PubMed Health⌕ Search

Biomedical subjects

D Seldin

Publications and source records attributed to D Seldin.

9 recordsLinked to original sources
PubMed2000

Carcinoembryonic antigen immunoscintigraphy complements mammography in the diagnosis of breast carcinoma.

BACKGROUND: An adjunctive noninvasive test that is predictable and highly specific for breast carcinoma would complement the high false-positive rate of mammography in certain patients. METHODS: This prospective, multicenter study evaluated the accuracy, safety, and immunogenicity of carcinoembryonic antigen (CEA) antibody imaging in women with known or suspected breast carcinoma. Scintigraphic breast images were obtained approximately 3-8 hours after the administration of technetium 99m ((99)Tc) labeled anti-CEA Fab' and correlated with histopathology. RESULTS: The (99)Tc labeled anti-CEA Fab' detected tumor CEA expression in 46 of 49 women (94%) initially entered with known primary breast carcinoma regardless of histology or serum CEA levels. In women scheduled for biopsy confirmation of mammographic and physical examination findings, 104 (99)Tc labeled anti-CEA Fab' studies had a sensitivity of 61% (17 of 28 cases) and a specificity of 91% (69 of 76 cases). In total, (99)Tc labeled anti-CEA Fab' detected 52 of 62 invasive ductal carcinomas, 5 of 5 invasive lobular carcinomas, and 3 of 6 noninvasive tumors (2 ductal carcinomas in situ and 1 intracystic papillary carcinoma). Tumor size significantly affected sensitivity (P = 0.041), with 11 of 14 missed lesions </= T1, and proliferative histology significantly affected specificity (P = 0.012), with 5 of 7 false-positive tumors being premalignant. In 50 breast carcinoma patients, (99)Tc labeled anti-CEA Fab' also demonstrated axillary lymph node involvement regardless of serum CEA levels, with a sensitivity of 80% when more than three lymph nodes were positive. No immune response or other meaningful side effects occurred. CONCLUSIONS: (99)Tc labeled anti-CEA Fab' had high specificity and positive predictive values for breast carcinoma and the majority of false-positive studies were associated with an increased risk of malignancy. Improved imaging techniques, including dedicated gamma cameras for breast and axillary lymph node imaging, will likely improve the test's sensitivity for smaller lesions.

Adult↗
PubMed1999

Basolateral Na+ pump modulates apical Na+ and K+ conductances in rabbit cortical collecting ducts.

Previous studies indicated that an acute elevation of peritubular K+ enhances K+ secretion and Na+ reabsorption in the isolated perfused cortical collecting duct (CCD) from rabbit kidneys [S. Muto, G. Giebisch, and S. Sansom. Am. J. Physiol. 255 (Renal Fluid Electrolyte Physiol. 24): F108-F114, 1988]. To determine the underlying cellular mechanisms, we used microelectrode techniques to assess the membrane properties of collecting duct cells in isolated perfused CCDs of control and desoxycorticosterone acetate (DOCA)-treated rabbits following acute stimulation of the basolateral Na+-K+ pump by rapidly increasing the bath solution from 2.5 to 8.5 mM K+. This induced in both groups of tubules, first, a short-lasting hyperpolarization and, second, a sustained phase of depolarization of transepithelial, basolateral, and apical membrane voltages. Whereas the transepithelial conductance (GT) and fractional apical membrane resistance (fRA) remained unchanged during the initial phase of hyperpolarization, during the depolarization, GT increased and fRA decreased. Perfusion of the lumen with solutions containing either amiloride or Ba2+ attenuated the high K+-induced apical electrical changes, and basolateral strophanthidin abolished both apical and basolateral electrical responses during elevation of K+ in the bath. From these results we conclude the following: 1) acute elevation of basolateral K+ activates the basolateral Na+-K+ pump, which secondarily elevates the apical Na+ and K+ conductances; 2) DOCA pretreatment increases the basolateral K+ conductance and augments the response to the rise of K+ of both basolateral Na+-K+ pump activity and apical cation conductances.

Animals↗
PubMed1990

Nephrolithiasis and bone involvement in primary hyperparathyroidism.

PURPOSE: The purpose of this study was to compare patients with primary hyperparathyroidism with and without nephrolithiasis with regard to (1) biochemical profile, and (2) presence and extent of bone involvement. PATIENTS AND METHODS: Of 70 unselected patients enrolled in a longitudinal study on the natural history of primary hyperparathyroidism, 62 who underwent complete bone densitometry evaluation were considered. The patients had mild hypercalcemia (2.77 +/- 0.02 mmol/L), as well as elevated parathyroid hormone levels by mid-molecule, N-terminal, and immunoradiometric assays. Bone densitometry was assessed by dual-photon absorptiometry of the lumbar spine and femoral neck, and single-photon absorptiometry of the forearm. RESULTS: Eleven of the 62 patients (18%) had nephrolithiasis. There was no difference in serum parathyroid hormone levels, calcium, phosphorus, serum 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D3 between those with and without kidney stones. Total daily urinary calcium excretion was higher among those who formed stones (8.2 +/- 1.0 mmol versus 6.1 +/- 0.4 mmol, p less than 0.05), but not when expressed per mmol of creatinine (0.72 +/- 0.07 versus 0.69 +/- 0.04). Urinary hydroxyproline was also higher in patients who formed stones (58 +/- 11 mg/24 hours versus 37 +/- 2 mg/24 hours; p less than 0.05). Hypercalciuria occurred in 39% of the entire cohort (n = 24), and in 33% (n = 17) of those without stones. Only 29% (n = 7) of those with hypercalciuria had nephrolithiasis. Calcium excretion correlated positively with serum 1,25-dihydroxyvitamin D3 (r = +0.32, p less than 0.05), and negatively with forearm bone mineral density (all patients: r = -0.34, p less than 0.05; hypercalciuric patients: r = -0.53, p less than 0.05). Circulating 1,25-dihydroxyvitamin D3 levels were elevated in a similar proportion of (1) all patients (31%, n = 19); (2) those with nephrolithiasis (27%); and (3) those without stones (31%). Bone mineral density was less than 80% of normal in 61% of patients, but forearm, femoral neck, and lumbar spine density were indistinguishable among those with and without stones. CONCLUSIONS: Cortical bone demineralization occurs to the same extent and frequency in patients with and without nephrolithiasis, and these two subgroups share similar biochemical and bone densitometric profiles. The pathophysiologic events leading to renal and skeletal involvement in primary hyperparathyroidism may be less selective than previously believed, as evidenced by: (1) increased urinary hydroxyproline in patients with nephrolithiasis, and (2) documentation that urinary calcium excretion reflects not only vitamin D status, but bone resorption was well.

Bone Density↗
PubMed1989

Effects of tamoxifen on spinal bone density in women with breast cancer.

Bone densitometry (L2-L4) was performed on 10 postmenopausal women with breast cancer after 0, 6, and 12 months of tamoxifen treatment; the results were compared with data from 10 normal controls. The patients and controls differed significantly at 6 (P less than .05) and 12 (P less than .003) months. The tamoxifen group showed a nonsignificant mean gain in bone mineral density after 6 and 12 months of treatment (+0.024 +/- 0.014 and +0.022 +/- 0.018 g/cm2, respectively), whereas the controls showed a nonsignificant mean loss of bone mass at 6 months (-0.012 +/- 0.018 g/cm2) and a statistically significant loss of bone density after 12 months (-0.024 +/- 0.01 g/cm2). These preliminary data suggest that tamoxifen use is associated with preservation of bone mass during the first year of treatment.

Aged↗
PubMed1989

Skeletal disease in primary hyperparathyroidism.

Most patients with primary hyperparathyroidism in the 1980s do not have evidence of bone disease when they are evaluated by conventional radiography. We sought to determine whether skeletal involvement can be appreciated when more sensitive techniques, such as bone densitometry and bone biopsy, are utilized. We investigated 52 patients with primary hyperparathyroidism. They had mild hypercalcemia, 2.8 +/- 0.03 mmol/liter (11.1 +/- 0.1 mg/dl), low normal phosphorus, 0.9 +/- 0.03 mmol/liter (2.8 +/- 0.1 mg/dl), and no symptoms or specific radiological signs of skeletal involvement. The greatest reduction in bone mineral density was found at the site of predominantly cortical bone, the radius (0.54 +/- 0.1 g/cm; 79 +/- 2% of expected), whereas the site of predominantly cancellous bone, the lumbar spine (1.07 +/- 0.03 g/cm2), was normal (95 +/- 3% of expected). The site of mixed composition, the femoral neck (0.78 +/- 0.14 g/cm2), gave an intermediate value (89 +/- 2% of expected). Preferential involvement of cortical bone with apparent preservation of cancellous bone in primary hyperparathyroidism was confirmed by percutaneous bone biopsy. Over 80% of patients had a mean cortical width below the expected mean, whereas cancellous bone volume in over 80% of patients was above the expected mean. The results indicate that the majority of patients with asymptomatic primary hyperparathyroidism have evidence by bone densitometry and bone biopsy for cortical bone disease. The results also indicate that the mild hyperparathyroid state may be protective of cancellous bone. The therapeutic implications of these observations await further longitudinal experience with this study population.

Biopsy↗
PubMed1984

Interleukin 3: A differentiation and growth factor for the mouse mast cell that contains chondroitin sulfate E proteoglycan.

Mouse mast cells were differentiated and grown by culturing bone marrow cells in medium containing 2 X 10(-10) M purified interleukin 3 (IL 3). The cells obtained were similar in ultrastructure, membrane antigen phenotype, proteoglycan type, and lipid products generated upon immunologic activation to mast cells differentiated in culture by WEHI-3-conditioned medium (WEHI-3-CM) and by concanavalin A (Con A) splenocyte-conditioned medium. Phenotypically, these cells expressed IgE receptors and H-2 antigens and were recognized by a monoclonal antibody (B23.1) that did not react with mouse serosal heparin-containing mast cells. The classic phenotypic markers of mouse T cells or macrophages were not detected. The mouse mast cells differentiated with IL 3 as well as those differentiated in WEHI-3-CM incorporated [35S]sulfate into a nonheparin proteoglycan of 150,000 to 200,000 m.w. Most of the 35S-labeled macromolecules were degraded by chondroitinase ABC to yield only two disaccharides, which co-chromatographed on ascending thin layer chromatography with delta Di-4S and delta Di-diSE; thus, the proteoglycan in these cells is composed of chondroitin sulfate E glycosaminoglycans. After sensitization with monoclonal IgE, washing, and antigen activation, the IL 3 differentiated cells released the preformed mediator beta-hexosaminidase and generated and released two major classes of lipid mediators. The quantities of leukotriene C4 (LTC4), leukotriene B4 (LTB4), and platelet-activating factor (PAF-acether) generated/10(6) cells were 17, 3.0, and 3.1 ng, respectively. The ratio of these three lipid mediators was similar to that obtained from mast cells differentiated in WEHI-3-CM and in Con A-conditioned medium. Thus, T cell-derived IL 3 is the component present in the conditioned media that is required for differentiation and growth of the subclass of mast cells containing chondroitin sulfate E proteoglycan, designated E-MC. The IL 3-dependent E-MC may represent the in vitro counterpart of the T-cell-dependent mucosal mast cell, suggesting in turn that the production of LTC4 and LTB4 and of PAF-acether may play a role in adaptive intestinal immunity to helminthic parasites.

Animals↗
PubMed1981

Acid hydrolases and tryptase from secretory granules of dispersed human lung mast cells.

beta-Hexosaminidase, beta-glucuronidase, arylsulfatase, and tryptase were each released along with histamine from dispersed purified human lung mast cells of 40 to 80% purity by rabbit IgG anti-human IgE. The net per cent release ratio of each enzyme to histamine was determined over all doses of antibody employed to activate the mast cells and over all time points after activation, and indicated the per cent of each enzyme stored in secretory granules along with histamine. By multiplying the net per cent release ratio of each enzyme to histamine by total enzyme content in a preparation of 10(6) mast cells, values for secretory granule content per 10(6) mast cells were found to be 3.8 U for beta-hexosaminidase, 0.03 U for beta-glucuronidase, 0.03 U for arylsulfatase, and 0.9 U for tryptase. Subtype analysis of beta-hexosaminidase by diethylaminoethyl- (DEAE) cellulose chromatography revealed that the B isomer predominates in human mast cell secretory granules, whereas the A isomer predominates in secretory granules of the rat mast cell. Tryptase, the predominant neutral protease of the human mast cell secretory granule, has a m.w. of 130,000 by gel filtration chromatography, whereas the major neutral protease of the rat mast cell is chymotryptic and of 25,000 m.w. The presence of acid hydrolases, a tryptase, and histamine in human mast cell secretory granules suggests that the activated mast cell plays a direct role in the production of acute and subacute inflammation.

Arylsulfatases↗