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Biomedical subjects

T W Martin

Publications and source records attributed to T W Martin.

At least 19 recordsLinked to original sources
PubMed2005

Convection in vibrated annular granular beds.

The response to vibration of a granular bed, consisting of a standard cylindrical geometry but with the addition of a dissipative cylindrical inner wall, has been investigated both experimentally (using positron emission particle tracking) and numerically (using hard sphere molecular dynamics simulation). The packing fraction profiles and granular temperature distributions (in both vertical and horizontal directions) were determined as a function of height and distance from the axis. The two sets of results were in reasonable agreement. The molecular dynamics simulations were used to explore the behavior of the granular bed in the inner wall-outer wall coefficient of restitution phase space. It was observed that one could control the direction of the toroidal convection rolls by manipulating the relative dissipation at the inner and outer walls via the coefficients of restitution, and with several layers of grains it was seen that double convection rolls could also be formed, a result that was subsequently confirmed experimentally.

Journal Article↗
PubMed2002

Molecular basis of mitomycin C resistance in streptomyces: structure and function of the MRD protein.

Mitomycin C (MC) is a potent anticancer agent. Streptomyces lavendulae, which produces MC, protects itself from the lethal effects of the drug by expressing several resistance proteins. One of them (MRD) binds MC and functions as a drug exporter. We report the crystal structure of MRD and its complex with an MC metabolite, 1,2-cis-1-hydroxy-2,7-diaminomitosene, at 1.5 A resolution. The drug is sandwiched by pi-stacking interactions of His-38 and Trp-108. MRD is a dimer. The betaalphabetabetabeta fold of the MRD molecule is reminiscent of methylmalonyl-CoA epimerase, bleomycin resistance proteins, glyoxalase I, and extradiol dioxygenases. The location of the binding site is identical to the ones in evolutionarily related enzymes, suggesting that the protein may have been recruited from a different metabolic pathway.

Amino Acid Sequence↗
PubMed2000

The functional implications of the dimerization of the catalytic subunits of the mammalian brain platelet-activating factor acetylhydrolase (Ib).

The mammalian brain contains significant amounts of the cytosolic isoform Ib of the platelet-activating factor acetylhydrolase (PAF-AH), a unique type of PLA2. This oligomeric protein complex contains three types of subunits: two homologous (63% identity) 26 kDa catalytic subunits (alpha(1) and alpha(2)) which harbor all the PAF-AH activity, and the 45 kDa beta-subunit (LIS1), a product of the causal gene for Miller-Dieker lissencephaly. During fetal development, the preferentially expressed alpha(1)-subunit forms a homodimer, which binds to a homodimer of LIS1, whereas in adult organisms alpha(1)/alpha(2) and alpha(2)/alpha(2) dimers, also bound to dimeric LIS1, are the prevailing species. The consequences of this "switching" are not understood, but appear to be of physiological significance. The alpha(1)- and alpha(2)-subunits readily associate with very high affinity to form homodimers. The nature of the interface has been elucidated by the 1.7 A resolution crystal structure of the alpha(1)/alpha(1) homodimer (Ho et al., 1997). Here, we examined the functional consequences of the dimerization in both types of alpha-subunits. We obtained monomeric protein in the presence of high concentrations (>50 mM) of Ca2+ ions, and we show that it is catalytically inactive and less stable than the wild type. We further show that Arg29 and Arg22 in one monomer contribute to the catalytic competence of the active site across the dimer interface, and complement the catalytic triad of Ser47, Asp192 and His195, in the second monomer. These results indicate that the brain PAF-acetylhydrolase is a unique PLA2 in which dimerization is essential for both stability and catalytic activity.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1998

Structure of the gangrene alpha-toxin: the beauty in the beast.

The crystal and molecular structure of the Clostridium perfringens alpha-toxin crowns over a century-long research into the mechanisms of pathogenesis of gas gangrene. The structure reveals a two-domain enzyme, with a catalytic all-helical N-terminal domain, and a C-terminal domain similar in its jelly-roll topology to those found in pancreatic lipase and lipoxygenases.

Bacterial Toxins↗
PubMed1994

Response to upright exercise after cardiac transplantation.

There is little information on the hemodynamic response to upright exercise in patients who have undergone cardiac transplantation. We compared the hemodynamic and metabolic response to upright bicycle exercise in 11 patients with heart transplants and 12 controls. Patients performed two tests--a steady-state test with a right heart catheter and a maximal incremental test. During steady-state exercise at 20% of their predicted maximum workload, patients with heart transplants had a higher (mean +/- SD, p < 0.05) heart rate (108 +/- 11 vs. 96 +/- 15 beats/min), mean systemic blood pressure (116 +/- 17 vs. 101 +/- 11 mmHg), mean pulmonary artery pressure (29 +/- 9 vs. 22 +/- 3 mmHg), mean pulmonary wedge pressure (14 +/- 6 vs. 9 +/- 2), pulmonary (302 +/- 101 vs. 220 +/- 50 d-sec-cm-5-m2) and systemic (2049 +/- 531 vs. 1459 +/- 520) resistance indices, and lactate concentration (3.4 +/- 1.7 vs. 1.7 +/- 0.4 mmol/l), and a lower stroke index (39 +/- 8 vs. 50 +/- 8 ml/m2) compared with controls. Cardiac index, right atrial pressure, and mixed venous oxygen saturation were similar. During the maximal exercise test, patients with heart transplants achieved a significantly lower percentage of predicted maximum heart rate (77 +/- 13 vs. 91 +/- 8%), workload (70 +/- 25 vs. 102 +/- 23%), oxygen consumption (63 +/- 11 vs. 108 +/- 19%), and ventilation (67 +/- 18 vs. 89 +/- 15%) compared with controls. Heart transplant patients also had a lower blood pressure and anaerobic threshold. We conclude that heart transplant patients have an altered hemodynamic and metabolic response to upright bicycle exercise.

Adult↗
PubMed1993

White therapists' differing perceptions of black and white adolescents.

The literature provides evidence that therapists' misunderstanding of minority cultures may be responsible for higher dropout rates and difficulty in forming congruent problem conceptualization. In this study, therapists' perceptions of the behaviors of black and white adolescents were examined. One group of 20 psychotherapists was presented with a scenario involving a white adolescent and a second group of 20 psychotherapists was presented with an identical scenario involving a black adolescent. The therapists rated the clinical significance of each of the behaviors that were present in the scenario. The behaviors of the black adolescent were rated overall as less clinically significant than the behaviors of the white adolescent. In addition, there were differences in the perceptions of specific behaviors. It is suggested that findings from this type of study can help identify misperceptions about a client's culture, which can aid in designing curricula for training therapists to be culturally sensitive.

Adolescent↗
PubMed1993

Demonstration of coexistent B-cell lymphoma and therapy-related acute myelogenous leukemia in lymph nodes by flow cytometry and immunohistochemistry. Case report and review of the literature.

A 58-yr-old white woman, with a 9-yr history of non-Hodgkin's lymphoma with recurrences and multi-modality therapy, presents with acute leukemia and residual lymphadenopathy. By flow cytometric analysis, cytochemistry, and cytomorphology, the leukemia is classified as acute myelogenous leukemia (AML), M4, and the lymph nodes are found to contain residual NHL in addition to an AML infiltrate. Immunohistochemistry performed on the lymph nodes correlates with the flow cytometric data. A review of the literature of AML secondary to therapy for non-Hodgkin's lymphoma is also conducted. There are no documented cases in the English literature of simultaneous involvement of lymph nodes by residual lymphoma and an AML infiltrate. Thus, this report is unique in the simultaneous involvement of lymph nodes by residual lymphoma and therapy-related AML. It emphasizes the application and usefulness of flow cytometry and immunohistochemistry in such cases.

Female↗
PubMed1992

Comparison of adenosine, dipyridamole, and dobutamine in stress echocardiography.

OBJECTIVE: To compare adenosine, dipyridamole, and dobutamine in stress echocardiography with regard to sensitivity, specificity, accuracy, and side effects. DESIGN: Crossover, blinded comparison, with coronary angiography serving as the criterion standard. SETTING: U.S. Army tertiary care hospital. PARTICIPANTS: Forty participants, 25 with coronary disease and 15 without coronary disease. Patients were eligible if they had coronary angiography within 6 weeks of stress testing or if they had a risk for coronary disease of less than 5%. MEASUREMENTS: Left ventricular wall motion was recorded after dobutamine (0.38 mg/kg body weight), adenosine (0.84 mg/kg body weight), and dipyridamole (0.84 mg/kg body weight) stress testing. Stress echocardiographic evaluation was considered to be abnormal if the patient developed new or progressive wall motion abnormalities. The rate of side effects for the types of echocardiography and the patient preference were recorded. MAIN RESULTS: The sensitivity of dobutamine stress echocardiography (76%; 95% CI, 59% to 93%) was significantly higher than that of adenosine echocardiography (40%; CI, 21% to 59%; P less than 0.001) and that of dipyridamole echocardiography (56%; CI, 37% to 75%; P = 0.019). The specificity of adenosine testing (93%; CI, 80% to 100%) was significantly higher than that of dobutamine echocardiography (60%; CI, 35% to 85%; P = 0.008) and that of dipyridamole echocardiography (67%; CI, 43% to 91%; P = 0.028). Symptoms were more frequent with adenosine echocardiography (100%) than with dipyridamole (88%; P less than 0.001) or dobutamine (80%; P less than 0.001) echocardiography. Treatment for persistent symptoms was required in more patients after dipyridamole echocardiography (40%) than after dobutamine (12%; P less than 0.001) or adenosine (0%; P less than 0.001) echocardiography. More patients preferred dobutamine (48%) or dipyridamole (40%) echocardiography to adenosine echocardiography (12%; P less than 0.001). CONCLUSIONS: Dobutamine stress echocardiography is more sensitive and is better tolerated than adenosine or dipyridamole stress echocardiography. Adenosine echocardiography is more specific than dobutamine or dipyridamole echocardiography and is less likely to cause persistent symptoms.

Adenosine↗
PubMed1992

Effect of exercise on indices of valvular aortic stenosis.

Changes in the physiologic state of the patient may affect indices of valvular aortic stenosis. We determined the effects of supine exercise on the Gorlin valve area, Cannon valve area, aortic valve resistance, and a modified stroke work loss index in 80 patients with aortic stenosis. Exercise caused a significant increase in the Gorlin and Cannon valve area, while work loss and valve resistance decreased significantly. The average percent change in work loss, 12.2%, was lower than the other indices (P less than 0.02), i.e., 15.3% for valve resistance, 18.6% for the Gorlin area, and 19.3% for the Cannon area. The correlation between the rest and exercise measurements was highest for work loss (r = 0.94), compared to 0.93, 0.88, and 0.89 for the other 3 indices, respectively. In patients with a Gorlin area below 1 cm2, exercise caused a significant decrease in work loss, but not Cannon area or valve resistance. However, the percent change was significantly lower and the correlation was better with the work loss index. We conclude that the work loss index is less affected by supine exercise than other indices of aortic stenosis.

Aortic Valve↗
PubMed1992

Comparison of exercise electrocardiography and dobutamine echocardiography.

It is uncertain whether dobutamine echocardiography is a better test than exercise electrocardiography for the detection of coronary disease in patients who can exercise. We compared the hemodynamics, sensitivity, and specificity of these tests in 24 patients, 16 with coronary disease and 8 controls. The tests were performed within six weeks of one another and were interpreted without knowledge of other clinical data. The exercise electrocardiogram was considered abnormal if the patient developed one mm of ST-segment depression, while the dobutamine test (up to 40 micrograms/kg/min) was considered abnormal if the patient developed ST-segment depression or a left ventricular wall motion abnormality. Exercise testing resulted in a higher heart rate (145 +/- 29 vs. 110 +/- 24, p less than 0.001) and blood pressure (176 +/- 31 vs. 148 +/- 24, p less than 0.001). Dobutamine testing was 25% more sensitive than exercise testing (94 vs. 69%, 95% confidence interval for difference is 0 to 50%, p = 0.09), while exercise testing was 38% more specific (88 vs. 50%, 95% confidence interval for difference is -3 to 79%, p = 0.14). We conclude that exercise results in a higher heart rate and blood pressure than dobutamine infusion. Differences in sensitivity and specificity are inconclusive, but indicate that the sensitivity of exercise testing is, at best, equivalent to dobutamine testing, while any increase in specificity with dobutamine testing, compared with exercise testing, would not be clinically significant.

Aged↗
PubMed1992

Use of arm crank exercise in the detection of abnormal pulmonary gas exchange in patients at low altitude.

BACKGROUND: The measurement of arterial blood gases, P(A-a)O2 and VD/VT, during cycle ergometry is the "gold standard" for the assessment of pulmonary gas exchange. However, some patients are unable to perform cycle ergometry because of other medical problems. STUDY OBJECTIVE: To determine whether arm crank exercise could be used to reliably detect gas exchange abnormalities compared to cycle ergometry. PARTICIPANTS: Fifteen patients with a variety of pulmonary disorders, who were referred for exertional dyspnea. DESIGN: All patients performed maximal arm crank and cycle exercise. Arterial blood gases, VO2, VCO2, and VE were measured at rest and during exercise. RESULTS: Compared to peak cycle exercise (mean +/- SD), PaO2 (85 +/- 14 vs 75 +/- 13 mm Hg), SaO2 (94 +/- 2 vs 91 +/- 4 percent), VD/VT (0.21 +/- 0.07 vs 0.19 +/- 0.08), and pH (7.37 +/- 0.04 vs 7.34 +/- 0.03) were significantly higher during peak arm crank exercise. The P(A-a)O2 (18 +/- 13 vs 29 +/- 12 mm Hg) was narrower, and PaCO2 (29 +/- 3 vs 29 +/- 4 mm Hg) and PAO2 (104 +/- 4 vs 103 +/- 4 mm Hg) were similar. Six patients had normal gas exchange during cycle exercise at low altitude (P[A-a]O2 less than or equal to 27 mm Hg, PaO2 greater than or equal to 65 mm Hg, VD/VT less than or equal to 0.18) and nine were abnormal. Utilizing criteria specific for arm crank at low altitude, the same six patients had normal gas exchange (P[A-a]O2 less than or equal to 13 mm Hg, PaO2 greater than or equal to 85 mm Hg, VD/VT less than or equal to 0.26), and the remaining nine were abnormal. The P(A-a)O2 during peak arm crank was the most useful criterion in identifying patients with abnormal gas exchange. CONCLUSION: Proposed criteria for arm crank exercise testing accurately identified all patients with normal and abnormal pulmonary gas exchange during cycle exercise. The data from the present study suggest that arm crank can be an acceptable alternative exercise testing modality for the assessment of pulmonary gas exchange.

Adult↗
PubMed1991

Coexistence of essential thrombocythemia and chronic lymphocytic leukemia.

A patient with chronic lymphocytic leukemia (CLL) and essential thrombocythemia is described. The two disorders were diagnosed synchronously. This association was not treatment related. Review of the literature revealed an additional 9 case reports of CLL associated with myeloproliferative disorders, but none with essential thrombocythemia.

Aged↗
PubMed1991

Gas exchange during maximal upper extremity exercise.

STUDY OBJECTIVE: to characterize gas exchange and cardiopulmonary performance during maximal progressive arm crank exercise. DESIGN: Cardiopulmonary variables were measured and arterial blood gases were determined in blood samples obtained from an indwelling radial arterial catheter during arm crank exercise (34 watts/min). Arm crank exercise was compared to maximal leg exercise performed by a different but comparable group of subjects from a previous study. PARTICIPANTS: 19 healthy young (mean +/- SEM: 20 +/- 1 yr) black males. RESULTS: Peak arm crank exercise resulted in lower values compared to peak leg exercise for: power (129 +/- 2 vs 253 +/- 10 W), VO2 (2.17 +/- 0.04 vs 3.26 +/- 0.14 L/min); VCO2 (2.9 +/- 0.11 vs 4.32 +/- 0.17 L/min); HR (168 +/- 3 vs 189 +/- 3 beats/min); AT (1.15 +/- 0.05 vs 1.83 +/- 0.07 L/min); and VE (101 +/- 2 vs 144 +/- 8 L/min), respectively. Arm crank exercise (baseline vs peak) elicited an impressive improvement in PaO2 (85 +/- 1 to 97 +/- 1 mm Hg), no change in SaO2 (96 +/- 0.2 to 96 +/- 0.2 percent), no significant increase in P(A-a)O2 (3 +/- 0.7 to 5 +/- 0.9 mm Hg) and an appropriate trending decrease in VD/VT (0.22 +/- 0.01 to 0.17 +/- 0.01). Peak arm crank values were significantly different from peak cycle exercise for PaO2 (82 +/- 2.2 mm Hg), SaO2 (93 +/- 0.4 percent), P(A-a)O2 (21 +/- 1.9 mm Hg) and VD/VT (0.08 +/- 0.01). At comparable levels of VO2 for arm crank and cycle exercise (2.17 +/- 0.04 vs 2.26 +/- 0.08 L/min), significant differences were observed for PaO2 (97 +/- 1.4 vs 81 +/- 1.9 mm Hg); SaO2 (96 +/- 0.2 vs 94 +/- 0.4 percent); P(A-a)O2 (5 +/- 0.9 vs 14 +/- 1.5 mm Hg); and VD/VT (0.17 +/- 0.01 vs 0.08 +/- 0.01), respectively. CONCLUSIONS: Maximal arm crank exercise represents a submaximal cardiopulmonary stress compared to maximal leg exercise. The differences in gas exchange observed at peak exercise between arm crank and leg exercise for the most part reflect the lower VO2 achieved. However, the persistence of these gas exchange differences even at a comparable level of VO2 suggests that factors other than VO2 may be operative. These factors may include differences in alveolar ventilation, CO2 production, ventilation-perfusion inequality, diffusion, and control of breathing.

Adult↗
PubMed1990

Ca2(+)-dependent synthesis of prostaglandin I2 and mobilization of arachidonic acid from phospholipids in cultured endothelial cells permeabilized with saponin.

The feasibility of using saponin as a permeabilization agent to study the effect of free Ca2+ concentration ([Ca2+]f) on prostaglandin I2 (PGI2) synthesis and mobilization of arachidonic acid from membrane phospholipids was investigated in cultured bovine pulmonary artery endothelial cells (BPAEC). Treatment of BPAEC with 20 micrograms/ml saponin caused selective permeabilization of the plasma membrane as determined by measurements of the release of lactate dehydrogenase and beta-hexosaminidase. In cells prelabeled with [3H]arachidonic acid for 22 h, permeabilization with 20 micrograms/ml saponin induced PGI2 synthesis and release of [3H]arachidonic acid from membrane phospholipids. These effects were dependent upon [Ca2+]f in the range 72 nM to 5 microM. Release of [3H]arachidonic acid from phospholipid classes was determined in suspensions of BPAEC prelabeled with [3H]arachidonic acid and permeabilized with 20 micrograms/ml saponin. At [Ca2+]f optimal for PGI2 synthesis, 16.2% of the total incorporated [3H]arachidonic acid was released from phosphatidylinositol (3.4%), phosphatidylethanolamine (3.5%) and phosphatidylcholine (9.3%). The time course and dependence upon [Ca2+]f of [3H]arachidonic acid release from phospholipids correlated with PGI2 synthesis. The amount of PGI2 synthesized in permeabilized BPAEC was similar to that in cell cultures treated with the calcium ionophore A23187. In comparison, however, PGI2 synthesis induced by A23187 was associated with less release of [3H]arachidonic acid from membrane phospholipids, e.g., 2.3% versus 16.2%. The greater loss of [3H]arachidonic acid from phospholipids in saponin-permeabilized BPAEC was most likely due to the loss of cell integrity and/or nonspecific effects of the detergent on phospholipases. Despite these limitations, the Ca2+ dependence observed for PGI2 synthesis and [3H]arachidonic acid mobilization suggest that saponin-permeabilization may provide a useful system for studies of the intracellular events triggered by the rise in intracellular Ca2+ which culminate in PGI2 synthesis.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Phosphatidylcholine hydrolysis stimulated by phorbol myristate acetate is mediated principally by phospholipase D in endothelial cells.

The mechanism of phosphatidylcholine (PC) degradation stimulated by phorbol myristate acetate (PMA) was investigated in bovine pulmonary artery endothelial cells prelabeled with [methyl-3H]choline ([3H]choline) or [9,10-3H]myristic acid ([3H]myristic acid). Both labels were selectively incorporated into PC, and addition of PMA stimulated comparable losses of 3H from PC in cells prelabeled with [3H]choline or [3H]myristate. In cells prelabeled with [3H]choline, the loss of 3H from PC correlated with a rapid increase in intracellular free [3H]choline. The increase in intracellular [3H]choline stimulated by PMA was not preceded by an increase in any other 3H-labeled PC degradation product. PMA did not stimulate the formation of PC deacylation products in cells prelabeled with [3H]choline. In permeabilized cells prelabeled with [3H]choline, PMA stimulated the formation of [3H]choline but not [3H]phosphocholine. In intact cells prelabeled with [3H]myristate, the loss of 3H from PC induced by PMA correlated with the formation of [3H]phosphatidic acid ([3H]PA) and [3H]diacylglycerol. In the presence of ethanol, PMA stimulated the formation of [3H]phosphatidylethanol ([3H]PEt) at the expense of [3H]PA. The time-course of [3H]PEt formation was similar to the time-course of intracellular [3H]choline formation in cells stimulated with PMA. These data taken together support the notion that PC degradation in endothelial cells stimulated with PMA is mediated principally by phospholipase D. PC breakdown via phospholipase D was not observed in cells treated with phorbol esters incapable of interacting with protein kinase C. Activation of phospholipase D by phorbol esters was inhibited by long-term pretreatment of cells with PMA to down-regulate protein kinase C and by pretreatment of the cells with staurosporine. These data support the notion that activation of phospholipase D by phorbol esters is dependent upon protein kinase C.

Alkaloids↗