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Biomedical subjects

D Cooper

Publications and source records attributed to D Cooper.

At least 19 recordsLinked to original sources

Transendothelial migration of neutrophils involves integrin-associated protein (CD47).

Inflammation is a primary pathological process. The development of an inflammatory reaction involves the movement of white blood cells through the endothelial lining of blood vessels into tissues. This process of transendothelial cell migration of neutrophils has been shown to involve neutrophil beta 2 integrins (CD18) and endothelial cell platelet-endothelium cell adhesion molecules (PECAM-1; CD31). We now show that F(ab')2 fragments of the monoclonal antibody B6H12 against integrin-associated protein (IAP) blocks the transendothelial migration of neutrophils stimulated by an exogenous gradient of the chemokine interleukin 8 (IL-8; 60% inhibition), by the chemotactic peptide N-formyl-methionylleucylphenylalanine (FMLP; 76% inhibition), or by the activation of the endothelium by the cytokine tumor necrosis factor alpha (98% inhibition). The antibody has two mechanisms of action: on neutrophils it prevents the chemotactic response to IL-8 and FMLP, and on endothelium it prevents an unknown but IL-8-independent process. Blocking antibodies to IAP do not alter the expression of adhesion proteins or production of IL-8 by endothelial cells, and thus the inhibition of neutrophil transendothelial migration is selective. These data implicate IAP as the third molecule essential for neutrophil migration through endothelium into sites of inflammation.

Antibodies, Monoclonal

Oral capsaicin provides temporary relief for oral mucositis pain secondary to chemotherapy/radiation therapy.

Pain from oral mucositis afflicts from 40% to 70% of patients receiving chemotherapy or radiation therapy. Current methods of clinical pain management (for example, topical anesthetics, systemic analgesics) have limited success. In a pilot study, we examined the ability of oral capsaicin to provide temporary relief of oral mucositis pain. Capsaicin, the active ingredient in chili peppers, desensitizes some neurons and has provided moderate pain relief when applied to the skin surface. Oral capsaicin in a candy (taffy) vehicle produced substantial pain reduction in 11 patients with oral mucositis pain from cancer therapy. However, this pain relief was not complete for most patients and was only temporary. Additional research is needed to fully utilize the properties of capsaicin desensitization and thus optimize analgesia.

Administration, Oral

P-selectin interacts with a beta 2-integrin to enhance phagocytosis.

P-selectin is an adhesion molecule for myeloid cells that seems to be essential for the development of cellular inflammatory responses. We show that adhesion of neutrophils to purified and recombinant P-selectin enhances the phagocytosis of unopsonized zymosan particles as judged by the number of cells ingesting particles (30.2 +/- 5.8 vs 14.5 +/- 4.0, p = 0.002) and the number of particles ingested per cell (percentage increase 58.3 +/- 4.4%. p = 0.0002). The enhanced phagocytosis was inhibited by Abs to CD18 or CD11b, suggesting that P-selectin alters beta 2-integrin function. The enhancement was only seen in the presence of cations allowing the integrin to assume a particular extracellular conformation. Furthermore, P-selectin, although not altering the total expression of CD18 on neutrophils, significantly increased the binding of mAb 24, which detects an activation-dependent epitope. Our results support a signaling role for P-selectin in influencing beta 2-integrin function.

Animals

Early detection of de novo hepatitis C infection in patients after liver transplantation by reverse transcriptase polymerase chain reaction.

BACKGROUND: Reverse transcriptase polymerase chain reaction (RT-PCR) can detect the viral genome and show hepatitis C recurrence in patients who undergo transplantation for chronic hepatitis C viral (HCV) infection. We investigated the utility of an RT-PCR-based HCV assay for early detection of viral RNA in de novo HCV infection after liver transplantation. METHODS: Pretransplantation antibodies and explanation HCV viral RNA status were obtained from 117 patients. Follow-up liver biopsy specimens were examined for evidence of hepatitis activity. Plasma samples during the period of time of the biopsy were assayed for HCV antibody and viral RNA. RNA was extracted from samples and reverse transcribed to cDNA. cDNA was amplified by PCR, and products were detected by liquid hybridization. RESULTS: Clinical hepatitis developed in seventeen of 117 patients who, before transplantation, were HCV antibody negative and explant viral RNA negative. Ten patients were plasma PCR negative and had known non-hepatitis C causes for the biopsy findings. Of the remaining seven patients, five (70%) were plasma RT-PCR positive before seroconversion in matched plasma samples. CONCLUSIONS: In liver transplant patients, the incidence of de novo clinical hepatitis is low, and HCV viral RNA in de novo clinical hepatitis C infection can be detected in the absence of HCV antibodies.

Base Sequence

Varicella-zoster virus infection in Romanian children infected with the human immunodeficiency virus.

OBJECTIVE: Varicella-zoster virus (VZV) infections can cause severe disease in immunocompromised individuals. To evaluate the spectrum of VZV infections in human immunodeficiency virus (HIV)-infected children, we retrospectively analyzed all the cases of VZV infection in a cohort of children cared for at a hospital for infectious diseases in Bucharest, Romania. METHODS: The records of 391 HIV-infected children admitted to the acquired immunodeficiency syndrome pavilion of Colentina Hospital during the period January 1, 1991, through March 31, 1992, were reviewed for evidence of VZV infection. The diagnosis of varicella or zoster was made clinically and information was collected concerning course of the illness, number of skin lesions, and clinical evidence of complications. Lymphocyte subpopulation typing, as an estimate of immune function, was performed by either a standard fluorescent activated flow cytometric method or by immunofluorescent technique. RESULTS: Thirty-eight cases of varicella (9.7%) and seven cases of zoster (1.8%) were adequately documented among the 391 records reviewed. The duration of varicella was prolonged; in 57% of the children it was greater than 10 days. Forty percent of children with varicella developed a complication, including superinfection of the skin, pneumonia, or thrombocytopenia. None of the children developed clinical hepatitis or encephalitis. Two children (5%) died during varicella, both of respiratory failure. None of the 7 children with zoster had chronic, recurrent, or disseminated lesions. Lymphocyte subset analysis was available for 22 of 38 children with varicella and 3 of 7 children with zoster. Fifteen of the 22 children had normal, age-adjusted, absolute CD4 counts within 3 months of the diagnosis of varicella. All 3 children with zoster who had lymphocyte subset analysis had low CD4 counts and absolute numbers. None of the 45 children received antiretroviral therapy and only 1 child with varicella and 1 with zoster received acyclovir. CONCLUSIONS: The spectrum of VZV infection in this hospitalized group of HIV-infected children was broad. The majority (57%) experienced a prolonged course of disease and a higher rate of complications than normal children hospitalized with varicella.

CD4-Positive T-Lymphocytes

Use of a novel technique of cutaneous lavage for diagnosis of Lyme disease associated with erythema migrans.

OBJECTIVE: Determining the microbial cause of cellulitis is often difficult. In this study, a novel two-needle lavage technique was used to culture Borrelia burgdorferi from the skin of suspected erythema migrans lesions. DESIGN: The yield of lavage cultures for B burgdorferi was compared with that of a 2-mm skin biopsy sample. SETTING: A Lyme disease diagnostic center located in an area in which Lyme disease is epidemic. PATIENTS: Forty-five patients with suspected erythema migrans who had not been treated with antimicrobial agents. INTERVENTION: Cutaneous lavage of the advancing edge of a suspected primary erythema migrans lesion was done for all 45 participants, 33 of whom also had a skin biopsy of the same lesion at an identical (14) or an adjacent (19) site. MAIN OUTCOME MEASURES: Growth of B burgdorferi in in vitro culture. RESULTS: Lavage fluid cultures grew B burgdorferi in 13 (29%) of the 45 cases (95% confidence interval [CI], 16% to 44%). Among the 33 cases in which both lavage and skin biopsy cultures were done, the yield of lavage culture was less than that of biopsy culture (P less than .09, 12/33 vs 20/33). If contaminated cultures are excluded, this difference is significant (P less than .05, 12/30 vs 20/27). CONCLUSION: Cutaneous lavage is a new diagnostic technique for recovery of B burgdorferi from erythema migrans lesions that has potential applicability to other types of cutaneous infections.

Biopsy

Growth of the normal human lower urinary tract from 12 to 21 weeks gestation.

Normal development of the human lower urinary tract was studied between the 14th and 20th week of gestation using 3 modes of fixation. Fixation by direct distension provides a high degree of reproducibility of parameters used to study the growth of the fetal bladder. Using this method, fetuses ranging from 12 to 21 weeks gestation were studied. Results obtained demonstrate that the length of the bladder, the inter-ureteric distance, and the distance between the apex of the trigone and the distal tip of the urethra occur in a linear mode. Furthermore, the rate of growth of the male urethra was evidently higher when compared to that of the female from the 12th week of gestation. Data from this work can be used for a more accurate assessment of cases with abnormal lower urinary tract development.

Female

Photosensitivity, abnormal porphyrin profile, and sideroblastic anemia.

Cutaneous photosensitivity in a 43-year-old man with idiopathic sideroblastic anemia associated with an abnormal porphyrin profile is reported. This condition was associated with elevated free erythrocyte porphyrin, plasma protoporphyrin, urine porphyrins (predominantly coproporphyrin), stool porphyrins (predominantly protoporphyrin), decreased ferrochelatase activity, and deletion of portions of the long arms of chromosomes 18 and 20. Five other patients with sideroblastic anemia and abnormal porphyrin profiles have been described; all but one of these patients had photosensitivity. The porphyrin profile of this patient is similar to that of three other previously described patients.

Adult

Antithyroid drug effects on function and growth of FRTL-5 cells.

Although antithyroid drugs (ATDs) are known to exert their effects by inhibiting iodide organification within the thyroid follicular cell, a full understanding of their mechanisms of action is lacking. In this study the effects of methimazole (MMI) and propylthiouracil (PTU) on thyrotropin (TSH) and thyroid-stimulating immunoglobin (TSI)-stimulated cAMP production and growth in FRTL-5 cells was investigated. MMI, but not PTU, inhibited TSH-stimulated cAMP production, but only at the very highest concentration (10(-3) M): 0.3 +/- 0.01 vs 0.79 +/- 0.13 pmol/micrograms protein (p < 0.01). Neither MMI nor PTU inhibited TSI-stimulated cAMP production at any dose. Neither MMI nor PTU exhibited an inhibitory effect on TSH- or TSI-stimulated cell growth, as measured by [3H]-thymidine incorporation. These observations suggest that high concentrations of MMI may act to control thyroid function by inhibiting receptor-mediated cAMP production. Although decreases in thyroid gland size frequently occur during ATD therapy, neither MMI nor PTU exhibited any effect on TSH- or TSI-stimulated thyroid cell growth.

Animals

The management of acute laryngo-tracheo-bronchitis (croup): a consensus view.

The management of croup relies upon the traditional clinical skills of observation and examination. Parental involvement is essential and the appropriate reassurance of the patient is important. Endotracheal intubation is required only in a small percentage of children whose airway is compromised to such a degree as to produce fatigue and/or near occlusion.

Adrenal Cortex Hormones

Diagnosis of early Lyme disease by polymerase chain reaction amplification and culture of skin biopsies from erythema migrans lesions.

Current laboratory diagnosis of Lyme disease relies on tests for the detection of antibodies to Borrelia burgdorferi, the etiologic agent of the disease. These tests are often unreliable because of a lack of sensitivity and specificity and test-to-test variability. The purpose of this study was to evaluate the sensitivity and specificity of polymerase chain reaction (PCR) amplification for detection of B. burgdorferi in skin biopsy specimens. Forty-six 2-mm skin biopsy samples were obtained from 44 patients with a clinical diagnosis of erythema migrans, 9 of whom were receiving antibiotic therapy at the time of biopsy. Specimens were ground in BSK medium with separate aliquots taken for culture and PCR. Of the specimens from the untreated group, 57% (21 of 37) were positive by culture and 22% (8 of 37) were culture negative; 22% (8 of 37) of the cultures were uninformative because of contamination. By comparison, 22 (59%) of 37 specimens were positive by PCR amplification. Of 21 culture-positive samples, 13 (62%) were also positive by PCR analysis. Thus, the sensitivity of the PCR was 59 to 62%, based on either a clinical or cultural diagnosis of untreated Lyme disease. None of the nine specimens from antibiotic-treated patients grew in culture, whereas two of the nine were positive by PCR analysis. Given the complexity and time required for culture, PCR is a promising technique for the diagnosis of early Lyme disease.

Base Sequence

A computer-aided socket design procedure for above-knee prostheses.

A computer-aided socket design procedure (CASD) has been developed whereby an above-knee socket shape can be created based on anthropometric measurements taken from an amputee. The anthroometric measurements are used to select a subset of three reference shapes from a Reference Shape Library stored in the computer in the form of three-dimensional numerical data. Transformation procedures then scale the reference shapes at each cross-sectional level to match the amputee's cross-sectional areas. Blending of the three shapes is determined by tissue mass weighting factors, to yield a single custom socket configuration, known as the "basic socket shape." Subsequent graphical procedures in the CASD system allows further sculpting of the shape in the form of interactive adjustments of the numerical data to reach the socket shape desired by the prosthetist. The resultant shape data can then be transferred to a computer numerically controlled (CNC) milling machine to carve a model of the socket shape.

Artificial Limbs

To what extent do interactive pictures promote recall?

In four experiments, a total of 352 subjects viewed word pairs alone or accompanied by pictures, after which they were given a cued-recall test. Although Exps. 1 and 2 showed that recall of brand names was similar with separate and with interactive pictures, it was argued that the latter provided a cue enabling subjects to combine the separate components mentally. In Exp. 3, recall of both low concrete nouns and brand names was enhanced with interactive pictures and the effect was replicated in Exp. 4 with subjects who were learning English. These results offer hope to advertisers who wish to use interactive pictures whose relationship to their names is indirect.

Adolescent

Urbanisation and women's health in Khayelitsha. Part I. Demographic and socio-economic profile.

Demographic and socio-economic data and information on migration patterns and urban/rural links was collected from 722 households in the formal housing area and the serviced and the unserviced site areas of Khayelitsha; 659 women and 61 men were interviewed. Thirty-eight per cent of the population were aged under 15 years and 77% under 35 years. There was a predominance of females in the 5-35-year age group. There was a mean of 4.9 persons per household, and 93.5% of sites contained 1 dwelling. Of the 659 female respondents, 7% had received no formal education, 39% had primary school education, and 54% had secondary school education. Unemployment among women was 45%. Domestic service accounted for 66.2% of formal employment. Of all women 86% were unskilled, 71.9% had been born in a 'homeland', and 69.7% had migrated to an urban area before 1985. Ties to the rural areas were strong, particularly in the 'shack' areas. 'New arrivals' to an urban area were young, mostly unemployed, and lived in the worst environmental conditions. In the unserviced 'shack' areas, 47.5% of women had migrated to an urban area in the last 5 years. There are important target areas for a study of the health effects of urbanisation and for possible interventions. This study tends to confirm the 'quadruple' oppression of women in Khayelitsha, on the basis of race, social class and gender and as new arrivals in an urban environment.

Adolescent

Urbanisation and women's health in Khayelitsha. Part II. Health status and use of health services.

A study was conducted among women in Khayelitsha to determine the relationship between urbanisation, health status and use of health services; 722 households were visited, and 659 female respondents provided information on acute and chronic illness for the 3,229 individuals who were members of their households. In addition, they provided information concerning their reproductive health, AIDS awareness, knowledge of cervical smears and use and knowledge of health services. Acute illness was reported for 4.3% of the study population, the commonest complaints being diarrhoea, abdominal pain and upper respiratory infections; 4.4% reported chronic illness, the commonest complaints being hypertension and tuberculosis; 16.2% of women reported gynaecological illness; 86% had of heard of AIDS (although their knowledge of transmission and prevention was poor); and 45% had heard of cervical smears. Patterns of illness and knowledge and use of health services vary in the different areas of residence of Khayelitsha. This appears to be related to urbanisation, age, and environmental and socio-economic factors.

Black or African American