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Biomedical subjects

H W Lim

Publications and source records attributed to H W Lim.

At least 55 records · Page 3Linked to original sources
PubMed1999

Evaluation of the photosensitive patient.

Evaluation of photosensitivity involves the following sequential steps. A history is useful to evaluate possible exposure to know photosensitizers, characteristics of the light-induced eruption, family history, and possible involvement of other organ systems. Distribution and morphology of the cutaneous lesions should help to delineate the disorder. Phototesting is helpful in documenting decrease in the minimal erythema doses. Photopatch testing is indicated when history and physical examination suggest the possibility of photoallergic dermatitis. Other useful investigations include skin biopsy, antinuclear antibody panel, and when appropriate, plasma porphyrin.

Dermatitis↗
PubMed1999

The cutaneous porphyrias.

Deficiencies of 7 enzymes in the heme biosynthetic pathway result in the development of porphyrias. Two of the porphyrias, aminolevulinate dehydratase deficiency porphyria and acute intermittent porphyria do not have cutaneous findings. Cutaneous findings in the other porphyrias could be subdivided into acute phototoxicity and subacute phototoxicity. In addition, 2 of the porphyrias, hereditary coproporphyria and variegate porphyria have both cutaneous and neurovisceral findings. Now that chromosomal assignments for all the genes of the defective enzymes have been mode, prenatal diagnosis is possible for congenital erythropoietic porphyria, and in vitro gene therapy has been successfully performed for congenital erythropoietic porphyria and erythropoietic protoporphyria.

Dermatitis, Phototoxic↗
PubMed1999

HIV, UV and immunosuppression.

Cutaneous diseases are common manifestations of infection with human immunodeficiency virus (HIV). Phototherapy with ultraviolet B (UVB) and photochemotherapy with 8-methoxypsoralen plus UVA (PUVA) have been used successfully to treat several of these skin conditions, including psoriasis, folliculitis, pruritus, and eczema. However, in view of the known immunosuppressive effects of UV radiation, concerns have been raised about potential adverse effects of UV on persons infected with HIV. In the following report, we review the effects of UV in HIV-infected cell lines in vitro, in animal models, as well as in human studies. Based on currently available data, UV radiation, as used in phototherapy and photochemotherapy, appears to have no adverse effects in HIV-infected individuals.

Animals↗
PubMed1999

Extracorporeal photochemotherapy for cutaneous T-cell lymphoma: a 9.7-year experience.

Cutaneous T-cell lymphoma (CTCL) is an indolent lymphoma usually of CD4+ T lymphocytes in which the aggressive treatment for the advanced stages does not increase survival. Photopheresis has been established as an alternative modality for the therapy of erythrodermic CTCL and reportedly improves survival in patients with advanced stages of the disease. The objective of this study is to review the experience of treating patients with erythrodermic CTCL with extracorporeal photochemotherapy (ECP) at the New York Veteran Affairs Medical Center/NYU Medical Center between September 1987 and April 1997. Forty-one patients with erythrodermic CTCL (stages III and IV) received photopheresis; 25 of them fulfilled the inclusion criterion, i.e., the completion of greater than or equal to 6 cycles of photopheresis. Skin score was defined as a product of severity and percentage of involved surface area. Complete clinical response was defined as disappearance of measurable disease for at least one month, and partial response was defined as greater than or equal to 50% clearance of measurable disease for at least one month. The profile of the patients was: 20 men, 5 women; average age: 64.2 years; 17 patients had stage III disease, and 8 had stage IV disease. Five of the 25 patients (20%) achieved complete clinical response, another 15 (60%) had partial response, and 5 (20%) had no response. The mean time (+/- SD) to achieve complete clinical clearance was 12.6 +/- 10 months (range: 4-30 months) and the mean time (+/- SD) to obtain partial clinical response, including complete response, was 9.7 +/- 5.3 months (range: 4-17 months). Remission duration ranged from 9 to 67 months. The median survival time from the time of initiation of photopheresis is estimated at 70 months. The complete responder group had a lower median CD4/CD8 ratio compared to the non-responders at baseline (3.8 vs 7.2, respectively), although the difference was not statistically significant (P = 0.40). At the time of maximal response, the CD4/CD8 ratio of the complete responder group decreased towards normal values (median = 1.2), whereas this ratio increased among the non-responders (median = 11.0; P = 0.04). Side effects were minimal. Extracorporeal photochemotherapy is an effective and safe treatment for erythrodermic CTCL. In some of these patients, it can induce a long-term and complete clinical remission.

Female↗
PubMed1999

Absolute requirement of macrophages for the development and activation of beta-cell cytotoxic CD8+ T-cells in T-cell receptor transgenic NOD mice.

The development of autoimmune diabetes in NOD mice results from selective destruction of beta-cells by a T-cell-dependent autoimmune process. However, the mechanisms that control the generation of beta-cell cytotoxic T-cells in vivo are poorly understood. We recently established 8.3-T-cell receptor (TCR)-beta transgenic NOD mice that show a selective acceleration of the recruitment of CD8+ T-cells into the islets of prediabetic animals, resulting in rapid beta-cell destruction and early onset of diabetes. This study was initiated to determine the role of macrophages in the development and activation of diabetogenic CD8+ T-cells in 8.3-TCR-beta transgenic NOD mice. Inactivation of macrophages in these transgenic mice resulted in the complete prevention of diabetes. When splenic T-cells from macrophage-depleted 8.3-TCR-beta transgenic NOD mice were transfused into severe combined immunodeficiency disease (NOD.scid) mice, none of the recipients developed diabetes up to 10 weeks after transfer, while most of the recipients of T-cells from age-matched control 8.3-TCR-beta transgenic NOD mice became diabetic. When intact NOD islets were transplanted under the renal capsule of macrophage-depleted 8.3-TCR-beta transgenic NOD mice, the majority of the grafted islets remained intact, while most of the islets grafted into age-matched, control 8.3-TCR-beta transgenic NOD mice were destroyed within 3 weeks after transplantation. The depletion of macrophages in these mice resulted in a decrease in the Th1 immune response along with an increase in the Th2 immune response because of significant decreases in the expression of macrophage-derived cytokines, particularly interleukin-12, and a decrease in beta-cell-specific T-cell activation, as shown by significant decreases in the expression of Fas ligand (FasL), CD40 ligand (CD40L), and perforin, as compared with control mice. We conclude that macrophages are absolutely required for the development and activation of beta-cell cytotoxic CD8+ T-cells in 8.3-TCR-beta transgenic NOD mice.

Animals↗
PubMed1998

Prevention of cardiac hypertrophy in mice by calcineurin inhibition.

Hypertrophic cardiomyopathy (HCM) is an inherited form of heart disease that affects 1 in 500 individuals. Here it is shown that calcineurin, a calcium-regulated phosphatase, plays a critical role in the pathogenesis of HCM. Administration of the calcineurin inhibitors cyclosporin and FK506 prevented disease in mice that were genetically predisposed to develop HCM as a result of aberrant expression of tropomodulin, myosin light chain-2, or fetal beta-tropomyosin in the heart. Cyclosporin had a similar effect in a rat model of pressure-overload hypertrophy. These results suggest that calcineurin inhibitors merit investigation as potential therapeutics for certain forms of human heart disease.

Animals↗
PubMed1998

A second form of phenylalanine ammonia-lyase from leaf mustard.

Phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) catalyzes the elimination of ammonium ion from L-phenylalanine in a variety of plants and fungal species. PAL was previously purified and characterized from leaf mustard in our laboratory. In the present study, we purified a second phenylalanine ammonia-lyase (PAL II) from leaf mustard by a combination of ion exchange chromatography and gel filtration. PAL I and PAL II migrate at a different rate on native polyacrylamide gel electrophoresis. It consists of four subunits, each having the molecular mass of about 37,000 Da. Its isoelectric point and Km value for L-phenylalanine were found to be 5.4 and 3.8 x 10(-5)M, respectively. The purified enzyme has an optimum pH and temperature of 8 and 45 degree C, respectively. It is activated about 2-fold by caffeic acid (1 mM), whereas it is inhibited to 15% by Zn2+ (1 mM). However, the physiological role of PAL II remains unknown.

Amino Acids↗
PubMed1998

Early-stage HIV infection and hepatitis C virus infection are associated with elevated serum porphyrin levels.

BACKGROUND: Porphyria cutanea tarda is known to be associated with HIV infection and hepatitis C virus (HCV). OBJECTIVE: Our purpose was to evaluate whether early infection with HIV, with or without HCV infection, is associated with elevated serum porphyrin levels. METHODS: Serum porphyrin levels were measured in samples obtained from 103 patients with early HIV infection. The results were compared with those of 89 late-stage HIV-positive patients and 78 HIV-negative patients. RESULTS: The highest median porphyrin level was in early-stage HIV-positive/HCV-positive samples, followed in decreasing order by those in early-stage HIV-positive/HCV-negative, late-stage HIV-positive/HCV-positive, late-stage HIV-positive/HCV-negative, HIV-negative/HCV-positive, and HIV-negative/HCV-negative groups. Elevated porphyrin levels were independently associated with early-stage HIV infection (P < .0001) and HCV infection (P = .03). CONCLUSION: This finding suggests abnormal porphyrin metabolism is most noticeable in early-stage HIV infection; it becomes less severe with the progression of HIV disease.

Adult↗
PubMed1998

Effect of soluble complement receptor type 1 on porphyrin-induced phototoxicity in guinea pigs.

The effect of recombinant human soluble complement receptor type 1 (sCR1) on the porphyrin-mediated phototoxic reaction was evaluated in guinea pigs. Phototoxicity was induced in the animals by intraperitoneal injection of hematoporphyrin derivative (HpD), followed by irradiation at a wavelength range of 320-450 nm. sCR1 administration decreased CH50 titers in a dose-dependent fashion, while it only moderately suppressed HpD/radiation-induced ear swelling at a high dose. These findings suggest that phototoxic dermatological changes in cutaneous porphyrias are not solely due to complement activation.

Animals↗
PubMed1997

Purification and properties of phenylalanine ammonia-lyase from leaf mustard.

Phenylalanine ammonia-lyase (PAL, EC 4.3.1.5), the first enzyme in phenylpropanoid biosynthesis, catalyzes the elimination of ammonium ion from L-phenylalanine. In the present study, PAL was purified through ammonium sulfate fractionation, DEAE-cellulose chromatography, Sephadex G-200 chromatography, and Q-Sepharose chromatography from the cytosolic fraction of leaf mustard (Brassica juncea var. integrifolia). It consists of 4 subunits, each having an estimated molecular weight of about 40,000 on SDS-polyacrylamide gel electrophoresis (SDS-PAGE). The optimal pH and temperature of the purified enzyme are 9.0 and 45 degrees C, respectively. Its activity is inhibited by Zn2+ ion, and it is strongly activated by caffeic acid. The purified PAL seems to have some characteristics different from those obtained with other PALs.

Amino Acids↗
PubMed1997

UVB phototherapy is an effective treatment for pruritus in patients infected with HIV.

BACKGROUND: Pruritus in patients positive for HIV may be debilitating. OBJECTIVE: Our purpose was to evaluate the efficacy of UVB therapy in the treatment of pruritus in patients positive for HIV. METHODS: Twenty-one male HIV-positive patients with intractable pruritus (14 with eosinophilic folliculitis and 7 with primary pruritus) were treated three times weekly with UVB phototherapy. Pruritus was quantified with use of a subjective score of 0 (none) to 10 (severe). RESULTS: Mean CD4 counts at the initiation of therapy were 91.0 +/- 31.9 cells/microliter. Pruritus scores before and after treatment were 8.6 +/- 0.4 and 2.2 +/- 0.5, respectively (p < 0.001). The mean number of treatments to achieve maximal improvement was 20.7 +/- 2.3, with a cumulative UVB dose of 3399.1 +/- 597.4 mJ/cm2. No significant difference was found between the group with eosinophilic folliculitis and the group with primary pruritus. CONCLUSION: UVB phototherapy can produce significant relief of pruritus and improvement in the quality of life in patients positive for HIV.

Adult↗
PubMed1997

Role of viral infection in porphyria cutanea tarda.

HIV infection is associated with abnormal porphyrin metabolism. While HCV infection alone is thus far not associated with significant abnormal porphyrin levels, it does contribute to further elevation of porphyrin levels in patients already infected with HIV. These infections alone are not sufficient to induce the development of clinical porphyria. However, they render patients susceptible to having symptomatic porphyria upon exposure to other porphyrinogenic agents.

Disease Susceptibility↗
PubMed1997

Chronic actinic dermatitis associated with human immunodeficiency virus infection.

Chronic actinic dermatitis is a photodistributed, eczematous dermatitis that preferentially affects elderly men and persists for months to years. Its occurrence in individuals infected with human immunodeficiency virus (HIV) has been described in five patients. We report four additional cases of this uncommon, chronic photodermatosis associated with HIV infection. In two of the patients, photosensitivity was a presenting disorder leading to the diagnosis of HIV infection. All patients were men of skin type VI with a mean age of 50 years, all had decreased minimal erythema doses to ultraviolet B, three of the four patients had decreased minimal erythema doses to ultraviolet A and all had CD4 cell counts of < 200 x 10(6)/L.

Adult↗