Role of mouse and human class II transgenes in susceptibility to and protection against mouse autoimmune thyroiditis

Four cases of ocular myopathy are presented. Their clinical, electromyographical and hystological signs are discussed comparatively with clinical forms described in the literature. One case was of pure ocular myopathy, without the affectation of other skeletal muscles. The other three cases were included in the descendent ocular myopathy, presenting a motor deficiency at the centure and inferior member levels. In all cases modifyings have been found in the EMG trajectory and the muscular biopsy of skeletal and/or ocular muscles.     

Control of monocyte influx in glomerulonephritis in transplanted kidneys in the rat

Induction of anti-Thy-1 nephritis in different strains of inbred rats results in phenotypically different types of renal diseases. In Wistar and Lewis (LEW) rats, a transient influx of ED1+ macrophages occurs 24 hours after injection of anti-Thy-1 antibodies, whereas this does not occur in F344 rats. The present experiments were designed to investigate the role of the kidney in the regulation of the monocyte influx in this model. To dissociate the role of the immune system from local intrarenal factors in the control of monocyte influx, anti-Thy-1 nephritis was induced in LEW rats with an F344 kidney transplant and in F344 rats with a LEW kidney allograft. Acute rejection episodes were prevented by treatment with an anti-CD4 monoclonal antibody. Control rats received a syngeneic kidney graft. Monocyte influx after injection of anti-Thy-1 antibodies was found in the glomeruli of both LEW and F344 kidneys removed from LEW recipients, whereas there was no demonstrable monocyte influx after infusion of anti-Thy-1 antibodies in either LEW or F344 kidneys removed from F344 recipients. Monocyte infiltration correlated with the subsequent expansion of the mesangial extracellular matrix. The inability to attract monocytes was not due to the lack of glomerular expression of chemokines, because F344 and LEW glomeruli demonstrated a similar expression of monocyte chemoattractant protein-1 (MCP-1). Differences in the ability to activate the complement system were excluded. We conclude that the immune system controls the glomerular influx of monocytes and that the reaction of the mesangial cells is probably controlled by combinations of cytokines produced during the inflammatory process.     

Changes in the morphology of sympathetic preganglionic neurons parallel the development of autonomic dysreflexia after spinal cord injury in rats

Following spinal cord transection (SCT), sensory input to the spinal cord causes increases in arterial pressure that are small in rats 1 week after SCT, but become large and well established by 2 weeks. Moreover, sympathetic preganglionic neurons (SPNs) undergo atrophy by 1 week after SCT, and regeneration of these neurons may be an important factor in the etiology of this autonomic dysreflexia. Therefore, we examined the morphology of SPNs 2 weeks after SCT using retrograde transport of the cholera toxin subunit B. The dendritic arbors of SPNs were re-established by 2 weeks after SCT. This regeneration parallels the time course of the development of autonomic dysreflexia after cord injury in the rat, and may play a role in initiating this disorder.     

Effect of ranitidine on intragastric pH in clinically normal neonatal foals

OBJECTIVE: To determine intragastric pH in newborn foals and to examine the effect of i.v. or oral administration of an H2-receptor antagonist on intragastric pH. DESIGN: Prospective controlled study. ANIMALS: 6 healthy mixed-breed neonatal foals. PROCEDURE: Intragastric pH was measured, using an antimony electrode. Foals were monitored on days 2, 4, and 6 after birth, and each received 3 treatments. The pH was recorded for 4 hours before treatment and for 10 hours after ranitidine administration (2 mg/kg [0.91 mg/lb] of body weight, i.v.; 6.6 mg/kg [3 mg/lb], PO) or 20 hours after corn syrup administration. Mean and median pH and percentage of time pH was > or = 4 were calculated. RESULTS: Mean intragastric pH significantly increased for 5 hours after i.v. administration of ranitidine, compared with baseline data. Percentage of time intragastric pH was > or = 4 increased significantly for 4 hours after ranitidine administration, and median pH increased significantly for hours 2 to 4 after administration. Oral administration of ranitidine significantly increased mean and median pH for hours 2 to 8 after administration and percentage of time pH was > or = 4 for hours 2 to 7 after administration. CLINICAL IMPLICATIONS: Neonatal foals have highly acidic gastric fluid. Intravenous or oral administration of ranitidine significantly increased intragastric pH for 4 and 8 hours, respectively. Suckling affected intragastric pH and underscored the need for frequent feeding of neonatal foals.     

Valvular interstitial cells express angiotensinogen and cathepsin D, and generate angiotensin peptides

Cells capable of de novo angiotensin (Ang)II generation in the heart remain unidentified. High-density angiotensin converting enzyme (ACE) binding has been localized to sites of high collagen turnover, such as heart valve leaflets and their valvular interstitial cells (VIC). VIC express ACE mRNA and their membrane-bound ACE utilizes AngI as substrate. Whether VIC also express angiotensinogen (Ao) and an aspartyl protease, and whether they generate AngI and II de novo, is presently unknown. We sought to address these questions in serum-deprived cultured VIC. Ao, renin and cathepsin D (Cat-D) mRNA expression was addressed by RT-PCR. Production of Ao, AngI and AngII peptides were measured in VIC-culture media by radioimmunoassay (RIA). Immunoreactive Cat-D was detected by immunofluorescein labeling and Western blotting. Cat-D and renin activities were determined by spectrofluorometric and autoradiographic methods and AngI generation by RIA. Results showed (a) expression of Ao and Cat-D both at mRNA and protein levels; (b) AngI and AngII peptides in culture media; (c) acceleration of AngII production by exogenous AngI (1 nmol/l), which was blocked by lisinopril (0.1 mumol/l); (d) that dexamethasone (0.1 mumol/l) increased AngII production; (e) a 46 kDa immunoreactive Cat-D protein by Western blotting; (f) aspartyl protease activity, using chromogenic and 125I-labeled Ao as substrates, inhibited by pepstatin-A; and (g) the absence of renin mRNA and activity. It is concluded that at both the mRNA and protein levels, cultured VIC express Ao and Cat-D, and can generate AngI and AngII peptides by the action of a non-renin protease Cat-D and ACE, respectively. VIC therefore appear to represent a constitutive nonendothelial cell found in adult rat heart valve leaflets, which are capable of de novo Ang peptide generation.     

Viral hepatitis prophylaxis

Acute viral hepatitis is the most usual cause of jaundice and acute liver failure, whereas chronic viral hepatitis is the major cause of liver cirrhosis and hepatocellular carcinoma. Taking into the consideration the morbidity and mortality of such lesions, their prophylaxis is a mandatory procedure. In this review we discuss the general measures and the active and passive immunoprophylaxis against hepatitis A. B and Yellow fever, and the general management of hepatitis C. D. and E virus infection.     

Genetic analysis of mecillinam-resistant mutants of Caulobacter crescentus deficient in stalk biosynthesis

Stalk synthesis in Caulobacter crescentus is a developmentally controlled and spatially restricted event that requires the synthesis of peptidoglycan at the stalk-cell body junction. We show that the beta-lactam antibiotic mecillinam prevents stalk synthesis by inhibiting stalk elongation. In addition, mecillinam causes an increase in the diameter of the stalk at the stalk-cell body junction. We describe two mutations that confer resistance to mecillinam and that prevent stalk elongation. These mutations are probably allelic, and they map to a locus previously not associated with stalk synthesis.     

Penetration enhancement by menthol combined with a solubilization effect in a mixed solvent system

The improvement in solubility of indomethacin due to the presence of menthol in various cosolvent systems consisting of water, alcohol and propylene glycol was examined by a mixture design in this study. A proper model to quantitatively describe the effect of menthol at different concentrations on the solubility of indomethacin was compared based on the statistical parameters provided by DESIGN-EXPERT. Then three cosolvent systems with the addition of menthol to solubilize indomethacin to extents of 1.0, 1.5 or 2.0% w/v were selected. The penetration of indomethacin through nude mouse skin from these three cosolvent systems with the addition of 0-12% menthol was investigated and followed by a discussion on the penetration mechanism. The results showed that menthol was able to improve drug solubility to different extents for different cosolvent systems. Optimally, a cosolvent system with an equal ratio of the three solvents, water, alcohol and propylene glycol, showed the highest extent of improvement in the solubility at all concentrations of menthol. The enhancement factors for indomethacin penetration due to menthol in different cosolvent systems were compared, based either on the permeation coefficient (Kp) or the separate overall effects on the skin (Flux). Both comparisons gave similar results. The influence of menthol was more significant compared to that of the cosolvent systems and the extent of this influence increased with an increase in the amount added, reaching a maximum at a specific amount of menthol for each different cosolvent system.     

Bax is an important determinant of chemosensitivity in pediatric tumor cell lines independent of Bcl-2 expression and p53 status

Susceptibility of a tumor cell to undergo chemotherapy-induced apoptosis appears to be dependent upon the balance of proapoptotic and survival factors that are expressed within any given cell. We have chosen to evaluate how expression of several of these proteins influences chemosensitivity of a panel of 10 pediatric tumor cell lines chosen from three tumor histiotypes: neuroblastoma, rhabdomyosarcoma, and pediatric glial tumors. The proteins evaluated were p53 and six members of the Bax/Bcl-2 family: three proapoptotic proteins (Bax, Bak, and Bcl-xS) and three survival factors (Bcl-2, Bcl-xL, and Mcl-1). We investigated whether there was any relationship between endogenous expression of these proteins and chemosensitivity (or resistance) to three chemotherapeutic agents that directly damage DNA (doxorubicin, actinomycin D, and topotecan) and a mitotic spindle poison (vincristine). Even though exogenous overexpression of wild-type p53 has been associated with a chemosensitive phenotype in several model systems we demonstrated no such relationship in these studies. In addition, expression levels of Bcl-2, Bcl-xL, Bcl-xS, Bak, or Mcl-1 did not correlate with sensitivity or resistance to the four drugs. However, there was a statistically significant correlation between endogenous levels of Bax protein and sensitivity to both doxorubicin and actinomycin D. We conclude that even though many proteins such as p53 and Bcl-2 have been shown to influence drug response when exogenously overexpressed in model systems, in unmodified cell lines endogenous protein levels may not generate the same results. We have demonstrated that endogenous Bax expression was the only protein found to be associated with chemosensitivity across the three different tumor histiotypes and propose that analysis of Bax may be a more useful prognostic indicator for tumor response to therapy than either p53 or Bcl-2.