Left ventricular diastolic function in patients with type-I diabetes mellitus (based on pulsed Doppler echocardiographic data)

Diastolic function was studied of left ventricle by pulse Doppler echocardiography in 42 patients with type I diabetes mellitus (DM) and 46 essentially healthy individuals. In DM patients diastolic function was manifested by rise in peak velocity of atrial filling, decrease in ratio of peak velocity of early filling to that of late one, increase in left ventricular end-diastolic pressure. The findings available suggest the atrial phase has an important part in the structure of diastole in DM patients because of a combined influence of tachycardia and increased rigidity of left ventricular myocardium. Values for early filling in the patients did not differ from those in controls. A conclusion is drawn to the effect that in DM patients tachycardia and hypercatecholaminemia may partly mask disturbances in relaxation.     

Localized contact formation by erythrocyte membranes: electrostatic effects

The topology of the contact seam of human erythrocytes adhered by dextran, an uncharged polymer, has been examined. Particular attention has been paid to the influence of electrostatic intermembrane interactions since their magnitude and range can be accurately estimated. Normal cells formed a continuous seam, whereas erythrocytes with pronase-modified glycocalices formed localized contact points on adhesion in 72 kDa dextran in buffered 145 mM NaCl. The dependence of the inter-contact distance lambda on dextran concentration [D] over the range 2-6% w/v, was given by lambda = C[D]-0.62, where C was a constant. The index of [D] was independent of dextran molecular mass over the range 20 to 450 kDa. The inter-contact distance for pronase-pretreated cells in 6% w/v 72 kDa dextran increased from 0.78 to 1.4 microns as [NaCl] was reduced through the range 145 to 90 mM and the suspending phase was maintained at isotonicity by using sorbitol to replace NaCl. The formation and lateral separation of the contact points are discussed from the perspective of linear interfacial instability theory. The theory allows a quantitative explanation for the experimentally observed dependence of inter-contact distance and of disturbance growth rate on change in electrostatic interaction. The results suggest that the dominant wavelength, determining the inter-contact distance, is established on approaching membranes when the layers of cell surface charge are separated by a perpendicular distance of < 14 nm (bilayer separation of 24 nm).     

Identification of a class 3 aldehyde dehydrogenase in human saliva and increased levels of this enzyme, glutathione S-transferases, and DT-diaphorase in the saliva of subjects who continually ingest large quantities of coffee or broccoli

Human saliva was tested for the presence of cytosolic class 3 aldehyde dehydrogenase, glutathione S-transferases alpha, mu, and pi, and DT-diaphorase, enzymes that are known to catalyze the biotransformation of many xenobiotics, including some that are carcinogens and some that are antineoplastic agents. Each of these enzymes was found to be present in this fluid. Inducers of these enzymes are known to be abundantly present in the human diet, especially in certain vegetables and fruits. Further investigation revealed that the salivary content of these enzymes rapidly, coordinately, and markedly increased upon daily consumption of relatively large amounts of coffee or broccoli. The enzyme activities of interest rapidly returned to basal levels when these substances were removed from the diet. Given the important role that cytosolic class 3 aldehyde dehydrogenase, the glutathione S-transferases, and DT-diaphorase are thought to play in determining the carcinogenic potential of some cancer-producing agents as well as the cytotoxic potential of some antineoplastic agents, and assuming that their salivary levels reflect their tissue levels, quantification of the salivary content of one or more of these enzymes, a noninvasive and relatively easy undertaking, could be useful in: (a) preliminarily assessing the chemopreventive potential of various diets and drugs; (b) establishing the optimal dose and schedule in Phase I clinical trials for any putatively chemopreventive diets or drugs of interest; and (c) the rational selection and use of chemotherapeutic agents, since several are inactivated, and a few are activated, by these enzymes; alternatively, the antineoplastic agent could be selected first and then a diet that enables the agent to achieve its full therapeutic potential would be selected based on whether high or low enzyme activity would be favorable in that regard. Such measurements may also be useful as an indicator when exposure to carcinogenic/teratogenic/otherwise toxic environmental/industrial/dietary agents that induce these enzymes is suspected.     

Differential display of genome subsets containing specific interspersed repeats

A genomic differential display method was developed that analyzes many restriction fragment length polymorphisms simultaneously. Interspersed repeat sequences were used to reduce DNA sample complexity and to target genomic subsets of interest. This work focused on trinucleotide repeats because of their importance in human inherited diseases. Immobilized repeat-containing oligonucleotides were used to capture genomic DNA fragments containing sequences complementary to the oligonucleotide. Captured fragments were amplified by PCR and fluorescently labeled using primers complementary to the repeat sequence and/or to the known sequences ligated to the ends of the restriction fragments. The labeled PCR fragments were displayed by size on a high-resolution automated fluorescent DNA sequencing instrument. Although there was a conservation in the overall pattern of displayed genome subsets, many clear and reproducible differences were detected when genomes from different individuals were compared. Fewer differences were detected within, than between, monozygotic twin pair genomes. In control experiments, the method distinguished between Huntington disease alleles with normal and expanded CAG repeat lengths.     

Macrophages, multinucleated giant cells, and apoptosis in HIV+ patients and normal blood donors

Clearance of apoptotic debris is carried out by cells of the monocyte/macrophage lineage and, as other macrophage functions, it can be altered in AIDS, leading to the accumulation of apoptotic cells observed in this disease. In this study we evaluated the ability of macrophages from human immunodeficiency virus (HIV)-infected patients to differentiate and to clear apoptotic debris in prolonged in vitro cultures. Peripheral blood mononuclear cells (PBMC) from infected hemophilia patients were cultured in the absence of exogenously added stimulators and the organization and morphological characteristics of the cultures were analyzed and correlated with clinical staging of the patients. Cell aggregates of different sizes involving macrophages and lymphocytes were formed in cultures from asymptomatic HIV+ patients (CDC groups II-III) and controls and in 4/7 group IV C2 HIV+ patients. In order to obtain viable and organized cultures, cells had to be handled carefully, allowing contact and undisturbed sedimentation in round-bottom tubes. Multinucleated giant cells (MGC) were formed through macrophage fusion after 5 days of culture in HIV- controls, group II and III patients, and some of the group IV C2 patients, while scarce formation of MGC was observed in AIDS patients or patients with advanced HIV disease. This paucity was correlated with impaired dead cell removal and accumulation of apoptotic debris. Viability of macrophages and MGC was reduced after 15 days. MGC and the macrophages (either free or in cell aggregates) were able to remove dead cells, clearing the cultures of cell debris. Furthermore, in group II and III HIV+ hemophilic patients, increased macrophage-MGC phagocytic activity, suggesting in vivo activation, was frequently observed. In HIV+ patients with AIDS or advanced HIV disease (CDC groups IV A, IV C1, and IV D) dead cell removal was impaired and apoptotic debris accumulated. Long-term cultures of unstimulated PBMC are an interesting model for studying the role of macrophages and/or MGC in the removal of dead cells as well as examining the cellular milieu in which HIV replicates in an individual host.     

Ultrastructural criteria that prove the similarities between amphibian and human tumors

The relationship between selected foods and nutrients and breast cancer risk was investigated in strata of age and menopausal status using data from a case-control study on breast cancer conducted between June 1991 and April 1994 in six Italian areas. Cases were 2,569 women with histologically confirmed incident breast cancer admitted to the major teaching and general hospitals of the study areas; controls were 2,588 women with no history of cancer admitted to hospitals in the same catchment area as cases for acute, nonneoplastic, nongynecological conditions unrelated to hormonal or digestive tract diseases or to long-term modifications of diet. Dietary habits were investigated using a validated food frequency questionnaire, including 78 foods or food groups. Among food groups, bread was directly and significantly related to breast cancer risk in older women and, consequently, in postmenopause, whereas the protection conferred by fish consumption was stronger in postmenopause and that exerted by raw vegetables was stronger in premenopause. Among nutrients, unsaturated fatty acids were inversely related to breast cancer risk, the association being stronger in postmenopausal and elderly women. The pattern was similar for total fats. For starch, available carbohydrates, and total proteins, no heterogeneity emerged across strata of age and menopausal status. Among micronutrients, protection diminished with increasing age for beta-carotene and calcium, whereas no heterogeneity emerged for vitamin E. Thus this age-specific analysis of the largest investigation to date on diet and breast cancer did not show any consistent pattern of breast cancer risk in relation to selected dietary factors across strata of age and menopausal status.     

Characterization of a high capacity calcium transport system in mitochondria of the yeast Endomyces magnusii

The Ca2+ transport system of Endomyces magnusii mitochondria has been shown previously to be activated by spermine. Here we report it to be regulated also by low, physiological ADP concentrations, by the intramitochondrial NADH/NAD+ ratio, and by Ca2+ ions. The combination of all these physiological modulators induced high initial rates of Ca2+ uptake and high Ca2+-buffering capacity of yeast mitochondria, enabling them to lower the medium [Ca2+] to approximately 0.2 microM. The mechanisms of stimulation by these agents are discussed.     

Spatial organization of electrical processes in the brain: problems and solutions

Theoretical questions of the spatial organization of electrical activity in the brain are discussed in terms of a multilevel realization of the synergetic principle for formation of functional systems underlying behavior and mental function. The role of the spatial-temporal superimposition of coherent structures of biopotentials in generating fields of increased activity in the cerebral cortex is discussed, these being responsible for integrative and associative functions. A hypothesis is proposed regarding the relationship between the energy and information factors of coherent structures as one of the important characteristics describing the efficiency of energy-informational processes. Emphasis is placed on the need for considering not only linear, but also nonlinear associations of biopotentials in considerations of the form and functional sense of their spatial organization.