Pathways of succinate formation and their contribution to improvement of cardiac function in the hypoxic rat heart

Hypoxia led to a dramatic acceleration of amino acid breakdown together with succinate synthesis in the rat heart. Our data do not confirm the simultaneous conversion of aspartate and glutamate to succinate, which has been repeatedly assumed in the literature (7, 8, 21, 28-30), but rather suggest that different pathways are involved during developing hypoxia and that glutamate is the sole source for anaerobic succinate production from endogenous sources in the glucose-perfused heart. Perfusion of hypoxic rat hearts with 2-oxoglutarate, malate, and fumarate (5 mM each) increased succinate formation three- to fourfold. The beneficial effects of these substances on left ventricular systolic pressure, end diastolic pressure, and time of recovery may be due to the elevated content of ATP in these hearts compared to hypoxic controls with glucose as the sole substrate. However, the maintenance of a high rate of anaerobic glycolysis in hearts perfused with 2-oxoglutarate, malate, and fumarate and not the small stimulation of succinate synthesis is considered to be the most important mechanism of cardiac protection. A proposed pathway assumes that malate, after dehydration to fumarate, may serve as an alternative electron acceptor for cytosolic NADH during conditions of oxygen deficiency, thereby cancelling glycolytic inhibition.     

A subfamily of alphoid repetitive DNA shared by the NOR-bearing human chromosomes 14 and 22

The nucleotide sequence of members of an alpha-repeat subfamily shared by human chromosomes 14 and 22 is presented. This subfamily is organized into a higher-order repeat unit composed of a tandem repetition of an ordered array of four related but distinct 340-bp repeat dimers. An analogous situation has been described for a related but distinct subfamily shared by chromosomes 13 and 21. These two subfamilies were further shown not to be present on the homologous chimpanzee chromosomes and therefore must have arisen by rearrangement of the human genome after separation of the two species. The sequence homology between the 13/21 and the 14/22 subfamilies is about 85%. The 14/22 subfamily represents the only major alphoid DNA species on these two chromosomes and is not present elsewhere in the human genome. Fluorescent in situ hybridizations show that sequences from the 13/21 and 14/22 subfamilies can be used as specific markers for their respective chromosomes.     

v-myc alters the response of a cloned mouse mammary epithelial cell line to lactogenic hormones

Several oncogenes have now been implicated in mammary carcinogenesis. We investigated the phenotypic effects of expressing three representative oncogenes in mammary epithelial cells. v-myc (coding for a nuclear protein), v-Ha-ras (a G-protein homologue) and v-fgr (a tyrosine kinase) genes were introduced into the nontumorigenic clone 14 of the mouse mammary epithelial cell line COMMA-1D. Their effects upon growth and differentiation were determined. Anchorage-independent growth was induced by all three oncogenes with low efficiency. v-Ha-ras and v-fgr induced tumorigenicity in nude mice. The effect of oncogenes upon parameters unique to mammary epithelial cells in vitro was assayed. Both v-myc and v-fgr abolished the ability of clone 14 to grow as three-dimensional branching structures in hydrated collagen gel. v-fgr completely and v-myc partially inhibited the expression of the epithelium specific cytokeratins. Clone 14 can be induced to produce the beta-casein milk protein by the combination of the lactogenic hormones, dexamethasone, insulin, and PRL. Introduction of v-myc into clone 14 cells resulted in an estimated 50-fold increased induction of beta-casein protein and at least a 60-fold increase in beta-casein mRNA. The number of cells stained with anti-beta casein antibodies also showed a 10-fold increase after v-myc introduction. This still required the synergistic action of all three lactogenic hormones. Thus v-myc can alter the normal response of mammary epithelial cells to lactogenic hormones.     

Hemodynamic interactions between intrinsic blood flow control mechanisms in the rat kidney

In order to reconcile the controversial concepts of myogenically and tubuloglomerular-feedback (TGF)-mediated control of renal vascular resistance, a hypothesis is advanced according to which both mechanisms interact hemodynamically because of their serial arrangement. Whereas the myogenic mechanism is suggested to be localized in the more upstream segments of the preglomerular resistance vessels, the TGF mechanism is assumed to control the pre- and/or postglomerular vascular segment(s), close to the glomerular vascular pole. The efferent vascular resistance, however, is assumed to function generally akin to a 'passive' flow resistor. These assumptions together with elementary hemodynamic considerations, allow formulation of a simple renal hemodynamic model whose quantitative predications regarding the characteristics of RBF, GFR and TGF control are remarkably consistent with the literature: (1) the magnitude of TGF response is mainly dependent upon the myogenic cooperative amplification and (2) although the TGF mechanism is not involved in the autoregulative control of RBF and GFR, changes of the TGF function may shift the autoregulation curve to higher or lower RBF and blood pressure levels.     

Restriction analysis of Thiobacillus ferrooxidans DNA using pulsed field electrophoresis]

The DNA of Thiobacillus ferrooxidans digested by any of the five restriction endonucleases (DraI, EcoRI, Eco321, HindIII, XbaI) was studied by electrophoresis in the pulsating differently directed electric fields (PF). The influence of PF conditions on the sized row of the divided DNA fragments was studied. Only the XbaI restriction endonuclease was shown to cleave the Thiobacillus ferrooxidans DNA into a number of fragments permitting one to define the sizes of fragments and genome (no more than 2300 bp). The prospects of using the restriction analysis of Thiobacillus ferrooxidans wild type culture for improving its properties in obtaining heavy metals are discussed.     

Lesion and regeneration in the medial cerebral cortex of lizards.

The cerebral cortex of Squamate reptiles (lizards and snakes) may be regarded as an archicortex or "reptilian hippocampus". In lizards, one cortical area, the medial cortex, may be considered as a true "fascia dentata" on grounds of its anatomy, connectivity and cyto- chemo-architectonics of its main zinc-rich axonal projection. Moreover, its late ontogenesis and postnatal development support this view. In normal conditions, it shows delayed postnatal neurogenesis and growth during the lizard's life span. Remnant neuroblasts in the medial cortical ependyma of adult lizards seasonally proliferate. The late-produced immature neurocytes migrate to the medial cortex cell layer where they differentiate and give off zinc-containing axons directed to the rest of cortical areas. This results in a continuous growth of the medial cortex and its zinc-rich axonal projection. Perhaps the most important characteristic of the lizard medial cortex is that it can regenerate after having been almost completely destroyed. Recent experiments in our laboratory have shown that chemical lesion of its neurons (up to 95%) results in a cascade of events; first, those related with massive neuronal death and axonal-dendritic retraction and, secondly, those related with a triggered neuroblast proliferation and subsequent neo-histogenesis, and the regeneration of an almost new medial cortex that shows itself undistinguishable from a normal undamaged one. This is the only report to our knowledge that an amniote central nervous centre may regenerate by new neuron production and neo-histogenesis. Perhaps the medial cortex of lizards may be used as a model for neuronal regeneration and/or transplant experiments in mammals or even in primates.