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Biomedical subjects

S Sakai

Publications and source records attributed to S Sakai.

At least 217 records · Page 12Linked to original sources
PubMed1996

Different carcinogenesis in the gastric remnant after gastrectomy for gastric cancer.

BACKGROUND: The incidence of gastric remnant cancer after surgery for gastric malignancies has been increasing. The interval between previous operations and the diagnosis of gastric remnant cancer, location of cancer development, and histologic type were different from those after surgery for benign diseases. However, very little is known about the reasons for these differences. Patients with gastric cancer already have cancer-related gastric mucosal changes at gastrectomy, and they undergo a wide range of dissection of nerve distribution to the stomach due to lymph node dissection. Therefore, the effects of preliminary administration of a carcinogenic agent and denervation of the gastric mucosa on tumorigenesis in the gastric remnant were investigated. METHODS: Using male Wistar rats, N-methyl-N'-nitro-N-nitroguanidine (MNNG; 50 mg/L) was given in drinking water for 10 weeks. The animals were then assigned into four groups of those undergoing Billroth I (B-I) gastrectomy or Billroth II (B-II) gastrectomy, with and without denervation. Subdiaphragmatic truncal vagotomy was performed in the denervated group. Thirty weeks after gastrectomy, the following investigations were performed: histologic examination and periodic acid-Schiff-Alcian blue (PAS-AB) staining of the gastric mucosa by immunohistochemistry of proliferating cell nuclear antigen (PCNA). RESULTS: In macroscopic findings, the groups undergoing nitrosoguanide (NG) gastrectomy with denervation showed a significant increase in the development of whitish, nodular changes in the gastric body. These changes mainly consisted of intestinal metaplasia in microscopic findings. In the NG gastrectomy group, the cancer developed at a lower rate of incidence at the anastomotic site and in the gastric body (1 of 11 rats and 1 of 11 rats, respectively). Conversely, a higher incidence of cancer development (5 of 13 rats) in the gastric body was observed in the group that underwent NG gastrectomy with denervation. Furthermore, the denervation group showed a significant increase in the PCNA labeling index and a distinct increase in the staining of Alcian blue positive mucin in the mucosa of the gastric body. The cancers that developed in the gastric body showed horizontal growth and were accompanied by intestinal metaplasia. In contrast, the cancers that developed in the gastric stumps showed downward growth, and were always accompanied by adenocystic proliferation, but not intestinal metaplasia. CONCLUSIONS: Different processes of carcinogenesis in the gastric remnant are postulated after the surgery for gastric malignancies. The developed cancer is defined by its location and the gastric mucosal changes that developed at the time of gastrectomy.

Animals↗
PubMed1996

Endogenous endothelin-1 participates in the maintenance of cardiac function in rats with congestive heart failure. Marked increase in endothelin-1 production in the failing heart.

BACKGROUND: Although it was demonstrated that circulating endothelin-1 (ET-1) levels are elevated in congestive heart failure (CHF), the production and roles of ET-1 in the failing heart are not known. We investigated the production of ET-1 in the heart and the density of myocardial ET receptors in rats with CHF. We also investigated the effects of intravenously infused BQ-123, an endothelin(A) (ETA) receptor antagonist, on both heart and myocardial contractility in rats with CHF. METHODS AND RESULTS: We used the left coronary artery-ligated rat model of CHF (CHF rats). Three weeks after surgery, the rats developed CHF. Plasma ET-1 concentration was significantly higher in the CHF rats than in the sham-operated rats (P<.01). In the left ventricle, the expression prepro-ET-1 mRNA was markedly higher in the CHF rats than in the sham-operated rats. The peptide level of ET-1 in the left ventricle was also significantly higher in the CHF rats than in the sham-operated rats (500+/-41 versus 102+/-10 pg/g tissue, P<.01). Myocardial ET receptors were significantly higher in the CHF rats than in the sham-operated rats (243+/-20 versus 155+/-17 fmol/mg protein, P<.05). In the CHF rats, intravenous BQ-123 infusion (0.1 mg x kg(-1) x min(-1) for 120 minutes) significantly decreased both heart rate (P<.01) and LV+dP x dt(max) (P<.05) but not mean blood pressure. BQ-123 infusion did not affect these hemodynamic parameters in the sham-operated rats. CONCLUSIONS: In the present study, we demonstrated that the production of ET-1 in the heart is markedly increased and that the density of myocardial ET receptors is significantly elevated in the CHF rats. Intravenous BQ-123 infusion significantly reduced both heart rate and LV+dP/dt(max) in the CHF rats but not in the sham-operated rats. Therefore, the ET receptor-mediated signal transduction system in the heart appears to be markedly stimulated in the CHF rats, and endogenous ET-1 may be involved in the maintenance of the cardiac function in these rats.

Animals↗
PubMed1996

Solitary cavernous hemangioma of the duodenum: report of a case.

Vascular lesions of the duodenum, including hemangioma, are rare causes of gastrointestinal bleeding. We herein describe a 52-year-old woman with a solitary cavernous hemangioma of the duodenum that caused chronic gastrointestinal bleeding. Repeated upper gastrointestinal endoscopy and a barium meal study revealed a solitary vascular tumor in the fourth portion of the duodenum, although the initial investigations including selective angiography were unsuccessful. A wedge resection of the duodenum was performed and microscopical examination showed a cavernous hemangioma. Vascular lesions should therefore also be considered in the differential diagnosis of patients with gastrointestinal bleeding of unknown origin.

Diagnosis, Differential↗
PubMed1996

Expression of interferon-alpha receptor mRNA in the liver in chronic liver diseases associated with hepatitis C virus: relation to effectiveness of interferon therapy.

To investigate whether interferon-alpha receptor (IFN-alpha Rc) expression was related to the effectiveness of interferon therapy in hepatitis C virus (HCV)-associated chronic liver disease (CLD). IFN-alpha Rc mRNA was investigated by reverse transcription polymerase chain reaction (RT-PCR) in liver biopsies and peripheral blood mononuclear cells (PBMCs) from 40 patients with HCV-associated CLD who subsequently received IFN-alpha therapy. IFN-alpha Rc mRNA in the liver was detected in 18 of 20 (90%) responders to IFN and in 5 of 20 (25%) non-responders (P < 0.01). In PBMCs, IFN-alpha Rc mRNA was detected in all patients regardless of response to IFN. Increased histological hepatitis activity and liver fibrosis were significantly related to the absence of IFN-alpha Rc mRNA. The HCV-RNA genotype showed no significant relationship to IFN-alpha Rc mRNA expression. Our results suggest that IFN-alpha Rc mRNA expression in the liver, but not in PBMCs, is closely associated with the effectiveness of IFN-alpha therapy in HCV-associated CLD.

Antiviral Agents↗
PubMed1996

Intradermal administration of lipopolysaccharide in treatment of human cancer.

Lipopolysaccharide (LPS) has been recognized as a potent antitumor agent in animal tumor models; however, its use in human cancer therapy has been limited to only one trial, in which LPS from Salmonella was given intravenously. It was not very successful because of poor tumor response and was also toxic. We originally developed LPS prepared from Pantoea agglomerans (LPSp), and this was a well-purified, small-molecular-mass (5 kDa) agent. We chose intradermal rather than intravenous administration in the hope that the former would release LPS slowly into the bloodstream, and thus be less toxic while preserving antitumor activity. In our animal tumor models, intradermal administration was indeed less toxic and more beneficial for tumor regression than intravenous administration. We made a pilot study with intradermal administration of LPSp on the treatment of ten advanced cancer patients. Five of them had evaluable tumor, which had failed earlier to respond to conventional chemotherapy. Cyclophosphamide was also administered in this trial, in anticipation of its synergistic effect with LPSp. In this study LPSp was injected intradermally into each patient twice a week, starting with an initial dose of 0.4 ng/kg, and raising it to 600 or 1800 ng/kg. A 400-mg/m2 dose of cyclophosphamide was given intravenously every 2 weeks. After completion of the dose escalation, the treatment was continued for at least 4 months, and it was found that 1800 ng/kg LPSp was well tolerated. A significant level of cytokines was observed in the sera for at least 8 h. These results indicate higher tolerable doses and remarkably more continuous induction of the cytokines than were reported in a previous study by others using intravenous administration. Three of the five evaluable tumors showed a significant response to our combined therapy. Intradermally administered, LPS was less toxic and elicited a tumor response in combination with cyclophosphamide; it can thus can be applied to cancer treatment even in humans.

Administration, Cutaneous↗
PubMed1996

Is there a circadian variation in plasma concentrations of etoposide given by prolonged continuous infusion?

The prolonged continuous infusion of low-dose etoposide is a new approach to treating cancer. Whether or not a circadian variation in the plasma levels of etoposide existed was investigated in nine patients with non-small-cell lung cancer. Etoposide was infused for 14 days and blood samples were obtained every 4 h for 1 day. There was no significant circadian variation, and the observed small within-day variations seemed to lack clinical significance.

Aged↗
PubMed1996

Antinociceptive action of mitragynine in mice: evidence for the involvement of supraspinal opioid receptors.

Mitragynine is a major alkaloidal constituent extracted from the young leaves of Mitragyna speciosa Korth. (Rubiaceae). We investigated an antinociceptive activity of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) injection of this alkaloid by the tail-pinch and hot-plate tests in mice, and evaluated the mechanisms of the action using naloxone, an opioid receptor antagonist. Mitragynine (5.0-30 mg/kg, i.p. and 1.0-10 micrograms/mouse, i.c.v.) exerted a dose-dependent antinociceptive activity which was maximal at 15-45 min after injection in the tail-pinch and hot-plate tests, but it did not induce a morphine-like behavioral change. the antinociceptive actions of i.p. mitragynine were completely abolished by both s.c. (2 mg/kg) and i.c.v (10 micrograms/mouse) naloxone. The action of i.c.v. mitragynine (10 micrograms/mouse) was also antagonized by i.c.v. naloxone (10 micrograms/mouse). These results indicate that mitragynine itself can induce antinociception by acting in the brain, and that the supraspinal opioid systems are at least partly involved in the antinociceptive action of mitragynine in mice.

Analgesia↗
PubMed1996

Arterialised venous groin flap: case report.

A defect of the right cheek, mastoid and inferior auricular region in a 16-year-old female after resection of a squamous cell carcinoma was covered with a free arterialised venous groin flap. As the conventional groin flap did not include the superficial circumflex iliac artery, one of the two superficial circumflex iliac veins was arterialised and the other was used as the draining vein. Part of the flap underwent full-thickness necrosis; however, the area that survived was enough to cover the defect.

Adolescent↗
PubMed1996

Sclerosing encapsulating peritonitis in patients undergoing continuous ambulatory peritoneal dialysis: a report of the Japanese Sclerosing Encapsulating Peritonitis Study Group.

Patients undergoing continuous ambulatory peritoneal dialysis (CAPD) who developed sclerosing encapsulating peritonitis (SEP) were retrospectively studied in 130 centers in Japan. Among 6,923 patients undergoing CAPD between 1980 and 1994 only 62 (0.9%) given CAPD developed SEP. There were 38 men and 24 women, ranging in age from 20 to 87 years (average age, 48.3 years). These 62 patients developed SEP 10 to 138 months (average, 65.4 months) after starting CAPD. The average frequency of peritonitis before developing SEP was 3.3 times. Five of the 62 patients with SEP had no history of peritonitis, and 27 (43.5%) of them died of various causes in the study period. The major causes of death were almost invariably related to problems concerning bowel obstruction or complications of surgery, such as malnutrition or septicemia. It was concluded that SEP is one of the most serious complications of CAPD, and constant surveillance is necessary to detect SEP in patients during CAPD.

Adult↗
PubMed1996

Acceptability of patients with brain metastases for clinical trials of chemotherapy for metastatic non-small-cell lung cancer.

This study was conducted to determine whether patients with brain metastases from non-small-cell lung cancer (NSCLC) should be included in clinical trials of chemotherapy. Patients with metastatic NSCLC and good performance status were studied. The survival of patients with brain metastases was compared with that of patients without brain metastases. Of 100 eligible patients, 22 had brain metastases at diagnosis. The median survival time was poorer in patients with brain metastases than in other patients with metastatic NSCLC (96.5 vs. 181.5 days). However, the difference in survival was not significant on univariate analysis (p = 0.106). Multivariate analysis confirmed that the prognostic value of brain metastases was limited in this sample (p = 0.129). There was little difference in survival curves during the first 8 weeks. Patients with brain metastases who have good performance status and minimal neurologic symptoms can be observed for approximately 8 weeks in clinical trials to determine their response to chemotherapy. However, it is doubtful that patients with brain metastases would be eligible for phase III trials, in which survival is an endpoint.

Adult↗
PubMed1996

Hepatitis B virus with X gene mutation is associated with the majority of serologically "silent" non-b, non-c chronic hepatitis.

Hepatitis B virus (HBV) with X gene mutations has been a putative pathogen of chronic hepatitis without serological markers of known hepatitis viruses. The aim of this study was to reconfirm whether the HBV with the X gene mutation is associated with these serologically "silent" non-B, non-C (NBNC) chronic hepatitis, alcoholic liver disease (ALD) and autoimmune hepatitis (AIH). HBV DNA was amplified from serum and sequenced in 30 patients with NBNC chronic hepatitis in comparison with 20 patients with ALD and 5 patients with AIH. HBV DNA was identified in 21 patients (70%) in NBNC chronic hepatitis by nested polymerase chain reaction while only one patient (5%) in ALD and none in AIH showed HBV DNA. Eighteen (85.7%) of the 21 identified HBV DNAs had an identical 8-nucleotide deletion mutation at the distal part of the X region. This mutation affected the core promoter and the enhancer II sequence of HBV DNA and created a translational stop codon which truncated the X protein by 20 amino acids from the C-terminal end. All the HBV DNAs had a precore mutation at the 83rd nucleotide resulting in disruption of HBe antigen synthesis. These results indicate that HBV mutants are closely associated with the majority of serologically "silent" NBNC chronic hepatitis cases and the population of such mutant HBV DNAs is not uniform.

Adult↗
PubMed1996

Therapeutic drug monitoring in 21-day oral etoposide treatment for lung cancer.

We aimed to determine whether or not therapeutic drug monitoring is applicable to 21-day oral etoposide treatment for lung cancer. As the starting dose, a 25-mg capsule of etoposide was taken orally three times daily (75 mg/body). To achieve the target concentration range of 1.0 to 1.5 micrograms/ml, the dose was changed to two (50 mg/body) or four (100 mg/body) times a day from day 5, depending on the mean concentration obtained on days 3 and 4 (Cbefore). The mean concentration was calculated by use of a limited sampling model we constructed previously. Among 26 courses in 15 patients, two patients experienced grade 4 leukopenia plus neutropenia, and one of them died on day 20. Because nausea/emesis prevented the planned dose escalation in one patient, we excluded two courses of this patient from the pharmacokinetic analysis of dose modification. Among 5 courses with dose reduction, the Cbefore of 1.7 +/- 0.1 (microgram/ml, mean +/- SE) was decreased to 1.3 +/- 0.2 after day 5 (Cafter). Among 7 courses with dose escalation, the Cbefore of 0.9 +/- 0.0 was increased to the Cafter of 1.2 +/- 0.1. Among the remaining 12 courses without dose modification, the Cbefore and the Cafter were 1.2 +/- 0.0 and 1.3 +/- 0.1, respectively. Hematologic toxicities tended to correlate with the drug concentration. TDM is thus applicable to oral etoposide given according to this schedule, and a larger study is now needed to confirm that the therapeutic efficacy is improved by introducing TDM.

Administration, Oral↗
PubMed1996

Therapeutic drug monitoring of etoposide in a 14-day infusion for non-small-cell lung cancer.

We investigated whether a constant plasma concentration could be obtained by the individualized administration of low-dose, prolonged-infusional etoposide. Etoposide was infused for 14 days at 40 mg/m2/day initially in patients with inoperable non-small-cell lung cancer. The infusion rate was modified based upon the etoposide concentration at 24 h following the initiation of the infusion (C24) to achieve a target concentration of 1.5 microgram/ml. We postulated that severe toxicities could be avoided by maintaining the steady-state concentration at less than 2 microgram/ml, while antitumor activity could be expected if the steady-state concentration was maintained at more than 1 microgram/ml. In a total of 21 courses in 12 patients, the mean etoposide dose was 35+/-6 mg/m2 daily. The C24 was 1.8+/-0.4 microgram/ml and ranged from 1.1 to 2.9 microgram/ml. Following dose modification, the mean concentration from 96 to 336 h (C mean) was 1.6+/-0.2 microgram/ml and ranged from 1.2 to 2.0 microgram/ml. The toxicities were well-tolerated except for one patient with WHO grade 4 leukopenia and neutropenia who developed infectious complications. There were no treatment-related deaths. Following dose modification, the inter-patient variability was decreased successfully. Although this pharmacologically-guided method needs to be validated using more patients, it could be used for therapeutic drug monitoring.

Aged↗
PubMed1996

Life-threatening cardiac involvement throughout life in a case of Costello syndrome.

Costello syndrome is characterized by poor postnatal growth, mental retardation, curly hair, coarse face, loose skin of the hands and feet, and nasal papillomata. Patients with Costello syndrome have a high incidence of cardiac involvement, such as arrhythmias, hypertrophic cardiomyopathy, or congenital anomalies. The importance of cardiac involvement in Costello syndrome has not been strongly emphasized thus far, although arrhythmia and hypertrophic cardiomyopathy are both serious forms of cardiac involvement. We report the case of a Japanese girl with Costello syndrome, who experienced life-threatening cardiac involvement throughout her life.

Anus Neoplasms↗
PubMed1996

Use of recombinant tissue-type plasminogen activator to treat massive pulmonary embolism after cesarean section: a case report.

A 30-year-old primigravida, delivering by cesarean section, went into shock with cardiac arrest due to pulmonary thromboembolism. Thrombolytic therapy with recombinant-tissue-type plasminogen activator (rt-PA) induced a rapid improvement in both the hemodynamic and respiratory conditions. This case shows the marked efficacy of rt-PA in treating massive pulmonary thromboembolism. Close attention must be given to the patient in such a case, however, because the risk of hemorrhagic complication exists.

Adult↗
PubMed1996

Intrahepatic expression of pro-inflammatory cytokine mRNAs and interferon efficacy in chronic hepatitis C.

To investigate the relationship between intrahepatic cytokine expression and interferon (IFN) response in chronic hepatitis C [CH(C)], interleukin (IL)-1 beta, -2, -4, -6, -8, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and TNF-beta mRNAs were investigated semiquantitatively by reverse transcription polymerase chain reaction using serial liver biopsies taken before and after IFN-alpha treatment from 24 patients with CH(C), including 12 responders and 12 non-responders. Before IFN treatment, IL-2, TNF-beta, IFN-gamma and IL-8 mRNA were associated with severe hepatitis activity whereas IL-4 mRNA was associated with weak hepatitis activity, regardless of IFN response. IL-2, TNF-beta and IFN-gamma mRNAs were significantly greater in IFN non-responders. After IFN treatment a complete response to IFN was significantly associated with the disappearance of these pro-inflammatory cytokines, whereas non-responders retained the expression of cytokine mRNA as before IFN treatment. Our results indicated that IFN-alpha treatment may modulate the intrahepatic cytokine network, and this may be one mechanism of IFN-alpha that reduces hepatitis activity, aside from an anti-viral effect. A difference in cytokine network may be involved in IFN response in CH(C).

Adult↗
PubMed1996

Breast lesions: correlation of contrast medium enhancement patterns on MR images with histopathologic findings and tumor angiogenesis.

PURPOSE: To compare qualitative and quantitative magnetic resonance (MR) mammographic features of breast lesions with histopathologic findings, especially tumor angiogenesis. MATERIALS AND METHODS: Seventy-three patients (72 women, one man; aged 30-78 years; mean age, 51.0 years) with suspicious breast lesions underwent MR imaging. Noncontrast medium-enhanced localization imaging and then gadolinium-enhanced dynamic fast spoiled gradient-recalled-echo (SPGR) imaging were performed in all patients. In selected patients, subtraction fast SPGR images were obtained. The Pearson and Spearman correlation tests were used to determine the strength of the relationships between enhancement parameters and microvessel determinations. RESULTS: Time intensity curve type correlated with microvessel density grade (Spearman rank correlation test: r = .90, P < .001). The steepest slope of contrast medium uptake correlated with microvessel counts (Pearson correlation test; r = .83, P < .001). Peripheral enhancement in invasive carcinomas (n = 9) correlated with high peripheral and low central microvessel densities, which were associated with desmoplasia and/or necrosis. Internal septations (n = 2) were seen only in fibroadenomas. CONCLUSION: The density and distribution of microvessels may play major roles in the determination of the initial rate of contrast medium uptake and the heterogeneity of tumor enhancement.

Adult↗