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Biomedical subjects

D M Williams

Publications and source records attributed to D M Williams.

At least 199 records · Page 11Linked to original sources
PubMed1991

Vascular endothelium: a potential role in HIV infection and the pathogenesis of Kaposi's sarcoma: observations and speculations.

Kaposi's sarcoma (KS) has become a source of interest in recent years primarily for its strong association with the acquired immune deficiency syndrome (AIDS). Endothelial cells (EC) are central to inflammation and can regulate coagulation and leucocyte emigration and may be central to the development of the disease. As they are also capable of being infected by HIV in vivo, this infection may contribute to the immunosuppressive effects of HIV seen in AIDS. Recent work has shed new light on the mechanisms involved in EC proliferation. The aim of this article is to review such evidence implicating EC in the development of KS. Additionally, hypotheses will be put forward to explain the mechanism of the vascular proliferation in KS and the possible role of EC in HIV infection. There is therefore enormous potential for the therapeutic targeting of endothelium to control these diseases.

Endothelium, Vascular↗
PubMed1991

Cladistic methods and chromophyte phylogeny.

An examination of systematic methods is undertaken to establish interrelationships within the chromophytic algae, focussing on their relationship to the Oomycota. Evidence from both molecular and morphological studies suggests that the Oomycota appeared before the pigmented chromophytes. Theories on the origin of the chromophyte chloroplast are examined in the light of these findings.

Chloroplasts↗
PubMed1991

Evaluation of the inferior vena cava with intravascular US after Greenfield filter placement.

An animal model was used to evaluate the utility of intravascular ultrasound (US) imaging of the inferior vena cava (IVC) following Greenfield filter placement. Ten Greenfield filters were placed in the IVCs of five sheep and three dogs. Experimentally induced thrombi were injected into four filters at the time of placement. Intravascular US and cavography were performed 4 weeks after filter implant. The imaging studies were evaluated for demonstration of filter position, orientation, and leg distribution, as well as prediction of caval wall penetration by filter hooks. Experimentally induced and spontaneous intrafilter thrombi were also imaged. Findings were compared with those of postmortem examination. Exact filter position and orientation were most simply and accurately demonstrated on radiographs. Filter leg distribution and extent of intrafilter thrombus were best evaluated on intravascular US images. The prevalence of caval wall penetration was underestimated with both studies. The results of this animal study suggest that the information about the IVC provided at cavography and intravascular US following Greenfield filter placement may be complementary.

Animals↗
PubMed1991

Intravascular ultrasound imaging of vascular responsiveness in isolated perfused canine arteries.

We investigated the feasibility of using intravascular ultrasound imaging to analyze vascular physiology in various arterial beds. Canine superficial femoral, external iliac, and common carotid arteries were harvested and suspended and perfused in a bath of oxygenated, heated, physiologic salt solution. A 6-Fr, 20-MHz ultrasound imaging catheter was inserted into the lumen of the arteries and serial images were acquired after bolus injections of either serotonin or normal saline into the extravascular bathing medium. Serotonin resulted in a significant time- and dose-dependent decrease in cross-sectional area in muscular femoral arteries (P less than .001): -5.2% with 10(-8) M serotonin, -15% with 10(-7) M, and -28% with 10(-6) M. Histologically transitional iliac arteries demonstrated less marked changes, while elastic carotid arteries demonstrated no significant changes. Our results indicate that intravascular ultrasound may be used to quantify and differentiate responses to vasoconstrictive agents in different vascular beds.

Animals↗
PubMed1991

Neither awake nor sleep blood pressures better predict target-organ effect.

We sought to assess the strengths of commonly used ambulatory blood pressure (ABP) parameters as predictors of transmitral flow/velocity ratio (E/A) and the dimensions that govern the left ventricular (LV) mass index. ABP, E/A, and LV dimensions were assessed in 47 subjects, with inclusion of 45 in the final data analysis. The results of four weekly (96 h total) ABP studies were averaged for each subject. No single ABP parameter immerged as a "best predictor." Furthermore, casual blood pressures taken at the beginning of the echo examination had predictive strength for LV mass which was similar to that of the ambulatory data. In the present study, neither awake nor sleep ABPs differed significantly with respect to correlations with indices of LV structure.

Adult↗
PubMed1991

Effect of tobacco and alcohol consumption on the Langerhans cell population of human lingual epithelium determined using a monoclonal antibody against HLADR.

Tobacco and alcohol consumption are known predisposing factors to the development of oral cancer, though the mechanism by which they act is unclear. The density of Langerhans cells (LC) has been shown to decrease in the uterine cervix of smokers, possibly indicating reduced immune surveillance and increased risk of malignant change. This study examined biopsies of normal human lateral border of tongue taken from 41 necropsies whose histories of tobacco and alcohol consumption were known. LC were identified in fixed, wax-embedded sections using a monoclonal antibody to HLADR and an immunoperoxidase technique. The mean density of LC in smokers of the equivalent of 11 or more cigarettes daily was significantly higher than moderate and non-smokers when counts were expressed per mm epithelial surface and basement membrane length. There were no significant differences in LC numbers in relation to alcohol consumption, age or sex, but there was a significant interaction between tobacco and alcohol. The results suggest that either human oral LC respond to external toxins, or that physical changes in the epithelial barrier induced by such toxins necessitate the presence of more LC to maintain the integrity of the epithelium.

Adolescent↗
PubMed1991

Altered patterns of keratin expression in oral hairy leukoplakia: prognostic implications.

To establish why the lateral border of tongue is the site of predilection for the development of hairy leukoplakia (HL) and to understand its likely behavior, the pattern of keratin expression was compared in 8HL lesions with matched controls in an immunocytochemical study. Keratins 7, 8, 18 were absent in HL and normals; uniform basal keratin 19 was present in normals but much reduced in HL. Loss of conformationally sensitive epitopes of keratin 14 in lower epithelial layers was seen in HL. Overall expression of non-cornifying keratins 4/13 was reduced in HL and completely lost in the parakeratin zone. Expression of the high-turnover keratins 6/16 was reduced in HL. The HL keratin phenotype suggests that no dysplastic change is likely, but in contrast there is enhanced differentiation, which suggests a benign course for the condition.

Adult↗
PubMed1991

Production of colony-stimulating factors during pneumonia caused by Chlamydia trachomatis.

The colony-stimulating factors (CSFs) are cytokines involved in the production, differentiation, and activation of host phagocytes. During murine infection with Chlamydia trachomatis (MoPn), plasma CSF levels increased in euthymic (nu/+) and athymic (nu/nu) BALB/c mice. Levels declined later in infection, with the nu/+ mice resolving the infection but the nu/nu mice succumbing by day 16. Either live or heat-killed Chlamydia organisms could induce CSF increases on day 7 postchallenge in nu/+ mice; however, by day 14, only mice challenged with live organisms maintained high plasma levels. CSFs were also produced by spleen cells of nu/+ and nu/nu mice in response to Chlamydia antigen. Spleen cell CSF production was detectable by days 3 to 5 postinfection. In nu/+ mice, spleen cell CSF production was elevated throughout the rest of the time course but in nu/nu mice fell significantly at day 14. Like the plasma CSF activity (CSA) production, spleen cell CSA production on day 7 was seen in mice challenged with either live or heat-killed Chlamydia organisms, but on day 14 only nu/+ mice challenged with live organisms maintained significant CSA production. To further characterize the T-cell dependence of CSA production, spleen cells of nu/+ mice were depleted of T cells or T-cell subsets before producing supernatants. On day 14 postinfection, the CD4+ lymphocyte was the major producer of CSFs. Additionally, there were different types of CSFs secreted by nu/+ and nu/nu mice as determined by the ability of spleen cell supernatants to support the granulocyte-macrophage CSF/interleukin 3-dependent cell line FDCP-1. Supernatants from nu/+ mice had 4 to 8 times the level of FDCP-1 CSF activity of the supernatants from nu/nu mice. These results support the evidence that nu/+ mice were producing some CSFs by T-cell-dependent mechanisms. This is the first report of CSF production in vivo during Chlamydia infection. Furthermore, we show that CSFs are produced by both T-cell-dependent and T-cell-independent mechanisms. The capacity of the CSFs to increase the production and effector function of phagocytes may be important to host defenses.

Animals↗
PubMed1991

Normal postnatal androgen production and action in isolated micropenis and isolated hypospadias.

To try and find out if a defect in androgen biosynthesis or action could be responsible for the incomplete virilisation seen in boys with isolated hypospadias and isolated micropenis, androgen receptor binding was studied in genital skin fibroblasts established from 18 boys with isolated micropenis and 19 boys with isolated hypospadias. The production of gonadotrophins and testosterone was also measured in the boys with micropenis. There was no evidence of gonadotrophin deficiency, or of a defect in testosterone biosynthesis in the boys with micropenis, and there was no evidence of a quantitative or qualitative defect of androgen binding in either group. These isolated abnormalities may be the result of transient defects in androgen synthesis or action, or both, during a critical phase of embryogenesis.

Adolescent↗
PubMed1991

Penetrating atherosclerotic aortic ulcer with dissecting hematoma: control of bleeding with percutaneous embolization.

A case is presented in which left subpleural hematoma and hemothorax resulted from a penetrating atherosclerotic aortic ulcer with an aortic pseudoaneurysm and intramedial hematoma. Percutaneous transfemoral embolization of the ulcer with use of coils and thrombin resulted in stabilization of the patient's hemodynamic status. The patient died 6 days later of pneumonia. In certain clinical situations, treatment of bleeding from penetrating aortic ulcers with percutaneous embolization may stabilize the patient's condition, allowing elective surgical intervention.

Aged↗
PubMed1991

Structure-function relationship of hammerhead ribozymes as probed by 2'-modifications.

Hammerhead ribozymes containing 2'-fluoro- or 2'-aminonucleotides were prepared by automated chemical synthesis. Incorporation of 2'-fluorouridines, 2'-fluorocytidines or 2'-aminouridines did not appreciably decrease catalytic activity. The presence of 2'-aminocytidines, however, reduced the activity about 20-fold. No catalytic activity could be measured for ribozymes in which all adenosines were replaced by the 2'-fluoro analogue in presence of MgCl2. No single position could be found responsible for this loss of activity. In an attempt to construct ribozymes to hydrolyse HIV-RNA in the 5'-LTR region several constructs were tested on synthetic substrate as well as on run-off transcripts of about 1000 nucleotides length.

Antiviral Agents↗
PubMed1990

Incorporation of a complete set of deoxyadenosine and thymidine analogues suitable for the study of protein nucleic acid interactions into oligodeoxynucleotides. Application to the EcoRV restriction endonuclease and modification methylase.

A complete set of dA and T analogues designed for the study of protein DNA interactions has been prepared. These modified bases have been designed by considering the groups on the dA and T bases that are accessible to proteins when these bases are incorporated into double-helical B-DNA [Seeman, N. C., Rosenberg, J. M., & Rich, A. (1976) Proc. Natl. Acad. Sci. U.S.A. 73, 804-808]. Each of the positions on the two bases, having the potential to interact with proteins, have been subject to nondisruptive, conservative change. Typically a particular group (e.g., the 6-NH2 of dA or the 5-CH3 of T) has been replaced with a hydrogen atom. Occasionally keto groups (the 2- and 4-keto oxygen atoms of T) have been replaced with sulfur. The base set has been incorporated into the self-complementary dodecamer d(GACGATATCGTC) at the central d(ATAT) sequence. Melting temperature determination shows that the modified bases do not destabilize the double helix. Additionally, circular dichroism spectroscopy shows that almost all the altered bases have very little effect on overall oligodeoxynucleotide conformation and that most of the modified oligomers have a B-DNA type structure. d(GATATC) is the recognition sequence for the EcoRV restriction modification system. Initial rate measurements (at a single oligodeoxynucleotide concentration of 20 microM) have been carried out with both the EcoRV restriction endonuclease and modification methylase. This has enabled a preliminary identification of the groups of the dA and T bases within the d(GATATC) sequence that make important contacts to both proteins.

Adenosine↗
PubMed1990

Interaction of the EcoRV restriction endonuclease with the deoxyadenosine and thymidine bases in its recognition hexamer d(GATATC).

A set of dA and T analogues suitable for the study of protein DNA interactions have been incorporated into the central d(ATAT) sequence within d(GACGATATCGTC). The individual analogues have one potential protein contact (either a hydrogen-bonding group or a CH3 group capable of a van der Waals interaction) deleted. In general, the modified bases do not perturb the overall structure of the dodecamer, enabling results obtained to be simply interpreted in terms of loss of protein DNA contacts. We have used the modified oligodeoxynucleotide set to study the recognition of DNA by the EcoRV restriction endonuclease [recognition sequence d(GATATC)]. The kcat and Km values for the set have been determined, and a comparison with results seen with the parent oligodeoxynucleotide (containing no modified bases) has been carried out. Three classes of results are seen. First, some analogues lead to no change in kinetic parameters, meaning no enzyme contact at the altered site. Second (this is seen for most of the modified oligodeoxynucleotides), a drop in the kcat/Km ratio relative to the parent is observed. This comes mainly from a decrease in kcat, implying that the endonuclease uses the interaction under study to lower the transition-state barrier rather than to bind the substrate. Analyses of these results show that the drop in kcat/Km is what would be expected for the simple loss of a hydrogen bond or a CH3 contact between the enzyme and the oligodeoxynucleotide. This implies a contact of these types at these sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1990

Molecular recognition in the minor groove of the DNA helix. Studies on the synthesis of oligonucleotides and polynucleotides containing 3-deaza-2'-deoxyadenosine. Interaction of the oligonucleotides with the restriction endonuclease EcoRV.

An improved procedure for the preparation of 3-deaza-2'-deoxyadenosine (d3CA) is described which is suitable for the synthesis of gram quantities of this analogue. Using phosphoramidite chemistry d3CA has been incorporated into the Eco RV restiction endonuclease recognition sequence (underlined) present in the self-complementary dodecamer d(GACGATATCGTC). The modified oligonucleotides have been thoroughly characterised by nucleoside composition analysis, circular dichroism and thermal melting studies. Studies with Eco RV show that incorporation of d3CA into either the central or outer dA-dT base-pair results in a substantial reduction in the rate of cleavage. The two-step conversion of d3CA to 3-deaza-2'-deoxyadenosine-5'-O-triphosphate (d3CATP) via the 5'-O-tosylate is also described. d3CATP is not a substrate in the poly[d(AT)].poly[d(AT)] primed polymerisation for either E. coli DNA polymerase I or Micrococcus luteus DNA polymerase. In a more detailed kinetic analysis d3CATP was shown to be a competitive inhibitor of E. coli DNA polymerase I with respect to dATP.

Adenosine Triphosphate↗