Biomedical subjects

D Thomason

Publications and source records attributed to D Thomason.

6 recordsLinked to original sources

PubMed2001

Fludarabine and melphalan-based conditioning for patients with advanced hematological malignancies relapsing after a previous hematopoietic stem cell transplant.

Severe regimen-related toxicity often complicates second transplant procedures performed in patients with hematological malignancies that have relapsed after an initial hematopoietic stem cell (HSC) transplant. Therefore, we studied the safety and efficacy of a reduced-intensity fludarabine and melphalan based conditioning regimen in 11 patients who had relapsed following an autologous (n = 7) or allogeneic (n = 4) HSC transplant. All patients received allogeneic peripheral blood HSC from either an HLA-identical (n = 7) or an HLA-mismatched (n = 4) relative. Diagnoses included AML (n = 9), ALL (n = 1), or Hodgkin's disease (n = 1). Only one patient was in complete remission at the time of second transplant. The median interval between first transplant and relapse was 163 days (range 58-1885). Recipients of HLA-mismatched transplants received antithymocyte globulin in addition to fludarabine and melphalan as part of the conditioning regimen. All 11 patients received acute GVHD prophylaxis consisting of tacrolimus and methotrexate. Ten of 11 patients achieved hematopoietic engraftment with a median time to absolute neutrophil count >0.5 x 10(9)/l and to platelet count of >20 x 10(9)/l of 14 and 19 days, respectively. All engrafting patients achieved 100% donor chimerism on initial analysis, except for one with persistent leukemia at day +19. Two patients experienced grade 3 regimen-related toxicity, manifesting as acute renal failure. Acute GVHD grades 2-4 occurred in two recipients and chronic GVHD in four. The 100-day mortality from all causes was 36%. Ten of 11 patients (91%) died a median of 140 days (range 9-996) after the second transplant. The causes of death included relapse (n = 5), sepsis (n = 4), and idiopathic pneumonia syndrome (n = 1). One patient with AML survives in remission at 880 days post-transplant. We conclude that fludarabine- and melphalan-based conditioning promotes full donor chimerism, even following HLA-mismatched transplants. However, the regimen may be more beneficial when applied to patients undergoing allogeneic HSC transplantation earlier in their disease course.

Adult↗

PubMed1989

Exercise effects on the size and metabolic properties of soleus fibers in hindlimb-suspended rats.

The soleus atrophies rapidly when a rat is subjected to hindlimb suspension (HS), probably as a result of a decrease in the force encountered by the muscle. To test this premise, adult female rats were HS and half the rats were exercised (HS-EX) on a treadmill for 1.5 h.d-1 at 20 m.min-1 and a 30% grade. After 4 weeks, the midbelly of the soleus was prepared for histochemical analysis. Fibers were typed as dark or light staining for myosin ATPase, alkaline preincubation. Fiber size and quantitative histochemical enzyme activities of succinate dehydrogenase (SDH) were determined using a computer enhanced image processing system. In comparison to age-matched controls, the soleus wet weight was 69 and 30% smaller in HS and HS-EX rats. The mean cross sectional area of the dark ATPase fibers was reduced by 46 and 18% and light ATPase fibers by 69 and 48% in the HS and HS-EX, respectively. The percent dark ATPase fibers increased from 10% in the control rats to 19 and 17% in the HS and HS-EX. In both suspended groups, SDH activities in light ATPase fibers were 40% higher than control. The SDH activity of the dark ATPase fibers of HS-EX was 20% higher than control, while the dark ATPase fibers of HS were similar to control. To determine the degree to which these increases in SDH could be related to reductions in fiber size rather than increases in the actual amount of protein, integrated activity (activity/min x area) was calculated per fiber.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

Formation of calcium-parvalbumin complex during contraction. A source of "unexplained heat"?

Computer simulation of the kinetics of the distribution of Ca between troponin, parvalbumin and the sarcoplasmic reticulum, during contraction and relaxation shows that parvalbumins can contribute significantly to the rate of relaxation and to the post contractile translocation of calcium. The binding of Ca to parvalbumin is an exothermic process which may account for about 20% of the 'unexplained heat' during contraction.

Animals↗

PubMed1982

Parvalbumins and muscle relaxation: a computer simulation study.

The distribution of Ca2+ and Mg2+ among the 'regulatory' cation binding sites of troponin (T-sites) and the strong, Ca2+-Mg2+ binding sites of troponin and parvalbumins (P-sites) in the sarcoplasm of a muscle was calculated. At rest, 60% of the T-sites were metal free, while 92% of the P-sites were loaded with Mg2+. In response to a Ca2+ pulse, troponin-calcium (T-Ca) complexes were rapidly formed, while the binding of Ca2+ to P-sites was limited by the slow rate of dissociation of the parvalbumin-magnesium (P-Mg) complexes. Muscle activation was not prevented by a high content of parvalbumins. Parvalbumin and the sarcoplasmic reticulum (SR) pump were complementary relaxing factors that removed Ca2+ from the cytosol and from the T-sites. Parvalbumins dominated the first part of relaxation, while the action of the SR was essential to ensure the return to a very low level of free Ca2+ ion and of T-Ca. After relaxation, a large fraction of the Ca2+ pulse was still bound to parvalbumins and returned slowly to the SR during the recovery. When the SR activity was reduced, the presence of parvalbumins preserved a fast rate of relaxation, at least for a few contractions. This may have a high adaptive value in cold-blooded animals.

Amphibians↗

PubMed1978

The accumulation and elimination of tissue residues after feeding pentachloronitrobenzene to White Leghorn cockerels.

Day-old White Leghorn cockerels were fed graded levels (10, 50, 100, and 1000 ppm) of pentachloronitrobenzene (PCNB) containing pentachlorobenzene (PCB), tetrachloronitrobenzene (TCNB), and hexachlorobenzene (HCB) at trace contaminants, for 12 weeks. Bioaccumulation of PCNB and its metabolites in tissues does not appear to occur to any major extent. The contaminants of PCNB, HCB, and PCB were found to accumulate to a greater degree in adipose tissue than does PCNB itself. TCNB was also detected in adipose tissue and in trace amounts in other tissues. PCNB accumulated to the highest concentration in body fat followed by gizzard and kidney. Only traces of PCNB were found in heart, liver, leg, and heart muscle. Metabolites, pentachloroaniline (PCA), and pentachlorphenylmethylsulfide (PCMS) were found in only trace quantities following the feeding of 1000 ppm PCNB. Half-life values for the depletion of the contaminants of PCNB, PCB, and HCB were determined in adipose tissue of cockerels; values as high as 53 and 95 days were found for PCB and HCB, respectively.

Adipose Tissue↗

PubMed1970

Effect of Intramuscular or Intrahepatic Injections of Clostridium perfringens on Rabbit Serum Lactate Dehydrogenase.

Serum lactate dehydrogenase (LDH) activity, LDH isoenzyme pattern, phospholipase C activity, phosphorous level, hemoglobin, and erythrocyte osmotic fragility were followed in rabbits after intramuscular (IM) or intrahepatic (IH) injections of Clostridium perfringens. On the first day after IM injection, there was a drop in LDH activity; this was followed by an increase of LDH activity on the third and sixth day. On the seventh day, LDH activity began to decline, and by the ninth day it had almost returned to normal. On the sixth day after IM injection, there was an increase in serum LDH isoenzyme 5, hemoglobin, and erythrocyte osmotic fragility, but the increase of erythrocyte osmotic fragility and serum hemoglobin could not be attributed to phospholipase C activity since that enzyme was not detected nor was there an increase in serum phosphorus. C. perfringens was recovered by culturing the wound of IM-injected rabbits but not recovered from IH-injected rabbits. Rabbits injected IH showed no change from normal values in any of the tests performed.

Journal Article↗