Cardiac vagal responsiveness during development in spontaneously hypertensive rats

In the present study we sought to determine the effect of age, hypertension and endogenous angiotensin on the chronotropic responses to vagal stimulation in urethane anesthetized-normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). After beta-adrenoceptor blockade with atenolol, the right and left vagal nerves were stimulated with graded frequencies between 1 and 32 Hz in 5-, 8- and 22-week-old animals. At all ages and in both strains, there was a strong linear relationship between the degree of bradycardia and the log of the stimulation frequency. At the age of 5 weeks, the bradycardia to stimulation of the right vagus was greater in SHR than that observed in WKY (P<0.05). However, in 8- and 22 week-old animals, no differences were observed between the response to vagal stimulation in WKY and SHR. Thus, there was an age-dependent increase in the response to right vagal stimulation in WKY, but no such trend in SHR. No significant age-dependent changes in left vagal responses were observed in either strain. Left vagal responses were approximately half of the response to right vagal stimulation at all ages in SHR and in 8-22 week WKY, but similar to right vagal responses in 5 week WKY. Administration of the angiotensin converting enzyme inhibitor perindopril, which effectively blocked the formation of endogenous angiotensin, did not affect responses to vagal stimulation at any age, in either strain. These results suggest that the baroreflex vagal deficit observed in adult SHR compared to WKY is not due to a difference in the responsiveness of the cardiac vagal neuroeffector mechanism nor due to an effect of circulating angiotensin II. Furthermore, the enhanced vagal bradycardia observed in very young SHR which was due primarily to the earlier establishment of the adult vagal response pattern may indicate accelerated vagal development in this strain compared to WKY.     

Serum heat shock protein 70 levels and lung cancer risk: a case-control study nested in a large cohort study.

Chronic inflammation contributes to the process of carcinogenesis, but few epidemiologic studies have examined associations with risk of lung cancer. Relationships between lung cancer risk and serum levels of both heat shock protein 70 (Hsp70) and high-sensitivity C-reactive protein (hsCRP) were investigated in a case-control study nested in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. Serum samples and lifestyle information were collected at baseline from 39,242 men and women between 1988 and 1990. Of these, 240 deaths from lung cancer were identified through 1999, and 569 controls were matched for sex, age, and study area. Serum levels were measured in 189 cases and 377 controls for Hsp70 and in 209 cases and 425 controls for hsCRP. Odds ratios (95% confidence intervals) across quartiles, adjusted for confounding factors, including smoking habits, were 0.83 (0.44-1.58), 1.41 (0.77-2.60), and 1.84 (0.92-3.71) for Hsp70 (P(trend) = 0.042) and 1.13 (0.67-1.91), 0.66 (0.38-1.16), and 1.19 (0.70-2.02) for hsCRP (P(trend) = 0.941). In males, odds ratios (95% confidence intervals) across quartiles were 1.30 (0.59-2.84), 1.74 (0.83-3.67), and 2.49 (1.06-5.85) for Hsp70 (P(trend) = 0.029). High levels of serum Hsp70 might thus be associated with increased risk of lung cancer among Japanese males, although further studies are needed to clarify associations between chronic inflammation and lung cancer.     

Thyroid Lymphoma of Mucosa-Associated Lymphoid Tissue with Monoclonal Gammopathy Occurring in an Atomic Bomb Survivor: Report of a Case

(Received for publication on Dec. 14, 1998; accepted on July 13, 1999)     

Nonoperative Treatment of Reperforated Duodenal Ulcer: Report of Three Cases

During the period between 1983 and 1998, a total of 58 patients were admitted to the surgical department of Akita Red Cross Hospital with acute duodenal perforation. Of these 58 patients, 16 were treated operatively and 42 were treated nonoperatively. Among the 38 men and 4 women who received nonoperative treatment, 3 developed reperforation. The incidence of reperforation was 7.1% and the mean average interval from the initial treatment until reperforation was 3.5 years. Endoscopic biopsy and/or serum anti-H. pylori IgG measurement revealed Helicobacter pylori infection in all three patients. No serious complications developed during the nonoperative treatment of reperforation in these three patients, and their recovery was uneventful. The hospital stay ranged from 10 to 18 days, with a mean stay of 12 days after the first perforation and from 14 to 18 days, with a mean stay of 15.6 days after the reperforation. Nonoperative treatment proved successful as a life-saving procedure for reperforation of a duodenal ulcer in all three patients. Received: September 7, 1999 / Accepted: May 30, 2000     

The prognostic significance of overexpression of the decoy receptor for Fas ligand (DcR3) in patients with gastric carcinomas

Abstract. Background: The FasL-Fas system has an important role in mediating immune-cytotoxic killing of cells such as virus-infected or tumor cells. It was recently reported that there is a soluble decoy receptor (DcR3), which binds to FasL and inhibits FasL-induced apoptosis, and certain tumors may escape FasL-dependent immune-cytotoxic attack by expressing a decoy receptor that blocks FasL. We evaluated whether DcR3 has clinical relevance in actual human gastric cancers. Methods: . The expression of DcR3 was investigated by Northern blot analysis in a series of 84 primary gastric carcinomas and compared with clinicopathological features and prognosis. The DcR3 expression level was analyzed and quantified densitometrically. The location of DcR3 mRNA in gastric carcinoma tissue was detected by in situ hybridization. Results: The frequency of DcR3 overexpression was 26% (22 of 84 surgical specimens). The DcR3 expression level was significantly associated with lymph node metastasis and pathological stage, but did not correlate with tumor size, metastatic status, or histological type. In situ hybridization demonstrated that DcR3 mRNA was expressed in tumor cells. When the patients were followed up for 63 months, DcR3 overexpression was found to be associated with a significantly shortened duration of overall survival compared with findings in patients having normal DcR3 expression. Conclusion: The DcR3 decoy receptor for FasL may be involved in the progression of gastric cancer. Further evaluation of these possible roles of DcR3 and the regulation of DcR3 expression in malignant cells will be critically important for the development of new strategies for controlling the growth of malignant cells that escape host immune surveillance. Received: July 19, 2001 / Accepted: December 21, 2001     

Multiplexed analysis of post-PCR fluorescence-labeled microsatellite alleles and statistical evaluation of their imbalance in brain tumors.

Detection of the loss of chromosomal regions in cancerous tissues has diagnostic and prognostic relevance, and the development of a reliable and cost-effective technique for this is clinically important. Here we present an efficient technique for quantitative detection of microsatellite alleles, using a post-PCR fluorescence-labeling procedure and multiplexed analysis. We also present a new statistical method for the interpretation of the data that permits reliable and sensitive evaluation of the allelic status of sampled DNA. A high-resolution analysis of allelic imbalance on chromosomes 1p, 10 and 19q in 28 glioma samples of various types using this method revealed that allelic imbalances are more frequent than have been reported, suggesting the diagnostic value of this method in examining the genetic profiles of gliomas.     

Trojan p16 peptide suppresses pancreatic cancer growth and prolongs survival in mice.

PURPOSE: The tumor suppressor gene p16INK4A is inactivated frequently in a large number of human cancers, and many investigators have attempted to restore the function of p16 using the p16 wild-type gene and viral vectors. In this study, we treated the tumor-bearing animals with the p16-derived synthetic peptide coupled with the Antennapedia carrier sequence, which we designated as Trojan p16 peptide. EXPERIMENTAL DESIGN: Injections (i.p.) of the Trojan p16 peptide (100 microg/mouse/day) were given for 3 weeks in the AsPC-1 and BxPC-3 s.c. tumor models. Tumor growth, histopathology, and TUNEL staining of the tumor and toxicity of the animals were evaluated. To examine its influence on the survival of tumor-bearing mice, Trojan p16 was administered in the AsPC-1 peritoneal dissemination model. RESULTS: In the AsPC-1 s.c. tumor model, a significant growth inhibition was obtained by the Trojan p16 treatment when compared with the three control treatments, i.e., vehicle, unconjugated form of p16, or Trojan peptide alone. Tumor growth inhibition was almost complete in the BxPC-3 tumor, a relatively slow growing tumor. Neither hematological cytotoxicity or body weight loss were observed. Histopathology of the BxPC-3 s.c. tumor in the Trojan p16 treatment group revealed marked vacuole formation and apoptotic death of cancer cells. In the AsPC-1 peritoneal dissemination model, the survival curve of mice treated with Trojan p16 was significantly longer than that of control. CONCLUSIONS: These results provide evidence that the Trojan p16 peptide system, a gene-oriented peptide coupled with a peptide vector, functions for experimental pancreatic cancer therapy.     

A quantitative evaluation of active gelatinolytic sites in uterine endometrioid adenocarcinoma using film in situ zymography: association of stronger gelatinolysis with myometrial invasion.

Collagen matrix degradation by malignant tumor cells plays an essential role in the process of tumor invasion and metastasis. The purpose of this study was to detect in situ gelatinase activity in endometrioid adenocarcinomas of the uterine corpus. In order to carry out quantitative evaluation, autoexposure time (AET) on gelatin-coated film (film in situ zymography: FIZ) was measured. The gelatinase activity was located primarily within cancers and was prominently suppressed by the addition of a chelating agent to the film. This suggests that matrix metalloproteinases (MMPs) play an important role in the gelatinase activity. The gelatinase activity in the normal endometrium is almost negligible, despite positive immunoreactivity for MMP-2 and -9. Tumor tissues that had invaded more than half of the myometrium showed significantly higher activity than those that had invaded less than half. There was no significant difference in gelatinase activity among tumor stages, grades, vessel invasion or immunoreactivity for MMPs, with the exception that stage 2b cancers showed higher activity than stage 1a. The study suggested that the level of MMP-mediated gelatinolysis is an important factor for myometrial invasion in uterine endometrioid adenocarcinoma. Thus, a quantitative assessment of active gelatinolysis using FIZ and AET should be a useful tool in evaluating in situ matriolytic activity in local myometrial invasion by uterine endometrioid adenocarcinoma.