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Biomedical subjects

D M Carter

Publications and source records attributed to D M Carter.

At least 91 records · Page 5Linked to original sources
PubMed1980

Plasma levels of 8-methoxypsoralen determined by high-pressure liquid chromatography in psoriatic patients ingesting drug from two manufacturers.

We have adapted a rapid and sensitive high-pressure liquid chromatographic technique (HPLC) to measure plasma levels of 8-methoxypsoralen (8-MOP) in 22 psoriatic patients receiving photochemotherapy with 8-MOP and long-wave ultraviolet light (PUVA). In this procedure, 1 ml plasma samples containing ammidin as an internal standard are extracted with benzene. After evaporation under nitrogen the residue is redissolved in methylenechloride:acetonitrile, 95:5, and chromatographed using a normal phase HPLC system with a 10 mu silica particle column and a UV detector at 254 nm. The sensitivity of the method is 10 ng/ml plasma. Plasma concentrations of 8-MOP were measured between 2 and 4 hr after ingestion of therapeutic doses of 8-MOP provided by 2 manufacturers. Mean 8-MOP plasma levels were 27 +/- 35 ng/ml plasma 2 hr after ingestion of the only drug presently available on the U.S. market, 8-MOP (Elder). These values were significantly below (p less than 0.001) those obtained with 8-MOP (Roche) which were 104 +/- 79 ng/ml plasma. A number of patients on 8-MOP (Elder) did not have detectable levels of 8-MOP 2 hr after ingestion. The time course patterns also differed, possibly indicating a slower and less complete absorption for 8-MOP (Elder). Repeated time course studies in the same patient were reproducible although the absolute concentrations showed some variation. Preliminary evidence indicates that the plasma levels of 8-MOP have therapeutic relevance.

Adolescent↗
PubMed1980

Chlorpromazine phototoxicity: growth inhibition and DNA-interaction in normal human fibroblasts.

Growth was impaired in normal human skin fibroblasts following treatment with chlorpromazine and long-wave ultraviolet light (UV-A). The degree of impairment was dose dependent to chlorpromazine within the concentration range tested, 2.5-20 microgram/ml, in the presence of UV-A, 1 J/cm2. Pre-irradiated chlorpromazine at a concentration of 20 microgram/ml had no effect on fibroblast growth. Chlorprotixene, a thioxanthene compound structurally similar to chlorpromazine at a concentration of 10 microgram/ml, was not phototoxic in this system. The effects of chlorpromazine and UV-A on fibroblast DNA were studied using the technique of zone sedimentation in alkaline sucrose. In the absence of light chlorpromazine did not affect sedimentation of DNA. After UV-A irradiation at 20 degrees or 0 degrees C in the presence of chlorpromazine, labeled DNA sedimented more slowly indicating that it had been reduced to smaller fragments. No evidence for interstrand DNA cross-links was found. Chlorpromazine alone or in combination with UV-A did not alter the size of the DNA. These results with cultured fibroblasts indicate that the phototoxic action of chlorpromazine at 366 nm is at least partially explained by interaction with DNA and is not due to the effects of cytotoxic photoproducts.

Cell Count↗
PubMed1979

Interstrand crosslinks in DNA of phage lambda after exposure to 8-methoxypsoralen and trimethylpsoralen in the presence of light.

Two medically useful photosensitizing furocoumarins, 8-methoxypsoralen (8-MOP) and 4,5'8-trimethylpsoralen (TMP) were compared with respect to their abilities to produce interstrand crosslinks in DNA. DNA from bacteriophage lambda, labeled with 32P, was subjected to sedimentation in alkaline sucrose gradients following exposure to several concentrations of 1 of the 2 psoralens and irradiation (UV-A, 360 nm) for various times. In alkaline sucrose gradients, crosslinked DNA molecules sediment about 1.4 times faster than undamaged DNA strands and the proportion of molecules carrying crosslinks can be estimated with reasonable accuracy. At equimolar psoralen concentrations (2 x 10(-7)M, or 4 x 10(-5)M) and with increasing irradiation times, the rate of production of crosslinked DNA was 4 to 30 times greater for TMP than for 8-MOP. Differences in the therqpeutic efficacy of 8-MOP and TMP in various clinical situations may be accounted for by the types of photoadducts formed by each drug as well as by their solubilities, rates of absorption and rates of metabolic degradation.

Coliphages↗
PubMed1979

Psoralen-DNA cross-linking photoadducts in dyskeratosis congenita: delay in excision and promotion of sister chromatid exchange.

Dyskeratosis congenita is a rare X-linked recessive disease, characterized by mucosal leukokeratosis, nail dystrophy, telangiectasia, reticulated hyperpigmentation, pancytopenia, and a heightened susceptibility to infection and malignancy. We exposed cultured fibroblasts and peripheral leukocytes from normal persons and from 2 unrelated young adult men with dyskeratosis congenita to 4,5',8-trimethylpsoralen and ultraviolet light. We than compared certain of their responses. Labeled DNA from fibroblasts exposed to 4,5',8-trimethylpsoralen and ultraviolet light showed fast-sedimenting DNA, a pattern we interpreted as evidence that cross-linking, psoralen-DNA photoadducts had been formed by the treatment. Fast-sedimenting DNA persisted for 24 hr in dyskeratosis congenita cells but disappeared from normal cells during a 24-hr repair period. Cultured peripheral blood leukocytes from persons with this syndrome similarly exposed to 4,5',8-trimethylpsoralen and ultraviolet light developed more sister chromatid exchanges than did cells from normal persons. These data suggest that a heightened susceptibility in DNA cross-links may be of fundamental importance in the etiology of dyskeratosis congenita.

Adolescent↗
PubMed1978

Greater promotion in sister chromatid exchanges by trimethylpsoralen than by 8-methoxypsoralen in the presence of UV-light.

The number of sister chromatid exchanges (SCEs) was determined in normal human leukocytes following exposure in vitro to UV light (365 nm, UV-A) and either 8-methoxypsoralen (8-MOP) or 4,5'8 trimethylpsoralen (TMP). Both psoralens produced an increase in SCEs, proportional to UV dose and concentration of drug. Neither drug alone nor UV alone promoted SCEs. The number of SCEs per cell was greater in leukocytes irradiated in the presence of TMP than in the presence of equimolar 8-MOP. At equimolar concentrations, TMP formed more cross-links than did 8-MOP. The difference in the effects of these 2 agents on various cell functions may relate to quantitative and qualitative differences in the photoadducts they form.

Chromatids↗
PubMed1976

Effect of pigment on photomediated production of thymine dimers in cultured melanoma cells.

It was the aim of these studies to determine whether the presence of intracellular melanin quantitatively alters the rate of production of thymine dimers in DNA of irradiated cells in culture. Pigmented and nonpigmented Cloudman mouse melanoma cells were selected assuming that the two cell lines differ primarily in their content of melanin pigment. Cells were cultivated in tritiated thymine in order to label their DNA and were then exposed to ultraviolet (UV) irradiation (260 nm, 500-2000 ergs/mm2). Neither cell line survived these doses of irradiation. DNA was extracted immediately following irradiation and was subjected to acid hydrolysis. The presence of thymine dimers was determined by two-dimensional paper chromatography. The percent of labeled thymine recovered as thymine dimer was calculated and was found to be a linear function of UV dose for both cell lines. The rate of formation of dimers in the nonpigmented cells was nearly twice that in the pigmented cells. These data demonstrate the photoprotective property of intracellular melanin in shielding isolated cells from one type of photomediated injury to DNA.

Animals↗
PubMed1976

8-methoxypsoralen and UVA promote sister-chromatid exchanges.

8-Methoxypsoralen (8-MOP) and long-wave UV light (UVA 365 nm) are now being use to treat vitiligo and psoriasis. Cultured human lymphocytes exposed to these agents in vitro show an increased infrequency of sister chromatid exchanges, related to 8-MOP-DNA photoadducts. Although these data raise questions regarding the biologic consequences of this therapeutic regimen, it is unknown whether 8-MOP and UVA cause mutations or extracutaneous somatic cell recombinants in vivo. Exchanges may represent cellular repair of DNA damage.

Cells, Cultured↗
PubMed1976

Alopecia areata and Down syndrome.

The skin of 214 institutionalized patients with the Down syndrome was carefully examined. There were 19 cases of alopecia areata and four cases of vitiligo. Since persons with the Down syndrome are predisposed to immunological deficiency in thymus-dependent (T-cell) function, findings from the skin examinations suggest that immunologic factors might contribute to the increased incidence of vitiligo and alopecia areata seen in the Down syndrome. Syringoma was also common and affected female patients twice as frequently as male patients.

Adenoma↗
PubMed1975

Ultrastructure of the skin in mucopolysaccharidoses. Studies performed before and after plasma infusion therapy.

Skin biopsy specimens of two siblings with Hunter syndrome and two siblings with type B Sanfilippo syndrome were examined by electron microscopy, at six-month intervals, before and after plasma infusion therapy. Electron-lucent, membrane-bound vacuoles were seen in fibroblasts, Schwann cells, and in mononuclear cells both before and after the infusions. Based on the ultrastructural, clinical, and biochemical findings, it was concluded that there was no therapeutic benefit from these plasma infusions.

Child↗