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Biomedical subjects

W H Clark

Publications and source records attributed to W H Clark.

At least 109 records · Page 6Linked to original sources

Phenotypic characteristics of cells derived from precursors of human melanoma.

Of 66 specimens from benign melanocytic nevi, including common acquired and congenital nevi, Spitz tumors (epithelioid cell nevi), and melanocytic nevi with dysplasia, 57 could be grown in tissue culture. The cultured cells were identified as melanocytes by the presence of premelanosomes and melanosomes. Cells from 28 of 32 nevus cultures grew in an anchorage-independent way in soft agar with a colony-forming efficiency between 0.001 and 1%. Clones derived from single cells and soft agar-selected colonies showed marked phenotypic heterogeneity, but all had a limited life span and did not undergo transformation in culture. These cells were nontumorigenic in nude mice. Cultured nevus cells expressed antigens present on melanoma but absent on normal fibroblasts and/or melanocytes as tested with monoclonal anti-melanoma antibodies. The anti-melanoma antibodies bound equally well to dysplastic, congenital, and common acquired nevi. Antigens are released by nevus cells similar to melanoma cells.

Antigens, Neoplasm↗

Target blue nevus.

In two cases of target blue nevi of the foot, both lesions displayed a distinctive concentric pigmentary variation. This correlated histologically with a peripheral alteration of dermal collagen accompanied by a focal regression or differentiation of blue nevus cells. The resulting distinctive target blue nevus can be clinically differentiated from a malignant melanoma.

Adult↗

The relationship between plasma membrane lipid composition and physical-chemical properties. III. Detailed physical and biochemical analysis of fatty acid-substituted EL4 plasma membranes.

Murine leukemia EL4 cells were modified by supplementation of culture media with fatty acids for 24 h. A plasma membrane-enriched fraction was prepared from substituted and normal cells. Analyses were performed to determine fatty acyl composition, phospholipid headgroup composition and cholesterol content. The two major membrane phospholipids, phosphatidylethanolamine (PE) and phosphatidylcholine (PC) were isolated by thin-layer chromatography and ESR measurements were done on liposomes prepared from these lipids as well as on the intact plasma membrane preparations. Slight perturbations in overall plasma membrane lipid composition were observed when EL4 cells were supplemented with a single exogenous fatty acid. This may be consistent with the idea that the incorporation of exogenous fatty acid induces compensatory changes in membrane lipid composition. On the other hand, we observed no significant difference in two ESR motional parameters between the unsubstituted control and various fatty acid-substituted plasma membranes. ESR measurements carried out on PE and PC liposomes derived from 17:0- and 18:2c-substituted membranes also failed to detect major differences between these liposomes and those made from normal EL4 phospholipids. In the case of liposomes prepared from 18:2t,-substituted membranes, the order parameter was significantly changed from the normal. However, the change was in opposite directions in PE and PC, perhaps accounting for the fact that no change parameter is seen in intact 18:2t-substituted plasma membrane. Measurements of order parameter (S) in mixed lipid vesicles showed that at up to 50 mol% mixture of a synthetic PC with plasma membrane PC, the value of S was only marginally different from that of the plasma membrane PC vesicles. We interpret these data as an indication that the two ESR parameters used are not sufficiently sensitive to detect changes due to modifications of the acyl chain composition of a complex biological membrane.

Animals↗

Ecdysteroid induction of cell surface contacts in a Drosophila cell line.

Drosophila Kc cells are usually spherical in shape and are relatively free of cell-cell contacts. Soon after exposure to 20-hydroxyecdysone they develop extensions, assume a fibroblastic shape, and closely adhere to adjacent cells by means of cell-cell contacts to form large multicellular aggregates. This adhesive nature is enhanced with trypsin treatment without disruption of cell shape. Simultaneous addition of 20-hydroxyecdysone and juvenile hormone results in diminished aggregate formation without preventing the changes in cell shape. These factors point to the possibility that 20-hydroxyecdysone stimulates modifications in the cell surface that may be important during embryological differentiation. Key words Kc cells, aggregations, recognition, juvenile hormone.

Animals↗

Relationship between patients' early recognition of melanoma and depth of invasion.

The correlation between time to diagnosis and thickness of lesion in patients with superficial spreading melanoma was explored. Charts of 245 patients diagnosed since 1976 were reviewed for data on lesion duration and time since elevation (as perceived by patients); and the degree of elevation (if any); thickness, and diameter of lesion (as measured histologically). No correlation emerged between time to diagnosis and the biologic state of disease as reflected by thickness. The majority of melanomas in this series were not recognized by patients in an early, pre-elevation, low-risk phase. Whether an emphasis on identification of melanoma in this phase will lead to an increase in the percent of patients presenting with biologically early, curable disease remains to be tested.

Back↗

Pilar neurocristic hamartoma: its relationship to blue nevus and equine melanotic disease.

A unique pigmented lesion, judged to be a hamartoma of neural crest origin, occurring in a female patient, is compared with equine melanotic disease, The characteristic perifollicular arrangement of pigment-laden spindle cells is remarkably similar in both. Previously described patch- and plaque-like blue nevi in humans are also closely related. Light and ultrastructural features showed differentiation toward both nevus cells and Schwann cells, and it is proposed that the lesion be termed pilar neurocristic hamartoma.

Adolescent↗

Expression of DR antigens in freshly frozen human tumors.

DR antigens are thought to function as differentiation antigens and to restrict immune recognition between T cells and B cells, monocyte/macrophages, Langerhan's cells, and endothelial cells. These antigens are commonly found on tissue culture lines from metastatic melanomas and tumors of lymphocyte derivation but are notably uncommon on cell lines from other malignancies. Using frozen tissue sections, a monoclonal antibody (WI 691-13-17) known to detect an epitope common to all DR alloantigens on the beta (light) chain of DR antigens, and a two-step indirect immunoperoxidase technique, DR antigens were found on all metastatic lesions tested and on many primary tumors and their histogenetic precursors. The technique of using monoclonal antibodies in indirect immunoperoxidase staining of freshly frozen tissue allows individual cells to be assessed for antigen expression and presumably more accurately reflects in vivo antigen expression than results obtained from cells selected by tissue culture methods.

Antibodies, Monoclonal↗

Use of monoclonal antibodies in detection of melanoma-associated antigens in intact human tumors.

The use of antimelanoma monoclonal antibodies on tissue sections using a two-step indirect immunoperoxidase technique is reported. Antibodies 691-13-17 and 691-I5-Nu4B reacted with dysplastic nevus cells and all melanomas tested, but not with normal skin melanocytes, intradermal nevi, or lentigines. Antibody 691-13-17, directed against DR antigen, reacted also with Langerhan's cells, macrophages, and a subpopulation of lymphocytes. Antibody 691-I5-Nu4B reacted only with melanomas. The technique allows analysis of the expression of antigens by tumor cells in situ.

Adult↗

Malignant melanoma in renal-transplant recipients.

14 patients who developed cutaneous malignant melanoma (CMM) after renal transplantation were studied. Histological review of the primary melanomas revealed that all 10 evaluable patients had a precursor naevus from which the CMM arose, 7 of which were dysplastic, and that 13 of the 14 patients had an abnormal host response to the tumour, characterised by absence of the usual lymphocyte/ macrophage infiltrate. These observations suggest that CMM in renal-transplant recipients evolves from precursor naevi in immunosuppressed patients who are unable to mount an appropriate cellular immune response to neoplastic cells. The clinical detection of dysplastic naevi offers an opportunity to identify in advance those immunosuppressed patients who are prone to melanoma and to modify their medical management accordingly.

Adult↗

Topical chemotherapy of dysplastic melanocytic nevi with 5% fluorouracil.

A therapeutic response to topical fluorouracil in a patient with the large atypical nevus syndrome is presented. Six of the patients' dysplastic melanocytic nevi were treated with topical fluorouracil. Four common acquired melanocytic nevi from normal individuals were also treated. All six dysplastic nevi responded with inflammation, ulceration, and subsequent disappearance of the lesion, while the four control melanocytic nevi remained unchanged. Although we do not presently advocate the therapeutic use of fluorouracil for large atypical nevi until its safety and efficacy have been established, the response reported herein may herald an important advance in the therapy of these troublesome lesions that are known to be histogenetic precursors of malignant melanoma.

Administration, Topical↗

Dysplastic nevus syndrome: a phenotypic association of sporadic cutaneous melanoma.

Clinical photographs of 79 prospectively studied cases of non-familial cutaneous malignant melanoma were reviewed; special attention was directed to the distribution pattern of coexistent melanocytic lesions. A group of 15 patients had moles on the covered buttock area. Seven of these patients had large clinically atypical nevi, and biopsies of these nevi showed severe melanocytic dysplasia. Residual elements of melanocytic dysplasia were identified in five of the primary melanomas in this group of patients. It is suggested that these patients represent a distinctive syndrome, the Dysplastic Nevus Syndrome (DNS) and that they are at increased risk for development of primary cutaneous malignant melanoma. The clinically and histologically distinctive dysplastic nevi of these patients are identical to the precursor lesion for melanoma that we have previously described in a familial context, the B-K mole syndrome. This paper represents the first description of this form of dysplasia in non-familial melanoma.

Adult↗

Clinical characteristics of early cutaneous melanoma.

Clinical characteristics of the primary tumor in 786 patients with superficial spreading melanoma were studied in a prospective sequential series of patients from the Melanoma Clinical Cooperative Group. The most useful features for early diagnosis were change in size and change in color, present in 71% and 55% respectively of patients with level II lesions. Increase in height of lesion correlated with more advanced disease. Ulceration and bleeding were predominantly found in advanced primary lesions and are consequently of limited use in early recognition. Awareness of the historical and clinical features of the primary tumor should result in early recognition and cure of most primary superficial spreading melanomas.

Adult↗

Fine structure of the unistellate sperm of the shrimp, Sicyonia ingentis (Natantia).

Sperm of the prawn Sicyonia ingentis were studied cytochemically and ultrastructurally. Striking cytological differences were noted between these natantian sperm and previously studied reptantian sperm. In general, the S. ingentis sperm are composed of a spherical main body that is partially encompassed by a morphologically diverse cap region, from which extends a single appendage or spike. The main body houses an uncondensed, Feulgen-positive nuclear region that is partially surrounded by a cytoplasmic band. A single layer of small, 600 A, vesicles lines the periphery of the cytoplasmic band. Large membranous vesicles extend from the inner surface of the cytoplasmic band into the nuclear region. The nucleus is separated from the cap or acrosomal complex by a dense plate and a highly organized crystalline lattice, which is composed of geometric squares that are approximately 350 A in dimension. The cap region also contains convoluted membrane pouches; a central granular core; spherical bodies; an electron-dense, saucer-shaped plate; and a large anterior granule. The convoluted membrane pouches and anterior granule are periodic acid-Schiff (PAS) positive. The anterior granule also demonstrates RNAase-stable red fluorescence with acridine orange staining. A spiralled spike, approximately 6 micron long, extends from the anterior end of the cap. The cap and spike are bound by a double membrane, which results from the fusion of the plasma membrane and the convoluted pouch membrane. The sperm's acrosome is thought to be composed of the two PAS-positive cap components and the spike.

Acrosome↗

Association of actin with sperm centrioles: isolation of centriolar complexes and immunofluorescent localization of actin.

The centrioles of cnidarian sperm associate with striated specializations (pericentriolar processes) during spermiogenesis. Three functions have been proposed for the role of these structures: (a) an anchoring mechanism for the sperm flagellum, (b) a signal-transmitting mechanism for communication between sperm head and tal, and (c) a contractile mechanism involved in motor function of the sperm flagellum. To investigate these proposed functions, we developed a technique for the isolation and purification of Hydractinia sperm distal centriles with attached pericentriolar processes. SDS polyacrylamide electrophoretic profiles of whole sperm and pericentriolar process proteins revealed a prominent protein that comigrates with rabbit and penaeid shrimp muscle actin. To label and localize actin in hydroid spem, we produced in rabbits a highly specific antiserum to invertebrate actin that cross-reacts with both invertebrate and vertebrate muscle and nonmuscle actin. Immunofluorescent double antibody labeling of hydroid sperm with antiactin has demonstrated the presence of actin in the pericentriolar process region of the sperm. In earlier reports, it has been proposed that pericentriolar processes, if contractile, could alter the mid-piece asymmetry of hydroid sperm, facilitating the directional motility that these cells demonstrate in respone to egg-released chemoattractants. The present results support this hypothesis.

Actins↗