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Biomedical subjects

D M Carter

Publications and source records attributed to D M Carter.

At least 73 records · Page 4Linked to original sources
PubMed1986

Local environment of chronic wounds under synthetic dressings.

Local wound environment under oxygen-permeable and oxygen-nonpermeable dressings in patients with chronic ulcers was investigated. The oxygen tensions under both these dressings were very low or zero. Wound fluid was more acidic under the nonpermeable hydrocolloid dressing than under the oxygen-permeable polyurethane dressing. Bacterial growth studied in vitro was retarded at the more acidic pH similar to that found under the hydrocolloid dressing. Viable and functioning neutrophils were found under both the polyurethane and hydrocolloid dressings, with a greater percentage of viable cells under the polyurethane film. Our data suggest that these synthetic dressings create hypoxic conditions in which wound healing occurs whether or not the dressing is permeable to oxygen. Furthermore the local wound environment can be modified by use of synthetic dressings.

Aged↗
PubMed1986

Skin cancer in the elderly.

This article discusses the relation between aging and development of nonmelanoma skin cancer. Possible age-related risk factors for development of such cancers are cumulative exposure to ultraviolet irradiation from the sun, decreased DNA repair capacity, decreased immunosurveillance, reduced melanocyte density, and altered dermal matrix. Clinical features of basal-cell carcinoma, squamous-cell carcinoma, and keratoacanthoma are discussed.

Aged↗
PubMed1985

A membrane protein preferentially expressed by a subpopulation of immature lymphoid cells, epidermal basal keratinocytes, and other epithelial cells.

A murine monoclonal antibody, designated EL-1, was raised by immunization with a human malignant T cell line. It reacted specifically with a membrane antigen expressed on T and B lymphoblastoid cell lines, a subpopulation of normal thymocytes and bone marrow lymphocytes, lymphocytes from a subset of patients with non-B, non-T cell acute lymphoblastic leukemia or T cell acute lymphoblastic leukemia and epithelial stem cells. The latter reactivity was especially striking in the skin, where only basal epidermal keratinocytes and epidermal appendages, including eccrine sweat glands, sebaceous glands and hair follicles, stained positively. A human epidermoid carcinoma cell line was also stained by EL-1. Suprabasilar keratinocytes and acellular keratin did not stain. However, in vitro proliferating fetal lung fibroblasts stained positively. Membrane immunoprecipitation analysis demonstrated that the antigen recognized by antibody EL-1 is a single protein of molecular weight 105 kilodaltons which did not change with exhaustive chemical reduction. Metabolic radiolabeling studies demonstrated that this protein is synthesized by the cell and not merely taken up from the culture medium. This antibody can be useful in studying keratinocyte differentiation in epidermal malignancies and normal skin.

Animals↗
PubMed1985

Purification and in vitro growth of human epidermal basal keratinocytes using a monoclonal antibody.

We have made a new monoclonal antibody, EL-2, and used it with an immunorosetting procedure combined with Ficoll-Hypaque gradient centrifugation to purify and culture basal keratinocytes. Immunofluorescence of cell suspensions and immunoperoxidase staining of tissue sections demonstrate that EL-2 reacts with malignant cell lines, activated lymphocytes and monocytes, and basal keratinocytes. Sequential immunoprecipitation studies demonstrate that monoclonal antibodies EL-2 and 4F2 detect the same membrane protein. However, we have extended previous studies by making the new observation that both EL-2 and 4F2 react with cultured melanocytes. Basal keratinocytes were purified from single-cell epidermal suspensions by incubation with EL-2 followed by rosetting with rabbit antimouse IgG antibodies covalently linked to bovine red blood cells. Rosetting (basal) keratinocytes were separated from EL-2 negative cells by Ficoll gradient centrifugation. We obtained basal keratinocyte populations of greater than 90% purity as assessed by reactivity with EL-2 and another basal keratinocyte-specific monoclonal antibody, HCl. Langerhans cell, fibroblast, and melanocyte contamination was negligible. Cultures of basal keratinocytes were enriched in EL-2-reactive cells throughout the entire 19 days of culture studied. EL-2 is being used to characterize disorders of keratinocyte proliferation; EL-2 reacted with both squamous and basal cell carcinomas. EL-2 stained only the basal layer of lesional skin from patients with psoriasis, pityriasis rubra pilaris, and Darier's disease. Purification of basal keratinocytes will be important in biochemical and functional studies of normal skin and in establishing long-term keratinocyte lines from normal cells.

Antibodies, Monoclonal↗
PubMed1984

Oxygen modulates growth of human cells at physiologic partial pressures.

We have examined the growth of human diploid fibroblasts (WI-38 and IMR90) as a function of initial seeding density and oxygen tension. Cells at young and mid-passage levels were subcultivated in Dulbecco's modified Eagle's medium with 10% fetal bovine serum at 0.005, 0.01, 0.03, 0.1, 0.3, 1, and 2 X 10(4) cells/cm2. Flasks were equilibrated before and after seeding with 1 of 10 gas mixtures containing the desired oxygen tension (9-591 mm Hg) and placed in incubators that measure and maintain a preset oxygen tension. The partial pressure of oxygen (PO2) in media of all flasks was determined at harvest. Cells were shielded from light of wavelength less than 500 nm. Cell growth varied inversely with oxygen tension and seeding density. At 50 cells/cm2, growth was maximal at PO2 9 and 16 mm Hg. Growth was progressively inhibited as the oxygen tension was increased. The population doubling increase at 14 d was 8.6 for PO2 9 and 16 mm Hg, 5.8 for PO2 42 mm Hg, 3.8 for PO2 78 mm Hg, 3.8 for PO2 104 mm Hg, and 3 for PO2 138 mm Hg. As the seeding density was increased, the differences in growth at PO2 less than 140 mm Hg were progressively minimized, such that at seeding densities of 10(4) cells/cm2 there was little difference in the rate of exponential growth or the final saturation density of cells cultivated between PO2 9 and 96 mm Hg. At all seeding densities tested, growth was progressively inhibited when the PO2 was increased greater than 140 mm Hg. The seeding density dependence of oxygen's influence on cellular growth is not explained by oxygen consumption of higher density cultures. Oxygen acts directly on the cells and not by destroying some essential medium component. We have found that oxygen regulates the growth of human cells under pressures of oxygen physiologic to humans, and that oxygen toxicity contributes to the seeding density dependence of cellular growth commonly seen in cell culture.

Cell Count↗
PubMed1984

Low-sulfur hair syndrome associated with UVB photosensitivity and testicular failure.

A 16-year-old male patient had a syndrome that included growth retardation, mental retardation, hair shaft abnormalities, neurosensory hearing loss, contractures of the fifth fingers, ultraviolet B (UVB) photosensitivity, small testicular size, and elevated levels of follicle-stimulating hormone. Reduced hair sulfur content and a characteristic pattern of light and dark birefringent bands, seen when hairs were viewed with polarization microscopy, were typical of the low-sulfur hair syndrome. UVB photosensitivity and testicular failure have not previously been identified as components of this syndrome.

Adolescent↗
PubMed1984

Quantitative tests for psoralens in the blood: methods and uses in monitoring psoralen and longwave radiation therapy.

Variability in 2 factors determines the therapeutic success of photochemotherapy with psoralens and UV radiation at 320-400 nm (PUVA): biochemical properties of the photosensitizing drug used and characteristics of the source of irradiation. Fine-tuning of PUVA therapy is achieved by delivery to the patient of the phototoxic dose of UV radiation at the precise time of peak bioavailability of the photosensitizing psoralen; thus it depends on accurate means for measuring the 2 variables. The UV emission is easily measured, but bioavailability of photosensitizing drugs is not. Blood levels provide information about the photosensitivity of the patient and thus relate to therapeutic efficacy. The oral dose of 8-methoxypsoralen (8-MOP) cannot be used to predict what plasma levels of the drug will be achieved. Dissolution and absorption of 8-MOP are affected by the form of the preparation. Absorption rates vary far more than do elimination rates in the same population of patients, but individual differences in metabolism of the drug have not been documented. Maximum therapeutic benefit varies from individual to individual. It may be influenced by factors affecting absorption, distribution, and metabolism of the drug and by skin type and degree of skin pigmentation.

Blood Proteins↗
PubMed1982

Photopromotion of sister chromatid exchanges by psoralen derivatives.

Several derivatives of 8-methoxypsoralen and 4,5'8-trimethylpsoralen were compared with respect to their photopromotion of sister chromatid exchanges. Peripheral blood leukocytes from heparinized blood of human volunteers were cultivated for 24 h. Selected flasks received psoralens (6.5 X 10(-8) M) and/or were irradiated (UV-A, 365 nm, 0.9 J/cm2). Bromodeoxyuridine (20 micrograms/ml) was added and flasks were further incubated for 48 h when colchicine was added. Spreads of mitotic chromosomes were prepared, stained with Hoechst 33258 and Giemsa, and scored for the number of sister chromatid exchanges (SCEs) per 100 chromosomes. Results were: Control (16.5); 8-methoxypsoralen (23.9); 5'-methyl-8-methoxypsoralen (25.7); 4-methyl-8-methoxypsoralen (27.8); 4,5'-dimethyl-8-methoxypsoralen (31.9); 4'-methoxymethyl, 4,5'8-trimethylpsoralen (42.9); 4'aminomethyl, 4,5'8-trimethylpsoralen-hydrochloride (59.1); 4'hydroxymethyl,4,5'8-trimethylpsoralen (75). In general, the psoralens with strong affinity for DNA as determined by KD values promoted more SCEs than did those with lower affinity. Trimethylpsoralen and its derivatives promoted more SCEs than did 8-methoxypsoralen and its derivatives, which may be indicative of relative DNA cross-linking potential.

Cells, Cultured↗
PubMed1981

Cell cycle analysis of cultured mammalian cells after exposure to 4,5',8-trimethylpsoralen and long-wave ultraviolet light.

Cell cycle analysis was used to study the the effect of 4,5'8-trimethylpsoralen (TMP) and long-wave ultraviolet light (UV-A) on cultured mammalian cells. DNA distribution patterns were measured for murine melanoma cells (a cloned line of Cloudman S91) and a strain of diploid human skin fibroblasts (CRL 1295) using both a microfluorimetry procedure and flow cytometry. The untreated cells and those receiving TMP along and UV-A alone had identical DNA content as assessed at several posttreatment intervals (0-72 hr). The majority of cells in control groups contained a G1 DNA content, whereas exposure to TMP (2 x 10(-7) M) plus UV-A (1 Joule/cm2) led to the accumulation of cells in the G2 phase. These observations were similar for each cell type and both analytical techniques were in excellent agreement. The finding that psoralen plus UV-A induces a phase-specific G2 blockade in cultured cells has important implications for understanding the mechanisms which account for enhanced pigmentation and suppression of cellular proliferation following exposure to these agents in vivo.

Animals↗
PubMed1981

Proliferative response patterns of human fibroblasts after photoinjury with 4,5',8-trimethylpsoralen.

The extent of growth suppression and recovery following exposure to 4,5',8-trimethylpsoralen (TMP) plus UV-A irradiation was studied in 3 diploid human fibroblast strains. Inhibition of cellular proliferation was dose-dependent within the concentration range of TMP that was tested (1-4 X 10(-7) M), using a constant level of UV-A (0.24 J/cm2). The population generation (doubling) times for all cell strains were progressively lengthened under these conditions while maximal cell densities were reduced. At 2-4 X 10(-7) M TMP in the presence of UV-A, there was a triphasic pattern of growth which consisted of (1) proliferative activity during the first 24-36 hr, followed by; (2) complete growth inhibition for variable periods of time and; (3) a recovery period of log phase proliferation that was not as vigorous as measured for untreated cells. There were also declines in the percentage of cells labeled with 3H-Tdr at various times after TMP-UV-A treatment. These measurements were essentially identical for the three fibroblast strains evaluated. In that the cells employed for these investigations were derived from embryonic pulmonary tissue, neonatal foreskin and the buttock skin of an adult male, it seems unlikely that donor age and tissue source were important variables in determining growth response patterns after TMP-UV-A exposure. Because proliferative recovery was attenuated after this photochemical injury, we conclude that the biologic effect(s) of TMP-UV-A extend beyond the known period of psoralen-DNA cross-link removal.

Adult↗
PubMed1981

Dose-response relations in phototoxicity due to 8-methoxypsoralen and UV-A in man.

Serum levels and skin photosensitivity following different oral doses of 8-methoxypsoralen (8-MOP) were studied in 8 healthy volunteers. Two hours after ingestion of drug, serum levels of 8-MOP determined by high pressure liquid chromatography correlated well with oral dose. Serum concentrations after 8-MOP doses of 0.3, 0.6 and 0.9 mg/kg bodyweight were 25.9 (+/- 7.2), 148.9 (+/- 24.4) and 311.4 (+/- 55.6) ng/ml (mean and SEM) respectively. The minimal phototoxic dose (MPD) of UVA 2 hr after ingesting 8-MOP was determined in 6 volunteers for each of the 3 before-mentioned 8-MOP doses. The UV-A doses correlated inversely with the serum level for each individual (r = 0.92 +/- 0.02 SEM). For higher 8-MOP doses the numerical product of UV-A dose and 8-MOP serum concentration in each individual tended to be constant, indicating a reciprocal relationship between 8-MOP and UV-A doses in this interval. This did not hold true for the lowest 8-MOP-dose. These data confirm the relevance of using 8-MOP blood level determinations in monitoring psoralen-UV-A phototoxicity.

Adult↗