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Biomedical subjects

D M Williams

Publications and source records attributed to D M Williams.

At least 181 records · Page 10Linked to original sources
PubMed1992

Microspectrophotometric determinations of rod visual pigments in some adult and larval Australian amphibians.

Visual pigments from the red rods of adults of eight species of Australian anuran amphibians, from a variety of habitats, were analyzed by microspectrophotometry. The lambda max in all cases fell between 502 nm and 506 nm, and the absorption spectra were well fitted by an A1-based visual pigment template curve. Red rod pigments were also analyzed for a number of tadpoles. In some cases the data were best fitted with an A1-based visual pigment template, in other cases with an A2-based template, and finally some tadpoles appeared to have mixtures of the two pigments.

Animals↗
PubMed1992

Androgen receptor gene mutations identified by SSCP in fourteen subjects with androgen insensitivity syndrome.

The androgen insensitivity syndrome (AIS) is a disorder of male sexual development resulting in a wide range of clinical phenotypes. AIS is classified into two phenotypic forms: complete (CAIS) and partial (PAIS). To determine the molecular basis of the phenotypic diversity in AIS, we have studied 27 subjects (13 CAIS, 14 PAIS), spanning the full range of AIS phenotypes. We report the results of a mutation screen of the androgen receptor gene. The coding regions of the gene were amplified by the polymerase chain reaction and screened for single strand conformation polymorphisms to identify mutations. This was followed by DNA sequencing of putative mutant segments. Androgen receptor gene mutations were identified in nine CAIS and five PAIS subjects. Two of the CAIS mutations in exon A resulted in frameshifts. A third CAIS mutation resulted in the deletion of a single amino acid from the ligand binding domain of the receptor. All other mutations caused single amino acid substitutions in the ligand binding domain. These results suggest that mutations affecting the ligand binding domain of the androgen receptor are the most frequent cause of AIS, although some cases of PAIS may be the result of other, as yet undefined, genetic lesions.

Androgens↗
PubMed1992

Cytokine control of Leishmania infection in the BALB/c mouse: enhancement and inhibition of parasite growth by local administration of IL-2 or IL-4 is species and time dependent.

The therapeutic potential of locally injected interleukin-2 (IL-2) or interleukin-4 (IL-4) was studied in the footpads of Leishmania mexicana or Leishmania major infected BALB/c mice. The disease state was measured both pathologically, by measuring lesion size, and parasitologically, by counting total parasite numbers from infected footpads. IL-2 (0.5 microgram/dose) or IL-4 (0.1 microgram/dose) was administered either early, 1 day and/or 15 days after infection, or late, after palpable lesions had developed. Results differed markedly depending on which Leishmania species was used and at what time during the course of disease that therapy commenced. Both L. major and L. mexicana infections, as measured by footpad thickness and parasite number, were exacerbated if IL-4 was injected into the infected footpads early, during the first two weeks of infection. Paradoxically, late intralesional injection (i.e. after measurable lesions had developed) of IL-4 markedly inhibited both lesion size and parasite growth in L. major, though not L. mexicana, infected mice. IL-2 had no measurable effect on the course of L. major infections no matter when or how often, the infected footpads of mice were treated. However, early administration of IL-2 did exacerbate L. mexicana lesion and parasite growth while late treatment had no effect. Generally, but not always, increases in footpad size correlated with increases in parasite number.

Animals↗
PubMed1992

Inhibition of human endothelial cell proliferation in vitro in response to n-butyrate and propionate.

The study aimed to investigate the effects of n-butyrate and propionate on the proliferation and viability of human endothelial cells in culture. Proliferation was assessed by a 24-hour bromodeoxyuridine pulse labelling and immunoperoxidase method and viability was assessed by a colorimetric viability (MTT) assay. Endothelial cells were isolated from human umbilical vein by collagenase digestion. Experiments were performed on 96-well plates and cultures were exposed to different concentrations of n-butyrate and propionate for 2 days. n-butyrate and propionate caused significant reductions in the proliferation of endothelial cells at concentrations of 1.25 mM and 10 mM respectively (p less than 0.05); the reduction in proliferation was dose-dependent for both agents. n-butyrate was a more potent inhibitor of proliferation than propionate. However, there were no significant effects on the viability of the cells with both agents up to the highest concentrations tested (25 mM). The data indicate that n-butyrate and propionate inhibit endothelial cell proliferation which may contribute to the pathogenic effects of dental plaque in periodontal disease.

Analysis of Variance↗
PubMed1992

Effect of gamma interferon on resolution of murine chlamydial genital infection.

Mice infected in the genital tract with the Chlamydia trachomatis agent of mouse pneumonitis were treated with monoclonal rat anti-gamma interferon (anti-IFN-gamma) antibody to determine whether IFN-gamma participated in the resolution of the infection. In two experiments, anti-IFN-gamma antibody treatment resulted in significantly prolonged infections. In support of these data, passive administration of recombinant IFN-gamma to chronically infected nu/nu mice was able to bring about resolution of the infection in some animals.

Animals↗
PubMed1992

Chlamydia trachomatis pneumonia induces in vivo production of interleukin-1 and -6.

Cytokine induction during Chlamydia trachomatis pneumonia may alter the pathogenesis or course of disease. We examined interleukin-1 (IL-1) and IL-6 production by measuring mRNA and bioactivity in murine lungs. mRNA and bioactivity for IL-1 alpha, IL-1 beta, and IL-6 increased after Chlamydia infection. These cytokines may be important in regulating host defenses against C. trachomatis.

Animals↗
PubMed1992

Acute traumatic aortic rupture: intravascular US findings.

Traumatic aortic rupture is a lethal injury that requires immediate diagnosis and surgical repair. The authors report a case of acute aortic rupture in which aortography demonstrated a subtle intimal discontinuity at the cephalic margin of the aortic spindle. Intravascular ultrasound (US) imaging of the aorta demonstrated a mural flap and a small, contained hematoma. Intravascular US may have a role in enabling confirmation or clarification of subtle aortic abnormalities.

Adult↗
PubMed1992

Penetrating atherosclerotic ulcers of the descending thoracic aorta: evaluation with CT and distinction from aortic dissection.

Penetrating atherosclerotic ulceration of the aorta is a poorly understood entity that clinically mimics classic aortic dissection but has imaging features that are distinctly different. In a review of 16 patients with penetrating atherosclerotic ulceration, patients were typically hypertensive (n = 14), and they experienced chest or back pain (n = 13). All patients had an abnormal chest radiograph, with diffuse (n = 14) or focal (n = 2) enlargement of the descending thoracic aorta. Features at contrast material-enhanced computed tomography (CT) included intramural hematoma (n = 16), focal ulcer (n = 15), displaced intimal calcification (n = 13), pleural and/or extrapleural fluid (n = 7), mediastinal fluid (n = 4), and a thick or enhancing aortic wall (n = 6). The chest radiograph and CT findings were compared in patients treated conservatively (n = 9) and surgically (n = 7). These findings did not correlate with the need for surgery. Eight of nine conservatively treated patients were asymptomatic after treatment with antihypertensive medication. Contiguous dynamic contrast-enhanced CT of the aorta enables distinction of ulceration from dissection, which is particularly important in the hemodynamically unstable patient because the surgical management of ulceration is more extensive than that for aortic dissection.

Aged↗
PubMed1992

Role of the androgen receptor in male sexual differentiation.

The two androgens responsible for all aspects of male sexual differentiation are testosterone and dihydrotestosterone. The action of both these steroids is mediated by a specific intracellular receptor, the androgen receptor, which is a member of the nuclear receptor superfamily. The androgen receptor gene has been cloned and is located on the X chromosome at Xq11-12. Mutations of this gene have been found in subjects with both complete and partial androgen insensitivity. In a study of 27 subjects with the androgen insensitivity syndrome, we have identified mutations in 14, using a rapid mutation screening assay. The same technique has also been used to determine carrier status in an affected family. We have also identified a mutation in two brothers who show perineal hypospadias as the only evidence of undervirilisation. Familial severe hypospadias should therefore be included as part of the phenotypic spectrum of partial androgen insensitivity. The study of naturally occurring mutations of the androgen receptor gene is providing further information on the function of the androgen receptor and its role in normal male sexual differentiation.

Dihydrotestosterone↗
PubMed1992

Male pseudohermaphroditism: clinical management, diagnosis and treatment.

Male pseudohermaphroditism (MPH) is a disorder of sexual differentiation whereby the external genitalia are at variance with a male karyotype and the presence of testes. Abnormalities of Leydig cell function are an important cause of MPH, but postnatal age must be considered when interpreting the testosterone response when HCG stimulation is used as a diagnostic test. Androgen insensitivity is also a common cause of MPH; the specific defect in androgen receptor function is currently the subject of intense study, using a combination of biochemical assays and molecular analysis of the androgen receptor gene. The treatment of MPH is influenced by genital tissue responsiveness to androgens and the technical complexity of reconstructive surgical procedures. There is a need for information on the outcome of MPH treatment regarding pubertal development, sexual performance and fertility.

Androgens↗
PubMed1992

Compatibility of ceftazidime and aminophylline admixtures for different methods of intravenous infusion.

OBJECTIVE: Aminophylline and ceftazidime are sometimes used concurrently in patients with respiratory disorders. Parenteral aminophylline usually is administered as a constant infusion, and ceftazidime is given intermittently or less commonly as a constant infusion. We evaluated the stability and compatibility of the two drugs when aminophylline is given as a constant intravenous infusion and ceftazidime is administered simultaneously either through a y-site (piggyback method) or as a continuous infusion (constant infusion method). DESIGN: The chemical stability of intravenous aminophylline and ceftazidime in dextrose 5% and NaCl 0.9% for both methods was studied. Three different formulations of ceftazidime from the same manufacturer were studied (minibag using reconstituted ceftazidime, premixed minibag, and ceftazidime arginine). For the piggyback and constant infusion methods, samples were collected at 0, 1, and 2 hours; and 0, 6, and 24 hours, respectively. All experiments were conducted in triplicate. Samples were analyzed in duplicate by a stability-indicating HPLC assay method. OUTCOME MEASURE: Ceftazidime and aminophylline were considered stable if concentrations remained above 90 percent of the original concentrations over the time periods studied. RESULTS: Ceftazidime was determined to be compatible with aminophylline in the piggyback method. In contrast, when aminophylline and ceftazidime were admixed in the same intravenous container (constant infusion method), the two drugs were not stable. CONCLUSIONS: These data indicate that aminophylline and ceftazidime admixtures are incompatible when prepared in the same intravenous container, which may occur if both are given as a constant infusion. The two drugs are compatible when the ceftazidime is piggybacked into a primary intravenous set in which aminophylline is administered as a constant infusion.

Aminophylline↗
PubMed1992

Asthma in children.

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Adrenal Cortex Hormones↗
PubMed1991

Properties of 2'-fluorothymidine-containing oligonucleotides: interaction with restriction endonuclease EcoRV.

2'-Fluorothymidine (Tf) was synthesized via an improved procedure with (diethylamino)sulfur trifluoride. The compatibility of the analogue with DNA synthesis via the phosphoramidite method was demonstrated after complete enzymatic digestion of the oligonucleotides d(Tf11T) and d(Tf3T), the sole products of which were 2'-fluorothymidine and thymidine in the expected ratio. The 2'-fluorothymidine was also incorporated into the EcoRV recognition sequence (underlined), within the complementary oligonucleotides d(CAAACCGATATCGTTGTG) and d(CACAACGATATCGGTTTG). Thermal melting characteristics of these duplexes showed a significant decrease in stability only when both of the thymidine residues in one of the strands were replaced. In contrast, when all of one strand of a duplex contained 2'-fluorothymidine, as in d(Tf11T).d(A12), a substantially higher Tm and cooperativity of melting was observed relative to the unmodified structure. EcoRV cleaved a duplex that contained a 2'-fluorothymidine at the scissile linkage in each strand at two-thirds of the rate obtained for the unmodified structure. A duplex containing two 2'-fluorothymidine residues in one strand and none in the other was cleaved at one-third of the rate in its unsubstituted strand, whereas the cleavage rate was reduced to 22% in its modified strand.

Base Sequence↗
PubMed1991

Quantitative measurement of tissue perfusion and diffusion in vivo.

Magnetic resonance imaging techniques designed for sensitivity to microscopic motions of water diffusion and blood flow in the capillary network are also exceptionally sensitive to bulk motion properties of the tissue, which may lead to contrast artifact and large quantitative errors. The magnitude of bulk motion error that exists in human brain perfusion/diffusion imaging and the inability of cardiac gating to adequately control this motion are demonstrated by direct measurement of phase stability of voxels localized in the brain. Two methods are introduced to reduce bulk motion phase error. The first, a postprocessing phase correction algorithm, reduces coarse phase error but is inadequate by itself for quantitative perfusion/diffusion MRI. The second method employs orthogonal slice selection gradients to define a column of tissue in the object, from which echoes may be combined in a phase-insensitive manner to measure more reliably the targeted signal attenuation. Applying this acquisition technique and a simplistic model of perfusion and diffusion signal attenuations yields an estimated perfusion fraction of 3.4 +/- 1.1% and diffusion coefficient of 1.1 +/- 0.2 x 10(-5) cm2/s in the white matter of one normal volunteer. Successful separation of perfusion and diffusion effects by this technique is supported in a dynamic study of calf muscle. Periods of normal blood flow, low flow, and reactive hyperemia are clearly distinguished in the quantitative perfusion results, whereas measured diffusion remained nearly constant.

Algorithms↗
PubMed1991

Differential morphological changes in human polymorphonuclear leucocytes induced by culture products of Porphyromonas (Bacteroides) Gingivalis W50 and its colonial variants with reduced virulence.

The colonial variants of W50, derived after growth in a chemostat and previously designated W50/BP1, W50/BR1 and W50/BE1, produced black-, brown- and beige-pigmented colonies, respectively, and showed reductions in mouse virulence and proteolytic activity correlating with their reduced pigmentation. Incubation of glass-adherent polymorphonuclear leucocytes with culture supernatants from the virulent, highly proteolytic, black-pigmented strain produced significant changes in morphology when compared with changes among sterile bacterial growth medium treated, control polymorphonuclear leucocytes. Large, non-polar cells (greater than or equal to 18 microns dia) increased by 130% (p less than 0.01) while polarized and small non-polar cells (less than 18 microns dia) decreased by 48 and 30% (p less than 0.05), respectively. Changes in percentages of the different morphological forms of polymorphonuclear leucocyte after exposure to the culture supernatant from the less virulent W50/BR1 variant showed similar, though less marked trends, while the avirulent W50/BE1 variant failed to produce significant changes in any morphological category. The specific activities of trypsin-like enzyme in the culture supernatants of the different variants were greater in black-pigmented than brown-pigmented and least in the beige-pigmented variant, thus correlating with the morphological changes in polymorphonuclear leucocytes. Morphological changes similar to those seen with culture supernatants from black-pigmented strains were reproduced by exposure of polymorphonuclear leucocytes to commercially available trypsin type II and prior heat treatment of these culture supernatants abolished the shape changes in polymorphonuclear leucocytes. Thus a bacterial, trypsin-like enzyme may play a role in the morphological changes observed.

Adult↗