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Biomedical subjects

D C Williams

Publications and source records attributed to D C Williams.

At least 145 records · Page 8Linked to original sources
PubMed1984

Diaphanography as a means of detecting breast cancer.

Diaphanography (lightscanning) is a noninvasive method of examining the breast by transillumination using visible or infrared light. It was compared to xeromammography in 1,000 patients, 91 of whom had biopsy. There were 34 malignant tumors, of which 29 were detected by xeromammography and 26 by lightscanning; 27 patients with positive lightscans were not biopsied. All patients with true-positive lightscans also had positive mammograms. Major criteria of malignancy on diaphanography included an area of light absorption and abnormal or hypervascularity. These criteria could be demonstrated on retrospect on 6 scans previously considered negative; one xeromammogram previously interpreted as negative was diagnosed as positive on retrospect. Diaphanography may be sensitive enough to warrant further investigation.

Adolescent↗
PubMed1984

Surgery and the GMENAC report: a reality test.

Concern for a possible oversupply of physicians caused the Secretary of Health and Human Services to create the Graduate Medical Education National Advisory Committee (GMENAC) to analyze the nation's supply and requirements for physicians. Issued in 1980, the GMENAC Report projected an aggregate surplus of 70,000 physicians in 1990. Surgeons in particular were projected to exceed requirements by 40%. I evaluated the GMENAC parameters using the quantitative methodology initially developed for the 1970 Study on Surgical Services for the United States. This assessment of the GMENAC projections indicated increased population-based use of surgical intervention and projected wide interspecialty variation in average surgeon productivity with an even larger excess of surgeons than that projected for 1990 by GMENAC.

General Surgery↗
PubMed1983

Synergistic inhibition of [3H]muscimol binding to calf-brain synaptic membranes in the presence of L-homocysteine and pyridoxal 5'-phosphate. A possible mechanism for homocysteine-induced seizures.

L-Homocysteine and pyridoxal 5'-phosphate (PxyP) inhibited [3H]muscimol binding to freeze-thawed, Triton-treated calf brain membranes (containing high-affinity muscimol-binding sites: Kd 9.5 +/- 0.6 nM, Bmax 5.2 +/- 0.2 pmol/mg protein). The homocysteine--pyridoxal-5'-phosphate (Hcy-PxyP) thiazine complex had no effect. L-Homocysteine was found to be a partially competitive inhibitor, thus demonstrating an allosteric inhibition with Ki value of 1.96 mM for free receptor and Ki of 13 mM for receptor-muscimol complex. PxyP was shown to be a two-site pure competitive inhibitor of [3H]muscimol binding with cooperativity of PxyP binding such that Ki values for PxyP of 20 mM and 2.1 mM were found. L-Homocysteine and PxyP when added simultaneously to binding assays, caused a greater degree of inhibition than that observed at the same total specific concentration of either inhibitor alone. This synergistic inhibitory effect was shown to be due to a homocysteine-induced increase in the affinity of PxyP-binding sites. Three alternative models are suggested to explain the observed synergistic effects whereby it is proposed that PxyP and [3H]muscimol binding is mutually exclusive, while L-homocysteine with PxyP and L-homocysteine with muscimol, exhibit non-exclusivity. Non-linear regression analysis of binding data was undertaken in order to substantiate conclusions drawn from graphical procedures and in an attempt to ascertain which mathematical model best fitted the experimental data describing the synergistic inhibitory effects of L-homocysteine and PxyP. This synergistic inhibitory effect of PxyP and L-homocysteine on the post-synaptic gamma-aminobutyric acid receptor may provide a basis for explanation of the mechanism of homocysteine-induced seizures.

Animals↗
PubMed1983

Immunocytochemical demonstration of human proinsulin chimeric polypeptide within cytoplasmic inclusion bodies of Escherichia coli.

Immunocytochemical techniques were used to identify human proinsulin chimeric protein in cytoplasmic inclusion bodies of genetically modified Escherichia coli. Antibodies to proinsulin chimeric protein (human proinsulin coupled at its amino-terminus to a portion of the E. coli tryptophan E gene product) were localized in E. coli using post-embedding staining with protein A-peroxidase labelling for transmission electron microscopy. The observable distribution of the labelled antibody was limited to that portion of the E. coli cytoplasm occupied by inclusion bodies. The localization of human peptides as insoluble masses within the bacterial cytoplasm has important implications in relation to the synthesis, recovery and purification of pharmacologically useful substances produced through the application of recombinant DNA technology.

Bacterial Proteins↗
PubMed1983

Chlorpromazine inhibits mitosis of mammalian cells.

Chlorpromazine (CPZ) at minimally effective concentrations accumulates mammalian cells in mitosis without lethal effects on the cells. Star-metaphase morphology similar to effects seen with classical antimitotic compounds probably results from the preferential action of CPZ on a specific class of microtubules--the pole-to-pole microtubules of the mitotic spindle. At CPZ concentrations of 8 X 10(-6) M, flow cytometry indicates no effect of CPZ on the progress of cells through phases of the cell cycle other than mitosis (M). These results suggest a possible mechanism for toxic side effects of CPZ in man such as granulocytopenia and light sensitization.

Animals↗
PubMed1982

Cytoplasmic inclusion bodies in Escherichia coli producing biosynthetic human insulin proteins.

Escherichia coli that has been genetically manipulated by recombinant DNA technology to synthesize human insulin polypeptides (A chain, B chain, or proinsulin) contains prominent cytoplasmic inclusion bodies. The amount of inclusion product within the cells corresponds to the quantity of chimeric protein formed by the bacteria. At peak production, the inclusion bodies may occupy as much as 20 percent of the Escherichia coli cellular volume.

Cloning, Molecular↗
PubMed1982

The serum levels of some trace and bulk elements in cancer patients.

The levels of copper, zinc, calcium, manganese and magnesium have been monitored in the sera of patients suffering from various types of cancer. Only serum copper appeared to be of any diagnostic significance, its levels being above the normal reported range in the breast cancer, leukaemia and Hodgkin's lymphoma patients. In the case of breast cancer, serum copper is progressively elevated according to the stage of the disease. Serum calcium levels were also significantly lower in patients with tumours of the breast, gastrointestinal tract and cervix. The results suggest that serum copper levels could be of prognostic significance in breast cancer patients receiving radiotherapy.

Adolescent↗
PubMed1982

Serum galactosyl transferase levels in patients with advanced cancer.

Serum galactosyl transferase was significantly higher in patients with various types of cancer than in age-matched controls. The highest serum enzyme levels were observed in the breast and respiratory cancer, followed by ovarian and gastrointestinal tumours; whereas the enzyme activity in prostatic cancer patients was not significantly higher than in the control subjects. In the cancer patients the serum levels of this enzyme were not significantly higher in the presence of metastases. In terminally ill patients, the serum enzyme activity decreased proportionately in accordance with the progression of their disease.

Adult↗
PubMed1981

Surgeons and surgery in Rhode Island, 1970 and 1977.

In the 1970s the likelihood of an oversupply of physicians in the United States began to be recognized by health-manpower analysts. The number of surgeons available to meet the population's needs was of particular concern. Using data from 1970 on four representative geographic areas, including Rhode Island, investigators in the Study on Surgical Services for the United States (SOSSUS) found operative workloads of surgeons to be light by any standard; they recommended several actions to limit the number of physicians performing operations. I repeated the 1970 SOSSUS analysis of Rhode Island, using data from this state for 1977. Comparison of the results for 1970 and 1977 indicated that, at least in this state, little or no progress had been made in reducing the excess of surgical manpower. As of 1977, the SOSSUS recommendations were having no demonstrable impact in Rhode Island. The number of surgeons was continuing to increase without apparent need, as judged by operative workloads.

General Surgery↗
PubMed1981

Fibrinogen is the receptor for the endogenous lectin of human platelets.

Washed platelets activated by alpha-thrombin, gamma-thrombin, thrombocytin or the ionophore A23187 (ref. 3) lose their disk shape, produce pseudopodia and become cohesive. This cohesiveness is accompanied by the expression of an endogeneous haemagglutinin which, although apparently bound to the platelet membrane, is dependent on cell secretion. The interaction of this agglutinin with appropriate receptors on other platelets is believed to be responsible for aggregation. We report here that platelets can be prepared which lack agglutinin activity but have receptor function, that afibrinogenaemic platelets lack receptor activity, and that fibrinogen is the receptor for the agglutinin secreted by activated platelets.

Blood Platelets↗
PubMed1981

Purification of porphobilinogen deaminase from Euglena gracilis and studies of its kinetics.

1. Porphobilinogen deaminase [porphobilinogen ammonia-lyase (polymerizing), EC 4.3.1.8] from Euglena gracilis was purified more than 200-fold. 2. The enzyme has a molecular weight of 41 000 +/- 2000, does not contain a chromophoric prosthetic group, and appears not to require metal ions for activity. 3. The stoicheiometry of the overall reaction at pH 7.4 was shown to be: 4 Porphobilinogen leads to uroporphyrinogen-I + 4 NH4+. This stoicheiometry for porphobilinogen and uroporphyrinogen was also observed over a wide range of pH values. 4. Initial-velocity studies showed a hyperbolic dependence of velocity on substrate concentration, demonstrating the existence of a displacement-type mechanism. 5. Vmax. varied with pH as a typical bell-shaped curve, indicating that two ionizable groups with pK values of 6.1 and 8.9 are important for catalysis. A plot of Vmax./Km against pH showed a single ionization (pK 8.2) to influence binding of substrate.

Ammonia-Lyases↗