Langerhans cells develop from a lymphoid-committed precursor

Langerhans cells (LCs) are specialized dendritic cells (DCs) strategically located in stratified epithelia, such as those of the skin, oral cavity, pharynx, esophagus, upper airways, urethra, and female reproductive tract, which are exposed to a wide variety of microbial pathogens. LCs play an essential role in the induction of T-lymphocyte responses against viruses, bacteria, and parasites that gain access to those epithelial surfaces, due to their high antigen capture and processing potential and their capacity to present antigen peptides to T cells on migration to the lymph nodes.(1) Although LCs have been classically considered of myeloid origin, recent reports, which demonstrate the existence of lymphoid DCs derived from multipotent lymphoid precursors devoid of myeloid differentiation potential,(2-5) raise the question of the lymphoid or myeloid origin of LCs. The present study shows that mouse lymphoid-committed CD4(low) precursors, with the capacity to generate T cells, B cells, CD8(+) lymphoid DCs, and natural killer cells,(26) also generate epidermal LCs on intravenous transfer, supporting the view that LCs belong to the lymphoid lineage. (Blood. 2000;96:1633-1637)     

Adrenal angiosarcoma: report of a case

Adrenal epithelioid angiosarcoma is an extremely rare tumor. Even if such tumors are very aggressive, a long survival may occasionally be observed after an adrenal ectomy. A 70-year-old woman suffering from persistent right flank pain showed a 5-cm right adrenal mass plus a 2-cm liver mass at the radiologic workup, and both were suspected of being malignant. No adrenal hypersecretion was demonstrated. During an explorative median laparotomy the right adrenal gland with the whole periadrenal tissue and locoregional lymph nodes was removed. A histological examination revealed an adrenal angiosarcoma. The resection margin was tumor-free with no lymph node infiltration. The liver mass turned out to be a cistobiliary adenoma. Since no distant metastases were observed, no adjuvant chemotherapy was performed. After an 18-month follow-up the patient is still well with no sign of a relapse. When this rare adrenal tumor is encountered and curative treatment is attempted initially extensive surgical procedures are essential. Received: April 16, 2001 / Accepted: November 20, 2001     

Prevalence and progression of mitochondrial diseases: a study of 50 patients

We report 50 patients with various clinical phenotypes of mitochondrial disease studied over the past 10 years in a large urban area (Madrid Health Area 5). The clinical phenotypes showed a large variety of abnormalities in molecular biology and biochemistry. The prevalence of mitochondrial diseases was found to be 5.7 per 100,000 in the population over 14 years of age. Clinical and electrophysiological assessment reveal signs of neuropathy in 10 patients. Electromyographic findings consistent with myopathy were obtained in 37 cases. Six patients died of medical complications. Disease phenotype influenced survival to some degree (P < 0.01). Age of onset and gender were not associated with differences in survival. Mitochondrial disease is thus far more common than expected and a common cause of chronic morbidity.     

Indolo[3,2-b]carbazole inhibits gap junctional intercellular communication in rat primary hepatocytes and acts as a potential tumor promoter

Indole-3-carbinol (I3C) is a naturally occurring substance that shows anti-carcinogenic properties in animal models. Besides its clear anti-carcinogenic effects, some studies indicate that I3C may sometimes act as a tumor promoter. Indolo[3,2-b]carbazole (ICZ), which is formed in the acidic environment of the stomach after intake of I3C, has a similar structure to, and shares biological effects with, the well-known tumor promoter 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Therefore, we hypothesized that ICZ could be responsible for the potential tumor-promoting activity of I3C. The aim of the present study was to investigate the effect of ICZ on gap junctional intercellular communication (GJIC) in primary cultured rat hepatocytes co-cultured with the rat liver epithelial cell line WB-F344. Indolo[3,2-b]carbazole inhibited GJIC in the rat hepatocytes in a dose- and time-dependent manner. Significant inhibition was observed after 8 and 12 h of treatment with 1 and 0.1 micro M ICZ, respectively. Maximum GJIC inhibition (cell-cell communication only 5% of control values) was observed after 24-48 h of ICZ treatment. Continued exposure to 1 micro M ICZ suppressed GJIC until approximately 120 h. Both ICZ and TCDD treatment reduced the Cx32 mRNA level as well as the plasma membrane Cx32 staining. Indolo[3,2-b]carbazole increased the Cyp1a1, Cyp1a2 and Cyp1b1 mRNA levels concurrently with an increase in 7-ethoxyresorufin O-deethylase (EROD) activities. Maximum EROD activity and Cyp1a1 mRNA levels were observed after approximately 12 h, whereas Cyp1a2 and Cyp1b1 mRNA levels peaked after 48 h. This study shows that ICZ may possess tumor promoter activity down-regulating GJIC by mechanisms, which seem to include activation of the Ah receptor and/or Cyp1 activity. Further studies are needed in order to clarify the anticarcinogenic/carcinogenic effects of I3C and ICZ before high doses of I3C may be recommended as a dietary supplement.     

Rodent Endosonography to Monitor Esophageal Cancer

Animal models of luminal cancers are important to understand and assess chemopreventive and chemotherapeutic interventions. However, the ability to assess tumor growth and response without animal sacrifice is limited. We assessed the ability of luminal sonography to assess the presence of tumor and its size in a surgical esophagojejunostomy model of esophageal cancer. Luminal sonography had a sensitivity of 88%, specificity of 100%, and accuracy of 93% in identifying the esophageal cancers. The tumor dimensions on luminal sonography were within 11% of autopsy measurements. Minimal tumor dimension was 2 mm and maximum 6.2 mm. The procedure was feasible without technical difficulty. In conclusion, rodent endosonography is a useful technique that can accurately determine the presence of tumors as well as their dimensions.     

Serum levels of coenzyme Q10 in patients with amyotrophic lateral sclerosis

Summary. To elucidate whether serum coenzyme Q₁₀ levels are related with the risk for amyotrophic lateral sclerosis (ALS), we compared serum levels of coenzyme Q₁₀ and the coenzyme Q₁₀/cholesterol ratio, in 30 patients with ALS and 42 matched controls using a high performance liquid chromatography technique. The mean serum coenzyme Q₁₀ levels and the coenzyme Q₁₀/cholesterol ratio did not differ significantly between the 2 study groups. These values were not influenced by the clinical form (spinal vs. bulbar) of ALS, and they did not correlate with age, age at onset, and duration of the disease. These results suggest that serum coenzyme Q₁₀ concentrations are unrelated with the risk for ALS. Received September 1, 1999; accepted January 4, 2000     

Mitochondrial dysfunction associated with a mutation in the Notch3 gene in a CADASIL family

BACKGROUND: Cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by recurrent subcortical ischemic strokes and dementia caused by mutations in the Notch3 gene. In Drosophila melanogaster, Notch signaling has a pleiotropic effect, affecting most tissues of the organism during development. OBJECTIVE: To characterize a potential mitochondrial dysfunction associated with mutations in the Notch3 gene. METHODS: Biochemical, histochemical, molecular, and genetic analyses were performed on muscle biopsy specimens and fibroblasts obtained from patients of a Spanish family with CADASIL. Additional biochemical and molecular analyses of the N(55e11) mutant of D. melanogaster were performed. RESULTS: In muscle biopsy specimens, a significant decrease was found in the activity of complex I (NADH [reduced form of nicotinamide adenine dinucleotide] dehydrogenase), and in one patient, histochemical analysis showed the presence of ragged-red fibers with abnormal cytochrome c oxidase staining. Reduced fibroblast activity of complex V (ATP synthase) was found. Supporting data on patients with CADASIL, it was found that the mutation N(55e11) in Drosophila decreases the activity of mitochondrial respiratory complexes I and V. CONCLUSIONS: Mitochondrial respiratory chain activity responds, directly or indirectly, to the Notch signaling pathway. Mitochondrial dysfunction in patients with CADASIL may be an epiphenomenon, but results of this study suggest that the pathophysiology of the disease could include a defect in oxidative phosphorylation.     

The effect of adding group-based counselling to individual lifestyle counselling on changes in dietary intake. The Inter99 study – a randomized controlled trial

Background  

Few studies have investigated the specific effect of single intervention components in randomized controlled trials. The purpose was to investigate the effect of adding group-based diet and exercise counselling to individual life-style counselling on long-term changes in dietary habits.     

Anthropometric Measurements and Epithelial Ovarian Cancer Risk in African–American and White women

Previous studies of anthropometric factors and ovarian cancer risk have been inconsistent and none have evaluated the association among African–American women. Data from a population-based, case–control study of 593 cases and 628 controls were used to evaluate ovarian cancer risk in relation to weight, height, body mass index (BMI) and waist-to-hip ratio (WHR). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed and established risk factors were adjusted for using logistic regression models, stratified by race. Among all races, weight at age 18, WHR, weight and BMI one year prior to interview were associated with elevated ovarian cancer risk. When stratified by race, the association between WHR and ovarian was similar among Whites and among African Americans. However, African–American women in the fourth quartile of height had an elevated risk of ovarian cancer (OR = 3.2; 95% CI = 1.3–7.8), but this risk was not apparent in Whites (OR = 1.0; 95% CI␣ = 0.7–1.4). These findings support the hypothesis that obesity is an important risk factor of ovarian cancer among African–Americans and Whites and also suggest that height may be a risk factor specific to African–Americans.^★ This work was performed at the Duke University Comprehensive Cancer, Durham, NC, USA.