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.     

Long-term maintenance of hematopoietic stem cells does not require contact with embryo-derived stromal cells in cocultures

We recently established that two midgestation-derived stromal clones--UG26-1B6, urogenital ridge-derived, and EL08-1D2, embryonic liver-derived--support the maintenance of murine adult bone marrow and human cord blood hematopoietic repopulating stem cells (HSCs). In this study, we investigate whether direct HSC-stroma contact is required for this stem cell maintenance. Adult bone marrow ckit+ Ly-6C- side population (K6-SP) cells and stromal cells were cocultured under contact or noncontact conditions. These experiments showed that HSCs were maintained for at least 4 weeks in culture and that direct contact between HSCs and stromal cells was not required. To find out which factors might be involved in HSC maintenance, we compared the gene expression profile of EL08-1D2 and UG26-1B6 with four HSC-nonsupportive clones. We found that EL08-1D2 and UG26-1B6 both expressed 21 genes at a higher level, including the putative secreted factors fibroblast growth factor-7, insulin-like growth factor-binding proteins 3 and 4, pleiotrophin, pentaxin-related, and thrombospondin 2, whereas 11 genes, including GPX-3 and HSP27, were expressed at a lower level. In summary, we show for the first time long-term maintenance of adult bone marrow HSCs in stroma noncontact cultures and identify some secreted molecules that may be involved in this support.     

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).     

Association analysis of a polymorphism in the G‐protein stimulatory α subunit in patients with major depression*

Growing evidence suggests that G‐proteins may be involved in pathogenesis and treatment of affective disorders. Several studies have reported altered levels and/or activities of stimulatory G‐proteins in depression. The aim of this study was to investigate whether a polymorphism in the stimulatory α subunit of G‐proteins (T/C point mutation in exon 5; ATT → ATC at codon 131) is associated with major depression or response to antidepressant treatment. Therefore, we performed a case‐control association study with 212 depressive patients and 137 healthy, unrelated controls. There was no evidence for an association between the investigated polymorphism in the Gα_s gene and major depression, as well as to treatment response. The results of our study are in concordance with recently published findings which do not support the hypothesis that the gene for the stimulatory α subunit of G‐proteins is a major susceptibility factor in the pathophysiology of major depression. © 2002 Wiley‐Liss, Inc.     

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.