Association of MASP2 polymorphisms and protein levels with rheumatic fever and rheumatic heart disease

MASP-2 is a key protein of the lectin pathway of complement system. Several MASP2 polymorphisms were associated with MASP-2 serum levels or functional activity. Here we investigated a possible association between MASP2 polymorphisms and MASP-2 serum levels with the susceptibility to rheumatic fever (RF) and rheumatic heart disease (RHD). We haplotyped 11 MASP2 polymorphisms with multiplex sequence-specific PCR in 145 patients with history of RF from south Brazil (103 with RHD and 42 without cardiac lesion [RFo]) and 342 healthy controls. MASP-2 levels were determined by ELISA. The low MASP-2 producing p.377A and p.439H variants were negatively associated with RF (P = 0.02, OR = 0.36) and RHD (P = 0.01, OR = 0.25). In contrast, haplotypes that share the intron 9 – exon 12 g.1961795C, p.371D, p.377V and p.439R polymorphisms increased the susceptibility to RHD (P = 0.02, OR = 4.9). MASP-2 levels were associated with MASP2 haplotypes and were lower in patients (P < 0.0001), which may reflect protein consumption due to complement activation. MASP2 gene polymorphisms and protein levels seem to play an important role in the development of RF and establishment of RHD.     

The liver in infectious mononucleosis

Summary 1. Twenty-two patients with infectious mononucleosis were studied by liver biopsy and paper electrophoresis of the serum proteins. The findings were compared with a similar group of 30 patients with infectious hepatitis.2. The essential histologic features of infectious mononucleosis were the presence in the hepatic sinusoids and portal tracts of chronic inflammatory cells resembling small lymphocytes, with essentially no parenchymal cell damage. Admixed with this lymphocytic infiltrate, but in relatively minimal numbers, were a few plasma cells and polymorphonuclear leukocytes. In addition, in infectious mononucleosis there were, with rare exceptions, no lipochrome-containing Kupffer cells. Thus, in the majority of cases, the histologic picture was distinct from that seen in infectious hepatitis. Only in comparing a few of the more severe infectious mononucleosis cases with subsiding infectious hepatitis cases was there any tendency for the two pictures to merge, and the distinction on histologic grounds between the two entities could be made in the great majority of cases.3. The most commonly seen abnormalities in the paper electrophoretic patterns of sera obtained from patients with infectious mononucleosis were decreased albumin, increased gamma globulin, not infrequent but variable changes in alpha₂ globulin, and the presence of abnormal proteins migrating with mobilities intermediate to alpha₂ and beta, and beta and gamma globulins. The abnormalities observed in infectious hepatitis were similar to those of infectious mononucleosis, except that in hepatitis alpha₂ globulin was decreased more consistently, gamma globulin increased less frequently, and beta globulin, which was normal in practically all the cases of infectious mononucleosis, was increased in a considerable number of cases.4. Treatment of patients with infectious mononucleosis need not include prolonged bed rest and restriction of activity in an effort to avoid the development of chronic liver disease.     

Common sense in the treatment of pilonidal disease

Summary The management of pilonidal cyst disease in a large military hospital is described. Of special interest to the military practice is the “buddy” system, in which patients help one another to keep their wounds clean and dry. The specific objectives of our technic are: 1) obtaining excellent hemostasis by the use of zinc peroxide paste; 2) avoiding recurrences by an open-wound method of treatment; 3) preservation of a pad of subcutaneous tissue over the postsacral fascia, thus reducing long-term morbidity by insuring a mobile scar; 4) decreasing the duration of hospitalization, achieved by frequently drying the wounds with warm air. Read at the meeting of the American Proctologic Society, Hollywood, Florida, April 12 to 16, 1970. The opinions or assertions contained herein are those of the authors and are not to be construed as official or as reflecting the views of the Navy Department.     

IL‐4‐induced gene 1 maintains high Tob1 expression that contributes to TCR unresponsiveness in human T helper 17 cells

Human Th17 cells have a limited proliferative capacity compared to other T‐cell subsets. We have shown that human Th17 cells display impaired IL‐2 production due to IL‐4‐induced gene 1 (IL4I1) upregulation. Here, we show that in human Th17 cells, IL4I1 also maintains high levels of Tob1, a member of the Tob/BTG (B‐cell traslocation gene) antiproliferative protein family, which prevents cell‐cycle progression mediated by TCR stimulation. Indeed, Th17 cells exhibited higher levels of Tob1 than Th1 cells in both resting and TCR‐activated conditions. Accordingly, the expression of positive regulators of the cell cycle (cyclin A, B, C, and E and Cdk2), as well as of Skp2, which promotes Tob1 degradation, was lower in Th17 cells than in Th1 cells. Tob1 expression in human Th17 cells correlated with both RAR (retinoic acid receptor)‐related orphan receptor C (RORC) and IL4I1 levels. However, RORC was not directly involved in the regulation of Tob1 expression, whereas IL4I1 silencing in Th17 cells induced a substantial decrease of Tob1 expression. These data suggest that IL4I1 upregulation in human Th17 cells limits their TCR‐mediated expansion not only by blocking the molecular pathway involved in the activation of the IL‐2 promoter, but also by maintaining high levels of Tob1, which impairs entry into the cell cycle.     

Influences of Sex, Habitat, and Seasonality on Heavy-Metal Concentrations in the Burrowing Crab (Neohelice Granulata) From a Coastal Lagoon in Argentina

Cadmium, chromium, copper, and manganese concentrations were determined in hepatopancreas of both sexes as well as in eggs at different embryonic development stages of the burrowing crab Neohelice granulata (Brachyura, Varunidae) from Mar Chiquita Coastal Lagoon, a biosphere reserve from Argentina, during a period of 1 year, to assess the bioaccumulation of metals associated with sex and seasonality. Furthermore, metal levels in associated superficial sediment samples were also determined. Two different “cangrejales,” one in a mudflat and another one in a salt marsh, were studied. The results showed high concentrations of copper within the hepatopancreas, which was considered a strong reflection of high exposure of N. granulata to this metal. Metal accumulation in hepatopancreas from both study sites and sexes did not present significant differences, as did seasonality. In this sense, both spring and summer metal levels in hepatopancreas were the greatest. Eggs did not present differences in metal accumulation, with the exception of manganese, between sites or between crabs at different embryonic stages. For this metal, eggs from female crabs inhabiting mudflats showed higher levels than those from inhabiting salt marshes. Moreover, eggs in the late embryonic stage also showed the highest manganese concentrations. Metal levels in sediments, however, were similar in both sites. These are the first results of metal level in biota and sediments in this particular environment. Such results could be used as a baseline for the monitoring of metal levels in future studies in Mar Chiquita Coastal Lagoon.     

Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response

Congenital nephrogenic diabetes insipidus (NDI) is a rare disease caused most often by mutations in the vasopressin V2 receptor (AVPR2). We studied a family which included a female patient with NDI with symptoms dating from infancy. The patient responded to large doses of desmopressin (dDAVP) which decreased urine volume from 10 to 4 I/day. Neither the parents nor the three sisters were polyuric. The patient was found to be a compound heterozygote for two novel recessive point mutations in the aquaporin-2 (AQP2) gene: L22V in exon 1 and C181W in exon 3. Residue Cys181 in AQP2 is the site for inhibition of water permeation by mercurial compounds and is located near to the NPA motif conserved in all aquaporins. Osmotic water permeability (Pf) in Xenopus oocytes injected with cRNA encoding C181W-AQP2 was not increased over water control, while expression of L22V cRNA increased the Pf to approximately 60% of that for wild-type AQP2. Co-injection of the mutant cRNAs with the wild-type cRNA did not affect the function of the wild-type AQP2. Immunolocalization of AQP2-transfected CHO cells showed that the C181W mutant had an endoplasmic reticulum-like intracellular distribution, whereas L22V and wild-type AQP2 showed endosome and plasma membrane staining. Water permeability assays showed a high Pf in cells expressing wild-type and L22V AQP2. This study indicates that AQP2 mutations can confer partially responsive NDI.