Cytokeratin provides a specific marker for human arachnoid cells grown in vitro

Cells from cranial and spinal arachnoid membranes of humans were grown in culture. Their growth characteristics, morphology and details of their cytoskeletal composition are described. Arachnoid membranes, obtained at autopsy, were finely minced and incubated in tissue culture medium. Monolayers of cells of homogeneous morphology grew from these tissue fragments. The cells were flat and polygonal. They divided slowly to form non-overlapping monolayers of low cell density. Electron microscopic examination of cultured arachnoid cells revealed numerous desmosome-like tight junctions and abundant intermediate filaments (tonofilaments). Both morphological features are characteristic of arachnoid cells in situ, but not of cells in the fibroblast-rich dura mater. Immunofluorescence microscopy with monoclonal antibodies demonstrated cytokeratin in the cytoplasm of primary cultures of arachnoid cells. Thus we demonstrated that these cultured cells retained certain of the specific differentiated properties of arachnoid cells in situ and that they are not fibroblasts (which lack tight junctions and cytokeratins). To our knowledge, there have been no previous reports of in vitro growth of arachnoid cells. This in vitro model should be useful in studying the response of arachnoid cells to a variety of substances thought to be involved in the chronic inflammatory condition of the meninges known as arachnoiditis.     

The Drosophila tissue polarity gene starry night encodes a member of the protocadherin family.

The tissue polarity genes control the polarity of hairs, bristles and ommatidia in the adult epidermis of Drosophila. We report here the identification of a new tissue polarity gene named starry night (stan). Mutations in this essential gene alter the polarity of cuticular structures in all regions of the adult body. The detailed polarity phenotype of stan on the wing suggested that it is most likely a component of the frizzled (fz) pathway. Consistent with this hypothesis, stan appears to be downstream of and required for fz function. We molecularly cloned stan and found that it encodes a huge protocadherin containing nine cadherin motifs, four EGF-like motifs, two laminin G motifs, and seven transmembrane domains. This suggests that Stan functions in signal reception, perhaps together with Fz.     

ERp46 binds to AdipoR1, but not AdipoR2, and modulates adiponectin signalling

The pleiotropic effects of the insulin-sensitizing adipokine adiponectin are mediated, at least in part, by two seven-transmembrane domain receptors AdipoR1 and AdipoR2. Recent reports indicate a role for AdipoR-binding proteins, namely APPL1, RACK1 and CK2β, in proximal signal transduction events. Here we demonstrate that endoplasmic reticulum protein 46 (ERp46) interacts specifically with AdipoR1 and provide evidence that ERp46 modulates adiponectin signalling. Co-immunoprecipitation followed by mass spectrometry identified ERp46 as an AdipoR1-, but not AdipoR2-, interacting protein. Analysis of truncated constructs and GST-fusion proteins revealed the interaction was mediated by the cytoplasmic, N-terminal residues (1-70) of AdipoR1. Indirect immunofluorescence microscopy and subcellular fractionation studies demonstrated that ERp46 was present in the ER and the plasma membrane (PM). Transient knockdown of ERp46 increased the levels of AdipoR1, and AdipoR2, at the PM and this correlated with increased adiponectin-stimulated phosphorylation of AMPK. In contrast, adiponectin-stimulated phosphorylation of p38MAPK was reduced following ERp46 knockdown. Collectively these results establish ERp46 as the first AdipoR1-specific interacting protein and suggest a role for ERp46 in adiponectin receptor biology and adiponectin signalling.     

Making access to health care more equal: the role of general medical services.

The Resource Allocation Working Party (RAWP) recognised the need to consider both health authority and primary care services in achieving its objective. RAWP and the subsequent Advisory Group on Resource Allocation (AGRA) found (but did not publish) considerable variation in resources used by both services but could not find a clear relation between them. Statistics provided by the DHSS were used to compare spending by 80 area health authorities in 1980-1 with expenditure per head on general medical services by their corresponding family practitioner committees. There was considerable variation in the provision of resources for both services and no clear relation between the variations in spending on each service. Only 40 of the 80 areas had both health authority and family practitioner committee spending levels within 10% of "target." Subregional inequalities in resources tend to be related to variations in admission rates, which in turn are related to general practitioners'' referral behaviour. These results emphasise the importance of finding out more about inequalities in the provision of general medical services and their relation to the use of hospital services. They also suggest that RAWP''s aim of equality of opportunity of access to health care resources may be achieved only if general medical services are brought into the equation as well.     

Nutrition and muscle potassium: differential effect in rat slow and fast muscles

The effects of malnutrition on intracellular K+ activity, (alpha K)i, and membrane potential, Em, were measured by means of double-barrelled K+-selective microlectrodes in the soleus and gastrocnemius muscles of the rat. (alpha K)i and Em were measured in vivo in normal anaesthetized animals and in rats subjected to one of two diet restrictions: a 2-day fast or a long-term hypocaloric diet. In the soleus muscle, (alpha K)i fell by similar amounts in both 2-day fasted and long-term hypocalorically fed rats, while Em depolarized significantly only in hypocalorically fed rats. In the gastrocnemius muscle, neither the 2-day fast nor the hypocaloric diet affected (alpha K)i or Em. It is suggested that the selective loss of K+ from the soleus muscle may be related to its activity pattern.     

Effects of short-term injection of gonadotrophins on ovarian follicle development in hypogonadal (hpg) mice

Twice daily injections of purified ovine and human FSH were used to investigate the control of ovarian follicle development in hypogonadotrophic hypogonadal (hpg) mice. Treatment for 5 days with doses greater than 3 micrograms resulted in a significant increase in the total number of growing follicles and the development of antral follicles. This was associated with increases in uterine weights and vaginal opening, indicating that steroidogenesis had also been stimulated. Further studies of the effects of combined injections of FSH and LH, linked with morphological analysis of ovarian interstitial cells, suggested that any contribution of background or contaminating LH to the effects of the FSH injections was minimal. It therefore appears that, in mice, FSH alone is capable of stimulating an increase in the initiation of follicle growth, of triggering the development of antral follicles, and supporting ovarian steroidogenesis.