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Biomedical subjects

I A Silver

Publications and source records attributed to I A Silver.

At least 19 recordsLinked to original sources
PubMed1979

Cellular energy metabolism, trans-plasma and trans-mitochondrial membrane potentials, and pH gradients in mouse neuroblastoma.

A method for quantitative evaluation of transmembrane electrical potential and pH gradients across a subcellular compartment in an intact cell is presented. This approach has been applied in studies of mouse neuroblastoma C-1300 clone NB41A3, in which the transmembrane electrical potential and pH gradients and the mitochondrial volume percent have been determined. Membrane potentials and pH gradients were measured by two different methods. Equilibrium distributions of [(3)H]triphenylmethyl phosphonium and [(14)C]-thiocyanate ions gave calculated apparent membrane potentials of -77.0 and -29.6 mV, respectively, at 20-25 degrees C; a value of -60.8 mV was obtained from microelectrode measurements. Equilibrium distributions of weak acids ([(14)C]trimethylacetic acid and 5,5-di[(14)C]methyl-2,4-oxazolidine-dione) and of weak bases ([(14)C]dimethylamine and [(14)C]trimethylamine) gave calculated upper and lower limits of the pH gradient (Delta pH = pH(e) - pH(i)) of -0.14 and -0.21 pH unit, respectively. The microelectrode measurements showed that the intracellular pH is within 0.1 of a pH unit or less of the extracellular pH over the extracellular pH range of 7.35-6.85. The mitochondrial volume percent calculated on the basis of the measured cytochrome c content is 5.6 +/- 1.2% and compares well with estimates of 5.4 +/- 1.1% obtained from 25 electron micrographs. Measurements of the cellular energetic parameters gave values within the range found in other cells and perfused organs. Comparison of the results of the microelectrode and equilibrium measurements permits estimates of the electrical potential and pH gradients across the mitochondrial membrane (mitochondria-to-cytoplasm gradients) to be made and suggests that the trans-mitochondrial membrane protonmotive force in the intact cell cannot be greater than -143 mV.

Animals↗
PubMed1979

The mechanics of wound healing.

This paper discusses the factors which affect the healing of wounds at the tissue and organ levels. It covers some of the problems which complicate the sequence of healing and considers the mechanisms involved in regeneration and repair of tissues. The factors associated with the stimulus and sequence of healing and their interactions are also reviewed.

Animals↗
PubMed1979

Mechanism of the cerebrocortical vasodilatation during anoxia.

The possible role of cerebrocortical ion homeostasis, NAD/NADH redox state and of cortical oxygen tension was investigated in the initiation of hypoxic cortical vasodilatation. In addition, changes in cerebrocortical extracellular concentrations of Na+, K+, and Cl- during anoxia were studied. The results were as follows. a) The cerebrocortical reflectance decrease, e.g. cerebral vasodilatation, lagged behind the cortical pO2 decrease by 1-2 sec, but preceded the decrease of arterial blood pressure and ECoG as well as the extracellular Na+, K+, Cl- increases by 20-30 sec. Since the cortical pO2 decreased first and the ion changes lagged behind the onset of vasodilatation by 20-30 sec, it is suggested that the CBF increase in hypoxia is mediated via the cortical pO2 decrease. b) A significant NAD reduction was already present after 20 sec. of nitrogen breathing. Since the ECoG and MABP decreased, and K+ activity increased much later than this, it is presumed that the NAD reduction during the first 30-40 sec of anoxia indicates an increased rate of glycolysis, but not mitochondrial hypoxia. c) In the predepolarization phase a 17% K+, 4% Na+, 5% Cl- increase is probably the result of a reduction of the extracellular spaces caused by water movement and by the migration of Na+ and Cl- from the extracellular to the intracellular space. The large K+, Na+, Cl- changes during terminal depolarization can be interpreted as a result of the failure of the membrane bound Na+ -K+ pump and of the altered ion permeability of the cell membranes.

Action Potentials↗
PubMed1979

Effect of arterial hypoxia on the cerebrocortical redox state, vascular volume, oxygen tension, electrical activity and potassium ion concentration.

The effect of different degrees of arterial hypoxia on cerebrocortical NAD/NADH redox state, reflectance, oxygen tension, extracellular potassium ion concentration, ECoG and arterial blood pressure was investigated in rats. The results may be summarized as follows. a) The decrease of cortical pO2 preceded the dilatation of cortical vessels by 15-20 sec but the changes in cortical extracellular potassium ion concentration, ECoG and arterial blood pressure started later than the vasodilatation. These results give further support to the regulatory role of cortical pO2 decrease in the initiation of cerebrocortical vasodilatation during arterial hypoxia. b) Since the K+ concentration of the brain cortex and the ECoG did not change in mild arterial hypoxia, the significant NAD reduction obtained in this experimental group is likely to be of cytoplasmic origin. The same conclusion applies to the initial periods of severe arterial hypoxia. On the basis of the extent of NAD reduction during various degrees of arterial hypoxia it is concluded that about 30% of the NAD reduction occurring in anoxia is of cytoplasmic origin. c) When the animals were ventilated with a gas mixture containing 4-7% oxygen, the brain cortex became nearly anoxic, partly because of the gradual decrease of arterial blood pressure. Finally, the mechanism of potassium leakage is identical under prolonged severe arterial hypoxaemia and on anoxic terminal depolarization.

Action Potentials↗
PubMed1979

The significance of clinical assessment of brain tissue oxygenation in different pathological conditions: an overview.

The development of methods of measurement of brain oxygenation in man is reviewed and the possible clinical potential of some new and established laboratory techniques is evaluated. Advantages and problems associated with the various approaches are considered together with the difficulties that are encountered in interpretation of data obtained and the factors that may increase such difficulties. It is concluded that invasive techniques that can only be used intraoperatively are of limited value but may be helpful in confirming the edges of ischemic areas or the restoration of adequate local blood flow. Chronically implanted devices have been useful in detecting epileptic foci and in evaluation of anesthetic regimes in patients with brain lesions. Infrared spectroscopy may offer possibilities for noninvasive whole brain monitoring in patients, but the method lacks resolution.

Brain↗
PubMed1979

Resorption of insoluble, heterologous, fluorescein-collagen sponges in sensitized and non-sensitized rats.

Sponges of insoluble bovine collagen were slowly resorbed over a 35-day period when implanted under the back skin of rats. The cellular picture was typical of a mild foreign-body reaction. The reaction to fluorescein-labelled collagen sponges was similar but there was evidence also of a weak immunological response. An acute inflammatory reaction with massive oedema was elicited when fluorescein-labelled collagen sponges were implanted in rats previously sensitized to either fluorescein-collagen or fluorescein-bovine serum albumin. The early invasion by PMN leucocytes subsided after 4 days and caused no observable breakdown of the sponge. The implanted material was rapidly encapsulated by fibrous tissue which was then resorbed along with the sponge between the 7th and 12th day. Macrophages were very active in the sponge at this time, sometimes forming giant cells. Fibroblasts were invading from the periphery with the development of the granulation tissue. The small residue which remained after this time was overrun by granulation tissue and was slowly resorbed up to the 35th day. Throughout the period of study there was only a weak local immunological response after the 28th day. The level of circulating antibodies against the fluorescein hapten was high, but the titre for the antibodies against bovine collagen remained low. The significance of these findings in the pathological destruction of connective tissue is discussed.

Absorption↗
PubMed1978

Cellular microenvironment in relation to local blood flow.

The investigation was designed to identify microenvironmental factors that might be important in the regulation of local blood flow. Cellular microenvironment in terms of Po2, pH, [K+], [Cl-], [Ca2+] and lactate was measured in rat brain by means of specific microelectrodes. Vascular endothelium was stained in vivo with Thioflavine S. Local blood flow was measured with micro hydrogen electrodes. Some intracellular measurements of pH were made in conjunction with extracellular measurements. The main findings were that local autoregulation responses and blood flow changes in response to imposed hypoxic changes were very rapid (1-1.5 s). Microflow responses to changes in local cell activity were limited to a region not more than 250 micron in diameter. Increased blood flow in acute hypoxia occurred within 1-2 s of the fall in tissue Po2 and was much more rapid than changes in either pH or potassium. Intracellular pH changed within 10 s of the onset of severe hypoxia but in all cases the blood flow followed the Po2 much more closely than any other parameter. It is suggested that changes in capillary endothelium and local membrane transmission may play a part in autoregulatory mechanisms.

Animals↗
PubMed1977

Effect of oxygen tension on cellular energetics.

Simultaneous measurements of the mitochondrial [NAD+]/[NADH], the cytoplasmic [ATP]/[ADP] x [Pi], and the respiratory rate were carried out in suspensions of cultured kidney cells in a range of defined oxygen tensions. The results show that as the extracellular oxygen concentration falls there is a decrease in the respiratory rate, which is accompanied by a decrease in the [ATP]/[ADP] and a progressive reduction of cytochrome c. Even at low O2 tensions the mitochondrial respiratory chain between the NAD couple and cytochrome c remains at near equilibrium with the ATP synthesizing reactions. It is concluded that limited oxygen supply affects cellular metabolism at much higher concentrations than the P50 value for the oxygen dependence of respiration, but the respiratory rate remains relatively unchanged due to compensatory changes in the [ATP]/[ADP] X [Pi] and progressive reduction of cytochrome c. These metabolic changes may form a basis for the phenomenon of tissue oxygen sensing at near physiological oxygen tensions.

Adenine Nucleotides↗