF or TPO. Anti-TPO antibodies did not inhibit the effects of SCF on enriched cells but did inhibit the effects of TPO on those cells. We further examined the effects of TPO, SCF, and IL-3 on other populations of murine hematopoietic progenitor cells. Either TPO or SCF as a single cytokine could maintain murine Lin-, Sca-1+, c-Kit+, CD34- marrow cells, which are the most dormant cells. In addition, IL-3 increased Lin-, Sca-1-, c-Kit+ cells more than did SCF and TPO but did not stimulate Lin-, Sca-1+, c-Kit+, CD34- cells more. These results indicate that TPO as well as SCF may be key regulators in the proliferation of murine hematopoietic early progenitor cells.

Animals↗

Antisense TRPM-2 oligodeoxynucleotides chemosensitize human androgen-independent PC-3 prostate cancer cells both in vitro and in vivo.

Although numerous chemotherapeutic regimens have been evaluated for patients with hormone-refractory prostate cancer, none has improved survival. Testosterone-repressed prostate message-2 (TRPM-2), which is highly up-regulated after androgen withdrawal and during androgen-independent progression in prostate cancer, has been shown to inhibit apoptosis induced by various kinds of stimuli. The objectives in this study were to test whether antisense (AS) oligodeoxynucleotides (ODNs) targeted against TRPM-2 enhance chemosensitivity in human androgen-independent prostate cancer PC-3 cells both in vitro and in vivo. Initially, the potency of 10 AS ODNs targeting various regions of the TRPM-2 mRNA were evaluated, and the AS ODN targeted to the TRPM-2 translation initiation site (AS ODN#2) was found to be the most potent sequence for inhibiting TRPM-2 expression in PC-3 cells. Despite significant dose-dependent and sequence-specific suppression of TRPM-2 expression, AS ODN#2 had no effect on growth of PC-3 cells both in vitro and in vivo. However, pretreatment of PC-3 cells with AS ODN#2 significantly enhanced chemosensitivity of Taxol (paclitaxel) and mitoxantrone in vitro. Characteristic apoptotic DNA laddering and cleavage of poly(ADP-ribose) polymerase were observed after combined treatment with AS ODN#2 plus paclitaxel or mitoxantrone but not with either agent alone. In vivo administration of AS ODN#2 plus either paclitaxel or mitoxantrone significantly decreased PC-3 tumor volume by 80 or 60%, respectively, compared with mismatch control ODN plus either paclitaxel or mitoxantrone. In addition, terminal deoxynucleotidyl transferase-mediated nick end labeling staining revealed increased apoptotic cells in tumors treated with AS ODN#2 plus paclitaxel or mitoxantrone. These findings confirm that TRPM-2 overexpression confers resistance to cytotoxic chemotherapy in prostate cancer cells and illustrates the potential utility of combined treatment with AS TRPM-2 ODN plus chemotherapeutic agents for patients with hormone-refractory prostate cancer.

Androgens↗

Inhibitory effect of TAS-301, a new synthesized constrictive remodeling regulator, on renarrowing after balloon overstretch injury of porcine coronary artery.

The purpose of this study was to determine the efficacy and the possible mechanism of action of a recently synthesized drug, TAS-301 [3-bis(4-methoxyphenyl)methylene-2-indolinone], on stenosis after balloon overstretch injury of porcine arteries. We measured the diameter of vessels by angiography and conducted histological analysis. The oral administration of TAS-301 kept dilated the angiographic luminal diameter of injured segment 4 weeks after overstretch injury and reduced calculated stenosis ratio in a dose-dependent manner, significantly reducing it at doses of 30 and 100 mg/kg. Histopathological analysis showed that TAS-301 significantly reduced the adventitial area at doses of 30 and 100 mg/kg with moderate reduction of the neointimal area, resulting in the larger residual lumen. In an in vitro assay, TAS-301 dose dependently inhibited the proliferation of adventitial fibroblasts stimulated by basic fibroblast growth factor or transforming growth factor-beta(1). In addition, the drug reduced adventitial fibroblast-mediated three-dimensional collagen gel contraction. These findings indicate that TAS-301, the first compound developed for targeting the constrictive remodeling, showed a high inhibitory potency on coronary artery stenosis of micropigs after injury, mainly due to inhibition of adventitial fibroblast proliferation and of the contractile ability of myofibroblasts. Our results suggest the strong possibility that TAS-301 may be efficacious for prevention of restenosis after angioplasty and the need to examine the therapeutic usefulness of this drug in clinical trials.

Angioplasty, Balloon, Coronary↗

Antisense Bcl-2 oligodeoxynucleotides inhibit progression to androgen-independence after castration in the Shionogi tumor model.

Progression to androgen-independence remains the main obstacle to improving survival for patients with advanced prostate cancer. Although Bcl-2 expression in normal prostatic epithelial cells is low or absent, Bcl-2 is highly up-regulated in prostate cancer cells after androgen withdrawal and during progression to androgen-independence. Here, we test the efficacy of antisense Bcl-2 oligodeoxynucleotide (ODN) therapy administered adjuvantly after castration to delay time to androgen-independent recurrence in the androgen-dependent mouse Shionogi tumor model. Treatment of Shionogi tumor cells in vitro with antisense Bcl-2 ODN inhibited Bcl-2 expression in a dose-dependent and sequence-specific manner. Systemic administration of antisense Bcl-2 ODN in mice bearing Shionogi tumors beginning 1 day postcastration resulted in a more rapid regression of tumors and a significant delay of emergence of androgen-independent recurrent tumors. Furthermore, despite significant reduction of Bcl-2 expression in tumor tissues, antisense Bcl-2 ODN had no effect on Bcl-2 expression in normal mouse organs. These findings illustrate the potential utility of antisense Bcl-2 therapy for prostate cancer in an adjuvant setting with androgen ablation.

Androgens↗

Castration-induced apoptosis of androgen-dependent shionogi carcinoma is associated with increased expression of genes encoding insulin-like growth factor-binding proteins.

Insulin-like growth factor (IGF)-I has well-characterized mitogenic and antiapoptotic effects that are essential for maintenance of the normal prostate and may be important during regression of the normal prostate and/or prostate tumors induced by androgen-targeting therapies for prostate cancer. IGF-I activity is modulated by IGF-binding proteins (IGFBPs). Here we examine IGFBP expression during regression of androgen-dependent Shionogi carcinoma tumors after castration. In this model, we observe a 90% reduction in Shionogi tumors by 10 days postcastration. Northern blotting of RNA from tumors collected at various times after castration indicates a rapid induction of IGFBP-5 concomitant with apoptotic regression of tumors, as detected by Apoptag staining of tumor sections after castration. IGFBP-5 mRNA was not detectable in tumors from control animals, but levels increased 120-fold in tumors 3 days after castration. The mRNAs for IGFBP-3 and 4 were abundant in Shionogi tumors from intact mice and decreased to -33% and -20% of control, respectively. Castration had no significant effect on IGFBP-2 expression. Treatment with calcium channel blockers inhibited castration-induced apoptosis and tumor regression and also significantly inhibited up-regulation of IGFBP-5 after castration. These data provide strong evidence for a functional role of IGFBP-5 expression in mediating the apoptosis induced by androgen deprivation in androgen-dependent neoplasia.

Amlodipine↗

Increased angiogenin expression in the tumor tissue and serum of urothelial carcinoma patients is related to disease progression and recurrence.

BACKGROUND: The progression of solid tumors is at least partly dependent on angiogenesis, the induction of which is mediated by several angiogenic factors, including angiogenin (ANG). The authors evaluated the expression of ANG in the tumor tissue and serum of patients with urothelial carcinoma. METHODS: The expression of ANG in 5 human bladder carcinoma cell lines and 24 urothelial carcinomas (10 superficial carcinomas and 14 invasive carcinomas) and in corresponding normal urothelial tissues was investigated by reverse transcriptase-polymerase chain reaction and Northern blot analysis. Serum levels of ANG in 52 healthy volunteers and in 135 patients with urothelial carcinomas (81 superficial carcinomas and 54 invasive carcinomas) were measured by using a sandwich enzyme immunoassay. RESULTS: ANG mRNA transcripts were detected in all of the bladder carcinoma cell lines, urothelial carcinomas, and normal tissues. The mean level of ANG expression in invasive urothelial carcinomas was 4-fold higher than in superficial carcinomas and 5-fold higher than in normal tissues. The mean serum ANG concentration for invasive urothelial carcinoma patients (514.6+/-211.1 ng/mL) was significantly higher than for superficial urothelial carcinoma patients (381.7+/-169.3 ng/mL) and healthy volunteers (337.5+/-71.4 ng/mL). The overall survival rate of patients with elevated serum levels of ANG was significantly lower than that of patients with normal levels. Moreover, among the 47 patients with advanced urothelial carcinoma who underwent complete resection, the disease free survival rate of patients with elevated serum levels of ANG was significantly lower than that of patients with normal levels. CONCLUSIONS: These results indicate that ANG is strongly expressed in the tumor tissue and is present in high levels in the serum of patients with invasive urothelial carcinoma compared with superficial carcinoma patients and that elevation of serum ANG level could be used as a novel predictor of the prognoses of patients with urothelial carcinoma.

Adult↗

Effects of prenatal exposure to styrene on neurochemical levels in rat brain.

Styrene was evaluated to determine its neurochemical effects in the offspring of rats exposed during the gestation period. Maternal Wistar rats were exposed to 0, 50 or 300 ppm styrene during gestation days 6 to 20 and the neurochemical effects on their offspring were compared with their pair-feeding and ad lib. feeding controls. The cerebrum weights at birth on day 0 were significantly lower than those for an ad lib. feeding control group. Neurotransmitter analyses showed decreases of neuroamines, especially 5-hydroxytryptamine and homovanillic acid in the cerebrum of newborn offspring of dams receiving a 300 ppm styrene exposure compared with the ad lib. fed control group and homovanillic acid was also decreased compared to the pair-feeding control. On postnatal day 21, the styrene-exposure pups showed a significant decrease of 5-hydroxyindoleacetic acid in the frontal neocortex compared with the ad lib. control group. In the hippocampus a significant decrease of 5-hydroxyindoleacetic acid was observed compared with both control groups. Moreover, the ratio of 5-HIAA/5-HT in the hippocampus was significantly decreased among the styrene-exposure groups. The 50 ppm styrene exposed group induced increase of concentrations of 5-hydroxytryptamine in the striatum. These results suggest that prenatal styrene exposure affects the developing fetal brain in terms of a few signs of neurochemical alteration.

3,4-Dihydroxyphenylacetic Acid↗

Structural requirement of leucine for activation of p70 S6 kinase.

The addition of leucine induced activation of p70S6k in amino acid-depleted H4IIE cells. Whereas the activation of p70S6k by leucine was transient, the complete amino acid stimulated p70S6k more persistently. The effect of leucine on p70S6k was sensitive to rapamycin, but less sensitive to wortmannin. Using various amino acids and derivatives of leucine, we found that the chirality, the structure of the four branched hydrocarbons, and the primary amine are required for the ability of leucine to stimulate p70S6k, indicating that the structural requirement of leucine to induce p70S6k activation is very strict and precise. In addition, some leucine derivatives exhibited the ability to stimulate p70S6k and the other derivatives acted as inhibitors against the leucine-induced activation of p70S6k.

Amino Acids↗

Trans-activator Tax of human T-cell leukemia virus type 1 enhances mutation frequency of the cellular genome.

Tax protein of human T-cell leukemia virus type 1 (HTLV-1) is a potent trans-activator of specific sets of target genes, and on the other hand, it is a trans-repressor of other sets of genes. It is also an inhibitor of the tumor suppressor protein p16(INK4a) and thus has been thought to contribute to induction of adult T-cell leukemia (ATL). We examined the mutagenic effects of Tax on a cellular gene, hypoxanthine guanine phosphoribosyltransferase (hprt), and LacI gene in lambda shuttle vector exogenously integrated in Big Blue Rat-2 (BBRat-2) cells. Expression of Tax in BBRat-2 cells enhanced the frequency of HPRT(-) phenotype severalfold. Tax-expressing cell clones, BBTax-1 and -2 established from BBRat-2 cells, gave rise to an average mutation frequency of 5.9 x 10(-5) in LacI gene, but Tax-negative cell clones, BBRat-C1 and -C2, showed 2. 1 x 10(-5). The 2.8-fold increase in mutation frequency in the presence of Tax indicates that Tax expression enhanced mutation frequency in chromosomal DNA. However, neither the mutation spectrum of base transitions, transversions, and deletions/insertions nor the loci of the mutations were significantly affected by Tax expression. These findings indicate that Tax has the capability to induce random mutations and suggest that Tax would be able to modulate cellular phenotypes through mutation of the cellular genome.

Animals↗

Elevation of serum levels of urokinase-type plasminogen activator and its receptor is associated with disease progression and prognosis in patients with prostate cancer.

BACKGROUND: Several investigators have revealed that urokinase-type plasminogen activator (uPA) and its receptor (uPAR) are overexpressed in serum as well as in tumor tissues in patients with various types of cancer. In this study, we examined whether the serum levels of uPA and uPAR could be used as predictors of the progression and prognosis of prostate cancer. METHODS: Serum levels of uPA and uPAR in 54 healthy controls, 62 patients with benign prostatic hypertrophy (BPH), and 72 patients with prostate cancer were measured by a sandwich enzyme immunoassay. RESULTS: The mean serum levels of uPA and uPAR in patients with prostate cancer were significantly higher than those in healthy controls and patients with BPH. Furthermore, the serum uPA and uPAR levels in prostate cancer patients with metastasis were significantly elevated compared with those in patients without metastasis. Among patients who underwent radical prostatectomy, the serum levels of uPA and uPAR in patients with pathologically organ-confined disease were significantly lower than in those with advanced disease. The overall survival rate of prostate cancer patients with elevated serum levels of either uPA or uPAR, or of both, was significantly lower than that of patients with normal serum levels of uPA and uPAR. CONCLUSIONS: The results of this study indicate that the elevation of serum levels of either uPA or uPAR, or of both, could be used as new predictors of progression and prognosis in patients with prostate cancer.

Aged↗

Scintigraphic demonstration of renal cell carcinoma with I-131-6beta-iodomethyl-19-norcholesterol: a case report.

Extraadrenal abnormal uptake on adrenocortical scintigraphy has been reported rarely in the normal gallbladder, lipid cell tumor of the ovary, or in clear cell type renal cell carcinoma. Clear cell type renal cell carcinoma contains glycogen and cholesterol like the adrenal gland, but the uptake of the radionuclide I-131 cholesterol has been reported to be low and not sufficient to image it. Right renal and adrenal masses were incidentally discovered on abdominal CT scan in a patient with chronic renal failure resulting in bilateral acquired cystic kidney disease. Adrenocortical scintigraphy done to know the nature of the adrenal mass showed high uptake corresponding to the right renal mass and the right adrenal mass. Clear cell type renal cell carcinoma and adrenal adenoma with prominent clear cells were histologically confirmed on hematoxylin-eosin stain and in an immunohistochemical study with renal cell antibody. Not only low-density lipoprotein receptors mediated uptake but also overall replacement of the right non-tumorous renal parenchyma by acquired cysts may have played a role in imaging the renal cell carcinoma on adrenocortical scintigraphy.

19-Iodocholesterol↗