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Biomedical subjects

S Sato

Publications and source records attributed to S Sato.

At least 433 records · Page 24Linked to original sources

Sensitivity to paclitaxel is not related to p53-dependent apoptosis in ovarian cancer cells.

We conducted this study to determine whether the sensitivity of ovarian cancer cells to paclitaxel (PTX) relates to cells undergoing p53-dependent apoptosis. Human ovarian adenocarcinoma cell lines (SK-OV-3, KF and KP cells) were used in this study. In SK-OV-3 and KP cells, which have a homozygous deletion of the TP53 gene, wild-type TP53 gene-transduction markedly enhanced the sensitivity to cisplatin (CDDP), but did not enhance the sensitivity to PTX. In all cells, the apoptotic index was increased by CDDP or PTX. After exposure to CDDP, p53 and Bax protein expression increased and Bcl-xL expression decreased in the KF cells and TP53 gene-transducted SK-OV-3 cells. However, these proteins did not change in KP cells. Therefore, the role of p53 in CDDP-induced apoptosis depends upon the cell type. In contrast, TP53 gene status did not correlate with PTX-induced cytotoxicity in any of the cell lines with differing apoptotic pathways. In conclusion, the sensitivity to PTX may not be related to p53-dependent apoptosis in ovarian cancer cells.

Antineoplastic Agents↗

Reduced expression of CD44 variant 9 is related to lymph node metastasis and poor survival in squamous cell carcinoma of tongue.

Expression of CD44v9 was immunohistochemically studied in 120 biopsy specimens from primary squamous cell carcinoma (SCC) of the tongue and correlated with clinicopathological findings of the SCCs. The tumors were classified into three groups according to immunostaining pattern of CD44v9; 53 cases with distinct positivity in all cancer cells except for those in the central part of nests (Group 1, non-reduced group), 42 cases with reduced expression in peripheral cells of nests (Group 2, reduced group), and 25 cases with complete disappearance of the expression in one or more nests (Group 3, negative group). Nineteen of 25 (76%) tumors in Group 3 and 14 of 42 (33%) in Group 2 exhibited lymph node metastasis, compared with only 8 of 53 (15%) in Group 1. The average survival time in Groups 1, 2 and 3 was 4496+/-204, 3866+/-379 and 2719+/-359 days, respectively and became shorter with the reduction of CD44v9 expression. These results suggest that the down-regulation of CD44v9 in SCC of the tongue may relate to the detachment of tumor cells from primary lesions, establishment of lymph node metastasis and consequently the death of patients.

Adult↗

Beneficial effect of Cyclosporin A on acute hepatic injury induced by galactosamine and lipopolysaccharide in rats.

Cyclosporin A (CsA), a potent immunosuppressive agent, is used clinically to prevent allograft rejection after organ transplantation. Although recent experimental studies show that CsA prevents severe hepatic injury associated with tumor necrosis factor-alpha (TNF-alpha), the efficacy of CsA has not been confirmed. In the present study, we evaluated whether CsA protects against the severe hepatic injury induced by simultaneous administration of D-galactosamine (GaIN, 200 mg/kg) and lipopolysaccharide (LPS, 10 µg/kg) into the portal vein. The method of CsA (10 mg/kg) was divided into four groups; i.e. preinjection (24 and 2 h before administration of GaIN and LPS), concomitant single-injection, multiple-interval injection (0, 3, 6, 9 and 15 h after administration of GaIN and LPS) and no treatment. In the group receiving multiple-interval injections of CsA, liver function parameters (total bilirubin, asparate aminotransferase and alanine aminotransferase levels in sera) were significantly improved and the development of massive hepatic necrosis was significantly prevented, but no improvement of liver function parameters or histological changes was shown either the pre- or concomitant single-injection groups. The serum levels of TNF-alpha and interferon-gamma showed no differences between the no treatment and multiple-interval injection groups. However, the serum level of interleukin 8 and neutrophil infiltration into the liver tissue after 24 h GaIN and LPS administration were significantly lower than those of the control group. The apoptotic index of liver tissue using the TUNEL method was not significantly different. Our data suggest that CsA protects against acute hepatic injury, if it is administered at the appropriate time during the course of hepatic injury.

Journal Article↗

Regional differences in cerebral glucose metabolism in cirrhotic patients with subclinical hepatic encephalopathy using positron emission tomography.

Although it is recognized that abnormalities of glucose metabolism occur substantially throughout the brain in cirrhotic patients with subclinical hepatic encephalopathy (SHE), little attention has been paid to these abnormalities in situ due to technical difficulties. The aim of this study is to clarify the regional differences of cerebral glucose metabolism (CMRglu) in patients with or without SHE using positron emission tomography (PET). Fifteen patients with posthepatitic cirrhosis and 13 control subjects underwent PET imaging of the brain using 2-[18F]fluoro-2-deoxy-D-glucose. Neurological tests included the digit symbol and block design subtests from the Wechsler Adult Intelligence Scale. Auditory brain stem reaction and electroencephalogram were also used in diagnosis of SHE. Regions were defined as frontal, parietal, occipital, basal ganglia, and the white matter. The CMRglu value in the grey matter of SHE is lower than that of control, particularly in the frontal and temporal regions and basal ganglia (P<0.05, respectively). The CMRglu values in the grey matter of non-SHE and control are almost the same, excepting the basal ganglia. The CMRglu value in the basal ganglia of non-SHE is higher than that of control and SHE. The CMRglu value in the grey matter of SHE is depressed as compared to both non-SHE and control. These data suggest that the abnormalities of cerebral glucose metabolism may be a contributing factor in SHE.

Journal Article↗

Analysis of biochemical and virological efficacy of human lymphoblastoid interferon (IFN) in patients with compensated type C liver cirrhosis: comparative study between increase in individual IFN dose and prolonging of treatment period, using a multicenter randomized controlled trial.

A controlled trial was conducted to compare the efficacy of interferon (IFN) between two groups of patients with type C liver. Thirty-five patients were randomly assigned to group A (17 patients) or group B (18 patients). The former received 3 megaunits (MU) of human lymphoblastoid IFN six days per week for two weeks, followed by three days per week for 50 weeks; the latter group received 6 MU six days per week for two weeks followed by three days per week for 24 weeks. The percentages of biological sustained responders (B-SR) and virological sustained responders (V-SR) were 29.4 and 23.5%, respectively, in group B, and 17.6% for both in group A. The therapeutic effects were not different between two groups. HCV genotype 2 accounted for significantly higher percentage of B-SR and V-SR (both 57.1%, respectively). These findings indicate that IFN is effective in type C cirrhosis with genotype 2.

Adult↗

Calmodulin-dependent and -independent apoptosis in cell of a Drosophila neuronal cell line.

This study was undertaken to reveal apoptotic pathways in neurons using a Drosophila neuronal cell line derived from larval central nervous system. We could induce apoptotic cell death in the cells by a Ca2+ ionophore (A23187), a protein kinase inhibitor (H-7), an RNA synthesis inhibitor (actinomycin D) and a protein synthesis inhibitor (cycloheximide). All the apoptosis induced by each chemical required Ca2+ ions, although the origin of Ca2+ ions were different: apoptosis induced by A23187 was dependent on extracellular Ca2+ ions whereas those by the other three chemicals utilized intracellular Ca2+ ions. Furthermore, different reactions to W-7, a calmodulin inhibitor, were found: W-7 prevented the cell death by each of the three chemicals but not by A23187. Based on the results, we proposed that the apoptotic pathways are classified into two types in individual cells. One pathway induced by H-7, actinomycin D or cycloheximide is calmodulin-dependent (pathway H), and another induced by A23187 is calmodulin-independent (pathway A).

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Involvement of CYP3A4 in the metabolism of bromperidol in vitro.

In this study, human cytochrome P450 isoenzymes (CYP1A2, CYP2C19, CYP2D6, and CYP3A4) expressed in a cell line were used to elucidate their roles in the metabolism of bromperidol. We found that CYP3A4 catalyzes the N-dealkylation of bromperidol and its metabolite, reduced bromperidol. CYP3A4 also catalyzes the dehydration of bromperidol to bromperidol 1,2,3,6-tetrahydropyridine, metabolizes bromperidol to bromperidol pyridinium, and catalyzes the oxidation of reduced bromperidol back to bromperidol. CYP1A2, CYP2C19, and CYP2D6 do not catalyze these reactions.

Aryl Hydrocarbon Hydroxylases↗

Distribution of zinc-binding metallothionein in cirrhotic liver of rats administered zinc.

This study was undertaken in order to investigate the effect of zinc (Zn) administration on induction of Zn-binding metallothionein in rat liver with thioacetamide-induced cirrhosis, and the localization of metallothionein in the liver. Normal and cirrhotic rats received intraperitoneal injections with or without Zn. Subsequently, metal analyses, purification of metallothionein by gel filtration and immunohistochemical assessments of metallothionein were carried out. Although in Zn-injected cirrhotic rats, the Zn contents in the liver and plasma increased significantly depending upon the dose of Zn, the Zn contents in the liver and plasma of the cirrhotic rats were lower than those of normal rats after the same dose of Zn. The results of gel filtration also showed that the levels of Zn-metallothionein in the cirrhotic liver were reduced in comparison with those of the normal liver. By the immunohistochemical method, the presence of metallothionein in the parenchymal areas but not in the fibrotic areas of the cirrhotic liver was confirmed. These results suggested that the induced metallothionein was only located in the parenchymal areas. The metallothionein induced in the parenchymal areas was considered to play a role in protecting the parenchymal cells against the progression of fibrosis, because metallothionein has been thought to be involved in the cellular defense against oxidative stress.

Animals↗

Characterization of autoantibodies to endothelial cells in systemic sclerosis (SSc): association with pulmonary fibrosis.

To determine the prevalence and the characterization of antibodies to endothelial cells in patients with SSc, serum samples from 80 patients with SSc, 20 patients with systemic lupus erythematosus (SLE), and 20 healthy control subjects were examined by ELISA using cultured human umbilical vein endothelial cells (HUVEC), indirect immunofluorescence analysis (IIF), and immunoblotting using cytoplasmic extract of HUVEC. IgG and/or IgM isotype anti-endothelial cell antibodies (AECA) were demonstrated by ELISA in 43 of 80 patients with SSc (54%), in 15 of 20 patients with SLE (75%), and in none of 20 healthy control subjects. Immunofluorescence analysis on HUVEC substrate showed homogeneous cytoplasmic staining. Immunoblotting demonstrated that these patients had antibodies directed to one or several antigens of approximately 60, 90, 110 and 140 kD, and the most common responses were to the 90-kD antigen. By the immunofluorescence method using HUVEC, affinity-purified anti-90-kD antibodies showed identical cytoplasmic staining to that produced by sera positive for AECA. Furthermore, AECA were closely correlated with pulmonary fibrosis in patients with SSc. These findings suggest that patients with SSc have abnormal antibodies to endothelial cell antigens, and support the hypothesis that endothelial dysfunction is involved in the development of this disease.

Adult↗

Decreased expression levels of L-selectin on subsets of leucocytes and increased serum L-selectin in severe psoriasis.

L-selectin is a leucocyte adhesion molecule involved in leucocyte interactions with vascular endothelial cells. Following leucocyte activation L-selectin is endoproteolytically released from the cell surface. To assess whether psoriasis vulgaris results in systemic leucocyte activation, we examined expression levels of L-selectin on subsets of peripheral blood leucocytes from patients with psoriasis (n = 25) and normal control subjects. Serum levels of soluble L-selectin were quantified by ELISA in patients with psoriasis (n = 75), pustulosis palmaris et plantaris, and contact dermatitis, as well as normal control subjects. Psoriasis severity was evaluated by psoriasis area and severity index (PASI). L-selectin expression levels on CD4+ T cells, B cells, monocytes, and neutrophils from patients with severe-type psoriasis (PASI > or = 15) was significantly decreased compared with leucocytes from normal control subjects. Furthermore, L-selectin expression on CD4+ T cells showed good inverse correlation with PASI scores. Monocyte L-selectin expression was restored when the skin lesions of psoriasis were remitted. The frequencies of L-selectin+ CD4+ T cells or L-selectin+ CD8+ T cells from patients with psoriasis were almost normal. Serum L-selectin levels in patients with severe-type psoriasis were significantly higher than those in normal control subjects. These results suggest that subsets of leucocytes may be activated in psoriasis, and that L-selectin expression levels on some leucocyte subsets, especially CD4+ T cells, tend to correlate with disease severity of psoriasis.

Adult↗

Novel mutations of the ACTH receptor gene in a female adult patient with adrenal unresponsiveness to ACTH.

We report a 30-year-old female with adrenal unresponsiveness to ACTH. Her clinical features included no adrenal crisis despite poor drug compliance, poor pubic hair development (Tanner stage 2), well-developed breasts (Tanner stage 5), and regular menstrual cycles. Endocrinological data included blood ACTH 1500 pmol/l, cortisol 18 nmol/l, dehydroepiandrosterone sulphate below 0.26 micromol/l, activated renin 0.37 pmol/l, and aldosterone 3.4 nmol/l. Direct sequencing and allele-specific amplification revealed two novel mutations in the ACTH receptor gene. One was transition from guanine to adenine at nucleotide position 1002, resulting in substitution of aspartate for asparagine at codon 103, and the other was transition from cytosine to thymine at nucleotide 1104, leading to substitution of arginine for tryptophan at codon 137. The present findings lend additional credence to the notions that adrenal androgens play an important role in female pubic hair development and that ovarian development takes place independently of adrenarche.

Adrenal Gland Diseases↗

Evaluation of the PhysioFlex closed-circuit anaesthesia machine.

The concentrations of nitrous oxide, sevoflurane and oxygen in the circle system of a closed-circuit anaesthesia machine, the PhysioFlex, were measured in seven patients. During anaesthesia, the settings for each gas were changed and their concentrations recorded. At the induction of anaesthesia, it took 80-510s (median 190s) for the end-tidal sevoflurane concentration to reach 2.0%, and 920-2640s (median 1500s) for the oxygen in the breathing circuit to reach 30%. At this time, the nitrous oxide concentration was 60+/-3% (mean+/-SD). During anaesthesia, it took 90-480s (median 140s) for the end-tidal sevoflurane concentration setting to decrease from 3.0 to 1.0%, and 90-400s (median 110s) to return from 1.0 to 3.0%. When the inspired oxygen was increased from 30 to 50%, circuit concentrations reached equilibrium in 40-60s (median 40s), and when decreased from 50% back to 30%, equilibrium took 310-470s (median 450s). During recovery from anaesthesia, inspiratory sevoflurane concentration took 40-70s (median 50s) to decrease to 0.2%. The PhysioFlex provided adequate control of sevoflurane and oxygen concentrations, but not of increasing nitrous oxide concentrations.

Adult↗

Protective effect of vaccination with culture supernate of M. hyopneumoniae against experimental infection in pigs.

The protective activity of Mycoplasma hyopneumoniae inactivated vaccine prepared from sedimented whole cells and cell-free culture supernates was evaluated experimentally using hysterectomy-produced, colostrum-deprived pigs in which mycoplasmal pneumonia had been induced. The culture supernate vaccine containing less than 10(1) colour-changing units (CCU)/0.2 ml of M. hyopneumoniae significantly (P < 0.05) reduced the percentage of lung lesions compared to controls (3.2 +/- 3.9 vs. 12.2 +/- 2.2%), whereas the sedimented whole cells vaccine containing 10(10) CCU/0.2 ml of organisms provided variable protection (18.7 +/- 16.5 vs. 12.2 +/- 2.2%). Serum from the pigs vaccinated with culture supernate reacted with six protein bands of 97, 89, 65, 46, 42 and 41 kDa by immunoblot analysis. From these results, we conclude that vaccination with culture supernate of M. hyopneumoniae can provide protection against M. hyopneumoniae infection and that these antigens in the culture supernate may be closely related to the reduction of lung lesions.

Animals↗

Relative power contributions of unit discharges simultaneously recorded in the mesencephalic reticular formation.

In order to investigate mutual interactions between neuronal discharges in the mesencepahlic reticular formation, relative power contributions (RPC) were estimated during sleep-wake cycles and serotonin (5HT)-depleted conditions by the administration of parachlorophenylalanine (PCPA). The RPC for most of the neurons dominated in the lower frequency range below 0.4 Hz during rapid eye movement (REM) sleep and the PCPA-treated conditions, which were qualitatively reproduced by the neural network model under global disinhibition. The results supported the hypothesis that the peculiar dynamics of neuronal activities during REM sleep, 1/f fluctuations, were generated by neuronal interactions augmented by the release from the global inhibition of 5HT.

Animals↗

Endomyometriosis arising in the uterosacral ligament: a case report including a literature review and immunohistochemical analysis.

We report a case of endomyometriosis arising in the left uterosacral ligament of a 29-year-old woman. The central cavity of the uterine-like mass was lined by pseudo-stratified columnar epithelium and endometrial stroma. The wall of the cyst consisted of bundles of smooth muscle cells. Immunohistochemical analysis demonstrated both alpha-estrogen receptor and progesterone receptor immunoreactivities in the epithelial, stromal and smooth muscle cells. A relatively high proliferating activity was also demonstrated in these cells by Ki-67 immunostaining. These findings suggest that the mass was hormone dependent and had a relatively rapid evolution.

Adult↗

A comparative clinical study of pneumonia by penicillin-resistant and -sensitive Streptococcus pneumoniae in a community hospital.

OBJECTIVE: This study aimed to determine the clinical difference of pneumonia between penicillin-resistant and penicillin-sensitive Streptococcus pneumoniae. METHODOLOGY: Forty-nine cases in 46 patients of pneumococcal pneumonia were studied from December 1992 to May 1997. There were 24 cases (in 22 patients) of penicillin-resistant pneumococci (PRSP) pneumonia which were compared with 25 cases (in 24 patients) with penicillin-sensitive pneumococci (PSSP). RESULTS: Both the mean age and the underlying disease states did not differ between the two groups. However, hospital-acquired pneumonia and previous use of antibiotics were observed in eight (33.3%) and 12 (50.0%) patients in PRSP compared with three (12.0%) and two (8.0%) in PSSP, respectively. The clinical efficacy rate and bacteriological eradication rates were 87.5 and 87.5% in PRSP compared with 87.5 and 87.0% in PSSP, respectively. Minimum inhibitory concentration (MIC) of antibiotics against 30 pneumococcal isolates was examined, and 10 strains ranged from 0.10-0.78 microg/mL and five strains were more than 1.56 microg/mL against penicillin G, while the MIC showed higher resistance to other antibiotics except for the carbapenems. Serotyping of the isolates by antiserum revealed differences in the predominant types PRSP (19F) and PSSP (6A,9V) [corrected]. CONCLUSIONS: We must care for not only community-acquired infection but also nosocomial transmission of PRSP pneumonia. Most patients with infections due to PRSP tended to have a milder illness with a good outcome (no patient died). As such it appears that empiric therapy for pneumococcal pneumonia does not require modification from what is recommended at present. However, in patients with infection due to highly resistant strains, and who are not responding to conventional therapy should have their treatment modified according to subsequent susceptibility testing.

Anti-Bacterial Agents↗

Trans-mesosigmoid cutaneous ureterostomy.

BACKGROUND: A new method was developed in order to create a single stoma cutaneous ureterostomy in which both ureters traverse the abdominal cavity and yet are buttressed by the mesosigmoid and covered by its visceral peritoneum. METHODS: The long mesenterium which is attached to the most mobile part of the sigmoid colon was used for the bilateral ureteral pathway. Tunnels for the ureteral path were made just underneath the visceral peritoneum on the bilateral side of the mesosigmoid. Through the tunnels both ureteral ends were brought from the retroperitoneal space to the mesenterocolonic junction (MCJ) and the MCJ is then approximated and sutured to the inside of the ureteral tract through the abdominal wall. The ureters brought outside the skin, are conjoined and sutured to the V skin flap. Eight patients who carried a high risk for operation and/or had a bladder tumor judged to be incurable underwent this cutaneous ureterostomy. RESULTS: All cases except one with low urinary output could be managed without catheter indwelling during the follow-up period. Three patients suffered from paralytic ileus and one required laparotomy for mechanical ileus during the short postoperative period. Postoperative excretory urography evaluated 14 kidneys during the follow-up period from 2 to 61 months and showed normal upper urinary tract in 11 and a mildly hydronephrotic tract in three. CONCLUSIONS: Transmesosigmoid cutaneous ureterostomy provides a single catheterless stoma even when the available ureters are relatively short. It appears to be a good method for supravesical urinary diversion when indicated.

Aged↗

Case of mesothelioma of the tunica vaginalis testis with characteristic findings on ultrasonography and magnetic resonance imaging.

A case of mesothelioma of the right tunica vaginalis testis in a 32-year-old man is reported. Trans-scrotal ultrasonography revealed hydrocele and multiple nodular masses measuring 1.0-4.5 cm in size attached to the parietal vaginal layer. Magnetic resonance imaging demonstrated more clearly nodular masses with irregular surfaces lined on the hydrocele cavity. Histologic diagnosis of the tumor when orchiectomized was mesothelioma. The patient has been free of disease for approximately 3 years since the treatment.

Adult↗