P-cadherin expression is associated with high-grade ductal carcinoma in situ of the breast

Cadherins are calcium-dependent cell-cell adhesion glycoproteins, separated into several subclasses with distinct adhesive specificities and tissue distribution, which play an important role in many cellular events. We analyse the expression of E-, N- and P-cadherin in a series of ductal carcinoma in situ (DCIS) of the breast, since this disease represents a heterogeneous group, with different risks of progression to invasive breast carcinoma. We also studied the correlation between cadherin expression and DCIS classification systems, namely the Van Nuys and the Holland et al. classification, this latter based on cytonuclear differentiation and cell polarity. Our results showed that, regardless the classification applied, P-cadherin expression is strongly associated with high histological grade of DCIS (P=0.0047) and lack of estrogen receptors (P=0.0008). The use of Holland et al. classification showed a significant correlation between P-cadherin expression and decreased cell polarity (P=0.01). In conclusion, P-cadherin expression seems to be more relevant in DCIS pathogenesis than the altered expression of any other cadherin, including the decrease of E-cadherin expression.     

The N-linked glycan g15 within the V3 loop of the HIV-1 external glycoprotein gp120 affects coreceptor usage,cellular tropism,and neutralization

We have studied infectivity and neutralization of X4, R5, and R5X4 tropic HIV-1 mutants, which are lacking N-linked glycosylation sites for glycans g13, g14, g15, and g17 in the V3 loop region of gp120. X4-tropic NL4-3 mutants lacking combinations of g14/15 or g15/17 showed markedly higher infectivity in CXCR4-specific infection. The role of g15 in CCR5-specific infection was investigated using viruses with high (NL-918, R5-monotropic), medium (NL-991, R5-monotropic), and low (NL-952, R5X4-dualtropic) CCR5-specific infectivity. For NL-991, a reduction of infectivity on GHOST-CCR5 cells was observed for a mutant lacking g15. For NL-952 mutants all lacking g15, a complete loss of CCR5-specificity was observed and NL-952 was shifted from R5X4 to X4 tropism. For all mutants of NL4-3, NL-991, and NL-952, where the lack of g15 markedly influenced infectivity or coreceptor usage, neutralization was enhanced. In contrast, NL-918 mutants with or without g15 showed no difference in neutralization and no difference in GHOST-CCR5 infection rates. Thus, for viruses with a low or medium CCR5-specificity the role of g15 for changing CCR5-usage and sensitivity to neutralization was more significant than for viruses with high infection rates on GHOST-CCR5 cells. Our data demonstrate that V3 glycans play an important role in the usage of CXCR4 and CCR5. The lack of g15 was relevant for a more efficient use of CXCR4, whereas interaction with CCR5 was facilitated in the presence of g15. This study also demonstrates that glycan g15 is involved in blocking of neutralizing antibodies and shifting HIV tropism from R5X4 to X4.     

Ambulante indirekte Blutdrucklangzeitmessung bei primärer und sekundärer Hypertonie

Summary Ambulatory 24 hour blood pressure measurements were performed in 21 patients with various forms of secondary hypertension and were compared with the blood pressure profile of a matched group of patients with primary hypertension. Patients with renovascular (n=8) and renoparechymal hypertension (n=8), and with primary hyperaldosteronism (n=4) showed no significant fall in systolic blood pressure during the sleeping period (00-03 a.m.) and in systolic and diastolic blood pressure in the early morning (06 a.m.) as compared with essential hypertensives. However, in a single case of hypertension due to coarctation of the aorta the 24 hour blood pressure profile is not different from essential hypertension.Thus, ambulatory 24 hour blood pressure recording is a good method for screening secondary forms of hypertension.

     

Effect of danazol in immune thrombocytopenic purpura

Danazol and vinblastine are effective in many patients with chronic immune thrombocytopenic purpura (ITP). To evaluate the mechanism of action of these drugs, we studied six consecutive patients with chronic ITP treated with danazol and one treated with vinblastine. All the patients responded clinically without a notable change in the level of platelet-associated IgG. Instead, the clinical response to therapy was associated with a decrease in the number of monocyte binding sites for monomeric IgG (Fc receptors). In one patient, clinical relapse was associated with a spontaneous 2.7-fold increase in the number of monocyte Fc (IgG) receptors, without a change in the level of platelet-associated immunoglobulin. A decrease in the number of monocyte Fc (IgG) receptors following vinblastine infusion was associated with a clinical remission. We conclude that the clinical course of ITP may be influenced by the expression of monocyte or macrophage Fc (IgG) receptors. Danazol and vinblastine may mediate their clinical effect, at least in part, by influencing the number of available Fc (IgG) receptors on phagocytic cells.     

Hypothalamic hypothyroidism and XXY/XY sex chromosome mosaicism. Report of a case

An 18-year-old boy with clinical features of Klinefelter's syndrome in whose case the buccal smear was chromatin-negative and chromosomal analysis of peripheral blood revealed 46 XY karyotype is described. Diagnosis was confirmed by demonstration of an XXY cell line in cultured skin fibroblasts. Low circulating thyroxine levels were found despite absence of clinical hypothyroidism, and TSH was barely detectable. The studies are consistent with an isolated deficiency of thyrotropin-releasing hormone in a patient with XY/XXY mosaicism.     

Human monocyte functional heterogeneity: monocyte fractionation by discontinuous albumin gradient centrifugation

Human monocytes subserve many roles in the immune response. It is not clear, however, whether this functional heterogeneity reflects the action of different monocyte subpopulations. We separated human blood monocytes into distinct populations using a discontinuous (15-35%) serum albumin gradient technique. We examined if any of a number of monocyte functions were preferentially expressed by these five monocyte subsets. Monocytes in the 25% and 30% albumin fractions possessed more Fc (IgG) and C3 receptor activity than did monocytes in either of the 15, 20 or 35% fractions. In addition, monocytes isolated in the more dense albumin fractions were enriched for the capacity to support pokeweed mitogen-induced B-cell differentiation. All gradient fractions were equally capable of binding Raji cells and inhibiting Raji cell incorporation of [3H]thymidine. These data indicate that fractionation of monocytes by a discontinuous albumin gradient is an effective method to enrich for those monocytes with certain functional characteristics.