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Biomedical subjects

G F Murphy

Publications and source records attributed to G F Murphy.

At least 181 records · Page 10Linked to original sources
PubMed1983

Local immune response in basal cell carcinoma: characterization by transmission electron microscopy and monoclonal anti-T6 antibody.

We examined lesional and perilesional skin from nine basal cell carcinomas occurring in six patients to determine the role of local immunity in the pathogenesis of these neoplasms. Marked hyperplasia of Langerhans cells and indeterminate cells as defined by monoclonal anti-T6 antibody was observed in lesional and perilesional skin of most specimens. Ultrastructurally, Langerhans cells were observed in the dermis and above the basement membrane zone where mitotic activity was documented. Apposition of Langerhans cells and indeterminate cells with degenerating and necrotic neoplastic keratinocytes and with exocytotic lymphocytes was frequently encountered. Zonal necrosis of carcinoma cells was often immediately peripheral to exocytotic lymphoid cells. These observations support the contention that an active local immunologic response is related to the biologic behavior of some basal cell carcinomas.

Adult↗
PubMed1983

Histiocytosis-X: in situ characterization of cutaneous infiltrates with monoclonal antibodies.

Cutaneous lesions in three cases of histiocytosis-X were studied by light microscopy, electron microscopy, and immunoperoxidase technics. In each case, Birbeck granule-containing histiocytosis-X cells infiltrated the epidermis and were apposed to lymphocytes. The histiocytosis-X cells and normal Langerhans cells stained with anti-T6 and anti-I1 (Ia-like) antibodies but were negative with anti-T3, anti-T8, anti-M1, and anti-lysozyme antibodies. In addition, the histiocytosis-X cells also stained with anti-T4 antibodies, which react with T-cells associated with helper/inducer phenotype. This study supports the hypothesis that histiocytosis-X cells are abnormal Langerhans cells. The presence of T4/T6-positive cells in cutaneous disease may be a marker for abnormal Langerhans cells.

Antibodies, Monoclonal↗
PubMed1983

T6 is superior to Ia (HLA-DR) as a marker for Langerhans cells and indeterminate cells in normal epidermis: a monoclonal antibody study.

Previous studies in our laboratory using immunoelectron microscopy have shown that anti-T6 monoclonal antibody reacts with all epidermal Langerhans cells in normal skin. Comparison of the number of T6-positive (+) epidermal cells with Ia (HLA-DR) (+) cells, as defined by the monoclonal antibodies, anti-I1 and anti-I2, disclosed that these latter markers significantly underestimated Langerhans cell and indeterminate cell numbers (p less than 0.01 and p less than 0.001, respectively) when employed in a sensitive 4-step immunoperoxidase procedure. Thus, it appears that all epidermal Langerhans cells and indeterminate cells are not Ia-positive as defined in this system and that Ia(+)/T6(+) and Ia(-)/T6(+) subsets exist. These subsets may be analogous to the Ia(+) and IA(-) subsets of macrophages, in which the former are responsible for antigen interaction with T cells.

Adult↗
PubMed1983

Location of HLA-A,B,C antigens in dendritic cells of normal human skin: an immunoelectron microscopic study.

The distribution of the major histocompatibility antigens HLA-A,B,C, (HLA) on dendritic cells of normal human skin was studied by immunoelectron microscopy and a 4-step immunoperoxidase technique utilizing monoclonal antibodies. Light microscopy revealed peripheral staining for HLA of epidermal and pilar infundibular keratinocytes. In the epidermis, the staining was present from the basal layer to the upper stratum spinosum. In the follicles below the level of the infundibulum, HLA was detected only on rare intraepithelial dendritic cells. These dendritic cells could not be identified in the epidermis due to the HLA staining of the surrounding keratinocytes. Similar cells stained diffusely with anti-T6 antibody; the keratinocytes did not. Immunoelectron microscopy demonstrated: (1) the presence of HLA staining of keratinocyte membranes from the stratum basalis to the level of the upper stratum spinosum and in the pilar infundibulum, (2) the possible absence of HLA on melanocytes, (3) the presence of focal HLA staining of the membranes of epidermal and follicular dendritic cells that contained Birbeck granules and were, therefore, Langerhans cells, (4) dendritic mononuclear cells within the follicular epithelium, which although devoid of Birbeck granules, exhibited similar reactivity with anti-HLA antibody. These findings suggest that HLA antigens are present on the membranes of Langerhans cells, but are not demonstrable on melanocytes in normal human skin.

Antibodies, Monoclonal↗
PubMed1983

Ultrastructural documentation of HLA-DR antigen reactivity in normal human acrosyringial epithelium.

We have observed that monoclonal antibodies directed against human Ia-like antigens react with a subset of epidermal keratinocytes as well as Langerhans cells in normal human skin. Membrane reactivity for HLA-DR antigen in flattened ductal keratinocytes and in adjacent cuticular cells forming the acrosyringial lumen was observed using immunoelectron microscopy. It should be recognized that Ia-positive acrosyringial keratinocytes represent a potential source of contamination in methods designed to study and isolate Langerhans cells using antibodies directed against HLA-DR antigens. Teleologic considerations of HLA-DR antigen expression in the acrosyringium are discussed.

Adult↗
PubMed1983

In situ identification of T6-positive cells in normal human dermis by immunoelectron microscopy.

Monoclonal anti-T6 antibody, which reacts with the majority of cortical thymocytes but not peripheral T cells, also reacts with human epidermal Langerhans cells, as shown by a four-step immunoperoxidase method and immunoelectron microscopy. To define whether T6-positive cells are also present in normal human dermis, we used these techniques to demonstrate two immunologically distinct populations of histiocyte-like cells in normal human dermis. The first population contains cells devoid of phagolysosomes or Birbeck granules. These cells react with anti-T6 antibody, but not with monoclonal anti-T3 antibody which defines peripheral T cells, and are found predominantly in and around dermal lymphatic vessels. The second is composed of phagolysosome-containing cells which do not react with anti-T6 antibody or anti-T3 antibody. Because to date, Langerhans cells are the only cells in normal human epidermis that react with anti-T6 antibody, these data provide immunological evidence for a specific link between Langerhans cells and a T6-positive dermal mononuclear cell, possibly the so-called indeterminate cell. In addition, application of these techniques should, for the first time, permit the immunological distinction of these T6-positive mononuclear cells from other cells bearing Ia antigens, such as dermal histiocytes and certain lymphocytes, in normal and diseased skin.

Antibodies, Monoclonal↗
PubMed1983

Distribution of cell surface antigens in histiocytosis X cells. Quantitative immunoelectron microscopy using monoclonal antibodies.

We have shown previously that cells comprising the cutaneous infiltrates of histiocytes X (HXCs), like Langerhans cells (LCs), react with monoclonal anti-T6 antibody. HXCs also react with anti-T4/4b and anti-Ia-like antibodies. To further define the patterns of antibody reactivity in HXCs, we performed immunoelectron microscopy on two clear-cut cases of histiocytosis X using the immunoperoxidase technique. The reaction product of diaminobenzidine, indicating anti-T6 antibody reactivity, was easily detected along cell membranes of HXCs and at sites of possible endocytosis. Anti-T4/4b and anti-Ia antibodies had less cell membrane reactivity. Computerized image analysis aided in discriminating the patterns of anti-T6 antibody in HXCs and from LCs and confirmed that anti-T6 antibody staining was the most intense of the antibodies evaluated. These findings (1) document antigenic similarities and differences between HXCs and LCs on an ultrastructural level, (2) add support to the concept that HXCs are abnormal proliferations of LCs, and (3) demonstrate the association of the cell surface antigen, T6, with apparent endocytotic activity.

Antibodies, Monoclonal↗
PubMed1983

Organelle-specific injury to melanin-containing cells in human skin by pulsed laser irradiation.

Physical models predict that ultraviolet laser radiation of appropriately brief pulses can selectively alter melanin-containing cellular targets in human skin. We exposed skin of normal human volunteers to brief (20 nanosecond) 351-nm wave length pulses from a XeF excimer laser, predicting that those cells containing the greatest quantities of melanized melanosomes (lower half of the epidermis) would be selectively damaged. Transmission electron microscopy revealed the earliest cellular alteration to be immediate disruption of melanosomes, both within melanocytes and basal keratinocytes. This disruption was dose dependent and culminated in striking degenerative changes in these cells. Superficial keratinocytes and Langerhans cells were not affected. We conclude that the XeF excimer laser is capable of organelle-specific injury to melanosomes. These findings may have important clinical implications in the treatment of both benign and malignant pigmented lesions by laser radiations of defined wave lengths and pulse durations.

Biopsy↗
PubMed1983

Selective thermal effects with pulsed irradiation from lasers: from organ to organelle.

Specific damage by selectively absorbed, pulsed lasers can be predicted based on physical models. Thermally mediated alterations can be confined to pigmented targets from the level of subcellular organelles (e.g., melanosomes) to large multicellular tissue structures (e.g., blood vessels) by the appropriate manipulation of wavelength and pulse duration. Highly selective damage to human cutaneous microvessels in vivo is shown to occur after 0.3-microseconds 577-nm dye laser pulses; the epidermis and dermal structures other than vessels are spared. Observations in an animal model suggest that hemorrhage or, at lower doses, selective intravascular coagulation and permanent microvascular hemostasis occur. Highly selective damage to melanized cells and to single melanosomes in situ was shown to occur after single 20-ns 351-nm pulses from a XeF excimer laser. Basal-cell- and melanocyte-specific necrosis is followed by gross hypopigmentation. In this case there is no evidence of vascular damage. The most likely modes of selective alterations include localized thermal denaturation, vaporization, and shock-wave generation. Means of predicting and controlling histologically selective radiant heating effects in skin are suggested.

Animals↗
PubMed1982

Primary lymphoma of bone: the relationship of morphologic diversity to clinical behavior.

Since primary lymphoma of bone (PLB) exhibits morphologic diversity and variability in individual survival, we analyzed the relationship between histopathologic features and biological behavior in 33 patients treated at the Massachusetts General Hospital. Three major histologic subgroups were identified, based on a variety of criteria, the most important of which were the predominance of cells with or without nuclear clefts and the degree of pleomorphism. The probability of NED survival at five years was 64% for patients with tumor predominantly composed of cleaved cells, 13% for those with tumors classified in the noncleaved cell tumor group, and 0% (no survivors) for the pleomorphic subgroup. When tumors were subclassified according to the size of the predominant cell (small versus large), this parameter was found to be of no value in preceding NED survival. Factors that could have potentially influenced the results were analyzed. Since this is a retrospective review, the questions addressed in this study should be further studied in a prospective way.

Adolescent↗
PubMed1982

Neutrophilic eccrine hidradenitis. A distinctive type of neutrophilic dermatosis associated with myelogenous leukemia and chemotherapy.

On two occasions, erythematous edematous plaques developed on the left side of the neck and the left shoulder of a man undergoing induction chemotherapy for acute myelogenous leukemia. The lesions resolved after several days in both instances. Histologically, numerous neutrophils surrounded and focally infiltrated the eccrine secretory coils, in which epithelial necrosis was observed. The "fixed" nature of the plaques and temporal relationship to chemotherapy suggest that the lesions represent an unusual reaction to chemotherapeutic agents. It is possible that this unique clinicopathologic picture represents a neutrophilic dermatosis associated with leukemia.

Adult↗
PubMed1982

Lymphocytes and necrosis of the cutaneous microvasculature in malignant atrophic papulosis: a refined light microscope study.

Malignant atrophic papulosis is a disease characterized by multiple distinctive cutaneous and often lethal visceral infarctions. In some individuals, the diagnosis is not made until the skin manifestations are noted in a seriously ill patient with gastrointestinal and/or central nervous system disease. In other individuals, the disorder may pursue a benign course with only skin manifestations for many years. Using refined light microscopy to examine the skin lesions, the extensive nature of the necrotic microvascular alterations, a predominant lymphocytic infiltrate, and neural changes are documented. These findings suggest that the cutaneous lesions of malignant atrophic papulosis may result from a lymphocyte-mediated necrotizing vasculitis that affects the entire cutaneous microvasculature.

Adult↗
PubMed1982

Effect of chronologic aging and ultraviolet irradiation on Langerhans cells in human epidermis.

The effect of aging on epidermal Langerhans cells (LC) and on their response to a single ultraviolet (UV) exposure was studied in skin biopsy specimens of healthy adults, 4 aged 22-26 yr and 7 aged 62-86 yr. In unirradiated skin, old adults had fewer LC than young adults, 5.8 +/- 1.1 versus 10.0 +/- 0.8 (mean +/- SEM) per 3 mm wide cross-section (p = .015). Following irradiation with 3 times the minimal erythema dose, recognizable LC were absent in all but 2 subjects within 24 hr. However, LC number fell less rapidly in old adults and was almost unchanged at 4 hours (5.8 +/- 1.1 versus 5.0 +/- 1.2), while in young adults LC number decreased from 10.0 +/- 0.8 to 3.3 +/- 1.3 during the same period (p less than .05). Other changes noted in both young and old subjects following irradiation included cytoplasmic vacuolization, frequent apposition of LC to severely damaged keratinocytes, and the finding of LC in the basal layer of the epidermis rather than exclusively suprabasilarly as in control sections. These data demonstrate an age-associated loss of epidermal LC and slowing of LC response to UV irradiation. UV-induced LC changes appear qualitatively similar in young and old adults and include histological evidence of cellular damage, transient association of LC with damaged keratinocytes, and possible migration of LC from the irradiated epidermis within 24 hr.

Adult↗