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Biomedical subjects

M A Baker

Publications and source records attributed to M A Baker.

At least 91 records · Page 5Linked to original sources
PubMed1986

Elevated CSF osmolality inhibits thermoregulatory heat loss responses.

The effect of intracerebroventricular (icv) infusions of hypertonic NaCl or sucrose on thermoregulatory responses to heat was studied in conscious rabbits to test the idea that brain osmoreceptors are involved in the inhibition of evaporative heat loss and elevation of body temperature in dehydrated mammals at high ambient temperature (Ta). In rabbits hydrated ad lib and resting at a Ta of 33 degrees C, icv infusion (3.4 microliter/min) of hypertonic (1,500 mosm) NaCl or sucrose in artificial cerebrospinal fluid (ACSF) produced a significant reduction in respiratory frequency (f) and in ear skin temperature (Te) and a rise in brain temperature (preoptic area, Tpoa). icv infusion of ACSF alone or ACSF + NaCl at 500 and at 750 mosm had no effect on f or on Te or Tpoa. Infusion of NaCl + ACSF at 1,000 mosm reduced f but did not affect Te or Tpoa. In hydrated rabbits, icv infusion of 1,500 mosm NaCl abolished the rise in f and in Te elicited by POA heating at Ta of 25 degrees C. In dehydrated rabbits at 33 degrees C, f was below hydrated levels and icv infusion of water (6.8 microliter/min) produced a reversible elevation in f. These findings suggest that brain osmoreceptors can influence thermoregulation in hot environments.

Animals↗
PubMed1985

Regeneration of membrane sialic acid after neuraminidase treatment of leukemic granulocytes.

Granulocytes from patients with chronic myelogenous leukemia (CML) were studied for their ability to regenerate surface sialic acid following treatment with Vibrio cholera neuraminidase (VCN) in vitro. Immediately after neuraminidase treatment, CML and normal granulocytes showed similar incorporation of radioactivity after surface labelling with sodium periodate/potassium-H3-borohydride (PI/BH3(4)). CML granulocytes treated with neuraminidase then incubated for 18 h in nutrient medium showed strikingly increased PI/BH3(4) labelling, usually greater than initial pretreatment values, consistent with a rapid reappearance of sialic acid in the cell membrane. This pattern was not seen in normal granulocytes. The aberrant regeneration of sialic acid in CML granulocytes in vitro could be inhibited by addition of 3 X 10(-6) M retinoic acid, suggesting either a direct effect on membrane glycoconjugate synthesis or an association with granulocyte differentiation.

Cell Membrane↗
PubMed1985

Inhibition of thermal panting by intracarotid infusion of hypertonic saline in dogs.

Six dogs were surgically prepared with a right carotid loop and with the left common carotid artery ligated low in the neck. Respiratory frequency (f) and body temperature (Tb) were measured while the animals were at rest in a warm chamber (36-40 degrees C) in four separate experiments: 1) right intracarotid infusion of hypertonic NaCl; 2) right intracarotid infusion of isotonic NaCl; 3) intravenous infusion of hypertonic NaCl; and 4) no infusions. In a fifth experiment, right and left jugular and cephalic venous blood samples were collected before, during, and after the hypertonic intracarotid infusions. A 10-min infusion of hypertonic NaCl into the right common carotid artery elevated right jugular plasma osmolality by 33 mosmol/kg H2O, left jugular plasma osmolality by 26 mosmol/kg H2O, and cephalic plasma osmolality by 8 mosmol/kg H2O. A significant reversible drop in f and a rise in Tb occurred during hypertonic intracarotid infusions. Neither intracarotid infusion of isotonic NaCl nor intravenous infusion of hypertonic NaCl affected f or Tb. In experiments with no infusion, f and Tb did not change. It is concluded that brain receptors sensitive to extracellular solute concentration are able to influence the rate of thermoregulatory panting. This may underlie, in part, the reduced evaporation and elevated body temperatures that occur in dehydrated mammals exposed to heat.

Animals↗
PubMed1985

Increased activity of a specific sialyltransferase in chronic myelogenous leukemia.

Granulocytes from patients with chronic myelogenous leukemia (CML) are morphologically identical to their normal counterparts but show marked differences in circulation patterns and in some membrane properties. We have previously shown that there is abnormal lectin binding to CML granulocytes, and aberrant sialylation of membrane glycoproteins. To examine the changes in sialylation of CML granulocytes further, we have studied membrane preparations from CML and normal granulocytes for specific sialyltransferase activity. Because sialyltransferase enzymes are specific for the configuration of the acceptor group, enzyme activity was assayed by measuring transfer of sialic acid from CMP-14C-sialic acid to substrates of defined structure. As compared with those of normal counterparts, CML extracts catalyzed a 50% higher overall rate of sialylation of asialofetuin, a substrate possessing both N- and O-linked acceptors. Studies of enzyme specificity utilizing porcine and ovine submaxillary mucins, antifreeze glycoprotein and alpha-1 acid glycoprotein as acceptors showed that the increased sialylation by CML extracts was due primarily to substrates with the O-linked Gal beta 1----3GaINAc acceptor group. These data suggest that sialyltransferase activity is increased in CML granulocytes compared to normal granulocytes and that the increased enzyme activity is specific for O-linked Gal beta 1----3GaINAc. This enzyme activity may be directly responsible for the abnormal membrane sialylation and pathophysiological behavior of these cells.

Asialoglycoproteins↗
PubMed1985

Effect of dietary selenium and injected gold thioglucose on adjuvant-treated rats.

Gold (Au) thioglucose, which has been used in the treatment of rheumatoid arthritis, inhibits selenium (Se)-glutathione peroxidase. Since Au and Se play roles in inflammation, the effects of dietary Se (0, 0.2, and 2.0 ppm for 10 weeks) and injected gold thioglucose (5 mg Au/day/kg body weight for 28 days) in adjuvant-treated rats were investigated. Au toxicity was evidenced by lower body weights and higher tissue weight/body weight ratios for kidneys and spleens of Au-treated rats. Adjuvant-induced inflammation, measured by paw thickness, was not influenced by dietary Se, although Au decreased inflammation in Se-deficient rats. Liver glutathione peroxidase activity was depressed by Se deficiency and by Au. Sulfhydryl levels in liver soluble fraction and plasma were highest for Se-deficient rats. Among liver, kidney, spleen, and plasma, thiobarbituric acid reactants were highest in kidneys of Au-treated rats and lowest in plasma of rats fed 2 ppm Se. gamma-Glutamyltranspeptidase activity in plasma indicated liver damage in Se-deficient rats. Kidney PGE2 output in 24-hour urine samples was unaffected by Au, Se, or adjuvant. Au-Se interactions in vivo are complex, but decreased glutathione peroxidase activity in Au-injected rats suggests that Se nutrition of Au-treated rheumatoid arthritis patients may be a practical concern.

Animals↗
PubMed1985

Effects of pyrimidine antagonists on sialic acid regeneration in HL-60 cells.

Because alterations in cell membrane sialoglycoconjugates can affect the behavior of neoplastic cells, we investigated the effects of in vitro treatment with antimetabolites used in cancer therapy on the expression of membrane sialic acid in cultured HL-60 leukemic cells. In these studies, cells were incubated with Vibrio cholerae neuraminidase to remove surface sialic acid. Reappearance of membrane sialic acid during drug treatment was followed (a) by measuring changes in radioactive surface labeling of viable cells with sodium metaperiodate-sodium[3H]-borohydride, (b) by measuring the decline in accessible surface galactosyl receptor sites which occurred coincident with membrane sialic acid replacement, and (c) by measuring the incorporation of [3H]glucosamine into membrane-associated neuraminidase-labile sialic acid. We were especially interested in learning whether drugs that affect intracellular pools of cytidine triphosphate (CTP), an important nucleotide intermediate in sialylation reactions, could inhibit regeneration of membrane sialic acid. 3-Deazauridine, a competitive inhibitor of CTP synthetase, depleted CTP pools and curtailed surface membrane resialylation with little or no effect on synthesis of de novo sialic acid from precursor sugars. The addition of cytidine restored CTP pools and sialic acid regeneration. Acivicin, a glutamine antagonist, also depleted CTP pools and curtailed surface membrane resialylation. In addition, it retarded de novo synthesis of sialic acid. The addition of cytidine restored intracellular CTP pools and sialic acid regeneration. However, both cytidine and guanosine were required to restore sialic acid synthesis from precursor sugars. 1-beta-D-Arabinofuranosylcytosine, a competitive inhibitor of sialic acid synthetase and of sialyltransferase, inhibited both de novo sialic acid synthesis and membrane resialylation. Only the latter effect was reversed by the addition of exogenous cytidine. Hydroxyurea, an agent shown previously to inhibit glycoconjugate production in hamster fibroblasts, curtailed membrane resialylation and de novo synthesis of sialic acid without depleting CTP pools. Doxorubicin, at levels that caused marked arrest of cell proliferation, had no effect on sialic acid synthesis or expression on the membrane surface. These data suggest that antimetabolites, apart from their cytotoxic effects or effects on cellular growth, may directly inhibit the expression of membrane sialic acid.(ABSTRACT TRUNCATED AT 400 WORDS)

3-Deazauridine↗
PubMed1985

Effect of gold on selenium and glutathione peroxidase activities in rat tissues.

Gold (Au) thioglucose, used to treat inflammatory diseases such as rheumatoid arthritis, inhibits the selenium (Se)-dependent glutathione peroxidase. The present study examines the ability of Au to act either as a Se antagonist or as a GSH peroxidase inhibitor in vivo. The effects of gold thioglucose loading on Se distribution, and on Se-dependent GSH peroxidase and GSH S-transferase, were examined in rats fed three dietary levels of Se (0, 0.2, and 2.0 ppm), and with or without adjuvant-induced inflammation. Kidney, liver, spleen, testes, and erythrocytes were selected for study based upon their high Se content and their ability to concentrate Au. Au loading increased kidney, liver, and spleen Se concentrations, and this effect was dependent upon dietary Se levels. Rats fed Se-supplemented diets had higher levels of Au in kidney, liver, and spleens than did rats fed a Se-deficient diet. Au loading decreased GSH peroxidase activity in kidney, liver, and erythrocytes. The decrease in GSH peroxidase in kidney and liver, and the increase in Se concentration in these tissues, suggest that Au-Se complexes may have limited the biosynthesis of the enzyme. Au affects Se distribution, and Se concentrates Au in tissues with a high lysosomal content.

Animals↗
PubMed1984

Cardiovascular and respiratory responses to heat in dehydrated dogs.

The effect of dehydration on rectal temperature, respiratory frequency, upper respiratory evaporation, cardiac output, and common carotid blood flow was studied in large mongrel dogs at rest at ambient temperatures between 25 and 45 degrees C. Measurements were made in animals hydrated ad libitum and when they had been dehydrated by removal of drinking water. In hydrated animals, mean body weight was 31.6 +/- 1.7 (SE) kg and plasma osmolality was 296 +/- 2 mosmol/kg H2O. Dehydration decreased body weight to 28.2 +/- 1.5 kg and increased osmolality to 328 +/- 5 mosmol/kg H2O. At all ambient temperatures, every dehydrated animal had a higher rectal temperature, lower respiratory frequency, lower upper respiratory evaporation, lower cardiac output, and lower common carotid blood flow. Rectal temperature, measured in seven animals, was constant as ambient temperature was raised from 25 to 45 degrees C in both the hydrated and dehydrated state, but was elevated by 0.72 degrees C in dehydrated animals. Hypothalamic temperature, measured in two animals, was elevated less than rectal temperature when they were dehydrated. Upper respiratory evaporation and respiratory frequency, measured in seven animals, increased with increasing ambient temperature in both the hydrated and the dehydrated dogs, but were lower at every ambient temperature in dehydrated animals. Cardiac output, measured in five animals, was lower in dehydrated animals at every ambient temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Cardiac output of dogs exercising in the heat.

We measured cardiac output and central blood temperature in five large dogs (27 kg mean body wt) running at 7.5 km/h for 30 min at two work loads and at low and high ambient temperature (Ta). Each animal ran on a level treadmill (O2 cost about 4 times that of resting) at 25 and 35 degrees C Ta and at a 20% slope (O2 cost about 10 times that of resting) at 25 and 35 degrees C Ta. Cardiac output (CO) was the same at 15 and 30 min of exercise at both work loads and both TaS. CO was higher at 35 degrees C Ta at both work loads. Blood temperature rose 0.6 degrees C during exercise on the level treadmill at 25 degrees C and stabilized after the 15th min of exercise. On the level treadmill at 35 degrees C, blood temperature increased by 1.9 degrees C after 30 min. During 30 min of running at 20% slope, blood temperature increased by 3.2 degrees C at 25 degrees C and by 4.6 degrees C at 35 degrees C. At these work loads the dog is able to increase CO during exercise in the heat. This response is similar to that of humans doing moderate exercise in the heat but is in contrast to that of humans doing heavy exercise in the heat, in whom CO shows a drop or no change compared with cool conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Thermoregulatory responses to exercise in dehydrated dogs.

Measurements of rectal temperature (Tre), water lost by evaporation (Eresp) and drooling, cardiac output (CO), and common carotid blood flow (CCBF) were made in dogs (mean hydrated wt 31.0 +/- 1.5 kg) running for 1 h on a level treadmill at 7.5 km/h at an ambient temperature of 25 degrees C. Each animal was studied when it was hydrated ad libitum and when it had been dehydrated by removal of drinking water until 9-10% of the initial body weight had been lost. Dehydrated exercising animals had significantly higher Tre and lower rates of Eresp, CO, and CCBF. Tre and Eresp were measured in seven animals. Average Tre during running was 39.11 +/- 0.10 degrees C in hydrated and 39.80 +/- 0.25 degrees C in dehydrated animals (P less than 0.01). Average Eresp during running was 3.9 +/- 0.3 g/min in hydrated animals and 2.3 +/- 0.3 g/min in dehydrated animals (P less than 0.01). Average CO during exercise, measured in five animals, was 11.1 +/- 0.7 1/min in the hydrated state and 8.6 +/- 0.5 1/min in the dehydrated state (P less than 0.01). Unilateral CCBF during exercise, measured in four animals, was 602 +/- 40 ml/min in the hydrated state and 418 +/- 22 ml/min in the dehydrated state (P less than 0.01). Water lost by drooling in seven exercising animals was 41.5 +/- 11 g/h when they were hydrated and 0.6 +/- 0.4 g/h when they were dehydrated. It is concluded that dehydrated dogs doing mild exercise can save water by reducing Eresp and regulating body temperature above hydrated levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Mechanism of action of divicine in a cell-free system and in glucose-6-phosphate dehydrogenase-deficient red cells.

Favism is an acute hemolysis occurring in glucose-6-phosphate dehydrogenase (G6PD)-deficient (Mediterranean variant) individuals after intake of fava beans. Divicine (D), 2,6-diamino-4,5-dihydroxypyrimidine, is present in high amounts in the beans, and is suspected to play a role in hemolysis. Its mechanism of action was studied in a cell-free system and in G6PD (Mediterranean variant)-deficient red cells (RBC). Upon hydrolysis of the inactive beta-glucoside vicine, reduced divicine is formed. Oxygen acts as a one- or two-electron acceptor; superoxide anion and hydrogen peroxide are formed, respectively, together with the semiquinoid free-radical form of D. This free radical gives an electron spin resonance (ESR) signal, which is similar to that of the alloxan free radical. Added reduced glutathione (GSH) is rapidly oxidized with a stoichiometry of one to one, and the ESR signal is abolished. Additional GSH is oxidized by hydrogen peroxide and by a slow redox cycle which continuously regenerates oxidized D. The fast-direct and the slow-indirect oxidation result in nonstoichiometric oxidation of GSH. D added to G6PD-deficient RBC rapidly oxidizes GSH with an end point kinetics and a stoichiometry of one to one. Hydrogen peroxide and superoxide anion are scavenged in the RBC and no redox cycling is taking place. No GSH is regenerated even after long incubation periods. After the primary event, i.e., oxidation of GSH and--SH groups, a number of metabolic, rheologic, and membrane modifications, together with increased erythrophagocytosis take place in G6PD-deficient, D-treated RBC only.(ABSTRACT TRUNCATED AT 250 WORDS)

Ascorbic Acid↗
PubMed1984

Immunotherapy for chronic myelogenous leukemia: survival not affected by treatment in the stable phase.

Thirty-one consecutive patients with chronic myelogenous leukemia were treated in the chronic phase with immunotherapy in addition to chemotherapy. Immunotherapy consisted of Bacillus Calmette-Guérin and allogeneic myeloblasts given by vaccination, and chemotherapy comprised busulfan p.o. in most patients. No randomly allocated control group was designated, but patient characteristics appear to be typical of those of other published groups. Twenty-eight of 31 patients were followed from diagnosis to death, and the three remaining patients were followed for over 5 years. The median survival of the patients in our group was 37 months. There was a constant rate of decline in survival with time, with a mean annual death rate of 30% per year. Twenty-five of the 31 patients terminated in blast crisis. One of 21 patients achieved complete remission in blast crisis of myeloid or indeterminate type, and three of four patients achieved complete remission for blast crisis of lymphoid type. The median survival, the rate of decline in survival, and the remission rate in blast crisis do not appear to differ from those of comparable groups of patients treated with chemotherapy alone.

Adult↗
PubMed1984

Aberrant sialylation of granulocyte membranes in chronic myelogenous leukemia.

Peripheral blood granulocytes from patients with chronic myelogenous leukemia (CML) were studied for accessibility of membrane sialic acid and galactose residues to sodium borohydride-3H radiolabeling after oxidation with sodium metaperiodate (PI/B3H4) or with galactose oxidase (GO/B3H4). Granulocytes from untreated patients with chronic myelogenous leukemia showed increased radiolabeling with PI/B3H4, and decreased labeling with GO/B3H4 when compared to normal granulocytes. Granulocytes from leukemic patients receiving chemotherapy showed normal labeling patterns. Gel electrophoresis of membrane extracts showed that the changes in PI/B3H4 and GO/B3H4 reactivity of CML cells were distributed over all membrane protein bands. Our data suggest that CML granulocyte membrane proteins are aberrantly sialylated, with decreased accessibility of galactose residues, and that these changes may be reversed by clinical drug treatment.

Cell Membrane↗
PubMed1983

Central nervous system toxicity of high-dose cytosine arabinoside.

Ten patients with refractory acute leukemia were treated with high-dose cytosine arabinoside (Ara-C) infusions. Nine patients had previously achieved at least one complete remission using standard chemotherapy protocols that include cytosine arabinoside. Eight of the ten had been on maintenance therapy. Twelve courses of treatment were given, with the cytosine arabinoside infused over 1-2 hours in a dose of 3 gm/m2. Each course consisted of 12 to 16 doses given at 12-hour intervals. The drug was generally well tolerated but five patients developed central nervous system symptoms characterized by ataxia, dysphasia, nystagmus, dysdiadochokinesis, and a decreased level of consciousness. These changes began 3 to 34 days after the initiation of therapy and were severe at the time of death in two of the patients. One complete and one partial remission, lasting 2.5 months and 1 month, respectively, were documented. This experience suggests that high-dose Ara-C is of limited usefulness in refractory acute leukemia and may be frequently associated with significant neurotoxicity.

Acute Disease↗