Search PubMed⌕ Search

Biomedical subjects

S Hoffman

Publications and source records attributed to S Hoffman.

At least 19 recordsLinked to original sources
PubMed1995

Breast cancer after breast augmentation with silicone implants.

BACKGROUND: Although epidemiological studies have failed to demonstrate an increased incidence of breast cancer in women who had undergone prior prosthetic augmentation mammoplasty (PAM), it has been reported that when breast cancer arises in this group it presents mostly in a palpable form and at a more advanced stage. This is thought to be secondary to suboptimal mammographic evaluation caused by the masking effect of the implant. This study was undertaken to determine, in our experience, whether breast cancer arising in women who had undergone PAM could be detected in a prepalpable form by mammography and whether it presented at a more advanced stage as compared with nonaugmented women with breast cancer. METHODS: The charts of 22 patients, treated by at least one of the authors, in whom 23 breast cancers developed after PAM (group A) were retrospectively reviewed. The comparison groups consisted of 611 nonaugmented patients who underwent 636 procedures for the treatment of primary breast cancer at our institution (group B) and the surveillance, epidemiology, and end results (SEER) data (group C). Parameters studied were mode of detection, tumor size, axillary lymph node involvement, and histopathology. RESULTS: No significant differences between the groups were found in mean tumor size (group A vs. group B), the incidence of preinvasive cancer (group A vs. group B) or axillary lymph node involvement (group A vs. group B and group A vs. group C). Breast-preserving surgery was performed significantly less in augmented patients (group A vs. group B). CONCLUSION: We conclude that prepalpable and preinvasive breast cancer can be detected in the PAM patient by mammography and that the stage of presentation in this group is not significantly different than in nonaugmented patients. Total mastectomy is preferred over breast-preserving procedures for the treatment of breast cancer in the PAM patient.

Adult↗
PubMed1995

Q-fever pneumonia in the Negev region of Israel: a review of 20 patients hospitalised over a period of one year.

BACKGROUND: Three-hundred and forty-six patients with community acquired pneumonia were included in a prospective study of patients hospitalised over a 12-month period in the Soroka Medical Center in Beer-Sheva, Israel. Q-fever pneumonia (QFP) was diagnosed in 20 patients (5.8%). A detailed epidemiological and clinical description of this disease, is presented. METHODS: QFP was diagnosed by conventional criteria using a commercial immunofluorescent assay. RESULTS: The age of patients was 41 +/- 14 years (mean +/- S.D., range 20-69). Twelve of the patients were males. No concomitant or chronic disease was present in 16 patients. Chest radiograms revealed alveolar or air space pneumonia in 10 patients, bronchopneumonia in nine and interstitial pneumonia in one patient. The mean febrile period was 10.5 +/- 5.3 days. There was serological evidence of co-infection with Mycoplasma pneumonia in six patients, and with Legionella pneumophila in one patient. Patients treated with beta-lactam antibiotics recovered as quickly as those treated with tetracyclines or erythromycin. CONCLUSIONS: The Negev region of Israel is an endemic area for Q-fever. The diagnosis of QFP can be made only on the basis of a specific serological test. Clinical, radiologic or laboratory findings are not diagnostically definitive. The importance of specific therapy is unclear.

Adult↗
PubMed1995

NCAM polypeptides in heart development: association with Z discs of forms that contain the muscle-specific domain.

Previous studies of neural cell adhesion molecule (NCAM) cDNAs have revealed an alternatively spliced set of small exons (12A, 12B, 12C, and 12D) that encode a region in the extracellular portion of the molecule known as the muscle-specific domain (MSD). The entire MSD region can be expressed in skeletal muscle, heart, and skin; only exons 12A and 12D have been found in brain. These studies did not reveal which NCAM polypeptides contain the MSD region or the immunohistochemical distribution of these NCAM molecules. To address these questions, we prepared antibodies against the oligopeptides encoded by exons 12A and 12B and by exons 12C and 12D, and we used these antibodies to study the forms of NCAM containing the MSD region expressed during embryonic chicken heart development. These antibodies recognize certain forms of NCAM found in the heart, but they do not recognize brain NCAM. In the heart, each of the splice variants of NCAM (large cytoplasmic domain, small cytoplasmic domain, and small surface domain) that differ in their mode of attachment to the plasma membrane or in the size of their cytoplasmic domain is expressed in a form that contains and in a form that lacks the MSD region. No microheterogeneity is observed in the size of NCAM molecules containing the MSD region, even at the level of cyanogen bromide fragments, suggesting that exons 12A-D are expressed as a single unit. Depending on the site and the stage of development, the percent of NCAM molecules containing the MSD region can vary from nearly 0 to 100%. In general, this percentage increases during development. In immunohistochemical studies of hearts from stage 18 embryos, forms of NCAM containing the MSD region colocalized with Z discs. No other adhesion molecules were found in this distribution at this early stage of development. Studies on isolated cells in vitro demonstrate that the colocalization with Z discs of NCAM molecules containing the MSD region does not depend on cell-cell contact, and they raise the possibility that this form of NCAM is involved in cell-extracellular matrix interactions. The association of NCAM molecules containing the MSD region with Z discs suggests that this form of NCAM is involved in early myofibrillogenesis.

Alternative Splicing↗
PubMed1995

The interaction of the retina cell surface N-acetylgalactosaminylphosphotransferase with an endogenous proteoglycan ligand results in inhibition of cadherin-mediated adhesion.

We have previously shown that the binding to cells of a monoclonal antibody directed against the chick neural retina N-acetylgalactosaminylphosphotransferase (GalNAcPTase) results in inhibition of cadherin-mediated adhesion and neurite outgrowth. We hypothesized that the antibody mimics the action of an endogenous ligand. Chondroitin sulfate proteoglycans (CSPGs) are potential ligands because they inhibit adhesion and neurite outgrowth and are present in situ at barriers to neuronal growth. We therefore assayed purified CSPGs for their ability to inhibit homophilic cadherin-mediated adhesion and neurite outgrowth, as well as their ability to bind directly to the GalNAcPTase. A proteoglycan with a 250-kD core protein following removal of chondroitin sulfate chains (250-kD PG) inhibits cadherin-mediated adhesion and neurite outgrowth whether presented as the core protein or as a proteoglycan monomer bearing chondroitin sulfate. A proteoglycan with a 400-kD core protein is not inhibitory in either core protein or monomer form. Treatment of cells with phosphatidylinositol-specific phospholipase C, which removes cell surface GalNAcPTase, abolishes this inhibitory effect. Binding of the 250-kD core protein to cells is competed by the anti-GalNAcPTase antibody 1B11, suggesting that 1B11 and the 250-kD core protein bind to the same site or in close proximity. Moreover, soluble GalNAcPTase binds to the immobilized 250-kD core protein but not to the immobilized 400-kD core protein. Concomitant with inhibition of cadherin mediated adhesion, binding of the 250-kD core protein to the GalNAcPTase on cells results in the enhanced tyrosine phosphorylation of beta-catenin and the uncoupling of N-cadherin from its association with the cytoskeleton. Moreover, the 250-kD PG is present in embryonic chick retina and brain and is associated with the GalNAcPTase in situ. We conclude that the 250-kD PG is an endogenous ligand for the GalNAcPTase. Binding of the 250-kD PG to the GalNAcPTase initiates a signal cascade, involving the tyrosine phosphorylation of beta-catenin, which alters the association of cadherin with the actin-containing cytoskeleton and thereby inhibits adhesion and neurite outgrowth. Regulation of the temporal and spatial expression patterns of each member of the GalNacPTase/250-kD PG interactive pair may create opportunities for interaction that influence the course of development through effects on cadherin-based morphogenetic processes.

Animals↗
PubMed1994

Functional characterization of antiadhesion molecules.

Cytotactin, cytotactin binding (CTB) proteoglycan, and several other extracellular matrix (ECM) proteins and proteoglycans are described as antiadhesion molecules because they inhibit cell spreading and attachment to normally permissive ECM proteins. For cytotactin and CTB proteoglycan, this effect appears to be due to the binding of these proteins to their cell-surface receptors, which initiates a transmembrane signal that inhibits cell spreading. In contrast, the binding of fibronectin or laminin to its cell-surface receptors promotes cell spreading. Cell behavior may be regulated in a variety of systems by the interplay between these two opposing signals. For example, eosinophils on laminin spreading, form numerous foci containing filamentous actin, and remain viable in culture. In contrast, eosinophils on a mixture of laminin and cytotactin do not spread or form foci containing filamentous actin and the maintenance of viability is inhibited. In another system designed to model the immune surveillance of tumors, monocytes migrate in response to tumor necrosis factor through a gel comprised of a mixture of basement membrane proteins (Matrigel). Migration is blocked if the gel is coated with cytotactin. This result is of particular significance because cytotactin is expressed at high levels in the stroma of adult breast tissue surrounding tumors but only at low levels in normal breast tissue. These observations suggest that inflammation and the immune surveillance of tumors are among the processes regulated by cytotactin.

Animals↗
PubMed1992

Species diversity of neuronectin and cytotactin expression patterns in the vertebrate central nervous system.

Two extracellular matrix proteins of brain tissue, neuronectin (NEC1) and cytotactin (CT), are disulfide-bonded multimers of M(r) 180,000-250,000 subunits. The previously known distribution of these molecules is, however, very different. Human NEC1 is found throughout the white matter of rostral segments of the adult central nervous system (CNS) but not in rostral gray matter or in caudal CNS segments, including the cerebellum. In contrast, CT is absent or expressed at a low level in the adult chicken cerebrum but highly expressed in the cerebellum. Despite these differences in distribution, results obtained with antibodies that recognize NEC1 and CT in several vertebrate species indicate that these molecules are identical or at least closely related: (1) alpha NEC1 antibodies recognize proteins affinity-purified with CT-binding proteoglycan; (2) proteins recognized by alpha NEC1 and alpha CT antibodies in cells constitutively expressing the molecules, cells in which expression is induced by growth factors and phorbol ester and cells treated with tunicamycin (to block glycosylation) are identical in subunit composition and mobility on SDS gels; (3) the removal of NEC1 from culture supernatants by immunoprecipitation removes all molecules reactive with alpha CT antibodies and vice versa; (4) immunoblots of brain extracts with alpha NEC1 and alpha CT antibodies yield identical results. Having demonstrated the structural similarity between NEC1 and CT, we reexamined their distribution in the CNS. Surprisingly, the temporal and spatial distribution pattern of NEC1/CT varied greatly among species. Immunohistochemical and immunoblot experiments with adult human CNS tissues revealed significant levels of NEC1/CT in rostral but not caudal segments. In contrast, in cows and pigs the molecule is found throughout the CNS. Adult rat and mouse brains show regionally restricted expression of NEC1/CT in several areas of the cerebrum--distinct from those showing NEC1/CT in the human--and in the molecular layer of the cerebellum. Tests with fetal and newborn tissues revealed that CNS development in humans, cows and pigs is not accompanied by the marked decline in NEC1/CT levels or the changes in subunit composition found in the chicken CNS. The marked species diversity in temporospatial expression patterns suggests that intrinsic and/or extrinsic elements controlling the expression of NEC1/CT have diverged during vertebrate evolution.

Animals↗
PubMed1992

A human recombinant haemoglobin designed for use as a blood substitute.

The need to develop a blood substitute is now urgent because of the increasing concern over blood-transmitted viral and bacterial pathogens. Cell-free haemoglobin solutions and human haemoglobin synthesized in Escherichia coli and Saccharomyces cerevisiae have been investigated as potential oxygen-carrying substitutes for red blood cells. But these haemoglobins cannot be used as a blood substitute because (1) the oxygen affinity in the absence of 2,3-bisphosphoglycerate is too high to allow unloading of enough oxygen in the tissues, and (2) they dissociate into alpha beta dimers that are cleared rapidly by renal filtration, which can result in long-term kidney damage. We have produced a human haemoglobin using an expression vector containing one gene encoding a mutant beta-globin with decreased oxygen affinity and one duplicated, tandemly fused alpha-globin gene. Fusion of the two alpha-globin subunits increases the half-life of this haemoglobin molecule in vivo by preventing its dissociation into alpha beta dimers and therefore also eliminates renal toxicity.

Animals↗
PubMed1992

Patient and provider satisfaction with medical care.

BACKGROUND: This study compares patient and provider satisfaction with medical care and waiting time in a large family medicine residency program. Few published studies have dealt with both patient and provider perceptions. METHODS: Telephone interviews were conducted with 156 adult, English-speaking patients who were randomly selected from daily appointment schedules. The patients were asked to rate their satisfaction with 10 aspects of medical care and to estimate the length of time they waited to see their physicians. Sixty-five family health care providers responded to the same survey items through a self-administered questionnaire. RESULTS: In general, 97% of patients and 89% of providers were satisfied with the overall medical care provided at the family health center. Approximately 8% of patients and 22% of providers were dissatisfied with waiting time, and 11% of patients and nearly 60% of providers were dissatisfied with appointment scheduling. Patients' estimates of waiting time for care (mean = 16.1 minutes) were significantly shorter than providers' estimates (mean = 27.5 minutes). Patients who were dissatisfied with the length of waiting time estimated waiting 41.8 minutes, while satisfied patients estimated waiting 13.3 minutes (P less than .001). CONCLUSIONS: Family medicine patients reported higher levels of satisfaction with medical care than did providers. Both groups were the least satisfied with access to care.

Adolescent↗
PubMed1991

Risk factors for falls as a cause of hip fracture in women. The Northeast Hip Fracture Study Group.

BACKGROUND: Although even in the elderly most falls are not associated with fractures, over 90 percent of hip fractures are the result of a fall. Few studies have assessed whether the risk factors for falls are also important risk factors for hip fracture. METHODS: To examine the importance of risk factors for falls in the epidemiology of hip fracture, we performed a case-control study of 174 women (median age, 80 years) admitted with a first hip fracture to 1 of 30 hospitals in New York and Philadelphia. Controls, matched to the case patients according to age and hospital, were selected from general surgical and orthopedic surgical hospital services. Information was obtained by direct interview. RESULTS: As measured by the odds ratio, increased risks for hip fracture were associated with lower-limb dysfunction (odds ratio = 1.7; 95 percent confidence interval, 1.1 to 2.8), visual impairment (odds ratio = 5.1; 95 percent confidence interval, 1.9 to 13.9), previous stroke (odds ratio = 2.0; 95 percent confidence interval, 1.0 to 4.0), Parkinson's disease (odds ratio = 9.4; 95 percent confidence interval, 1.2 to 76.1), and use of long-acting barbiturates (odds ratio = 5.2; 95 percent confidence interval, 0.6 to 45.0). Of the controls, 44 (25 percent) had had a recent fall. The case patients were more likely than these controls to have fallen from a standing height or higher (odds ratio = 2.4; 95 percent confidence interval, 1.0 to 5.7). Of those with hip fracture the younger patients (less than 75 years old) were more likely than the older ones (greater than or equal to 75 years old) to have fallen on a hard surface (odds ratio = 1.9; 95 percent confidence interval, 1.04 to 3.7). CONCLUSIONS: A number of factors that have been identified as risk factors for falls are also associated with hip fracture, including lower-limb dysfunction, neurologic conditions, barbiturate use, and visual impairment. Given the prevalence of these problems among the elderly, who are at highest risk, programs to prevent hip fracture should include measures to prevent falls in addition to measures to slow bone loss.

Accidental Falls↗
PubMed1991

Expression of adhesion molecules during the formation and differentiation of the avian endocardial cushion tissue.

The expression of cytotactin, the cytotactin-binding (CTB) proteoglycan, and the neural cell adhesion molecule, N-CAM, was examined during the development of the avian endocardial cushion tissue (ECT). N-CAM was present in the cardiac mesoderm from its earliest time of development. At the time when endothelial cells converted to mesenchyme and began to migrate, they ceased their expression of N-CAM. Cytotactin and CTB proteoglycan were present in the cardiac jelly (into which the ECT cells migrate) in patterns that were correlated with cell migration. At early times of migration (stage 18), the region of the cardiac jelly near the endocardium contained cytotactin in the vicinity of the migrating cells. During later migration (stage 22), cytotactin remained associated with the leading zone of cell migration, but its expression began to decrease in areas where cells had accumulated. After ECT cell migration had ceased, cytotactin expression decreased, remaining high only in the peripheral portion of the aorticopulmonary septum and absent from its ridges. CTB proteoglycan was expressed during early migration at high levels in and adjacent to the myocardium. By stage 22, its distribution had become more uniform throughout the ECT regions and in the myocardium. The combined results of this study suggest that cytotactin, CTB proteoglycan, and N-CAM each play a distinct, critical role in pattern formation in the early heart.

Animals↗
PubMed1991

Synthesis of wild type and mutant human hemoglobins in Saccharomyces cerevisiae.

We have expressed human alpha and beta-globin cDNA clones from separate, synthetic galactose-regulated hybrid promoters contained on a single plasmid in Saccharomyces cerevisiae. Co-expression of the alpha and beta-globin chains in S. cerevisiae results in the assembly of these proteins into soluble tetrameric hemoglobin that accumulates to 3-5 percent of the total cell protein. Endogenously produced heme is incorporated into the tetramer and the protein produced is functionally and structurally indistinguishable from human Ao hemoglobin. This expression system has been used to produce both wild type hemoglobin and a low O2-affinity hemoglobin mutant that has oxygen binding and dissociation characteristics similar to human whole blood. The yeast expression system we describe may be suitable for the production of a recombinant hemoglobin based blood substitute as well as for detailed structure-activity studies of human hemoglobin.

Amino Acid Sequence↗
PubMed1991

The erythrocytes in paroxysmal nocturnal haemoglobinuria of intermediate sensitivity to complement lysis.

The sensitivity to lysis by complement of the erythrocytes of 56 patients with paroxysmal nocturnal haemoglobinuria (PNH) was compared to the membrane expression of decay accelerating factor (DAF, CD55), membrane inhibitor of reactive lysis (MIRL, CD59) and acetylcholinesterase (AChE). Most patients (36/50 72% in whom the analysis could be made) appeared to have erythrocytes of intermediate sensitivity to complement in the blood. These cells appeared as a discrete population of cells (PNH II cells), as a 'tail' of cells slightly less sensitive than the predominant PNH III cells (previously called PNH IIIb cells), or as a continuous spectrum of cells sensitive to complement. The PNH III cells totally lacked all three proteins (DAF, MIRL, AChE) by flow cytometric analysis whereas PNH I cells appeared to have normal or nearly normal amounts of each. The cells of intermediate sensitivity (PNH II) had coordinately decreased expression of all three proteins; the level of expression of DAF and MIRL paralleled the sensitivity of the cells to the haemolytic action of complement.

Acetylcholinesterase↗