[Systemic lupus erythematosus with anti-phospholipid syndrome complicated with polyneuropathy].
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Adult↗
Biomedical subjects
T Satoh
Publications and source records attributed to T Satoh.
Androgen metabolism in regenerating liver of male rats: evidence for active uptake and utilization of testosterone.
The role of androgen in the regenerative process of the liver remains unclear. Male Sprague-Dawley rats were subjected to either 70% hepatectomy or sham operation. Immediately after surgical procedures, rats were injected with 0.3 µCi/g of body weight [3H]-testosterone from the inferior vena cava. The radioactivities of the remnant liver were counted for 0-24 h. For measurement of sex hormones and their metabolizing enzymes activities in the regenerating liver, the same experiments were also conducted, in which the rats were sacrificed up to 120 h. The plasma and hepatic testosterone, dihydrotestosterone(DHT) and estradiol were determined by radioimmunoassays. Uptake of [3H]-testosterone in the regenerating liver was significantly higher during the first 6 h. 5alpha-reductase I and DHT were increased in parallel to the hepatocyte proliferation which was assessed by proliferating cell nuclear antigen (PCNA) labeling index. On the other hand, hepatic 3alpha-hydroxysteroid dehydrogenase level did not alter but aromatase activity significantly decreased after 70% hepatectomy. These results suggest that during the early phase of liver regeneration, testosterone was actively uptaken from the plasma by the regenerating liver and was converted into DHT by elevated hepatic 5alpha-reductase enzyme. Thus androgens might play a crucial role in liver regeneration.
Journal Article↗
Growth and gene expression profile analyses of endometrial cancer cells expressing exogenous PTEN.
The PTEN tumor suppressor gene encodes a multifunctional phosphatase that plays an important role in inhibiting the phosphatidylinositol-3-kinase pathway and downstream functions that include activation of Akt/protein kinase B, cell survival, and cell proliferation. Enforced expression of PTEN in various cancer cell lines decreases cell proliferation through arrest of the cell cycle, accompanied in some cases by induction of apoptosis. We used cDNA microarrays containing 4009 cDNAs to examine changes in gene-expression profiles when exogenous PTEN was induced in PTEN-defective cells. The microarrays and subsequent semi-quantitative reverse transcription-PCR analysis revealed transcriptional stimulation of 99 genes and repression of 72 genes. Some of the differentially expressed genes already had been implicated in cell proliferation, differentiation, apoptosis, or cell cycle control, e.g., overexpression of PTEN-induced transactivation of cyclin-dependent inhibitor 1B (p27Kip1) and 2B (p15INK4B), members of the TNF receptor family, tumor necrosis factor-associated genes, and members of the Notch-signaling and Mad families. To our knowledge this is the first report of transactivation of those genes by PTEN. The genes differentially expressed in our experiments also included many whose correlation with cancer development had not been recognized before. Our data should contribute to a greater understanding of the broad spectrum of ways in which PTEN affects intracellular signaling pathways. Analysis of expression profiles with microarrays appears to be a powerful approach for identifying anticancer genes and/or disease-specific targets for cancer therapy.
Adenoviridae↗
Three-dimensional estimation of the distribution and size of putative functional units in rat gustatory cortex as assessed from the inter-neuronal distance between two neurons with correlative activity.
Two neurons recorded simultaneously in rat gustatory cortex often show, when the oral mucosa is stimulated with effective taste solutions, correlative activities (CAs), which can be quantified with a cross-correlation technique. It has been suggested that the CAs are involved in taste quality discrimination and the neuron pairs with CA (CA pairs) may function as a unit (putative functional unit). The present experiment was undertaken (1) to determine the three-dimensional size of putative functional units in rat gustatory cortex on the basis of the interneuronal distance (IND) in individual CA pairs, and (2) to examine to what extent the CA is related to the intrapair similarity in taste responses. The findings were as follows: (1) The CAs occurred in 30 out of 55 pairs with INDs < or =270 microm and often at INDs <100 microm. (2) The numbers of putative functional units were calculated tentatively by using the longest or the mean INDs; at least 200 or over 4,000 units, respectively. (3) In the CA pairs, the "best taste" was identical (homo-type) in many pairs, the "taste profiles" were often similar, and the temporal courses of taste responses resembled each other in more than one half of the pairs. A possible role of hetero-type pairs was discussed. (4) In a small number of cases, troughs were observed in the CCs, suggesting the involvement of local inhibitory neurons. In conclusion we point out that nearby neurons are prone to CA, if (1) their best tastes are identical, (2) their taste profiles are similar, and (3) the temporal patterns of taste response resemble each other.
Action Potentials↗
Isolation and characterization of the rat prolactin-releasing peptide gene: multiple TATA boxes in the promoter region.
The prolactin-releasing peptide (PrRP) gene is a novel bioactive peptide expressed in very restricted regions in the brain. To explore the molecular mechanism of PrRP gene expression, we cloned and characterized the gene and its promoter region. The gene spans approximately 2.4 kb and contains three exons and two introns. 3'RACE analysis showed that a polyadenylation signal 103 bp downstream from the stop codon was functional. Primer extension analysis indicated three transcriptional start sites (TSSs) 92, 199, and 325 bp upstream from the translational start site. Interestingly, in addition to the putative binding sites for SP1-1, AP-2, and Oct-2A, three characteristic TATA boxes were identified close to these TSSs. Transient transfection study using a series of deletion mutants revealed that the middle TATA box is important for the promoter activity. Furthermore, the cloned 1.6 kb promoter region was active only in neuron- and pituitary-derived cell lines, and the promoter region -1600 approximately -800 bp worked as a negative regulatory element. We demonstrated for the first time, the genomic organization and promoter function of the PrRP gene, and this knowledge will facilitate elucidation of transcriptional control of the PrRP gene.
3' Untranslated Regions↗
Efficacy of a 14-day course of oral ciprofloxacin therapy for acute uncomplicated pyelonephritis.
This study aimed to evaluate the efficacy and safety of oral antibacterial treatment with fluoroquinilone for acute uncomplicated pyelonephritis Thirteen female patients with acute uncomplicated pyelonephritis were treated with oral fluoroquinilone (ciprofloxacin; CPFX). They received 200 mg of the drug three times a day while febrile (3-5 days). Once they become afebrile, the same dose of the drug, given twice a day, was given for another 9-11 days. The mean duration of the course of CPFX was 14 days. Symptoms were evaluated, and laboratory examinations, including urine culture and measurement of the minimal inhibitory concentration (MIC) of CPFX were conducted before treatment, and 3, 7, 14, 21, and/or 28 days after the initiation of the treatment. Of the 13 patients, only 5 needed to be hospitalized, and the period of hospitalization was only a few days. On the 14th day after the commencement of treatment, bacteriologic and clinical cure rates were 100%. Escherichia coli was the most common uropathogen, being isolated from the urine of 8 patients. No clinical relapse of the disease was found during a follow-up period of up to 4 weeks. The patients tolerated the drug well without developing any serious adverse effects. Oral antimicrobial chemotherapy with fluoroquinolone, given on an outpatient or short-term hospitalization basis, achieved satisfactory bacteriological and clinical outcomes in the treatment of acute uncomplicated pyelonephritis. This treatment regimen is indicated for patients with this disease who are not in a serious condition with complications such as shock.
Acute Disease↗
Effect of dexmedetomidine on the release of [3H]-noradrenaline from rat kidney cortex slices: characterization of alpha2-adrenoceptor.
The presynaptic modulation of [3H]-noradrenaline (NA) release from rat kidney cortex slices, a method used for the first time, was investigated. Rat kidney cortex slices were loaded with [3H]-NA and the release of radioactivity at rest and in response to field stimulation was determined. The alpha(2)-adrenoceptor agonist, dexmedetomidine inhibited the stimulation-evoked release of NA from kidney slices in a concentration-dependent manner, whereas alpha(2)-adrenoceptor antagonist CH-38083 (7,8-methyenedioxy-14-alpha-hydroxyalloberbane HCl), an alpha(2)-adrenoceptor antagonists, enhanced it. When dexmedetomidine and BRL-44408, a selective alpha(2A) antagonist, were added together, the effect of dexmedetomidine was significantly antagonized. In contrast, ARC-239 (2-(2,4-(o-piperazine-1-yl)-ethyl-4,4-dimethyl-1,3-(2H, 4H)disoguinolinedione chloride), a selective alpha(2B)-antagonist, had no effect on the release and failed to prevent the effect of dexmedetomidine. Prazosin, an alpha(1)- and alpha(2B/C)-adrenoceptor antagonist enhanced the release evoked by field stimulation. It is therefore suggested that there is a negative feedback modulation of NA release at the sympathetic innervation of kidney cortex, and dexmedetomidine, a clinically used anesthetic adjunct inhibits the release via activation of alpha(2C)-adrenoceptors.
Adrenergic alpha-2 Receptor Agonists↗
Expression of glutathione S-transferase pi (GST-pi) in human malignant ovarian tumors.
OBJECTIVES: In recent years, glutathione S-transferase pi (GST-pi) has attracted much attention and has been studied as a mechanism of multidrug resistance of tumors to anticancer drugs. In the present study, we immunohistologically measured the expression of GST-pi in tumor tissues using surgical specimens obtained from patients with malignant ovarian tumors. METHODS: Of 137 patients with malignant ovarian tumors treated and managed during a period of 20 years since the establishment of Tsukuba University Hospital, 117 patients were selected as subjects because of the presence of complete data on their clinical courses as well as paraffin blocks preserved in a good condition. GST-pi in these specimens was immunohistochemically stained to determine the correlation between GST-pi stainability and clinical outcomes. Stainability was graded as 0 when GST-pi was completely absent, 1 when less than 20% of tumor cells were stained, 2 when 20--60% were stained, and 3 when more than 60% were stained. RESULTS: When the correlation between stainability and clinical outcomes was analyzed with Kaplan--Meier method, excluding stage Ia cases that did not receive adjuvant chemotherapy at our hospital, significantly better clinical outcomes were observed in the low stainable group, compared with the high stainable group (P<0.01--0.05, Cox--Mantel test, Wilcoxon's test). CONCLUSION: Since the stainability for GST-pi was high in tumors of histological types with strong resistance to anticancer drugs, and better clinical outcomes were observed in cases having a lower stainability score, the expression of GST-pi was thought to play some role in the resistance of malignant ovarian tumors to anticancer drugs.
Adenocarcinoma, Clear Cell↗
Halothane decreases impulse-dependent but not cytoplasmic release of dopamine from rat striatal slices.
Using in vitro superfusion techniques and electrical field stimulation, a volatile anesthetic, halothane, decreased impulse-dependent vesicular release, but did not affect amphetamine-induced cytoplasmic release of dopamine (DA) from the rat striatal slice preparations loaded with [3H]-DA. Contrary to previous in vivo studies, halothane at concentrations applied (1% to 4%) did not enhance the release of DA from slice preparation in which the cell bodies were absent, and therefore, the possible site of action was located on the axon terminals. In this in vitro experiment, halothane decreased the fractional release of DA in a concentration-dependent manner and attenuated the increase of impulse-dependent DA release when amphetamine or nomifensine administration was combined with electrical stimulation. D2-receptor agonists (quinpirole and apomorphine) reduced the release, and antagonists (sulpiride and haloperidol) enhanced the release of DA. In the presence of halothane, D2-receptor antagonists had no effect on DA release. It is concluded that halothane may have some modulatory effect on D2-receptor mediated presynaptic control of DA release.
Action Potentials↗
A small dose of midazolam decreases the time to achieve hypnosis without delaying emergence during short-term propofol anesthesia.
STUDY OBJECTIVE: To evaluate the effect of a small dose of midazolam (10 microg kg(-1)) on induction and emergence during short-term propofol anesthesia and to investigate the effects of subsequent administration of flumazenil. DESIGN: Double-blinded, prospective, randomized study. SETTING: Operating room of a medical college hospital. PATIENTS: 30 male ASA physical status I and II patients (ages 51 to 75) scheduled for minor surgery under spinal anesthesia. INTERVENTIONS: Patients were randomly allocated to one of three groups: the placebo-propofol-placebo (PP) group, the midazolam-propofol-placebo (MP) group, or the midazolam-propofol-flumazenil (MF) group. After administering placebo or midazolam (10 microg kg(-1)), propofol 250 microg kg(-1) min(-1) was infused. Immediately after confirming that the patient was hypnotized, we terminated the propofol infusion and administered placebo or flumazenil (5 microg kg(-1)). MEASUREMENTS: The dose and the times required to achieve hypnosis (the first endpoint) and to emerge from anesthesia (the second endpoint). The plasma concentration at each endpoint was determined. MAIN RESULTS: Midazolam significantly decreased the dose and time needed to achieve hypnosis [PP vs. MP, 66 +/- 14 vs. 48 +/- 15 mg, 260 +/- 55 vs. 179 +/- 44 sec, respectively (mean +/- SD)]. Thus, the plasma concentration of propofol at hypnosis was significantly lower (PP vs. MP, 3.31 +/- 0.78 vs. 2.41 +/- 0.57 microg mL(-1)). The time to emerge from anesthesia was not prolonged by midazolam, and was further shortened by administration of flumazenil (PP, MP vs. MF, 237 +/- 77, 207 +/- 71 s vs. 126 +/- 56 sec, respectively). Flumazenil also reversed the reduction in propofol concentration induced by midazolam at emergence (PP, MP, and MF, 0.54 +/- 0.17, 0.37 +/- 0.15, and 0.59 +/- 0.22 microg mL(-1), respectively). CONCLUSIONS: Coadministration of 10 microg kg(-1)midazolam decreases the dose and time required to achieve hypnosis with propofol induction without delaying emergence from anesthesia. Additional administration of flumazenil further shortens the time to emerge from midazolam-propofol anesthesia.
Adjuvants, Anesthesia↗
High-dose flumazenil potentiates the hypnotic activity of propofol, but not that of thiopental, in ddY mice.
BACKGROUND: Flumazenil is a specific benzodiazepine agonist, which is reported to have a partial benzodiazepine agonist-like effect at a high dose. This study investigated the effects of flumazenil and midazolam on the hypnotic dose of propofol and thiopental in ddY mice, using a behavioral model. METHODS: Mice were given either propofol or thiopental intravenously to induce hypnosis, which was defined as a loss of the righting reflex. The mice were pre-treated with flumazenil (0.05, 0.1, or 0.2 mg kg(-1)) or midazolam (0.1 or 0.2 mg kg(-1)), and given propofol or thiopental after a 30-s delay. RESULTS: Pre-treatment with flumazenil (0.1 or 0.2 mg kg(-1)) significantly decreased the hypnotic dose of propofol compared to the control group (9.3+/-0.39 [8.5-10.0] or 9.0+/-0.28 [8.5-9.6] vs. 10.8+/-0.42 [9.9-11.6] mg kg(-1) (ED50+/-SEM and [95% confidence interval]) P<0.05), but not that of thiopental (9.1+/-0.30 [8.5-9.7] with 0.2 mg kg(-1) flumazenil vs. 9.3+/-0.42 [8.4-10.1] mg kg(-1) with saline). Midazolam reduced the hypnotic dose of both propofol and thiopental. Flumazenil antagonized the potentiating effect of midazolam (0.2 mg kg(-1)) on the hypnotic activity of propofol. CONCLUSIONS: These results suggest that the hypnotic activity of propofol is potentiated by the partial agonist activity of flumazenil in ddY mice.
Anesthetics, Intravenous↗
Comparison of plasma alpha glutathione S-transferase concentrations during and after low-flow sevoflurane or isoflurane anaesthesia.
BACKGROUND: We evaluated the effect of low-flow sevoflurane anaesthesia, in which compound A is generated, and isoflurane anaesthesia, in which compound A is not generated (n=13 in each group), on hepatocellular integrity using alpha glutathione S-transferase (GST). Alpha GST is a more sensitive and specific marker of hepatocellular damage than is aminotransferase activity and correlates better with hepatic histology. METHODS: Sevoflurane or isoflurane were delivered without nitrous oxide with a fresh gas flow of 1 l/min. Concentrations of compound A in the circuit were measured hourly, and plasma alpha GST concentrations were measured perioperatively. RESULTS: Mean duration of anaesthesia was 338+/-92 min in the sevoflurane group and 320+/-63 min in the isoflurane group. Mean compound A concentration in the sevoflurane group was 28.6+/-9.0 ppm. There was no significant difference in alpha GST concentrations between the sevoflurane and isoflurane groups during or after anaesthesia. CONCLUSION: These results indicate that low-flow sevoflurane and isoflurane anaesthesia have the same effect on hepatic function, as assessed by plasma alpha GST concentrations.
Adult↗
An assessment of a method of inflating cuffs with a nitrous oxide gas mixture to prevent an increase in intracuff pressure in five different tracheal tube designs apparatus.
We assessed the efficacy of inflating cuffs with a nitrous oxide gas mixture to minimise changes in intracuff pressure during anaesthesia. Patients were randomly assigned to one of five groups of 15 subjects each, and the trachea was intubated with the Profile Soft-Seal Cuff, Hi-Contour, Reinforced, Sheridan or Trachelon tracheal tubes. Cuffs were inflated with 40% nitrous oxide and cuff pressure was measured during anaesthesia with 67% nitrous oxide. Concentration of nitrous oxide in the cuff was measured at the end of anaesthesia. Cuff pressure increased slightly but significantly in the Reinforced and Trachelon groups. Nitrous oxide concentration in the Reinforced, Sheridan, or Trachelon groups was slightly but significantly higher than that in the Profile or Hi-Contour groups. Cuff pressure never exceeded 22 mmHg and there were no air leaks. Therefore, inflating cuffs with 40% N2O preserves stable cuff pressure in all five tracheal tubes, despite differences in cuff and pilot balloon design.
Adolescent↗
Topical glucocorticoids application induced an augmentation in the expression of IL-1alpha while inhibiting the expression of IL-10 in the epidermis in murine contact hypersensitivity.
The repeated application of glucocorticoids (GC) on the skin augmented the inflammatory response of both allergic and irritant contact dermatitis in our studies. In order to further clarify the mechanism of such an augmentation of contact hypersensitivity (CHS), we investigated the modulatory effects of cytokines in the epidermis after the administration of GC at challenged sites in CHS. Diflucortolone valerate was applied to BALB/c mice on alternate days for a total of nine times. On day 12, they were contact sensitized with dinitrofluorobenzene (DNFB). Next, on day 17, one day after the last application of GC, they were challenged with DNFB on the ear. The whole challenged ear lobes were removed after a hapten challenge and then were analysed by the RT-PCR method or underwent an immunohistochemical analysis. To clarify the modulatory effects of cytokines in vivo, DNFB sensitized mice pre-treated with GC were injected with rIL-10, IL-1 receptor antagonist (ra) and anti-IL-1alpha monoclonal antibody (mAb) and thereafter were challenged with DNFB. A RT-PCR analysis has demonstrated IL-10 mRNA to be detected in the challenged skin of non-GC-pretreated mice but not in that of GC-pre-treated mice after challenge. On the other hand, the expression of IL-1alpha mRNA in the challenged skin of mice pretreated with GC was more strongly detected that that in mice without GC-pretreatment. Furthermore, an immuno-histochemical analysis in the challenge showed the expression of IL-10 in the skin showed the expression of IL-10 in the challenged epidermis of the non-GC-pretreated mice but not in the GC-pretreated mice and IL-1alpha was also strongly expressed in the epidermis of the GC-pretreated mice. A subcutaneous injection of anti-IL-1alpha mAb or IL-1 ra inhibited the augmented CHS reaction in the GC-pretreated mice. A subcutaneous injection of rIL-10 also inhibited the augmentation of the CHS reaction in the GC-pretreated mice; however, no such inhibition was observed in the non-GC-pretreated mice. These results indicated that both an up-regulation of IL-1alpha production and the inhibition of the IL-10 production in the epidermis at the challenged skin sites in the GC-pretreated mice appear to play a critical role in the GC-induced augmentation of murine CHS.
Administration, Topical↗
Involvement of a urethane-sensitive system in timing the onset of gastrulation in Xenopus laevis embryos.
This paper describes success in delaying the onset of gastrulation in Xenopus laevis embryos without damage to their subsequent development by temporarily arresting cleavage with urethane. Exposure of X. laevis embryos to 150 mM urethane before gastrulation resulted in cleavage arrest and its removal led to cleavage resumption. During cleavage arrest, cyclic activities including nuclear replication and the M-phase-promoting factor cycle continued, although their duration was lengthened to nearly 1.8-fold that of the controls. Because of a 30-min time lag from removal of urethane to resumption of cleavage, as well as the retardation of cyclic activities during cleavage arrest, the development of embryos after a 60-min exposure to urethane lagged two cell cycles behind that of control embryos. Here, the two cell cycle delay is equivalent to 50 min at 22-23 degrees C. The start of gastrulation in exposed embryos was accordingly delayed about 50 min, although the delay in mid-blastula transition was as little as 20-25 min. Consistent results were obtained in embryos exposed to urethane for 90 or 120 min and those exposed to procaine or NH4Cl for 60 min. Although these results imply that delay in the start of gastrulation in exposed embryos is ascribed simply to delay in their development raised by cleavage arrest, at the same time they suggest that the onset of gastrulation is timed by systems sensitive to urethane, procaine and NH4Cl in X. laevis embryos.
Ammonium Chloride↗
Establishment and characterization of three new rat renal cell carcinoma cell lines from N-ethyl-N-hydroxyethylnitrosamine-induced basophilic cell tumors.
Three new rat cell lines (designated as BP13, BP30 and BP36B), derived from rat basophilic-type renal cell carcinomas induced with N-ethyl-N-hydroxyethylnitrosamine, were established and characterized. Passaged up to 100 times in vitro for 3 years, each cell line forms epithelial monolayers with cell cycles for BP13, BP30 and BP36B of 29, 21 and 17 h, respectively. Positive glucose-6-phosphate dehydrogenase (G6PD) and gamma-glutamyltransferase (gamma-GT) activity in their cytoplasm, but negative succinate dehydrogenase (SD) and slightly positive carbonic anhydrase type II (CA) localization indicates an origin from proximal tubules. Ultrastructural examination showed the presence of variable numbers of mitochondria and many microvilli and intracellular junctions on the plasma membrane. BP13 and BP30 were found to be tetraploid and BP36B diploid. BP13 has one marker chromosome 15p+, and BP36B an isochromosome of 1q. Anchorage-independent growth and tumorigenicity in immunosuppressed nude mice of BP13 and BP36B, but not BP30, proved their neoplastic nature. These three cell lines should provide useful tools for studying the biological characteristics of renal cell tumors.
Animals↗
Expression of the hepatocyte growth factor/c-Met pathway is increased at the cancer front in breast carcinoma.
Expression of hepatocyte growth factor (HGF) and c-Met (HGF receptor) has been reported in many neoplasms. We investigated coexpression of HGF and c-Met to determine the role of the HGF/c-Met pathway in breast carcinoma, especially at the cancer front. Eighty-eight cases of carcinoma of the breast were studied by immunohistochemistry and by in situ hybridization for HGF and c-Met expression. The staining pattern was termed "front accentuation pattern" when it was most conspicuous at the cancer front. HGF and c-Met proteins were expressed in cancer and stromal cells, with autocrine and paracrine patterns. The front accentuation pattern of c-Met was observed in cancer cells, but not in stromal cells. The front accentuation pattern was not observed in HGF. Coexpression of HGF and c-Met at the cancer front was correlated with histologic grade, reduced patient survival and a high Ki-67 labeling index. Our findings suggest that the HGF/c-Met pathway acts primarily as a mitogen, especially at the cancer front, in a paracrine manner and affects some clinical factors, including patient survival.
Adult↗
Composite glandular-endocrine cell carcinoma of the common bile duct.
A rare case of composite glandular-endocrine cell carcinoma of the common bile duct is presented. Histologically, this tumor consisted of adenocarcinoma and small-cell neuroendocrine carcinoma, with a transition between the two components. The two distinct areas of the tumor were immunohistochemically different, whereas the transitional zone exhibited characteristics of both areas. These features suggest that the tumor arose from a multipotential stem cell. Although it has been reported that the presence of neuroendocrine differentiation in carcinomas indicates a poor prognosis, the patient in the present case was well at the time of writing this report. This may be due to the fact that adenocarcinoma, which characteristically has a low proliferative activity, constituted the majority of the tumor.
Adenocarcinoma↗