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R Friedman-Birnbaum

Publications and source records attributed to R Friedman-Birnbaum.

At least 19 recordsLinked to original sources
PubMed2004

Familial Kaposi's sarcoma: a cluster of five Israeli cases.

AIM: Familial cases of Kaposi's sarcoma (KS) are rare, and have all been described in patients with the classical variant of the disease. The predisposition of classical Kaposi's sarcoma among Jews is well known. We herein describe five families, all Jews, in which two members have Kaposi's sarcoma. To our knowledge, this has been the largest reported series of familial Kaposi's sarcoma. PATIENTS AND METHODS: The clinical course, management and response to therapy were described and compared with other published cases. RESULTS: No similarity was found in any of the families in time and age of onset of the disease, or in the severity and course of the disease among the members of the same family. There was a high incidence of second neoplasms among these familial cases. CONCLUSIONS: We discuss the potential implications of second neoplasms based on our understanding of the pathogenesis of the disease, as well as the influence or predisposal of some genetic mechanisms to the development of Kaposi's sarcoma.

Age of Onset↗
PubMed2001

Rod-shaped bodies resembling birbeck granule-like structures in endothelial cells of dermal capillaries in generalized granuloma annulare.

A previous study demonstrated that, in generalized granuloma annulare in the epidermis, the Langerhans' cell section area and the number of Langerhans' cell granules or Birbeck granules per cell section were increased, suggesting an active state of these Langerhans' cells. Reexamination by transmission electron microscopy of the same tissue, but in samples also containing dermal tissue, from the same subjects revealed endothelial cells with rod-shaped bodies resembling Birbeck granules or Birbeck granule-like structures. This finding has not been previously described in blood vessels of human skin and is described here.

Capillaries↗
PubMed2000

A comparative immunohistochemical study of MART-1 expression in Spitz nevi, ordinary melanocytic nevi, and malignant melanomas.

BACKGROUND: The histopathologic differential diagnosis of Spitz nevus (SN) from malignant melanoma (MM) may be difficult. OBJECTIVE: We attempted to elucidate the pattern of expression of a newly recognized melanocyte-specific melanosomal protein MART-1 in routinely processed specimens of SNs, MMs, and ordinary melanocytic nevi (MNs) and to see whether it can help to differentiate between them. METHODS: Twenty SN, 22 MM, and 27 ordinary MN were immunostained with anti-MART-1 monoclonal antibody (clone A103). RESULTS: All SNs, MNs, and MMs demonstrated cytoplasmic staining for MART-1 in some of their tumor cells, of which 17 of 20 (85%) and 24 of 27 (89%) of SN and MN, respectively, demonstrated positive stainings in more than half of their tumor cells, as compared with only 10 of 22 (45%) of the MM (P <.05). The majority of lesions in all 3 types of tumors showed a homogeneous mode of staining, although MM tended to show a more heterogeneous pattern. A consistent pattern of stratification of staining with progressive descent into the dermis was not demonstrated in these tumors. CONCLUSION: MART-1 does not differentiate between SN, MM, and ordinary MN in a consistent pattern, but it may be used as a marker for these tumors.

Antigens, Neoplasm↗
PubMed2000

Epidemiological study of classic Kaposi's sarcoma: a retrospective review of 125 cases from Northern Israel.

BACKGROUND: The morphology of Kaposi's sarcoma is clinically and histologically the same in all clinical forms of the disease. However, there is a difference in the clinical and biological behaviour of the different forms of the disease. The behaviour also differs among individuals with the same form. The factors involved in the initiation and prognosis of the disease are still unknown. The classical form is more common in middle-aged Jews of East European or Mediterranean origin, people of Italian and southern Greek origin. Classic Kaposi's Sarcoma is seen relatively more frequently in Israel than in many other countries. OBJECTIVE: The aim of this study was to examine risk factors that influence the development and course of the disease. METHODS: This retrospective study includes 125 patients with Kaposi's sarcoma, all diagnosed and followed in the Department of Dermatology at Rambam Medical Center in Haifa. RESULTS: The group included 85 (68%) men and 40 (32%) women. Fourteen subjects received corticosteroid therapy and three were kidney transplant recipients. Age at onset of the disease was 21-87 years, with a mean age of 67. A total of 121 patients (96.8%) were Jews and four (3.2%) were non-Jews. A majority (61.6%) were of East European origin. The number of new cases each year was constant in relation to the general population, except for two peaks, one in 1970 and another in 1986-89. The lower limbs were involved in most patients. Extracutaneous involvement was present in 18.4%. Of all the subjects, 28 (22.4%) had diabetes mellitus and 21 (16.8%) had a second primary malignancy. The malignancies were of lymphoreticular origin in 10 patients, four in the urinary bladder, three had carcinoma of the large bowel and one of the pancreas. CONCLUSION: Our study shows similar clinical findings to those described in other series. The relatively high frequency of carcinomas of the colon and urinary bladder was not reported elsewhere. We observed a consistent rate of new cases each year with two peaks in 1970 and 1986-1989, the cause of which deserves explanation. Of interest is the relative rise in the number of females with Kaposi's sarcoma. A relative high risk for developing Kaposi's sarcoma has been found among Jews of Ashkenazi origin compared to those of other ethnic groups. Israeli-born subjects presented a relatively more aggressive course of disease than others.

Adult↗
PubMed2000

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Journal Article↗
PubMed2000

Androgenetic alopecia in heterozygous carriers of a mutation in the human hairless gene.

BACKGROUND: Androgenetic alopecia is considered to be genetically determined. Recently, a rare autosomal recessive form of hereditary alopecia, termed atrichia with papular lesions (APL), was found to result from mutations in the human hairless gene. OBJECTIVE: Our aim was to assess the pattern of androgenetic alopecia in heterozygous carriers of a deleterious mutation in the human hairless gene. METHODS: Healthy male second-degree relatives (n = 31) of patients affected with APL and belonging to a large consanguineous kindred were interviewed and given a Hamilton score of baldness. DNA was obtained from each subject and analyzed for the presence of a mutation in the human hairless gene known to affect this family. The age at onset and extent of baldness were compared in healthy homozygotes and heterozygous carriers of the mutation. RESULTS: Statistical analysis of the results revealed no differences in age at onset and extent of androgenetic alopecia between the two groups of subjects. CONCLUSION: The present study reports the first attempt to characterize the phenotype of heterozygous carriers of a mutation in the human hairless gene. It indicates that the presence of a deleterious mutation in one allele of the hairless gene does not affect the pattern of androgenetic hair loss.

Adult↗
PubMed1999

Atrichia with papular lesions resulting from a nonsense mutation within the human hairless gene.

Atrichia with papular lesions is a rare autosomal recessive form of alopecia characterized by hair loss soon after birth and the development during childhood of a diffuse papular rash. We have previously shown that this disorder results from a deleterious mutation in the human hairless gene, a gene also involved in the pathogenesis of a related but clinically distinct form of congenital alopecia, termed alopecia universalis congenita. In this report, we describe a novel nonsense mutation in exon 4 of the human hairless gene in a consanguineous kindred affected with atrichia with papular lesions. This report provides additional evidence for phenotypic heterogeneity among inherited atrichias and for an association between the papular rash of atrichia with papular lesions and nonsense mutations in the human hairless gene.

Alopecia↗
PubMed1999

Identification of a genetic defect in the hairless gene in atrichia with papular lesions: evidence for phenotypic heterogeneity among inherited atrichias.

Recently, we showed that atrichia with papular lesions (APL), a rare inherited form of alopecia, is transmitted as an autosomal recessive trait in a large inbred kindred of Israeli-Arab origin. Furthermore, we mapped the APL locus to a 5-cM region of chromosome 8p12 in this family. The human "hairless" gene is a candidate target gene for the disease mutation because it maps to the APL locus and because it was recently found to be mutated in a related but clinically distinct form of alopecia known as "alopecia universalis" or "congenital alopecia." In the present study, the coding sequence of the hairless gene was compared by reverse transcription-PCR in fibroblast cell lines derived from an affected patient and an unrelated individual. We identified a single-base deletion (3434delC) in the hairless gene that cosegregated with the disease phenotype in the family. This deletion is predicted to cause a frameshift mutation in the highly conserved C-terminal part of the hairless protein, a region putatively involved in the transcription factor activity of the hairless gene product. The present results are indicative of phenotypic heterogeneity in inherited atrichias caused by mutations in the hairless gene, suggesting different roles for the regions mutated in APL and in other forms of congenital atrichia during hair development.

Age of Onset↗
PubMed1999

Apoptosis, Fas and Fas-ligand expression in melanocytic tumors.

Impaired regulation of apoptosis is known to be associated with the development of various forms of cancer. Fas binding to its ligand, Fas ligand (Fas-L), has been shown to trigger apoptosis in various cell types. Fas-L is expressed by melanoma cells and has been suggested to play a role in melanoma escape from immune surveillance. In the present study, we assessed apoptotic activity and examined Fas and Fas-L expression in malignant melanomas, Spitz nevi and ordinary melanocytic nevi. We evaluated apoptotic activity using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling. Apoptotic activity was found to be minimal in melanomas and moderate in Spitz nevi. In contrast, common nevi demonstrated significant levels of apoptosis in the deep parts of the tumor. Fas was found to be expressed by all Spitz nevi, most melanocytic nevi and approximately half of the malignant melanoma specimens. Fas expression was also significantly more pronounced in Spitz nevus cells as compared with the two other tumors. The anti-Fas-L antibody was found to stain all three melanocytic tumors. Staining was shown to be stronger and more frequent in melanoma cells as compared to the nevus cells. Using the Spearman test, no significant correlation between Fas-L expression in melanoma cells and apoptosis in MM-infiltrating mononuclear cells was found, suggesting that Fas-L expression in melanoma cells may not be instrumental in their ability to escape immune mechanisms of defense. In contrast, increased levels of apoptosis in the deep parts of melanocytic nevi may reflect and possibly contribute to their benign nature.

Apoptosis↗
PubMed1998

Atrichia with papular lesions maps to 8p in the region containing the human hairless gene.

Atrichia with papular lesions (APL) (OMIM 209500) is a hereditary form of alopecia. Hair loss occurs soon after birth and is followed years later by the development of a diffuse papular eruption. Its mode of transmission is still uncertain. A related but clinically distinct form of alopecia, known as alopecia universalis (OMIM 203655), has recently been found to be associated with a mutation in the human hairless gene. The present report describes the largest consanguineous kindred of APL reported to date and provides strong evidence for autosomal recessive inheritance of this rare disorder. On the basis of a linkage analysis of this kindred using six microsatellite markers spanning the human hairless gene region, we found that the APL locus maps to chromosome region 8p12 in a 5 cM interval between marker D8S560 and marker D8S1739. A maximum lodscore of 3.7 was obtained with marker D8S1786, at a recombination fraction of 0. Our results suggest phenotypic variability at the hairless locus although they do not rule out the existence of a gene cluster associated with hair disorders in the same region.

Alopecia↗
PubMed1998

Reduced folate carrier (RFC-1) gene expression in normal and psoriatic skin.

Methotrexate is widely used in the treatment of severe psoriasis. However, little is currently known about the mechanisms underlying its therapeutic activity in the skin. Methotrexate has been shown to be carried into cells through the reduced folate carrier (RFC-1). The recent cloning and characterization of the human gene encoding this transmembranal carrier enabled us to investigate RFC-1 gene expression in human skin. Biopsies were obtained from the skin of healthy and psoriatic volunteers. RNA extracted from these biopsies was analyzed by the reverse transcriptase-polymerase chain reaction technique. While RFC-1 gene expression was barely detectable in the uninvolved skin of psoriatic patients and in the skin of healthy volunteers, high levels of RFC-1 transcripts were found in biopsies obtained from psoriatic plaques. To further investigate this pattern of gene expression, we studied skin biopsies by in situ hybridization with a labeled antisense riboprobe specific for the RFC-1 gene. The RFC-1 gene was found to be weakly expressed in the epidermis, in biopsies obtained from the skin of healthy subjects as well as in those from the uninvolved skin of psoriatic patients. In contrast, in biopsies obtained from psoriatic plaques, high levels of RFC-1 gene transcripts were found mostly in the spinous layer of the epidermis. These results suggest the existence of a specific methotrexate carrier in the human epidermis, and may bear relevance to the cutaneous manifestations of methotrexate toxicity.

Adult↗
PubMed1998

Immunophenotyping and T-cell receptor gamma gene rearrangement analysis as an adjunct to the histopathologic diagnosis of mycosis fungoides.

BACKGROUND: The histopathologic diagnosis of mycosis fungoides (MF) may be difficult. OBJECTIVE: Our purpose was to evaluate the role of immunophenotyping and T-cell receptor (TCR) gene rearrangement studies as an adjunct to the histopathologic diagnosis of MF. METHODS: Immunohistochemical studies with antibodies to CD4, CD5, CD7, and CD8 and TCR gamma gene rearrangement analysis with a polymerase chain reaction were performed on fresh-frozen material of patients with "classic" histology of MF, "inconclusive" histology, and benign inflammatory dermatoses. RESULTS: Clonal TCR gamma gene rearrangements were found in 11 of 16 (69%) of classic MF cases, in 3 of 19 (16%) of inconclusive cases, and in none of the 12 inflammatory dermatoses cases (P < .05 and P < .001, respectively). Only the mean CD7 counts were statistically significantly different between these 3 groups (MF < inconclusive < inflammatory). CONCLUSION: Inconclusive histology is probably a heterogeneous group in which CD7 counts and TCR gamma gene rearrangement studies might help to differentiate the MF cases from the benign cases.

Adolescent↗
PubMed1998

Diabetic dermopathy and internal complications in diabetes mellitus.

BACKGROUND: Diabetic dermopathy is the most common cutaneous marker of diabetes mellitus. The relationship of diabetic dermopathy to internal complications of diabetes mellitus, such as nephropathy, retinopathy, and neuropathy, is still unknown. METHODS: The possible role of diabetic dermopathy as a clinical sign of internal complications in diabetes mellitus was investigated. One hundred and seventy-three patients with diabetes mellitus, of whom 125 (72%) had insulin-dependent diabetes mellitus and 48 (28%) had non-insulin-dependent diabetes mellitus, were studied. RESULTS: Diabetic dermopathy was present in 69 (40%) of patients, statistically more significant in patients 50 years of age and older. The mean diabetic duration was significantly higher in patients with diabetic dermopathy than in those without. The associations of diabetic dermopathy with retinopathy, nephropathy, and neuropathy were each statistically significant, and the increased frequency of diabetic dermopathy correlated with an increased number of these three complications in each patient. CONCLUSIONS: Some of the factors that affect the development of internal complications in diabetes mellitus may play a role in the development of diabetic dermopathy, and diabetic dermopathy may serve as a clinical sign of an increased likelihood of these internal complications in diabetic patients.

Adolescent↗
PubMed1998

C-fos protein expression in Spitz nevi, common melanocytic nevi, and malignant melanomas.

The expression of c-fos protein was studied in formalin-fixed, paraffin-embedded sections of 11 compound Spitz nevi (SNs), 16 ordinary compound melanocytic nevi (MNs), and 17 malignant melanomas (MMs) using monoclonal antibody MAB1283 and an immunoperoxidase technique. Eleven (100%) SNs, 15 (94%) MNs, and 16 (94%) MMs showed positive reactions in some of the tumor cells (p = nonsignificant). In the majority of the tumors the staining was located in nuclei and graded as moderate to strong in intensity. The percentages of positively stained cells did not differentiate the three types of tumor, although they were higher in the melanocytic nevi. Most of the lesions with a significant dermal component did not show stratification of staining with progressive descent into the dermis. Positive staining for c-fos was also frequently found in the normal skin constituents within and adjacent to the melanocytic tumors. In conclusion, the pattern of expression of c-fos in routinely processed specimens does not differentiate between SNs, MNs, and MMs.

Cell Nucleus↗