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Biomedical subjects

W H Clark

Publications and source records attributed to W H Clark.

At least 73 records · Page 4Linked to original sources
PubMed1988

Patient and physician delay in melanoma diagnosis.

The sequence of events leading ultimately to the diagnosis and treatment of malignant melanoma was investigated. We conducted interviews with 275 patients and the physicians whom they had consulted regarding their suspicious lesions before their eventual referral to a melanoma center. An average of 1 year elapsed from the time that patients first noticed a new or changed lesion and the date of diagnosis. Major components of delay were attributable to both patients and physicians. An average of 6 months elapsed between patients' recognition of a new or changed lesion and their realization that the lesion was suspicious. For 21% of cases, at least 2 months elapsed between physicians' observation of lesions and a definitive diagnosis of malignant melanoma, and 13% were diagnosed a minimum of 4 months following a visit to the physician. Patients routinely cannot distinguish between melanomas and moles. Physicians do not always diagnose melanoma accurately or act promptly in response to suspicious lesions. We have yet to take adequate advantage of the unique opportunity for early detection and cure in this readily visible, rapidly increasing malignancy.

Adult↗
PubMed1988

Growth and phenotypic characteristics of human nevus cells in culture.

Nevus cells were isolated from the three cutaneous components, epidermis, basal layer, and dermis, of nonmalignant pigmented lesions and were cultured separately in the presence or absence of the phorbol ester 12-0-tetradecanoyl phorbol-13-acetate in medium that supports the rapid proliferation of melanocytic cells. The separation procedure used provided cultures that were essentially free from normal melanocytes (dermis) or fibroblasts (epidermis). In short term culture, nevus cells of all skin compartments expressed markers associated with differentiated melanocytes, such as presence of premelanosomes and melanosomes and elevated tyrosinase levels. Nevus cells also expressed melanoma-associated antigens, such as NGF-receptor, transferrin-related p97, proteoglycan, and HLA-DR as detected with monoclonal antibodies. After several subpassages, cells showed a decreased expression of melanoma-associated antigens, decreased tyrrosinase levels, and melanosomes could no longer be detected. Morphologically, these cells were similar to fibroblasts. The disappearance of melanoma-associated cell surface antigens was concomitant with the appearance of a melanocyte-associated 145 kd protein that might serve as a marker of fibroblast-like differentiation in nevus cells and normal melanocytes. Nevus cell cultures grown in the presence of 12-0-tetradecanoyl phorbol-13-acetate maintained a stable differentiated phenotype throughout their lifespan. As reported earlier, nevus cells in culture, irrespective of the presence or absence of 12-0-tetradecanoyl phorbol-13-acetate, have a finite lifespan in vitro, grow anchorage-independent in soft agar, but do not form tumors when xenografted to nude mice. These studies demonstrate that nevus cells isolated from the epidermal, basal layer, and dermal components of lesional skin can serve as models to characterize the initial steps of tumor progression in a human cell system.

Adolescent↗
PubMed1987

Hereditary melanoma and the dysplastic nevus syndrome: the risk of cancers other than melanoma.

We analyzed the prospective occurrence of cancers other than malignant melanoma in fourteen kindreds with hereditary cutaneous malignant melanoma and the dysplastic nevus syndrome. No significant excess of nonmelanoma cancers was documented, suggesting that hereditary cutaneous malignant melanoma/dysplastic nevus syndrome is not pleiotropic for other tumor types.

Dysplastic Nevus Syndrome↗
PubMed1987

Management of cutaneous melanomas of the female breast.

Primary melanomas of the skin of the breast are uncommon lesions. Fifty-four patients were surgically treated for this lesion during a 13-year period, accounting for 3.8 percent of a total of 1431 patients with cutaneous melanoma. Nineteen patients were female and 35 were male. Most recently, in patients with high-risk lesions, such as those exhibiting an aggressive vertical growth phase or a Clark level IV or V, attempts at curative resection have utilized wide and deep excision to the level of the pectoralis fascia with axillary lymph node dissection in selected cases. Reconstruction of the significant breast deficit in five female patients utilized the latissimus dorsi myocutaneous flap. This technique results in an improved aesthetic appearance when compared to primary closure or skin grafting. Donor-site morbidity is minimal. Long-term cancer surveillance is not impeded, and all five patients expressed satisfaction with the reconstruction. Four of the five female patients are currently alive with no evidence of disease at a mean follow-up of 55 months after definitive therapy.

Adolescent↗
PubMed1987

Biology of tumor progression in human melanocytes.

Tumor progression in the human melanocyte system can be delineated into 6 sequential stages. The first three steps represent nonmalignant melanocyte lesions from focal proliferations of structurally normal melanocytes to lesions with architectural and cytologic atypia. Primary melanoma may be divided into radial growth phase without competence for metastasis and vertical growth phase with metastatic competence. Melanocytes isolated from normal skin, nonmalignant pigmented lesions, and melanomas and maintained in culture have properties that are characteristic for each stage of tumor progression. Cytogenetic studies revealed nonrandom chromosomal abnormalities of advanced melanomas involving chromosomes 1, 6, and 7. Recent progress in tissue culture techniques has allowed studies of growth regulation of normal and malignant cells. Six growth factor receptor-growth factor systems seem to be of biologic significance in the melanocyte system: EGF, NGF, FGF, PDGF, insulin, and beta-TGF. Monoclonal antibodies have characterized a large number of antigens on melanocytes of the various stages of tumor progression, making melanoma one of the most widely studied human tumor systems.

Antigens, Neoplasm↗
PubMed1986

GD2 ganglioside biosynthesis is a distinct biochemical event in human melanoma tumor progression.

Gangliosides from cell cultures established from melanocytic lesions, representing different stages of melanoma tumor progression, were analyzed by chemical and immunological means on thin-layer chromatograms. The GD2 ganglioside and N-acetylgalactosaminyl transferase, which catalyzes the biosynthesis of GD2 from its precursor GD3, were detected in cultures established from advanced primary and metastatic melanomas, but not in cultures of normal melanocytes. Immunohistochemical studies on tissue sections from all progression stages confirmed GD2 expression only in these advanced lesions. A distinct biochemical event thus coincides with the onset of faster growth and acquisition of metastatic competence in human melanoma tumor progression.

Autoradiography↗
PubMed1986

Karyotypic evolution in human malignant melanoma.

Chromosome studies were performed on direct preparations, early passage cultures, and cell lines derived from melanocytic lesions of 37 patients. There were six congenital or common acquired nevi, six dysplastic nevi, one early primary melanoma (radial growth phase), three complex melanomas (RGP with foci of vertical growth phase), six advanced primary melanomas (VGP), and 26 metastases. The karyotype was normal in the six common nevi. A chromosomally abnormal clone with a single karyotypic alteration was found in two dysplastic nevi. All melanomas had clones with multiple cytogenetic changes. Nonrandom abnormalities involving translocations or deletions in the short arm of chromosome #1, either arm of chromosome #6, and/or extra copies of the short arm of chromosome #7 were present in all melanomas. These were not obviously associated with a particular stage of disease, except that the only nonrandom alteration in the early (RGP) melanoma involved chromosome #6. In four cases, cytogenetic data were available on both a primary melanoma and its metastases. In each instance there were common alterations (demonstrating the clonality of the disease), as well as additional changes in the metastases. Our findings indicate that demonstrable somatic genetic abnormalities increase in severity with clinical progression of melanocytic disease, but additional data are required to establish the significance of specific karyotypic changes (and the involved genes) in the clinical evolution of these disorders.

Chromosome Aberrations↗
PubMed1986

Induction of the acrosomal reaction in sperm from the white sturgeon, Acipenser transmontanus.

Sperm from the white sturgeon, Acipenser transmontanus possess an acrosome while the eggs possess numerous micropyles. The sperm undergo an acrosome reaction that includes exocytosis and process formation. This acrosomal reaction can be induced in freshwater with ionophore A23187, high pH, high Ca++, or egg water. In addition, this event is dependent on extracellular Ca++ and Mg++. Upon immersion of eggs in freshwater, a water-soluble jelly layer hydrates and forms a highly adhesive coating surrounding the eggs. Jelly release and hydration appears dependent on both a trypsin-like protease and Ca++ and Mg++ ions. Isolated egg jelly (110,000 dalton glycoprotein) does not possess acrosome reaction inducing activity. The acrosome reaction inducing activity in egg water resides in a water-soluble 66,000 dalton glycoprotein. Egg water appears species specific in its ability to elicit a response. Prior to freshwater exposure, the egg envelope possesses a water-insoluble glycoprotein with a molecular weight of 70,000 daltons. When isolated from polyacrylamide gels, the 70,000 dalton component induces acrosome reactions in a species specific manner. Following freshwater exposure, the egg envelope possesses the water-soluble 66,000 dalton glycoprotein in addition to the 70,000 dalton component. The 70,000-66,000 dalton conversion can be blocked by incubating eggs in freshwater containing inhibitors of trypsin-like proteases. Both the 66,000 dalton and 70,000 dalton glycoproteins originate and reside in layer three of the egg envelope.

Acrosome↗
PubMed1986

How well do physicians recognize melanoma and other problem lesions?

The alarming increase in the incidence of cutaneous malignant melanoma in the United States emphasizes the importance of its early detection and treatment. Early detection requires accurate clinical recognition of both malignant and precancerous skin lesions (dysplastic nevi). This study presents data on dermatologists' and nondermatologists' ability to diagnose skin lesions. A total of 105 nondermatologist physicians, from first-year residents to practicing physicians, and forty-eight dermatologists were asked to identify color slides or photographs of eleven cutaneous lesions, including malignant melanomas, dysplastic nevi, and innocuous lesions such as seborrheic keratoses and common moles. Diagnosis of cutaneous lesions was generally inaccurate among nondermatologists. Only 38% correctly identified four or more of the six melanomas as melanoma of any type, and 58% were unable to diagnose dysplastic nevi. Only 17% categorized their relevant training as excellent or good. Improved training in the diagnosis of skin lesions for practicing physicians and house staff is required if mortality from malignant melanoma is to be decreased in the United States.

Adult↗
PubMed1986

Human cutaneous nevi transplanted onto nude mice: a model for the study of the lesional steps in tumor progression.

Normal human cutaneous nevi were transplanted to the skin of nude mice and some of the grafts were treated topically with 7,12-dimethylbenz[a]anthracene (DMBA, 1.6 mumol weekly). Histologically proven human skin was present in 22 grafts. In the 9 untreated control grafts, the tendency of nevic cells to form nests and the number of nevomelanocytes decreased with time; the melanocytic cells showed no signs of hypertrophy or atypia. In most of the 14 specimens treated with DMBA, the nevomelanocytes showed distinct signs of hypertrophy. The cells were enlarged and often dendritic and were filled with melanin granules for which the transfer to keratinocytes appeared to be blocked. The nevomelanocytes of 4 of the 9 specimens treated with DMBA for greater than or equal to 82 days (9-16 DMBA applications), showed atypical enlarged nuclei with mitotic figures. Since atypia is one criterion for identifying precursors of transformed cells, the model of human nevi grafted onto nude mouse skin may be useful for studying the various steps involved in the progression of benign melanocytic nevi to malignant melanoma.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

A t(1;19) chromosome translocation in three cases of human malignant melanoma.

Abnormalities of chromosome 1, including trisomy for all or a portion of the long arm, have been frequently reported in many cancers. Anomalies of chromosome 19 are far less common, although a t(1;19)(q23;p13) translocation has been reported in association with pre-B-cell leukemia. We have observed a t(1;19)(q12;p13) translocation in three cases of advanced melanoma, with the translocation chromosome representing an extra dose of 1q in each instance. The breakpoint on 1q was within the centromeric heterochromatin, proximal to the site in pre-B-cell leukemia, but the breakpoint on 19p appeared identical. The gene for human insulin receptor has recently been mapped to this region of chromosome 19 (p13.2-13.3). This gene shares structural and sequence homologies with the epidermal growth factor receptor (erb-B oncogene) and members of the src family of oncogenes, suggesting that alterations in the insulin receptor, resulting from chromosomal translocation, could lead to a role in tumorigenesis. The present findings may permit this possibility to be examined in a neoplasm of neuroectodermal origin.

Chromosome Banding↗
PubMed1986

Assessment of survival rates with metastatic malignant melanomas.

Ten patients who survived for at least five years after the development of metastatic melanoma were compared with 45 other patients who died of disseminated disease. The difference between the groups was the persistent absence of internal organ involvement in the first group and its invariable presence in the latter group. In addition, it appeared that several of the primary tumors from the nonlethal group were thinner, located in a more favorable location and occurred with greater frequency in women. All of these features tend to be indicative of a lesser degree of biologic aggressiveness of these tumors. They may prove helpful in identifying those patients with metastatic disease who are potential long term survivors and, therefore, require continued aggressive treatment.

Adult↗
PubMed1985

The role of lymph node dissection for clinical stage I malignant melanoma of intermediate thickness (1.51-3.99 mm).

The survival times of patients who had an elective regional lymph node dissection was compared with that of those who did not undergo the procedure in a database of 72 patients with clinical Stage I melanoma of intermediate thickness (1.51-3.99 mm). All of the patients had been followed for 5 years or longer or until death. No significant differences were found in other reported prognostic factors, suggesting that the two groups were comparable. By multivariate analysis, a low mitotic rate, intermediate patient age, and the presence of an infiltrative lymphocytic response were found to be associated with favorable survival. There did not appear to be any association of elective regional lymph node dissection with survival; and it was concluded that such therapy should not be regarded as "standard" for clinical Stage I melanoma of intermediate thickness.

Actuarial Analysis↗