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Biomedical subjects

W L White

Publications and source records attributed to W L White.

At least 19 recordsLinked to original sources
PubMed1997

nm23--relationship to the metastatic potential of breast carcinoma cell lines, primary human xenografts, and lymph node negative breast carcinoma patients.

BACKGROUND: Since the discovery of nm23 (nonmetastatic) by Steeg et al. in 1988, a number of tumor cohort studies have shown an inverse relationship between the levels of expression of the nm23-H1 protein and disease aggressiveness and tumor metastatic potential. METHODS: The relationship between the expression of nm23 protein and the metastatic potential of human breast carcinoma was analyzed in cell lines, xenografts, and in a retrospective lymph node negative breast carcinoma population. The lymph node negative breast carcinoma study was comprised of 40 patients: 19 with nonrecurrent and 21 with recurrent disease. The 40 patients were matched according to age, cathepsin D, tumor size, percent S-phase, DNA ploidy, steroid receptor status, and tumor grade. Nm23-H1 protein levels in cell lines and xenografts were analyzed quantitatively using Western blot analyses and semiquantitatively in tissue sections using immunocytochemistry. Immunocytochemical analysis of lymph node negative breast tumors was graded as the percent of tumor staining positive for nm23 and the intensity of staining. The metastatic potentials of the cell lines and xenografts were assessed as the ability to form metastatic lesions in nude mice. In the lymph node negative breast carcinoma patients, the metastatic potential was characterized as the incidence of breast carcinoma recurrence. RESULTS: The MCF-7 cell line expressed four- and tenfold higher levels of nm23-H1 than the highly metastatic MDA-MB-435 and MDA-MB-231 cells, respectively. Among the xenografts and cell lines, there was an inverse correlation between nm23-H1 expression and metastatic potential in athymic nude mice (correlation coefficient [R] = -0.51). The differences between the levels of nm23-H1 among the metastatic and nonmetastatic cell lines and xenografts were not statistically significant. Statistical analyses indicated that neither the intensity nor the percent of tumor staining positive for nm23 expression was correlated to the recurrence of breast carcinoma in the lymph node negative patient population that had been matched for other clinical prognostic markers. CONCLUSIONS: There was an inverse correlation (R = 0.51) between the levels of nm23-H1 expression in cell lines and xenografts and the metastatic potential in nude mice. In the retrospective lymph node negative breast carcinoma population, no clear association was demonstrated between the expression of nm23 and breast carcinoma recurrence. This observation suggests the nm23 expression does not predict outcome in lymph node negative breast carcinoma patients.

Aged↗
PubMed1997

Response imagery: aftereffects and reminiscence.

In two experiments, subjects imagined themselves performing a tracking task under a massed practice schedule. After interpolated rest or no rest, subjects actually performed the criterion task. Some subjects' imagery was augmented with sounds that matched the temporal characteristics of the criterion task. These subjects produced greater aftereffects than subjects who imaged without augmentation or subjects provided with imagery augmentation matching a variation of the criterion. Reminiscence (performance gain attributed to interpolated rest) was demonstrated with imagery, except when the accompanying augmentation was faster than the criterion.

Female↗
PubMed1997

Malignant melanoma in situ colonizing basal cell carcinoma. A simulator of invasive melanoma.

Coexisting (collision) cutaneous neoplasms of various types and combinations are well documented but relatively uncommon. This report describes the unusual occurrence of a malignant melanoma in situ (MMIS) colonizing a basal cell carcinoma (BCC). A 69-year-old man was considered clinically to have a melanocytic neoplasm or a pigmented BCC of the right ear. Biopsy showed an MMIS, lentigo maligna type, juxtaposed to a typical BCC. The MMIS extended peripherally and into the BCC. Interspersed among the basaloid epithelial cell aggregates that extended 1.70 mm into the dermis were atypical melanocytes. Immunoperoxidase stains with high molecular weight cytokeratin (903) stained the basaloid keratinocytes but not the melanocytes. Conversely, HMB-45 and Mel-5 intensely stained the melanocytes throughout the BCC and in the epidermis but did not demonstrate any separate aggregates of invasive melanoma. These findings suggest that the position of the MMIS was a consequence of BCC colonization. Because the prognosis of malignant melanoma correlates most closely with the thickness of the lesion, this case poses a unique problem in predicting the biology of the lesion, which we believe should not be considered invasive melanoma.

Aged↗
PubMed1997

Myocardial apoptosis in a heterotopic murine heart transplantation model of chronic rejection and graft vasculopathy.

BACKGROUND: Apoptosis has been implicated in myocardial reperfusion injury and in experimental transplantation rejection. One mechanism of apoptosis is through the interaction of the cell-surface Fas receptor on target cells and the Fas ligand that is expressed on cytotoxic T cells. The purpose of this study was to look for evidence of myocardial Fas receptor, Fas ligand, and apoptosis in a murine heterotopic heart transplantation model of chronic rejection/graft vasculopathy. METHODS: Using the nick-end labeling technique, we examined a murine heterotopic heart transplantation model of chronic rejection/graft vasculopathy (strain B10.A to B10.BR) histologically for evidence of DNA fragmentation. MRNA for the Fas receptor, Fas ligand, and beta-actin was detected with reverse transcription-polymerase chain reaction. RESULTS: Hearts harvested after 30 and 60 days showed an intimal index of the allografts (0.5 +/- 0.1) (mean +/- standard error) that was at least five times more than syngeneic grafts and native (nontransplanted) hearts (p < 0.01). In situ nick end-labeling of partially degraded DNA with terminal deoxynucleotydil transferase showed an increase in apoptotic cells in allografts and syngeneic grafts compared with native hearts. Reverse transcription-polymerase chain reaction detected equal myocardial RNA signal intensity of Fas receptor and beta-actin in allografts, syngeneic grafts, and native hearts. In contrast, allografts showed a strong signal for the Fas ligand mRNA, a signal not seen in syngeneic grafts or native hearts. CONCLUSIONS: Apoptosis is occurring in both allografts and syngeneic grafts in this murine model of chronic rejection/graft vasculopathy, although distinct mechanisms may be involved.

Animals↗
PubMed1996

Desmoplastic malignant melanoma of the oral mucosa. An underrecognized diagnostic pitfall.

BACKGROUND: Although cutaneous desmoplastic malignant melanoma (DMM) has been well characterized, those arising from the oral mucosa have been less well defined. METHODS: We evaluated the clinical and pathologic features of three patients with biopsy-proven DMM examined at the North Carolina Baptist Hospital. Routine hematoxylin and eosin-stained slides were reviewed in all three cases. Sections from all cases were examined immunohistochemically using the avidin-biotin-peroxidase (ABC) technique and employing commercially available antibodies to the following antigens: S-100 protein, HMB-45, NK1C3, and cytokeratin (AE1/AE3). Appropriate positive and negative controls were utilized throughout these procedures. Clinical data were obtained from the patients' medical records. RESULTS: Age at diagnosis for the three male patients were 42, 64, and 75 years. Anatomically, these neoplasms arose from the left maxillary oral mucosa (two patients) and the vermilion border of the lower lip (one patient). Initial incisional biopsies of all three patients were misinterpreted as desmoid tumor (one patient) and squamous cell carcinoma (two patients), respectively. Histologically, all tumors were poorly circumscribed and composed of fascicles and bundles of spindle-shaped cells with hyperchromatic nuclei and associated with extensive stromal collagenization. Perineural invasion was noted in two tumors. An overlying atypical, intraepidermal melanocytic proliferation was observed in two tumors. Immunohistochemically, all three tumors showed positive immunoreactivity with S-100 protein and vimentin. One tumor also expressed HMB-45. Wide surgical incision was the primary mode of therapy in all patients. One patient also received multiple courses of radiation therapy and chemotherapy. One patient died of widespread metastatic disease. CONCLUSIONS: DMM of the oral mucosa is a rare, often unrecognized, form of malignant melanoma associated with a fibrosarcoma-like morphologic appearance and abundant collagenization. Meticulous attention to histomorphology and judicious use of immunohistochemical stains will help prevent misdiagnosis.

Adult↗
PubMed1996

Murine and pediatric myocardial growth factor mRNA expression using reverse transcription-polymerase chain reaction.

We utilized reverse transcription-polymerase chain reaction (RT-PCR) to examine the myocardial mRNA expression of growth factors in mice and children. Total cellular RNA was extracted from these tissues using acidified-phenol guanidinium thiocyanate. Optimal oligonucleotide primer pairs for RT-PCR were selected with the aid of the computer program Oligo 4.0. RT-PCR analysis of total cellular RNA demonstrated the measurable presence of the mRNA for the following growth factors in the myocardium of both mice and children: acidic fibroblast growth factor (aFGF), basic FGF (bFGF), insulin-like growth factor (IGF)-1, IGF-2, platelet-derived growth factor (PDGF)-A chain, PDGF-B chain, transforming growth factor (TGF)beta-1, TGFbeta-2, and TGFbeta-3. The amplified cDNA message for the growth factors and beta-actin migrated as a discrete band at the expected base pair number on agarose gels stained with the intercalating fluorescent dye ethidium bromide. Densitometry of the photographic negatives of these gels permitted the rapid and semiquantitative comparison of these factors. These data demonstrate the feasibility and reproducibility of utilizing RT-PCR for the specific detection and semiquantitation of mRNA expression of myocardial aFGF, bFGF, PDGF-A chain, PDGF-B chain, lGF-1, lGF-2, TGFbeta-1, TGFbeta-2, and TGFbeta-3 in mice and children.

Animals↗
PubMed1996

Behçet's disease. Report of twenty-five patients from the United States with prominent mucocutaneous involvement.

BACKGROUND: Behçet's disease is a multisystem disease that is rare in the United States. OBJECTIVE: The purpose of our study was to assess the characteristics and treatment of a series of patients with Behçet's disease in the United States. METHODS: A retrospective clinical review of 25 patients with Behçet's disease was performed, and histopathologic findings and therapeutic modalities were reviewed. RESULTS: All patients had oral and genital aphthae, and 22 of 25 patients had cutaneous lesions consistent with Behçet's disease. Eight of 25 patients had relatively severe systemic disease. Nine of 14 biopsy specimens showed a neutrophilic vascular reaction. Our therapeutic "ladder" included aggressive topical and intralesional corticosteroids, colchicine, dapsone, methotrexate, and thalidomide; we reserved systemic corticosteroids and immunosuppressive medications for severe ocular or severe systemic disease. CONCLUSION: This series of patients with Behçet's disease was characterized by patients with prominent mucocutaneous involvement and a low prevalence of ocular involvement. These findings may be attributed to patient selection from referral to a university dermatology clinic.

Administration, Topical↗
PubMed1996

Panniculitis: recent developments and observations.

Dermatopathologists rarely greet a biopsy of panniculitis with total confidence that a specific, definitive diagnosis will be rendered. As with many other areas in dermatopathology, our understanding of the pathogenesis of many forms of panniculitis is incomplete. This article examines a subset of panniculitis primarily from a pathogenetic standpoint, with the intention of providing a differential diagnosis for those cases in which ischemic changes are seen in the subcutis. The diverse group of conditions evoked by this approach also shares the distinction of having been the focus of nosologic and causative controversy, both historically and currently. In particular, stasis-associated sclerosing panniculitis, vascular calcification-cutaneous necrosis syndrome (calciphylaxis), oxalosis, and nodular vasculitis-erythema induratum are examined in depth. Erythema nodosum and variants, other granulomatous panniculitides, and panniculitides showing cytophagocytosis are also discussed with current perspectives.

Diagnosis, Differential↗
PubMed1996

Cutaneous metastasis of ocular malignant melanoma. An unusual presentation simulating blue nevi.

Cutaneous metastases from primary ocular melanoma are not well characterized in the literature, and the occurrence of cutaneous metastases in the absence of other systemic involvement is distinctly uncommon. A case of primary ocular malignant melanoma is reported in which the only evidence of metastatic disease initially was skin lesions that simulated cutaneous blue nevi. Knowledge of this patient's history of ocular malignant melanoma coupled with a review of the clinical and histopathologic specimens was necessary to arrive at the diagnosis. This case illustrates and characterizes an unusual presentation of cutaneous metastases of primary ocular melanoma.

Ciliary Body↗
PubMed1996

Chondrosarcomatous cutaneous metastasis. A unique manifestation of sarcomatoid (metaplastic) breast carcinoma.

Breast carcinoma is the most common origin of cutaneous metastasis in women but is usually of ductal or lobular histotypes. Sarcomatoid (metaplastic) carcinoma of the breast, although a well-established aggressive neoplasm, is very uncommon. The metaplastic elements span all types of mesenchymal differentiation and have been demonstrated to be derived from carcinomatous elements. Skin metastasis from such lesions is extremely rare. A case of metastatic sarcomatoid breast carcinoma to the skin is described in which the histology of the metastases was that of chondrosarcoma.

Aged↗
PubMed1996

Primary cutaneous Ewing's family sarcoma. Report of a case with immunostaining for glycoprotein p30/32 mic2.

The differential diagnosis of cutaneous small round cell malignancies is a relatively uncommon but recurrent problem that usually requires adjuvant techniques including special histochemical stains, immunohistochemistry (IHC), electron microscopy (EM), and cytogenetics (CG) to arrive at a definite answer. This report describes a case of a primary cutaneous malignancy that, after workup, fulfilled the criteria of extraskeletal Ewing's family sarcoma, which was corroborated by IHC with an antibody to glycoprotein p30/32 mic2 that is highly expressed in these neoplasms. The lesions consisted of a large nodular proliferation of poorly differentiated monotonous small round cells confined to the dermis and subcutaneous tissue. The cells had high nuclear to cytoplasmic (N/C) ratios, scattered prominent nucleoli, and indistinct cytoplasm. A periodic acid-Schiff (PAS) stain with and without diastase demonstrated abundant cytoplasmic glycogen. The glycogen was confirmed with EM, which did not show neurosecretory granules, but extensive sectioning of the tissue blocks demonstrated with light microscopy a single focus with pseudorosette formation. IHC was positive for monoclonal antibody (MAb) O13 to glycoprotein p30/32 mic2 and negative for lymphoid (CD45), neural (S-100, NF, GFAP), neuroendocrine (NSE), and muscle (MSA, desmin) markers. To the best of our knowledge, this is one of few reported cases of primary cutaneous (extraskeletal/extraosseous) Ewing's sarcoma (EEWS) and the first to use IHC with MAb O13, which recognizes the cell surface glycoprotein p30/32 mic2. This case further illustrates the continuum between EEWS and primitive peripheral neuroepithelioma and supports the unifying concept that these two entities are merely subtle morphologic variants of the same malignant neoplasm, which is better designated a Ewing's family sarcoma.

12E7 Antigen↗
PubMed1996

Magnetic resonance imaging versus bone scan for assessment of vascularization of the hydroxyapatite orbital implant.

We prospectively studied 10 patients who were status postenucleation and primary placement of the hydroxyapatite orbital implant. Both the technetium-99m bone scan and gadolinium-enhanced magnetic resonance images (MRI) were obtained on the same day at variable time points in the postoperative period in order to assess the degree of vascularization. Up to 78% of the bone scans were interpreted as being completely vascularized, while only 10% of the corresponding MRI scans were consistent with complete vascularization. Cost analysis showed that MRI was cost-effective imaging modality. We conclude that contrast-enhanced MRI provides a more accurate assessment of vascularization of the hydroxyapatite orbital implant when compared to bone scan.

Adolescent↗
PubMed1996

Nitric oxide synthase activity is up-regulated in melanoma cell lines: a potential mechanism for metastases formation.

Nitric oxide (NO) may be an important mediator of tumour angiogenesis and metastasis formation. Tumour cell derived NO may be important in the regulation of angiogenesis and vasodilatation of the blood vessels surrounding a tumour. The aims of the present study were, firstly, to determine whether malignant melanoma cells and normal melanocytes had nitric oxide synthase (NOS) activity (measured by the conversion of L-arginine to L-citrulline) and, secondly, to determine whether there was a difference in NOS activity between malignant and normal cell types. This paper assays NOS activity directly in lysates from normal human melanocyte and malignant melanoma cell lines. The enzyme activity was not inducible with bacterial lipopolysaccharide and could be heat denatured. The activity of NOS was demonstrated to be both NADPH- and calcium-dependent and it was inhibitable in a dose-dependent manner by the NOS inhibitor Nw-nitro-L-arginine methyl ester. We conclude that melanoma and melanocyte cells express a constitutive form of NOS. Finally, nitric oxide synthase activity in melanoma cell lines was found to be significantly greater than in normal melanocytes. These findings suggest that NO synthesis is elevated in malignant melanoma. An elevated NO concentration in melanoma is expected to promote metastases by maintaining a vasodilator tone in the blood vessels in and around the melanoma.

Cells, Cultured↗
PubMed1996

Extra-acral calcifying aponeurotic fibroma: a distinctive case with 23-year follow-up.

Calcifying aponeurotic fibroma (CAF) is an unusual but well-characterized soft tissue neoplasm that typically involves the digits of children and frequently recurs locally. This report describes a case from the subcutis of the lumbosacral region. A 26-year-old man initially presented at age 3 and developed three recurrences over a 23-year period each at approximately 8-year intervals (ages 10, 18, and 26). The microscopic findings in all recurrences showed a lobulated, poorly circumscribed proliferation of dense fibrous tissue containing epithelioid-like fibroblasts, multinucleated cells, and islands of metaplastic chondroid differentiation with focal calcification. Despite origin from an unusual anatomic site, this case reported herein demonstrates the classical morphologic features and clinical history of CAF which showed little in the way of morphologic evolution despite 23 years of persistence. The clinical and histologic features helpful in distinguishing CAF from infantile fibromatosis and soft tissue chondroma are discussed.

Adult↗
PubMed1995

Mucocutaneous criteria for the diagnosis of Behçet's disease: an analysis of clinicopathologic data from multiple international centers.

BACKGROUND: Although four of five of the new international criteria for the diagnosis of Behçet's disease relate to mucocutaneous lesions, disagreement exists as to the exact nature of cutaneous lesions (e.g., vessel-based vs follicular). OBJECTIVE: Our purpose was to review clinical data, clinical photographs, and skin biopsy specimens from multiple medical centers throughout the world to monitor current practice in the implementation of mucocutaneous diagnostic criteria for Behçet's disease. METHODS: Ten medical centers responded to a request to collaborate by sending clinical data, photographs of cutaneous lesions, and biopsy specimens from 22 patients. RESULTS: Of specimens from 22 patients, 14 revealed a histopathologic pattern of neutrophils containing perivascular and interstitial inflammation, whereas specimens from three patients revealed only mononuclear cells in a vessel-based pattern. Biopsy specimens from three patients revealed primarily folliculocentric inflammation and an additional two specimens were from erythema nodosum-like lesions. CONCLUSION: Perivascular inflammation was the predominant histopathologic finding in specimens of cutaneous lesions in this clinical series. Folliculocentric lesions could not be predicted on the basis of review of clinical photographs. Histopathologic assessment of cutaneous lesions is crucial if the proposal is accepted that exclusion of folliculocentric lesions is important to ensure accurate implementation of diagnostic criteria in patients with suspected Behçet's disease.

Adult↗
PubMed1995

Ocular adnexal lymphoma. A clinicopathologic study with identification of lymphomas of mucosa-associated lymphoid tissue type.

PURPOSE: Extranodal marginal zone B-cell lymphoma (low-grade B-cell lymphoma of mucosa-associated lymphoid tissue [MALT] type) is a distinctive type of lymphoma that usually arises in association with mucosa or other epithelial structures and has an indolent clinical course. The frequency and clinical features of MALT lymphomas in the ocular adnexa have not been well studied. METHODS: The authors examined the clinicopathologic features of ocular adnexal lymphoma, identified a subset of cases with MALT characteristics, and determined patient outcome. RESULTS: The 42 patients, 16 men and 26 women age 35-89 years (mean, 64) were followed an average of 4.8 years. Thirty-two patients had ocular adnexal involvement at presentation (primary ocular adnexal lymphoma) and 10 had a history of lymphoma that relapsed in the orbit (secondary ocular adnexal lymphoma). In the primary group, 23 patients had lymphoma confined to the ocular adnexa, 3 had a single lesion that invaded adjacent structures, and 6 had distant spread at the time of presentation. Twenty-five patients achieved a complete remission. Nine patients, including 6 patients whose disease was localized initially, had progression or relapse of disease in distant sites. At last follow-up, 21 patients were free of disease, 9 were alive with disease and 2 had died of lymphoma. In the secondary group, at last follow-up, 1 patient had died of other causes, free of lymphoma, 3 patients were alive with disease and 5 had died of lymphoma (outcome not known in 1 case). Using the recently described revised European-American lymphoma classification, we found 16 MALT lymphomas, 8 diffuse large B cell, 12 follicular center, 3 mantle cell, 1 B-small lymphocytic lymphoma, and 2 unclassifiable low-grade lymphomas. The most common type of primary lymphoma was MALT type (15 of 30 classifiable cases), and the most common secondary lymphoma was follicular center (6 of 10). No increased frequency of conjunctival or lacrimal gland involvement by MALT lymphomas was found. All 33 lymphomas with immunophenotyping were of B lineage. CONCLUSIONS: Ocular adnexal lymphomas are B-cell tumors that develop in older adults, predominantly among women. Primary orbital lymphomas have a favorable prognosis; a high proportion of them have MALT characteristics.

Adult↗
PubMed1995

Intercellular adhesion molecule 1 (ICAM-1) and bcl-2 are differentially expressed in early evolving malignant melanoma.

The expression of intercellular adhesion molecule 1 (ICAM-1), a molecule pivotal in many inflammatory and immune paracrine interactions, has been highly correlated with malignant melanoma (MM) progression. Because numerous parallels exist between tissues of neural crest origin and the immune system in the regulation of postmitotic cell survival, ICAM-1 expression was studied in MM and compared with that of B-cell lymphoma/leukemia 2 protein (bcl-2 oncoprotein), an important regulator in prolonging lymphoid cell survival by blocking programmed cell death. Frozen sections from 33 cases were studied by immunoperoxidase techniques: 14 primary MM (five in situ), nine metastatic MM (one epidermotropic), four melanocytic nevi, and six normal skin controls. The percentages of the cells that stained and their intensities (0-4+) were graded. Both ICAM-1 (90%, 3-4+) and bcl-2 (95%, 2-4+) were strongly expressed in all nine metastases, including the epidermotropic disease extension. Bcl-2 strongly decorated the tumor cells in all 14 cases of primary MM (80%, 2-4+); in the five in situ MM, bcl-2 stained the atypical melanocytes at the dermal-epidermal junction (DEJ) and throughout the epidermis (75%, 1-2+). In contrast, ICAM-1 was negative in the in situ MM. ICAM-1 expression became strong (85%, 2-4+) in the dermal component of early invasive disease. Both ICAM-1 and bcl-2 were expressed in melanocytic nevi, decreasing in intensity deep within the dermis as the nevus cells senesced ("matured"). Only bcl-2 was expressed in the normal melanocytes of the six skin controls. These data show that bcl-2 is constitutively expressed in normal melanocytes and melanocytic nevi and persists in the transformed cells of early and late MM. ICAM-1 is expressed only after dermal involvement occurs, both in melanocytic nevi and in invasive MM; it persists in metastatic disease. The coexpression of bcl-2 and ICAM-1 demonstrates another similarity between the immune and neural crest systems, but it does not define or necessarily imply any functional interaction between the two proteins. The intercellular relationship of these two molecules, if any, remains to be investigated.

Apoptosis↗