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Biomedical subjects

W H Clark

Publications and source records attributed to W H Clark.

At least 55 records · Page 3Linked to original sources
PubMed1991

Tumour progression and the nature of cancer.

The nature of neoplasia and its sometime end result, cancer, has been studied by exposition and explanation of the sequential lesions of tumour progression. Neoplastic lesions were divided into four classes on the basis of growth characteristics and whether lesional growth is confined to one or more tissue compartments. Class IA, the initial lesion, an orderly, probably clonal growth, usually differentiates and disappears. Class IB: Failure to differentiate accompanied by disorderly growth. Class IC: Randomly dispersed atypical cells, constituting a precursor state. Class II, intermediate lesions, apparently arising from the atypical cells, show temporally unrestricted growth within the tissue compartment of origin. Class III lesions, primary invasive cancers, show temporally unrestricted growth in two or more tissue compartments and metastasise along different paths, a property associated with extracellular matrix interaction. The metastatic pathways may result from different subsets of cells in the primary cancer. Class IV lesions are the metastases. It was concluded that, all neoplasms develop in the same way, have the same general behavioural characteristics, and, when malignant, all interact with the extracellular matrix of the primary and the secondary sites. The origins and development of cancer are considered to be pluralistic and not due to a discrete change in a cell, whose progeny, as a result of that discrete change, carries all of the information required to explain the almost limitless events of a neoplastic system.

Cell Division↗
PubMed1991

Dysplastic nevi as risk markers of sporadic (nonfamilial) melanoma. A case-control study.

The melanoma risk associated with dysplastic nevi outside the context of familial melanoma was studied by the case-control method. One hundred five newly diagnosed incident melanoma cases with negative family histories for familial melanoma and 181 controls (frequency matched for race, age, and sex) were studied by personal interview and cutaneous examination. The prevalence of dysplastic nevi was 41 (39%) of 105 in the cases and 13 (7%) of 181 in the controls. The odds ratio for dysplastic nevi by multiple logistic regression analysis simultaneously correcting for age, sex, eye color, hair color, actinic damage, freckles, and total number of nondysplastic nevi was 6.8 (95% confidence interval, 2.7, 16.9). This study supports the significance of dysplastic nevi as markers of increased risk for nonfamilial melanoma.

Case-Control Studies↗
PubMed1990

Development of cortical vesicles in Sicyonia ingentis ova: their heterogeneity and role in elaboration of the hatching envelope.

In the marine shrimp Sicyonia ingentis, ova lack cortical vesicles at spawning. Previous ultrastructural studies suggested that two different populations of cortical vesicles (dense vesicles and the ring vesicles) appear within 30 min post-spawning. These vesicles undergo sequential exocytosis (exocytosis of the dense vesicles followed by exocytosis of the ring vesicles) that leads to the formation of a hatching envelope around the ovum (see Pillai and Clark: Tissue & Cell 20:941-52, 1988). In the present study, lectins were used as molecular probes to study the development of cortical vesicles subsequent to spawning and the role of these vesicles in formation and elaboration of the hatching envelope. Isolated envelopes were screened with 11 different lectins to determine what group(s) were specific to the envelope glycoconjugates; Concanavalin A (Con A), Griffonia simplicifolia (GS II), Lens culinaris (LCA), and wheat germ agglutinin (WGA) bound to the envelopes. FITC-lectin studies of sectioned ova (fixed at various time points after spawning) utilizing WGA and LCA showed different labelling patterns. Data obtained at the light microscopical level indicated that WGA was specific to the dense vesicles and the outer portion of the envelope, while LCA exhibited specificity for the ring vesicles and the inner portion of the envelope. At the ultrastructural level, gold-LCA labelling was seen associated with the cisternal elements (containing ring-shaped structures), ring vesicles, and the inner layer of the fully formed envelope. These data demonstrated that 1) the ring vesicles are formed by fusion of cisternal elements containing ring-shaped structures; 2) the two species of cortical vesicles are chemically heterogeneous; and 3) the components of each type of vesicle contribute to different integral parts (the outer and inner layers) of the hatching envelope.

Animals↗
PubMed1990

Screening and surveillance of patients at high risk for malignant melanoma result in detection of earlier disease.

Screening, surveillance, and educational programs have been recommended for members of hereditary melanoma kindreds with dysplastic nevi, who are at very high risk for melanoma. For melanomas detected in a surveillance program offered to 555 such persons, the average thickness was 0.52 mm for 28 surveillance incident melanomas, 0.55 mm for 64 nonsurveillance incident melanomas, and 1.44 mm for 48 index lesions (p less than 0.001). The proportion of cases with level I or II invasion was 60.8%, 58.3%, and 36.2% respectively (p = 0.002). The nonsurveillance incident melanomas were diagnosed before entry into the surveillance program, but these patients were presumably aware of the earlier occurrence of two index melanomas in their families. These findings are consistent with a favorable effect of surveillance and education in a high-risk population and suggest that patient factors as well as physician factors may contribute to early diagnosis.

Dysplastic Nevus Syndrome↗
PubMed1990

Minimal deviation melanoma (halo nevus variant).

Twenty-eight cases of minimal deviation melanoma (MDM) in the histologic setting of halo nevus formed the basis for this study. Requisites for this study included at least one of the following: a remnant of a halo nevus in a MDM; remnants of both MDM and halo nevus in a common melanoma; and a MDM of Spitz or dermal type, or MDM arising in premalignant dysplasia in which the vertical growth components manifested distinctive cytologic features and cytophilia for lymphocytes. Many of the lesions apparently represented neoplastic progressions involving a population of cells at the dermal-epidermal interface (accretive growth). Some of the lesions qualified as dermal variants and apparently represented neoplastic progressions in a dermal component (interstitial growth). Most examples of MDM in this study were borderline in size (less than 1.00 mm in vertical dimensions). The borderline MDM were interpreted as brief (and in some cases perhaps ephemeral) neoplastic interludes. For the 12 cases with follow-up, there have been no metastases or local recurrences.

Adolescent↗
PubMed1990

Malignant melanoma simulants arising in congenital melanocytic nevi do not show experimental evidence for a malignant phenotype.

Proliferative neoplasms that resemble malignant melanoma may develop in large congenital melanocytic nevi, prenatally or in the neonatal period, although these lesions rarely show the progressive growth or behavioral characteristics of melanoma. This report describes the genetic, biologic, and immunologic characteristics of six tissue culture cell lines derived from two neoplasms present in congenital melanocytic nevi in two newborn infants. Both neoplasms had clinical and histologic features of malignant melanoma. Despite these features, cells from all lines were phenotypically benign, as evidenced by a normal karyotype, their expression pattern of pigment cell-associated antigens, absence of melanoma-associated ganglioside GD2, their mitogenic response to the tumor-promoting phorbol ester 12-0-tetradecanoyl phorbol-13-myristate, their inability to grow anchorage independently in soft agar, and prolonged but finite life span. The cells did not produce tumors in nude mice, but they remained viable at the injection site for over 7 months.

Antibodies, Monoclonal↗
PubMed1989

Model predicting survival in stage I melanoma based on tumor progression.

We used the lesional steps in tumor progression and multivariable logistic regression to develop a prognostic model for primary, clinical stage I cutaneous melanoma. This model is 89% accurate in predicting survival. Using histologic criteria, we assigned melanomas to tumor progression steps by ascertaining their particular growth phase. These phases were the in situ and invasive radial growth phase and the vertical growth phase (the focal formation of a dermal tumor nodule or dermal tumor plaque within the radial growth phase or such dermal growth without an evident radial growth phase). After a minimum follow-up of 100.6 months and a median follow-up of 150.2 months, 122 invasive radial-growth-phase tumors were found to be without metastases. Eight-year survival among the 264 patients whose tumors had entered the vertical growth phase was 71.2%. Survival prediction in these patients was enhanced by the use of a multivariable logistic regression model. Twenty-three attributes were tested for entry into this model. Six had independently predictive prognostic information: (a) mitotic rate per square millimeter, (b) tumor-infiltrating lymphocytes, (c) tumor thickness, (d) anatomic site of primary melanoma, (e) sex of the patient, and (f) histologic regression. When mitotic rate per square millimeter, tumor-infiltrating lymphocytes, primary site, sex, and histologic regression are added to a logistic regression model containing tumor thickness alone, they are independent predictors of 8-year survival (P less than .0005).

Female↗
PubMed1989

Antigenic profile of tumor progression stages in human melanocytic nevi and melanomas.

Sixteen monoclonal antibodies that were obtained after immunization of BALB/c mice with intact melanoma cells or extracts of melanoma cells were tested for reactivity with normal and malignant melanocytic cells in situ, using an immunoperoxidase technique on frozen tissue sections. Sections representing six histopathologically defined stages of tumor progression, ranging from normal melanocytes to highly malignant metastatic lesions, were used. Thirteen monoclonal antibodies (MAbs) did not stain normal melanocytes in situ, whereas three MAbs weakly stained between 1 and 12.5% of melanocytes in 6-22% of the skin sections examined. MAb B 73.1, which was produced by immunization of mice with human natural killer cells and which binds to the Fc receptor of natural killer cells and granulocytes, reacted exclusively with malignant cells that represent the last two stages of tumor progression, vertical growth phase (VGP) primary melanoma and metastatic melanoma. All other antibodies showed variable reactivity with benign proliferative lesions or radial growth phase (RGP), an early stage of primary melanoma. Staining by MAbs that were reactive with gangliosides, unknown antigens, receptors, and two proteins (120/94 kDa protein and 250 kDa glycoprotein) showed a gradual increase in subsequent stages of tumor progression. Two steps in tumor progression were characterized by significant quantitative changes in the expression of antigens detected by the MAbs used in this study. First, mature nevus cells showed significantly higher reactivity with a panel of six MAbs, when compared to normal melanocytes. Second, a separate panel of six MAbs discriminated between RGP and VGP primary melanoma cells. No significant differences in antigen expression were found between dysplastic nevus cells and RGP melanoma, except that some antigens (nerve growth factor receptor and GD2/GD3 gangliosides) appear to be expressed at lower levels in RGP lesions, nor did VGP primary and metastatic melanomas show significant differences in antigen expression. These results suggest that (a) tumor progression of melanocytic cells in vivo is accompanied by significant quantitative differences in the expression of antigens, (b) some of the antigens examined here are associated with biologically aggressive malignant lesions but not normal or premalignant melanocytic cells, and (c) RGP primary melanoma cells are antigenically more similar to nevus cells than to VGP primary melanoma cells.

Antibodies, Monoclonal↗
PubMed1989

Mapping the gene for hereditary cutaneous malignant melanoma-dysplastic nevus to chromosome 1p.

We used molecular genetic techniques and multipoint linkage analyses to locate the gene responsible for cutaneous malignant melanoma-dysplastic nevus. We evaluated 99 relatives and 26 spouses in six families with a predisposition to melanoma. Thirty-four family members had cutaneous malignant melanoma, and 31 of these 34 also had histologically confirmed dysplastic nevi. Twenty-four family members had dysplastic nevi alone. An analysis of the cosegregation of the cutaneous malignant melanoma-dysplastic nevus trait with 26 polymorphic DNA markers on the short arm of chromosome 1 demonstrated the presence of a gene for susceptibility to melanoma. The gene was located between an anonymous DNA marker (D1S47) and the gene locus for pronatrodilatin, a commonly used reference gene (PND), in chromosome band 1p36. The odds were greater than 260,000:1 in favor of linkage at this location.

Adolescent↗
PubMed1989

Inhibition of metastases of a human melanoma xenograft by monoclonal antibody to the GD2/GD3 gangliosides.

A human melanoma variant cell line was obtained from a lung metastasis that arose spontaneously after we inoculated melanoma cells sc into a nude mouse. In this model, IgG2a monoclonal antibody (MAb) ME 36.1 defining the GD2/GD3 gangliosides inhibited melanoma growth at the primary site and metastatic spread of the cells, whereas an IgG1 variant of MAb ME 36.1 inhibited lung metastasis formation only. Possible mechanisms of antitumor effects of MAb ME 36.1 are discussed.

Animals↗
PubMed1989

Reduced DNA repair in cultured melanocytes and nevus cells from a patient with xeroderma pigmentosum.

Patients with xeroderma pigmentosum (XP) have more than a 1000-fold increased risk of cutaneous melanoma. To determine if the XP DNA repair defect is present in cutaneous pigmentary cells, nevus cells and melanocytes from four large, pigmented nevi were cultured from a 12-year-old girl with XP. Cultured melanocytes showed dendritic morphologic features, contained mature melanosomes, and reacted with monoclonal antibody to tyrosinase. Nevus cells were spindle shaped and expressed nevus cell-associated antigens. Melanocytes, nevus cells, and dermal fibroblasts from the patient with XP all had a similar reduction in DNA repair: unscheduled DNA synthesis was 30% to 50% of that in normal fibroblasts following a 30 J/m2 ultraviolet dose. After a 6 J/m2 ultraviolet dose, the proliferative ability of XP nevus cells and fibroblasts was reduced to 10% of that of normal fibroblasts. This study indicates that cultured melanocytes and nevus cells express the characteristic XP DNA repair defect.

Cell Survival↗
PubMed1988

Cryopreservation of sperm from the marine shrimp Sicyonia ingentis.

Sperm from a marine shrimp, Sicyonia ingentis, were frozen to -196 degrees C using a variety of cooling rates and cryoprotectants. A cooling rate of 1 degree C/min resulted in minimal cell breakage. Sperm samples were frozen in solutions of known membrane stabilizers--trehalose, sucrose, proline, and glycerol. These compounds were somewhat effective but a dramatic increase in sperm viability was seen when DMSO was present in the freezing medium. Sperm viability was assessed using the in vitro acrosome reaction technique of Griffin et al. (1987). The highest sperm survival (56%) was obtained with samples frozen at 1 degrees C/min in a 5% (v/v) DMSO solution. No decrease in viability was seen in sperm samples stored in liquid nitrogen (-196 degrees C) for 1 month.

Animals↗
PubMed1988

Possible involvement of the chromosome region 10q24----q26 in early stages of melanocytic neoplasia.

A recent report described a translocation involving 10q24 in a compound nevus. We have examined our series of melanocytic tumors ranging from common nevi to metastatic melanomas with the following results. In 24 nevi (congenital or common acquired), no karyotypically abnormal clones were found. Two of 10 dysplastic nevi had abnormal clones: one had an unidentified marker chromosome, the other had a t(9;10)(p24;q24) translocation. Of the three complex primary melanomas studied (lesions with both radial and vertical growth phase present), one had a t(10;?)(q26;?) and one showed a loss of chromosome 10. Among 51 advanced melanomas (primary and metastatic), all but one had multiple alterations, and 18 of these had lost one or more copies of chromosome 10. The one invasive melanoma without multiple abnormalities had a complex three-way rearrangement: 46,XY,t(5;6;10) with breakpoints on chromosome 10 at both q23 and q25. These data support the view that the terminal region of 10q may harbor one or more genes involved in the early stages of melanocytic neoplasia.

Chromosome Aberrations↗