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Biomedical subjects

D M Williams

Publications and source records attributed to D M Williams.

At least 253 records · Page 14Linked to original sources

Enhanced adhesion of autologous lymphocytes to gamma-interferon-treated human endothelial cells in vitro.

An adhesion assay was developed using human umbilical vein endothelial cell cultures and autologous and allogeneic lymphocytes separated from cord blood. Endothelial monolayers cultured in plain or gamma-interferon (IFN gamma)-supplemented medium were cocultured with lymphocytes for 1 h and non-adherent lymphocytes removed by washing. Autologous and allogeneic lymphocytes exhibited significantly increased adhesion with IFN gamma-treated cells compared with untreated controls. The increased adhesion to IFN gamma-treated endothelial cells was significantly inhibited when autologous or allogeneic lymphocytes were pre-treated with saturating amounts of an anti-CD4 monoclonal antibody. The results indicate that IFN gamma enhances lymphocyte binding to endothelium and that the CD4 molecule may be involved in this process. This could be an important mechanism in targetting the migrating of T-helper (Th) cells to areas of chronic inflammation and in antigen presentation by endothelial cells.

Antibodies, Monoclonal↗

Support services in Canadian schools for the hearing impaired: 10 years later.

In January of 1977, a questionnaire regarding existing and desired professional support services was distributed to 20 schools for the hearing-impaired across Canada. Respondents were requested to provide information pertaining to the last few months of 1976. In December of 1986, a similar questionnaire was distributed to these schools, in order to update the information received 10 years earlier, and to compare current services to those desired 10 years ago. The survey also presented an opportunity to examine changes in focus, client population and number of schools for the hearing impaired in Canada. Despite the disparity between available and needed services in the schools, as well as the differences in support staff between them, it is clear that the schools are, for the most part, fairly well staffed by a good range of professionals. There is, however, a continued need for the review of current and future needs. The change from residential to day students, as well as the increase in the number of additionally handicapped students, requires changes in and re-assessment of support services. Continued research may assist in defining priorities in the area of support services as the needs of the schools change over time.

Audiology↗

The multinucleate cells in giant cell granulomas of the jaw are osteoclasts.

The giant cell granuloma of jaw is a well-vascularised lesion comprising a mononuclear cell infiltrate with a large number of giant cells. It has been suggested that the lesion is reparative in nature, rather than neoplastic, and that the giant cells are phagocytes accumulating in chronic reparative granulation tissue. However, the nature of the multinucleate giant cells never has been established. One possibility is that the constituent giant cells are osteoclasts. The authors assessed expression by the giant cells of several osteoclast-specific characteristics: excavation of bone; motility inhibition by calcitonin (CT); and binding of osteoclast specific monoclonal antibodies. Two tumors were disaggregated and incubated on slices of cortical bone in the presence and absence of CT. Both tumors were found to excavate bone, a function unique to osteoclasts. The giant cells also were responsive to CT, resulting in cytoplasmic quiescence and inhibition of bone resorption. Two osteoclast-specific monoclonal antibodies bound all the giant cells in one central and six peripheral tumors examined immunohistochemically. These results provide strong evidence for the osteoclastic nature of the giant cells. The presence of alkaline phosphatase-positive cells forming woven bone in giant cell granulomas suggests that osteoblasts are present in the lesion. As cells of osteoblastic lineage are known to regulate osteoclastic function, it may be that osteoblasts account for the characteristic infiltration of osteoclasts into giant cell granulomas of jaws, either as part of a reparative response by reactive osteoblasts or as an infiltrate induced by osteoblasts of aberrant function, as suggested for giant cell tumors of bone.

Antibodies, Monoclonal↗

Fashionable drugs.

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Anti-Bacterial Agents↗

Amlodipine pharmacokinetics in healthy volunteers.

In the present study we investigated the pharmacokinetics and comparative bioavailability of three oral doses of amlodipine in 12 healthy male volunteers. A randomized, open-label, three period crossover study design was employed. Each subject received, on three separate occasions a single oral dose of 2.5, 5 and 10 mg amlodipine. Standing diastolic blood pressure was reduced by 1.1, 4.8 and 8 mmHg six hours after 2.5, 5 and 10 mg amlodipine, respectively. There were no significant changes in pulse rate, nor on the EKG. The curves for the mean plasma concentrations versus time for the three doses showed parallel time-courses. Highly significant positive correlations were observed between dose and AUC (0-72 hrs) and between dose and Cmax. However, dose corrected AUC and Cmax were 10-20% lower with 2.5 mg, than with 5 and 10 mg. Peak levels were achieved 5.6 to 6.4 hours postdose. Half lives were 31.2, 33 and 36.8 hours for 2.5, 5 and 10 mg respectively. Headache was the most common side effect, and was more frequently observed with the highest dose. In summary, linear relationships were found between the dose and the plasma levels of amlodipine. Decreases in standing diastolic blood pressure were also dose related. Because of its long half-life and gradual absorption, amlodipine should be effective in lowering blood pressure given once daily and the incidence of side effects due to rapid absorption should be minimized.

Adult↗

Copper deficiency anemia: altered red blood cell lipids and viscosity in rats.

To investigate membrane lipid abnormalities and their possible role in copper deficiency anemia, we studied lipids, osmotic fragility, and viscosity of red blood cells (RBCs) of rats fed diets containing 1.1 mg Cu/kg (deficient, Cu-) and 6.0 mg Cu/kg (supplemented, Cu+) at age 3 wk for 9 wk. Data show an increase in cholesterol of 43% and in phospholipids of 38% per cell in Cu- compared with Cu+ rats. Thin-layer chromatography of RBC lipids showed an increased amount of phospholipid-malonyldialdehyde adduct in Cu- (0.70 +/- 0.35% [means +/- SD] of total phospholipids) compared with Cu+ (0.29 +/- 0.19%) rats, suggesting increased membrane lipid peroxidation in Cu- RBC. Osmotic fragility of RBCs from Cu- rats was lower. RBC viscosity was significantly higher in Cu- than in Cu+ rats at shear rates of 23, 11.5, and 5.75 shear/s and was similar at shear rates 115 and 46 shear/s. Increased cell viscosity caused by lipid loading and crosslinking of membrane components caused by lipid peroxidation may have a role in the reduced RBC survival and anemia in Cu deficiency.

Animals↗

A medical school fellowship program for minority high school students.

The effectiveness of a research program for minority high school students was evaluated. The program, supported by funding from the National Institutes of Health, was begun in 1982; during the subsequent five years, there were 59 applicants and 38 participants in the program. Of the responding 20 participants, 12 were pursuing careers in science and medicine, and half of the 16 respondents with career plans reported that the program had influenced their career decisions. Overall and in each year, black male students were underrepresented in both the applicant pool and the participants as compared with the metropolitan high school population.

Adolescent↗

Multiple myeloma: infectious complications.

We review a ten-year experience in treating 60 patients with multiple myeloma. Infectious episodes occurred in 33 patients. Urinary tract infections caused by gram-negative organisms were the most frequent infections, and most of these were the result of catheterization. Pneumonia due to Streptococcus pneumoniae was encountered infrequently. This series confirms the emergence of gram-negative bacilli as the predominant pathogens in patients with multiple myeloma, and emphasizes the risk of instrumentation in these patients.

Adult↗

Acquired ichthyosis in a child with rhabdomyosarcoma.

A generalized ichthyosiform eruption developed in a 13-year-old boy three weeks before presentation with a paravertebral rhabdomyosarcoma. His skin returned to normal shortly after the onset of chemotherapy and remission of the tumor. This case is unusual because the ichthyosis developed acutely, following a generalized urticarial eruption, and also involved the palms and soles.

Adolescent↗

Immunocytochemical examination of immune cells in periapical granulomata and odontogenic cysts.

Monoclonal antibodies (mAbs) were used to determine the presence and distribution of immune cells including lymphocytes, macrophages and Langerhans cells, in normal periodontal ligament, periapical granulomata, periapical cysts and dental developmental cysts. Isolated T-lymphocytes, but not B-lymphocytes, were detected in specimens of non-inflamed periodontal ligament. Increased numbers of T and B lymphocytes were found in all of the lesions examined. Monocytes/macrophages were associated with most periapical granulomata, dental developmental cysts and all periapical cysts. Langerhans cells, intraepithelial lymphocytes, and monocytes/macrophages were not detected in the rests of Malassez but were found in some epithelia within periapical granulomata and in most epithelial linings of odontogenic cysts. Increased numbers of immune cells were seen around proliferative epithelia and adjacent to the epithelial linings of cysts. Epithelium, particularly that of odontogenic cysts, showed positive reactions for HLA-Dr, lysozyme and for alpha-1 antitrypsin. The presence of immune cells in periapical granulomata and odontogenic cysts, suggests that cell-mediated and humoral immunoreactions occur in these lesions and may be associated with the epithelial proliferation within the periapical lesions.

Adult↗

Patterns of keratin-expression in rests of Malassez and periapical lesions.

Using immunocytochemistry and a panel of monoclonal antibodies directed against various keratin polypeptides we examined specimens of normal periodontal ligament, periapical granulomas and inflammatory dental cysts. Epithelial elements with the appearance of rests of Malassez were identified in 6 specimens of normal periodontium and 10 periapical granulomas. Altered epithelium was present in 16 periapical granulomas and a lining epithelium in 10 inflammatory dental cysts. The patterns of binding of antibodies by these epithelia indicated that (a) keratin 19 was expressed by all epithelia, and (b) rests of Malassez also expressed keratin 5 but not large amounts of other keratins and (c) epithelial proliferation in periapical lesions was associated with increased expression of keratin 14, a marker of stratifying epithelia, new expression of keratins 4 and 13, differentiation markers for non-cornifying epithelia and variable, low levels of keratins 8 and 18, markers of simple epithelia. Proliferation of the epithelial rests of Malassez to form the lining of inflammatory dental cysts thus appears to be associated with a change from an unusual epithelial phenotype to that of a stratified non-cornifying epithelium in which some simple epithelial keratins are coexpressed.

Adolescent↗

Gamma interferon-mediated cytotoxicity related to murine Chlamydia trachomatis infection.

After infection with the mouse pneumonitis agent (MoPn; murine Chlamydia trachomatis), heterozygous (nu/+) but not nude athymic (nu/nu) mice produced enhanced amounts of gamma interferon (IFN-gamma) in vitro in response to MoPn antigen that exhibited cytotoxic activity when added to host cells already infected with chlamydiae. Antibody-complement lysis showed the cytotoxic activity to be dependent, at least in part, on L3T4+ T cells for production. The cytotoxic responses were directed primarily against Chlamydia-infected target cells, but a second type of toxicity was demonstrable against uninfected target cells after treatment of the generating cell population with anti-Lyt-2 antibody plus complement at certain time points after infection. This additional nonspecific cytotoxic activity was presumably due to a second factor (factor X) acting in concert with IFN-gamma. Lyt-2+ cells, however, also were shown to play a role in IFN-gamma production and cytotoxicity directed against infected targets at later time points after infection. Neutralization of IFN-gamma in the samples containing cytotoxic activity abrogated the cytotoxicity against both infected and uninfected targets, but cloned murine IFN-gamma exhibited toxicity in a dose-dependent manner only against infected target cells. The data provides evidence that cytotoxicity against infected targets is due to antigen-specific induction of IFN-gamma, but other cytokine activity, most demonstrable after removal of Lyt-2.2+ cells and cytotoxic to uninfected targets, also is present.

Animals↗

Feasibility of high-resolution, intravascular ultrasonic imaging catheters.

A small-aperture, prototype ultrasonic imaging system, typical of the size necessary to be embedded in a catheter, was developed to evaluate the feasibility of intravascular ultrasonic imaging catheters (UICs). The evaluation included in vitro imaging of postmortem samples of human femoral and iliac arteries with the UIC prototype and a high-resolution magnetic resonance (MR) proton imager. Excellent correlations between results from the UIC images, MR images, and tissue specimens were demonstrated. Although the current prototype is too large to be useful in examination of smaller vessels such as coronary arteries, the signal-to-noise ratio and resolution obtained indicate that imaging with intravascular UICs is feasible and may have significant diagnostic value.

Arteries↗

Intracardiac thrombus and tricuspid valve obstruction: a complication of Hickman catheter use.

The risk of catheter-related sepsis is well recognized in immunocompromised patients with an indwelling central venous line, but the hazard of thrombus involving the right atrium is less well known. We report the case of a child who died after intraartrial thrombus obstructed the tricuspid valve. The predisposing factors and available treatment strategies are discussed.

Catheterization, Central Venous↗

Hearing loss in a glue sniffer.

A case is presented of a 27-year-old glue sniffing woman with sensorineural hearing loss, optic atrophy and global brain damage. This form of addiction has not received much attention as a cause of otologic catastrophes, and should be borne in mind where similar cases come to the otolaryngologist.

Adult↗