Immunohistochemical analysis of 1,25-dihydroxyvitamin D3 receptor in cervical carcinoma

The immunohistochemical localization and expression of 1,25-dihydroxyvitamin D3 receptors (VDR) has been investigated in normal human cervical tissue (n = 15) and in cervical carcinomas (n = 23). VDR immunoreactivity (monoclonal antibody 9A7gamma) was compared with the staining patterns of transglutaminase K, cytokeratin 10 and Ki-67 in these tumours. Moderate to strong nuclear immunoreactivity for VDR was detected in almost all cervical carcinomas analysed. VDR staining was homogeneous, with no visual differences between individual tumour cells. Some 60% of normal cervical tissues revealed weak immunoreactivity for VDR. In normal cervical tissue, nuclear VDR staining was confined to the lower cervical layers, predominantly to the basal cell layer. Both the intensity of VDR immunostaining and the number of VDR-positive cells were up-regulated in cervical carcinomas compared with normal cervical tissue. No visual correlation was found for the coexpression of VDR with markers of proliferation and differentiation. Our findings indicate that: (1) cervical tissue may be a new target organ for therapeutically applied vitamin D analogues; (2) VDR is up-regulated at the protein level in cervical carcinomas compared with normal cervical tissue; (3) up-regulation of VDR in cervical carcinoma is induced not exclusively by alterations in epithelial differentiation or proliferation, but by different, unknown mechanisms; and (4) calcitriol and new vitamin D analogues exerting fewer calcaemic side-effects may be promising new drugs for the treatment or chemoprevention of metastasizing cervical carcinomas as well as of cervical precancerous lesions.     

The contribution of classical (beta1/2-) and atypical beta-adrenoceptors to the stimulation of human white adipocyte lipolysis and right atrial appendage contraction by novel beta3-adrenoceptor agonists of differing selectivities

The role of beta3- and other putative atypical beta-adrenoceptors in human white adipocytes and right atrial appendage has been investigated using CGP 12177 and novel phenylethanolamine and aryloxypropanolamine beta3-adrenoceptor (beta3AR) agonists with varying intrinsic activities and selectivities for human cloned betaAR subtypes. The ability to demonstrate beta1/2AR antagonist-insensitive (beta3 or other atypical betaAR-mediated) responses to CGP 12177 was critically dependent on the albumin batch used to prepare and incubate the adipocytes. Four aryloxypropanolamine selective beta3AR agonists (SB-226552, SB-229432, SB-236923, SB-246982) consistently elicited beta1/2AR antagonist-insensitive lipolysis. However, a phenylethanolamine (SB-220646) that was a selective full beta3AR agonist elicited full lipolytic and inotropic responses that were sensitive to beta1/2AR antagonism, despite it having very low efficacies at cloned beta1- and beta2ARs. A component of the response to another phenylethanolamine selective beta3AR agonist (SB-215691) was insensitive to beta1/2AR antagonism in some experiments. Because no [corrected] novel aryloxypropanolamine had a beta1/2AR antagonist-insensitive inotropic effect, these results establish more firmly that beta3ARs mediate lipolysis in human white adipocytes, and suggest that putative 'beta4ARs' mediate inotropic responses to CGP 12177. The results also illustrate the difficulty of predicting from studies on cloned betaARs which betaARs will mediate responses to agonists in tissues that have a high number of beta1- and beta2ARs or a low number of beta3ARs.     

Epididymal manifestations of urogenital tuberculosis

We report the case of a 33-year-old man with a severe Crohn's disease since the age of sixteen. He presented with acne and palmoplantar pustulosis associated with a right knee synovitis. Investigations revealed a major axial bone condensation. The association synovitis-acne-pustulosis-hyperostosis-osteitis leaded to the diagnosis of SAPHO syndrome associated with Crohn's disease.     

Activity-dependent regulation of NMDAR1 immunoreactivity in the developing visual cortex

NMDA receptors have been implicated in activity-dependent synaptic plasticity in the developing visual cortex. We examined the distribution of immunocytochemically detectable NMDAR1 in visual cortex of cats and ferrets from late embryonic ages to adulthood. Cortical neurons are initially highly immunostained. This level declines gradually over development, with the notable exception of cortical layers 2/3, where levels of NMDAR1 immunostaining remain high into adulthood. Within layer 4, the decline in NMDAR1 immunostaining to adult levels coincides with the completion of ocular dominance column formation and the end of the critical period for layer 4. To determine whether NMDAR1 immunoreactivity is regulated by retinal activity, animals were dark-reared or retinal activity was completely blocked in one eye with tetrodotoxin (TTX). Dark-rearing does not cause detectable changes in NMDAR1 immunoreactivity. However, 2 weeks of monocular TTX administration decreases NMDAR1 immunoreactivity in layer 4 of the columns of the blocked eye. Thus, high levels of NMDAR1 immunostaining within the visual cortex are temporally correlated with ocular dominance column formation and developmental plasticity; the persistence of staining in layers 2/3 also correlates with the physiological plasticity present in these layers in the adult. In addition, visual experience is not required for the developmental changes in the laminar pattern of NMDAR1 levels, but the presence of high levels of NMDAR1 in layer 4 during the critical period does require retinal activity. These observations are consistent with a central role for NMDA receptors in promoting and ultimately limiting synaptic rearrangements in the developing neocortex.     

Applying a feminist analysis model to selected nursing studies of women with HIV

Women's mental health has been linked to oppression and to oppressive practices in health care. Feminist approaches to health care delivery and research have been suggested as a remedy for the subtle and overt oppression faced by women, and many nurses have used feminist principles to conduct and report their research and to critique existing studies. Though nursing authors have identified useful feminist guides for conducting and reporting research, few examples of the practice of feminist critiques of research are available in the nursing literature. This analysis synthesizes and adapts feminist principles from nursing literature and presents a feminist model to review selected nursing research reports of women with human immunodeficiency virus (HIV). A convenience sample of eight articles from nursing journals was examined for statements or implications that the author(s) (a) perceived the purposes of the study as benefiting women, (b) demonstrated an awareness of the structures and policies that oppress women, (c) were sensitive to issues of diversity, (d) were committed to social change, and (e) recognized the female participants' strengths. The selected articles were found to meet many of the feminist criteria, although these principles were not always explicitly addressed in the articles.     

The role of nitric oxide and NMDA receptors in the development of motor neuron dendrites

Nitric oxide (NO) has been implicated in the establishment of precise synaptic connectivity throughout the neuroaxis in several species. To determine the contribution of NO to NMDA receptor-dependent dendritic growth in motor neurons, we administered the NMDA antagonist MK-801 to wild-type mice and neuronal nitric oxide synthase (nNOS) knock-out mice between postnatal days 7 and 14. Compared to saline-treated wild-type animals the number of dendritic bifurcations was significantly reduced in nNOS knock-out animals and MK-801-treated wild-type animals. There was no significant difference in dendritic bifurcation between MK-801-treated wild-type, MK-801-treated nNOS knock-out, and saline-treated nNOS knock-out animals, suggesting that nNOS knock-out and NMDA receptor block had similar effects. The path of the longest dendrite and the number of primary dendrites was the same in all treatment groups, indicating an effect specific to bifurcation. Sholl analysis revealed that differences in bifurcation numbers occurred between 160 and 320 micrometers from the cell body, the distance at which second, third, and fourth order dendrites are most prevalent. Dendrite order analyses confirmed a significant reduction in numbers, but not lengths, of third and fourth order dendrites in nNOS knock-out and drug-treatment groups. Finally, immunohistochemical examination of the developing spinal cord indicated that NMDA receptors and nNOS are colocalized within interneurons surrounding the motor neuron pool. These results support the view that at least part of NMDA receptor-dependent arborization of motor neuron dendrites is mediated by the local production of NO within the developing spinal cord.     

Taking down the walls: a nurse manager's experience in acute care and home care

Changes in the health care system are stimulating trends in where and how nursing services are delivered. Nurse managers are responsible for the overall management of the nursing work unit and must be prepared to practice in settings other than acute care. Home care is a rapidly growing practice that emerges as patients are discharged from the hospital sooner with ongoing medical and nursing needs. The job responsibilities of a nurse manager remain similar across practice settings, including the transition from acute care to home care. A detailed checklist highlights specific similarities and differences in the nurse manager's role in acute care and home care settings. As the walls of the practice setting are taken down, nurse managers must build on current knowledge and creatively develop new skills to remain successful in ongoing job responsibilities.     

Differentiation-specific enhancer activity in transduced keratinocytes: a model for epidermal gene therapy

Active sequences from the laminin alpha1 and alpha2 chain carboxyl-terminal globular domains (G domain) have been identified by screening overlapping synthetic peptides in a number of biological assays (Nomizu et al. [1995] J. Biol. Chem. 270:20583-20590; Nomizu et al. [1996] FEBS Lett. 396:37-42). We have tested the activity of these peptides in submandibular gland explants of embryonic day 13 mice to determine the functional sites involved in organ development. The laminin alpha1 chain peptide, RKRLQVQLSIRT (residues 2719-2730 and designated AG-73), significantly inhibited epithelial branching morphogenesis. In contrast, other cell adhesive laminin alpha1 chain peptides including the AASIKVAVSADR and NRWHSIYITRFG failed to inhibit the branching. MG-73, a homologue of AG-73 from the laminin alpha2 chain, did not inhibit the branching. The alpha2 chain peptide had no effect, which may be due to the low levels of this laminin chain in day 13 mice. Laminin alpha2 chain-specific monoclonal antibodies strongly reacted with the basement membranes of developed acini but only weakly stained embryonic day 13 submandibular epithelium. The expression of E-cadherin and alpha6 integrin, as detected by immunofluorescence, were unchanged in both AG-73 and control scramble peptide-treated epithelial cells of the explants. In contrast, immunostaining of nidogen/entactin showed that explants treated with AG-73 for 3 days had a discontinuous basement membrane. Explants treated for 3 days with control peptide showed a normal basement membrane. These results suggest that the region containing the AG-73 sequence of the laminin alpha1 chain is crucial for development of submandibular gland at early embryonic stages. The discontinuous basement membrane in AG-73-treated explants may indicate an important role for this region in basement membrane assembly.     

Amplified enzyme-linked-immunofilter assays enable detection of 50-10(5) bacterial cells within 1 hour

1. The hydrolysis of organophosphate pesticides (OP) and nerve gases by serum paraoxonase (PON1) is an important factor determining their toxicity to mammals including man. The PON1 gene contains 2 polymorphic sites at amino acid positions 55 (L-->M) and 192 (G-->A, classically defined as the A and B genotypes) which result in several alloenzymes of PON1 in human serum. 2. The 192 polymorphism has previously been shown to affect PON1 activity. We have investigated the effect of both polymorphisms on the hydrolysis of paraoxon by serum from 279 healthy human subjects. 3. The 55 polymorphism significantly influenced PON1 activity. MM homozygotes had over 50% less activity towards paraoxon compared to the LL and LM genotypes regardless of the 192 genotype (P < 0.001). 4. Multiple regression analysis indicated that the 192 polymorphism, 55 polymorphism and serum PON1 concentration were responsible for 46, 16 and 13% of the variation in PON1 activity, respectively (all P < 0.001). None of the other parameters investigated significantly affected PON1 activity. 5. Therefore both PON1 polymorphisms affect the hydrolysis of paraoxon. AA/MM and AB/MM individuals may be potentially more susceptible to OP intoxication. 6. Genotyping individuals for both PON1 polymorphisms may provide a method for identifying those individuals at most risk of OP poisoning. The effect of PON1 polymorphisms on activity may also explain why some Gulf War Veterans have developed Gulf War Syndrome and some have not.