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Biomedical subjects

W H Clark

Publications and source records attributed to W H Clark.

At least 19 recordsLinked to original sources
PubMed1992

Preloading of micromolar intracellular Ca2+ during capacitation of Sicyonia ingentis sperm, and the role of the pHi decrease during the acrosome reaction.

In studying the mechanism controlling the sperm acrosome reaction (AR) in the marine shrimp Sicyonia ingentis, intracellular Ca2+ and pH were measured using the fluorescent indicators Fura-2 and Fluo-3 for Ca2+, and SNARF-1 for pH. Capacitated sperm possessed an apparent resting Ca2+ concentration of 1-2 microM which remained constant upon induction of the AR with egg water. Uncapacitated sperm had extremely low Ca2+ levels and did not respond to egg water. These results suggest that, while in other species the Ca2+ is elevated to micromolar levels during initiation of the AR, S. ingentis sperm are preloaded with Ca2+ during capacitation and the trigger for the AR is downstream of the Ca2+ increase. The notion that Ca2+ influx is not involved at the actual time of the AR in capacitated S. ingentis sperm is supported by the inability of Ca2+ ionophore A23187 to induce the AR and the ineffectiveness of Ca2+ channel antagonists to block egg water-induced AR. Measurements of capacitated sperm pH showed a significant decrease during the first 10-15 min of the AR, which did not correlate temporally to either acrosomal exocytosis (at 5 min post-induction) or filament formation (after 45 min). Inhibition of egg protease activity required for induction of filament formation did not inhibit the pH drop, indicating that intracellular acidification is not the final trigger for filament formation, although it may be required prior to action of the protease.

Acrosome↗
PubMed1992

Extracellular Mg2+ induces an intracellular Ca2+ wave during oocyte activation in the marine shrimp Sicyonia ingentis.

In contrast to most systems in which oocyte activation is triggered by the fertilizing sperm, Sicyonia ingentis oocytes are activated by seawater Mg2+ during spawning. S. ingentis oocytes were spawned into Mg(2+)-free seawater and microinjected with the fluorescent Ca2+ indicator Fluo-3 to study the effects of added Mg2+ on intracellular Ca2+ levels. The Mg2+ induced a wave of fluorescence across the oocyte that traveled at a speed of 13 +/- 3 microns/sec. Extracellular Ca2+ was not required for induction of the wave. Treatment with Ca2+ ionophore in Mg(2+)-free medium or a localized injection (0.3% oocyte volume) of 3-5 microM Ca2+ also initiated the wave; injection of 250 mM Mg2+ (up to 1.5% oocyte volume) had no effect. Microinjection of 750 microM EGTA (final) suppressed the Mg(2+)-induced wave, while an identical concentration of EDTA had no inhibitory effect. Subsequent to the initial Mg(2+)-induced intracellular Ca2+ increase, a second Ca2+ increase was observed at approximately 15 min postspawning; the timing of this second increase appeared to be independent of when the Mg(2+)-induced wave was initiated, thus an event associated with spawning may be involved. While oocytes in normal seawater were monospermic, those in Mg(2+)-free seawater were polyspermic, suggesting a role for the Mg(2+)-induced Ca2+ wave in regulating sperm entry into the oocyte.

Animals↗
PubMed1992

Cleavage and gastrulation in the shrimp Sicyonia ingentis: invagination is accompanied by oriented cell division.

Embryos of the penaeoidean shrimp Sicyonia ingentis were examined at intervals during cleavage and gastrulation using antibodies to beta-tubulin and DNA and laser scanning confocal microscopy. Cleavage occurred in a regular pattern within four domains corresponding to the 4-cell-stage blastomeres and resulted in two interlocking bands of cells, each with similar spindle orientations, around a central blastocoel. Right-left asymmetry was evident at the 32-cell-stage, and mirror-image embryos occurred in a 50:50 ratio. Gastrulation was initiated by invagination into the blastocoel at the 62-cell-stage of two mesendoderm cells, which arrested at the 32-cell-stage. Further invagination and expansion of the archenteron during gastrulation was accompanied by rapid and oriented cell division. The archenteron was composed of presumptive naupliar mesoderm and the blastopore was located at the site of the future anus of the nauplius larva. In order to trace cell lineages and determine axial relationships, single 2- and 4-cell-stage blastomeres were microinjected with rhodamine-dextran. The results showed that the mesendoderm cells which initiated gastrulation were derived from the vegetal 2-cell-stage blastomere, which could be distinguished by its slightly larger size and the location of the polar bodies. The mesendoderm cells descended from a single vegetal blastomere of the 4-cell-stage. This investigation provides the first evidence for oriented cell division during gastrulation in a simple invertebrate system. Oriented cell division has previously been discounted as a potential morphogenetic force, and may be a common mechanism of invagination in embryos that begin gastrulation with a relatively small number of cells.

Animals↗
PubMed1979

Early recognition of cutaneous melanoma.

Criteria for the early recognition of malignant melanoma include appreciation of variegation in color and irregularity of lesion border and pigment pattern. Application of these criteria should result in the diagnosis of cutaneous melanoma in its premetastatic surgically curable phase.

Adult↗
PubMed1979

Multiple primary melanoma.

From a series of 712 patients with melanoma, 38 patients (5.3%) had more than one primary melanoma. Twenty-four patients had two primaries, 11 patients had three, 2 patients had four, and 1 patient had eight. Twelve patients (32%) had one or more synchronous primaries. Forty-five percent of all multiple primaries were diagnosed within the first year. Microstaging by level and depth was determined prior to treatment and in patients with nonsynchronous primaries, 83% had a subsequent melanoma equal or less advanced than the original. Twenty-six patients with Stage I primaries were skin-tested with DNCB prior to therapy. No significant differences in delayed cutaneous hypersensitivity reactions were found between multiple primary and matched controls with only a single melanoma. Four of 10 patients with multiple primaries treated with adjuvant BCG or BCG-tumor cell vaccine developed subsequent melanomas suggesting that immunotherapy with BCG will not prevent the development of a new primary melanoma. Survival in patients with Stage I and II multiple primary melanomas was improved compared to Stage I and Stage II patients with a single primary. This study suggests that prognosis in multiple primary melanomas is better reflected by the most advanced primary based on microstaging and the presence or absence of regional lymph node metastases than by multiplicity.

Adult↗
PubMed1979

Reactivity of monoclonal anti-melanoma antibodies with melanoma cells freshly isolated from primary and metastatic melanoma.

Human melanoma cells, freshly obtained from nine primary and metastatic melanoma cases, were tested for binding of monoclonal anti-melanoma antibodies produced in vitro by hybridoma clones. Monoclonal anti-melanoma antibodies bind to melanoma cells but do not react with nonmalignant cells obtained from the same patients or with cells obtained from giant hairy nevus. These results confirm the existence of tumor-specific antigens. Binding of monoclonal antibodies to melanoma cells of several origins, primary or metastatic, from different patients suggests the existence of tumor antigens shared by human melanoma cells. The binding pattern of different antibodies to various cells also predicts the existence of more than one tumor-specific antigenic determinant on melanoma cells.

Animals↗
PubMed1979

Cutaneous melanoma in a patient with neurofibromatosis.

Although neurofibromatosis and cutaneous melanoma are both diseases of neuroectodermal origin, reports of their association are rare. The case history of a patient with histologically documented neurofibromatosis and a nodular melanoma unrelated to a cafe-au-lait spot or congenital nevus is reported, and the literature reviewed. The appearance of only one patient with neurofibromatosis in a series of 900 patients with melanoma suggests that these diseases are probably not associated with greater frequency than that predicted by chance alone.

Adult↗
PubMed1979

Malignant melanoma in the Sinclair miniature swine: an autopsy study of 60 cases.

Sinclair miniature swine spontaneously develop multiple cutaneous melanomas which have the ability to metastasize and regress. This study, based on 60 necropsies, documents the similarity of the pathology of the cutaneous malignant melanomas and the organ distribution of metastasis to human melanoma. The invasive cutaneous melanomas have an intraepidermal component analogous to human superficial spreading melanoma. The pathology of the spontaneous regression, characterized by a series of cellular events beginning with a mononuclear inflammatory infiltrate and leading to depigmentation and fibrosis, is likewise similar to cutaneous regression in human melanoma. Just as with human melanoma,metastasis was correlated with deeply invasive cutaneous tumors. Because of both the biologic and histologic similarity of this animal model to human melanoma, the Sinclair miniature swine should serve as an important resource in continuing the study of melanoma.

Animals↗
PubMed1978

Precursor lesions in familial melanoma. A new genetic preneoplastic syndrome.

In seven consecutive melanoma-prone families, pigmented lesions with distinctive clinical and histologic characteristics occurred in 18 of 20 melanoma patients (90%) and 24 of 43 first-degree relatives (56%). Recognition of these lesions led to the detection of early-stage melanoma in six family members. This syndrome appears to represent an autosomal dominant trait and may serve as a cutaneous marker to identify persons at high risk for melanoma.

Adult↗
PubMed1978

Precursor lesions in familial melanoma.

Familial occurrences of malignant melanoma may be related to an inherited syndrome of precursor cutaneous lesions with distinct clinical and histologic features. Recognition of the syndrome in the relatives of melanoma patients identifies a subset of family members at high risk for melanoma, facilitating their early diagnosis and treatment. Further studies of these families may provide insight into the biology of malignant melanoma and the pathophysiology of malignant transformation in benign nevi.

Female↗
PubMed1978

Origin of familial malignant melanomas from heritable melanocytic lesions. 'The B-K mole syndrome'.

Distinctive melanocytic moles are described in 37 patients from six melanoma families. Among the family members examined by the authors, 15 of 17 patients with melanoma and 22 of 41 nonmelanoma relatives had the unique moles. The clinical and histological features of these moles have been designated the "B-K mole syndrome." The clinical features of the syndrome include the presence of less than 10 to greater than 100 moles prominent of the upper trunk and extremities, and variability of mole size (5 mm to 15 mm), outline, and color combination. Histologically, B-K moles show atypical melanocytic hyperplasia, lymphocytic infiltration, delicate fibroplasia, and new blood vessels that occur within a compound nevus or de novo. The transformation of two B-K moles into malignant melanomas was documented photographically.

Adolescent↗
PubMed1977

Comparison of the classification by microscopic level (stage) of malignant melanoma by three independent groups of pathologists.

The ability of groups of pathologists to classify and stage malignant melanoma varies with their familiarity with the new nomenclature proposed for that process. Primary lesions of malignant melanoma from 79 patients were independently examined and classified by community pathologists, university pathologists, and a referee pathologist all without access to each others diagnoses. The diagnoses of these groups were compared for agreement in variety of melanoma as well as depth of dermal penetration (stage or level). Greatest success (agreement with the referee) of both the community pathologists and the university pathologists was achieved when assessment of level of invasion (+/- 1) of the referee was compared (community pathologists = 94% +/- 12% agreement, university pathologists = 99% +/- 2% agreement). Our survey demonstrates that only a relatively small number of community pathologists (23%) employ the new nomenclature, but they do so with a facility equal to that of the university pathologists. Based upon this study and our continuing experiences, we recommend the review of all primary lesions of malignant melanoma by a pathologist or group experienced in the diagnosis and microscopic staging of the disease.

Diagnostic Errors↗
PubMed1976

Primary malignant melanoma of the urinary bladder.

A melanin-synthesizing tumor of the urinary bladder was studied by light and electron microscopy. Careful clinical evaluation did not reveal evidence for a primary melanoma elsewhere in the patient. The clinical presentation, course of the disease, and demonstration of melanocytes in the bladder epithelium and malignant melanocytes comprising the tumor by light and electron microscopy indicated that the neoplasm was a primary malignant melanoma arising in the bladder.

Aged↗
PubMed1976

Melanocytic lesions of the eyelid skin.

We described the three histogenetic forms of cutaneous melanoma--lentigo maligna melanoma, superficial spreading melanoma, and nodular melanoma. The first two forms have a flat spreading component or radial growth phase in the epithelium as well as in the invasive or vertical growth phase. Formerly these two lesions may have been confused with one another. Nodular melanoma has only the vertical growth phase. Examples of lentigo maligna melanoma and superficial spreading melanoma were found in eyelid lesions involving both the skin and conjunctiva. The distinctive histopathology of the cutaneous lesion was retained in the conjunctiva.

Aged↗
PubMed1976

Malignant melanomas of the conjunctiva.

A retrospective study of 23 conjunctival melanomas using the Clark classification revealed that the three most common forms of melanoma described in the skin--lentigo maligna melanoma (Hutchinson's freckle with melanoma), superficial spreading melanoma, and nodular melanoma--can be recognized in the conjunctiva. As in the skin, lentigo maligna melanoma appears to be associated with a good prognosis compared to the prognosis associated with superficial spreading melanoma. These two forms of melanoma are both associated with an intraepithelial stage and had previously been grouped under one designate, cancerous melanosis. They can be distinguished histologically although definite clinical differentiation will be determined in the future. Some melanomas with an intraepithelial stage, however, cannot be definitely classified. Relating all conjunctival cancerous melanoses to Hutchinson's melanotic freckle is no longer justified.

Adult↗
PubMed1976

The accuracy of predicting lymph nodes metastases in malignant melanoma by clinical examination and microstaging.

Since 1971, a prospective treatment regimen for primary cutaneous malignant melanoma performed by a single clinician has revealed the following early observations: 1) A significantly higher number of females with level II disease; 2) No recurrences or metastases to date in 29 patients with level II lesions treated by appropriate surgery; 3) The apparent clinical predictability of lymph node metastases in the group microstaged at level III. 4) An inability to predict lymph node metastases (or their delayed development) in patients with level IV disease; 5) A correlation between lymph node metastases and the development of disseminated disease.

Female↗