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Biomedical subjects

G L Wantzin

Publications and source records attributed to G L Wantzin.

At least 19 recordsLinked to original sources
PubMed1989

Rapid recovery of Langerhans cell alloreactivity, without induction of autoreactivity, after in vivo ultraviolet A, but not ultraviolet B exposure of human skin.

For therapeutic medical, cosmetic, and recreational reasons, humans expose themselves to increasing amounts of UVA. However, little is known of the photobiologic events associated with cutaneous carcinogenesis and photoaging that occur as a result of UVA exposure. UVB exposure of human skin abrogates the function of epidermal CD1+DR+ Langerhans cells and induces the appearance of CD1-DR+ non-Langerhans cell APC. This non-Langerhans cell APC population activates autoreactive immunoregulatory T cells that lead to suppressor-effector T cell function. In this report we show that, similarly to UBV, UVA exposure abrogates the function of CD1+DR+ Langerhans cells. However, in contrast to UVB, there is rapid recovery of Langerhans cell antigen-presenting cell activity and that CD1-DR+ non-Langerhans cell APC failed to appear to a significant degree. In keeping with the lack of CD1-DR+ epidermal cells, UVA exposed epidermal cells harvested 3 days after exposure functioned similarly to normal epidermis in that they activated alloreactive T cells but not autoreactive T cells in the absence of added Ag. This was in contrast to UVB irradiated epidermal cells that potently activate autoreactive T cells and contain CD1-DR+ cells. Thus, although both UVA and UVB initially depletes and inactivates CD1+DR+ Langerhans cells, the subsequent APC function of epidermal cells exposed to UVA differ profoundly from that of cells exposed to UVB. UVA radiation is less carcinogenic than UVB; differences in host responses to UV tumors may be linked to the rapid recovery of Langerhans cell function and the lack of induction of CD1-DR+ non-Langerhans cell APC after UVA exposure.

Adult↗
PubMed1989

DNA analysis by flow cytometry in cutaneous T-cell lymphomas.

DNA histograms of skin and blood specimens from 64 patients with known or suspected cutaneous T-cell lymphoma (CTCL) have been examined and compared with normal blood mononuclear cells and skin biopsy samples from 50 patients with various benign cutaneous conditions (i.e. patch test infiltrates, eczema, psoriasis, lichen planus, atopic dermatitis) in an attempt to establish whether DNA measurements by flow cytometry may improve the early recognition of CTCL. The results indicate that right-skewed G0/G1 peaks are seen frequently in both benign disorders and known and suspected CTCL. Such peaks may reflect increased stainability of DNA due to chromatin dispersion during cell activation and/or cell proliferation and do not constitute reliable evidence of malignancy. In contrast, discrete aneuploid DNA peaks are confined to malignant lesions, but are seen almost exclusively in the advanced stages in which the diagnosis can be established easily based on routine histological criteria. These data indicate that DNA measurements by flow cytometry is of only limited help in the early recognition of CTCL and support the view that the lymphoid infiltrate in early CTCL may be reactive (rather than neoplastic) or alternatively may contain only minor reactive (rather than neoplastic) or alternatively may contain only minor populations of abnormal (malignant) cells which cannot be detected by currently available DNA measurement techniques.

Adult↗
PubMed1989

Serological markers of primary HIV infection.

39 persons with an incidentally discovered seroconversion from HIV antibody negative (Ab-) to antibody positive (Ab+) state as measured by an enzyme-linked immunosorbent assay (ELISA) were investigated for the presence of (1) HIV antigen (Ag) and (2) immunoblotting test (IBT) Ab in serum samples collected within the year before seroconversion. 13 (33%) of the patients were HIV Ag+ at some time before seroconversion. However, the collection of samples was not done systematically and the samples from patients who had at least 1 sample collected within 3 months before seroconversion were thus compiled separately. This group consisted of 58 samples from 19 patients and among these none were HIV Ag+ earlier than 11 weeks before seroconversion, but the prevalence of HIV Ag+ samples was rising towards seroconversion and 10 patients (53%, 95% confidence limits: 29-76%) became HIV Ag+ in this 11-week period. Further, among all patients 13 (33%) were IBT Ab+ 4-50 days (median: 14 days) before seroconversion. Finally, among 18 patients with signs and symptoms consistent with an acute HIV infection 10 were HIV Ag+, as opposed to 4 HIV Ag+ patients among 21 without symptoms (p = 0.041).

Adolescent↗
PubMed1989

The development of a Ki-1-positive large cell non-Hodgkin's lymphoma in pagetoid reticulosis.

A case of the disseminated variant of pagetoid reticulosis is described which progressed after many years of disease to a large cell anaplastic (Ki-1) lymphoma of T-cell type. The lymphoma cells showed abnormal cellular DNA and a high proliferative rate, as revealed by immunophenotypic examination and single-cell DNA measurements. The cells were positive for activation associated antigens and expressed a T-helper/inducer phenotype. A similar phenotype was expressed by the neoplastic cells in the co-existing lesions of pagetoid reticulosis. These findings support the view that pagetoid reticulosis is a variant of the cutaneous T-cell lymphomas which originates from activated lymphoid cells and which may on occasion progress to a potentionally more aggressive lymphoid malignancy.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Increased number of circulating suppressor T-lymphocytes in sun-induced multiple skin cancers.

The distribution of peripheral lymphocyte subsets was studied in fifteen patients with multiple nonmelanoma skin cancers, selected according to history of ultraviolet (UV) or X-ray exposure. The skin cancer was associated with previous heavy exposure to UV light in seven patients, and past exposure to x-rays in eight patients. In the UV group, the helper T-lymphocytes/suppressor T-lymphocytes (Th/Ts) ratio was abnormally low (P less than 0.01) compared with the ratios of the x-ray and control groups. The low Th/Ts ratio was associated with an absolute increase in the number of Ts. This suggests that heavy sun exposure may cause a permanent increase in the number of Ts in certain persons. These extra T-lymphocytes may in turn prevent immune rejection of transformed keratinocytes.

Adult↗
PubMed1988

Hepatitis B in symptomless Danish homosexual men.

Forty eight symptomless homosexual men attending a sexually transmitted disease (STD) clinic and found by screening to have hepatitis B surface antigen (HBsAg) were followed up for a median of 10 (range six to 26) months to characterise their liver disease. Initially 33/50 (66%) of the men had increased serum liver enzyme activity and 19/47 (40%) had increased serum immunoglobulin G concentrations. Liver biopsy specimens showed acute hepatitis B in 12 (39%) and chronic hepatitis B in 19 (61%) of the 31 patients who underwent liver biopsy. The course of the infection was: acute hepatitis B in 14/48 (29%), chronic persistent hepatitis B in 23/48 (48%), chronic aggressive hepatitis B in 8/48 (17%), and cirrhosis in 3/48 (6%) of the patients. Antibodies against human immunodeficiency virus (HIV) were present in 16/45 (36%) of the patients, but the presence of antibodies to HIV did not influence the course of hepatitis B in the observation period.

Adult↗
PubMed1988

AIDS related changes in pattern of sexually transmitted disease (STD) in an STD clinic in Copenhagen.

Testing for antibodies against human immunodeficiency virus (HIV) was introduced in 1984 in this major sexually transmitted disease (STD) clinic in Copenhagen, which is attended by about 10,000 new patients each year. From 1984 to 1987 the proportion of patients examined for antibodies to HIV rose from 6% to 32%. The overall incidence of HIV antibody positivity decreased from 30% in 1984 to 3% in 1987, the combined result of decreased positivity in high risk patients tested and increased screening in low risk patients. HIV antibody positivity has been confined largely to homosexual men and drug addicts. Since 1985, however, 21 out of 2623 (0.8%) heterosexuals who were not drug addicts were found to be HIV antibody positive. During 1984-6 the incidence of STDs most often encountered in high risk groups (syphilis and gonorrhoea) decreased by 64% and 41% respectively, whereas the incidence of diseases most often diagnosed in low risk groups (condylomata acuminata and genital herpes) increased by 70% and 34% respectively in the same period. The addition of HIV infection to the list of STDs requires the allocation of more resources to the STD clinics to enable these clinics to handle this new problem. Screening for all patients attending an STD clinic for antibodies to HIV must be considered, and in our area it would be cost effective.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Seroconversion to human immunodeficiency virus (HIV) in persons attending an STD clinic in Copenhagen.

1,182 males and 155 females attending an STD clinic from June 1984 to October 1985 were investigated for the presence of antibodies to human immunodeficiency virus (HIV). 348 (29.5%) of the males and 5 (3.2%) of the females were antibody positive (ab+). 237 of the males were initially antibody negative (ab-) and were tested more than once, and during a 16-month period 40 of these seroconverted from ab- to antibody positive. The mean follow-up period of these 40 patients was 7.1 months, and thus the seroconversion rate is estimated to be 2.4% per month. Samples from 37 of these were available for HIV antigen testing. 19 of the patients were antigen positive in the latest ab- sample and accordingly, 18 patients were antigen negative in the latest ab- sample. No difference was found between the mean follow-up periods of those with and those without HIV antigen in the latest ab- serum and the presence of HIV antigen in serum was not associated with symptoms of acute HIV infection. After 20 months of follow-up, none (0.0-8.8%, 97.5% confidence limits) of the 40 patients have developed AIDS or AIDS-related complex.

Adolescent↗
PubMed1987

Lymphomatoid papulosis. A follow-up study of 30 patients.

Thirty patients, 13 female and 17 male, have been followed from 3 months to 22 years (mean, 81 months; median, 63 months) and special studies have been performed on a proportion of these in order to try to predict malignant evolution. Age at onset was from 20 to 70 years (mean, 43 years; median, 42 years). Duration of disease was from 1 to 30 years (mean, 119 months; median 161 months). Seven patients also had parapsoriasis en plaque or plaque-stage mycosis fungoides at the time of diagnosis and one patient had erythroderma. None of the 22 uncomplicated lymphomatoid papulosis patients developed malignant cutaneous lymphoma during the period of observation, while the remaining 8 patients who had concurrent parapsoriasis en plaque, mycosis fungoides, or erythroderma did not deteriorate further. Single-cell deoxyribonucleic acid (DNA) measurements on the dermal infiltrate were done in 13 patients and were abnormal in 7 patients. Two of these had greatly abnormal DNA histograms and at the same time an abnormal clinical presentation with multiple nodules and tumors. The remaining five patients had DNA histograms that indicated a potential for malignancy. Monoclonal antibody studies were performed on skin biopsy specimens of 10 patients. The dermal infiltrate was dominated by T-helper lymphocytes and some Hodgkin and Reed-Sternberg cells could be detected by the antibodies Ki-1, Ki-24, and Ki-27. Human T-lymphotropic virus type I (HTLV-I) antibodies were found in 3 of 18 patients examined. Treatment with psoralens plus ultraviolet A (PUVA) was effective (partial or complete remission) in six patients but they relapsed at cessation of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Dose response and time course for induction of T6- DR+ human epidermal antigen-presenting cells by in vivo ultraviolet A, B, and C irradiation.

In vivo ultraviolet (UV) exposure of human skin abrogates the antigen-presenting function of T6+ DR+ Langerhans cells and induces the appearance of antigen-presenting T6- DR+ epidermal melanophages. UV-exposed epidermal cells containing T6- DR+ epidermal antigen-presenting cells, in contrast to unexposed epidermal cells containing T6+ DR+ Langerhans cells, potently activate autoreactive regulatory T cells in the absence of exogenous antigens. Autoreactive T cells may be important for regulation of other immune responses such as those which occur in photosensitive lupus erythematosus and in immune surveillance of UV-induced skin cancers. It is therefore imperative to determine the factors that govern their appearance in the skin. It was found that UVB and UVC, but not UVA, induced a dose-dependent appearance of T6- DR+ epidermal melanophages. The optimal time of appearance was 2 or 3 days after UVB and UVC exposure. In contrast, UVA was a poor inducer of T6- DR+ cells at all doses and all time points tested. Although UVA was a poor inducer of T6- DR+ epidermal cells, UVA radiation resulted in depletion of T6+ DR+ Langerhans cells from the epidermis, as did UVB and UVC radiation. This differential effect of UV wave bands on the immunocompetent cells in human skin may be related to the greater potential of UVB exposure to induce skin cancers and to exacerbate systemic lupus erythematosus.

Adult↗
PubMed1987

Genotypic analysis of cutaneous T-cell lymphomas.

The gene encoding the beta-chain of the T-cell antigen receptor (TCR) has been analyzed for evidence of rearrangement in skin, blood, and lymph node specimens from 23 cases of known or suspected cutaneous T-cell lymphoma (CTCL). Two cutaneous large cell lymphomas, 4 cases of Sézary syndrome, and 5 cases of advanced (tumor) stages of mycosis fungoides showed clonal rearrangement of the TCR beta-chain gene in all samples, including lymph nodes in which histologic examination revealed only dermatopathic lymphadenitis. These results indicate that DNA analysis provides a valuable means for improving the diagnosis of extracutaneous disease in advanced stages of CTCL. In contrast, the gene was in a germline configuration in all samples from 12 patients with plaque stages of mycosis fungoides or suspected early CTCL, suggesting that in these 2 conditions the T-cell proliferation is either polyclonal or contains very few monoclonal (i.e., neoplastic) cells.

Adolescent↗
PubMed1987

UVB and UVC, but not UVA, potently induce the appearance of T6- DR+ antigen-presenting cells in human epidermis.

Non-Langerhans cell, antigen-presenting T6- DR+ epidermal cells (EC) appear 3 days following broad band ultraviolet radiation exposure of human skin and are responsible for the increased antigen presentation capacity of EC seen 3 days after UV exposure. To determine the UV wavelengths that induce T6- DR+ EC, volar forearm skin of 10 human volunteers was irradiated in vivo with 4 minimal erythema doses (MED) each of pure UVA (mean 482 J cm-2), UVB (mean 0.390 J cm-2), and UVC (mean 0.397 J cm-2). The purity of the light sources was as follows: UVB, 98% of the emission was in the UVB range; UVC, 97% of the irradiance was in the UVC range; UVA, 100% of the energy had wavelengths longer than 340 nm. Three days after UV irradiation with 4 MED of each wavelength band, suction blister-derived EC suspensions were prepared from the UV-exposed and unirradiated sites. Percentages of T6+ DR+ Langerhans cells (LC) and T6- DR+ EC were quantitated. Relative to control EC, which contained 2.4 +/- 0.3% T6+ DR+ LC, the mean percentage (+/- SEM) of T6+ DR+ LC contained within UV-exposed EC was significantly decreased as follows: UVB, 0.5 +/- 0.2%; UVC, 0.9 +/- 0.1%; UVA, 0.5 +/- 0.2% (n = 10). T6- DR+ EC, absent in control EC, were induced both by UVB, 5.2 +/- 1.7% and UVC; 1.5 +/- 0.4%. Despite the use of more than 1200 times greater doses in J cm-2 of UVA than UVB and UVC, UVA was a poor inducer of T6- DR+ EC (0.5 +/- 0.2%) and in about half of these individuals, T6- DR+ EC were undetectable. The UV wavelengths for induction of T6- DR+ EC lies predominantly within the UVB band, but also to a lesser extent within the UVC band. These wavelengths appear to be analogous to both the wavelengths for generation of increased host susceptibility to UV-induced murine tumors and to the wavelengths for UV-induced systemic suppression of contact hypersensitivity. However, our data indicate that UV wavelengths for decreasing the number of T6+ DR+ LC in humans differs from the wavelengths for induction of systemic suppression of contact hypersensitivity in mice. Taken together, these data suggest that the appearance of T6- DR+ EC, but not the disappearance of T6+ DR+ LC, following UV exposure may be related to the induction of such antigen-specific suppressor T cells.

Antigen-Presenting Cells↗