Oxidated sterols--a contributing factor in atherogenesis?

Sterols are not only important metabolic precursors, they are also indispensable structural components of cell membranes. There is some evidence that synthesis of cholesterol is regulated by oxidized derivatives of cholesterol. They are able to inhibit the key enzyme of cholesterol synthesis, i.e. 3-hydroxy-3-methylglutaryl-CoA-reductase. In addition, oxidized sterols are inserted into the lipid bilayer of the cell membrane as cholesterol analogues. This insertion results in serious disturbances of morphology and function of the membrane. In animal models oxidized sterols have angiotoxic effects; they are also found in atheromas of human arteries. Therefore they may be a causative factor in atherogenesis.     

Cell-matrix interactions during development and apoptosis of the mouse mammary gland in vivo.

Epithelial cell survival is dependent on extracellular signals provided by both soluble factors and by adhesion. In the mammary gland, extensive apoptosis of epithelial cells occurs rapidly when lactation ceases, but the mechanism of apoptosis induction is not known. In tissue culture, mammary epithelial cells require laminin as a survival ligand and specific beta1 integrins are necessary to suppress apoptosis. To explore the possibility that dynamic changes in cell-matrix interactions contribute to the onset of apoptosis during mammary involution in vivo, a detailed immunohistochemical analysis of the expression of integrin subunits and their extracellular matrix ligands during mouse mammary gland development has been performed. The kinetics of apoptosis were determined by using tissue samples obtained from virgin, pregnant, lactating, and involuting gland. The maximal elevation of apoptosis occurred within 24 hr of weaning as determined by histologic analysis and caspase-3 staining. A wide variety of laminin subunits, together with nidogen-1 and -2, and perlecan were identified within the basement membrane region of epithelial ducts, lobules, and alveoli in both human and mouse mammary gland. However, no change in the distribution of any of the basement membrane proteins or their cognate integrin receptors was observed during the transition from lactation to apoptosis. Instead, we discovered that altered ligand-binding conformation of the beta1 integrin to a nonbinding state coincided with the immediate onset of mammary apoptosis. This finding may provide a novel dynamic mechanism for inhibiting the transduction of extracellular matrix survival signals, thereby contributing to the onset of apoptosis in a developmental context in vivo.     

Toxoplasmosis in hairy-cell leukaemia

Toxoplasma serology was performed in 28 patients with hairy-cell leukaemia and was positive in eight patients (29%). In two patients (7%) reactivated toxoplasmosis was proven by either isolation of Toxoplasma gondii or by significant antibody titre rise with generation of specific IgM-antibodies. In four patients (14%), a clinical diagnosis of active toxoplasmosis was based on signs and symptoms, serologic tests, and response to specific treatment. The high proportion of patients in which active toxoplasmosis was proven or probable (six; 21%) may be related to the presence of severe monocytopenia. In patients with hairy-cell leukaemia developing fever of unknown origin and myositis, toxoplasma serology should be performed, particularly because treatment of active toxoplasmosis usually is successful.     

The effect of mind-body interventions on psychological and pregnancy outcomes in infertile women: a systematic review

Archives of Women's Mental Health - Preliminary evidence suggests that mind-body interventions, including mindfulness-based interventions and yoga, may be effective in reducing mental health...     

Alpha7 integrin mediates neurite outgrowth of distinct populations of adult sensory neurons

The successful regeneration of peripheral branches of sensory neurons following injury is attributed to the presence of neurotrophins and interaction of regenerating axons with the extracellular matrix. Here, we show that the laminin receptor, alpha7beta1 integrin is a crucial mediator of neurite outgrowth from distinct populations of sensory neurons. Following sciatic nerve crush, alpha7 integrin is expressed by medium-large diameter, NF200-immunoreactive (IR), and medium diameter, CGRP-IR, neurons, but very few small diameter non-peptidergic neurons. The functional significance of alpha7 integrin expression following injury was addressed using dissociated adult rat and mouse sensory neurons. By using function-blocking antibodies and neurons isolated from alpha7 integrin null mice, we demonstrate that NGF- and NT-3-stimulated neurite outgrowth is reduced in the absence of alpha7 integrin signaling. In contrast, GDNF-stimulated neurite outgrowth is less dependent on alpha7 integrin. These results define an essential interaction between alpha7 integrin and laminin for mediating neurite outgrowth of subpopulations of injured adult sensory neurons.     

Assessment of apoptosis in human breast tissue using an antibody against the active form of caspase 3: relation to tumour histopathological characteristics.

Apoptosis is of important significance in the pathogenesis of cancer. Many methods are available for the measurement of apoptosis but the 'gold standard' is to identify apoptotic cells by their morphological features using microscopy. Caspase 3 is a cytosolic enzyme that is activated only in cells committed to undergo apoptosis. The activation of caspase 3 precedes the development of the classical morphological features of apoptosis. Using immunohistochemistry with an antibody against the active form of caspase 3, the apoptotic index (AI) was measured in 116 samples of human breast tissue (22 normal/benign and 94 invasive carcinomas). The AI obtained by measuring caspase activation has a strong correlation with the AI derived by morphological assessment (r = 0.736, P < 0.01). The AI is higher in the invasive group than in the benign group (P = 0.008), and in invasive cancer high AI is associated with high tumour grade (P = 0.013), positive node status (P < 0.001) and negative steroid receptor status (P = 0.001 for ER; P = 0.004 for PR). No significant association is observed between AI and tumour size. Measurement of apoptosis by immunohistochemistry using an antibody against the active form of caspase 3 is therefore reliable and correlates strongly with morphological assessment.     

Comparative diagnostic value of the calcium-pentagastrin test versus the tolbutamide test in a patient with a somatostatinoma

We describe a patient with a small somatostatinoma of the papilla of Vater without clinical evidence for diabetes mellitus, diarrhea, steatorrhea, or cholelithiasis, showing normal plasma basal levels for somatostatinlike immunoreactivity. The diagnosis was based on histologic and immunohistochemical analysis of tumor tissue and hypersomatostatinemia induced by the calcium-pentagastrin test. Before removal of the tumor both diagnostic tests recommended for the detection of a somatostatinoma, a tolbutamide test and a calcium-pentagastrin test, were performed. Whereas the calcium-pentagastrin test provoked a markedly elevated plasma somatostatin level in association with a depressed plasma neurotensin level, the tolbutamide test surprisingly did not. After removal of the tumor the calcium-pentagastrin test no longer induced hypersomatostatinemia. Further studies are needed to determine whether the calcium-pentagastrin test is a more reliable diagnostic test than the tolbutamide test in somatostatinomas with normal plasma basal levels.     

Identification of the sequence required for expression of the 2H4 epitope on the human leukocyte common antigens

The anti-2H4 antibody, which subdivides the T4+ population of human T lymphocytes into T4+, 2H4+ suppressor-inducer cells and T4+, 2H4- helper cells, recognizes an epitope on a subset of the human leukocyte common antigens (LCAs). LCAs are a family of cell surface glycoproteins generated from a single gene by the differential usage of three exons near the NH2-terminus. Using cDNA clones corresponding to four of the different forms of LCA molecules, extracellular domains of the LCA molecules were synthesized in vitro. Immunoprecipitation of these molecules with the anti-2H4 antibody demonstrated that exon A is required for the expression of the 2H4 epitope.