Comparative Case-referent Study of Risk Factors among Hormone-related Female Cancers in Japan

To assess the impact of reproductive and anthropometric factors as a risk indicator for female cancers in hormone-related organs, i.e., the breast, endometrium and ovary, we conducted a comparative case-referent study using data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan. The case group consisted of 1,465, 133 and 99 women who had first been diagnosed as having breast, endometrial and ovarian cancer, respectively. The referents were 25,488 female first-visit outpatients who had not previously been diagnosed with any type of cancer. The odds ratios (ORs) and their 95% confidence intervals (95%CI) were estimated using an unconditional logistic regression model. An inverse association with experience of delivery and a positive association with body mass index (BMI) and with change of BMI after 20 years of age, were observed consistently for all three cancer sites. We observed similar risk and protective factors for breast and endometrial cancer, but the effect of reproduction and overweight condition (BMI≥25) were more prominent in endometrial cancer. Although the present study failed to find site-specific risk factors for ovarian cancer, the results provided evidence that being overweight and/or weight gain in adult life is a common risk factor for all three cancer sites. The results obtained from this study suggested that avoidance of weight gain may reduce the risk of female hormone-related cancers.     

ABCA4 gene mutations in Japanese patients with Stargardt disease and retinitis pigmentosa

PURPOSE: To evaluate photoreceptor cell-specific adenosine triphosphate (ATP)-binding cassette transporter (ABCA4) gene mutations in Japanese patients with Stargardt disease (STGD) and the correlation of these mutations to clinical phenotypes. METHODS: Serum was obtained from 10 unrelated Japanese patients with STGD and 96 unrelated Japanese patients with autosomal recessive retinitis pigmentosa (arRP). All 50 ABCA4 gene exons of the patients with STGD were screened for mutations by a combination of single-strand conformation polymorphism analysis and polymerase chain reaction (PCR) direct-sequencing techniques. By restriction enzyme digestion, primer extension analysis, and PCR direct sequencing techniques, the patients with arRP were screened for three segregated, presumably null ABCA4 gene mutations observed in Japanese patients with STGD. RESULTS: Three novel, presumably null mutations of the ABCA4 gene, IVS7-45_952delinsTCTGACC, IVS12+2T-->G, and 1894delA, were identified. The Arg2149stop mutation that had been found in a white patient with STGD in a prior study was also found in a Japanese patient. Two arRP-affected siblings and two unrelated patients with STGD were found to be homozygous for the same IVS12+2T-->G mutation, and three other arRP-affected siblings were carriers of the IVS12+2T-->G mutation and/or the IVS7-45_952delinsTCTGACC mutation. These three siblings with arRP showed only atrophic degeneration in the macula early after the onset of the disease, and STGD had been diagnosed. CONCLUSIONS: Three novel ABCA4 gene mutations were identified in Japanese patients with STGD and arRP. Mutations in the ABCA4 gene can cause panretinal degeneration that changes its clinical appearance from STGD to arRP over time.     

A repeated 28-day oral dose toxicity study of nonylphenol in rats,based on the ‘Enhanced OECD Test Guideline 407’ for screening of endocrine-disrupting chemicals

A 28-day repeated oral dose toxicity study of nonylphenol (NP) was performed for an international validation of the ‘Enhanced OECD Test Guideline 407’ paying particular attention to the sensitivity of individual endocrine-related parameters. Sprague-Dawley rats, each group consisting of ten males and ten females, were administered NP once daily by gavage at doses of 0 (control), 10, 50, or 250 mg/kg body weight. At 250 mg/kg, three females died or became moribund during the experiment. At this dose, hepatic and renal toxicity was evident in both sexes with increase of relative liver and kidney weights as well as histopathological changes, such as centrilobular liver cell hypertrophy and a variety of renal tubular lesions, and alteration of serum biochemical parameters, some of them being evident from 50 mg/kg in females (glucose and inorganic phosphates). Hematologically, development of anemia was evident at 250 mg/kg in both sexes. Regarding endocrine-related effects, increase of thyroid weight in males was detected from 50 mg/kg. At 250 mg/kg, males exhibited reduction of relative weights of the ventral prostate and seminal vesicles, and females developed irregular estrous cyclicity and vaginal mucosal hyperplasia. Although changes in serum hormone levels were detected in both sexes, magnitude of the changes was small to be regarded as a low toxicological significance. In summary, repeated oral doses of NP to rats for 28 days resulted in hepato-renal toxicity from 50 mg/kg and anemia at 250 mg/kg. Effects on the endocrine system were observed from 50 mg/kg, and assessment of weights and histopathology of endocrine-related organs and estrous cyclicity may be valid in a battery for detecting endocrine effects of NP. The no-observed-adverse-effect level of NP was estimated to be 10 mg/kg per day.     

Contemporary outcomes after superficial femoral artery angioplasty and stenting: the influence of TASC classification and runoff score

OBJECTIVE: A recent randomized trial suggested nitinol self-expanding stents (SES) were associated with reduced restenosis rates compared with simple percutaneous transluminal angioplasty (PTA). We evaluated our results with superficial femoral artery (SFA) SES to determine whether TransAtlantic InterSociety Consensus (TASC) classification, indication for intervention, patient risk factors, or Society of Vascular Surgery (SVS) runoff score correlated with patency and clinical outcome, and to evaluate if bare nitinol stents or expanded polytetrafluoroethylene (ePTFE) covered stent placement adversely impacts the tibial artery runoff. METHODS: A total of 109 consecutive SFA stenting procedures (95 patients) at two university-affiliated hospitals from 2003 to 2006 were identified. Medical records, angiographic, and noninvasive studies were reviewed in detail. Patient demographics and risk factors were recorded. Procedural angiograms were classified according to TASC Criteria (I-2000 and II-2007 versions) and SVS runoff scores were determined in every patient; primary, primary-assisted, secondary patency, and limb salvage rates were calculated. Cox proportional hazard model was used to determine if indication, TASC classification, runoff score, and comorbidities affected outcome. RESULTS: Seventy-one patients (65%) underwent SES for claudication and 38 patients (35%) for critical limb ischemia (CLI). Average treatment length was 15.7 cm, average runoff score was 4.6. Overall 36-month primary, primary-assisted, and secondary rates were 52%, 64%, and 59%, respectively. Limb salvage was 75% in CLI patients. No limbs were lost following interventions in claudicants (mean follow-up 16 months). In 24 patients with stent occlusion, 15 underwent endovascular revision, only five (33%) ultimately remained patent (15.8 months after reintervention). In contrast, all nine reinterventions for in-stent stenosis remained patent (17.8 months). Of 24 patients who underwent 37 endovascular revisions for either occlusion or stenosis, eight (35%) had worsening of their runoff score (4.1 to 6.4). By Cox proportional hazards analysis, hypertension (hazard ratio [HR] 0.35), TASC D lesions (HR 5.5), and runoff score > 5 (HR 2.6) significantly affected primary patency. CONCLUSIONS: Self-expanding stents produce acceptable outcomes for treatment of SFA disease. Poorer patency rates are associated with TASC D lesions and poor initial runoff score; HTN was associated with improved patency rates. Stent occlusion and in-stent stenosis were not entirely benign; one-third of patients had deterioration of their tibial artery runoff. Future studies of SFA interventions need to stratify TASC classification and runoff score. Further evaluation of the long-term effects of SFA stenting on tibial runoff is needed.     

Surgical treatment of esophageal carcinoma in patients eighty years of age and older

Before 1979, no patient 80 years of age or older had been operated on at our institution for esophageal cancer, while in the middle period (1980–1984), three patients were operated on, and postoperative pulmonary complications and operative death occurred in 66.7 and 33.3%, respectively. However, in the recent period (1985–1990), there was no postoperative morbidity or mortality in the five cases over age 80. On the other hand, there were 12 patients over age 80 who did not undergo operation, of whom all died of cancer. In the eight operated patients over age 80, two cases are still alive 17 and 34 months after operation. According to the above findings, when the patient's general condition is evaluated to be sufficient to tolerate the operation and the cancer is judged to be resectable, esophageal resection is thought to be indicative in all patients over eighty. © 1993 Wiley-Liss, Inc.     

A simplified, sensitive immunohistochemical detection system employing signal amplification based on fluorescyl-tyramide/antifluorescein antibody reaction: its application to pathologic testing and research.

The catalyzed signal amplification (CSA) technique, based on the peroxidase-mediated deposition of haptenized tyramide and also known as tyramide signal amplification and catalyzed reportor deposition systems, is widely accepted as a signal amplification method for immunohistochemistry and in situ hybridization. In this study, we examined the applicability of a new simplified CSA system employing fluorescyl-tyramide (FT) to pathologic testing and research with formalin-fixed, paraffin-embedded tissues. By using the FT, instead of biotinyl-tyramide (BT) that is commonly employed in the CSA system with chromogen, nonspecific staining caused by endogenous biotin was completely avoided. The FT-CSA system loaded on the automated immunostaining equipment also allowed for more reproducible detection in short times. When applied to cyclin D1 immunostaining that is important in differentiation among small B-cell lymphomas, the system was useful in demonstrating its protein expression in mantle cell lymphomas considered negative or equivocally positive for cyclin D1 in a conventional immunodetection. In immunohistochemistry for phosphorylated proteins and murine hematologic markers that often require higher sensitivity than conventional methods, the FT-CSA system provided desirable staining results with intense signal amplification. Our results indicate that the simplified CSA system employing the FT can be useful in enlarging the target range for routine immunohistochemistry due to its high applicability.     

Antigenic variation of H1N1, H1N2 and H3N2 swine influenza viruses in Japan and Vietnam

The antigenicity of the influenza A virus hemagglutinin is responsible for vaccine efficacy in protecting pigs against swine influenza virus (SIV) infection. However, the antigenicity of SIV strains currently circulating in Japan and Vietnam has not been well characterized. We examined the antigenicity of classical H1 SIVs, pandemic A(H1N1)2009 (A(H1N1)pdm09) viruses, and seasonal human-lineage SIVs isolated in Japan and Vietnam. A hemagglutination inhibition (HI) assay was used to determine antigenic differences that differentiate the recent Japanese H1N2 and H3N2 SIVs from the H1N1 and H3N2 domestic vaccine strains. Minor antigenic variation between pig A(H1N1)pdm09 viruses was evident by HI assay using 13 mAbs raised against homologous virus. A Vietnamese H1N2 SIV, whose H1 gene originated from a human strain in the mid-2000s, reacted poorly with post-infection ferret serum against human vaccine strains from 2000-2010. These results provide useful information for selection of optimal strains for SIV vaccine production.     

Pregnancy outcome in recurrent aborters is not influenced by Chlamydia IgA and/or G

PROBLEM: It is unclear whether chlamydia infection influences the miscarriage rate and immunological factors in patients with recurrent miscarriage. METHOD OF STUDY: Chlamydia DNA, IgA and IgG to Chlamydia trachomatis, natural killer cell activity, complement 3 (C3), C4, hemolytic complement, antinuclear antibodies, antiphospholipid antibodies, prolactin, activated partial thromboplastin time, prothrombin time and fibrinogen were examined in 504 patients with a history of two or more consecutive first-trimester miscarriages. Subsequent pregnancy outcomes were compared between cases with and without antibodies to C. trachomatis. RESULTS: Totals of 10 of 30 and 48 of 201 patients receiving no medication miscarried subsequently with and without chlamydia infection. Chlamydia IgA and/or IgG were associated with a high level of C3 but not other immunological and coagulatory parameters. CONCLUSION: Antibodies to C. trachomatis do not influence subsequent pregnancy outcome in patients with a history of recurrent miscarriage.     

Influence of Chewing and Clenching on Salivary Cortisol Levels as an Indicator of Stress

PURPOSE: The purpose of this study was to investigate the effects of chewing and clenching on salivary cortisol levels as an indicator of stress. MATERIALS AND METHODS: Seventeen healthy dentulous subjects were given arithmetic exercises to perform within a 20-minute time limit in order to elicit stress (stress loading). In the first experiment (chewing), after stress loading, the subjects were asked to chew a paraffin wax while reading printed material (books, magazines, etc.) in silence for 10 minutes. The same procedure was then carried out again for control purposes, but this time the subjects were not required to chew wax. In the second experiment (light clenching), after stress loading, the subjects were required to carry out 5 seconds of light clenching followed by 5 seconds of rest repeatedly over a 3-minute period. The whole 3-minute process was repeated a total of three times. The control data for this second experiment consisted of measurements taken during the rest periods. Saliva specimens were collected in both experiments both before stress loading and after each procedure during 1-minute intervals to measure cortisol levels. RESULTS: In the chewing experiment, salivary cortisol levels were significantly reduced by chewing, compared with those in the controls (p < 0.05). This reduction in salivary cortisol was observed during chewing over a 10-minute period following stress loading. In the clenching experiment, salivary cortisol levels also showed a significant reduction during clenching, compared with those in the controls (p < 0.05). CONCLUSIONS: These results suggest that chewing and clenching promote relaxation in subjects under stress.