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Biomedical subjects

S A Cohen

Publications and source records attributed to S A Cohen.

At least 19 recordsLinked to original sources
PubMed2006

Onset and saturation of ion heating by odd-parity rotating magnetic fields in a field-reversed configuration.

Heating of figure-8 orbit ions by odd-parity rotating magnetic fields (RMF(O)) applied to an elongated field-reversed configuration (FRC) is investigated. The largest energy gain occurs at resonances (s congruent to omega(R)/omega) of the RMF(O) frequency, omega(R), with the figure-8 orbital frequency, omega, and is proportional to s2 for s-even resonances and to s for s-odd resonances. The threshold for the transition from regular to stochastic orbits explains both the onset and saturation of heating. The FRC magnetic geometry lowers the threshold for heating below that in the tokamak by an order of magnitude.

Journal Article↗
PubMed2005

A prospective assessment of mortality in chronic spinal cord injury.

STUDY DESIGN: Prospective mortality study. OBJECTIVE: To assess the relationship between comorbid medical conditions and other health-related factors to mortality in chronic spinal cord injury (SCI). SETTING: Boston, MA, USA. METHODS: Between 1994 and 2000, 361 males >/=1 year after injury completed a respiratory health questionnaire and underwent pulmonary function testing. Cause-specific mortality was assessed over a median of 55.6 months (range 0.33-74.4 months) through 12/31/2000 using the National Death Index. RESULTS: At entry, mean (+/-SD) age was 50.6+/-15.0 years (range 23-87) and years since injury was 17.5+/-12.8 years (range 1.0-56.5). Mortality was elevated (observed/expected deaths=37/25.1; SMR=1.47; 95% CI=1.04-2.03) compared to US rates. Risk factors for death were diabetes (RR=2.62; 95% CI=1.19-5.77), heart disease (RR=3.66; 95% CI=1.77-7.78), reduced pulmonary function, and smoking. The most common underlying and contributing causes of death were diseases of the circulatory system (ICD-9 390-459) in 40%, and of the respiratory system in 24% (ICD-9 460-519). CONCLUSIONS: These results suggest that much of the excess mortality in chronic SCI is related to potentially treatable factors. Recognition and treatment of cardiovascular disease, diabetes, and lung disease, together with smoking cessation may substantially reduce mortality in chronic SCI.

Adult↗
PubMed2002

Benign metastasizing leiomyoma.

Benign metastasizing leiomyoma is a rare clinical entity that has been described in several previous reports. Although the exact pathophysiology of the disease is unknown, two predominant theories exist: (1) metastasis from an existing leiomyoma (commonly seen with uterine leiomyoma) or (2) multicentric leiomyomatous growths rather than actual metastases. We present an interesting case in which several elements of the patient's history complicated the differential diagnosis.

Adrenal Gland Neoplasms↗
PubMed2001

Homogeneous preparation of fluorescent-derivatized insulin and its application to competitive chromatographic immunoassays.

A homogeneously labeled insulin sample was prepared using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) as the fluorescent-labeling reagent, and this was successfully applied to a chromatographic immunoassay. This labeled insulin was prepared by tagging all the three amino groups with AQC. Both CE and chromatographic immunoassay experiments indicated that the prepared insulin still kept its immunoaffinity to its antibody. It was observed that appropriate concentrations of acetonitrile (ACN) were efficient in lowering the quenching of the fluorescent signal of tagged insulin, in keeping the dilute, tagged insulin in solution, and in improving its peak shape during a chromatographic immunoassay. The tagged insulin was found to be 20-400 times more sensitive than native insulin detected under ultraviolet detection conditions. A competitive chromatographic immunoassay system was set up and calibrated. The system was used for analyses of an insulin-spiked urine sample, with a 96% recovery obtained.

Acetonitriles↗
PubMed2001

Homogeneous fluorescent derivatization of large proteins.

A method of homogeneously derivatizing large proteins for highly sensitive analysis is described. Homogeneity of the derivative was realized by tagging all the free amino groups of proteins. With this method, alpha-chymotrypsinogen A, ovalbumin and bovine serum albumin were derivatized with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC). Prior to the derivatization, all the proteins were reduced and alkylated. After reacting the resulting unfolded proteins with excessive amounts of AQC, the samples were analyzed with matrix assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS) to determine the derivatization degree. The results indicated that all three proteins had been, or had almost been, fully derivatized. HPLC and CE were used for characterizing these protein derivatives. Under the optimized fluorescence detection conditions, the detectability of the tagged proteins was 2400-6200 times better than that detected at UV 280 nm, 170-300 times better than detected at UV 214 nm, and 150-420 times better than measured with their native fluorescence.

Electrophoresis, Capillary↗
PubMed2001

Femtomole peptide mapping by derivatization, high-performance liquid chromatography, and fluorescence detection.

A highly sensitive peptide mapping method using derivatization and fluorescence detection is described. Bovine cytochrome c was digested using a buffer compatible with the derivatization that followed. The derivatization was performed with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate. The peptide mapping of the tagged digest was conducted with both HPLC and capillary LC (CLC) systems. A capillary LC-electrospray ionization mass spectrometer (MS) was set up for measuring the molecular weights of the tagged peptides. Optimization was made of the conditions used for digestion, derivatization, and mapping. MS measurements of the tagged peptides suggested that there was only one derivatization product produced from all peptides (except one) and that all the identified peptides were fully tagged. Peptide mapping of the tagged digest reviews a larger number of peptides, covering almost the entire sequence. Peptide mapping of a 20 fmol amount of tagged digest was readily performed with the CLC system. By using derivatization and fluorescence detection, the sensitivity of peptide mapping could be improved 2000 times compared to that observed with uv detection of untagged peptides.

Amino Acid Sequence↗
PubMed2001

Voltage-gated sodium channel (SkM1) content in dystrophin-deficient muscle.

The membrane cytoskeleton is increasingly considered as both an anchor and a functional modulator for ion channels. The cytoskeletal disruptions that occur in the absence of dystrophin led us to investigate the voltage-gated sodium channel (SkM1) content in the extensor digitorum longus (EDL) muscle of the dystrophin-deficient mdx mouse. Levels of SkM1 mRNA were determined by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). A C-terminal portion of the mouse-specific SkM1 alpha-subunit cDNA (mScn4a) was identified first. SkM1 mRNA levels were as abundant in mdx as in normal muscle, thus suggesting that the transcriptional rate of SkM1 remains unchanged in mdx muscle. However, SkMI density in the extrajunctional sarcolemma was shown to be significantly reduced in mdx muscle, using confocal immunofluorescence image analysis. This decrease was found to be associated with a reduction in the number of SkM1-rich fast-twitch IIb fibres in mdx muscle. In addition, lowered SkM1 sarcolemmal labelling was found in all mdx fibres regardless of their metabolic type. These results suggest the existence of a perturbation of SkM1 anchorage to the plasma membrane. Such an alteration is likely to be related to the 50% decrease in mdx muscle of the dystrophin-associated syntrophins, which are presumed to be involved in SkM1 anchorage. However, the moderate reduction in SkM1 density (-12.7%) observed in mdx muscle argues in favour of a non-exclusive role of syntrophins in SkM1 anchorage and suggests that other membrane-associated proteins are probably also involved.

Animals↗
PubMed2001

Compartment syndrome associated with lithotomy position and intermittent compression stockings.

BACKGROUND: Compartment syndrome is a condition in which increased tissue pressure within a limited tissue space compromises the circulation and function of the contents of the space. CASE: A 43-year-old black woman, para 3, had repair of a recurrent vesicovaginal fistula. She was placed in a low lithotomy position with thigh length sequential compression sleeves. The procedure lasted more than 5 hours. On postoperative day 1, she complained of pain in her right leg and foot. Compartment syndrome was diagnosed and emergency fasciotomy was done. CONCLUSION: Gynecologists should be aware of the possibility of compartment syndrome during prolonged procedures with patients in the lithotomy position. Concomitant intermittent compression sleeves might further increase the risk. Early diagnosis and treatment of compression syndrome are essential to minimize long-term neurovascular morbidity.

Adult↗
PubMed2001

Endoscopic retrograde cholangiopancreatography and the pancreas: when and why?

Historically, endoscopic retrograde cholangeopancreatography (ERCP) has played a unique role as a diagnostic and therapeutic modality for diseases of the pancreas. Despite the advent of new imaging techniques, ERCP continues to play a central role in the evaluation and treatment of pancreatitis of various causes. Endoscopic cholangiography and stenting remain mainstays in the palliation of inoperable obstructive jaundice in patients with cancer of the pancreas.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed2001

Pancreas divisum: endoscopic therapy.

Pancreas divisum is a common congenital variation that can be associated with pancreatic disease. Symptomatic patients with divisum must be classified according to clinical presentation and morphologic findings. Response to endoscopic therapy is best in patients with ARP, of whom 75% benefit. Results in patients with chronic pancreatitis and pain but without objective pancreatitis are mixed, and patients should be carefully selected.

Congenital Abnormalities↗
PubMed2001

Epithelioid hemangioendothelioma of the maxilla: case report and review of literature.

Epithelioid Hemangioendothelioma (EH) is a rare, low-grade malignant vascular tumor, first defined as a soft tissue tumor by Enzinger and Weiss in 1982. The tumor was later reported in virtually all sites, including liver, lung, brain, and bone. The epithelioid neoplastic cells are of endothelial origin, staining positive for Factor VIII and CD-34. In our review of EH of bone medline literature, and including the present case report, a total of 73 cases were found. Forty-one (56%) patients had multifocal bone involvement and thirty-two (44%) patients had solitary EH of bone. Resection was the primary recommended treatment. Visceral involvement appears to affect prognosis and survival adversely. We report a case of EH of the maxilla, which occurred in a 32-year-old male.

Adult↗
PubMed2000

A carboxy-terminal alpha-helical segment in the rat skeletal muscle voltage-dependent Na+ channel is responsible for its interaction with the amino-terminus.

Cytoplasmic segments of the adult rat skeletal muscle sodium channel alpha-subunit (rSkM1) comprise a major portion (approximately 40%) of the total protein and are involved in channel functions both general, such as inactivation, and isoform-specific, for example, protein kinase A modulation. Far ultraviolet circular dichroism measurements of synthetic peptides and overexpressed fusion proteins containing individual channel cytoplasmic segments suggest that cytoplasmic domains of rSkM1 contain ordered secondary structures even in the absence of adjoining transmembrane segments. Intrinsic fluorescence experiments with a nested set of carboxy-terminal deletion proteins confirm a specific interaction between the channel's amino- and carboxy-termini and identify residues 1716-1737 in the carboxy-terminus as the region that binds to the amino-terminus. Circular dichroism measurements suggest that this same region is organized as an alpha-helix and that electrostatic forces may contribute to this association. The interaction of the amino- and carboxy-termini is not accompanied by secondary structure changes detectable by circular dichroism spectroscopy, but a decrease in intrinsic fluorescence indicates that this association is accompanied by a change in the environment of Trp1617.

Animals↗
PubMed2000

Potential future clinical applications for the GPIIb/IIIa antagonist, abciximab in thrombosis, vascular and oncological indications.

Abciximab (ReoPro) is a mouse-human chimeric monoclonal antibody Fab fragment of the parent murine monoclonal antibody 7E3, and was the first of these agents approved for use as adjunct therapy for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention (PCI). Abciximab binds with high avidity to both the non-activated and activated form of the GPIIb/IIIa receptor of platelets, the major adhesion receptor involved in aggregation. Additional cardiovascular indications for abciximab are unstable angina, carotid stenting, ischemic stroke and peripheral vascular diseases. Abciximab also interacts with two other integrin receptors; the a av b b3 receptor, which is present in low numbers on platelets but in high density on activated endothelial and smooth muscle cells, and a aMb b2 integrin which is present on activated leukocytes. Cell types that express integrins GPIIb/IIIa and a av b b3 such as platelets, endothelial and tumor cells have been implicated in angiogenesis, tumor growth and metastasis. Since abciximab interacts with high avidity to integrins GPIIb/IIIa and a av b b3, it is reasonable to assume that it may possess anti-angiogenic properties in angiogenesis-related diseases, as well as anti-metastastatic properties in case of disseminating tumors expressing the target integrin receptors.

Abciximab↗
PubMed1999

Decreased sodium and increased transient outward potassium currents in iron-loaded cardiac myocytes. Implications for the arrhythmogenesis of human siderotic heart disease.

BACKGROUND: Patients with chronic iron overload may develop a cardiomyopathy manifested by ventricular arrhythmias and heart failure. We hypothesized that iron-loaded cardiomyocytes may have abnormal excitability. METHODS AND RESULTS: We examined a new model of human iron overload, the Mongolian gerbil given repeated injections of iron dextran. In ventricular myocytes, we measured iron concentration and distribution, action potential, sodium and potassium currents, and sodium channel protein. We showed for the first time that (1) the iron content of gerbil ventricular cardiomyocytes was increased to amounts similar to those of patients with iron-induced cardiomyopathy; (2) the overshoot and duration of the cardiac action potential decreased; (3) sodium current was reduced, steady-state inactivation was enhanced, and single-channel currents were unchanged; and (4) transient outward potassium current was increased, but inwardly rectifying potassium current was unchanged. Neonatal rat cardiomyocytes incubated with iron for 1 to 3 days showed similar changes, and levels of cardiac sodium channel proteins were unchanged. CONCLUSIONS: Abnormal excitability and heterogeneous cardiac iron deposition may cause the arrhythmogenesis of human siderotic heart disease.

Action Potentials↗
PubMed1999

AsGM1+ NK cells prevent metastasis of invading LD-MCA-38 tumor cells in the nude mouse.

BACKGROUND: Although the liver is a potent tumor cell killing organ it is frequently the site of lethal metastases often signifying the endstage for patients with colorectal cancers. Enhancing hepatic-associated immunity remains elusive until the interactions among hepatic nonparenchymal cells (NPC) are deciphered. We sought to modulate the cellular components of the hepatic immune system of mice with anti-NK and anti-T-cell-neutralizing antibodies in order to determine the cell type most efficacious in preventing liver metastasis. MATERIALS AND METHODS: Liver-derived murine colon adenocarcinoma (LD-MCA-38) cells were injected into the ileocolic vein (ICV) of immunocompetent and immunodeficient C57BL/6 mice. Mice were pretreated 1 day prior to tumor cell injection with one of three antibodies: anti-AsGM1, Anti-NK1.1, or Anti-Thy1.2. On Day 21 laparotomy was performed to determine the extent of hepatic tumor foci. The number of hepatic tumor foci was recorded and compared by the Wilcoxon rank sum test. RESULTS: Mice pretreated with anti-AsGM1 or Anti-NK1.1 developed a massive increase in the number of hepatic tumor foci and decreased survival compared to the control treated mice. Pretreatment with anti-Thy1.2 antibody resulted in a significant decrease in the number of hepatic tumor foci. LD-MCA-38 tumor cells were unable to colonize the liver of C57BL/6 athymic nude mice; however, anti-AsGM1 antibody abolished this antimetastatic effect. There was no difference in the extent of hepatic metastasis and survival between immunodeficient C57BL/6 bg/bg and their conventional littermates bg/+. CONCLUSION: AsGM1+ NK cells exhibit a significant antitumor response in the absence of T-cells. The concept of stimulating NK cell activity and suppressing T-cell function may enhance liver-associated immunity and serve as a deterrent for blood-borne tumor cells metastasizing to the liver.

Adenocarcinoma↗