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Biomedical subjects

H W Lim

Publications and source records attributed to H W Lim.

At least 73 records · Page 4Linked to original sources

The effect of L-cysteine and N-acetylcysteine on porphyrin/heme biosynthetic pathway in cells treated with 5-aminolevulinic acid and exposed to radiation.

The effects of L-cysteine (LC) and N-acetylcysteine (NAC) on porphyrin accumulation in a human dermal microvascular endothelial cell line (HMEC-1) and a human epidermoid carcinoma cell line (A431) loaded with 5-aminolevulinic acid (ALA) and exposed to ultraviolet A (UVA) and blue light radiation were determined. Porphyrin accumulation was decreased in the presence of 0.1-7.5 mM LC (24.8%-31.4% suppression in HMEC-1 cell; 35.8%-48.9% suppression in A431 cells), and in the presence of 0.1-10.0 mM NAC (30.9%-58.0% suppression in HMEC-1 cells; 8.5%-45.3% in A431 cells). The suppression occurred in a LC or NAC dose-dependent fashion. The above was associated with partial reversal of suppression of ferrochelatase (FeC) activity in HMEC-1 cells and in A431 cells. As compared to FeC activity in cells treated with ALA and irradiation, enzyme activity was higher (by 31.9%-62.1%) in the presence of LC (1.0 mM or 5.0 mM) and in the presence of NAC (1.0 mM or 5.0 mM). These data indicate that LC and NAC have protective effects on porphyrin- and irradiation-induced diminution of FeC activity in HMEC-1 cells and A341 cells in vitro.

Acetylcysteine↗

Abnormal serum porphyrin levels in patients with the acquired immunodeficiency syndrome with or without hepatitis C virus infection.

OBJECTIVE: To define the contributions of human immunodeficiency virus (HIV) and hepatitis C virus infections to the development of porphyria cutanea tarda. DESIGN: Analysis of serum porphyrin levels in a cohort of 167 subjects. Serum samples were divided into 4 groups corresponding to the status of HIV and hepatitis C virus infections: positive-positive, positive-negative, negative-positive, and negative-negative. SETTING: Serum samples positive for HIV were obtained from the serum bank of an acquired immunodeficiency syndrome-HIV research center, and HIV-negative samples were obtained from a regional blood center. MAIN OUTCOME MEASURES: Spectrofluorometric measurement of serum porphyrin levels. RESULTS: The median values of porphyrin were 2.31 nmol/L (interquartile range [difference between the 25th and 75th percentiles]: 4.55) in the positive-positive group, 1.99 nmol/L (interquartile range: 1.63) in the positive-negative group, 1.31 nmol/L (interquartile range: 1.58) in the negative-positive group, and 1.14 nmol/L (interquartile range: 0.92) in the negative-negative group. The fluorescence emission spectra of samples with elevated porphyrin levels were identical with that reported for porphyria cutanea tarda. Elevated porphyrin levels were significantly associated with HIV infection (P < .001) and were observed in patients with an elevated level of alanine aminotransferase (P = .03). Infection with hepatitis C virus was also associated with an elevation in porphyrin levels, although the increase was not statistically significant (P = .16). Porphyrin levels in patients positive for HIV were not correlated with serum urea nitrogen or creatinine levels. None of the patients had symptomatic porphyria cutanea tarda. CONCLUSIONS: Factors associated with increased serum porphyrin levels included HIV infection, elevated alanine aminotransferase levels, and, to a lesser extent, hepatitis C virus infection. These findings suggest that patients with the above risk factors are potentially predisposed to the development of symptomatic porphyria cutanea tarda on further exposure to hepatotoxic agents.

Acquired Immunodeficiency Syndrome↗

Results of evaluation of 203 patients for photosensitivity in a 7.3-year period.

BACKGROUND: Although photosensitivity disorders have been well described, their incidence in a referral institution had not been studied. OBJECTIVE: The purpose of this study was to evaluate the incidence of photosensitivity disorders, including photocontact dermatitis, in an academic medical center. METHODS: The results of the assessment of 203 consecutive patients, all of whom had phototests, referred for the evaluation of photosensitivity disorders during a 7.3-year period were reviewed. RESULTS: The mean age was 50 years, and 63% of the patients were women. The most frequent diagnoses were polymorphous light eruption (26% of the total patient population), chronic actinic dermatitis (17%), photoallergic contact dermatitis (8%), systemic phototoxicity to therapeutic agents (7%), and solar urticaria (4%). Positive photopatch reactions, patch test reactions, or both were observed in 40 (29%) of the 138 tested patients. The frequencies of the positive photopatch test reactions were sunscreens (57%), fragrances (18%), and antimicrobial agents (13%). Of the positive patch test responses, fragrances elicited 47% of the total positive reactions, followed by sunscreens (39%) and antimicrobial agents (7%). CONCLUSION: Polymorphous light eruption, chronic actinic dermatitis, and photoallergic contact dermatitis were the most frequently made diagnoses. Sunscreens, fragrances, and antimicrobial agents were the most common clinically relevant photoallergens and allergens.

Academic Medical Centers↗

Is dermatologic usage of coal tar carcinogenic? A review of the literature.

BACKGROUND: Coal tar ointments have been used for decades in the treatment of various dermatoses, most notably eczema and psoriasis. Occupational exposure to coal tar poses an increased risk of developing cutaneous malignancies. The evidence of an increased risk of skin cancer in humans, as a result of dermatologic usage of tar, however, is conflicting. OBJECTIVE: A consensus on the carcinogenicity of tar is sought. METHODS: The existing literature (in vitro, animal, and human studies) on this subject is reviewed. RESULTS: The carcinogenicity of coal tar has clearly been demonstrated by in vitro and animal studies, and appears to be potentiated by concomitant use of ultraviolet radiation. Systemic absorption of mutagens from topically applied tar has been demonstrated in humans. Epidemiologic studies in humans, however, have not definitively shown an increase in skin cancer with therapeutic use of tar. CONCLUSIONS: Conclusive evidence for the carcinogenicity of tar used in dermatologic practice is lacking. Further controlled studies are necessary.

Animals↗

Etretinate as an effective adjunctive therapy for recalcitrant palmar/plantar hyperkeratosis in patients with erythrodermic cutaneous T cell lymphoma undergoing photopheresis.

BACKGROUND: Patients with erythrodermic cutaneous T cell lymphoma (CTCL) frequently have debilitating hyperkeratosis of the palms and soles that is refractory to therapy. OBJECTIVE: To evaluate the efficacy of etretinate as an adjunctive therapy for recalcitrant palmar and plantar hyperkeratosis in erythrodermic CTCL patients undergoing photopheresis. METHODS: Five patients with erythrodermic CTCL and recalcitrant palmar and plantar hyperkeratosis were given etretinate (0.8 mg/kg per day) while undergoing photopheresis therapy. RESULTS: There was a rapid and marked improvement of the hyperkeratosis in all patients. CONCLUSION: Etretinate is a safe and effective adjunctive treatment for recalcitrant palmar and plantar hyperkeratosis in erythrodermic CTCL patients undergoing photopheresis.

Aged↗

The effect of porphyrin and radiation on ferrochelatase and 5-aminolevulinic acid synthase in epidermal cells.

The effects of ultraviolet A (UVA) and blue light on ferrochelatase protein, and its mRNA level, in 5-aminolevulinic acid (ALA)-loaded A431 cells was evaluated. Western blot analysis of ferrochelatase protein showed a protein band of 43 kDa. There was a decrease in the protein concentration 24 h and 48 h after irradiation of these cells. In contrast, as judged by Northern blot analysis, there was no change in ferrochelatase mRNA level. Measurement of ALA synthase activity showed an ALA dose-dependent but radiation-independent decrease of enzyme activity, suggesting an end-product feedback inhibition. Since reactive oxygen species generated by porphyrin-induced photochemical reaction may be involved in the decrease in ferrochelatase protein, the effect of scavengers of reactive oxygen species was evaluated by measuring porphyrin accumulation in irradiated, ALA-loaded A431 cells. Porphyrin accumulation was significantly decreased in the presence of singlet oxygen scavenger sodium azide (0.05 mM, 40.6% suppression) or hydroxyl radical scavenger mannitol (5.0 mM, 45.0% suppression). These data suggest that the photochemical reaction induced by porphyrin and irradiation resulted in a decrease in ferrochelatase protein content, but had no effect on ferrochelatase mRNA level nor on ALA synthase activity. The decrease in protein was partly mediated by the reactive oxygen species.

5-Aminolevulinate Synthetase↗

Efficacy of ultraviolet B phototherapy for psoriasis in patients infected with human immunodeficiency virus.

To evaluate the efficacy of ultraviolet B (UVB) phototherapy for the treatment of psoriasis in patients infected with human immunodeficiency virus (HIV), the response of 14 patients was compared to that of matched seronegative control individuals. All patients were evaluated prior to treatment (baseline) and after 21 treatments for the extent of total body surface area (TBSA) involvement and the quantification of scale, erythema, and thickness of plaques using a scale of 0 (absent) to 4 (severe). The only concomitant medication allowed was salicylic acid in petrolatum. The cumulative score for scale, erythema, and thickness improved 1.9 +/- 0.5 [mean +/- standard error of mean (SEM)] in the HIV group and 2.4 +/- 0.3 in controls. There was 40.9 +/- 7.3% reduction of TBSA involvement in the former and 38.4 +/- 7.6% reduction in the latter group. None of the differences was statistically significant. There was no statistically significant difference in the response to therapy among various stages of immunosuppression in the HIV group. There was also no deterioration of immune status in this group. UVB phototherapy is an effective treatment for psoriasis in patients infected with HIV. The response is identical to that of matched control individuals.

Administration, Cutaneous↗

The effect of ALA and radiation on porphyrin/heme biosynthesis in endothelial cells.

To study porphyrin biosynthesis in human microvascular endothelial cells, HMEC-1 cells, a transformed human microvascular endothelial cell line, were incubated with 5-aminolevulinic acid (ALA), the precursor of endogenous porphyrins, and porphyrin accumulation was measured spectro-fluorometrically. The HMEC-1 cells accumulated porphyrin in a concentration-related and a time-dependent fashion. Protoporphyrin was the predominant porphyrin accumulated in the cells. The effect of light on protoporphyrin accumulation was evaluated by exposing the ALA-loaded HMEC-1 cells to ultraviolet-A (UVA) and blue light, followed by another incubation with ALA for 2-24 h. Enhancement of protoporphyrin accumulation in irradiated HMEC-1 cells was observed 2-24 h after irradiation, which was associated with a decrease in ferrochelatase protein and activity. Porphyrin accumulation from ALA after irradiation was significantly decreased when catalase (750-3000 U/mL, 29.3-44.3% suppression) or superoxide dismutase (270 U/mL, 36.4% suppression) was present during irradiation. These data demonstrate that HMEC-1 cells were capable of porphyrin biosynthesis, and that exposure of protoporphyrin-containing HMEC-1 cells to UVA and blue light, which includes the Soret band spectrum, decreased the ferrochelatase activity and its protein. These changes were mediated, at least in part, by reactive oxygen species.

Aminolevulinic Acid↗

Phototoxicity and photoallergy.

Phototoxic and photoallergic reactions resulting from a combined exposure to photosensitizing chemicals and light are common. Diagnosis of such reactions requires an understanding of its clinical presentation and recognition of commonly encountered photosensitizers. Phototesting allows identification of the photosensitizer and appropriate management of the patient.

Humans↗

The porphyrias and hepatocellular carcinoma.

Hepatocellular carcinoma probably represents the final step of the effects of the various precipitating agents for porphyria cutanea tarda, such as alcohol, drugs, hormones, and hepatitis C infection. Risk factors associated with its development include male gender, age over 50 years, liver fibrosis or cirrhosis, and a long history (over 10 years) of symptomatic porphyria cutanea tarda.

Adult↗

Photopheresis for the treatment of cutaneous T-cell lymphoma.

Since its introduction in 1987, photopheresis has provided an additional modality in the treatment of patients with CTCL; it should probably be considered as the first line of treatment for patients with the erythrodermic stage disease. It is clear that in the responders, significant improvement in the quality of life can be achieved. The toxicity is minimal. As compared with historical control groups, patients treated with photopheresis have a prolonged survival. Although the precise therapeutic mechanism is yet to be fully elucidated, substantial evidence implicates increased immunogenicity of class I associated peptides specific for the malignant cells. Additional issues to be resolved include the role of adjunctive therapy, cost effectiveness of this treatment modality, and applicability to nonerythrodermic stages of CTCL.

Humans↗

Chronic actinic dermatitis. An analysis of 51 patients evaluated in the United States and Japan.

BACKGROUND AND DESIGN: We studied the clinical and photobiologic features of 51 patients with chronic actinic dermatitis who were evaluated at three institutions. The following criteria for patient selection were used: (1) a persistent eczematous eruption in the sun-exposed areas of greater than 3 months' duration; (2) decreased phototest results; and (3) when available, histologic changes of a dermal infiltrate of lymphocytes and macrophages, with or without epidermal spongiosis and atypical mononuclear cells in the dermis and epidermis. RESULTS: The 51 patients had a mean age of 62.7 years, a male-to-female ratio of 2.6:1, and a mean duration of eruption of 5.8 years. The most common abnormal results of the phototests were decreased minimal erythema doses to both UV-A and UV-B, followed by decreased minimal erythema doses to UV-A alone. Patients with abnormally low responses to UV-A or visible light and normal minimal erythema doses to UV-B had the same clinical profile as the overall patient population. Aside from protection from sunlight, treatment modalities that have been used include PUVA (8-methoxypsoralen and UV-A) photochemotherapy, azathioprine, hydroxychloroquine sulfate, and, for recalcitrant cases, cyclosporine. CONCLUSIONS: Chronic actinic dermatitis is a persistent photodermatosis associated with abnormal phototest responses to UV-A, and/or UV-B, and/or increased sensitivity to visible light; histopathologic changes are consistent with photodermatitis. Treatment consists of combinations of topical and oral medications.

Chronic Disease↗

Chronic actinic dermatitis. An immunohistochemical study of its T-cell antigenic profile, with comparison to cutaneous T-cell lymphoma.

Chronic actinic dermatitis (CAD) describes a persistent photosensitivity disorder in the absence of continued exposure to photosensitizers; it is characterized by a T-cell infiltrate within the epidermis and dermis. The purpose of this study was to characterize the T-cell infiltrate better immunohistochemically. Serial cryostat sections of fresh-frozen punch biopsy specimens of skin were analyzed in 11 patients with CAD and 3 patients with erythrodermic cutaneous T-cell lymphoma (CTCL). Monoclonal antibodies against the pan T-cell, pan B-cell, and T-cell subsets and the T cell-receptor (TCR) antigens were used. CD8-positive (T-suppressor-cytotoxic) cells were predominant in the epidermis of CAD, while CD4-positive (T-helper) cells were predominant in the epidermis and dermis of CTCL. CDw29-positive (T-memory) cells were predominant in all cases. The number of BF1 (beta-chain constant region of the TCR)-positive cells approximated the number of CD3-positive cells in all CAD cases but was significantly lower than the number of CD3-positive cells in two of three cases of CTCL. There was no clustering or preferential staining with any of the beta-chain variable-region antibodies in any of the specimens. These results indicate that CAD has a characteristic immunophenotype distinct from that of most cases of CTCL and that discordance between BF1 and CD3 expressions did not occur in the CAD cases.

Antigens, Differentiation, T-Lymphocyte↗

Effect of porphyrin and irradiation on heme biosynthetic pathway in endothelial cells.

To study porphyrin biosynthesis in human umbilical vein endothelial cells (EC), cultured EC were incubated with delta-aminolevulinic acid (ALA), the precursor of porphyrin synthesis, and porphyrins generated were measured spectrofluorometrically. EC accumulated porphyrins in an incubation time-dependent and ALA dose-dependent fashion. Porphyrin accumulation was enhanced by CaMg EDTA, a ferrochelatase inhibitor, suggesting the participation of ferrochelatase. The effect of porphyrin and irradiation on porphyrin accumulation was evaluated by exposing porphyrin-containing EC to the UVA and blue light, followed by incubation with ALA for 2-48 h. Decreased porphyrin accumulation 2-48 h after the irradiation was noted at all the time-points examined. However, no alteration of ferrochelatase activity was observed, suggesting that the decrease in porphyrin levels was due to suppression of the activity of the other enzymes in the earlier steps of the heme biosynthetic pathway.

Aminolevulinic Acid↗