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Biomedical subjects

B R Smoller

Publications and source records attributed to B R Smoller.

At least 91 records · Page 5Linked to original sources
PubMed1995

Expression of bcl-2 protein and Ki-67 nuclear proliferation antigen in benign and malignant cutaneous T-cell infiltrates.

The bcl-2 protein prolongs cell life by inhibiting apoptosis. Its expression has been studied in a variety of normal tissues and lymphomas but there is minimal information available concerning bcl-2 expression by benign and malignant cutaneous T-cells. Therefore, we investigated bcl-2 expression in a wide variety of cutaneous T-cell infiltrates using one- and two-color immunohistologic techniques. bcl-2 was expressed by the majority of lesional CD3+ T-cells in most cases. This included 22/26 cases of mycosis fungoides (MF), 3/3 cases of non-MF cutaneous T-cell lymphoma, 5/5 cases of lymphomatoid papulosis, 4/4 cases of T-cell rich cutaneous lymphoid hyperplasia, 2/3 cases of bullous pemphigoid, 2/2 cases of discoid lupus erythematosus and 1/1 case of lichen planus. Titration experiments and comparative studies of tonsil section positive controls revealed that, relative to mantle zone B-cells, there was over- expression of bcl-2 by a variable subset of T-cells in most cases. Assessment of multiple biopsies in a subset of MF cases showed stable expression of bcl-2 over intervals of up to two years. In contrast to the widespread expression of bcl-2 in both early and advanced MF skin lesions, abundant expression of the nuclear proliferation antigen, Ki-67, was skewed toward advanced MF skin lesions. Ten percent or more Ki-67+ cells were present in 5% of patients with patches/thin plaques, 38% with moderate plaques, 64% with thick plaques and 100% with tumor nodules.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1995

Use of CD34 in assessing the relationship between stroma and tumor in desmoplastic keratinocytic neoplasms.

It has been hypothesized that the ability for neoplastic growth of epithelial-derived neoplasms depends upon the stroma. There are currently some studies which show that the stroma surrounding basal cell carcinomas (BCC) is derived from the tumor. In contrast, other studies provide evidence that the stroma is a host-derived response to the tumor. In order to further examine the nature of stroma enveloping cutaneous epithelial neoplasms, we examined a series of tumors which contain abundant stroma, including morpheic type BCC (MBCC), desmoplastic trichoepitheliomas (DTE), and microcystic adnexal carcinomas (MAC). The spindle-shaped cells surrounding the epithelial islands of the two malignant tumors, MBCCs and MACs, were negative in 70% and 100% of cases, respectively, for CD34. In contrast, the spindle-shaped cells surrounding the islands of the benign DTEs were positive for CD34 in 80% of cases. The results suggest that whereas stromal cells surrounding DTEs resemble the CD34-positive perifollicular cells, the spindle-shaped stromal cells surrounding MBCC and MAC are CD34 negative, and may be derived from sources other than the normal mesenchymal tissue surrounding cutaneous appendages.

Antigens, CD34↗
PubMed1995

Progesterone receptor positivity supports hormonal control of syringomas.

Syringomas may be at least partially under estrogen and/or progesterone influence, as they are more common in women and are known to proliferate at puberty. During pregnancy and the premenstrual period an increase in tumor size has also been described. We examined nine syringomas using immunohistochemical markers for estrogen (ER) and progesterone (PR) receptors. Scattered tumor cells displaying nuclear and cytoplasmic staining for ER were noted in one of the nine cases. Intense nuclear and cytoplasmic staining for PR was noted in most (> 80%) of the neoplastic cells in 8/9 syringoma cases. Current immunohistochemical evidence supports the theory that syringomas are under hormonal control.

Adolescent↗
PubMed1995

bcl-2 expression in primary malignancies of the skin.

BACKGROUND AND DESIGN: Basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma (MM) are the three most common malignant neoplasms that arise in the skin. Deregulation of oncogene function not infrequently leads to an increased rate of cellular proliferation. However, the expansion of malignant cells can also occur if programmed cell death is inhibited. The oncogene bcl-2 participates in the regulation of apoptosis (programmed cell death). In view of this, we determined the presence and possible role of bcl-2 in primary cutaneous malignancies. Routine paraffin sections of formalin-fixed BCCs, SCCs, MMs (primary and metastatic), actinic keratoses, and SCCs in situ were labeled with anti-bcl-2 monoclonal antibody using a biotin-avidin-immunoperoxidase procedure. RESULTS: Twenty-three BCCs were examined and all expressed cytoplasmic bcl-2. Two of 20 SCCs were positive. One of these had patchy, diffuse staining, and the other stained in only small foci. None of eight SCCs in situ and none of eight actinic keratoses expressed bcl-2. Sixteen of 18 MMs expressed bcl-2. CONCLUSIONS: The bcl-2 gene product has been found to inhibit apoptosis. Our preliminary results suggest that the expression of bcl-2 is present quite consistently in BCCs and MMs, but not in SCCs or precursor lesions. The expression (or lack thereof) of bcl-2 may reflect the difference in the regulation of cell turnover between these tumors, or histogenetic differences.

Basal Cell Carcinoma↗
PubMed1995

bcl-2 expression in melanocytic nevi. Insights into the biology of dermal maturation.

BACKGROUND AND DESIGN: Recently, a new category of oncogenes has been discovered that regulate programmed cell death. The bcl-2 oncogene has been found to inhibit cellular death without affecting cellular proliferation. In the skin, bcl-2 expression is limited to cells along the basal cell layer. However, we also noticed that resting melanocytes appeared to express bcl-2. We examined the expression of bcl-2 and its possible role in the biology of benign melanocytic proliferations. Routine paraffin sections of formalin-fixed tissue were labeled with anti-bcl-2 monoclonal antibody, and expression of bcl-2 was detected by a biotin-avidin-immunoperoxidase procedure. RESULTS: We examined 13 congenital, 11 acquired, and six atypical or dysplastic nevi for expression of bcl-2. Expression of bcl-2 was observed in 11 of 13 congenital nevi. All 11 acquired nevi and 6 nevi with architectural disarray and cytologic atypia expressed bcl-2. Both junctional and intradermal melanocytes expressed bcl-2 in a perinuclear and cytoplasmic pattern. Within neurotized areas, bcl-2 became significantly weaker and totally absent. CONCLUSIONS: In mature tissues, bcl-2 expression is quite limited. It appears to be restricted to pluripotential stem cells that serve as a reservoir for tissue that is constantly undergoing renewal, such as the hematopoietic cells and the intestinal mucosa. In the skin, bcl-2 expression has been previously reported to be limited to the epidermal basal cell layer and proliferation zones. Our results indicate that resting melanocytes and melanocytic nevi regularly express bcl-2.

Aging↗
PubMed1995

Differentiation and clonality of lesional lymphocytes in small plaque parapsoriasis.

BACKGROUND: Small plaque parapsoriasis is an idiopathic chronic dermatosis characterized by patches on the trunk and extremities that are often smaller than 5 cm in diameter and that sometimes have a digitate contour. These latter cases are often referred to as digitate dermatosis. Histopathologic examination reveals a mild superficial perivascular lymphocytic infiltrate associated with mild spongiosis and parakeratosis. To characterize this disease more completely, we analyzed the differentiation and clonality of lesional lymphocytes using immunohistologic and molecular biologic methods. OBSERVATIONS: We studied five cases using a frozen-section immunoperoxidase technique. In each case, there was a predominantly CD4+ T-cell infiltrate admixed with CD8+ T cells, Langerhans cells/indeterminate cells, and macrophages. In three cases, the clonality of lesional T cells was studied by denaturing gradient gel electrophoresis of polymerase chain reaction-amplified T-cell receptor-gamma gene rearrangements. Two cases showed a dominant clonal pattern, while one case exhibited a polyclonal pattern. Clinical follow-up disclosed persistent disease in one of the two clonal cases, while lesions in the other clonal case and the polyclonal case gradually resolved. CONCLUSIONS: Our findings indicate that small plaque parapsoriasis is a clinically indolent, histopathologically nonspecific, predominantly CD4+ T-cell-mediated disease that, at least in some cases, contains a dominant T-cell clone. These features put small plaque parapsoriasis into a category with certain other members of the parapsoriasis group, namely, pityriasis lichenoides and lymphomatoid papulosis, which have been shown to be clonal T-cell disorders despite their clinically benign course. It remains to be determined if the dominant T-cell clones identified in some cases of small plaque parapsoriasis can ever be the direct precursors of overt cutaneous T-cell lymphomas.

Adult↗
PubMed1995

Estrogen and progesterone receptors and anti-gross cystic disease fluid protein 15 (BRST-2) fail to distinguish metastatic breast carcinoma from eccrine neoplasms.

Cutaneous metastases of breast carcinoma can be histologically similar to primary skin tumors with eccrine differentiation. We compared the immunohistochemical staining characteristics of 15 metastatic breast carcinoma skin lesions in 12 patients to those of a series of primary eccrine tumors using estrogen receptor, progesterone receptor, and anti-gross cystic disease fluid protein-15 markers. Anti-gross cystic disease fluid protein-15 positivity was noted in 7 of 15 breast carcinoma skin metastases, 0 of 5 benign eccrine tumors, 1 of 6 microcystic adnexal carcinomas, and 1 of 1 metastatic sweat gland adenocarcinoma. Estrogen receptor positivity was found in 1 of 15 metastatic breast carcinoma skin lesions, 0 of 5 benign eccrine tumors, 2 of 8 microcystic adnexal carcinomas, and 1 of 1 metastatic sweat gland adenocarcinoma. Progesterone receptor positivity was identified in 15 of 15 metastatic breast carcinoma skin lesions, 2 of 5 benign eccrine tumors, 5 of 8 microcystic adnexal carcinomas, and 1 of 1 metastatic sweat gland adenocarcinomas. These results indicate that standard immunohistochemical staining for estrogen receptors, progesterone receptors, and gross cystic fluid protein-15 markers will not reliably distinguish primary (or metastatic) eccrine tumors from cutaneous metastases of breast carcinoma.

Adenocarcinoma↗
PubMed1994

Risk of secondary cutaneous malignancies in patients with long-standing mycosis fungoides.

BACKGROUND: Patients with mycosis fungoides (MF) are frequently treated with UV light and psoralen (PUVA), nitrogen mustard, and electron beam irradiation, modalities known to predispose persons to development of cutaneous malignancies. OBJECTIVE: We assessed the relation between these therapeutic modalities and the development of secondary cutaneous malignancies. METHODS: We reviewed the charts of all patients observed during the past year. RESULTS: We found that 7 of 71 patients had cutaneous neoplasms in an average follow-up time of 8.3 years. Orthovoltage radiation was used in five of seven cases and PUVA in four of seven. Five of seven patients had multiple neoplasms. CONCLUSION: The risk of the development of second malignancies from the treatment of MF is relatively small and appears to be related to the type of therapy.

Carcinoma in Situ↗
PubMed1994

Benign lymphangioendothelioma.

We describe a 40-year-old white man with a red-brown, indurated plaque on the proximal aspect of his right thigh. The lesion had been present since birth, and the patient had a 20-year clinical history of recurrent cellulitis in the same area. The histopathologic features of the lesion included permeation of the dermis by flattened, endothelium-lined channels without cellular atypia, hemorrhage, or inflammation. The endothelial cells were stained intensely with monoclonal antibody anti-CD34 (clone MY10). In addition, antibodies to factor VIII antigen, HLA-DR, smooth muscle actin, ICAM-1, and the lectin Ulex europaeus labeled the luminal cells. The basement membrane of the channels stained with anti-type IV collagen and laminin. Desmin-positive cells were abundant adjacent to the channels. Factor XIIIa stained both mononuclear cells and occasional dendritic cells in the perivascular area. Ki-67 immunolabeling could not be demonstrated on fresh or frozen tissue. Electron microscopy revealed the presence of both tight junctions and a well-formed, continuous basement membrane but the absence of Weibel-Palade bodies.

Adult↗
PubMed1994

Cutaneous angiosarcoma as a second malignancy in a lymphedematous leg in a Hodgkin's disease survivor.

Angiosarcoma is a rare and highly malignant neoplasm. Cutaneous angiosarcoma not associated with postmastectomy lymphedema is rare. There are only eight reported cases of development of cutaneous angiosarcoma in a lymphedematous extremity in a patient with preexisting malignancy other than breast cancer. This is the first reported case of development of cutaneous angiosarcoma in a lymphedematous extremity in a Hodgkin's disease survivor. A review of cutaneous angiosarcoma associated with lymphedema and a discussion of the pathogenesis of angiosarcoma are included.

Adolescent↗
PubMed1994

bcl-2 expression reliably distinguishes trichoepitheliomas from basal cell carcinomas.

Trichoepitheliomas (TE) are benign follicular neoplasms which are frequently confused with basal cell carcinomas (BCC). It is important to distinguish these entities precisely, as the treatments and prognoses are different. To this end, we stained a series of formalin-fixed, paraffin-embedded specimens of unequivocal TE and BCC with antibodies directed against bcl-2, an oncogene associated with programmed cell death, and known to be overexpressed in some malignant tumours. The TE showed staining of tumour cells limited to the outermost layer of the proliferation. The BCC tumour cells demonstrated diffuse staining throughout the tumour nodules. This difference in staining pattern was then applied to more equivocal cases, and seemed clearly to separate the entities. The observed findings may prove to be of diagnostic help in distinguishing borderline cases, and also offer some possible explanations for the biological differences between these neoplasms.

Basal Cell Carcinoma↗
PubMed1994

Immunofluorescent analysis of the basement membrane zone in lichen planus suggests destruction of the lamina lucida in bullous lesions.

Lichen planus is an inflammatory dermatosis which is characterized histologically by an intense lymphocytic infiltrate at the dermal epidermal junction. This frequently results in disruption of the basement membrane zone, occasionally causing clinical blisters. In order to better understand the specific portion of the basement membrane zone which is disrupted by the lymphocytic infiltrate, we examined 7 cases of lichen planus with antibodies directed against anchoring filaments (GB3), the bullous pemphigoid antigen, anchoring fibrils (type VII collagen) and type IV collagen. In lesions without separation at the BMZ, all antibodies were strongly expressed, as in normal skin. In lesions with early separation, there was a focal decrease in GB3 staining, but types VII and IV collagen labelled normally. In lesions resulting in blisters, GB3 staining was essentially absent, and anti-types IV and VII collagen remained, but stained in a disrupted, less discrete pattern. The bullous pemphigoid antigen showed only slight deviation from the normal staining pattern. These findings suggest that the basement membrane zone in lichen planus is disrupted in the lamina lucida region. The lamina densa and sub-lamina densa zones remain intact even in bullous lesions of lichen planus.

Autoantigens↗
PubMed1994

T lymphocytes bearing the gamma/delta T-cell receptor in cutaneous lesions of dermatitis herpetiformis.

T lymphocytes bearing the gamma/delta T-cell receptor are a rare component of normal human GI epithelium and skin. Recently, however, an unusually high percentage of T lymphocytes with gamma/delta receptors has been described in gastrointestinal biopsies from patients with dermatitis herpetiformis, implicating the gamma/delta T cell subset in the pathogenesis of this disease. We investigated a possible role for this subset of lymphocytes in the pathogenesis of the cutaneous lesions of dermatitis herpetiformis. Using a standard immunoperoxidase technique, we labelled perilesional skin biopsies from patients with dermatitis herpetiformis and other inflammatory dermatoses with monoclonal antibodies to CD3, CD4, CD8, alpha/beta T cell receptor, gamma/delta T cell receptor, and IL-2 receptor. We found no differences in the percentage of gamma/delta positive T lymphocytes in skin lesions of dermatitis herpetiformis as compared to other selected inflammatory conditions. These findings suggest that the pathogenesis of the cutaneous lesions of dermatitis herpetiformis is not mediated through gamma/delta T cells, and that the cutaneous lesions may develop through mechanisms different from those operative in the gastrointestinal tract.

Dermatitis Herpetiformis↗
PubMed1994

Semipermeable dressings improve epidermal barrier function in premature infants.

Infants of less than 32 wk gestation have a defective epidermal barrier, with increased skin permeability and transepidermal water loss (TEWL). We studied the effect of a nonadhesive semipermeable dressing on the epidermal barrier of premature infants and on fetal skin transplanted to nude mice. Fifteen infants with a mean estimated gestational age of 27.7 wk and 16 human fetal skin grafts (estimated gestational age, 23-26 wk) transplanted to eight nude mice were studied. One lower leg (or skin graft) was treated and the other left untreated as a control. In the infants, TEWL was measured on control skin and treated skin (both through the dressing and after temporary dressing removal) on d 0, 1, 2, 4, and 7. Bacterial and fungal cultures were also performed. In the mice, TEWL and skin blood flow were measured on d 0, 2, and 4. Biopsies were obtained on d 4 for a cell proliferation assay, histology, and electron microscopy. Treated infant skin showed a consistently lower bacterial number and a significantly decreased TEWL (measured through the dressing). There was also a significantly lower TEWL on the treated side, measured after temporary dressing removal, on d 1, 2, 4, and 7, documenting improved epidermal barrier function. The animal study revealed decreased TEWL and a nearly 2-fold greater d-4 keratinocyte proliferation (p = 0.01) in treated skin and decreased blood flow on d 4 in control skin (p = 0.01). There was no significant difference in the volume density of membrane coating granules or the morphology of intercorneocyte spaces.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗