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Biomedical subjects

C M Smith

Publications and source records attributed to C M Smith.

At least 307 records · Page 17Linked to original sources
PubMed1978

Stimulation of lead absorption by vitamin D administration.

Two methods for the determination of lead absorption have been developed using the rat as the test animal. One is an everted intestinal sac method in which the time course of 210Pb transport across intestinal wall can be followed in vitro; and the other, 210Pb absorption from the intestine following gastric intubation can be followed in vivo. By using these techniques it can be clearly demonstrated that vitamin D markedly enhances lead absorption. Both techniques provide evidence that the distal small intestine is the major site of lead absorption and the site of greatest vitamin D stimulation. Lead acetate is apparently absorbed to the extent of 45% as it passes through the small intestine at a concentration of 0.01 mM.

Animals↗
PubMed1978

The effect of metabolic state on incorportion of [14C] pantothenate into CoA in rat liver and heart.

The effect of metabolic or hormonal status on CoA biosynthesis was studied by comparing the rates of incorporation of [14C]-panthothenate into CoA in fasted and glucose-fed rats. Rat hearts and livers were freeze-clamped 1.5 hours after intravenous injection of [14C] pantothenate. CoA, pantothenate, and other pathway intermediates were separated by chromatography of tissue extracts on DEAE cellulose paper. Compared to the fasted rats, rats forced-fed glucose 0.5 hours before pantothenate injection 69% lower incorporation of radioactivity into CoA in liver, a 69% lower specific radioactivity of liver CoA, a 63% lower specific radioactivity of liver mitochondrial CoA, and a 44% lower incorporation of radioactivity in CoA in heart. The accumulation of labeled pathway intermediates was negligible. The cysteine content of liver was equal for the two conditions. There was no difference in level of unacylated CoASH for fasted and glucose-fed rats, suggesting that hormonal effects on degree of CoA acylation are not involved in this regulator mechanism. The specific radioactivities and concentrations of pantothenate in heart or liver were also nearly equal for the two conditions, so the regulatory mechanism does not involve hormonal effects on pantothenate uptake into tissues. Thus, the effect of glucose-feeding (and related changes of metabolite and insulin-glucagon levels) on the incorporation o[14C] pantothenate into CoA is exerted at a locus on the biosynthetic and/or degradative pathway between pantothenate and CoA.

Animals↗
PubMed1977

Determination of hydrazine metabolites of isoniazid in human urine by gas chromatography.

A method is described for the determination of isoniazid, acetylisoniazid, acetylhydrazine, diacetylhydrazine and hydrazine in urine. Isoniazid, acetylhydrazine and hydrazine are reacted in aqueous solution with p-chlorobenzaldehyde to form hydrazones. Following the addition of appropriate internal standards, these hydrazones are then extracted into an organic solvent and determined by gas chromatography using a nitrogen-sensitive detector. Acetylisoniazid and diacetylhydrazine are determined similarly after hydrolysis to isoniazid and acetylhydrazine, respectively.

Acetylation↗
PubMed1977

The systemic use of procaine in the treatment of the elderly: a review.

This article is a review and evaluation of the world literature on the systemic use of procaine in the treatment of the aging process and the common chronic diseases of later life. Included are data from 285 articles and books, describing treatment in more than 100,000 patients in the past 25 years. Except for a possible antidepressant effect, there is no convincing evidence that procaine (or Gerovital, of which procaine is the major component) has any value in the treatment of disease in older patients. If procaine has an antidepressant effect, there is some likelihood that this accounts for the reports of decreased complaints referable to the musculoskeletal, cardiovascular, endocrine sexual, gastrointestinal and respiratory systems.

4-Aminobenzoic Acid↗
PubMed1977

Purine metabolism in isolated rat hepatocytes.

The metabolism of adenine, hypoxanthine, guanine, and adenosine was studied in rat liver cell suspensions, prepared by collagenase perfusion. Oxygen supply was a critical variable in the preparation and subsequent incubationof the cells, as judged on the basis of the ratio of radioactivity in ATP to that in ADP after incubation with [14C]adenine. This ratio is suggested as an additional criterion of cell function. Adenine nucleotides synthesized from [14C]adenine were slowly catabolized to allantoin, with little incorporationof radioactivity into other purine compounds. [14C]Adenine is thus suitable for prelabelling the adenine nucleotide pool. [14C]Guanine and [14C]hypoxanthine were rapidly catabolized to allantoin, whereas nucleotide synthesis was low. [14C]Adenosine was initially phosphorylated and deaminated at about equal rates, but with continued incubation catabolic products predominated. Isolated hepatocytes were found suitable for studies of purine metabolism, in which the liver has important functions for the whole organism.

Adenine↗
PubMed1977

Fructose-induced adenine nucleotide catabolism in isolated rat hepatocytes.

The mechanism of fructose-induced nucleotide catabolism was studied using isolated rat hepatocytes in which the adenine nucleotide pool was prelabelled with [14C]adenine. Incubation of these cells with fructose caused a rapid depletion of the adenine nucleotides and a corresponding increase in allantoin. There was no accumulation of radioactivity in adenosine in the presence or absence of the adenosine deaminase inhibitor 9-erythro-(2-hydroxy-3-nonyl)adenine. This confirms the previous hypothesis that fructose-induced adenine nucleotide catabolism occurs by way of AMP deaminase (AMP amino-hydrolase, EC 3.5.4.6).

AMP Deaminase↗
PubMed1977

Effects of GTP on cyclic AMP concentrations in intact Ehrlich ascites tumor cells.

Experiments were conducted to test the hypothesis that intracellular concentrations of guanosine triphosphate (GTP) regulate the activity and hormonal sensitivity of adenylate cyclase in intact cells. By appropriate treatments, the GTP concentrations of Ehrlich ascites tumor cells could be varied between 28% and 680% of control values. Cyclic AMP concentrations were measured before and after addition of epinephrine in cells containing this range of GTP concentratins. Basal cyclic AMP concentrations were unaffected by changes in GTP concentrations. In cells containing lowered concentrations of GTP, the cyclic AMP concentration following addition of epinephrine was half that in control cells. Elevation of GTP concentrations above normal and had no effect on cyclic AMP concentrations following epinephrine treatment.

Adenylyl Cyclases↗
PubMed1976

Interactions of the components of the prothrombinase complex.

The interaction of components of the prothrombinase complex, i.e. bovine Factor X or Factor Xa, bovine Factor V or Factor Va, phospholipid, and Ca2+, in various combinations was studied primarily by a gel filtration technique. In experiments, in which phospholipids ranging from those isolated from naturally occurring sources to those long chain (18 : 1) as well as short chain 6 : 0 and 7 : 0 fatty acids prepared by chemical and enzymatic synthesis were used, it was evident that a net negative surface charge on the lipid dispersions was one of the important requirements for interaction. Though the short chain fatty acid phospholipids interacted with the proteins of the prothrombinase complex, there was invariably a diminution in the activity of the enzyme complex. It was established that Factor V or Va did not bind Ca2+ and that the binding of either of these factors with phospholipids (with a net negative charge) was not dependent on Ca2+. However, the interaction of Factor X or Factor Xa with phospholipids with a negative charge required Ca2+. It was shown that Factor X could bind to the same type of lipid of lipid surface as that noted for Factor Xa. Of interest was the apparent difference in the phospholipid binding characteristics of the two variant forms of bovine plasma Factor X, i.e. X1 and X2, which might in part explain the differences in their specific activities. Of importance was the lack of demonstrable complex formation between Factors II, X and V in the absence of phospholipids and/or in the presence or absence of Ca2+. The significance of these results as they might apply to the configuration of the prothrombinase complex and its interaction with prothrombin plus the usefulness of the short chain fatty acid phospholipid in exploring these lipid-protein interactions are discussed.

Animals↗
PubMed1976

The activation of factor V by factor Xa or alpha-chymotrypsin and comparison with thrombin and RVV-V action. An improved factor V isolation procedure.

Bovine plasma factor V has been isolated by a preparative procedure involving barium sulfate adsorption, QAEC extraction, poly(ethylene glycol) precipitation, and finally chromatography on a desulfated Sepharose 6B column. Factor V was recovered as a single peak in yields of 35-40% with a specific activity of 50-70 representing a purification of 1000-2000-fold relative to the starting plasma. The apparent molecular weight of the purified factor V was 439,000 +/- 5000. On sodium dodecyl sulfate gel and analytical gel electrophoresis, this factor V preparation showed multiple bands, but results are inconclusive with regard to a possible subunit structure for this factor. The purified factor V was stable for at least 1-2 weeks when stored at 4 degrees C in 0.2 M Tris-acetate, 50 mM CaCl2, 10% glycerol, pH 7.5. When stored at -20 degrees C in 50% glycerol, this preparation was stable for several months. Treatment of the purified factor V with bovine factor Xa, RVV-V, thrombin, or chymotrypsin (but not trypsin) led to a seven- to ten-fold increase in clotting activity and a concomitant decrease in apparent molecular weight. The latter was comparable for each activation system yielding the following average molecular weight values: factor VaSa, 246,000-, factor Va RVV-V, 251,500; Factor Vathr, 239,000; alpha-chymotrypsin, but not trypsin, can activate plasma factor V yielding a product similar to that observed with the above activators. The molar quantities of each of the activators required varied considerably with thrombin having the highest specific activity and factor Xa the lowest. Activation by factor Xa was greatly facilitated by the addition of phospholipid. In the presence of a mixture of phosphatidylcholine/phosphatidylserine (1:1, w/w), the activation of factor V by factor Xa plus Ca2+ required one-third the amount of factor Xa protein as that required in the absence of phospholipid. Even though each of these activators appears to act in an enzymatic manner, the chemical nature of the conversion is unknown at this time.

Animals↗
PubMed1976

Relative importance of alternative pathways of purine nucleotide biosynthesis in Ehrlich ascites tumor cells in vivo.

Several alternative pathways of purine nucleotide synthesis coexist in cells and the relative importance of each pathway for maintaining purine nucleotide concentrations in cells have been studied. Specific inhibitors were used to block these synthetic routes in Ehrlich ascites tumor cells in vivo and the effect of inhibiting each pathway was evaluated by measuring intracellular purine nucleotide concentrations by high-speed liquid chromatography. The results of this study indicate that adenosine triphosphate and guanosine triphosphate concentrations of Ehrlich ascites tumor cells are maintained primarily by purine biosynthesis de novo although other pathways do make significant contributions.

AMP Deaminase↗
PubMed1976

The proliferation of transplanted haematopoietic cells derived from bone marrow and fetal liver.

The proliferation of transplanted murine haematopoietic cells, derived from the femoral bone marrow of young adults and from the liver on the sixteenth day of gestation, has been compared under standardized conditions. Suspensions of bone marrow cells contained 9-6+/-0-9 CFU per 10(5) cells (sm) and suspensions of fetal liver cells contained 3-7+/-0-5 CFU per 10(5) cells (Sl).Sl/Sm = 0-4. The mean diameter of colonies established by cells derived from bone marrow was 1-3+/-0-3 mm (established mean volume, Vm = 1-2 mm3) and the mean diameter of colonies established by cells derived from fetal liver was 1-7+/-0-1 mm (estimated mean volume, Vl ;-6 mm3). Vl/Vm ;-2. The relationship between the weight of the spleen and the number of bone marrow cells injected into lethally irradiated recipients 10 days previously has been confirmed, and a similar relationship between the weight of the spleen and the number of fetal liver cells injected has been demonstrated. An arbitrarily defined difference of 50 mg between the weight of the spleen in untreated irradiated controls and the weight of the spleen in irradiated recipients of haematopoietic cells has been observed 10 days after the administration of 2-2 x 10(6) bone marrow cells (Dm) or 3-0 x 10(6) fetal liver cells (Dl). Dm/Dl = 0-7. The calculated values of Dm/Dl (relative proliferative capacity), Sl/Sm (relative stem cell content) and Vl/Vm (relative clone size) are in good agreement with the values estimated using the equation Dm/Dl = Sl/Sm x Vl/Vm.

Animals↗
PubMed1976

Ethanol effects on muscle spindle afferent activity and spinal reflexes.

The effects of ethanol on muscle spindle afferent activity and on the mono- and polysynaptic reflexes were examined in cats. Ethanol was administered incrementally as intravenous infusions of 0.7 g/kg of ethanol 30 minutes apart; mean arterial blood alcohol concentrations reached 30 minutes after the first and fourth infusions were 1.1 and 3.8 mg/ml, respectively. Ethanol produced modest, dose-related increases in the afferent activity from muscle spindles in spinal- and pentobarbital-anesthetized cats. Mean phasic and static discharge frequencies were both increased approximately 10 impulses/sec after infusions of a total of 2.8 g/kg. In unanesthetized animals, comparable blood levels of ethanol were associated with mild to marked motor incoordination. The mean amplitudes of the mono- and polysnaptic reflexes in spinal animals, elicited with supramaximal single shocks to the muscle nerve, were depressed to 92 and 84% of control levels, respectively, after 0.7 g/kg and continued to fall to 50 and 60% of control levels after 2.8 g/kg of ethanol. Ethanol failed to depress preferentially polysynaptic reflexes. It is concluded that the spindle afferent excitation was involved in the motor effects of ethanol but that it was insufficient to explain fully the skeletomotor alterations produced by ethanol; rather, ethanol actions at peripheral and spinal and, perhaps, supraspinal sites all appear to be involved in ethanol-induced impairment of motor function.

Achilles Tendon↗
PubMed1976

Inhibitors of hypoxanthine metabolism in Ehrlich ascites tumor cells in vitro.

One hundred and sixty-one purine analogs and derivatives were tested for their ability to inhibit ten parameters of purine metabolism in Ehrlich ascites tumor cells incubated in vitro with radioactive hypoxanthine. Sixty-seven compounds were inhibitory against at least one parameter and 30 were inhibitory against two or more.

Adenosine Diphosphate↗