Effect of dietary protein on Masheri-induced drug metabolising enzymes

The modulation of drug metabolising enzymes by Masheri extract (ME) and Benzo(a)Pyrene [B(a)P] was studied in male Sprague Dawley rats fed different dietary protein levels. Two groups of 21 days old male Sprague Dawley rats were put on a high protein diet (SHP) with 20% Casein, and a low protein diet (SLP) with 3% Casein semisynthetic based diets for 12 weeks. The SLP fed animals showed lower basal levels of the Phase I activating enzymes viz. Cytochrome P450, Benzo(a)Pyrene hydroxylase, Benzphetamine demethylase and Phase II glutathione detoxification system viz. Glutathione (GSH) and Glutathione-S-transferase. ME and B(a)P treatment significantly depleted the glutathione detoxification system in the SLP group whereas an opposite effect was observed in the SHP group. Interstingly, ME and B(a)P treated rats in the SLP group showed a higher percent increase in the hepatic and pulmonary Phase I enzyme activities than those observed in the treated ME/B(a)P treated SHP rats. Furthermore, both ME and B(a)P significantly decreased the hepatic pool of vitamin A while a concomittant increase in that of vitamin C was observed.     

Classical and anaplastic seminoma: difference in survival

Classical and anaplastic seminoma are traditionally treated with radiation therapy and are said to have the same prognosis. A retrospective study was undertaken of 90 seminoma patients treated with radiation therapy between 1961 and 1985. The classical group consisted of 71 patients of whom 50 had stage I and 21 had stage II disease. The anaplastic group consisted of 19 patients of whom ten had stage I and nine had stage II disease. The median follow-up time was 64 months for the entire group. The 10-year relapse-free survival rate for the classical group was 94% and for the anaplastic group was 70% (P less than .05). For patients with classical stage I disease, the relapse-free actuarial survival rate was 98%; for patients with anaplastic stage I disease, it was 64% (P less than .02). For the classical stage II disease group, the relapse-free actuarial survival rate was 84% and for the anaplastic stage II disease group, 75% (P less than .70). Four patients in the classical group (6%) had relapses; of these, one patient had local recurrence of tumor, and three had distant metastases. In the anaplastic group, four patients (21%) had relapses; two patients had local recurrence of tumor, and two had distant metastases. Therefore the data suggest a difference in survival and relapse rates between classical and anaplastic seminoma.     

BRCA2与LIM结构域蛋白FHL2的相互作用

目的：应用酵母双杂交方法筛选BRCA2相互作用蛋白编码基因，验证其相互作用并研究其功能联系。方法：以BRCA2基因3′端片段构建酵母双杂交质粒，筛选正常人乳腺上皮细胞cDNA库，获得编码相互作用蛋白的基因，采用免疫共沉淀、哺乳细胞双杂交和荧光酶测定等方法进一步验证蛋白间相互作用和功能联系．结果：采用酵母双杂交系统筛选，获得了多个编码BRCA2相互作用蛋白的基因，其中包括已知的FHL2蛋白；免疫共沉淀和哺乳动物细胞双杂交试验显示BRCA2和FHL2在体内特异性结合，并证实FHL2在体内形成同源二聚体；转录活性分析发现BRCA2与FHL2有协同转录激活作用。结论：发现BRCA2与FHL2蛋白间相互作用和功能联系，为BRCA2功能研究提供了新的方向。     

Progressive dilated cardiomyopathy in a patient with longstanding and complete prednisone-induced hematological remission of idiopathic hypereosinophilic syndrome

Summary A female patient is described in whom the diagnosis of idiopathic hypereosinophilic syndrome (HES) with heart disease and peripheral neuropathy was made at the age of 32 years. Although prednisone induced a prompt and longstanding complete hematological remission, progressive and eventually intractable heart failure developed, and the patient died 6 years later. Endomyocardial biopsy at diagnosis showed infiltration with intact and disintegrated eosinophils and Charcot-Leyden crystals. Echocardiographic follow-up (including Doppler-Echocardiography) revealed mitral regurgitation with thickening and impaired motility of the posterior mitral leaflet, as well as progressive dilated cardiomyopathy. At autopsy, a diffuse interstitial fibrosis with patchy prominence in an eccentric hypertrophic and highly dilated heart was found. There were no significant endocardial thickening and no mural thrombi. In contrast to the findings of the initial endomyocardial biopsy, autopsy revealed no eosinophilic infiltrate.In this case, eosinophil-induced heart disease manifested as dilated cardiomyopathy, without endocardial fibrosis as originally described by Löffler. We speculate, that eosinophils have been deposited predominantly in the myocard at an early stage of disease, and — activated locally — secreted their granule proteins producing an initial damage to capillary endothelial cells and myocytes. After prednisone-induced clearance of eosinophils from blood and tissues, progressive, self-perpetuating interstitial fibrosis of the myocard and loss of myocytes eventually resulted in end-stage dilated cardiomyopathy.Abkürzungsverzeichnis HES idiopathic hypereosinophilic syndrome - UBBC unsaturated vitamin B₁₂ binding capacity - ECP eosinophil cationic protein - MBC major basic protein - EDD end-diastolic diameter of the left ventricle - LA left atrium diameter - LVEDP left ventricular end-diastolic pressure - NIH National Institutes of Health     

Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation

The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403 amino acid dual specificity phosphatase (protein tyrosine phosphatase; PTPase), was shown recently to play a broad role in human malignancy. Somatic PTEN deletions and mutations were observed in sporadic breast, brain, prostate and kidney cancer cell lines and in several primary tumours such as endometrial carcinomas, malignant melanoma and thyroid tumours. In addition, PTEN was identified as the susceptibility gene for two hamartoma syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD families and seven BZS families was screened for germline PTEN mutations. PTEN mutations were identified in 30 of 37 (81%) CD families, including missense and nonsense point mutations, deletions, insertions, a deletion/insertion and splice site mutations. These mutations were scattered over the entire length of PTEN , with the exception of the first, fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD mutations identified in this exon. Seven of 30 (23%) were within the core motif, the majority (five of seven) of which were missense mutations, possibly pointing to the functional significance of this region. Germline PTEN mutations were identified in four of seven (57%) BZS families studied. Interestingly, none of these mutations was observed in the PTPase core motif. It is also worthy of note that a single nonsense point mutation, R233X, was observed in the germline DNA from two unrelated CD families and one BZS family. Genotype-phenotype studies were not performed on this small group of BZS families. However, genotype-phenotype analysis inthe group of CD families revealed two possible associations worthy of follow-up in independent analyses. The first was an association noted in the group of CD families with breast disease. A correlation was observed between the presence/absence of a PTEN mutation and the type of breast involvement (unaffected versus benign versus malignant). Specifically and more directly, an association was also observed between the presence of a PTEN mutation and malignant breast disease. Secondly, there appeared to be an interdependent association between mutations upstream and within the PTPase core motif, the core motif containing the majority of missense mutations, and the involvement of all major organ systems (central nervous system, thyroid, breast, skin and gastrointestinal tract). However, these observations would need to be confirmed by studying a larger number of CD families.      

Response from lieberman and colleagues

Respond on comments on Lieberman's article: Cyclosiloxanes Produce Fatal Liver and Lung Damage in Mice. Environ Health Perspect 107:161-165     

Combining capecitabine and gemcitabine in patients with advanced pancreatic carcinoma: a phase I/II trial.

PURPOSE: Preclinical studies indicate positive interactions between capecitabine, an oral fluorouracil precursor, and gemcitabine, the current standard treatment for advanced pancreatic carcinoma (APC). In this study, we investigated the addition of capecitabine to gemcitabine treatment for patients with APC. PATIENTS AND METHODS: This multicenter study included patients na?ve to chemotherapy who had histologically or cytologically confirmed, nonresectable or metastatic pancreatic carcinoma. Gemcitabine was given at a fixed dose of 1,000 mg/m(2) on days 1 and 8 of a 21-day cycle. Capecitabine was given in increasing doses orally bid for 14 days followed by a 1-week rest. The maximum-tolerated dose (MTD) was defined as one dose level below the dose causing dose-limiting toxicity (DLT) in >or= one third of a cohort of six patients. We included an additional 15 patients at the MTD. RESULTS: Thirty-six patients were included. DLT occurred at a dose of 800 mg/m(2) bid of capecitabine and consisted of myelotoxicity and mucositis. Hand-foot syndrome was not observed, and other toxic effects were mild. Thus, in this regimen, the recommended dose of capecitabine is 650 mg/m(2) bid. In 27 patients with measurable disease, we observed one complete and four partial remissions. In addition, significant drops (> 50% from baseline value) of the tumor marker CA 19-9 occurred in 14 of 24 assessable patients. CONCLUSION: The combination of capecitabine and gemcitabine is well tolerated, with apparent efficacy in patients with APC. Therefore, it is currently being compared with gemcitabine monotherapy in a phase III study.     

Riesgo de enfermar y morir por cáncer de mama en Castilla-La Mancha (1975–1998)

Background. To know the temporary tendency in the mortality due to breast cancer in Castilla-La Mancha (CLM, Spain) between 1975 and 1998. Patients and methods. The mortality data are from the Registry of Mortality of CLM. Crude and standardized mortality rates are calculated. In order to evaluate the tendency, we use the Poisson’s log- linear model. We have calculated the accumulated rate to die and the accumulated risks to die and to become ill. Results. Between 1975 and 1998, 2.44% of all deaths in CLM women were consequence of a breast cancer. The crude rate increased from the 14.55 by 100,000 in 1975 to 25.23 by 100,000 in 1998, with an annual average increase of 1.49%. The average age of death increased until the 67 years old in 1998 as opposed to the 59 years old of 1975. The risk of dying of a breast cancer increased in the period from 1.4% in 1975 to 2.34% in 1998. Conclusion. Mortality by breast cancer has raised until 1993, when it begun to decrease. In general, women with breast cancer die elderly, and young women have increased risk to fall ill.     

Epidemiologic aspects of pediatric multiple trauma in a Spanish urban population

BACKGROUND/PURPOSE: Trauma is still the most frequent cause of mortality and disability in childhood and adolescence. An epidemiologic prospective study on children under 16 years of age with multiple trauma (MT) was conducted in a large Spanish urban university hospital over a 6-year period. METHODS: Of 1,937 children admitted at the pediatric trauma unit for musculoskeletal injuries from March 1988 until March 1994, 56 patients including 37 boys and 19 girls had MT. MT was considered when at least 2 long bones were fractured or there was a fracture of 1 long bone combined with an injury of 4 other major anatomic regions (face and neck, thorax, abdomen, or neural system). The severity of injuries was evaluated according to the modified injury severity score (MISS). RESULTS: Injury to pedestrians was the most frequent cause of MT (54%). The overall mortality rate of the series, including those children dying during transport to the hospital was 11.5%. The average MISS for the whole group was 15 (range, 5 to 59). Head trauma was the most frequent associated injury (52%), two thirds of which were considered minor injuries (Glasgow Coma Scale >15). Seventy-seven fractures were registered, 10% of which were open fractures. External fixation was the most common surgical technique among operated fractures. The average hospitalization period was 16 (median, 13; range, 1 to 150) days. Children with a MISS above 18 points showed a significant longer hospitalization period (mean, 31 +/- 45 days) as compared with those with MISS below 18 points (mean, 10 +/- 7 days; P < .05). There was a strong correlation between the MISS and both the period of hospitalization at the pediatric intensive care unit and the total length of hospital stay. CONCLUSIONS: Pedestrian accidents caused by motor vehicles in children playing at the street contributed most significantly to MT in the urban pediatric population. Special care for prevention must be taken in the age group of 6 to 10 years. Head injury was the main cause of death in children with multiple trauma. MISS was found to be a good predictor of survival and duration of hospital stay in pediatric MT.