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Biomedical subjects

I Horkay

Publications and source records attributed to I Horkay.

At least 19 recordsLinked to original sources
PubMed1997

bcl-2 vs p53 protein expression and apoptotic rate in human nonmelanoma skin cancers.

BACKGROUND: A failure in the apoptotic response after severe genomic damage could facilitate cell transformation and tumor development, and a constitutive overexpression of either p53 or bcl-2 protein in nonapoptotic tumor cells could signify a defective bax-mediated apoptosis. OBJECTIVES: To investigate whether a negative correlation occurs between these 2 proteins in nonmelanoma skin cancer and whether overexpression of either protein is associated with a low rate of spontaneous apoptosis. DESIGN: Immunohistochemical study of nonmelanoma skin cancer archive material. SETTING: University referral center. PATIENTS: White patients with tumors on sun-exposed skin areas (ie, 17 basal cell carcinomas and 22 squamous cell carcinomas). MAIN OUTCOME MEASURES: Positivity for p53 and bcl-2 were scored semiquantitatively on 4 levels, and the percentages of apoptotic cells were determined. RESULTS: A significant negative correlation between p53 and bcl-2 expression was found in the basal cell carcinomas, but not in the squamous cell carcinomas, largely attributable to the low level of bcl-2 staining in the squamous cell carcinomas. Squamous cell carcinomas have a significantly higher number of apoptotic cells than basal cell carcinomas: 1.1% vs 0.6%, respectively. This spontaneous apoptosis decreases with increasing bcl-2 (in basal cell carcinoma), whereas it does not appear to be related to p53 level expression. CONCLUSIONS: These results indicate that a disturbance in either p53 or bcl-2 suffices to enhance skin tumor formation by suppressing apoptosis; bcl-2 appears to reduce the rate of spontaneous apoptosis, but an aberrant p53 expression does not, and this factor may solely affect the apoptosis from exogenous genotoxicity.

Apoptosis↗
PubMed1996

Porphyria cutanea tarda and chronic lymphoid leukemia.

A case of a familial porphyria cutanea tarda (PCT-II) is reported in which the clinically overt form of PCT was provoked by factors relating to chronic lymphoid leukemia (CLL). Typical lesions of PCT developed on a 55-year-old woman after several blood transfusions and chlorambucil treatment. Besides these provoking factors, cytomegalovirus (CMV) infection was diagnosed. Erythrocyte uroporphyrinogen decarboxylase activity was about 50% of normal in the patient and in her two children. This case supports the suggestion that development of PCT in patients with hematological disorders is more than coincidental but may in fact be provoked by exogenous factors relating to the treatment of leukemia.

Anemia, Hemolytic, Autoimmune↗
PubMed1994

[Pseudoporphyria].

A 46-year-old patient with chronic renal failure receiving maintenance haemodialysis for 3 years had a few months history of blister formation and skin fragility involving the face, arms and dorsa of the hands. In this case clinically mimicking porphyria cutanea tarda (PCT) no demonstrable abnormality in the porphyrin metabolism excretion was detected.

Diagnosis, Differential↗
PubMed1990

Formation of DNA adducts in the skin of psoriasis patients, in human skin in organ culture, and in mouse skin and lung following topical application of coal-tar and juniper tar.

Preparations of coal-tar and juniper tar (cade oil) that are used in the treatment of psoriasis are known to contain numerous potentially carcinogenic polycyclic aromatic hydrocarbons (PAH). Evidence of covalent binding to DNA by components of these mixtures was sought in a) human skin biopsy samples from 12 psoriasis patients receiving therapy with these agents, b) human skin explants maintained in organ culture and treated topically with the tars, and c) the skin and lungs of mice treated with repeated doses of the formulations following the regimen used in the clinic. DNA was isolated from the human and mouse tissues and digested enzymically to mononucleotides. 32P-Post-labeling analysis revealed the presence of aromatic DNA adducts in the biopsy samples at levels of up to 0.4 fmol total adducts/microgram DNA. Treatment of human skin in organ culture produced similar levels of adducts, while treatment with dithranol, a non-mutagenic therapeutic agent, resulted in chromatograms indistinguishable from those from untreated controls. In mouse skin, coal-tar ointment and juniper tar gave similar DNA adduct levels, with a similar time-course of removal: maximum levels (0.5 fmol/microgram DNA) at 24 h after the final treatment declined rapidly to 0.05 fmol/microgram at 7 d, thereafter declining slowly over the succeeding 25 d. However, while coal-tar ointment produced only very low levels of adducts in mouse lung (less than 0.03 fmol/microgram DNA), juniper tar produced adducts at a high level (0.7 fmol/microgram DNA) that were persistent in this tissue. These results provide direct evidence for the formation of potentially carcinogenic DNA damage in human and mouse tissue by components of these therapeutic tar preparations.

Administration, Topical↗
PubMed1990

Poly(ADP-ribose)-synthesis and excision repair in light sensitive skin disorders.

Several data suggest a relationship of poly(ADP-ribose) (PAR) synthesis to DNA repair and the influence of some trace elements on the semiconservative and unscheduled DNA synthesis (UDS). Previously we found certain alterations in the UV-light induced UDS and in the contents of trace elements in the lymphocytes of patients with light sensitive skin disorders. In the recent study in polymorphic light eruption, cutaneous porphyrias and xeroderma pigmentosum the PAR synthesis and zinc, copper and manganese contents in the chromatin of the lymphocytes (measured by neutron activation analysis) were investigated. UV induced PAR synthesis was generally lower in the cells of polymorphic light eruption and especially in xeroderma pigmentosum with a reduced repair capacity whereas in cutaneous porphyrias no difference was observed. Some correlations occurred between the contents of trace elements studied and UDS as well in each group tested. It seems that PAR investigations throw new light upon our understanding of the pathomechanism of photodermatoses.

DNA Damage↗
PubMed1984

Determination of zinc, copper, manganese, and iron in blood from patients with light-sensitive skin diseases.

It is known that some trace elements have an influence on the repair of UV light induced DNA damage. We have detected certain alterations in the excision repair of patients with photodermatoses. In these investigations of screening character the levels of zinc, copper, manganese, and iron were measured by means of atomic absorption spectrophotometry in the whole blood of 31 patients with polymorphic light eruption and 27 patients with cutaneous porphyrias. In active stage of polymorphic light eruption decreased zinc, copper, and iron concentrations and an increased manganese content were found. In remission only the zinc level was lower. In the active stage of cutaneous porphyrias a decreased zinc and iron content as well as an increased manganese level could be detected. A presumable connection between the findings and the rate of the excision repair is discussed.

Copper↗
PubMed1983

A study on cell-mediated immunity in polymorphic light eruption.

Polymorphic light eruption (PLE) can be defined as a delayed abnormal response to sunlight. In this paper some features of the presumable immune response were studied in 55 patients with PLE and the results were compared with the findings available in 58 cases with porphyria cutanea tarda (PCT). The mean intracutaneous reactivity index measured by skin tests of delayed type was normal in both diseases. The number of the active and total E-rosette-forming peripheral lymphocytes was significantly lower in the active stage of PLE whereas in remission normal values were found. In active PCT only the number of the total E-rosette-forming cells was decreased. The percentage of lymphocytes with so-called dot-like alpha-naphthyl acetate esterase enzyme reaction was reduced significantly in the active stage of PLE whereas in remission their number was normal. Changes observed in PLE seem to be functional and suggest the involvement of T lymphocytes in some phases of the hypersensitive cutaneous reaction induced by sunlight.

Adolescent↗
PubMed1980

[Combination therapy of porphyria cutanea tarda using chloroquine and bloodletting therapy].

14 patients with PCT were treated with phlebotomy combined with Chloroquine. 4 venesections were performed before Chloroquine-treatment administered intermittently twice weekly. The so-called flu-syndrome manifested itself in the majority of patients. The clinical symptoms of PCT regressed within 6 weeks to 4 months of treatment, and the urinary uroporphyrin excretion returned to normal within 6 weeks to 3 months. Besides the flu-syndrome no side-effects could be observed. There has been a clinical and biochemical remission for a year and a half in each case but one. Relapse occurred in one case only one year after treatment.

Adult↗
PubMed1979

Effect of chloroquine on DNA synthesis in the skin of DLE patients.

Changes in the semiconservative and excision repair DNA synthesis were studied autoradiographically in the skin of 12 patients with discoid lupus erythematosus during Chloroquine treatment (500 mg/day for 8 weeks). The originally increased rate of the semiconservative DNA synthesis in the area of the skin lesions returned to the normal level simultaneous with clinical improvement. No effect on the excision reapir DNA synthesis could be detected.

Adult↗
PubMed1978

Repair of DNA damage in light sensitive human skin diseases.

Repair of UV-light induced DNA damage and changes in the semiconservative DNA synthesis were studied by in vitro autoradiography in the skin of patients with lightdermatoses (polymorphous light eruption, porphyria cutanea tarda, erythropoietic protoporphyria) and xeroderma pigmentosum as well as in that of healthy controls. In polymorphous light eruption the semiconservative DNA replication rate was more intensive in the area of the skin lesions and in the repeated phototest site, the excision repair synthesis appeared to be unaltered. In cutaneous porphyrias a decreased rate of the repair incorporation could be detected. Xeroderma pigmentosum was characterized by a strongly reduced repair synthesis.

Adult↗
PubMed1977

Lymphocytotoxic antibodies in lightdermatoses.

Occurrence of lymphocytotoxic antibodies of the "cold type" was studied in 92 cases with various lightdermatoses. They were detected in the sera of 39% of the patients with cutaneous porphyrias and never in cases with polymorphous light eruption and other photodermatosis. Correlations between their presence and the duration of the porphyria as well as the severity of hepatopathy could be observed. The results indicate the importance of a long-standing tissue damage in the production of these antibodies. In addition the findings confirm the hypothesis according to which polymorphous light eruption does not belong to the lupus erythematosus entity.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1975

Photodermatoses induced by oral contraceptives.

The pathogenetic role of liver damage in photodermatoses induced by oral contraceptives was investigated. From among 121 cases with photodermatosis, it was in 4 cases of polymorphic light eruption-like dermatosis and in 2 cases of porphyria cutanea tarda that a longterm use of antibaby pills preceded the development of skin disease. Physical and biochemical studies of the liver of the patients suggested that the hepatotoxicity of the estrogen component of oral contraceptives can play a role not only in the pathomechanism of porphyric cases, but also in that of cases occurring with the clinical picture of polymorphic light eruption.

Adult↗