Ganglioside expression in tissues of mice lacking beta2-microglobulin

This study presents a comparative analysis of gangliosides from lymphoid (spleen and thymus) and other (brain, liver, lungs and muscle) tissues of C57BL/6 mice lacking the gene for beta2-microglobulin (beta2M), a constitutive component of the MHC class I molecule. Ganglioside fractions in the tissues of mice homozygous (beta2M-/-) and heterozygous (beta2M-/+) for the gene deletion were determined by high performance thin-layer chromatography (HPTLC), followed by immunostaining with specific polyclonal antibodies. Ubiquitous gangliosides GM3(Neu5Ac) and GM3(Neu5Gc) were the dominant gangliosides in the lungs of the control beta2M-/+ mice, whereas the homozygous knockout mice had substantially decreased expression of these structures. The lungs of the beta2M-/- mice also had reduced expression of T-lymphocyte-specific GM1b-type gangliosides (GM1b and GalNAc-GM1b). beta2M-deficient mice also had more GM1a and GD1a gangliosides in the liver, and several neolacto-series gangliosides were increased in the brain and lungs. This study provides in vivo evidence that the beta2M molecule can influence the acquisition of a distinct ganglioside assembly in different mouse organs, implicating its non-immunological functions.     

Short-term and long-term stimulation of Na+−H+ exchange in cortical brush-border membranes during compensatory growth of the rat kidney

The effect of unilateral nephrectomy on Na⁺–H⁺ exchange in rat renal cortical brush-border membrane vesicles (BBMV) was studied by the method of acridine orange fluorescence quenching. The exchanger activity in BBMV from remnant kidney increased rapidly by 70–75% within first 30 min following uninephrectomy. Only a slight further increase was found in later stages of renal growth, i.e. 30 min to 7 days following uninephrectomy. The changes in antiporter activity were restricted toV _max, whereas theK _m for Na⁺ was similar in control and compensatory growing kidney. The increase of Na⁺–H⁺ exchange at 15 min was not affected by actinomycin D in vivo, whereas the increase at 48 h was completely abolished indicating that protein synthesis could be involved in the late, but not in the initial stimulation of renal Na⁺–H⁺ exchange. The late, but not the initial stimulations of Na⁺–H⁺ exchange were associated with elevated activities of cortical (Na⁺+K⁺)-ATPase indicating that changes in antiporter activity precede those in the (Na⁺+K⁺)-pump. The early stimulation of Na⁺–H⁺ exchange in BBMV in one kidney was induced also by the occlusion of blood flow through the contralateral kidney for 15 min, without removing it. Thirty min after the occlusion was removed and the reflow established, the Na⁺–H⁺ exchange in BBMV from the intact kidney decreased to the control values. The observed modulations in renal Na⁺–H⁺ exchanger may be regulated by phosphorylation-dephosphorylation events. In support, the concentration of a well known protein kinase C activator, 1,2-diacylglycerol, in the cortical tissue of the remnant kidney increased up to 100% within 5 min following unilateral nephrectomy and preceded the increase in Na⁺–H⁺ exchange. The early stimulation of Na⁺–H⁺ exchange may be a trigger in initiating the kidney growth.     

A-raf oncogene localizes on mouse X chromosome to region some 10–17 centimorgans proximal to hypoxanthine phosphoribosyltransferase gene

The localization of the A-rafcellular oncogene on the mouse X chromosome has been determined using Xbal-restricted DNAs prepared from progeny of an interspecies backcross between the B6.CBA.R1 and the Spe/Pas mouse strains. This localization to the proximal part of the mouse X chromosome has been confirmed by the use of somatic cell hybrids, carrying partially deleted X chromosomes and suggests that the A-raf oncogene localizes to a region lying some 10–17 centimorgans proximal to the hypoxanthine phosphoribosyltransferase (Hprt) gene between the locus DXPas4and the locus DXPas7defined by the cross-reacting human X chromosome-specific probe DXS32 (M2C). This localization on the mouse X chromosome is compatible with the presence of the A-rafoncogene on the short arm of the human X chromosome between the centromere and Xp21.     

Heart in the elderly (views and considerations at the turn of the centuries)

The proportion of elderly people grows rapidly both in Croatia and worldwide, posing great health care, psychological, social, economic and other problems. In the elderly, cardiovascular diseases, especially coronary (ischemic) heart diseases, account for approximately 50% of all deaths. In contrast to previous opinions, recent studies show that aging per se does not substantially diminish the efficacy of heart pump unless affected by diseases, primarily atherosclerosis (atherothrombosis). Atherosclerosis, however, is not an inevitable component of old age, but a disease that can to a great extent be prevented, and hopefully even defeated in the near future. Of paramount importance is elimination of the major risk factors: cigarette smoking, hypertension, hyperlipidemia, diabetes mellitus, obesity, and physical inactivity, preferably in the form of primary prevention, primarily by the hygienic-dietetic measures, and by medication (antihypertensives, hypolipidemics), if necessary. The prevention should be initiated early enough to prevent the development of subclinical forms of the disease, because clinical manifestations (angina pectoris, myocardial infarction, serious ventricular arrhythmias, sudden death) occurring unexpectedly ('like a bolt from the blue') reflect a very advanced coronary disease. The management of these late complications, however admirable it may be (coronary dilatation--stents, coronary surgery, thrombolysis, resuscitation, electrotherapy, etc.), is only partially successful and in fact unavailable to the majority of the population, even in developed countries. Therefore, every individual should be informed about the main characteristics of the issue to be able to take active participation in the programs of primary prevention. Although the relative importance of particular risk factors decreases in old age, these factors are present in a higher number in the elderly which, along with the generally greater mortality rate, points to the need of all measures (primary and secondary) of prevention to be as carefully carried out in the elderly as in younger individuals.     

Increased central adiposity is associated with pro-inflammatory immunoglobulin G N-glycans

Background

Increased body fat may be associated with an increased risk of developing an underlying pro-inflammatory state, thus leading to greater risk of developing certain chronic conditions. Immunoglobulin G has the ability to exert both anti- and pro-inflammatory effects, and the N-glycosylation of the fragment crystallisable portion is involved in mediating this process. Body mass index, a rudimentary yet gold standard indication for body fat, has been shown to be associated with agalactosylated immunoglobulin G N-glycans.

Natural zeolite clinoptilolite increases the concentrations of sphingoid bases in the yeast Yarrowia lipolytica

In the present paper, we studied the effect of natural zeolite clinoptilolite on sphingolipid metabolism in the yeast Yarrowia lipolytica. We also investigated if zeolite addition had any impact on cell shape and size, as well as on the pH alterations during the culture growth. High performance liquid chromatography analysis of sphingoid bases obtained by acid hydrolysis of complex sphingolipids from Y. lipolytica showed that their concentrations markedly rose upon the zeolite addition. The largest increase among the identified molecular species of sphingoid bases was seen in C18 phytosphingosine, whose levels rose 6.2-fold and 22.3-fold after culturing cells for 24 and 36 hours respectively in the presence of finely ground zeolite. pH measurements of the culture medium showed a similarity between pH profiles of control and zeolite-supplemented cells, suggesting that ion-exchange capacity was not probably responsible for the observed change in sphingolipid metabolism. Scanning electron microscopy revealed that zeolite affected cell size and shape. Y. lipolytica cells grown in the absence of zeolite were oval-shaped with an average cell size of 0.7-2.7 microns, whereas when cultured with zeolite, they were round-shaped and larger, having an average cell size of 1.3-2.9 microns.