Biomedical subjects
Publications and source records attributed to D Thomas.
Poor economic conditions in Vietnam have encouraged large numbers of people seeking a better life in the West to join the flow of political refugees leaving the country as "boat people". We report the events surrounding one such group of people who were rescued from the South China Sea by the Outback 88 Task Group.
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Gel-permeation high-performance liquid chromatography (HPLC) and reversed-phase HPLC were used to separate a mixture of peptides, produced at pilot-plant scale by peptic hydrolysis of bovine haemoglobin. Volatile buffers were employed in both HPLC techniques in order to get an easy recovery of peptides for further applications. The method is more rapid than low-pressure gel filtration. Amino acid analysis and fast atom bombardment mass spectrometry confirmed the purity, and allowed accurate molecular weights to be determined, for isolated peptides. These data demonstrate that such efficient techniques, usually used to resolve hydrolysates obtained in batch with pure substrates and highly specific enzymes, can be employed to resolve complex enzymatic hydrolysates of crude protein.
Sorbitol, added as a depressor of water activity in the reaction medium of yADH, can modify the kinetic behaviour of the enzyme towards the four substrates tested: ethanol, propanol, butanol and pentanol, as well as towards the coenzyme NAD. All apparent Km values of the alcohol substrates and NAD decreased as the additive concentration increased. However, the additive-caused modifications of the enzyme activity were found to depend on the carbon-chain length of the alcohol substrate, in other words, the catalytic selectivity of the enzyme towards different substrates was changed by the additive. These results and supplementary experiments suggested that sorbitol may have two opposing effects on the enzyme: the positive effect leads the enzyme to adopt a conformation which is more accessible to its substrates; while the negative effect results in a diffusional constraint for the enzyme reaction. Observed results were the combination of the two opposing effects.
To determine the incidence of secondary cancers after bone marrow transplantation, we reviewed the records of all patients at our center who received allogeneic, syngeneic, or autologous transplants for leukemia (n = 1926) or aplastic anemia (n = 320). Thirty-five patients were given a diagnosis of secondary cancer between 1.5 months and 13.9 years (median, 1.0 year) after transplantation. Sixteen patients had non-Hodgkin's lymphomas, 6 had leukemias, and 13 had solid tumors (including 3 each with glioblastoma, melanoma, and squamous-cell carcinoma). There were 1.2 secondary cancers per 100 exposure-years during the first year after transplantation (95 percent confidence interval, 0.7 to 2.0). The rate declined to 0.4 (95 percent confidence interval, 0.2 to 0.7) after one year. The age-adjusted incidence of secondary cancer was 6.69 times higher than that of primary cancer in the general population. In a multivariate model, the predictors (and relative risks) of any type of secondary cancer were acute graft-versus-host disease treated with either antithymocyte globulin (relative risk, 4.2) or an anti-CD3 monoclonal antibody (13.6) and total-body irradiation (3.9). Two additional factors were associated with secondary non-Hodgkin's lymphomas: T-lymphocyte depletion of donor marrow (12.4) and HLA mismatch (3.8). We conclude that recipients of bone marrow transplantation have a low but significant risk of a secondary cancer, particularly non-Hodgkin's lymphoma.
1. Bistable (multiple stationary states) dynamic behaviour in the activity of glucose-6-phosphate dehydrogenase that was subjected to successive pH change was demonstrated in an open continuously stirred tank reactor. Although the enzyme under study did not exhibit an autocatalytic effect and was homogeneously distributed, bistability was shown to occur. 2. The successive pH changes of the enzyme solution corresponded to a pH transition (8.3 in equilibrium 2), i.e. an acidification (forward direction) and an alkalinization (reverse direction). By use of intrinsic protein fluorescence methods, a glucose-6-phosphate dehydrogenase conformational hysteresis was shown to exist concomitant with the pH transition before and after enzyme injection into the reactor. 3. The results obtained suggest that the enzyme behaves, conformationally, as a memory device that stores information about its pH history (i.e. the enzyme records information in its structure about the environment to which it was previously exposed) and transduces it in a non-linear dynamic fashion, producing the bistable behaviour observed in the open reactor.
A new approach for the study of an enzyme's relationship with its own reaction medium has been developed. One technique of micellar enzymology is the use of pseudohomogeneous systems composed of surfactant/water/organic solvent. In such systems, the physicochemical properties and textures of the medium depend on the relative ratios of the different components. Enzymes are catalytically active in such systems and up to the present have been studied in different microenvironments, such as micelles, microemulsions and lyotropic liquid crystals. Our purpose was to develop a system in which the enzyme could, by its activity, modify one of the components in such a way that the relative ratios among them changed sufficiently to produce a transition from one phase domain to another. The three components, water (or glucose in water), octanol and octyl-beta-D-glucoside, form a classical ternary water/oil/surfactant system. The relevant phase diagram shows different macroheterogeneous phases and microstructured domains. The enzyme beta-D-glucosidase hydrolyses octyl-beta-D-glucoside to form glucose and octanol. The enzyme was found to change the relative ratios of water (or glucose in water), octanol and octyl-beta-D-glucoside in such a manner that the physicochemical structure of the medium was modified. At the beginning of the reaction beta-D-glucosidase was present in a micellar solution of octyl-beta-D-glucoside in water. As the enzymatic reaction proceeded, the medium became biphasic. One of the two phases was the micellar solution of octyl beta-D-glucoside in water, while the other phase was either a microemulsion or a liquid crystalline phase. In addition the enzyme, through its catalytic activity, was able to modify the physiocochemical properties of the reaction medium.
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Different kinds of interactions involved in the properties of ovomucin gel formation from hen egg white were studied by combining physical and biochemical methods. A decrease in viscosity of the ovomucin gel was observed when it was subjected to chymotrypsin or sonication treatment. The viscosity decrease correlated with a change from non-Newtonian to Newtonian properties of the ovomucin gel. By treatment of the gel with either 5 M guanidinium HCl, 6 M urea, or 5% sodium dodecyl sulfate a change from non-Newtonian to Newtonian properties was also obtained. Although high ionic strength or sialic acid liberation from the ovomucin gel by neuraminidase treatment provoked a decrease in viscosity, it was not followed by a change in non-Newtonian properties. The results obtained suggest that different noncovalent interactions might be involved in gel formation. Electrostatic interactions (partially destroyed by sialic acid removal or 2 M NaCl) and hydrophobic interactions might be responsible for protein-mucin and mucin-mucin interactions. Other bonds susceptible to chymotrypsin treatment and sonication would be involved in the interaction between mucin subunits.
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In Saccharomyces cerevisiae the HOM2 gene encodes aspartic semi-aldehyde dehydrogenase (ASA DH). The synthesis of this enzyme had been shown to be derepressed by growth in the presence of high concentrations of methionine. In the present work we have cloned and sequenced the HOM2 gene and found that the promoter region of this gene bears one copy of the consensus sequence for general control of amino acid synthesis. This prompted us to study the regulation of the expression of the HOM2 gene. We have found that ASA DH is the first reported enzyme of the related threonine and methionine pathway to be regulated by the general control of amino acid synthesis.
Mortality, morbidity, quality of life, and left ventricular (LV) function were evaluated in 49 patients after aortic valve replacement with the St. Jude prosthesis. Total follow-up was 2577 patient-months; survivors were followed-up for 4 to 7 years by clinical examination and echocardiography. The actuarial survival rate at 6 years was 79.6%, and there were no valve-related deaths. The linearized rates for thromboembolism and hemorrhage were 0.93% and 3.26% per patient-year, respectively. In 34% of the survivors the quality of life was poor. In the first three postoperative months, patients with aortic stenosis (n = 12) had a significant decrease in the muscle cross-sectional area (p less than 0.01) and patients with aortic regurgitation (n = 11) had decreases in both LV end-diastolic diameter (p less than 0.05) and cross-sectional area (p less than 0.001). All of these results were maintained at 5 years without modification of LV systolic function. Despite the good overall results, six patients deteriorated and had major LV dilatation. Multivariate logistic regression analysis identified two independent preoperative variables associated with a poor outcome defined as death of LV dysfunction (p less than 0.05): age and end-diastolic diameter. Thus meticulous follow-up showed a high incidence of hemorrhage and a poor quality of life in many of the survivors. It was concluded that in high-risk patients (age and end-diastolic diameter) surgery should probably be considered earlier.
Despite the widespread availability and demonstrated efficacy of screening with the Papanicolaou smear, many women are screened irregularly or not at all. This study was designed to identify the barriers that prevent those women at risk for cervical cancer from being screened. Complete cervical cytology screening histories were taken during a population-based case-control study of invasive squamous cell carcinoma of the cervix involving 200 patients and their matched neighborhood controls. Smears taken during the previous 5 years were verified whenever possible. Ordinal logistic regression analysis was used to identify seven factors that significantly (P less than 0.05) and independently predicted regular recent screening among both cases and controls [failure to understand the importance and screening nature of cervical smears (-), expressed fears of embarrassment (-), having had a urogenital infection (+), number of pregnancies during the last 5 years (+), the number of pregnancies for which no prenatal care was sought (-), and knowledge of the recommended screening interval (+)], two variables that predicted screening among cases but not controls [age (-) and number of years of oral contraceptives use (+)], and one that predicted screening only among controls [years of living in the United States (+)]. Education, income, Latin heritage, being married, having a regular physician for one's medical care, and all other methods of birth control were significant predictors of screening in the univariate analyses, but were explained by the other more powerful predictors in the multivariate analysis.
A phase II trial of idarubicin (IDR-4 demethoxydaunorubicin) was carried out in patients with advanced breast cancer. A dose of 45 mg/m2 was given orally once every 3 weeks. A total of 66 eligible patients were entered into the trial, 56 of whom were evaluable for response (65 were evaluable for toxicity at least). Therapeutic activity was demonstrated with an overall objective response rate of 21% (95% CI: 11-32%). When used as a first-line treatment, the response rate was 33% (95% CI: 9-57%) but this dropped to 17% when the treatment was administered after chemotherapy. Nausea-vomiting was the most frequent and severe non-hematological toxicity observed (WHO grade 3-4: 29%). Loss of hair was noticed in 48% of the patients but only 4% suffered from complete alopecia. Moderate myelotoxicity was reported but no cardiac dysfunction was noticed. IDR could be very advantageous as compared to other anthracyclines, due to its simplicity of administration associated with the lack of risk of extravasation or chemical phlebitis and also the possibility of it being able to reduce cardiotoxicity. Even if the equiefficacy of IDR and DXR has not, as yet, been clearly demonstrated, IDR should be chosen with preference to DXR when administration is not suitable.
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Illumination of a system consisting of a vertical tube containing an unstirred homogeneous suspension of thylakoids in an imposed linear concentration gradient of an electron acceptor, 2,6-dichloroindophenol, gave rise to a one-dimensional banded pattern of the acceptor that evolved in a time-dependent manner. The spatial pattern was obtained only within certain parameters of the dichloroindophenol gradient and with certain concentrations of thylakoids. Various numbers of bands were obtained by varying the gradient parameters, the thylakoid concentration, or both. Pattern formation was reaction-dependent since inhibition of the water-splitting system, either by a physical (heating) or by a chemical (methylamine) method, resulted in abolition of the spatial periodicity. Obtaining the self-organized redox transition of dichloroindophenol in a gelled medium suggests that pattern formation in this system could be explained mainly by a reaction-diffusion mechanism.