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Biomedical subjects

R Nakano

Publications and source records attributed to R Nakano.

At least 37 records · Page 2Linked to original sources
PubMed1999

Transient increases of apoptosis and Bax expression occurring during radiotherapy in patients with invasive cervical carcinoma.

BACKGROUND: Apoptosis plays a crucial role in radiation therapy (RT) in various carcinomas. This study was designed to investigate the relation between apoptosis and RT in invasive squamous cell carcinoma (ISCC) of the uterine cervix METHODS: Thirty-five specimens were obtained from 7 patients with ISCC before and during a fractionated RT. The occurrence of apoptosis was examined by end labeling of DNA gel fractionation and in situ 3' end labeling of DNA. The expression of Bax and Bcl-2 proteins was investigated by immunohistochemical staining. RESULTS: Autoradiographic analysis revealed that high molecular weight DNA was predominant in the untreated ISCC specimens. However, a ladder-like pattern, characteristic of the apoptotic breakdown of DNA, was identified at doses of 900 cGy and 1980 cGy. At doses >1980 cGy, DNA laddering disappeared without any extensive smearing. Quantitative analysis of low molecular weight fragments of DNA revealed significant increases at doses of 900 cGy and 1980 cGy compared with those before RT and at doses of >1980 cGy. Labeling of DNA in situ indicated that cells undergoing apoptosis increased dramatically at a dose of 900 cGy. However, apoptotic cells decreased at a dose of 3960 cGy. In addition, a large fraction of tumor cells was immunonegative for Bcl-2 before and during RT. By contrast, immunoreactive Bax was observed intensely in many neoplastic cells at doses of 900 cGy and 1980 cGy. CONCLUSIONS: The current investigation indicates that low doses of RT result in apoptotic cell death in ISCC in association with the increased expression of Bax but not with increased Bcl-2 expression.

Aged↗
PubMed1999

Administration of prosaposin ameliorates spatial learning disturbance and reduces cavity formation following stab wounds in rat brain.

The effectiveness of prosaposin as a neurotrophic factor was investigated using rats with bilateral stab wounds, injecting 240 ng per day of prosaposin for 3 days. In Morris water maze task, after 3 weeks postoperation, the stab-wounds rats show significant impairment in acquisition compared with the sham-operated rats. In the transfer test the mean number of crossings of the platform place in stab-wounds was significantly lower than that in sham-operated rats (P < 0.01). The stab-wounds rats treated with prosaposin showed significant improvement (P < 0.05). The cavities following stab wounds in the rats treated with prosaposin were significantly smaller than those in the rats treated with (P < 0.05). Our data support that prosaposin is likely to be a new agent for brain injury.

Animals↗
PubMed1999

Apoptosis and the expression of Bax and Bcl-2 in squamous cell carcinoma and adenocarcinoma of the uterine cervix.

BACKGROUND: Apoptosis plays a crucial role in the suicide and turnover of cells in various tumors. This study was designed to investigate the relation between apoptosis and the histologic types of cell in invasive cervical carcinoma. METHODS: Cervical tissues were obtained from 19 patients with invasive squamous cell carcinoma (ISCC), 9 patients with invasive endocervical adenocarcinoma (IEAC), and 15 patients with myoma uteri (which were used as controls). Each tissue was rapidly frozen and/or fixed in Bouin's solution. The occurrence of apoptosis was examined by end labeling of DNA with (alpha-32P)dideoxyATP and electrophoretic fractionation and by end labeling of DNA in situ with digoxigenin-dideoxyUTP. The expression of Bcl-2 and Bax proteins was examined by immunohistochemical staining with appropriate antibodies. RESULTS: Autoradiographic analysis revealed that high molecular weight DNA was predominant in the normal cervical epithelium (NCE) and in ISCC. However, a ladder-like pattern of DNA fragments, characteristic of the apoptotic breakdown of DNA, was identified in IEAC. Quantitative analysis of low molecular weight fragments of DNA revealed a significant increase in IEAC but not in ISCC compared with NCE. Labeling of DNA in situ indicated that cells undergoing apoptosis were predominant among the neoplastic cells of IEAC. However, no apoptotic cells were noted in ISCC, with the exception of cells in some tumor nests. A large fraction of IEAC and ISCC was immunonegative for Bcl-2. Although the expression of Bax was detected weakly in a small fraction of ISCC, strong expression of Bax was observed in all cases of IEAC. CONCLUSIONS: Apoptosis appears to occur in the cancerous cells of invasive adenocarcinoma of the uterine cervix in association with a high level of expression of Bax but not of bcl-2.

Adenocarcinoma↗
PubMed1999

Cytotoxic T lymphocyte-mediated cell death in paraneoplastic sensory neuronopathy with anti-Hu antibody.

Paraneoplastic sensory neuronopathy (PSN) has been shown to harbor characteristic anti-neuronal autoantibody 'anti-Hu' in their sera and cerebrospinal fluid. Creation of animal models exhibiting clinical or pathological features seen in PSN by means of passive transfer of anti-Hu positive IgG has not been achieved. Although, anti-Hu antibody was shown to induce neuronal cell lysis in vitro, this result has not been reproduced so far. Since prominent T cell infiltration are seen in the central nervous system and posterior spinal ganglion of the patients with anti-Hu syndrome, we studied cytotoxic T cell (CTL) activity in peripheral mononuclear cells from a patient with PSN harboring anti-Hu antibody. The activated CD8+ T cells from the patient's venous blood were shown to lyse her own fibroblasts which were incubated with interferon-gamma to induce HLA class I molecules on their surface and the recombinant HuD protein was injected into the cells by microinjector. This is the first report showing the existence of CTL in a patient with PSN.

Autoantibodies↗
PubMed1999

Accumulation of neurofilaments and SOD1-immunoreactive products in a patient with familial amyotrophic lateral sclerosis with I113T SOD1 mutation.

OBJECTIVE: To report neuropathologic features of argyrophilic inclusions in the anterior horn cells, motor cortex Betz cells, and neurons of the medullary reticular formation, spinal posterior horn, and Clarke column in a Japanese case of familial amyotrophic lateral sclerosis with I113T substitution in exon 4 of the copper-zinc superoxide dismutase (SOD1) gene. METHODS AND RESULTS: These inclusions were stained pale pink on the hematoxylin-eosin stain and dark on the Bielschowsky stain. They were positive for antibodies to phosphorylated neurofilaments, ubiquitin, and SOD1. On electron microscopy, they consisted of abundant intermediate filaments of 10 to 20 nm in diameter with disordered array indicating neurofilaments. CONCLUSION: These findings suggest that the I113T mutation induces accumulation of neurofilaments and SOD1 in the central nervous system neurons.

Aged↗
PubMed1999

Mucosa-associated lymphoid tissue lymphoma of the duodenum forming multiple polypoid lesions: report of a case.

We report herein the case of a patient found to have mucosa-associated lymphoid tissue (MALT) lymphoma of the duodenum forming multiple polypoid lesions. Endoscopic examination revealed multiple small nodules with a yellow-white, rough surface in the duodenal bulb. Histopathological and immunological findings subsequently suggested low-grade B-cell MALT lymphoma. Cytologically, MALT lymphoma is similar to multiple lymphomatous polyposis (MLP); however, this case, which involved multiple polypoid lesions, was confirmed not to be MLP.

Aged↗
PubMed1999

Upright posture blunts postprandial splanchnic hyperemia in patients with cirrhosis and portal hypertension.

The aim of this study was to compare postprandial hemodynamic changes observed during assumption of the recumbent posture and upright posture in patients with cirrhosis and portal hypertension. Eleven patients with cirrhosis and portal hypertension were studied. Echo-Doppler examinations were performed to measure flow volume in the portal vein (PV), superior mesenteric artery (SMA), and splenic artery (SA) in the fasting condition. Collateral blood flow was indirectly calculated by determining the difference between the sum of SMA, SA, and PV blood flows. After these measurements were done, each patient received a standardized liquid meal and was then randomly assigned to either maintain supine or upright posture, in a crossover design, on 2 different days (recumbent day and upright day). On each study day, the above-mentioned measurements were repeated 30 min and 60 min after the meal. PV blood flow increased significantly after the meal on the recumbent day (P < 0.01) but not on the upright day (P = 0.78). Although there were significant postprandial increases in SMA blood flow on both study days (P < 0.01, P < 0.01), the effect was less pronounced on the upright day than on the recumbent day (P < 0.01). Postprandial SA blood flow showed no change on the recumbent day (P = 0.64), but decreased significantly on the upright day (P < 0.01). The calculated postprandial collateral blood flow increased significantly on the recumbent day (P < 0.05), but showed no change on the upright day (P = 0.53). These results suggest that the upright posture blunts postprandial splanchnic hyperemia in patients with cirrhosis and portal hypertension.

Aged↗
PubMed1999

Immunohistochemical localization of inhibin and activin subunits in human epithelial ovarian tumors.

OBJECTIVE: Our purpose was to examine the cellular localization of inhibin and activin subunits in human epithelial ovarian tumors. STUDY DESIGN: We examined the immunohistochemical localization of the alpha, betaA, and betaB subunits of inhibin in human mucinous and serous ovarian tumors including adenoma, cystic tumor with borderline malignancy, and adenocarcinoma. RESULTS: Immunostaining specific for the alpha, betaA, and betaB subunits of inhibin was observed in the tumor cells of the mucinous adenoma and the cystic tumor with borderline malignancy. We observed negative immunostaining specific for the alpha subunit and positive staining specific for the betaA and betaB subunits in the tumor cells of the mucinous adenocarcinoma. We did not observe any staining for the alpha subunit of inhibin in the serous tumors including benign adenoma, cystic tumor with borderline malignancy, and adenocarcinoma. However, positive staining results for the betaA and betaB subunits were observed in the serous tumor cells. CONCLUSION: Our results suggest that inhibins and activins might be secreted by the mucinous adenoma and the cystic tumor with borderline malignancy and that activins might be secreted by the mucinous adenocarcinoma and the serous tumors including benign adenoma, cystic tumor with borderline malignancy, and adenocarcinoma.

Activins↗
PubMed1999

Effect of transcatheter arterial chemoembolization on kidney hemodynamics and function in patients with cirrhosis and hepatocellular carcinoma.

BACKGROUND/AIMS: Transcatheter arterial chemoembolization (TACE) may have deleterious effect on the kidney in patients with cirrhosis and hepatocellular carcinoma. The aim of the study was to test this hypothesis. METHODS: Twenty-four patients with cirrhosis and hepatocellular carcinomas were included. They consisted of 16 patients undergoing a single TACE and eight patients undergoing diagnostic angiography. Doppler ultrasonography was used to measure hepatic artery pulsatility index (HA-PI) and renal artery pulsatility index (RA-PI) before and 1 day and 10 days after the procedure. Similarly, kidney function was assessed by measuring creatinine clearance. In addition, plasma renin activity, noradrenaline, and endothelin-1 were also measured. RESULTS: In patients receiving diagnostic angiography, no significant changes in HA-PI were observed after the procedure. In contrast, HA-PI increased significantly 1 day after the procedure (19%, p<0.01) in patients undergoing TACE, although it returned to baseline value 10 days after the procedure. In patients undergoing diagnostic angiography, no significant changes in RA-PI were observed after the procedure. Similarly, no detectable changes in RA-PI were noted in patients undergoing TACE. A transient small reduction in creatinine clearance was noted after the procedure in patients undergoing diagnostic angiography (-12%, p<0.05) and in those undergoing TACE (-11%, p<0.05). However, the effect was similar in the two groups (two-way ANOVA, p=0.72). No significant changes in plasma renin activity, noradrenaline, and endothelin-1 were observed after either diagnostic angiography or TACE. CONCLUSIONS: These results suggest that TACE per se has no deleterious effect on the kidney hemodynamics and function in patients with cirrhosis and hepatocellular carcinoma.

Aged↗
PubMed1999

PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance.

Agonist-induced activation of peroxisome proliferator-activated receptor gamma (PPAR gamma) is known to cause adipocyte differentiation and insulin sensitivity. The biological role of PPAR gamma was investigated by gene targeting. Homozygous PPAR gamma-deficient embryos died at 10.5-11.5 dpc due to placental dysfunction. Quite unexpectedly, heterozygous PPAR gamma-deficient mice were protected from the development of insulin resistance due to adipocyte hypertrophy under a high-fat diet. These phenotypes were abrogated by PPAR gamma agonist treatment. Heterozygous PPAR gamma-deficient mice showed overexpression and hypersecretion of leptin despite the smaller size of adipocytes and decreased fat mass, which may explain these phenotypes at least in part. This study reveals a hitherto unpredicted role for PPAR gamma in high-fat diet-induced obesity due to adipocyte hypertrophy and insulin resistance, which requires both alleles of PPAR gamma.

Adipocytes↗
PubMed1999

Differentiation of malignant lymphoma and non-lymphoma by an occlusive dressing method employing bromodeoxyuridine.

Although lymphoma cells can proliferate in skin tissue, lymphocytes which have infiltrated the skin due to inflammatory changes are generally unable to do so. It may be possible to differentiate malignant lymphomas from benign lymphocytic infiltrations in skin tissue by detection of cell cycle-related antigens. We developed a novel in vivo method for studying the cell kinetics of human skin using bromodeoxyuridine (BrdU) with an occlusive dressing. Following the application of BrdU, BrdU-labeled lymphoid cells were counted in the dermis. The patients studied included 22 with various types of lymphomas (lymphoma group) and 22 with different forms of inflammatory skin disease (non-lymphoma group). Skin specimens were obtained after applying occlusive adhesive plasters containing 2% BrdU dissolved in 0.9% sodium chloride solution and were then immunostained with anti-BrdU monoclonal antibody. The average percentages of labeled cells were 15.9 +/- 7.6% for the lymphoma group and 4.7 +/- 2.6% for the non-lymphoma group. This difference was statistically significant (p < 0.0001). Using this method, malignant lymphomas and benign lymphocytic infiltrations of the skin could be differentiated by counting BrdU-labeled lymphoid cells, and this method could help in determining a prognosis.

Biopsy↗
PubMed1999

Nocturnal decrease in vasopressin secretion into plasma in patients with multiple system atrophy.

To determine whether the nocturnal decrease in arginine vasopressin (AVP) secretion into the plasma, found in a patient with multiple system atrophy (MSA) reported previously, is a usual finding in MSA, the plasma AVP concentrations in 13 patients with MSA were measured every 4 hours during a 24 hour period. The plasma AVP concentrations in these patients showed significant daily variations and were the lowest during the night. This finding indicates that patients with MSA often exhibit nocturnal decrease in AVP secretion into the plasma. The results suggest the possibility that the system responsible for the daily variations in AVP secretion is involved in MSA.

Aged↗
PubMed1999

The vascular endothelial growth factor/fms-like tyrosine kinase system in human ovary during the menstrual cycle and early pregnancy.

In human ovaries, angiogenesis is known to be associated with the development of follicles and the formation of the corpus luteum (CL). A complex vascular network is formed within the thecal cell layer during follicular growth, and rapid neovascularization occurs toward the granulosa cell layer after ovulation. Vascular endothelial growth factor (VEGF) is a multifunctional cytokine, stimulating endothelial cell growth and enhancing microvascular permeability. A specific receptor for VEGF, fms-like tyrosine kinase (Flt-1), is expressed in vascular endothelial cells that mediates the action of VEGF. We examined the localization and expression of VEGF and Flt-1, using an immunohistochemical technique and RT-PCR analysis, in human follicles and corpora lutea during the normal menstrual cycle and early pregnancy. We measured concentrations of VEGF in extracts of human CL using an enzyme-linked immunosorbent assay during the luteal phase and early pregnancy. Immunostaining for VEGF was observed in granulosa cells from small antral follicles to preovulatory follicles. The staining was detected in thecal cells from medium-sized to preovulatory follicles. The intensity of the staining was gradually increased as a follicle grew. Flt-1 was localized in granulosa and thecal cells of preovulatory follicles as well as in endothelial cells. In the human CL, the intense staining for VEGF was observed in granulosa and thecal lutein cells, especially in the midluteal phase. The immunostaining for Flt-1 was faint in endothelial cells in the CL, whereas it was distinct in granulosa and thecal lutein cells. The concentrations of VEGF in lutein extracts were high in the early and midluteal phases and tended to decrease toward the late luteal phase. During early pregnancy, a measurable amount of VEGF was detected. RT-PCR analysis demonstrated that messenger ribonucleic acids encoding VEGF121, VEGF165, and Flt-1 were expressed in the CL. These results suggest that VEGF might have an autocrine role in the ovulatory process and luteal function as well as a paracrine role in angiogenesis.

Adult↗
PubMed1999

[Familial amyotrophic lateral sclerosis associated with mutant Cu/Zn superoxide dismutase as a conformational disease].

To investigate the molecular mechanism of mutant Cu/Zn superoxide dismutase (SOD) associated with familial amyotrophic lateral sclerosis (FALS), mutant (A1a4Thr, Gly85Arg, Gly93Ala, and two base-pair deletion in the 126th codon), as well as wild-type (wt), Cu/Zn SODs were expressed in COS7 cells. The formation of granular cytoplasmic aggregates accompanied by collapse of the cytoplasm was observed in cells expressing mutant Cu/Zn SODs, but not in cells expressing mutant Cu/Zn SODs. The aggregates contained ribosome-like particles and endoplasmic reticulum. These results suggest the possibility that mutant Cu/Zn SODs promote the formation of aggregates which are toxic to cells.

Amyotrophic Lateral Sclerosis↗
PubMed1998

Formation of granular cytoplasmic aggregates in COS7 cells expressing mutant Cu/Zn superoxide dismutase associated with familial amyotrophic lateral sclerosis.

To investigate the molecular mechanisms of the 'gain of toxic function' of mutant Cu/Zn superoxide dismutase (SOD) associated with familial amyotrophic lateral sclerosis (FALS), mutant (Ala 4 --> Thr, Gly 85 --> Arg, Gly 93 --> Ala, and two base-pair deletion in the 126th codon), as well as wild-type (wt), Cu/Zn SODs were expressed in COS7 cells. The formation of granular cytoplasmic aggregates accompanied by collapse of the cytoplasm was observed in cells expressing mutant (mt) Cu/Zn SODs, but not in cells expressing wt Cu/Zn SOD. The aggregates contained ribosome-like particles and endoplasmic reticulum. These results suggest the possibility that mt Cu/Zn SODs promote the formation of aggregates which are toxic to cells.

Amino Acid Substitution↗
PubMed1998

A leukotriene receptor antagonist, ONO-1078, modulates drug sensitivity and leukotriene C4 efflux in lung cancer cells expressing multidrug resistance protein.

ONO-1078 is a new class of peptide leukotriene receptor antagonist, and multidrug resistance protein (MRP) is a membrane tranporter of multiple anticancer drugs and endogenous leukotriene C4 (LTC4). We investigated the effects of ONO-1078 on drug sensitivity and LTC4-efflux in MRP-expressing lung cancer cells. Drug sensitivity, intracellular vincristine accumulation, and intracellular and extracellular LTC4 concentrations were measured with or without ONO-1078. The effect of ONO-1078 on MRP-mediated calcein-efflux was determined by flow cytometry. ONO-1078 (1 to 10 microM) dose-dependently enhanced the sensitivity of NCI-H520 cells to vincristine with the reduced accumulation, and also enhanced the sensitivity to doxorubicin and etoposide. ONO-1078 inhibited both LTC4- and calcein-efflux from the cells with increased intracellular accumulations. Our findings indicate that ONO-1078 modulates multidrug resistance and inhibits LTC4-efflux in lung cancer cells, by inhibition of MRP function.

ATP-Binding Cassette Transporters↗