SPARC, an extracellular matrix glycoprotein containing the follistatin module, is expressed by astrocytes in synaptic enriched regions of the adult brain

Although extracellular matrix (ECM) glycoproteins play important roles in neural development, their levels are generally believed to decrease in the adult brain. Immunohistochemical analysis indicates that the anti-adhesive ECM glycoprotein SPARC/osteonectin, which contains a follistatin ‘module’, is expressed in the adult rabbit nervous system. In the cerebellum, SPARC is present in Bergmann glia, with a strong signal along their radial fibres. SPARC, while enriched in membrane fractions, is not a transmembrane protein. In the hippocampus, colocalization of SPARC is observed in cells which express the astrocytic marker GFAP. The expression of SPARC by a subset of astrocytes, particularly in synaptic enriched areas, suggests a continuing role for the ECM in the adult brain.     

An analysis of astrocytic cell lines with different abilities to promote axon growth

The adult mammalian central nervous system (CNS) lacks the capacity to support axonal regeneration. There is increasing evidence to suggest that astrocytes, the major glial population in the CNS, may possess both axon-growth promoting and axon-growth inhibitory properties and the latter may contribute to the poor regenerative capacity of the CNS. In order to examine the molecular differences between axon-growth permissive and axon-growth inhibitory astrocytes, a panel of astrocyte cell lines exhibiting a range of axon-growth promoting properties was generated and analysed. No clear correlation was found between the axon-growth promoting properties of these astrocyte cell lines with: (i) the expression of known neurite-outgrowth promoting molecules such as laminin, fibronectin andN-cadherin; (ii) the expression of known inhibitory molecules such tenascin and chondroitin sulphate proteoglycan; (iii) plasminogen activator and plasminogen activator inhibitor activity; and (iv) growth cone collapsing activity. EM studies on aggregates formed from astrocyte cell lines, however, revealed the presence of an abundance of extracellular matrix material associated with the more inhibitory astrocyte cell lines. When matrix deposited by astrocyte cell lines was assessed for axon-growth promoting activity, matrix from permissive lines was found to be a good substrate, whereas matrix from the inhibitory astrocyte lines was a poor substrate for neuritic growth. Our findings, taken together, suggest that the functional differences between the permissive and the inhibitory astrocyte cell lines reside largely with the ECM.     

New latex reagent using monoclonal antibodies to capsular polysaccharide for reliable identification of both oxacillin-susceptible and oxacillin-resistant Staphylococcus aureus.

A new latex agglutination test (Pastorex Staph-Plus, Sanofi Diagnostics Pasteur), consisting of a mixture of latex particles coated with fibrinogen and immunoglobulin G for the detection of clumping factor and protein A and latex particles sensitized with monoclonal antibodies directed to Staphylococcus aureus serotype 5 and 8 capsular polysaccharides, was compared with three commercially available rapid agglutination methods for the identification of 220 isolates of S. aureus (61 oxacillin resistant) and 128 isolates of coagulase-negative staphylococci. The sensitivity for identification of S. aureus was high with the Pastorex Staph-Plus test (98.6%) compared with those of the other tests, which ranged from 91.8 to 84.5%. Test sensitivities for the identification of oxacillin-resistant S. aureus were as follows: Pastorex Staph-Plus, 95.1%; Pastorex Staph, 73.8%; Staphyslide, 72.1%; and StaphAurex, 49.2%.     

The consequences of H2 receptor antagonist — piroxicam coadministration in patients with joint disorders

Summary A randomised crossover study was performed in subjects with rheumatoid arthritis (or other arthropathies) to investigate if any alteration in the steady pharmacokinetics of the NSAID piroxicam (a drug which is extensively metabolised via cytochrome P450) or its major metabolites occurred as a result of coadministering either cimetidine or nizatidine.Twelve females and 2 males with mean age, weight, and albumin concentrations of 58 years, 61 kg, and 40 g·L^–1 respectively, completed the study. Comparisons were made between the following parameters: plasma piroxicam AUCs [AUC_0-24(P)], plasma 5-hydroxypiroxicam AUCs [AUC_0-24(5-OHP)], the ratio of these i.e. AUC_0-24(5-OHP):AUC_0-24(p), the % piroxicam daily dose excreted in urine as 5-hydroxypiroxicam (before and after glucuronidase incubation); and the mean of the steady state trough piroxicam, and 5-hydroxypiroxicam concentrations (obtained during each study phase in addition to the wash-out period).A statistically significant difference as a result of initiating either cimetidine or nizatidine was obtained only for the ratio AUC_0-23(5-OHP):AUC_0-24(P). This was indicative of a weak potential to inhibit piroxicam hydroxylation.No clinically significant alteration in the steady state pharmacokinetics of piroxicam occurred in these subjects as a result of cimetidine or nizatidine coadministration. Consequently it is unlikely that any adverse events would arise from these combinations.     

Phase II trial of piroxantrone in patients with recurrent and metastatic squamous cell carcinoma of the head and neck

Summary Twenty-two patients with recurrent or metastatic squamous cell carcinoma of the head and neck were treated with piroxantrone 150 mg/m² intravenously every 21 days. There were no objective responses. The 95% upper confidence bound for response is 15%. Primary toxicity was hematologic.     

Dysregulated Fas and Bcl-2 expression leading to enhanced apoptosis in T cells of multiple myeloma patients

We have previously reported the presence of activated (HLA-DR+) T cells in multiple myeloma (MM) patients. These cells produce high amounts of interleukin (IL)-2 and interferon (IFN)-gamma and generate a potent antiplasma cell activity after appropriate in vitro stimulation, but they are unable in vivo to hold in check the disease. Activated T cells are highly susceptible to apoptosis, a form of programmed cell death involved in the modulation of immune responses and regulated by molecules such as Fas (CD95) and bcl-2. The aim of this study was to determine the expression of Fas and bcl-2 antigens and the susceptibility to apoptosis in T cells of MM patients. Fas+ cells were significantly higher, whereas bcl-2+ cells were significantly lower in MM patients than in the controls. MM patients with the highest number of HLA-DR+ T cells showed the highest Fas and the lowest bcl-2 expression. Two-color cytofluorometric analysis confirmed in individual cells that HLA-DR+ T cells coexpressed Fas and lacked bcl-2. Susceptibility to apoptosis was then investigated to evaluate the consequence of dysregulated Fas and bcl-2 expression. The percentage of apoptotic cells after incubation in medium alone (spontaneous apoptosis) or in the presence of methylprednisolone (MP) or anti-Fas monoclonal antibody (triggered apoptosis) was significantly higher in MM and mainly restricted to HLA-DR+ T cells. Spontaneous apoptotosis was reverted by exogenous IL-2. In conclusion, MM T cells have a dysregulated expression of Fas and bcl-2 antigens that is associated with an enhanced susceptibility to apoptosis. These data may unravel a novel mechanism by which activated MM T cells are weakened in their ability to exert an effective antitumor activity in vivo.     

Excessive zinc ingestion. A reversible cause of sideroblastic anemia and bone marrow depression

Two patients with sideroblastic anemia secondary to zinc-induced copper deficiency absorbed excess zinc secondary to oral ingestion. The source of excess zinc was a zinc supplement in one case; in the other, ingested coins. In each case, the sideroblastic anemia was corrected promptly after removal of the source of excess zinc. These two cases emphasize the importance of recognizing this clinical entity, since the myelodysplastic features are completely reversible.     

Receptor-dependent regulation of the concentration of Ca2+ in the cytoplasm of thrombocytes in hypertensive patients

Platelet activation factor (PAF)-, ADP and vasopressin-induced increments of platelet Ca2+ concentration were measured by quin-2 in 64 patients with essential hypertension and 16 normal donors. Basal concentration of free Ca2+ was 87 +/- 4 nM in donors, 106 +/- 5 nM in patients with labile hypertension (LH) and 122 +/- 6 nM in those with stable hypertension (SH) (p less than 0.01). PAF, ADP and vasopressin, added to platelets, increased [Ca]in by 448 +/- 58, 397 +/- 66, and 277 +/- 50 nM, respectively, in the donors, by 473 +/- 57, 479 +/- 54 and 195 +/- 32 nM, in LH patients, and by 607 +/- 85, 584 +/- 73 and 245 +/- 41 nM in SH patients. There were no significant variations between the three samples, using the ANOVA test. In 20 patients, whose both parents had essential hypertension, [Ca]in increment was 738 +/- 8 nM for PAF, 682 +/- 90 nM for ADP, and 320 +/- 61 nM for vasopressin. In 19 patients, who admitted to no essential hypertension in the family, these parameters were significantly lower: 310 +/- 40 nM for PAF, 389 +/- 61 nM for ADP, and 147 +/- 26 nM for vasopressin. The demonstrated changes may be making an important contribution to the maintenance of elevated vascular tone and provide an evidence in favor of a genetically-predetermined EH variety.     

Keloids

Keloids are benign fibrous growths that result from an abnormal connective tissue response in certain predisposed individuals. Blacks form keloids more often than whites; however, the reason for this racial difference is not known. Trauma, foreign-body reactions, infections, and endocrine dysfunction have all been proposed as precipitating factors. Keloids are found most commonly on the ear lobes, shoulders, upper back, and midchest. They extend past the area of trauma and once present tend to remain stable. Although sometimes pruritic, painful, or tender, they are usually asymptomatic. Histologically, keloids are characterized by thick collagen bundles, abundant mucinous ground substance, few fibroblasts, and few if any foreign-body reactions. Although there have been many therapeutic modalities, most have had limited success. The most commonly used therapeutic approach is a combination of cryotherapy, intralesional steroid injections, surgical excision, and pressure devices.