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Biomedical subjects

K Wolff

Publications and source records attributed to K Wolff.

At least 217 records · Page 12Linked to original sources

Travelers' diarrhea in West Africa and Mexico: fecal transport systems and liquid bismuth subsalicylate for self-therapy.

The goals of this study were threefold: to compare the etiology of travelers' diarrhea in West Africa and Mexico, to evaluate two fecal transport systems for the recovery of enteropathogens, and to verify the efficacy of liquid bismuth subsalicylate (BSS) in different locations and under different entrance criteria for disease severity. The study populations consisted of 133 European tourists in West Africa and 112 American students in Mexico who had suffered from travelers' diarrhea. In 60% and 38% of the stool samples at the two study sites, similar proportions of enteropathogens were detected. A two-vial system consisting of Enteric Plus medium and polyvinyl alcohol fixative was slightly superior for identifying enteric pathogens than was a three-vial system with buffered glycerol saline, Cary-Blair medium with campylobacter antibodies, and polyvinyl alcohol fixative. In a parallel, double-blind, randomized trial, BSS significantly shortened disease duration at both study sites.

Aeromonas↗

The phenotypic spectrum of histiocytosis X cells.

Proliferating cells in histiocytosis X (histiocytosis X cells) share many structural and immunophenotypic features with Langerhans cells, leading to the assumption that histiocytosis X represents a proliferative disorder of Langerhans cells. Because, depending on their state of activation and/or differentiation, Langerhans cells exhibit a varying immunophenotype, we investigated whether histiocytosis X cells display a similar phenotypic heterogeneity and, if so, whether the heterogenous biological behavior of histiocytosis X is reflected by differences in the immunophenotype of the proliferating cells. In 21 patients suffering from different clinical manifestations of histiocytosis X, proliferating cells uniformly expressed class I and II alloantigens, T200, CD1, CD4, and S100 protein. In 12 of 21 cases, histiocytosis X cells additionally exhibited immunocytochemically detectable amounts of C3b and C3bi receptors and certain monocyte/macrophage antigens (CDw14, Ki-M1, Ki-M6). This immunophenotypic heterogeneity of histiocytosis X cells could not be correlated with clinical course, prognosis, and final outcome of the disease in a given patient. The capacity of histiocytosis X cells to immunophenotypically mimic various states of Langerhans cell activation and/or differentiation, however, underscores the concept of histiocytosis X as a proliferative disorder of Langerhans cell origin.

Adolescent↗

Sequential immunohistologic analysis of the skin following allogeneic bone marrow transplantation.

Graft-vs-host disease is generally viewed as an immunologically mediated disease. In search of additional tools for early diagnosis and an elucidation of the pathogenic mechanisms we investigated the expression kinetics of hemopoietic differentiation and class II alloantigens on both resident and passenger skin cells after bone marrow transplantation. HLA-DR antigens, which are found normally on the dendritic epidermal Langerhans cells only, are synthesized and expressed by keratinocytes within lesions of acute and chronic cutaneous graft-vs-host disease. Within non-lesional skin, however, during the course of cutaneous graft-vs-host eruptions, no clear cut expression of keratinocyte-bound HLA-DR antigens can be identified, suggesting that this phenomenon is locally restricted rather than generalized. Furthermore, our data indicate that within lesions clinically suggestive of cutaneous graft-vs-host disease but lacking diagnostic histopathologic criteria, KC-bound HLA-DR antigens can be readily identified. The second class II alloantigens investigated within the epidermis, the HLA-DQ antigens, were seen on Langerhans cells only and were not or only rarely detectable on keratinocytes. Several subtypes of CD3+ T lymphocytes were present in the epidermis of acute graft-versus-host lesions: one portion of CD3+ T lymphocytes also displayed the CD8 antigen; one portion, mainly localized within the basal layer, displayed the CD8 and/or the CD4 antigen; and one portion did not allow identification of CD8, CD4, or Leu7 antigens. In chronic cutaneous graft-versus-host lesions CD3+/CD8+ T lymphocytes predominated. CD1+ epidermal Langerhans cells were reduced in number and appeared rounded with blunt dendrites both in acute and chronic cutaneous graft-vs-host disease, but also, though to a lesser extent, within normal appearing skin from bone marrow transplanted patients without cutaneous graft-vs-host disease.

Adolescent↗

Recombinant gamma interferon and in vivo induction of HLA-DR antigens.

Recombinant human IFN-gamma, used for treatment of melanoma and renal carcinoma, was found to induce HLA-DR expression on human keratinocytes in vivo. HLA-DR antigens bound to keratinocytes of the basal and suprabasal layers of the epidermis were observed after intramuscular or intravenous injections of 0.5 mg/kg body weight IFN-gamma, 3 times a week. Keratinocyte-bound HLA-DR antigens were first observed at the beginning of the third or fourth week of treatment, but HLA-DQ and HLA-DP antigens were never detected on keratinocytes. The intracytoplasmic constant (gamma) chain of the class II molecules was also not detectable within the keratinocytes. Patients who received IFN-alpha 2 therapy, did not exhibit keratinocyte-bound HLA-DR antigens.

Female↗

Langerhans' cells are an actual site of HIV-1 replication.

Human epidermal Langerhans' cells (LC) are HLA-DR+/DQ+, CD1+, CD4+ dendritic antigen-presenting leukocytes. Based on the observation that in certain human immunodeficiency virus type 1 (HIV-1) infected individuals, LC are the only epidermal cells to react with monoclonal antibodies against HIV-1 isolate termed human T-lymphotropic virus IIIB/83 core proteins p17 and p24, we have proposed that LC can serve as a target for HIV-1. This contention was strengthened by the ultrastructural finding of HIV-1-like particles in the close proximity of LC and by the demonstration of signs of moderate to severe LC damage. Detailed electron microscopic analysis of skin and mucosal biopsies from an AIDS patient with p17/p24-positive LC now revealed not only mature HIV-1-like virions in the extracellular space surrounding LC and in intracytoplasmic LC vacuoles, but also developmental forms of HIV-1-like particles budding from LC surface membranes. Using peripheral blood derived monocytes/macrophages as targets for HIV-1 isolation, a virus isolate, designated human T-lymphotropic virus III WR-SK/86, was recovered from skin tissue from this patient by cocultivation and identified as unique by nucleic acid hybridization analysis. These findings now conclusively show that HIV-1 replicates in and is released from LC and support the concept that antigen-presenting cells (mononuclear phagocytes, LC) can serve as a reservoir for the acquired immunodeficiency syndrome virus.

AIDS-Related Complex↗

Verrucous malignant melanoma.

Five cases of verrucous malignant melanoma--a rare variant of melanoma that was described in 1967, but is rarely mentioned today--are presented and the clinical and histopathologic criteria defining this variant are discussed. The importance of this rare entity in the differential diagnosis of verrucous pigmented skin lesions is emphasized.

Adult↗

[The epidermis as an immune organ].

The epidermis possesses everything required for initiation of an immune response. It harbors antigen-presenting Langerhans cells, it produces immune modulatory cytokines, and (so far shown only in the murine system) it contains a distinct T cell population. Both upregulating and downregulating signals, leading to either sensitization or tolerance, are generated in the epidermis after exposure to antigens, and both have distinct cellular origins. While sensitizing and tolerogenic signals are usually balanced in such a way that Langerhans cell-generated sensitization is predominant, a breakdown of Langerhans cell function results in suppressive mechanisms. The structural and antigenic similarity between epidermis and thymus, the secretion of cytokines by keratinocytes, the migration of lymphocytes into the epidermis and the heterogeneity of TCR expression on Thy-1+ dendritic epidermal cells residing in (murine) epidermis and cell lines derived thereof all suggest that the epidermis is a site of postthymic or extrathymic T cell maturation.

Acquired Immunodeficiency Syndrome↗

[T- and B-cell double lymphoma: immunologic characterization using monoclonal antibodies].

The coexistence of two non-Hodgkin lymphomas in one patient is extremely rare. We describe a patient who suffered for 17 years from chronic lymphocytic leukemia of B-cell origin with bone marrow and peripheral blood involvement until he developed clinically typical mycosis fungoides of the skin. The neoplastic lymphatic cells in the skin infiltrates were T-cells of the helper/inducer phenotype and thus differed morphologically and by immunological markers from the neoplastic cells in peripheral blood and bone marrow. The clonal B-cell expansion was controlled well over many years by cytotoxic drug therapy, the cutaneous T-cell lymphoma only with limited success by oral photochemotherapy owing to lack of compliance. The patient died 3 years after the diagnosis of MF from a parallel exacerbation of both diseases. Extensive immunohistochemical studies verified the nature of both lymphomas in vivo and at autopsy.

Aged↗

[Scleromyxedema: immunosuppressive therapy with cyclophosphamide].

A 59-year-old male with scleromyxedema showed lichenoid papules over the large joints and buttocks; excessive skin folds, and generalized sclerosis of the skin similar to scleroderma; myopathy and arthritis; cardiovascular and cerebrovascular disease; and an abnormal monoclonal IgG-type protein in the serum. The progression of the disease, lack of established therapeutic modalities and the pronounced systemic involvement in this condition suggested a therapeutic trial employing monthly high-dose i.v. cyclophosphamide pulse therapy, together with low-dose prednisone on alternate days. The results were excellent and both subjective and objective symptoms improved dramatically. Controls performed at regular time intervals during a follow-up period of 12 months have failed to reveal any recurrence of the disease.

Cyclophosphamide↗

Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results.

Systemically disseminated cutaneous T-cell lymphoma is generally resistant to chemotherapy and radiotherapy. We tested a treatment involving the extracorporeal photoactivation of biologically inert methoxsalen (8-methoxypsoralen) by ultraviolet A energy to a form that covalently cross-links DNA. After oral administration of methoxsalen, a lymphocyte-enriched blood fraction was exposed to ultraviolet A (1 to 2 J per square centimeter) and then returned to the patient. The combination of ultraviolet A and methoxsalen caused an 88 +/- 5 percent loss of viability of target lymphocytes, whereas the drug alone was inactive. Twenty-seven of 37 patients with otherwise resistant cutaneous T-cell lymphoma responded to the treatment, with an average 64 percent decrease in cutaneous involvement after 22 +/- 10 weeks (mean +/- SD). The responding group included 8 of 10 patients with lymph-node involvement, 24 of 29 with exfoliative erythroderma, and 20 of 28 whose disease was resistant to standard chemotherapy. Side effects that often occur with standard chemotherapy, such as bone marrow suppression, gastrointestinal erosions, and hair loss, did not occur. Although the mechanism of the beneficial effect is uncertain, an immune reaction to the infused damaged cells may have restricted the activity of the abnormal T cells. This preliminary study suggests that extracorporeal photochemotherapy is a promising treatment for widespread cutaneous T-cell lymphoma.

Administration, Oral↗

Vegetating cicatricial pemphigoid. A new subset of the cicatricial pemphigoid spectrum.

A case with widespread vegetating-pustular skin lesions, oral erosions, ulcerations and scarring, and conjunctival synechiae is reported. Clinically, histopathologically, and by immunofluorescence and electron microscopy this patient combined the features of pemphigoid vegetans, as described by Winkelmann and Su, and the mucocutaneous type of cicatricial pemphigoid. This observation suggests that a third subset of cicatricial pemphigoid can now be added to the two existing ones, the mucocutaneous and Brunsting-Perry types, and the designation vegetating cicatricial pemphigoid is proposed for this heretofore undescribed condition.

Aged↗

Azathioprine in the treatment of pemphigus vulgaris. A long-term follow-up.

In a prospective long-term study, thirty-seven patients with severe generalized pemphigus vulgaris were treated with a combined corticosteroid-azathioprine regimen. Twenty-nine patients were available for complete follow-up lasting from 4 to 16 years after initiation of therapy. At the time of final evaluation, twenty-seven patients (93%) were alive; two deaths were unrelated to therapy; thirteen (45%) of the patients were free of disease and had not received treatment for up to 132 months; five of these patients had been off therapy for periods ranging from 60 to 132 months; eleven (38%) of the patients were clinically free of disease but still had low titers of antibodies and thus required low-dose maintenance therapy; five (17%) of the patients were well controlled but not completely free of disease. Side effects were rare and mostly related to corticosteroids. Of the original thirty-seven patients, only one death related to disease or therapy occurred and was due to pulmonary tuberculosis. It is concluded that azathioprine-corticosteroid treatment of pemphigus is highly effective and safe; it leads to long-term remissions in most patients and possibly to a cure in some.

Aged↗

In vivo epiluminescence microscopy of pigmented skin lesions. I. Pattern analysis of pigmented skin lesions.

The importance of recognizing early melanoma is generally accepted. Because not all pigmented skin lesions can be diagnosed correctly by their clinical appearance, additional criteria are required for the clinical diagnosis of such lesions. In vivo epiluminescence microscopy provides for a more detailed inspection of the surface of pigmented skin lesions, and, by using the oil immersion technic, which renders the epidermis translucent, opens a new dimension of skin morphology by including the dermoepidermal junction into the macroscopic evaluation of a lesion. In an epiluminescence microscopy study of more than 3000 pigmented skin lesions we have defined morphologic criteria that are not readily apparent to the naked eye but that are detected easily by epiluminescence microscopy and represent relatively reliable markers of benign and malignant pigmented skin lesions. These features include specific patterns, colors, and intensities of pigmentation, as well as the configuration, regularity, and other characteristics of both the margin and the surface of pigmented skin lesions. Pattern analysis of these features permits a distinction between different types of pigmented skin lesions and, in particular, between benign and malignant growth patterns. Epiluminescence microscopy is thus a valuable addition to the diagnostic armamentarium of pigmented skin lesions at a clinical level.

Basal Cell Carcinoma↗

In vivo epiluminescence microscopy of pigmented skin lesions. II. Diagnosis of small pigmented skin lesions and early detection of malignant melanoma.

Pattern analysis by epiluminescence microscopy of pigmented skin lesions was tested in a study of 318 small pigmented skin lesions that were diagnostically equivocal when examined with the naked eye. An improvement of clinical diagnosis was achieved by epiluminescence microscopy for practically all lesions, both benign and malignant, and was equally impressive for melanocytic and nonmelanocytic lesions. Improvement in diagnostic accuracy was as follows: for small nodular melanomas, from 50% to 70%; for superficial spreading melanoma in situ, from 46% to 80%; for invasive superficial spreading melanoma, from 64% to 90%; and for early lentigo maligna and lentigo maligna melanoma, from 67% to 88%. Conversely, the diagnosis of pigmented Spitz nevi improved from 46% to 93% and of pigmented basal cell carcinomas from 60% to 90%, which appears equally important because most of these lesions had clinically been considered to represent melanomas. The use of epiluminescence microscopy also resulted in considerable improvement in the diagnosis of dysplastic nevi, which was particularly helpful in making therapeutic decisions. Epiluminescence microscopy greatly expands the diagnostic armamentarium available for pigmented skin lesions at a clinical level and thus increases the chances of detecting or ruling out melanoma in its earliest stages.

Basal Cell Carcinoma↗

Epidermal Langerhans cells--a target for HTLV-III/LAV infection.

Langerhans cells (LC) are bone marrow-derived, Ia+, CD1+, CD4+, ATPase+ dendritic antigen-presenting cells within the human epidermis. Since the CD4 molecule has been implicated as a receptor structure for HTLV-III/LAV (human T-cell leukemia virus/lymphadenopathy-associated virus), we asked whether LC from HTLV-III/LAV-seropositive individuals display signs of HTLV-III/LAV infection. In skin biopsies from 7/40 HTLV-III/LAV-infected persons (1 asymptomatic carrier, 2 patients with acquired immunodeficiency syndrome (AIDS)-related complex and 4 patients with AIDS), LC were the only epidermal cells to react with a monoclonal antibody specific for the HTLV-III core protein p17. A varying percentage of p17+ LC were morphologically altered with blunt dendrites and poorly demarcated cellular contours. In one of these biopsies, the presence of LC-associated viral particles characteristic of HTLV-III/LAV as well as cytopathic changes in approximately one-third of the LC population were demonstrated by electron microscopy. These results strongly suggest that LC may harbor HTLV-III/LAV. The infection of LC with this retrovirus may have deleterious consequences for the immunologic functions of this cell system and may thus contribute to both the acquisition of immunodeficiency and the infectious and neoplastic complications of AIDS.

Acquired Immunodeficiency Syndrome↗

Differential expression of class II alloantigens by keratinocytes in disease.

The purpose of this study was to determine whether keratinocytes in certain disease states such as cutaneous T-cell lymphoma and lichen planus, express HLA-DR antigens (corresponding to the murine I-E antigens) only or whether they are also capable of expressing HLA-DQ antigens (analogues of the murine I-A antigens). Cryostat sections from 11 biopsies from cutaneous T-cell lymphoma and from 11 lichen planus biopsy specimens were submitted to indirect immunofluorescence and a 4-step immunoperoxidase method. This consists of applying monoclonal antibodies recognizing HLA-DR and HLA-DQ molecules and the intracytoplasmic invariant chain of the class II molecules. In 8 of the 11 cutaneous T-cell lymphoma specimens and in 3 of the 11 lichen planus biopsies concomitant expression of HLA-DR and HLA-DQ molecules by keratinocytes was detectable with the immunoperoxidase method. However, with the indirect immunofluorescence technique HLA-DQ antigens on keratinocytes could not be detected. The simultaneous expression of surface-bound HLA-DR antigens and intracytoplasmic gamma-chains was demonstrable in all cases investigated and with both the immunohistologic methods applied.

Epidermis↗

[The glucagonoma syndrome].

We report on our experience with two patients with glucagonoma syndrome and review the recent dermatologic literature. The clinical features are described with special emphasis on necrolytic migratory erythema, the characteristic cutaneous sign of glucagonoma syndrome. Using our histological and ultrastructural findings, we discuss the pathogenesis of necrolytic migratory erythema. Pathognomonic laboratory data and the diagnostic procedures recommended for the evaluation of patients with glucagonoma syndrome are presented. Finally, we discuss the differential diagnosis and describe therapeutic possibilities in the management of this syndrome.

Adenoma, Islet Cell↗