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Biomedical subjects

D M Williams

Publications and source records attributed to D M Williams.

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

A common protein binds to two silencers 5' to the human beta-globin gene.

The temporal sequence of expression of human globin genes during development suggests precise regulation of these genes. Recent studies have characterized a number of DNA sequences within or flanking the human beta-globin gene which are important in its regulation and several proteins which bind to these sequences have been identified. We have found two proteins which bind 5' to the human beta-globin gene. One of these proteins, which we designate BP1, binds to two sequences, one between -550 and -527 bp relative to the cap site, the other between -302 and -294 bp. A second protein, BP2, binds to sequences between -275 and -263 bp. The binding sites for both BP1 and BP2 are in two regions which function as silencers in a transient expression assay using the human erythroleukemia cell line K562. These results and others presented here suggest that BP1 may act as a repressor protein. Negative regulation seems to be an important component of tissue and developmental specific globin gene regulation.

Animals↗
PubMed1989

Persistent sialadenitis of the minor glands--stomatitis glandularis.

In a recurring lesion on the palate of a 60-year-old male, histological features of a chronic inflammatory disease of the minor salivary glands resembling those found in cheilitis glandularis were found. The similarities between the clinical and histological features of our case and cheilitis glandularis are discussed and the inherent nature of the disease emphasised. We propose the terms persistent sialadenitis of the minor glands or stomatitis glandularis, for this condition.

Humans↗
PubMed1989

Liver-tumor boundary detection: human observer vs computer edge detection.

As a preliminary step in computing tumor volume, we developed a computer edge detection program to define the liver-tumor interface in computed tomography (CT) images. Computer program performance was tested using CT images from a lucite liver/tumor phantom; from normal livers containing computer-generated pseudotumors of known size, object contrast, and liver-tumor edge gradients; and from 12 abdominal livers containing 19 focal tumors, eight with well-defined and 11 with ill-defined borders. Calculated sizes of the tumor phantom and pseudo-tumors were compared with measured volumes and predetermined cross-sectional areas, respectively. In the absence of a truth standard for the size of the focal hepatic tumors, computer-calculated cross-sectional areas of the tumors were compared with the measurements made by an experienced interpreter of CT images using the trackball cursor at the CT console. The console measurements were made five times on separate days during a one-week period. The variability in the measured areas of these tumors averaged 7.1% for the well-defined tumors and 14.0% for the poorly defined tumors (P = 0.05). The edge-linking algorithm systematically overestimated the volumes of individual slices of the hemispherical tumors in the lucite phantom. Nevertheless, because of algorithm failure in the slices containing the poles of the hemispheres, errors in total tumor volumes were -2.1% for the 5.1 cm radius tumor, +1.2% for the 2.7 cm radius tumor, and +15% for the 1.8 cm radius tumor. The edge-linking algorithm was reasonably successful in calculating areas of pseudotumors with object contrast of 3.0% or greater and steep edge gradients.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1989

Reassessment of cross-reactivity of spironolactone metabolites with four digoxin immunoassays.

Spironolactone and one of its metabolites, canrenone, cross-react with some digoxin immunoassays to result in erroneous serum digoxin concentrations. Recently, additional compounds, 7-alpha-thiomethylspirolactone (7-a-TMS) and 6-beta-hydroxy-7-alpha-thiomethylspirolactone (6-B-OH-7-a-TMS), have been reported to be quantitatively important metabolites of spironolactone. This study was initiated to evaluate the cross-reactivity of these metabolites, canrenone, and spironolactone with four different digoxin immunoassays. Blank serum was spiked with each compound to yield concentrations reported to occur in vivo. Samples were analyzed in duplicate by each of the following immunoassays: fluorescence polarization immunoassay (FPIA); affinity-column-mediated immunoassay (ACMIA); radioimmunoassay (RIA); and enzyme immunoassay (EIA). The 7-a-TMS metabolite cross-reacted with both the RIA and ACMIA methods. Apparent digoxin concentrations were as great as 0.39 ng/ml for this metabolite at the highest concentration evaluated, 600 ng/ml. At the lowest concentrations evaluated with the 7-a-TMS metabolite, 50 ng/ml, apparent digoxin concentrations as high as 0.28 ng/ml were reported. The 6-B-OH-7-a-TMS metabolite did not cross-react to a significant extent with any of immunoassays studied. Canrenone cross-reacted with the ACMIA method at a concentration of 100 ng/ml. The EIA method exhibited no apparent cross-reactivity with any of the compounds, whereas the FPIA method exhibited minimal cross-reactivity. The results of this study indicate that the 7-a-TMS metabolite cross-reacts to a significant extent with some immunoassays; however, this is not true for the 6-B-OH-7-a-TMS metabolite.

Adult↗
PubMed1989

Political theory and individualistic health promotion.

The grounding of the individualistic self-care-behavior approach to health promotion in classical liberal political theory is made explicit by uncovering the correspondence between the assumptions of the two. Questions are raised about whether the problems attributed to liberal theory are reflected in the results obtained with individualistic health promotion. It is suggested that for nurses to engage in socially responsible health promotion, they may need to reconceptualize health promotion using a feminist perspective.

Health Promotion↗
PubMed1989

Cytokeratin expression of the odontogenic epithelia in dental follicles and developmental cysts.

The patterns of cytokeratin expression in the epithelium of 5 dental follicles, 7 dentigerous cysts, 5 odontogenic keratocysts, 3 nasopalatine cysts and an epidermoid cyst have been studies using a panel of monoclonal antibodies. The epithelium of dental follicles and of developmental odontogenic cysts strongly expressed keratins 5 and 19 and showed weaker expression of keratins typical of stratified non-cornified and of simple epithelia. Staining with mAbs against the latter keratins varied with the degree of epithelial differentiation. Nasopalatine cysts strongly expressed simple epithelial keratins and the epidermoid cyst strongly expressed a marker of cornification. Odontogenic cysts thus appear to differ in their pattern of keratin expression from other oral developmental cysts and all derivatives of odontogenic epithelia appear to share similar basic patterns of cytokeratin expression.

Antibodies, Monoclonal↗
PubMed1989

Epithelial HLA-DR expression in labial salivary glands in Sjögren's syndrome and non-specific sialadenitis.

The expression of the Class II major histocompatibility antigen HLA-DR was quantified in the epithelial cells of labial salivary glands from patients with Sjögrens Syndrome (SS) and compared with similar expression in glands showing non-specific sialadenitis and normal controls. In all glands more duct cells were positive than acinar cells but only in sialadenitis and SS was strong epithelial staining seen. The proportions of duct and acinar cells expressing HLA-DR were increased between normals and sialadenitis (P less than 0.01) and between sialadenitis and SS (P less than 0.001). However, for all cases increased expression of HLA-DR correlated to the increased proportion of inflammatory cells in the gland (P less than 0.01). The results indicate that although HLA-DR is expressed on the epithelial cells in the glandular lesions of SS, this is not specific as it is also seen in sialadenitis. This supports the view that such expression is secondary to an inflammatory infiltrate and may not be of importance in initiating autoimmune tissue damage.

Adolescent↗
PubMed1989

Regional variation in Langerhans cell distribution and density in normal human oral mucosa determined using monoclonal antibodies against CD1, HLADR, HLADQ and HLADP.

The distribution, density and activation of Langerhans cells (LC) has been established in biopsies of normal human buccal mucosa, hard palate, lateral border and dorsum of tongue, floor of mouth and lip taken from sudden death post mortems. LC were identified in cryostat sections with monoclonal antibodies against CD1, HLADR, HLADQ and HLADP using an immunoalkaline phosphatase technique. The use of post mortem material was validated by comparison with biopsies taken from volunteers. LC were predominantly situated in the basal and immediately suprabasal layers of the epithelium. In floor of mouth, lip, lateral border and dorsum of tongue the cells were found along the length of the epithelium. In buccal mucosa, although LC showed fundamentally a similar distribution, a tendency to cluster around the connective tissue papillae was also noted. In hard palate LC were found parallel to the surface in the mid zone of the epithelium. No evidence of LC free areas was found. Dorsum of tongue had the highest density of LC per mm epithelial surface length (28.3 cells per mm) which was significantly greater (P less than 0.05) than buccal mucosa (25.2) which in turn had significantly more cells (P less than 0.05) than lip (22.4). The lowest density of LC was found in lateral border of tongue (17.6), hard palate (17.6) and floor of mouth (16.7). These sites had significantly fewer cells than lip, buccal mucosa and dorsum of tongue (P less than 0.05). Class II MHC molecules are necessary for antigen presentation and in all sites except buccal mucosa there was no significant difference between the number of cells expressing CD1, HLADR, HLADQ and HLADP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Vesiculobullous mucocutaneous disease: pemphigus vulgaris.

Pemphigus vulgaris is a potentially fatal autoimmune mucocutaneous disease in which oral lesions may be the initial and predominant manifestation. The disease is characterized by acantholysis in the immediately suprabasal layers of the stratified squamous epithelium, giving rise to blisters which readily rupture leaving erosions which show little tendency to heal. Immunogenetic studies indicate a marked genetic susceptibility to the disease, with the immune response-associated HLA-DR4 and DRw6 alleles being especially important. The trigger for autoantibody formation is unknown. The antigen in pemphigus vulgaris is probably a 130-140 kD cell adhesion molecule located in the cell membrane of basal and immediately suprabasal keratinocytes. Antibody binding to this antigen is likely to interfere with normal intercellular adhesion, leading to desmosomal detachment. Propagation of acantholysis and cell damage are attributable to complement activation, with deposition of the membrane attack complex on the keratinocyte cell membrane, and proteolysis due to increased plasminogen activator production. Steroid therapy is the treatment of choice, but significant mortality is still associated with the disease.

Acantholysis↗
PubMed1989

Characterization of gamma interferon-mediated cytotoxicity to chlamydia-infected fibroblasts.

Addition of murine recombinant gamma interferon (IFN-gamma) to mouse fibroblast cultures infected with Chlamydia psittaci was found to induce a cytotoxic response that was dependent on the concentration of IFN-gamma added and the multiplicity of infection given. No cytotoxicity was observed for uninfected cells treated with IFN-gamma, nor did infection alone elicit cytotoxicity. Cytotoxicity was detected only if IFN-gamma was present for at least the first 18 h of a 30-h incubation period. Cytotoxic activity was not observed when infected cells were treated with 50 micrograms of chloramphenicol per ml, a drug which inhibits differentiation of infectious elementary bodies to noninfectious reticulate bodies. Cytotoxic activity was restored if addition of chloramphenicol was delayed until 18 h postinfection. Addition of 100 U of penicillin per ml to infected host cells reduced but did not abolish cytotoxic activity. Treatment of host cells with as little as 0.2 microgram of cycloheximide per ml inhibited cytotoxicity without interfering with chlamydial growth. When addition of cycloheximide was delayed until 12 h after infection and IFN-gamma treatment, cytotoxicity was restored. These data indicate that IFN-gamma functions as a cytotoxic cytokine against chlamydia-infected fibroblasts. Cytotoxicity was found to be dependent on chlamydial multiplicity of infection, differentiation of chlamydiae to the metabolically active form, and host cell protein synthesis.

Animals↗
PubMed1989

Tumor necrosis factor alpha is a cytotoxin induced by murine Chlamydia trachomatis infection.

A mouse model of pneumonia caused by murine Chlamydia trachomatis (mouse pneumonitis agent) was used to demonstrate that whole spleen cells from both nude athymic mice (nu/nu) and heterozygous mice (nu/+) produced tumor necrosis factor alpha in vitro in response to mouse pneumonitis agent antigen. The tumor necrosis factor alpha measured in these supernatants by immunoassay was shown to have bioactivity in a cytotoxic assay in which uninfected target cells were used. This cytotoxicity was distinct from the gamma interferon-related cytotoxicity against C. trachomatis-infected targets that we described previously.

Animals↗
PubMed1989

Unsatisfactory hepatic perfusion after placement of an implanted pump and catheter system: angiographic correlation.

Thirty-five patients with scintigrams showing unsatisfactory hepatic artery perfusion after surgical placement of an implanted pump and catheter system were examined with selective angiography (33 cases) or digital subtraction angiography (DSA) during which the contrast material was injected through the side port of the pump (six cases). In 34 of 35 cases, the cause of the unsatisfactory (either extrahepatic or incomplete) hepatic perfusion was defined. DSA was definitive in only two cases, in which extrahepatic flow through collateral vessels was demonstrated. The cause of the perfusion defect was hepatic artery thrombosis in 14 cases, extrahepatic flow through collateral vessels in 14 cases, a misplaced catheter in four cases, and a short proper hepatic artery without adequate length for mixing in two cases. Although hepatic artery perfusion scintigraphy is the primary tool for evaluation of hepatic perfusion after catheter placement, angiography plays an important role in treating the subset of patients with unsatisfactory hepatic perfusion.

Antineoplastic Agents↗
PubMed1989

Hepatic arterial chemotherapy: role of angiography.

Hepatic arterial infusion chemotherapy increases the hepatic concentration of chemotherapeutic agents without increasing systemic toxicity. Both percutaneous (most commonly left transbrachial) and surgical approaches are currently used for infusion catheter placement. Surgical catheter and pump placement has proved to be a reliable means of delivering drugs to the liver and has been commonly used for hepatic arterial chemotherapy for metastatic colorectal carcinoma. Meticulous angiographic evaluation of the hepatic vascular anatomy, its variations, and hemodynamics is necessary for correct catheter placement to achieve total liver perfusion without significant extrahepatic perfusion. Satisfactory hepatic perfusion should be documented before drug infusion. Hepatic arterial radionuclide flow imaging with technetium-99m-labeled macroaggregated serum albumin remains the most reliable means of assessing hepatic perfusion following catheter placement. Transcatheter techniques have been used to facilitate catheter placement, to prevent gastrointestinal drug toxicity, and to correct unsatisfactory perfusion following surgical catheter placement.

Antineoplastic Agents↗
PubMed1989

The permeability of human oral mucosa and skin to water.

Specimens from four regions of oral mucosa (palate, buccal mucosa, lateral border of the tongue, and the floor of the mouth) and of abdominal skin were taken from 58 individuals at autopsy, for determination of permeability constants (Kp) to tritium-labeled water. Comparisons between fresh specimens and those stored at -80 degrees C revealed no significant effect on Kp as a result of freezing; similar results were found with use of specimens from corresponding regions of the pig. Values for Kp were significantly different for all of the tissue regions examined and ranged from 44 +/- 4 x 10(-7) cm/min for skin to 973 +/- 33 x 10(-7) cm/min for the floor of the mouth, which was the most permeable region. Similar differences were evident among corresponding regions of porcine oral mucosa and skin. Moreover, the Kp values obtained for human tissues were not significantly different from those of the pig, except for the floor of the mouth, which was more permeable in human than in pig tissue. The results reveal interesting differences in the permeability of human oral mucosa that might be related to susceptibility to mucosal disease in those conditions where local extrinsic etiological agents are implicated.

Abdomen↗
PubMed1989

Tobramycin administration and blood sampling through a dual-lumen peripheral intravenous catheter.

The objective of this study was to determine if a peripheral dual-lumen catheter could be used for accurate tobramycin blood concentration measurement when drug administration and blood sampling were undertaken through separate lumens of the catheter. Eleven adult volunteers received tobramycin 1.5 mg/kg iv infused over 30 minutes through the distal lumen of the dual-lumen catheter every eight hours for two doses. Multiple blood samples were obtained concurrently from the proximal lumen of the catheter and a single-lumen catheter in the contralateral arm after each dose. Blood samples were also obtained through the distal lumen before and 30 minutes after the end of the infusion. Accurate blood samples were obtainable through the dual-lumen catheter in only 5 of 11 subjects due to either infiltration or difficulties in catheter placement. In the subjects from whom accurate blood samples were obtained, approximately 20 minutes postinfusion was the amount of time required before measured tobramycin serum concentrations were similar between the arm in which the drug was infused (site of the dual-lumen catheter) and the contralateral arm. At standard times for obtainment of trough (just prior to the infusion) and peak (30 minutes after the end of a 30-minute infusion) tobramycin serum concentrations from the proximal lumen of the dual-lumen catheter were numerically similar to those obtained from the contralateral arm. This preliminary study indicates that the dual-lumen catheter provides accurate aminoglycoside concentrations when patent relative to blood withdrawal and if peak blood samples are obtained at least 30 minutes postinfusion through the recommended lumen. However, further study in a larger number of subjects is required before routine use of this device can be recommended.

Adult↗