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T Graham

Publications and source records attributed to T Graham.

At least 91 records · Page 5Linked to original sources
PubMed1987

Engraftment of dogs with Ia-positive marrow cells isolated by avidin-biotin immunoadsorption.

Previous work has shown failure of engraftment in lethally irradiated dogs when autologous marrow was depleted of Ia-positive cells with an anti-Ia antibody and complement before infusion. In the current study, we have utilized an avidin-biotin immunoadsorption procedure to obtain a population of highly enriched Ia-positive cells for autologous bone marrow transplantation in dogs given lethal irradiation. Dog marrow cells (2.4 to 7.0 X 10(9) cells) that contained 8.6% to 19.9% Ia-positive cells were treated successively with monoclonal antibody 7.2, which reacts with a framework determinant of Ia-antigen, and biotin-conjugated goat antimouse immunoglobulin. These treated cells were passed over a column of avidin-Biogel (polyacrylamide) and the adherent cells removed by mechanical agitation. Seven lethally irradiated dogs were transplanted with 5.9 to 33.4 X 10(6) recovered adherent cells per kilogram of which 69.0% to 88.0% were Ia-positive. All dogs had hematologic recovery; six are alive and well with durable engraftment and one died on day 15 posttransplant. They are immunologically normal as determined by lymph node and bone marrow biopsies, lymphocyte function, and immunophenotyping of peripheral blood and bone marrow cells. These data provide further evidence that canine hematopoietic stem cells express Ia-like antigens and that these cells are capable of complete hematopoietic and immunologic reconstitution in an autologous model.

Animals↗
PubMed1987

Canine pluripotent hematopoietic stem cells and CFU-GM express Ia-like antigens as recognized by two different class II-specific monoclonal antibodies.

A previous study showed failure of autologous engraftment in lethally irradiated dogs when marrow was treated before infusion with anti-class II antibody 7.2 and complement. The current study extended this observation to a second monoclonal antibody (HB10a) that identifies a different determinant on Ia-like molecules. These results suggest the presence of Ia-like antigens on pluripotent hematopoietic stem cells or on "accessory cells" needed for sustained engraftment to occur. To distinguish between these two possibilities, stem cell-depleted Ia-positive peripheral blood leukocytes obtained by discontinuous albumin density gradient were added as probable source of accessory cells to the marrow inoculum that was depleted of Ia-positive cells by treatment with antibody 7.2 and complement. Eight of ten dogs failed to show engraftment, providing further support for the hypothesis that pluripotent stem cells and not accessory cells were affected by cytolytic treatment. To provide direct evidence for the presence of Ia-like antigens on canine pluripotent hematopoietic stem cells, autologous transplants were performed using 0.7 to 13 X 10(6) Ia (7.2)-positive marrow cells per kg obtained with the help of fluorescence-activated cell sorter. Of three evaluable dogs, two showed sustained and complete engraftment, indicating that Ia-like antigens, as recognized by anti-class II antibody 7.2, are expressed at least on part of canine pluripotent hematopoietic stem cells. Concurrent in vitro studies revealed that canine CFU-GM also expressed Ia-like antigens as recognized by the class II-specific monoclonal antibodies 7.2 and HB10a.

Animals↗
PubMed1986

Multiple controls of oxidative metabolism in living tissues as studied by phosphorus magnetic resonance.

Three types of metabolic control of oxidative metabolism are observed in the various tissues that have been studied by phosphorous magnetic resonance spectroscopy. The principal control of oxidative metabolism in skeletal muscle is by ADP (or Pi/phosphocreatine). This conclusion is based upon studies of arm muscles of humans during steady-state exercise. A work-cost (Vm vs. Pi/phosphocreatine) relationship follows a Michaelis-Menten rectangular hyperbola, where Km values from 0.5 to 0.6 and Vmax values from 50 to 200 (at nearly constant pH) are found in linearized plots of the equation V/Vmax = 1/(1 + 0.6 phosphocreatine/Pi) where V is work level (which is equal to the velocity of the enzymatic reaction) and Vmax is the maximal work capacity that is a measure of the enzyme activity (E) of oxidative metabolism. Adaptation to exercise enhances the slope of the work-cost relationship and causes large changes in Vmax or E. A second metabolic control may enhance the slope of the work-cost relationship but not Vmax. For example, the initiation of exercise can lead to an improved characteristic that can be explained by 2-fold increased substrate delivery, for example, increased oxygen delivery by microcirculatory control. Cardiac tissue of the adult dog affords an example of optimal endurance performance adaptation and exhibits the steepest work-cost relationship observed and is attributed to a coordinated control of substrate delivery that may involve Ca2+ and inorganic phosphate control of NADH; control of O2 delivery may also be involved. The calculated work-cost relationship is similar to that observed in the beagle heart. The theoretical curve illustrates that the liability of multiple controls is a sharp break point in metabolic control at the end of the multiple control range--a possible cause of instability of cardiac performance at high V/Vmax.

Acidosis↗
PubMed1985

Muscle performance and metabolism in maximal isokinetic cycling at slow and fast speeds.

To provide a description of the metabolic changes in muscle during maximal dynamic exercise, muscle biopsies were obtained in five healthy subjects before and after 30 s of isokinetic exercise at two pedaling frequencies (60 and 140 rpm) associated with contrasting fatigue characteristics. Higher peak power was attained at 140 rpm (1,473 + 185 W) (mean +/- SE) than at 60 rpm (1,122 +/- 70 W), but the decline in power during 30 s (fatigue index) was greater at 140 rpm (61.6 +/- 3.2 vs. 21.5 +/- 2.4%), total work in 30 s being similar (18.1 +/- 1.10 vs. 20.1 +/- 1.10 kJ). Changes in the concentration of muscle metabolites were similar; creatine phosphate concentration fell to approximately 50% of resting values, and the glycolytic intermediates glucose 6-phosphate, fructose 6-phosphate, and fructose 1,6-biphosphate increased up to 30-fold. Muscle lactate concentration ([La-]) was 29.0 +/- 3.98 and 31.0 +/- 4.31 mmol/kg wet wt immediately postexercise at 140 and 60 rpm, respectively. Even after only 10 s exercise (n = 2), large increases were measured in glycolytic intermediates and [La-]. In the two subjects, muscle [La-] increased to 17.2 and 15.1 mmol/kg at 140 rpm and to 14.3 and 14.2 mmol/kg at 60 rpm. In this type of exercise, glycogenolysis is activated very rapidly at both pedal speeds; the changes in glycolytic intermediates were consistent with rate-limiting steps at the phosphofructokinase and pyruvate dehydrogenase reactions. The greater fatigue at the higher speed is not accompanied by different biochemical changes than at 60 rpm.

Adenosine Triphosphate↗
PubMed1983

Interaction of Dictyostelium discoideum alpha-mannosidase with beef liver phosphomannosyl receptor. Effect of alkaline phosphatase treatment.

Both intracellular and secreted alpha-mannosidase from D. discoideum bind quantitatively and specifically to immobilized phosphomannosyl receptor from beef liver. Almost all the intracellular enzyme molecules retain tight binding capacity subsequent to exhaustive alkaline phosphatase treatment. This supports the idea that uncovered phosphates are not essential for optimal recognition by the phosphomannosyl receptor. However, approximately 50% of the extracellular enzyme was converted to a weak binding form by the same treatment.

Alkaline Phosphatase↗
PubMed1981

Alcohol ingestion and man's ability to adapt to exercise in a cold environment.

Previous work from this laboratory indicated that when alcohol was ingested prior to performing two hours of mild exercise in a cold environment, subjects experienced greater heat loss and lower blood glucose levels. The present study expanded the protocol to three hours in order to establish if these detrimental effects continued when blood alcohol levels declined. Young, male volunteers (n = 6) ingested water, water and alcohol (2.5 ml/Kg) or water, alcohol (2.5 ml/Kg) and dextrose (50 gm/150 ml water) on different occasions. The 3 treatments were administered by a balanced design. Following fluid ingestion, the subject performed intermittent, bicycle work (40% VO2max) with a 20 min work--10 min rest pattern for 3 hr. in a -5 degrees C environment. VO2, R, and blood glucose data did not reveal any significant metabolic effects of alcohol. The water-alcohol ingestion resulted in a peak blood level (13.05 +/- 2.34 mM l-1) after 69 +/- 39 min. During the third hour there was a decline to 60% of the peak value. With dextrose, the peak level was less (9.29 +/- 2.62 mM . l-1) (p less than or equal to 0.05) and occurred almost one hour later (p less than or equal to 0.05). Generally the alcohol-dextrose data were similar to the previous study in that the alcohol treatment resulted in a significantly greater heat loss (p less than or equal to 0.05). During the third hour the skin and core temperatures remained constant in the control and alcohol-dextrose treatments; however, in the alcohol series the values rose and approached control levels. The study confirmed that moderate levels of blood alcohol can impair thermoregulation while performing mild exercise in a cold environment and thus alcohol ingestion prior to any activity in a cold environment is contraindicated. However, the impairment dissipates when the blood alcohol is metabolized. When alcohol is ingested with dextrose, the alcohol effects are reduced.

Adaptation, Physiological↗
PubMed1980

The effects of hypercapnia on metabolic responses to progressive exhaustive work.

Altering CO2 storage has been shown to influence lactate metabolism. However, the metabolic effects on man during physical activity have not been well documented. Subjects (n = 8) performed a progressive bicycle test (beginning at 0 and increasing 30 W every 4 min to exhaustion) on two occasions (once inspiring compressed air and once 4% CO2 and 21% O2). The work time, peak Vo2, VCO2, and HR achieved were the same in the two trials for each subject. The VI was significantly (p less than or equal to 0.05) elevated throughout the CO2 work and the recovery. The O2 debt increased from a mean of 5.87 to 7.761 with CO2, although the difference was not significant. Blood lactate was lower (p less than or equal to 0.05) from the onset of the work and throughout both the exercise and the 30 min. recovery period. Peak lactate was decreased from a mean of 9.59 to 6.99mM.1(-1). The oxygen cost of the work was not altered but the blood lactate response to the activity was significantly depressed. The reduction in lactate could be due to glycolytic inhibition and enhanced fat metabolism. The data support, but do not prove, this hypothesis.

Adult↗
PubMed1980

Histopathologic evaluation of livers of pregnant hamsters infected with Leptospira canicola.

Pregnant hamsters were inoculated with Leptospira canicola by an intraperitoneal route. Grossly, the livers were enlarged and pale yellow. On light microscopic examination, disruption of the hepatic cords, as well as granulation of hepatocyte cytoplasm, was evident. On electron microscopic examination, the livers had evidence of severe cellular degradation as early as post-inoculation hour (PIH) 24. At PIH 96, pathologic changes were more pronounced. The rough endoplasmic reticulum was swollen and there was membrane disruption. These changes were not observed in the livers of control animals. In addition, livers of the fetuses at PIH 72 exhibited severe degenerative changes.

Animals↗
PubMed1980

Muscle metabolites, force, and perceived exertion bicycling at varying pedal rates.

Muscle metabolites, force, and perceived exertion bicycling at varying pedal rates. Med. Sci. Sports Exercise, Vol 12, No. 5, pp. 345-351, 1980. The relative significance of central (VE, Vo2, heart rate) or peripheral (muscle tension, muscle metabolites) factors on perceived exertion (RPE) was investigated with bicycle exercise by varying pedal rate while maintaining a constant power output. Six healthy male subjects exercised at zero load, submaximal (70% Vo2max) and maximal exercise intensities with pedal rates of 40, 60, 80, and 100 rpm. With changing pedal rate and constant power output, there were numerous examples of significant changes in the central factors with no change in RPE and vice versa. Similarly, measures of muscle and blood lactate, NAD, glycogen, ATP, and CP failed to demonstrate any local metabolic factor that correlated with RPE. Force exerted on the pedals and the rate of force generation approximated RPE changes, but the detailed correlation analysis was nonsignificant. None of the central or peripheral factors alone are related to RPE. Thus, RPE must be derived from a number of peripheral and/or central factors in a complex manner.

Adult↗