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Biomedical subjects

D L Williams

Publications and source records attributed to D L Williams.

At least 361 records · Page 20Linked to original sources
PubMed1982

Statistical analysis of cytogenetic abnormalities in human cancer cells.

It is sometimes difficult to evaluate reports of "nonrandom" chromosome involvement in certain malignant diseases, since the "random" or expected distribution is seldom defined. Therefore, we have developed methods for the statistical analysis of cytogenetic abnormalities in human cancer cells with modal karyotypes in the diploid range (35-57 chromosomes). For this analysis, it is assumed that the expected gain or loss of each chromosome will occur with equal probability and structural abnormalities will involve each chromosome in proportion to its size. To perform this analysis, the total number of numerical and structural abnormalities is determined from the modal karyotypes of a series of histologically related tumors. The maximum expected values are determined by computer simulation for different levels of significance. Then the distributions of observed and expected abnormalities of each type are compared to identify nonrandom involvement. Preferential gain or loss is analyzed for each of the 24 different chromosomes, and preferential structural rearrangement is determined for each of the 48 chromosome arms. We have analyzed two series of karyotypic data to demonstrate the utility of this method. The rationale for the assumptions made as well as alternative approaches are discussed.

Chromosome Aberrations↗
PubMed1982

Inhibition of nitrosation of amines by thiols, alcohols and carbohydrates.

The addition of a number of simple alcohols and carbohydrates to reactions of nitrous acid with amines in dilute acid solution resulted in a reduction in the overall rate constant for N-nitrosation. The effects were not very large and complete suppression of nitrosation was not achieved. The results are all consistent with the rapid equilibrium formation of the corresponding alkyl nitrite which is virtually inactive as a direct nitrosating agent itself. Addition of the two thiols L-cysteine and N-acetylpenicillamine, however, had a much more marked effect and it was possible to prevent nitrosation of the amine completely in both cases. This findings was no doubt due to competition from the irreversible S-nitrosation. On the other hand the effect of S-methyl-L-cysteine and L-methionine was rather small. The results are all discussed in terms of the likely reaction mechanisms.

Alcohols↗
PubMed1982

Role of DNA repair genes and an R plasmid in conferring cryoresistance on Pseudomonas aeruginosa.

The resistance of Pseudomonas aeruginosa wild-type, uvr, pol and rec strains to ultraviolet (u.v.) light, X-rays and freezing and thawing was determined. An R plasmid, pPL1, which increased resistance of the wild-type uvr, and pol but not rec strains to u.v. light, increased the resistance of only rec and pol mutants to X-rays and freezing and thawing. These findings reinforce the idea of DNA as a target in the organism for freeze-thaw stress and suggest that freeze-thaw-induced DNA damage might be similar to that produced by X-rays but different from that produced by u.v. light.

DNA Repair↗
PubMed1982

Acute megakaryoblastic leukaemia associated with intrinsic platelet dysfunction and constitution ring 21 chromosome in a young boy.

A 3-year-old boy with pancytopenia and a paucity of circulating blast cells was found to have acute megakaryoblastic leukaemia. Histopathologic investigation of the bone marrow biopsy disclosed replacement by megakaryoblasts and mild-to-moderate reticulin fibrosis, the megakaryocytic origin of these cells was confirmed by their staining properties and by cross-reactivity with rabbit anti-rat platelet serum. Treatment with adriamycin and cytosine arabinoside induced a complete remission of this otherwise rapidly fatal disease. Before chemotherapy, the patient's platelets showed decreased aggregation in response to thrombin and adenosine diphosphate, as well as a defective thrombin-induced serotonin release reaction. Neither functional defect resolved after remission induction, indicating that the platelets were intrinsically abnormal. Most striking was the finding of a constitution chromosomal defect, a ring No. 21 chromosome, in addition to an abnormal malignant stem line. This appears to be the first reported instance of a constitutional r(21) chromosome associated with acute leukaemia.

Bone Marrow↗
PubMed1982

A model for dental workload measurement.

The primary purpose of the study was to develop a model that would provide an efficient and standardized approach to workload reporting in a non-fee (HMO-like) dental care system. The model was also designed to predict the dental personnel resource requirements in the system as the overall dental needs of the population were already known. To accomplish this, a set of 246 task/procedures representing the broad scope of dental practice was developed. For each task/procedure, a Best Time-weighted Estimate (BTE) in terms of average expected man-minutes of work required for accomplishment was developed from over 35,000 actual time measurements on patient visits to 29 US Army dental clinics located throughout the United States. Because of the nature of the specific task/procedure data, it was necessary to use four different mathematical models to produce statistically optimal BTEs. It was concluded that, cumulatively the BTEs developed for each task/procedure evaluated could be used as a basis for both the development of a Dental Care Composite Unit workload measure and the determination of overall dental personnel resource requirements in a non-free dental care system.

Dental Care↗
PubMed1982

Prognostic importance of chromosome number in 136 untreated children with acute lymphoblastic leukemia.

Leukemia cell karyotypes were determined at diagnosis for 136 of 159 consecutive patients with acute lymphoblastic leukemia (ALL) who were followed for up to 35 mo. Ninety patients (67%) had abnormal karyotypes. Five chromosome categories were designated, based on the distribution of modal numbers: hyperdiploid greater than 50 (n = 41), hyperdiploid 47-50 (n = 18), pseudodiploid (n = 28), normal (n = 46), and hypodiploid (n = 3). Treatment response was assessed for the categories in terms of time to failure (induction failure, first relapse, or death). Children in the hyperdiploid greater than 50 category had the best responses to treatment, with only 2 failures, and those in the pseudodiploid category had the poorest (p less than 0.001). The remaining 3 chromosome categories had intermediate responses and formed a third prognostic group. This same influence of chromosome number on time to failure was evident within the 2 clinical prognostic groups: high risk, signified by a leukocyte count greater than 100 X 10(9)/liter, meningeal leukemia, mediastinal mass, or the presence of blasts that formed rosettes with sheep erythrocytes at 37 degrees C, and standard risk, indicated by the absence of these features. The influence of chromosome number on time to failure was also the same within the historically favorable prognostic group that had common ALL. Results of a multivariate analysis indicated that chromosome number was the strongest single predictor of outcome (p less than 0.001) and was the only variable that added significant prognostic information to leukocyte count (p less than 0.001). The combination of chromosome number and leukocyte count should more clearly distinguish patients with ALL at low or high risk of relapse.

Asparaginase↗
PubMed1982

Regional distribution of myocardial blood flow measured by single-photon emission tomography: comparison with in vitro counting.

An emission computed tomography system (SPECT), which uses a single large-field-of-view gamma camera, was evaluated for its ability to measure the relative distribution of myocardial blood flow and to assess the effect of attenuation, scatter, and cardiac motion on the tomographic images. Normalized regional myocardial counts from the SPECT images of the living dogs correlated closely with those from the anatomic slices and the samples counted at necropsy except for an over-estimate of tracer in the perfusion defect (SPECT) 57.7 compared to tissue count 32.1; p less than 0.05. The differences were less for the other imaging conditions. Heart and thorax motion, attenuation, and scatter contributed less than 25% to the over-estimate of defect counts. We conclude that the SPECT system accurately reflects regional distribution of myocardial blood flow except for overestimation of flow in regions of perfusion defects. Small perfusion defects might therefore be missed, but no artifactual defects are created.

Animals↗
PubMed1982

Aneuploidy and percentage of S-phase cells determined by flow cytometry correlate with cell phenotype in childhood acute leukemia.

Cellular DNA content distributions of propidium-iodide-stained bone marrow blasts were determined by flow cytometry (FCM) for 225 untreated children with acute leukemia and were correlated with leukemia cell phenotype and karyotype. Aneuploidy of the primary malignant stem line was detected in 54 cases (24%): 51 hyperdiploid and 3 hypodiploid. A second stem line with approximately twice the DNA content of the primary stem line was recognized by FCM in 28 cases (23 ALL, 5 ANLL) and may be an important source of leukemia cell heterogeneity. The degree of DNA content abnormality detected by FCM was highly correlated (r = 0.98) with the number of whole chromosome gains or losses in the leukemia karyotype. Aneuploidy detectable by FCM was more frequent in acute lymphoblastic leukemia (ALL) (52 of 173, 30.1%) than in acute nonlymphoblastic leukemia (2 of 52, 3.8%) (p less than 0.001). In the ALL group, aneuploidy was significantly correlated with the cell surface expression of common ALL antigen: 46 of 127 antigen-positive cases were aneuploid compared to 6 of 46 antigen-negative cases (p less than 0.003). Only 2 of 21 cases of T-cell ALL without common ALL antigen had detectable aneuploidy, which was significantly less than in the common ALL group (p = 0.02). The median percentage of cells in S-phase was significantly greater for B-cell and erythrocyte rosette-positive T-cell ALL, than for the other phenotypic subgroups. We conclude that aneuploidy and S-phase cell percentage are correlated with the state of leukemia cell differentiation. The biologic basis for the correlation is not established, but may be linked to the process of malignant transformation.

Acute Disease↗
PubMed1981

Tropomyosin stability: assignment of thermally induced conformational transitions to separate regions of the molecule.

Tropomyosin was prepared from rabbit skeletal muscle and studied in a differential scanning calorimeter. The characteristics of the observed endotherms were studied as a function of p]H, salt concentration, oxidation state of Cys-190, and concentration of the divalent metal ions Ca2+ and Mg2+. The large shifts observed for the Tm values of the components of the endotherms with changing pH and salt concentration are consistent with electrostatic effects being an important determinant of the structural stability of tropomyosin. For reduced tropomyosin or tropomyosin blocked with N-ethylmaleimide, two endotherms were observed with Tm values of 41.5 and 52.5 degrees C at neutral pH in a low-salt buffer. For tropomyosin containing a disulfide link at Cys-190, two endotherms were observed with Tm values of 32 and 52 degrees C under the same conditions. The endotherm at 52 degrees C contains contributions from conformational transitions in two independent structural regions. An analysis of the heat-capacity profiles for the two large cyanogen bromide peptides, CN1A and CN1B, enabled the assignment of two components of the endotherms to structural transitions in the C-terminal region which includes Cys-190 and in the N-terminal region. Calcium and magnesium ions in the 1-10 mM range increased the stability of several of the regions of the structure, presumably by binding to localized areas of excess negative charge. Unfolding of tropomyosin in the 20-70 degrees C range is a multistep process and occurs with an average enthalpy of 4 cal g-1.

Animals↗
PubMed1981

Estrogen receptor and the development of estrogenic responses in embryonic chick liver.

We have examined the development of responsiveness to estrogen by embryonic chick liver with a view to determining common and unique factors involved in the establishment of different genomic responses to th e hormone. The major apoproteins of chick VLDL, apo VLDL-B and apo VLDL-II, both appear to be estrogen inducible at an earlier stage of of embryonic development than is vitellogenin. Apo VLDL-B, but not vitellogenin, exhibits a significant level of hepatic synthesis in the absence of estrogen treatment. This basal synthesis in the absence of estrogen treatment. This basal synthesis is tamoxifen-resistant and is detectable at very early stages of hepatic development, well before estrogen responsiveness is seen. Immunological cross-reactivity, electrophoretic behavior and the results of limited proteolysis mapping suggest that the apo VLDL-B synthesized under basal and estrogen-stimulated conditions is the same (or a very similar) protein. Inducibility of the VLDL apoproteins appears to parallel the appearance of the hepatic estrogen receptor system at days 10-12 while vitellogenin induction is delayed by several days. Cytosol receptor concentration undergoes a gradual increase up to the 19th day of development and thereafter declines. The properties of the 19-day receptor are very similar to those of cytosol receptor in hatched chickens, but the fall in concentration does not appear to be proportionately related to inducibility of estrogenic responses, as measured by the relative rates of synthesis in vitro.

Animals↗