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Biomedical subjects

T Williams

Publications and source records attributed to T Williams.

At least 235 records · Page 13Linked to original sources
PubMed1989

Mussel glue protein has an open conformation.

Both native glue protein from marine mussels and a synthetic nonhydroxylated analog were analyzed by far-uv CD under a variety of conditions. Analysis of the CD spectra using various models strongly suggest a primarily random coil structure for both forms of the protein, a fact also supported by the absence of spectral change for the glue protein upon dilution into 6 M guanidine hydrochloride. The nonhydroxylated analog, which consists of 20 repeats of the peptide sequence Ala-Lys-Pro-Ser-Tyr-Pro-Pro-Thr-Tyr-Lys, was further characterized by enzyme modification using mushroom tyrosinase. Enzymatic hydroxylation of tyrosines was found to be best fit by a model containing two rate constants, 5.6 (+/- 0.6) X 10(-3) and 7.2 (+/- 0.3) X 10(-2) min-1. At equilibrium, HPLC analysis of digests showed nearly 100% conversion of Tyr-9 and only 15 to 35% conversion of Tyr-5. The Chou and Fasman rules for predicting structure were applied to the repeat sequence listed above. The rules predict the absence of alpha helix and beta pleated sheets in the structure of this peptide. On the other hand, beta turns are predicted to be present with Tyr-5 being in the region of highest probability. These data suggest that the protein in solution has only a small amount of secondary structure.

Amino Acid Sequence↗
PubMed1989

A phase I clinical and pharmacological study of weekly intravenous infusions of piritrexim (BW301U).

Thirty-eight patients with advanced resistant cancers were enrolled on this study of piritrexim (PTX; BW 301U) administered intravenously weekly for 4 weeks. Of 50 courses of treatment begun, 39 evaluable 4-week courses of the drug were completed by this group of patients. Dosages ranged from 44 to 530 mg/m2/week. One patient at each dosage level received an initial weekly dose of PTX in oral form accompanied by pharmacokinetic blood sampling after the oral dose and also after a subsequent intravenous dose. Toxicities included mild nausea and vomiting, and moderate to severe peripheral vein phlebitis. Anemia and thrombocytopenia were the dominant hematological toxicities. One patient with pulmonary metastases from malignant fibrous histiocytoma experienced a 12-week partial response to PTX treatment at a dosage of 400 mg/m2/week. Pharmacokinetic analysis of plasma for PTX concentrations was accomplished utilizing a competitive protein binding assay. The estimated total body clearance ranged from 136 to 173 ml/min/1.73 m2. Mean terminal half-life after intravenous administration was 5.61 +/- 2.38 h (S.D.), and after oral administration was 5.72 +/- 2.04 h. Mean systemic bioavailability after oral administration was 75 +/- 56%.

Adult↗
PubMed1989

Toward the identification of CME content needs for primary care physicians.

While continuing medical education (CME) has been accepted as effective in changing the clinical behavior of participants, there is still uncertainty as to the most effective method of determining content that is practice relevant and clinically important to an identified population of participating physicians. This article proposes a model for developing a knowledge examination that can be administered to CME audiences to detect deficiencies of knowledge that will be helpful in CME program planning. It further proposes that such an instrument be based upon the following assumptions: (1) that core competencies can be identified by content specialists; (2) that the relevance to practice can be determined by reviewing practitioners who represent the target audience (content and face validity); (3) that eight management stages should be sampled by the instrument to assure that all management areas of clinical practice are included; (4) that the test items be tested and retained, revised, or discarded according to the results of item analysis (validity); (5) that test items should be written to represent application and problem-solving use of knowledge; (6) that medical problems for which test items are written should be selected on the basis of potential for improving mortality or morbidity. For example, in the case of cancer, most would agree that colorectal cancer represents an area where better application of current concepts would result in improved mortality rates. With use of a test instrument constructed on the basis of these assumptions, it should be possible to sample what physicians need to know that is relevant to their practices--the proactive model.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Competence↗
PubMed1989

Regulation of transcription factor AP-2 by the morphogen retinoic acid and by second messengers.

The expression of the transcription factor AP-2 recently has been shown to be enhanced during retinoic acid (RA)-induced differentiation of NT2 cells, a human teratocarcinoma cell line. Here we show that this induction of AP-2 mRNA is at the level of transcription and is transient, reaching a peak 48-72 hr after the addition of RA and declining thereafter, even in the continuous presence of RA. Increased levels of AP-2 mRNA are reflected in a similar elevation of AP-2 protein and accompanied by an increase in the AP-2-binding site-dependent transcriptional activity of a reporter gene. AP-2 also has been proposed to confer TPA and cAMP inducibility on promoters/enhancers containing AP-2-binding sites. We investigated the effect of these agents on the expression of AP-2 protein and mRNA. Our experiments demonstrate that expression of the AP-2 gene in HeLa cells is not elevated significantly by TPA or by a calcium ionophore and is not enhanced at all by agents that increase intracellular cAMP concentration. In fact, AP-2 mRNA is repressed by both TPA and the calcium ionophore A23187 through a delayed response. These data suggest that the AP-2-binding site-mediated cAMP and TPA responses are not regulated at the level of AP-2 expression but, rather, achieved either by post-translational changes in AP-2 or in conjunction with another protein.

1-Methyl-3-isobutylxanthine↗
PubMed1989

AIDS with disseminated histoplasmosis.

This report is a description of two Ohio cases of acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis, with discussion of diagnosis and treatment of this combination. The patient in case 1 developed disseminated histoplasmosis as the first significant symptomatic medical condition of his life. The patient in case 2 presented with severe pharyngitis, but without signs or symptoms specific to the lungs. Amphotericin B alone does not eradicate histoplasmosis in an AIDS patient. The best therapy at present is a full course of amphotericin B followed by a lifetime regimen of ketoconazole to prevent relapse. Family physicians in the District of Columbia, Texas, Maryland, Louisiana, Missouri, Illinois, Arizona, and Puerto Rico should be particularly vigilant in looking for the combination of these two diseases.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Some studies on the isolation and properties of pulmonary mast cells from the pig.

Mast cells were isolated by the enzymic dissociation of lung tissue from the pig. The responses of these cells to a variety of histamine liberators and anti-allergic drugs were examined. On the basis of these findings, the possible use of porcine pulmonary mast cells in the study of immediate hypersensitivity reactions is discussed.

Animals↗
PubMed1988

Screening for Chlamydia trachomatis infection in a pregnancy counseling clinic.

Five hundred twenty asymptomatic women attending a pregnancy counseling clinic were interviewed and screened for cervical Chlamydia trachomatis infection before therapeutic abortion. Overall, 56 (10.8%) women were culture positive for C. trachomatis. Restricting testing to women with risk factors for infection or who had cervical leukocytosis on Gram staining of cervical mucus, or who were seropositive for C. trachomatis antibodies proved impractical because of insensitivity or nonspecificity. We evaluated three chlamydia diagnostic tests to determine which test had the best performance characteristics. In comparison with culture, the direct fluorescent antigen test had a sensitivity of 89% and a positive predictive value of 78%, whereas the enzyme immunoassay had 96% and 69%, respectively. When analysis was redone with any two positive laboratory tests to define true infection status, the performance parameters of enzyme immunoassay were sensitivity 98%, specificity 98%, and positive predictive value 87%. We conclude that all women undergoing therapeutic abortion require testing for C. trachomatis infection and that enzyme immunoassay is the most effective and practical test in this group of women.

Abortion Applicants↗
PubMed1988

The mouse surfeit locus contains a very tight cluster of four "housekeeping" genes that is conserved through evolution.

The four identified alternating transcription units (Surf-1 to Surf-4) in the mouse surfeit locus are very tightly clustered, no two neighboring units being separated by more than 73 base pairs and the Surf-2 and Surf-4 transcription units overlapping by 133 base pairs at their 3' ends. All four surfeit genes, which are unrelated by sequence similarity, were found to have the properties of "housekeeping" genes, being expressed in a variety of differentiated mouse cell lines and containing unmethylated CpG-rich islands in the vicinity of their 5' ends. The unusual organization of the four surfeit genes was found not to be unique to the mouse: the same juxtaposition of the genes was found to be conserved in a number of different mammals, including humans. The four human surfeit genes were also found to be transcriptionally active.

Animals↗
PubMed1988

Cloning and expression of AP-2, a cell-type-specific transcription factor that activates inducible enhancer elements.

Human AP-2 is a sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to stimulate transcription of selected genes. Here, we report the isolation and characterization of a human cDNA clone containing the entire protein-coding region of AP-2. The deduced primary amino acid sequence of AP-2 does not contain a domain resembling any previously identified DNA binding motif. However, an interesting feature of the AP-2 protein is a clustered arrangement of proline and glutamine residues that have been found recently within the activation domains of other transcription factors. Expression of the AP-2 clone in bacteria yields a protein that binds to DNA and activates transcription in vitro in a comparable manner to native human AP-2. Transfection of cDNA clones into Drosophila cells indicates that the AP-2 gene product can also activate gene expression in vivo in a DNA template-dependent manner. Expression of endogenous AP-2 is repressed in a hepatoma cell line and stimulated following retinoic-acid-induced differentiation of a human teratocarcinoma cell line. This indicates that AP-2 may be a transcription factor involved in the control of developmentally regulated gene expression.

Amino Acid Sequence↗
PubMed1988

Unique requirement for the PyF441 mutation for polyomavirus infection of F9 embryonal carcinoma cells.

A point mutation at nucleotide 5258 in the enhancer of the polyomavirus host range mutant F441 permits productive infection of F9 embryonal carcinoma cells, which, when undifferentiated, are refractory to infection by wild-type polyomavirus. Synthetic oligonucleotides were used to construct viral genomes containing all four possible nucleotide pairs at nucleotide 5258. While all four of the viruses infected 3T6 cells efficiently, only F441, which has a guanosine in place of the wild-type adenosine in the early strand of DNA at position 5258, was able to infect F9 cells. Transfection assays with enhancer-dependent plasmid constructs expressing the chloramphenicol acetyltransferase gene under the control of the polyomavirus early promoter verified that only the F441 enhancer had any significant activity in F9 cells. DNase I footprinting showed that the F441 mutation creates a strong binding site for purified CCAAT box transcription factor, which is identical to nuclear factor 1. The three other mutations at nucleotide 5258 alter the affinity and the quality of factor binding at this site.

Base Sequence↗
PubMed1988

One of the tightly clustered genes of the mouse surfeit locus is a highly expressed member of a multigene family whose other members are predominantly processed pseudogenes.

The mouse surfeit locus is unusual in that it contains a number of closely clustered genes (Surf-1, -2, and -4) that alternate in their direction of transcription (T. Williams, J. Yon, C. Huxley, and M. Fried, Proc. Natl. Acad. Sci. USA 85:3527-3530, 1988). The heterogeneous 5' ends of Surf-1 and Surf-2 are separated by 15 to 73 base pairs (bp), and the 3' ends of Surf-2 and Surf-4 overlap by 133 bp (T. Williams and M. Fried, Mol. Cell. Biol. 6:4558-4569, 1986; T. Williams and M. Fried, Nature (London) 322:275-279, 1986). A fourth gene in this locus, Surf-3, which is a member of a multigene family, has been identified. The poly(A) addition site of Surf-3 lies only 70 bp from the poly(A) addition site of Surf-1. Transcription of Surf-3 has been studied in the absence of the other members of its multigene family after transfection of a cloned genomic mouse DNA fragment, containing the Surf-3 gene, into heterologous monkey cells. Surf-3 specifies a highly expressed 1.0-kilobase mRNA that contains a long open reading frame of 266 amino acids, which would encode a highly basic polypeptide (23% Arg plus Lys). The other members of the Surf-3 multigene family are predominantly, if not entirely, intronless pseudogenes with the hallmarks of being generated by reverse transcription. The role of the very tight clustering on regulation of expression of the genes in the surfeit locus is discussed.

Amino Acid Sequence↗