Interaction between cytochrome P450 gene polymorphisms and serum organochlorine TEQ levels in the risk of endometriosis

Exposure to dioxins and polychlorinated biphenyls (PCBs) has been suggested as a possible etiologic factor for endometriosis, but the association remains highly controversial. To assess whether cytochrome P450 (CYP) gene polymorphisms modulate the effect of dioxins and/or PCBs in endometriosis risk, we conducted a case-control study among infertile Japanese women. A total of 138 eligible women aged 20-45 were diagnosed laparoscopically and classified into three subgroups: control (no endometriosis), early endometriosis (stages I-II) and advanced endometriosis (stages III-IV). Neither CYP1A1 Ile462Val and CYP1B1 Leu432Val polymorphisms (genotypes with versus genotypes without the minor allele) nor serum dioxin and PCB toxic equivalency (TEQ) levels (low versus high) were independently associated with either early or advanced endometriosis risk. However, genotypes with the CYP1A1 462Val allele showed a statistically significant reduced risk of advanced endometriosis in combination with high serum dioxin TEQ levels (adjusted odds ratio = 0.13, 95% confidence interval: 0.02-0.76) (P for interaction = 0.08). Although no association was found between serum PCB TEQ level and advanced endometriosis in any stratum of CYP1B1 Leu432Val polymorphism, a statistically significant interaction was found (P for interaction = 0.05). CYP1A1 and CYP1B1 polymorphisms may modify the relation between environmental exposure to organochlorine and advanced endometriosis risk.     

Non-suture end-to-end anastomoses between polytetrafluoroethylene graft and vessels for blood access

BACKGROUND: Non-suture end-to-end anastomoses between polytetrafluoroethylene grafts and blood vessels were achieved using absorbable cuff material in experimental and clinical studies. The cuff was made of a synthetic biodegradable material, a lactic-glycolic acid copolymer, similar in composition to conventional absorbable surgical sutures. METHODS: In the experimental study, vascular anastomoses for prosthetic interposition of the infrarenal aorta in rabbits were created using the cuff method. Six months after surgery, the cuff anastomoses sites were examined angiographically and microscopically and found to be patent and smooth without neointimal hyperplasia. RESULTS: The cuff layer had been completely absorbed. The clinical application used a similar technique and involved the creation of forearm bridge graft fistula in twelve patients for hemodialysis. In eight patients, Doppler fistula flow rate ranged from 167 ml/min to 392 ml/min. Ten of the twelve patients continued dialysis uneventfully. The one-year patency rate was 78% (7/9). The longest patency period was 920 days and the graft access continued to maintain sufficient blood flow for hemodialysis. CONCLUSIONS: This absorbable cuff material is therefore well suited for the construction of prosthetic vascular end-to-end anastomoses.     

The prognosis and immunohistochemical evaluation of five perianal Paget's disease cases

Perianal Paget's disease is categorized as Paget's disease, which is epidermotropic neoplasm arising from the apocrine glands of perianal region, or Pagetoid spread invaded from rectal or anal canal cancer. It has been reported that the immunohistochemical staining of GCDFP15, the marker of the apocrine epithelium, and CK20 is used to be distinguished between Paget's disease and Pagetoid spread. Five patients with perianal Paget's disease who underwent a surgical operation had been treated in our department between 1997 and 2006. We analyzed the clinical findings and the treatment of these patients and investigated the expression of GCDFP15 and CK20 by immunohistochemical staining. All cases presented the redness around perianal regions, and 2 cases were recognized a tumor at the anal canal. We preoperatively diagnosed these cases as Pagetoid spread and others without tumor regions as Paget's disease. Surgical treatment was performed for all patients. As a result of immunohistochemical staining, 2 cases of Pagetoid spread were negative for GCDFP15, and positive for CK20. It was compatible with the preoperative diagnosis. Only one of 3 Paget's disease cases was positive for GCDFP15 and negative for CK20 resulting in the diagnosis of perianal Paget's disease. Based on the expression of negative for GCDFP15 and positive for CK20, others were seemed to be Pagetoid spread. A treatment strategy including surgical operation and chemotherapy is different between patients with Paget's disease and those with Pagetoid spread. Therefore, it is essential to investigate the expression pattern of GCDFP15 and CK20 using the tissue from the biopsy to identify the disease for appropriate treatment.     

Clinicopathological study of diffuse neurofibrillary tangles with calcification. With special reference to TDP-43 proteinopathy and alpha-synucleinopathy

Diffuse neurofibrillary tangles with calcification (DNTC) is a relatively rare presenile dementia that clinically shows overlapping symptoms of Alzheimer's disease and frontotemporal lobar degeneration (FTLD). DNTC is pathologically characterized by localized temporal or frontotemporal atrophy with massive neurofibrillary tangles, neuropil threads and Fahr's-type calcification without senile plaques. We tried to clarify the molecular basis of DNTC by immunohistochemically examining the appearance and distribution of accumulated alpha-synuclein (aSyn) and TAR DNA-binding protein of 43kDa (TDP-43) in the brains of 10 Japanese autopsy cases. We also investigated the clinically characteristic symptoms from the clinical charts and previous reports, and the correlations with neuropathological findings. The characteristic symptoms were evaluated using the Neuropsychiatric Inventory Questionnaire (NPI-Q). As a result, we confirmed the high frequency of neuronal cytoplasmic accumulation of aSyn (80%) and phosphorylated TDP-43 (90%) in DNTC cases. There was a significant correlation between some selected items of NPI-Q scores and the severity of the limbic TDP-43 pathology. The pathology of DNTC included TDP-43 and aSyn pathology with high frequency. These abnormal accumulations of TDP-43 might be involved in the pathological process of DNTC, having a close relationship to the FTLD-like psychiatric symptoms during the clinical course.     

Advanced paternal age associated with an elevated risk for schizophrenia in offspring in a Japanese population

OBJECTIVE: Advanced paternal age at birth as a risk for schizophrenia in the adult offspring has been reported in previous studies exclusively conducted in Western countries and Israel. The question has arisen whether this finding could be replicated in countries with socially and culturally different attitudes toward marriage, including factors such as age at marriage. To address this question, we conducted a case-control study of a Japanese population. METHODS: The subjects were representative inpatients with a DSM-IV diagnosis of schizophrenia. Unrelated healthy volunteers were recruited as control subjects. This study was conducted as one of a series of the projects by use of "The Mother and Child Health Handbooks (MCHHs)," from which information on parental characteristics around the time of birth, including parental ages at birth, had been extracted and recorded on computer. RESULTS: Ninety-nine subjects with schizophrenia and 381 healthy control subjects enrolled for the study. Advanced paternal, but not maternal, age was associated with an elevated risk for schizophrenia. Reproducibility of the association across different cultures is suggestive of a causal link.     

An autopsy case of miliary brain metastases]

A 57-year-old man was admitted to our hospital with a diagnosis of psychiatric emergency. His symptoms were similar to encephalitis, metabolic encephalopathy or acute depressive psychosis because of poor focal neurological signs. Laboratory examinations, including routine hematological and biochemical investigations, serum vitamin B1 B12 levels, and cerebrospinal fluid obtained by lumbar puncture, were normal. Brain CT was also normal, therefore it was difficult to make a diagnosis. But, we could clinically diagnose him as having pulmonary adenocarcinoma with numerous metastatic nodules of the brain. Because miliary lesions in the cerebral hemispheres, brainstem and cerebellum were disclosed on brain MRI. Furthermore, chest CT revealed the lung tumor in the left S8 area. In addition, laboratory examination showed a rise of tumor marker and cytologic examination of sputum revealed class V. Fluid-attenuated inversion recovery and contrast-enhanced MR images demonstrated more prominently miliary metastases, in particular lesions in the cerebral cortex, than T1- and T2-weighted images. There was neither edema in the surrounding region of metastatic nodules nor mass effect on all MR images. Spinal MRI showed no metastatic lesions. The patient died of respiratory failure at the age of 58, about eight months after the disease onset. The brain weighed 1,575 g. Neuropathological findings revealed diffuse miliary brain metastases located in all parts of the brain, except for the medulla oblongata. Histological examination disclosed multiple metastases from a well-differentiated adenocarcinoma with a predominant tubular pattern. There was neither edema nor glial reaction in the surrounding area of metastatic lesions. Many pseudorosettes were recognized and carcinoma cells, extending through perivascular spaces into the subarachnoid space, were noticed.     

Do NHS clinicians and members of the public share the same views about reducing inequalities in health?

Decisions about how to allocate resources in health care are as much about social value judgements as they are about getting the medical facts right. In this context, it is important to compare the social preferences of members of the general public with those of National Health Service (NHS) staff involved in service delivery. A questionnaire eliciting peoples' preferences over maximising life expectancy and reducing inequalities in life expectancy between the highest and lowest social classes was completed by 271 members of the UK public and 220 NHS clinicians. The two samples have different preferences with the general public showing a greater willingness than clinicians to sacrifice total health for a more equal distribution of health. These differences may highlight tensions between what the public wants and what clinicians want, and should be subject to further investigation.     

鲍曼不动杆菌ATCC19606多重耐性分析及耐药基因的克隆

鲍曼不动杆菌已成为重要的院内感染病菌。我们测定了鲍曼不动杆菌ATCC19606的药物最小抑制浓度（MIC），结果显示该菌株对多种抗菌药物都有很高的耐性，如链霉素、诺氟沙星、氯霉素、红霉素、四环索、氨苄西林及一些其他的抗菌染剂。利用大肠埃希菌超敏菌株KAM32作为宿主，从鲍曼不动杆菌ATCC19606染色体DNA中克隆耐药基因，共获得9个使宿主细胞产生耐药性的杂合质粒，其中1个为单一耐药，其余全部为多重耐药。根据药物特异性分析可知，具有不同耐药图谱的杂合质粒携带不同类型的耐药基因。由此揭示鲍曼不动杆菌ATCC19606的多重耐药有多种机制参与。     

Effect of Nma on growth inhibition by TGF-betaa in human gastric carcinoma cell lines

Non-metastatic gene A (nma) has a homologue DNA sequence to a gene of bone morphogenetic proteins and activin membrane-bound inhibitor (BAMBI), which negatively regulates TGF-beta signaling. In this study, we analyzed the functional homology between Nma and BAMBI in human gastric carcinoma cell lines. Various levels of nma mRNA expression were detected by the RT-PCR technique in all human gastric carcinoma cell lines. Then, Nma antisense and sense S-oligodeoxynucleotide (ODN) were used to analyze the response of TGF-beta to cell growth and invasion gastric carcinoma cell lines. The cell growth was inhibited by TGF-beta in Nma antisense S-ODN treatment gastric carcinoma cell lines, MKN28, MKN1, MKN74 and TMK1. TGF-beta reduced cell growth and invasive activity of MKN28 treated with Nma antisense S-ODN in a dose and time-dependent manner. Furthermore, lysates of Nma sense or antisense S-ODN treated MKN28 cells were immunoprecipitated with anti-TGFbetaR-I or anti-TGFbetaR-II antibody. The 29 kDa signal considered as Nma appeared in sense S-ODN treated MKN28 cells immunoprecipitated with anti-TGFbetaR-I. These results indicate that Nma negatively regulates TGF-beta signaling, consequently playing an important role as one of the escape mechanisms from TGF-beta-mediated growth control similarly to BAMBI, and induce cell growth and invasion in human gastric carcinoma cell lines.