Immunochemical differences between glucocorticoid receptors from corticoid-sensitive and -resistant malignant lymphocytes

We have explored the possibility of using antibodies against purified rat liver glucocorticoid receptors to study the immunochemical properties of glucocorticoid receptors from murine and human malignant lymphocytes. For this purpose, purified immune immunoglobulin G was covalently linked to Sepharose CL-4B. We then examined the ability of the affinity gel to recognize cytosolic [3H]triamcinolone acetonide-receptor complexes from the corticoid-sensitive (CS) and -resistant strains of mouse lymphoma P1798, from CS lymphocytes of patients with chronic lymphatic leukemia, and from a CS clone of human leukemic lymphoblasts in tissue culture (CH6). Mouse thymus was used as a source of glucocorticoid receptor from normal CS lymphocytes. Whereas the immunoaffinity column retained 70 to 84% of the 58- to 62-A (Stokes radius) [3H]triamcinolone acetonide-receptor complexes characteristic of the CS mouse and human lymphocytes, it failed to recognize the 27- to 28-A (Stokes radius) glucocorticoid receptor present in corticoid-resistant mouse lymphoma P1798 cells. Therefore, under appropriate experimental conditions, it was possible to demonstrate cross-reactivity between the antiserum against rat liver glucocorticoid receptor and the 58- to 62-A (Stokes radius) glucocorticoid receptor from species as diverse as mouse and humans.     

Radiotherapy of humero-scapular periarthritis using ultra-hard photons. Evaluation by MRI findings

OBJECTIVE: To determine the clinical implications of atypical glandular cells of uncertain significance (AGCUS) in cervical cytologic smears. STUDY DESIGN: Retrospective analysis. RESULTS: Eighty-eight of 32,181 (0.27%) cervical smears obtained during the study period contained AGCUS. Of the 47 women with AGCUS, 16 had intraepithelial or invasive neoplasms (34%; 95% confidence interval, 21-49%), including 9 low or high grade squamous intraepithelial lesions, 1 adenocarcinoma in situ of the cervix, 3 adenocarcinomas of the cervix, 2 adenocarcinomas of the endometrium and 1 adenoid basal cell carcinoma of the cervix. CONCLUSION: The high prevalence of cervical and endometrial neoplasia among women with the isolated finding of AGCUS on cervical cytologic smears warrants a thorough diagnostic evaluation.     

Peptides that mimic the group B streptococcal type III capsular polysaccharide antigen

In some but not all arterial beds, smooth muscle cell calcium-activated K+ channels (KCa channels) play a central role in the mediation of the vasodilator response to nitric oxide (NO) and other nitrates. We investigated the effect of nitrates on KCa channels in the relaxation of human coronary arteries by means of isometric contraction experiments in arterial rings. We also measured whole-cell currents in freshly isolated human coronary artery vascular smooth muscle cells via the patch-clamp technique. Sodium nitroprusside, diethylamine-nitric oxide complex sodium salt and isosorbide mononitratre completely relaxed rings preconstricted with 5 microM serotonin and produced dose-dependent relaxations of 5 microM serotonin-preconstricted human rings. The relaxations were inhibited by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-oxyl 3-oxide (10 microM), which neutralizes nitric oxide. The KCa channel blockers iberiotoxin (100 nM) and tetraethylammonium ions (1 mM) significantly inhibited SNP-induced relaxations of human coronary arteries. Moreover, in the patch-clamp experiments, SNP (1 microM) stimulated KCa currents and spontaneous transient outward K+ currents carried by Ca spark activated KCa channels. The SNP-induced (1 microM) KCa current was strongly inhibited by iberiotoxin (100 nM). These data show that activation of KCa channels in smooth muscle cells contributes to the vasodilating actions of nitrates and nitric oxide in human coronary arteries. This finding may have unique clinical significance for the development of antianginal and antihypertensive drugs that selectively target K+ channels and Ca sparks.     

Evidence from confocal fluorescence microscopy for a dense, reciprocal innervation between AVP-, somatostatin-, VIP/PHI-, GRP-, and VIP/PHI/GRP-immunoreactive neurons in the rat suprachiasmatic nucleus

The rat suprachiasmatic nucleus (SCN) consists of several classes of neurons which can be identified by their transmitter content. Knowledge of putative interaction between these different cell types is essential in order to understand the possibilities of information processing within the SCN. The aim of the present study was therefore to obtain more information about the mutual innervation between the main cell classes in the rat SCN, viz. those containing the neuropeptides arginine vasopressin (AVP), vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), gastrin-releasing peptide (GRP) and somatostatin respectively. For this purpose, vibratome sections were double-immunolabelled for seven different peptide combinations and subsequently analysed by high-resolution confocal laser scanning fluorescence microscopy. Attention was focused on axosomatic appositions, the occurrence and frequency of which were quantitatively estimated. Our analysis of double-immunolabelled sections demonstrated that some of the VIP- and some of the GRP-immunoreactive nerve cells and endings showed colocalization. Assuming, on the basis of literature data, that VIP and PHI are always colocalized at the cellular level, the five main cell classes in the SCN appeared to be interconnected, at least axosomatically, in the following reciprocal way: AVP <--> VIP/PHI, AVP <--> GRP, AVP <--> somatostatin, somatostatin <--> VIP/PHI, somatostatin <--> GRP, VIP/PHI <--> GRP, VIP/PHI/GRP <--> GRP, VIP/PHI/GRP <--> VIP/ PHI. In addition to this heterologous axosomatic innervation, these cell groups also showed substantial homologous innervation. Supported by electron microscope data from the literature showing the existence of axodendritic synapses for some of these peptide combinations, our findings strongly suggest that the rat SCN comprises a complex synaptic network with strong interactive capabilities, which is probably a requisite for its biological clock function.     

Tc-99m DTPA perfusion scintigraphy and color coded duplex sonography in the evaluation of minimal renal allograft perfusion

During the past two years, a growing number of mutations have been identified in three of the four members of the fibroblast growth factor receptor (FGFR) family as causing autosomal dominant disorders of skeletal and cranial development. These mutations map to the extracellular domain, the transmembrane domain, or the tyrosine kinase domain of these receptors. Recent studies demonstrate that a common mechanism, constitutive activation of receptors signaling, underlies most, if not all, of these disorders. This suggests a normal role for FGFRs in the negative regulation of bone growth.