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W H Clark

Publications and source records attributed to W H Clark.

At least 91 records · Page 5Linked to original sources
PubMed1985

An egg envelope component induces the acrosome reaction in sturgeon sperm.

The acrosome reaction in Acipenser transmontanus sperm can be induced by a 66,000 dalton glycoprotein that is present in Layer 3 (L3) of the egg envelope and in egg water only following exposure of the eggs to fresh water. When egg water is fractionated on Sepharose CL 6B, the 66,000 dalton glycoprotein-containing fractions possess acrosome reaction inducing activity. Egg water may be species-specific in its ability to elicit the acrosome reaction, as demonstrated by the fact that it has no effect on the sperm of Acipenser fulvescens. Egg jelly possesses no acrosome reaction, inducing activity. The major carbohydrate-containing component of the egg envelope is L3, a layer that contains galactose residues. L3 possesses a 70,000 dalton glycoprotein prior to freshwater exposure and lacks the 66,000 dalton component. If isolated from polyacrylamide gels, the 70,000 dalton glycoprotein elicits acrosome reactions in what appears to be a species specific manner. After freshwater exposure, L3 contains both the 70,000 dalton glycoprotein and the 66,000 dalton glycoprotein that is also present in egg water. The appearance of the 66,000 dalton inducer can be blocked by the incubation of eggs in fresh water containing inhibitors of trypsin activity. Thus, the soluble inducer in egg water may be proteolytically derived from a higher molecular weight complex in the egg envelope.

Acrosome↗
PubMed1985

Monoclonal antibody to a highly glycosylated protein reacts in fixed tissue with melanoma and other tumors.

A highly glycosylated protein with a molecular weight of 30,000 to 60,000 and a protein core of 20,000 daltons has been identified by antimelanoma monoclonal antibodies. The antigenicity of this melanoma-associated glycoprotein (MAG) was not destroyed in fixed paraffin-embedded melanoma tissue, and was present in malignant cells of cutaneous superficial spreading melanomas in skin (31/33) and in half of all metastatic melanomas examined (5/10). The antigen was not expressed by normal melanocytes. The strong reactivity of dysplastic nevi with the anti-MAG antibodies was comparable to that seen in radial growth phase melanoma. Antigen expression was much weaker in compound nevi where reactivity ranged from moderate in the junctional component and the upper dermis to absent at the base of the nevus.

Antibodies, Monoclonal↗
PubMed1985

Cutaneous malignant melanoma after Hodgkin's disease.

Eight cutaneous malignant melanomas occurred in 6 of 1405 patients with Hodgkin's disease, although the expected incidence rate was 0.77 (relative risk, 8; 95% confidence interval, 3 to 17). One melanoma was a thin, level II lesion less than 0.76 mm thick; the rest were mostly bulky, deeply invasive lesions despite close clinical surveillance. The melanomas spread aggressively; 3 of 6 patients died within 1 to 3 years. Two of the six patients developed a second primary malignant melanoma 1 year after the first. Two of six patients had biopsy-proven dysplastic nevus syndrome, a known precursor to cutaneous malignant melanoma, and an additional 3 patients had clinical evidence of dysplastic nevus syndrome. Histologically, the malignant melanomas showed a sparse inflammatory infiltrate, an abnormal host response seen previously in cutaneous melanomas developing in immunosuppressed patients. Dysplastic nevi may identify patients at highest risk who require modified medical management.

Adult↗
PubMed1985

High risk of malignant melanoma in melanoma-prone families with dysplastic nevi.

The risk of hereditary cutaneous malignant melanoma was evaluated in 401 members of 14 families with an autosomal dominant form of melanoma. We documented 127 primary melanomas in 69 family members, including 39 new melanomas diagnosed in 22 study participants from the time of first examination through a maximum of 8 years of follow-up. The 39 newly diagnosed melanomas occurred only in family members with dysplastic nevi, a known precursor of familial melanoma. Of 77 patients with dysplastic nevus syndrome without prior melanomas, 4 developed their first melanoma during prospective follow-up, as compared with 0.03 cases expected. The prospective age-adjusted incidence for melanoma was 14.3/1000 patients with dysplastic nevus per year, with a cumulative melanoma risk (+/- SE) of 7.2% (+/- 3.6) at 8 years. The actuarial probability of melanoma developing in family members with dysplastic nevi was 56.0% (+/- 10.1) from age 20 to age 59. This study confirms that dysplastic nevi are clinical markers of high risk for, and precursors of, hereditary melanoma.

Adolescent↗
PubMed1985

Characteristics of cultured human melanocytes isolated from different stages of tumor progression.

Normal melanocytes and melanocytes of normal nevi, primary melanoma in the radial (RGP) and vertical (VGP) growth phases, and metastatic melanoma exhibited and maintained phenotypic differences when grown in tissue culture or in experimental animals. Only metastatic and VGP primary melanoma cells were tumorigenic in athymic nude mice and had nonrandom chromosomal abnormalities involving chromosomes 1, 6, and 7. The colony-forming efficiency in soft agar was also highest in these two cell types. A cell line of RGP primary melanoma had characteristics of both benign and malignant cells: nevus-like morphology; nontumorigenicity in nude mice; but karyotypic abnormality of chromosome 6. It also had a ganglioside pattern similar to that of normal melanocytes but not melanomas, i.e., a high GM3 ganglioside content compared to the amounts of GM2, GD2, and GD3 gangliosides. Binding of monoclonal antibodies secreted by hybridomas generated by immunization of mice with VGP primary and metastatic melanoma was highest with cells and supernatants of cultures from advanced melanoma and least with nevus cells. There was no binding to normal melanocytes except with the monoclonal antibodies specific for nerve growth factor receptor or 9-O-acetyl-GD3 ganglioside. On the other hand, monoclonal anti-nevus antibodies bound to melanocytes, nevus cells, and RGP primary melanoma cells but not to VGP primary or metastatic melanoma cells. Cultured human melanocytic cells appear to be a unique model for the study of tumor progression.

Antibodies, Monoclonal↗
PubMed1984

Lack of association between intraocular melanoma and cutaneous dysplastic nevi.

The occurrence of uveal and cutaneous malignant melanoma and the dysplastic nevus syndrome in the same individual suggests an etiologic relationship among these diseases. Thus, the dysplastic nevus syndrome could be viewed as marking an increased risk of both cutaneous and ocular melanoma. We postulated that if such a relationship exists, patients with both forms of melanoma should have a high prevalence of dysplastic nevi. We examined 44 patients (31 women and 13 men ranging in age from 20 to 80 years) with uveal melanoma for evidence of cutaneous melanoma and dysplastic nevi. We also examined photographs of 46 patients (24 men and 22 women ranging in age from 19 to 67 years) with nonfamilial cutaneous melanoma to determine the prevalence of dysplastic nevi. We found a 4.5% prevalence of dysplastic nevi in patients with uveal melanoma, significantly lower than the 41% prevalence in patients with cutaneous melanoma (two of 44 patients vs 19 of 46 patients). This study indicates that uveal and cutaneous melanoma are not etiologically linked through dysplastic nevi and suggests that patients with uveal melanoma are no more likely to have cutaneous dysplastic nevi than the general population.

Adult↗
PubMed1984

Preoperative nuclear scans in patients with melanoma.

One hundred forty-one liver scans, 137 brain scans, and 112 bone scans were performed in 192 patients with clinical Stage 1 melanoma. One liver scan was interpreted as abnormal; liver biopsy of that patient showed no metastasis. There were 11 suggestive liver scans; three of the patients with suggestive liver scans had negative liver biopsies. The remaining eight patients were followed from 4 to 6 years and none of those patients developed clinical evidence of hepatic metastases. All of the brain scans were normal. Five patients had suggestive bone scans and none of those patients had manifested symptoms of osseous metastases with a follow-up of 2 to 4.5 years. This study demonstrates that the use of preoperative liver, brain and bone scan in the evaluation of patients with clinical Stage 1 melanoma is virtually unproductive.

Adolescent↗
PubMed1984

Cytogenetics of human malignant melanoma and premalignant lesions.

Chromosome studies were done on direct preparations, early passage cultures, and/or cell lines derived from melanocytic lesions of 17 patients. There were 5 nevi (3 dysplastic); 1 early primary melanoma (radial growth phase); 1 advanced primary melanoma (vertical growth phase) with multiple metastases; and 10 metastatic lesions. The 5 nevi had normal karyotypes, while each of the tumors had a predominantly abnormal karyotype. The early melanoma was pseudodiploid, including a 6p;22 translocation. Ten of the 11 advanced melanomas had one or more aberrations involving chromosome #1, with 9 having deletions or translocations of lp that involved the proximal segment 1p12----1p22 9 times in 8 lesions. Six advanced tumors had additional material involving 7q, including extra #7s (4 cases) and 7q+ (2 cases). Nine melanomas, including the early tumor, had alterations in chromosome #6. Three had additional copies of 6p (as iso6p or t6p); the others showed no consistent pattern. In one advanced tumor, the primary lesion and 5 metastases (removed seriatim over an 18-month period) had nearly identical karyotypes, indicating the clonal nature of the neoplasm. The nonrandom cytogenetic changes suggest that genes important in melanoma carcinogenesis are located on the proximal portion of 1p, on 7q, and on chromosome #6. More data on early lesions are needed to identify the relation of these various cytogenetic changes to the different stages of malignant melanoma development.

Cell Line↗
PubMed1984

A study of tumor progression: the precursor lesions of superficial spreading and nodular melanoma.

Six evident lesional steps of tumor progression form the neoplastic system that affects the human epidermal melanocyte: 1) the common acquired melanocytic nevus; 2) a melanocytic nevus with lentiginous melanocytic hyperplasia, i.e., aberrant differentiation; 3) a melanocytic nevus with aberrant differentiation and melanocytic nuclear atypia, i.e., melanocytic dysplasia; 4) the radial growth phase of primary melanoma; 5) the vertical growth phase of primary melanoma; and 6) metastatic melanoma. The common acquired melanocytic nevus is viewed as a focal proliferation of melanocytes, destined in most instances to follow a programmed pathway of differentiation that leads to disappearance of the nevus. If the pathway of differentiation is not followed, characteristic lesions result, and such lesions are regarded as the formal histogenetic precursors of melanoma. Such a developmental flaw is termed aberrant differentiation, and the resultant precursor lesion is designated melanocytic dysplasia. The vast majority of melanocytic nevi showing melanocytic dysplasia are terminal lesions that do not progress to melanoma. If melanoma is to develop via a precursor lesion, however, the nevus with melanocytic dysplasia is that precursor. When melanomas do develop, they develop focally within the precursor. The resultant primary melanoma itself does not follow a pathway of inexorable expansion of a population of melanoma cells in space and time. Rather, primary melanomas, with the exception of nodular melanoma, also evolve in a stepwise fashion. The first step, termed the radial growth phase, is characterized by the net enlargement of the tumor at its periphery, along the radii of an imperfect circle. Tumors in this stage of development show a characteristic pattern of growth within the epidermis and a distinctive form of invasion of the papillary dermis. Such melanomas are not associated with metastasis, and it is hypothesized that such tumors do not have competence for metastasis. For a melanoma to acquire competence for metastasis it must progress to the next step of tumor progression--the vertical growth phase. This lesional step is characterized by the appearance of a new population of cells within the melanoma, not an expansion of the cells forming the pre-existing radial growth phase. The net growth of the cells of the vertical growth phase is perpendicular to the directional growth of the radial growth phase. As a rule, the cells of the vertical growth phase grow in an expansile fashion, expansile as a balloon expands: a growth form characteristic of metastases.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1984

Invasive malignant melanomas lacking competence for metastasis.

Two stages of progression have been described in malignant melanomas, namely, the so-called "radial" and "vertical" phases of growth. We sought the presence or absence of vertical growth in 211 invasive cutaneous malignant melanomas. Disease-free survival in 146 patients with vertical growth was 63.7%, whereas 100% of 65 patients whose neoplasms lacked this feature survived 5 years or more after ablation of their lesions without evidence of recurrence or metastasis. Microstaging of patients with malignant melanoma by traditional means (level of invasion and thickness) identifies groups of patients at low and high risk of metastasis. Our data suggest that the absence of vertical progression of growth identifies a group of patients whose risk of metastasis is close to zero.

Humans↗
PubMed1983

The familial occurrence of cutaneous melanoma, intraocular melanoma, and the dysplastic nevus syndrome.

The occurrence of cutaneous melanoma and intraocular melanoma as double primary cancers in the same patient and in different members of the same family has suggested that these two forms of melanoma are etiologically related. It is theoretically possible that the link between these two pigment cell malignancies may be the dysplastic nevus syndrome, and patients with the dysplastic nevus syndrome may have an increased risk of intraocular melanoma and cutaneous melanoma. We studied two new kindreds in which cutaneous melanoma, intraocular melanoma, and the dysplastic nevus syndrome occurred and conducted neuro-ophthalmologic examinations of 26 patients with hereditary cutaneous melanoma or the dysplastic nevus syndrome, or both. In the one family studied in detail, the cutaneous melanoma predisposition came from the paternal bloodline, whereas the intraocular melanoma occurred in the maternal bloodline. The ophthalmologic examinations disclosed neither intraocular melanoma nor suspicious or atypical choroidal nevi. Our limited data suggested that the association of intraocular melanoma with cutaneous melanoma and dysplastic nevus syndrome may be coincidental.

Adult↗
PubMed1983

Dysplastic nevi on the scalp of prepubertal children from melanoma-prone families.

Four prepubertal children, all members of melanoma-prone families, developed pigmented scalp lesions that were diagnosed as dysplastic nevi. In three cases, the scalp lesions were the only evidence that the children were affected by the dysplastic nevus syndrome, a distinctive clinicopathologic entity that identifies persons at increased risk of malignant melanoma. In general, the skin of family members with dysplastic nevus syndrome does not show characteristic lesions until just prior to or with the onset of puberty. The presence of dysplastic nevi on the scalp may permit identification of at least some high-risk family members well prior to puberty. This should facilitate the early implementation of a melanoma prevention program for susceptible individuals and help ensure that melanomas are diagnosed early in their natural history, at a time when they are surgically curable.

Child↗
PubMed1983

Familial cutaneous malignant melanoma: autosomal dominant trait possibly linked to the Rh locus.

Segregation and linkage analyses were undertaken in families with multiple cases of cutaneous malignant melanoma (CMM) and a recently-described melanoma precursor, the dysplastic nevus syndrome (DNS). Clinical and laboratory data, including 23 genetic markers, were collected on 401 members of 14 high-risk kindreds. Pedigree analysis was compatible with an autosomal dominant mode of inheritance for the familial CMM trait. Although a similar model probably applies to the DNS trait as well, segregation analysis could not confirm the presence of a major locus. However, linkage analysis suggested that an autosomal dominant model was appropriate for the DNS, and that a DNS/CMM susceptibility gene may be located on the short arm of chromosome 1, within 30 map units of the Rh locus [maximum logarithm of odds (lod) score = 2.00].

Chromosomes, Human↗
PubMed1983

Optimal resection margin for cutaneous malignant melanoma.

Cutaneous malignant melanoma has traditionally been treated by "wide" local excision with a 5-cm margin of normal skin about the tumor. The rationale of wide excision for melanoma has never been clearly defined, but the procedure is known to be effective in preventing local recurrence. We studied 105 patients who had 109 primary melanomas in 1977 and related margin width of the definitive excision to the presence of satellites, to the subsequent development of local recurrence and in-transit metastases, and to survival. Survival was not dependent on margin width, and there were no incidences of local recurrence. Satellitosis and in-transit cutaneous metastasis indicate that a melanoma is capable of local recurrence; these phenomena occurred only in tumors whose thickness (Breslow) was greater than 2.0 mm. These data provide a rationale for wide excision of "thick" melanomas and support more modest local therapy for thin cutaneous melanoma.

Adult↗
PubMed1983

Production and characterization of monoclonal antibodies against human malignant melanoma.

The specific immunoreactivities of 31 monoclonal antibodies against human malignant melanoma were analyzed on a variety of malignant and nonmalignant human cells. Seven distinct groups were defined based on reactivity in radioimmunoassay and in mixed hemadsorption assay. The Group A antibody bound to 33% of short- and long-term cultured melanomas; Group B antibodies reacted with the majority of melanomas, astrocytomas, neuroblastomas, and fetal polygonal cells; and Group C antibodies bound to melanomas, teratocarcinomas, and to melanocytes grown in the presence of tumor-promoting phorbol esters. Antibodies of Groups D-G showed a less restricted binding pattern. In all groups, antibodies of IgG2b and IgM isotypes mediated complement-dependent lysis (CDC) and antibodies of IgG1, IgG2a, and IgG2b isotypes mediated antibody-dependent cell-mediated cytotoxicity (ADCC). Biochemical analysis indicated that 16 different proteins with molecular weights ranging between 28,000 and 500,000 were detected by the monoclonal antimelanoma antibodies.

Antibodies, Monoclonal↗