Congenital erythrocytosis with elevated erythropoietin level: an incorrectly set "erythrostat"?

It is well documented that IL-6 plays a critical role in B cell terminal differentiation, and in mucosal sites it stimulates proliferation and large-scale secretion of immunoglobulin by B cells, especially those committed to IgA production. The close juxtaposition of IL-6 mRNA+ cells to plasma cells in the intestinal lamina propria supports the proposition that IL-6 production in situ is an important factor determining the outcome of antibody responses at that site. However, it has not been established previously whether exogenous IL-6 could boost antibody responses in the intestine if administered with a challenge antigen. Using a resected gut loop (Thiry-Vella loop) model, we have been able to demonstrate that in mice with double loops, antibody containing cell responses to lumenal administration of ovalbumin were 50% greater in loops given intralumenal recombinant IL-6 with the challenge antigen, than in loops challenged with antigen alone. This demonstrates the efficacy of IL-6 in promoting accumulation of antibody secreting cells in the gut, and suggests a potential therapeutic role for IL-6 to enhance responses to mucosal vaccines.     

The ocular albinism type 1 gene product is a membrane glycoprotein localized to melanosomes

Ocular albinism type 1 (OA1) is an inherited disorder characterized by severe reduction of visual acuity, photophobia, and retinal hypopigmentation. Ultrastructural examination of skin melanocytes and of the retinal pigment epithelium reveals the presence of macromelanosomes, suggesting a defect in melanosome biogenesis. The gene responsible for OA1 is exclusively expressed in pigment cells and encodes a predicted protein of 404 aa displaying several putative transmembrane domains and sharing no similarities with previously identified molecules. Using polyclonal antibodies we have identified the endogenous OA1 protein in retinal pigment epithelial cells, in normal human melanocytes and in various melanoma cell lines. Two forms of the OA1 protein were identified by Western analysis, a 60-kDa glycoprotein and a doublet of 48 and 45 kDa probably corresponding to unglycosylated precursor polypeptides. Upon subcellular fractionation and phase separation with the nonionic detergent Triton X-114, the OA1 protein segregated into the melanosome-rich fraction and behaved as an authentic integral membrane protein. Immunofluorescence and immunogold analyses on normal human melanocytes confirmed the melanosomal membrane localization of the endogenous OA1 protein, consistent with its possible involvement in melanosome biogenesis. The identification of a novel melanosomal membrane protein involved in a human disease will provide insights into the mechanisms that control the cell-specific pathways of subcellular morphogenesis.     

Acute toxicity of several organophosphorous insecticides and protection by cholinergic antagonists and 2-PAM on Artemia salina larvae

Western blot analysis and indirect immunofluorescence microscopy were used to evaluate the fate of the aryl-hydrocarbon receptor (AhR) and aryl-hydrocarbon receptor nuclear translocator (Arnt) protein in culture cell models exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In wild-type (WT) murine Hepa-1c1c7 cells, AhR protein was depleted by 85% after 4 hr of TCDD treatment as measured in total cell lysates. In contrast, the concentration of Arnt protein was unaffected by TCDD treatment in WT cells. Analysis of the AhR with immunofluorescence microscopy revealed that nuclear translocation of the liganded AhR preceded its depletion from cells. AhR protein was depleted from Hepa-1 type I variants (that contain a concentration of AhR that is 10% of WT) with a similar time course and to the same maximal level observed in WT cells (85%). The EC50 for AhR depletion in Hepa-1 cells was 39 pm TCDD and correspond to the EC50 for induction of P4501A1 protein. Murine embryonic fibroblasts (NIH-3T3), rat aortic smooth muscle cells (A7), and murine skeletal muscle cells (C2C12) all exhibited >90% depletion of the AhR after 2-4 hr of TCDD treatment. Arnt concentration was not affected by TCDD in these cell lines. These results indicate that the liganded AhR is rapidly depleted within the nuclear compartment of hepatic and nonhepatic cells in a manner independent of the Arnt protein.     

Fast fluid-attenuated inversion-recovery (FLAIR) MRI in the assessment of intraaxial brain tumors

This study demonstrates the value of a fast fluid-attenuated inversion-recovery (FLAIR) technique in the assessment of primary intraaxial brain tumors. Twenty-one patients with primary intraaxial brain tumors were examined by T2-weighted, proton-density-weighted fast spin echo, fast FLAIR, and contrast-enhanced T1-weighted spin echo using identical slice parameters. The images were evaluated using quantitative and qualitative criteria. Quantitative criteria were tumor-to-background and tumor-to-cerebrospinal fluid (CSF) contrast and contrast-to-noise ratio (CNR). The qualitative evaluation was performed as a multireader analysis concerning lesion detection, lesion delineation, and image artifacts. In the qualitative evaluation, all readers found the fast FLAIR to be superior to fast spin echo in the exact delineation of intraaxial brain tumors (P < .001) and the delineation of enhancing and nonenhancing tumor parts. Fast FLAIR was superior in the delineation of cortically located and small lesions but was limited in lesions adjacent to the ventricles. Fast FLAIR provided a significantly better tumor-to-CSF contrast and tumor-to-CSF CNR (P < .001). The tumor-to-background contrast and tumor-to-background CNR of the fast FLAIR images were lower than those of T2-weighted spin-echo images but higher than those of proton-density-weighted spin-echo images. FLAIR images had more image artifacts influencing the image interpretation in only two patients. Signal hyperintensities at the ventricular border were present in 92% of the patients. They are common findings in fast FLAIR and should be included into the image interpretation.     

Prevention strategies for occupational low back pain

Ethnic comparisons are extremely important and useful for studying the HLA component involved in insulin-dependent diabetes mellitus (IDDM) predisposition. To date there have been only a few reports on the association of HLA loci and IDDM in Chinese. We report here a study on DQA1*Arg52, DQB1*nonAsp57, and DRB1*04 in IDDM children and control adults among Han Chinese living in Taiwan. One hundred and fourteen unrelated children (62 boys) with IDDM were studied. Their ages at diagnosis were between 0.3 and 15.0 years (6.8 +/- 3.6 years). The control population consisted of 120 randomly selected normal adults. DQA1*Arg52(+/+), DQB1*nonAsp57(+/+), and DRB1*04(+/-) were associated with IDDM (RR = 11.50, 2.21, and 2.82; p = 1.11 x 10(-15), 2.84 x 10(-3), and 1.98 x 10(-4), respectively). DQA1*Arg52, DQB1*nonAsp57, and DRB1*04 conferred risks for IDDM (RR = 12.79, 7.11, and 2.83; pc = 8.22 x 10(-4), 5.35 x 10(-3), and 5.68 x 10(-4), respectively). Combinations of DQA1*Arg52 and DRB1*04 conferred the highest risk for IDDM (RR = 19.64, pc = 5.4 x 10(-5)). DQA1*Arg52 was associated with IDDM in subjects with DQB1*nonAsp57+ (RR = 14.87, pc = 2.41 x 10(-4)) and DQB1*nonAsp57 was also associated with IDDM in subjects with DQA1*Arg52+ (RR = 8.41, pc = 1.54 x 10(-3)), suggesting that DQA1*Arg52 and DQB1*nonAsp57 are interacting. This study demonstrates that DQA1*Arg52, DQB1*nonAsp57, and DRB1*04 confer susceptibility for IDDM to Chinese children. A combination of DQA1*Arg52 and DRB1*04 confers the highest risk and it is suggested that a susceptibility gene might be situated between DQA1*Arg52 and DRB1*04 or both are synergistic. There is an interaction between DQA1*Arg52 and DQB1*nonAsp57 and homozygosity for DQA1*Arg52/DQB1*nonAsp57, which encodes four susceptibility DQ heterodimers, confers a high risk.     

An ultrastructural study of the phagocytosis of Burkholderia pseudomallei

Burkholderia pseudomallei causes melioidosis and is believed to be an intracellular pathogen in human and animal disease. The uptake of B. pseudomallei by mouse peritoneal macrophages and cells in tissue culture was examined by electron microscopy. In all the systems studied B. pseudomallei were phagocytosed and apparently inhibited the normal processes of intracellular killing. Destruction of the phagosome membrane occurred and the bacteria escaped into the cytoplasm.     

Inhibitory effect of Garcinia kola on lipid peroxidation in rat liver homogenate

Garcinia kola, (a herb grown in Nigeria; calorific value 358.54 k.cal/100 g) inhibited in vitro lipid peroxidation of rat liver homogenate in a dose dependent manner. The inhibitory activity of G.kola was not affected by heating (100 degrees C/10 min). The antioxidant component of G.kola was soluble in aqueous and ethanolic media. The active component(s) in G. kola responsible for its inhibitory activity on lipid peroxidation is tentatively identified as isoflavones.     

Studies of the coronary circulation in Chagas' heart disease

Pathogenesis of chronic Chagas' heart disease may include various disturbances in the coronary circulation, that could be responsible for the myocardial lesions seen in human hearts and in experimental models of the disease. In this paper we critically reviewed the anatomical and functional abnormalities described in chronic chagasic patients, pertaining to the so-called vascular pathogenetic theory of Chagas' disease. The epicardial coronary arteries are usually free of significant obstructive disease in nonselected groups of chagasic patients examined at autopsy or by coronary angiography. However, chagasic patients who were studied after an episode of acute myocardial infarction, show the same patterns of atherosclerotic coronary artery disease seen in the general nonchagasic population. Studies of chagasic patients with angiographically normal coronary arteries, by several scintigraphy methods, revealed myocardial perfusion abnormalities which may be caused by the microcirculatory derangements described in animals experimentally infected with the T. cruzi. Since hypoperfusion has been detected in regions with normal or mildly impaired wall motion, it is likely that the microvascular disturbances precede and may be causative mechanism for the subsequent myocardial damage. We speculate that hibernating ventricular areas may occur in chagasic patients, on the basis of the evidence gathered from these studies. Recent investigations of chronic patients with Chagas' disease and chest pain showed attenuation of the vasomotor responses to physiological and pharmacological stimuli, in the epicardial coronary arteries.