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Biomedical subjects

M Shepard

Publications and source records attributed to M Shepard.

16 recordsLinked to original sources
PubMed2001

Leishmaniasis recidivans recurrence after 43 years: a clinical and immunologic report after successful treatment.

We describe a patient with very late recurring leishmaniasis recidivans from whom lesional biopsy samples were obtained during and after topical steroid treatment that demonstrated the ability of the host to contain the parasite in the absence of therapy. Combination therapy with intralesional sodium stibogluconate and oral itraconazole was successful and immunologic data suggest that both CD4(+) and CD8(+) T cell subsets had roles in this disease process.

Animals↗
PubMed1992

Radiolabeled antibody targeting of the HER-2/neu oncoprotein.

The HER-2/neu oncogene encodes a Mr 185,000 transmembrane phosphoglycoprotein which is overexpressed in 25-35% of breast and ovarian neoplasms and portends a poor prognosis. We have studied the feasibility of targeting this oncoprotein, designated p185, with radioiodinated murine monoclonal antibodies (muMABs) 4D5 and 7C2, which recognize distinct epitopes on its extracellular domain. The rates of internalization and catabolism of these antibodies were analyzed by cellular radioimmunoassay and electron microscopy. After binding to NIH3T3 HER-2/neu cells, which show high surface expression of p185, the muMABs were endocytosed via coated pits, routed to lysosomes, and degraded. Approximately 44% of 125I-4D5 and 39% of 125I-7C2 were catabolized by tumor cells after 24 h. The biodistribution of radiolabeled 4D5 and 7C2 were evaluated in beige/nude mice bearing s.c. NIH3T3 HER-2/neu grafts. A high specificity of localization was seen with tumor:organ ratios of activity generally ranging from 5:1 to 30:1. However, the percentage injected dose of radioactivity per gram of tumor declined sharply from 25% at 24 h to 5% at 120 h postinjection. Treating the animals with 400-700 muCi 131I-4D5 caused a marked inhibition of tumor growth, although no mice were cured. Unlabeled 4D5 had no effect on tumor progression in this model, but administering 400-700 muCi of 131I-DA4-4, an isotype-matched irrelevant muMAB, resulted in an intermediate degree of growth retardation. Analysis of kinetic blood data and whole-body time-activity curves indicated that the irrelevant conjugate remained in the body 2-3 times longer than 131I-4D5. Radioiodinated anti-HER-2/neu muMABs are attractive agents for radioimmunodiagnosis and radioimmunotherapy of aggressive HER-2/neu-positive breast and ovarian carcinomas, but effective strategies for retarding intratumoral catabolism may be necessary to optimize their clinical utility.

3T3 Cells↗
PubMed1990

Direct interaction of a ligand for the erbB2 oncogene product with the EGF receptor and p185erbB2.

The erbB2 oncogene encodes a 185-kilodalton transmembrane protein whose sequence is similar to the epidermal growth factor receptor (EGFR). A 30-kilodalton factor (gp30) secreted from MDA-MB-231 human breast cancer cells was shown to be a ligand for p185erbB2. An antibody to EGFR abolished the tyrosine phosphorylation induced by EGF and transforming growth factor-alpha (TGF-alpha) but only partially blocked that produced by gp30 in SK-BR-3 breast cancer cells. In two cell lines that overexpress erbB2 but do not expresss EGFR (MDA-MB-453 breast cancer cells and a Chinese hamster ovary cell line that had been transfected with erbB2), phosphorylation of p185erbB2 was induced only by gp30. The gp30 specifically inhibited the growth of cells that overexpressed p185erbB2. An antibody to EGFR had no effect on the inhibition of SK-BR-3 cell colony formation obtained with gp30. Thus, it appeared that gp30 interacted directly with the EGFR and erbB2. Direct binding of gp30 to p185erbB2 was confirmed by binding competition experiments, where gp30 was found to displace the p185erbB2 binding of a specific antibody to p185erbB2. The evidence described here suggests that gp30 is a ligand for p185erbB2.

Animals↗
PubMed1990

ELISA for quantitation of the extracellular domain of p185HER2 in biological fluids.

The HER2/neu proto-oncogene encodes a receptor that belong to the tyrosine-specific protein kinase family. Amplification of the HER2 gene in patients with breast and ovarian cancer has been shown to predict poorer survival rates. In order to understand the role of HER2 in malignant and normal cells, it is necessary to devise assays that can quantitate expression levels of the HER2 gene product (p185HER2) in production samples, biopsy specimens and biological fluids. We have developed a simple, quantitative ELISA that uses two monoclonal antibodies directed against the extracellular domain of the HER2 gene product, p185HER2 (HER2 ECD). The assay has a detection range of 0.25-120 ng/ml, is precise and sensitive. The ability of this assay to detect biologically active rHER2 ECD is demonstrated by its correlation to a growth inhibitory bioassay (r = 0.92). The sandwich ELISA can also accurately quantitate rHER2 ECD in mouse and monkey serum. This assay should be useful for quantitating low levels of circulating rHER2 ECD in animals in which rHER2 ECD is being used as antigen for immunotherapy and in patients which 'shed' receptor.

Antibodies, Monoclonal↗
PubMed1987

Recombinant human TNF alpha stimulates production of granulocyte colony-stimulating factor.

Tumor necrosis factor alpha (TNF alpha) stimulates production of granulocyte colony-stimulating factor (G-CSF) protein and mRNA in fibroblast cells. In contrast, TNF beta is at least 1,000-fold less potent than TNF alpha in increasing levels of G-CSF and GM-CSF activity and mRNA. The fibroblasts produce G-CSF and GM-CSF mRNA in a coordinate fashion after exposure to TNF. The ability of TNF alpha to stimulate production of CSF in fibroblasts may be pivotal to regulation of hematopoiesis.

Adult↗
PubMed1982

A standardized plane for biparietal diameter measurement.

Biparietal diameter measurement is the most widely accepted means of determining gestational age. However, a standard anatomic plane for performing this measurement has not been established. Three hundred forty-four measurements on 256 patients who gave birth to normal infants were obtained and compared at various cranial levels based on brain anatomy. The results document that use of a standardized plane increases measurement reliability but does not significantly alter variability. We postulate that variability is based predominantly on biologic variation in fetal growth rates rather than on technical errors.

Cephalometry↗