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Biomedical subjects

E Hodak

Publications and source records attributed to E Hodak.

At least 19 recordsLinked to original sources
PubMed1996

The insulin-like growth factor 1 receptor is expressed by epithelial cells with proliferative potential in human epidermis and skin appendages: correlation of increased expression with epidermal hyperplasia.

Ligand-mediated activation of the insulin-like growth factor 1 (IGF-1) receptor is critical for epidermal keratinocyte proliferation in vitro, and its expression in normal and psoriatic epidermis suggests that it might regulate keratinocyte proliferation in vivo. In this study, we used a monoclonal antibody (alpha-IR3) that binds to the alpha-chain of this receptor to study its expression (i) in other epithelial cell types in human skin and (ii) in growth-activated epidermis associated with various cutaneous pathologies. In normal skin, IGF-1 receptors were expressed by basal epidermal keratinocytes as well as by basal-like or undifferentiated germinative epithelial cells associated with the follicular outer root sheath, sebaceous glands, and the hair matrix. There was minimal IGF-1 receptor expression in differentiating outer root sheath, hair shaft, and sebaceous epithelial cells. IGF-1 receptor expression in non-growth-activated epidermis of long-standing seborrheic keratoses was confined to the basal epidermal layer, as in normal epidermis. In contrast, hyperplastic epidermis undergoing "regenerative" differentiation (keratin 16+, Ki67+ suprabasal keratinocytes) from psoriasis, chronic skin wounds, and plaques of mycosis fungoides consistently showed increased expression of IGF-1 receptor. In these conditions, the region of expanded IGF-1 receptor expression delimited the epidermal zone of keratinocyte proliferation. In cultured keratinocytes, the subcellular localization of the IGF-1 receptor could be modulated from plasma membranes to the cell cytoplasm by ligand binding, suggesting that the in vivo cytoplasmic staining occasionally observed represents internalization of receptors following ligand stimulation. Our results suggest that cell surface IGF-1 receptors are widely expressed by epithelial cells with proliferative potential, that receptor expression can be modulated with differing epidermal growth states, and that these receptors are largely downregulated in highly differentiated epithelial cells.

Cell Division↗
PubMed1996

In vivo expression of the insulin-like growth factor-I (IGF-I) receptor in congenital pigmented nevi.

Growth of normal melanocytes, nevus cells and primary melanoma cells is enhanced by insulin/insulin-like growth factor-I (IGF-I) in vitro. It has been shown that a melanoma cell line possesses the IGF-I receptor which plays a role in activation of the chemotactic response. Little is known about the in vivo expression of the IGF-I receptor and its role in melanocytic lesions. In an immunohistochemical study, we investigated the expression of IGF-I receptor in frozen sections of congenital pigmented nevi from 10 patients (ages 8 months to 4 yrs) using the monoclonal antibody alpha IR3, which specifically recognizes the extracellular alpha subunit of the IGF-I receptor. The proliferative activity of the nevus cells was examined by staining with Ki67 monoclonal antibody (reactive with all actively cycling cells). IGF-I receptor was found to be widely expressed by the cell surface of the nevus cells. Membrane staining was occasionally stronger in the superficial portion of the congenital pigmented nevi. In contrast, Ki67-positive cells were only sparsely scattered throughout the nevi with some tendency to localization to the superficial portion. This study indicates that in vivo the IGF-I receptor is widely expressed by congenital pigmented nevus cells. As opposed to keratinocytes, in which IGF-I receptor expression defines the proliferation pool of the normal and disordered epidermis, the IGF-I receptor is expressed by all nevus cells, irrespective of their proliferative status. Further studies are needed to assess whether the IGF-I receptor expression can serve as a marker for increased risk for development of malignancy in various types of benign melanocytic lesions.

Cell Division↗
PubMed1996

Trichorrhexis nodosa: a manifestation of hypothyroidism.

A 23-year-old woman presented with diffuse white hair nodules, hair fragility, and the inability to grow long hair. Examination of specimens under the light microscope showed the morphologic characteristics of trichorrhexis nodosa. Results of tests revealed hypothyroidism. Treatment with a daily dose of 0.1 mg L-thyroxine sodium for six months restored euthyroidism and concurrently normalization of the hair defect was observed. The corrected hair defect observed after replacement therapy may point toward a causal relationship between hypothyroidism and trichorrhexis nodosa. To the best of our knowledge, this is the first report of trichorrhexis nodosa associated with hypothyroidism.

Adult↗
PubMed1996

Beneficial effect of granulocyte-colony stimulating factor in scleromyxoedema associated with severe idiopathic neutropenia.

The treatment of scleromyxoedema is notoriously difficult. We present a patient with long-standing diffuse scleromyxoedema associated with functional impairment who developed chronic idiopathic neutropenia complicated by recurrent life-threatening infections. Treatment with recombinant granulocyte--colony stimulating factor led to normalization of the neutrophil count, prevented further systemic infections, and unexpectedly was associated with a striking clinical improvement of her skin disorder and decrease in mucin deposition in the dermis.

Chronic Disease↗
PubMed1994

PUVA bath therapy strongly suppresses immunological and epidermal activation in psoriasis: a possible cellular basis for remittive therapy.

Psoriasis is characterized by alterations in both the epidermis and dermis of the skin. Epidermal keratinocytes display marked proliferative activation and differentiate along an "alternate" or "regenerative" pathway, while the dermis becomes infiltrated with leukocytes, particularly interleukin 2 (IL-2) receptor-bearing "activated" T cells. Psoralens, administered by the oral route, have therapeutic effects in psoriasis when photochemically activated by ultraviolet A light (PUVA therapy). Recently psoralen bath therapy has been introduced to more effectively deliver this agent to the diseased skin. We have correlated the efficacy of PUVA bath therapy with its effects on specific molecular and cellular parameters of disease, in 10 consecutive patients with recalcitrant psoriasis. Rapid clearing of lesions occurred in 8 out of 10 patients. Biopsies were taken from lesional and nonlesional skin before and after a single round of therapy, and observation was continued in our Clinical Research Center at The Rockefeller University. Enumeration of cycling keratinocytes with the Ki-67 monoclonal antibody showed that PUVA reduced cell proliferation by 73%. The pathological increase in insulin-like growth factor 1 (IGF-1) receptors was reversed, whereas epidermal growth factor (EGF) receptors, which are also increased in psoriasis, remained unchanged. Keratinocyte proteins that are expressed in abnormal sites of the epidermis during psoriasis, i.e., keratin 16, filaggrin, and involucrin, were, after PUVA treatment, localized to their normal sites. Epidermal and dermal T-lymphocytes (CD3+), as well as CD4+, CD8+, and IL-2 receptor+ subsets, were strongly suppressed by PUVA, with virtual elimination of IL-2 receptor+ T cells in some patients. Consistent with diminished lymphocyte activation, HLA-DR expression by epidermal keratinocytes was markedly reduced in treated skin. In comparison to cyclosporine treatment of psoriasis, PUVA therapy leads to more complete reversal of pathological epidermal and lymphocytic activation, changes which we propose to be the cellular basis for a more sustained remission of disease after PUVA treatment.

Adult↗
PubMed1994

Secondary milia following bullous erysipelas.

Secondary milia associated with bullous erysipelas developed in the right leg of a 64-year-old woman. The milia, measuring up to 6 mm, appeared one month after healing of the erysipelas. Findings of histopathologic and immunohistochemical studies showed that the milia were related to dilated eccrine ducts and not to the hair follicle. Topical treatment with 0.05 percent tretinoin cream resulted in almost full resolution of the lesions.

Eccrine Glands↗
PubMed1993

The appearance of Kaposi sarcoma during corticosteroid therapy.

BACKGROUND: Four epidemiologic types of Kaposi sarcoma (KS) are known: classic KS, endemic African KS, epidemic or acquired immunodeficiency syndrome-related KS, and KS associated with immunosuppressive therapy. In most of the latter patients, KS was reported to have developed after organ transplantation, particularly renal transplantation. Thirty-nine patients who have not had a transplant have been reported to have KS associated with corticosteroid therapy. METHODS: The authors studied 10 patients with the appearance of KS during corticosteroid therapy (6 men, 4 women; age range, 42-79 years) who were treated with corticosteroids for autoimmune disorders (5 patients), lymphoproliferative disorders (2 patients), and diseases unrelated to the immune system (3 patients). RESULTS: Genetically programmed susceptibility to corticosteroid-related KS was suggested by the descent of the study patients as well as most of those reported previously. The prognosis was guarded in all the study patients. CONCLUSIONS: Corticosteroids should be withdrawn to achieve clinical remission.

Adult↗
PubMed1993

Quantitative and qualitative assessment of plasma von Willebrand factor in classic Kaposi's sarcoma.

BACKGROUND: von Willebrand factor (vWF) is synthesized almost exclusively by endothelial cells and is stored there as ultra-high-molecular-weight multimers. The vWF multimers that are detected in the plasma are smaller than those stored within the endothelium. In two previous studies, comprising small series of cases with classic Kaposi's sarcoma (KS), an endothelium-derived tumor, increased levels of plasma von Willebrand factor antigen (VWF:Ag, the antigenic structure) were reported, suggesting that vWF:Ag may be a marker of endothelium proliferation. OBJECTIVE: Our purpose was to investigate the quantitative as well as qualitative alterations of plasma vWF in a large series of patients with classic KS at various stages of the disease. METHODS: Levels of plasma vWF:Ag were studied in 38 patients with classic KS confined to the skin at various stages of the disease and compared with a control group. Thirty-three patients had active KS (i.e., with skin lesions) and five were in remission. In five patients with active KS multimeric analysis of plasma vWF was also performed. RESULTS: The levels of vWF:Ag were significantly higher among KS patients than in the control group (n = 29, p < 0.01). Levels of vWF:Ag were also significantly higher in patients with active disease as compared with those in remission (p < 0.05). No correlation was found between vWF:Ag levels and the extent of KS. Analysis of the multimeric pattern of plasma vWF showed enhanced staining of all bands, particularly the intermediate and high molecular weight forms, which resemble the endothelial forms as opposed to normal circulating vWF multimers. CONCLUSION: Quantitative as well as qualitative alterations in plasma vWF were found in patients with KS, which may reflect the destruction or activation of endothelial cells within the lesions. vWF:Ag may serve as a marker of disease activity in classic KS; however, it is not a good marker for the extent of the disease.

Aged↗
PubMed1993

Kaposi's sarcoma with visceral involvement after intraarticular and epidural injections of corticosteroids.

Kaposi's sarcoma has been reported in patients receiving immunosuppressive therapy, most of whom are organ transplant recipients. The development of Kaposi's sarcoma after treatment with corticosteroids has been reported in only 38 patients who have not had acquired immunodeficiency syndrome or undergone organ transplantation. Cutaneous Kaposi's sarcoma developed 2 months after intraarticular steroid injections in a man with ulnar nerve entrapment. The lesions regressed spontaneously after 3 months but reappeared with visceral involvement 18 months later, shortly after initiation of a course of epidural steroid injections for treatment of low back pain. The cutaneous lesions and some visceral lesions rapidly regressed after cessation of treatment.

Administration, Topical↗
PubMed1993

A paraneoplastic mixed bullous skin disease associated with anti-skin antibodies and a B-cell lymphoma.

BACKGROUND: The full spectrum of bullous diseases associated with underlying cancers remains to be fully defined. OBSERVATION: We describe a patient with a mixed bullous disease exhibiting combined features of cicatricial pemphigoid and pemphigus and associated with a B-cell lymphoma producing an IgM paraprotein to intercellular antigens in human skin. The patient had the clinical features of cicatricial pemphigoid and the histologic and immunofluorescence abnormalities of both cicatricial pemphigoid and pemphigus. These included oral and cutaneous erosions; ocular scarring; subbasal and acantholytic intraepidermal bullae; and circulating and tissue-fixed basement membrane zone and intercellular antibodies. The antibodies were directed to a 140-kd antigen in dermal extracts of skin split with 1 mol/L of sodium chloride and to antigens with approximate molecular weights of 150, 180, 230, and 285 kd in the dermal extract. In contrast to paraneoplastic pemphigus, the intercellular antibodies did not react to mammalian bladder. The intercellular antibodies were of the IgM class and were associated with the paraprotein produced by the malignant B cells. CONCLUSIONS: We believe that this condition represents a novel bullous disease, which we refer to as paraneoplastic mixed bullous disease. This condition illustrates that distinct bullous diseases are associated with paraneoplastic syndromes and that at least one possible mechanism for such eruptions is the production of anti-skin antibodies by malignant B cells.

Autoantibodies↗
PubMed1992

Pachydermodactyly: first report in a woman.

Pachydermodactyly is a rare form of digital fibromatosis that is characterized by acquired, asymptomatic, protracted connective tissue swellings on the back and sides of a few proximal phalanges or proximal interphalangeal joints. This is the tenth reported case of pachydermodactyly. It has previously been reported only in men; to the best of our knowledge, this is the first woman described with this condition.

Adolescent↗
PubMed1992

Facial pyogenic granuloma-like lesions under isotretinoin therapy.

A male patient with severe cystic acne was treated with 13-cis-retinoic acid in a dosage of 1 mg/kg/day. Early flare-up of his acne and multiple pyogenic-like lesions on his face appeared during the second week of isotretinoin treatment. Histologic study of the lesions revealed granulation tissue. Possible etiologies for this phenomenon are discussed.

Acne Vulgaris↗