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.     

Tumors of the central nervous system in biopsy and autopsy material. 7th communication: neurinomas and neurofibromatoses with CNS involvement

In 1,491 autopsy cases with CNS tumors observed at the Pathological Institute of the Medical Academy of Erfurt in the period from 1953 to 1976 (54,946 autopsies) 72 cases (4.8%) with neurinomas were found. They comprise 67 solitary neurinomas, 1 bilateral acoustic neurinoma without other signs of neurofibromatosis, and 4 cases of neurofibromatosis with neurinomas of the CNS. Among the 68 cases with CNS neurinomas (neurofibromatoses excluded) 87% were acoustic neurinomas, 12% spinal tumors, and 1 case was located in the trigeminal nerve. In 60 (88%) of these 68 cases, the neurinoma was operated upon or clinically diagnosed, resp. The diameter of 18 (26%) neurinomas of the autopsy material was larger than 5 cm. Patients in the 6th decennium predominated in this series. The sex distribution revealed a preponderance of females over males (3:1). In 3 cases further CNS tumors (ependymoma, glioblastoma, meningioma) were found. Additionally, 3 cases had carcinomas of different localization (Table 5). Following tumors were seen in 9 cases of Morbus Recklinghausen with CNS involvement: 4 cases with multiple neurinomas, 3 meningiomas, 1 astrocytoma, 2 glioses and 1 angiomatous malformation (Table 6). Among 1,670 CNS tumors in biopsy material, 144 (8.6%) were neurinomas. 60% of them were located in the nervus acusticus, 40% spinally, mainly in the thoracic region. The 6th decennium was most affected, and females were more frequent than males (2:1) in our material. Nearly all CNS neurinomas were benign. Only 1 spinal tumors was classified as a malignant neurinoma. 2 of the 9 cases with Morbus Recklinghausen had malignant neurogenic tumors (neurofibrosarcomas).     

The role of complement in Ascaris suum induced histopathology

The role of complement in the histopathology of primary and challenge re-infection by Ascaris suum was assessed. Guinea-pigs deficient in C4 or depleted of the terminal components C3 to C9 by cobra venom factor (CVF) were employed. Pathological changes in the livers of complement-deficient guinea-pigs differed slightly from controls. The most striking findings were in the lungs of CVF-treated infected animals, where marked eosinophilic abscesses were observed following either a primary or repeat infection with Ascaris suum. Additionally, greater numbers of larvae were harvested from the lungs of both CVF-treated and C4-deficient infected guinea-pigs as compared with controls. Serum C4 levels varied over the first 7 days after primary infection, declining in several of the normal and CVF-treated animals, but remaining stable in others. The C4 levels remained unchanged in re-infected animals. The C3 to C9 levels remained within the normal range in both primary and re-infected guinea-pigs. The data suggests that complement is involved in the host responses to infection with Ascaris suum. In the absence of complement (C3 to C9), enhanced pulmonary eosinophilic infiltration and eosinophilic granuloma formation occur in both primary and re-infected animals.