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Biomedical subjects

Franjo Gruber

Publications and source records attributed to Franjo Gruber.

8 recordsLinked to original sources

The role of perforin-mediated apoptosis in lichen planus lesions.

Lichen planus is recognized as a T-cell-mediated disease. Histologically, it is characterized by the formation of colloid bodies representing apoptotic keratinocytes. The apoptotic process mediated by CD8(+) cytotoxic T lymphocytes (CTLs) and NK cells mainly involves two distinct pathways: the perforin/granzyme pathway and the Fas/FasL pathway. So far, little is known regarding the role of perforin-mediated apoptosis in lichen planus. In the present study, the expression and distribution of perforin, T and NK cell subsets in the epidermis and dermis of lesional and nonlesional lichen planus skin were studied. Skin biopsy specimens from lesional and nonlesional skin of ten patients with lichen planus and eight healthy persons were analysed by immunohistochemistry. Significant accumulation of T cells, particularly of CD4(+) and CD8(+) subsets, was found in both epidermis and dermis of lichen planus lesions compared with nonlesional and healthy skin. There were no significant differences in the incidence of NK cells (CD16(+) and CD56(+)) between lesional, nonlesional and healthy skin. Perforin expression was significantly upregulated in the epidermis of lichen planus lesions. In conclusion, accumulation of perforin(+) cells in the epidermis of lichen planus lesions suggest a potential role of perforin in the apoptosis of basal keratinocytes.

Adult↗

Acne vulgaris: myths and misconceptions among patients and family physicians.

The objective of the study was to evaluate the health beliefs and knowledge about acne among acne patients and family physicians. A total of 100 patients referred to a dermatologist for management of acne vulgaris and 120 family physicians completed questionnaires. The questionnaires consisted of questions about health beliefs, the natural course of the disease, the causes of acne, and a set of questions about the knowledge of acne therapy. Acne was considered as a trivial and transitory condition by 52% of the acne patients and 44% of the family physicians. The overall score of correct answers pertaining to the causes of acne among the acne patients and family physicians was 11 and 15%, respectively. The percentage of correct answers regarding the natural course of the disease was 6% for both subsets of subjects. Acne was believed to be curable by 96% of acne patients. Most patients (66%) believed that acne would improve immediately after the first treatment. The knowledge of isotretinoin teratogenecity was reasonable among family physicians (55% correct answers), but it was much lower for other side effects (9%). The overall score of correct answers regarding antibiotic therapy among family physicians was only 21%. Impact of the disease was underestimated by family physicians and also by acne patients. Overall knowledge pertaining to the causes, natural course and therapy was very low. Myths and misconceptions still exist among patients but also among family physicians.

Acne Vulgaris↗

Interleukin-2 receptor alpha-chain expression in patients with alopecia areata.

Interleukin-2 (IL-2) is a lymphokine produced by activated T-cells. Its receptor, IL-2R, is expressed on T-cells. Several clinical and experimental findings point towards IL-2 as a crucial mediator inducing immunologic reaction against human follicle in alopecia areata. The objective of our study was to analyze the expression of IL-2R as a sign of T-cell activation in scalp biopsies of patients suffering from alopecia areata. An immunohistochemical analysis was used to determine the difference in cytokine-regulated expression of IL-2R between 45 patients with active and stable phase of alopecia areata and 23 healthy control subjects. In the patients with alopecia areata in active phase, the expression of IL-2R in scalp biopsies was significantly stronger than that in the patients with stable disease and in controls. The increase of IL-2R+ cells in early phase of the disease could suggest that T-lymphocyte activation with IL-2 secretion and IL-2R expression may initiate the immune inflammatory mechanism of alopecia areata.

Adult↗

Roles of stress, stress perception and trait-anxiety in the onset and course of alopecia areata.

Clinical observations suggest that the nervous system, including psychological factors, can influence the onset and course of alopecia areata (AA). The aim of this study was to determine whether stressful life events, stress perception, and trait-anxiety are risk factors in the onset and course of AA. A group of 45 patients diagnosed with AA and a group of 45 healthy controls were participants in the study. The patients with AA were divided into two subgroups: patients with a first episode of AA and patients with recidivism of the disease. All participants completed questionnaires addressing sociodemographic, clinical and psychological aspects of their disorder. The frequency and types of stressful life events experienced over the previous six months were recorded. Lemyre and Tessier's Mesure de Stress Psychologique was used to measure emotional, cognitive, behavioral, and physiological aspects of distress. Anxiety was evaluated by the Spielberg's Trait Anxiety Inventory. The subgroups of AA and the control group, using the same numbers of subjects matched for age and sex, education level, marital and employment status, were statistically compared. The number of patients with four stressful life events over the previous 6 months was significantly higher in the group of AA patients with recidivism of disease compared to the control group (P=0.004). There were no differences among the other groups with respect to the frequency of life events. Examination of the relationships between the two groups regarding anxiety, as well as perceived distress, revealed that the groups differed significantly with respect to psychosocial variables studied. A significantly higher degree of trait-anxiety and perceived distress were observed among patients in both AA subgroups (first onset and recidivism of AA) than in the healthy control group. The highest scores for anxiety and stress perception among examined groups were obtained in the group with recidivism of AA (33.42 +/- 12.71 and 90.32 +/- 50.74, respectively). Trait-anxiety and stress perception constitutes risk factors that may influence the onset and exacerbation of AA. The present study does not provide evidence of a significant role of stress in the onset of AA. Life events may play an important role in triggering of some episodes.

Adult↗

Protein p53--structure, function, and possible therapeutic implications.

Cell cycle is driven by a number of positive and negative regulatory phosphorylation and dephosphorylation events that ultimately influence the activity of transcription factors. Normal skin architecture depends on the regulation mechanisms of cell proliferation and differentiation and on apoptosis. Complex interaction of different factors in the regulation of these mechanisms, aimed at maintaining constant desquamation, is often changed in skin diseases. The main difference between normal cells and tumor cells results from discrete changes in specific genes important for cell proliferation control mechanisms and tissue homeostasis. These genes are mainly proto-oncogenes or tumor-suppressor genes, and their mutation could play a role in cell hyperproliferation and carcinogenesis. Tumor-suppressor genes normally function as a physiological barrier against clonal expansion or mutation accumulation in the genome. They also control and arrest growth of the cells that hyperproliferate due to oncogene activity. Alteration or DNA damage in tumor-suppressor genes and oncogenes are considered key events in human carcinogenesis. Tumor-suppressor protein p53 is an important transcription factor, which plays a central role in the cell cycle regulation mechanisms and cell proliferation control, and its inactivation is considered a key event in human carcinogenesis. The role of p53 protein in the cell cycle, high proportion of tumors with mutated p53 gene, and accumulation of significant amount of knowledge on molecular biology of this protein make this molecule especially attractive for development of new therapeutic approaches. Main strategies for development of new antineoplastic therapies are based on "wild-type" p53 protein acting as a tumor suppressor, selective apoptosis inductor, and a protein able to arrest cell cycle.

Genes, p53↗

Angioimmunoblastic lymphadenopathy with dysproteinemia following doxycycline administration.

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is a primary lymphoproliferative T-cell disorder, currently classified as a peripheral T-cell non-Hodgkin's lymphoma. AILD is characterized by generalized lymphadenopathy, hepatosplenomegaly, immunological abnormalities, polyclonal hypergammaglobulinemia and anemia. We report a case of AILD in an 80-year-old male who presented with a generalized pruritic maculopapular eruption and fever following doxycycline administration. The maculopapular rash progressed to formation of confluent nodules, plaques and finally erythroderma with lymphadenopathy and hepatosplenomegaly. Blood analysis revealed an elevated erythrocyte sedimentation rate and polyclonal hypergammaglobulinemia. Lymph node biopsy showed almost complete effacement of the nodal architecture with diffuse proliferation of small vessels forming an arborizing network, surrounded by atypical lymphocytes, usually CD3+ CD4+ and occasionally CD3+ CD8+. There were also larger cells (immunoblastic shape) that displayed CD20 positively, some scattered plasma cells, and eosinophils. Histology of a cutaneous lesion showed spongiosis and infiltration of the epidermis by atypical lymphocytes with large hyperchromatic nuclei, perivascular dermal lymphocytic infiltrate (CD3+) mixed with plasma cells and occasional large immunoblasts (CD20+). During hospitalization the patient developed hemolytic anemia (Coombs positive) and lung metastases. The prognosis of AILD is generally poor, with a median survival of less than 20 months. Our patient died two and a half months after the diagnosis was made due to sepsis caused by Staphylococcus aureus isolated in hemoculture.

Aged↗

p53 protein expression and cell proliferation in non-neoplastic and neoplastic proliferative skin diseases.

AIMS AND BACKGROUND: The p53 protein is essential for the regulation of cell proliferation and its aberrant accumulation is usually seen in malignant tumors but also occurs in squamous epithelium of inflammatory skin diseases characterized by hyperproliferation. The aim of this study is to elucidate the role of the p53 tumor suppressor protein in the pathogenesis of different hyperproliferative, non-malignant and malignant skin diseases, and to determine the association between p53 overexpression and cell proliferation. We also investigated the influence of aging on p53 and Ki-67 protein expression. METHODS: One hundred and fifty skin specimens divided into 30 samples each of normal skin (NS), psoriatic skin (PS), keratoacanthomas (KA), basal cell carcinomas (BCC), and squamous cell carcinomas (SCC) were examined immunohistochemically to assess p53 and Ki-67 protein expression. RESULTS: p53 immunostaining of NS, PS, KA, BCC and SCC was detected in 39.0%, 46.7%, 66.7%, 80% and 86.7% of cases, respectively. Median values and ranges of p53 protein expression were as follows: 0.0% (range, 0.0-1.8%) in NS, 0.0% (range, 0.0-6.5%) in PS, 9.2% (range, 0.0-24.0%) in KA, 19.3% (range, 0.0-48.1%) in BCC and 30.1% (range, 0.0-68.1%) in SCC. p53- and Ki-67-positive cells were present in basal (NS) and suprabasal layers (PS), and not only in cancer nests of KA, BCC and SCC but also in dysplastic and even morphologically normal epidermis adjoining cancers. The positivity of p53 and Ki-67 proteins differed significantly among the groups, with no differences in p53 expression between NS and PS and in Ki-67 expression between PS and KA. Within all groups there was a significant correlation between p53 and Ki-67 expression. Lesion location and patient age, with the exception of location in PS and age in BCC, were significantly related to p53 and Ki-67 expression in all groups. CONCLUSIONS: Our findings suggest that p53 overexpression occurs mainly in neoplastic skin lesions, although it may also occur in squamous epithelium of inflammatory skin diseases such as PS, as well as in normal skin epithelium. It is associated with cell proliferation in normal as well as altered epithelium. p53 protein overexpression is an age-related process and significantly associated with sun exposure, especially in NS and PS but also in KA and SCC. Our findings suggest that Ki-67 rate and p53 protein expression reflect the degree of malignancy in the examined cutaneous neoplasms.

Adolescent↗

Hyalinosis cutis et mucosae: a 30 year follow up of a female patient.

Hyalinosis cutis et mucosae is an inherited disease, characterized by deposition of a hyaline-like substance in the dermis and internal organs. In the present study, we report a 30 year follow up in a female patient with hyalinosis cutis et mucosae treated using dermabrasion and oral retinoids. In our opinion, the lesion on uncovered body areas should be corrected as soon as possible to enable a normal psychophysical development. The lesions on skin and oral mucosa may be successfully removed without remission with dermabrasion in early childhood. In addition, oral retinoids in adulthood may produce some improvement.

Administration, Oral↗