Relationship between lipoprotein lipase and high density lipoprotein cholesterol in mice: modulation by cholesteryl ester transfer protein and dietary status

Plasma lipoprotein lipase (LPL) activity correlates with high density lipoprotein (HDL) cholesterol levels in humans. However, in several mouse models created either through transgenesis or targeted inactivation of LPL, no significant changes in HDL cholesterol values have been evident. One possible explanation for this species difference could be the absence of plasma cholesteryl ester transfer protein (CETP) activity in mice. To explore this possibility and further investigate interactions between LPL and CETP modulating HDL cholesterol levels in vivo, we examined the relationship between LPL activity and HDL levels in mice expressing the simian CETP transgene, compared with littermates not carrying the CETP gene. On a chow diet, increasing LPL activity was associated with a trend towards increased HDL levels (51 +/- 29 vs. 31 +/- 4 mg/dL highest vs. lowest tertiles of LPL activity, P = 0.07) in mice expressing CETP, while no such effects were seen in the absence of CETP (65 +/- 12 vs. 61 +/- 15 mg/ dL). Furthermore, in the presence of CETP, a significant positive correlation between LPL activity and HDL cholesterol was evident (r = 0.15, P = 0.006), while in the absence of CETP no such correlation was detected (r = 0.15, P = 0.36), highlighting the interactions between LPL and CETP in vivo. When mice were challenged with a high fat, high carbohydrate diet, strong correlations between LPL activity and HDL cholesterol were seen in both the presence (r = 0.45, P = 0.03) and absence (r = 0.73, P < 0.001) of CETP. Therefore, under altered metabolic contexts, such as those induced by dietary challenge, the relation between LPL activity and HDL cholesterol may also become evident. Here we have shown that both genetic and environmental factors may modulate the association between LPL activity and HDL cholesterol, and provide explanations for the absence of any changes in HDL values in mice either transgenic or with targeted disruption of the LPL gene.     

Reduced performance of male and female athletes at 580 m altitude

Patients with craniocervical mandibular (TMD) disorders can present with tinnitus as a primary or secondary complaint. The embryology and functional anatomy of the middle ear, temporomandibular joint, muscles of mastication and associated tendons, ligaments, blood vessels, nerves and lymphatics was found to be helpful in establishing etiologic concepts which relate tinnitus to these temporomandibular disorders. In addition to etiologic concepts, treatment modalities are described. The authors relate their experiences as well as those of others with different patient populations.     

Follicular vascularity--the predictive value of transvaginal power Doppler ultrasonography in an in-vitro fertilization programme: a preliminary study

The glnA gene from the human pathogen Streptococcus agalactiae was cloned from a genomic library prepared with the lambda phage vector lambdaDASHII. A 4.6-kb DNA fragment of one of the recombinant phages was subcloned in pUC18. This Escherichia coli clone expressed a 52-kDa protein encoded by a 1,341-bp open reading frame. The nucleotide sequence of the open reading frame and the deduced amino acid sequence shared a significant degree of homology with the sequences of other glutamine synthetases (GS). The highest homology was between our deduced protein and GS of gram-positive bacteria such as Bacillus subtilis, Bacillus cereus, and Staphylococcus aureus. Plasmids with the cloned streptococcal glnA were able to complement E. coli glnA mutants grown on minimal media. Rabbit antisera to streptococcal GS recombinant protein recognized not only the recombinant protein but also a similar-sized band in mutanolysin extracts of all group B streptococcal strains tested, regardless of polysaccharide type or surface protein profile. The amino acid sequence of the deduced protein had similarities to other streptococcal cell-surface-bound proteins. The possible functional role of the immunological features of streptococcal GS is discussed.     

Epstein-Barr virus uses HLA class II as a cofactor for infection of B lymphocytes

Infection of B lymphocytes by Epstein-Barr virus (EBV) requires attachment of virus via binding of viral glycoprotein gp350 to CD21 on the cell surface. Penetration of the cell membrane additionally involves a complex of three glycoproteins, gH, gL, and gp42. Glycoprotein gp42 binds to HLA-DR. Interference with this interaction with a soluble form of gp42, with a monoclonal antibody (MAb) to gp42, or with a MAb to HLA-DR inhibited virus infection. It was not possible to superinfect cells that failed to express HLA-DR unless expression was restored by transfection or creation of hybrid cell lines with complementing deficiencies in expression of HLA class II. HLA class II molecules thus serve as cofactors for infection of human B cells.     

Two-incision radial keratotomy for low myopia with astigmatism

PURPOSE: To evaluate the effectiveness of two-incision radial keratotomy (RK) in correcting low-magnitude refractive myopic astigmatism. SETTING: Two clinical study sites, one in St. Louis, Missouri, USA, the other in Caracas, Venezuela. METHODS: Fifty-seven eyes of 43 patients with low-magnitude myopic astigmatism had two-incision RK at one of two clinical study sites. In the initial phase of this series, 10 eyes with amblyopia at the 20/30 level had surgery at one center. Refractive keratotomy was performed with the radial incision placed in the plus cylinder axis of refraction. This axis was verified as the meridian of greatest corneal curvature by standard keratometry and computer-assisted corneal topographic analysis. Two eyes received a second operation (enhancement). RESULTS: Mean follow-up was 11.1 months (range 6 to 12 months). Mean preoperative and postoperative myopic spherical equivalent measured -1.42 diopters (D) +/- 0.51 (SD) and -0.14 +/- 0.39 D, respectively; the mean reduction was 1.28 +/- 0.59 D (P = .0001). Mean preoperative and postoperative refractive astigmatism was 1.41 +/- 0.45 D and 0.48 +/- 0.33 D, respectively (P = .0001). Mean preoperative and postoperative keratometric astigmatism was 1.26 +/- 0.54 D and 0.31 +/- 0.35 D, respectively, a mean reduction of 0.95 D (P = .0001). The surgical meridian was flattened by an average of 2.06 D by keratometry and the orthogonal meridian, by an average of 1.10 D. Preoperative uncorrected visual acuity (UCVA) was 20/40 or better in five (9%) eyes (range counting fingers to 20/40). Postoperative UCVA acuity was 20/40 or better in all eyes (mean acuity 20/25). In the nonamblyopic subgroup mean postoperative UCVA was 20/24. CONCLUSIONS: A limited number of radial incisions placed in the topographically confirmed axis of greatest curvature are effective in the treatment of low-magnitude myopic astigmatism.     

Histopathological variations among cases of Wilms'' tumor in Bangladesh and its relationship with prognosis

Both glucagon and glucagon-like peptide-1 (GLP-1) play an important role in the regulation of nutrient homeostasis. In this study, the tissue distributions of the expression of receptor genes for glucagon and GLP-1 were examined. Expression of glucagon receptor gene was detected in liver, kidney, ileum and pancreatic islets but not in brain. In contrast, expression of GLP-1 receptor gene was detected in brain, pancreas and pancreatic islets but not in liver, kidney, or ileum. To investigate the existence and characteristics of glucagon and GLP-1 receptors on pancreatic beta cells, expression of the receptor genes and translational regulation of the expression of the receptor genes by glucose were analyzed in a mouse pancreatic beta cell line, MIN6 cells. In the cDNA pool of MIN6 cells, both glucagon and GLP-1 receptor genes were identified and showed higher expression level in MIN6 cells cultured under high glucose condition than in those cultured under low glucose condition. These results suggest that glucagon and GLP-1 receptor genes are expressed in pancreatic beta cells and their expression is upregulated by glucose.     

Effects of hypertrophy on regional action potential characteristics in the rat left ventricle: a cellular basis for T-wave inversion?

BACKGROUND: In cardiac hypertrophy, ECG T-wave changes imply an abnormal sequence of ventricular repolarization. We investigated the hypothesis that this is due to changes in the normal regional differences in action potential duration. We assessed the contribution of potassium- and calcium-dependent currents to these differences. Both the altered sequence of ventricular repolarization and the underlying cellular mechanisms may contribute to the increased incidence of ventricular arrhythmias in hypertrophy. METHODS AND RESULTS: Rats received daily isoproterenol injections for 7 days. Myocytes were isolated from basal subendocardial (endo), basal midmyocardial (mid), and apical subepicardial (epi) regions of the left ventricular free wall. Action potentials were stimulated with patch pipettes at 37 degrees C. The ratio of heart weight to body weight and mean cell capacitance are increased by 22% and 18%, respectively, in hypertrophy compared with controls (P<.001). Normal regional differences in action potential duration at 25% repolarization (APD25) are reduced in hypertrophy (control: endo, 11.4+/-0.9 ms; mid, 8.2+/-0.9 ms; epi, 5.1+/-0.4 ms; hypertrophy: endo, 11.6+/-0.9 ms; mid, 10.4+/-0.8 ms; epi, 7.8+/-0.6 ms). The regional differences in APD25 are still present in 3 mmol/L 4-aminopyridine. Hypertrophy affects APD75 differently, depending on the region of origin of myocytes (ANOVA P<.05). APD75 is shortened in subendocardial myocytes but is prolonged in subepicardial myocytes (control: endo, 126+/-7 ms; epi, 96+/-10 ms; hypertrophy: endo, 91+/-6 ms; epi, 108+/-7 ms). These changes in APD75 are altered by intracellular calcium buffering. CONCLUSIONS: Normal regional differences in APD and the changes observed in hypertrophy are only partially explained by differences in I(tol). In hypertrophy, the normal endocardial/epicardial gradient in APD75 appears to be reversed. This may explain the T-wave inversion observed and will have implications for arrhythmogenesis.