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S Merritt

Publications and source records attributed to S Merritt.

At least 19 recordsLinked to original sources
PubMed2003

Comparison of water and lipid content measurements using diffuse optical spectroscopy and MRI in emulsion phantoms.

We present a quantitative comparison of lipid and water signals obtained from broadband Diffuse Optical Spectroscopy (DOS) and Magnetic Resonance Imaging (MRI). DOS and MRI measurements were performed on an identical set of emulsion phantoms that were composed of different water/soybean oil fractions. Absolute concentrations of water and lipid ranging from 35-94% and 63-6%, respectively were calculated from quantitative broadband near-infrared (NIR) absorption spectra (650-1000 nm). MR images of fat and water were separated using the three-point Dixon technique. DOS and MRI measured water and lipid were highly correlated (R(2) = 0.98 and R(2) = 0.99, respectively) suggesting that these techniques are complementary over a broad range of physiologically relevant water and lipid values. In addition, comparison of DOS derived concentrations to the MRI "gold standard" technique validates our quantitation approach and permits estimation of DOS accuracy and sensitivity in vivo.

Emulsions↗
PubMed2000

Identification of structural and functional domains in mixed lineage kinase dual leucine zipper-bearing kinase required for complex formation and stress-activated protein kinase activation.

Accumulating evidence suggests that mitogen-activated protein kinase signaling pathways form modular signaling complexes. Because the mixed lineage kinase dual leucine zipper-bearing kinase (DLK) is a large modular protein, structure-function analysis was undertaken to examine the role of DLK domains in macromolecular complex formation. DLK mutants were used to demonstrate that a DLK leucine zipper-leucine zipper interaction is necessary for DLK dimerization and to show that DLK dimerization mediated by the leucine zipper domain is prerequisite for DLK activity and subsequent activation of stress-activated protein kinase (SAPK). Heterologous mixed lineage kinase family members can be co-immunoprecipitated. However, the DLK leucine zipper domain interacted specifically only with the DLK leucine zipper domain; in contrast, DLK NH(2)-terminal region was sufficient to co-immunoprecipitate leucine zipper kinase and DLK. DLK has been shown to associate with the putative scaffold protein JIP1. This association occurred through the DLK NH(2)-terminal region and occurred independently of DLK catalytic activity. Although the DLK NH(2)-terminal region associated directly with JIP-1, this region did not interact directly with either DLK or leucine zipper kinase. Therefore, DLK may interact with heterologous mixed lineage kinase proteins via intermediary proteins. The NH(2)-terminal region of overexpressed DLK was required for activation of SAPK. These results provide evidence that protein complex formation is required for signal transduction from DLK to SAPK.

Adaptor Proteins, Signal Transducing↗
PubMed2000

The androgen receptor exon 1 trinucleotide repeat does not act as a modifier of the age of presentation in breast cancer.

The CAG repeat in exon 1 of the androgen receptor (AR) genes has been postulated as both a susceptibility allele and phenotypic modifier in BRCA1-associated breast cancers. We have analysed this repeat in a set of 178 breast cancer cases who have been selected only for age of presentation at 65 years or less. No effect of repeat length on age of presentation was found and there was no association between repeat length and family history. In combination with the data from other workers, our findings suggest that the androgen receptor repeat does not act as a modifier gene or susceptibility locus outside the context of the hereditary breast/ovarian cancer syndrome.

Adult↗
PubMed1998

cDNA cloning, in vitro expression, and biochemical characterization of cholinesterase 1 and cholinesterase 2 from amphioxus--comparison with cholinesterase 1 and cholinesterase 2 produced in vivo.

We have isolated cDNAs coding for the complete amino acid sequences of cholinesterase 1 (ChE1) and cholinesterase 2 (ChE2) from amphioxus. Both ChE transcripts have the characteristics of H-type catalytic subunits, which are inserted in the membrane via an ethanolamine-glycan-phosphatidylinositol anchor. The members of the catalytic triad of ChEs, the three pairs of cysteine residues involved in intrachain disulfide bonding, a cysteine near the carboxy terminal of both sequences, which could mediate interchain disulfide bonding, and 11 of the 14 aromatic amino acids that line the catalytic gorge of AChE are conserved. A remarkable difference between the two enzymes is in the region of the acyl-binding pocket, which plays an important role in determining substrate specificity in cholinesterases. ChE2 contains a sequence that resembles the acyl pocket of invertebrate ChE, while the acyl-binding site of ChE1 is novel. There are also differences between the two enzymes in the peripheral anionic site, which mediates inhibition by certain ligands. In vitro expression in COS-7 cells demonstrates that ChE2 hydrolyzes acetylthiocholine almost exclusively, while ChE1 hydrolyzes both acetylthiocholine and butyrylthiocholine. Both enzymes are inhibited comparably by BW284c51, but ChE1 is considerably more resistant to inhibition by propidium, ethopropazine, and eserine than is ChE2. Velocity sedimentation indicates that ChE1 and ChE2 are present as amphiphilic and nonamphiphilic G2 forms in vivo and in vitro. Another molecular form, which sediments at 17 S, is also present in vivo. Nondenaturing gel electrophoresis in conjunction with digestion by phosphatidylinositol-specific phospholipase C demonstrates that the vast majority of ChE1 and ChE2 is present as ethanolamine-glycan-phosphatidylinositol-anchored G2 forms in vivo. ChE1 also possesses an ethanolamine-glycan-phosphatidylinositol-anchor in vitro; however, ChE2 produced in vitro could not be detected on nondenaturing gels.

Acetylthiocholine↗
PubMed1998

Auto theft-related trauma.

OBJECTIVE: To determine the medical consequences and economic impact of caring for patients injured after motor vehicle crashes (MVC) involving stolen cars. METHODS: Presented is a case series of inpatients injured secondary to a MVC involving a stolen car from January of 1993 to December of 1994 and treated at a university Level I trauma center in Newark, New Jersey. During the time period of the study, 1,232 patients (either as the driver or passenger) were admitted after a MVC, 115 patients (8%) were identified as sustaining injuries secondary to a MVC involving a stolen car. Injuries after car theft represent 8% of all MVC-related admissions. Data collected included demographics, types of injuries, surgical intensive care unit and hospital lengths of stay, insurance status, hospital and physician charges, and ultimate outcome. RESULTS: Of the 84 men and 31 women, 66 were perpetrators, either as the driver (34) or passenger (32) of a stolen vehicle. Perpetrators were significantly younger and more likely to be male than victims. The overall mortality was 11%. An additional nine fatalities occurred at the scene of a MVC linked to a patient in this study. A high rate of speed and the presence of police pursuit seemed to be related to the severity of the crashes. The mean charges (hospital and physician) were over $34,000 per patient, and the aggregate charges for this cohort were greater than $3.6 million. Fifty-four percent of patients were uninsured. CONCLUSION: Injuries involving stolen cars are common in areas in which the activity has a high prevalence and can compose a significant percentage of a trauma center's MVC population. These data run contrary to the popular belief that auto theft is merely a crime against property, because the injuries sustained as a result of this criminal activity tended to be severe and were associated with a high fatality rate. Restricting police pursuit to only those instances in which other felonious activity is suspected may decrease the number of stolen car MVC. Additionally, the total amount of uncompensated care that these patients receive places another financial burden on limited health care and trauma center resources, which ultimately effects all other citizens.

Accidents, Traffic↗
PubMed1997

Low-energy impedance-compensating biphasic waveforms terminate ventricular fibrillation at high rates in victims of out-of-hospital cardiac arrest. LIFE Investigators.

INTRODUCTION: New automatic external defibrillators (AEDs), which are smaller, lighter, easier to use, and less costly make the goal of widespread AED deployment and early defibrillation for out-of-hospital cardiac arrest feasible. The objective of this study was to observe the performance of a low-energy impedance-compensating biphasic waveform in the out-of-hospital setting on 100 consecutive victims of sudden cardiac arrest. METHODS AND RESULTS: AEDs incorporating a 150-J impedance-compensating biphasic waveform were used by 12 EMS systems. Data were obtained from the AED PC card reporting system. Defibrillation was defined as conversion to an organized rhythm or to asystole. Endpoints included: defibrillation efficacy for ventricular fibrillation (VF); restoration of an organized rhythm at the time of patient transfer to an advanced life support (ALS) team or to the emergency department (ED); and time from AED power-on to first defibrillation. The AED correctly identified 44 of 100 patients presenting in VF as requiring a shock (100% sensitivity) and 56 of 100 patients not in VF as not requiring a shock (100% specificity). The time from 911 call to first shock delivery averaged 8.1 +/- 3.0 minutes. A single 150-J biphasic shock defibrillated the initial VF episode in 39 of 44 (89%) patients. The average time from power-on to first defibrillation was 25 +/- 17 seconds. At patient transfer to ALS or ED care, an organized rhythm was present in 34 of 44 (77%) patients presenting with VF. Asystole was present in 7 (16%) and VF in 3 (7%). CONCLUSIONS: Low-energy impedance-compensating biphasic waveforms terminate long-duration VF at high rates in out-of-hospital cardiac arrest. Use of this waveform allows AED device characteristics consistent with widespread AED deployment and early defibrillation.

Adult↗
PubMed1995

Tuberculin screening of trauma admissions at a university hospital. A preventive strategy.

OBJECTIVE: To determine the prevalence of tuberculosis (TB) infection in our trauma service population, namely, those patients who had positive Mantoux (purified protein derivative [PPD] [tuberculin]) tests. DESIGN: Prospective study. SETTING: Trauma service at a university hospital in Newark, NJ. PATIENTS AND METHODS: During a 9-month period, 110 admitted trauma patients underwent screening for TB. Of these patients, 20 had undergone recent PPD tests in the last 6 months, of which nine were positive. The remaining 90 patients underwent PPD and delayed-type hypersensitivity skin tests (anergy panel); five patients were unavailable for follow-up. The patients also answered questions regarding human immunodeficiency virus status, risk factors for TB infection, and clinical symptoms. RESULTS: The mean age of the study group was 34 years (age range, 13 to 69 years). Eighty-four percent of these patients were males who belonged to the high-risk socioeconomic, racial, and ethnic groups (poor, non-white). The tests for 15 patients (17%) were newly discovered to be positive for PPD. Eleven percent of the patients with negative PPD tests were anergic, thus raising the percentage of patients with positive PPD tests to 20%. The human immunodeficiency virus status was known in only 41% of the total patients. All patients with positive PPD tests had a chest x-ray film performed; of these patients, positive findings for TB were determined for one patient. Another patient had evidence of abdominal TB at laparotomy. All patients with positive PPD tests were given appointments in the pulmonary clinic for follow-up, and only three of 15 patients kept their appointments. CONCLUSIONS: Patients who were admitted to the trauma service were predominantly young males from high-risk groups with a high incidence of TB infection. Their admission to the trauma service was a unique opportunity for screening and implementing existing preventive programs.

Adult↗
PubMed1995

Falls: epidemiology and strategies for prevention.

Injury secondary to falls is a largely preventable public health problem. The records of 356 patients admitted following a fall to a level I trauma center over a 32-month period were reviewed to determine the epidemiology and to define possible prevention strategies. Falls constituted 9% of total trauma admissions during this time period and had a mortality of 11% (38 of 356). Two hundred ninety-seven falls were accidental, 36 were due to violent criminal behavior, 16 were from suicide attempts, and 7 were from house fires. Sixty-one children under the age of 13 fell; only one died. Falls out of windows accounted for 36% of these falls with over three-quarters of children falling from three stories or less. Elderly patients (age more than 64 years) accounted for only 44 (14%) of falls but over 50% of the deaths. This mortality rate occurred despite the fact that the majority of these falls were from relatively low heights. There were 224 adult falls (ages 18 to 64 years); 36% were occupation-related, and most were by construction workers, roofers, or painters. The remaining adult fall victims had a high rate of unemployment and alcohol and drug use. This study identified several groups where risk factors for falling permit targeted prevention strategies. A large percentage of children who fell were preschool males who fell from windows and this may be related to the lack of window guard legislation in our area.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidental Falls↗
PubMed1994

Transfusion of blood components to persons infected with human immunodeficiency virus type 1: relationship to opportunistic infection.

BACKGROUND: Although a recent study reported shorter survivals in human immunodeficiency virus type 1 (HIV-1)-infected patients who received transfusions, no study has analyzed the relationship in such patients between the frequency of opportunistic infection and transfusion. STUDY DESIGN AND METHODS: Records of 196 HIV-1-infected subjects with CD4 lymphocyte counts below 250 cells per mm3 were reviewed to determine if there were more opportunistic infections in patients who previously received transfusions than in those who received no transfusions. The decline in CD4 cells was also compared, and the frequency of transfusion reactions and red cell alloantibodies was assessed. RESULTS: The frequency of cytomegalovirus (CMV), wasting, and bacterial infections (p < 0.01), but not the frequency of Pneumocystis carinii pneumonia (PCP) (p > 0.2), was significantly increased in the patients who had previously received transfusions, and this effect was independent of CD4 count, race, or risk factor. The frequency of CMV infection, but not of PCP, was also related to the number of units of blood received (p < 0.01). Significant bacterial infections occurred primarily in persons with CMV infection, of whom there were more in the transfusion cohort. When analyzed separately in the group of patients without CMV infection, the frequency of bacterial infection was unrelated to transfusion. The death rate in those who received transfusions was also greater than that in patients who had never received a transfusion. None of the 130 patients who received red cell transfusions developed red cell alloantibodies. CONCLUSION: The higher incidence of certain infectious complications in HIV-1-infected patients who received transfusions indicates that the relationship of transfusion to virus activation in patients with acquired immunodeficiency syndrome and the potential benefits of modifying the preparation of blood components should be investigated further.

AIDS-Related Opportunistic Infections↗
PubMed1994

ThinPrep Processor. Clinical trials demonstrate an increased detection rate of abnormal cervical cytologic specimens.

The authors compared the accuracy of conventionally prepared smears and smears prepared by an automated, fluid-based, thin-layer processing device in the detection of cytologic abnormalities. A total of 3218 patients from five centers took part in this study, in which a single cervical sample was split into a matched pair. The conventional smear was made in the routine fashion; the remainder of the cells on the sampling device were rinsed into a transport-fixation fluid. A slide was then prepared from the solution using the thin-layer processor. Diagnostic findings identified on the two preparations were compared in a blinded fashion, and a discrepancy resolution procedure was used to eliminate screening differences. Overall, there was a high correlation in the diagnoses of the two methods. For low-grade or more severe disease, the thin-layer method resulted in a 13% increase in the rate of detection, as compared with the conventional Papanicolaou smear technique.

Cell Biology↗
PubMed1993

Measurement of functional ability in patients with coronary artery disease.

The purpose of this study was to examine measures of functional ability in a group (n = 60) of cardiac patients undergoing treadmill exercise tests. Functional ability was defined as the degree to which the individual is able to perform physical activity in the absence of symptoms. Instruments used were the Modified Harvard Alumni Scale (MHAS), the Symptom Scale (SS) comprised of the following subscales: angina (AS), shortness of breath (SOBS), and fatigue (FS); the overall Health Rating Index (OHRI); and the Goldman Specific Activity Scale (SAS). Concurrent validity was supported by the fact that the instruments were correlated with metabolic equivalents achieved on the treadmill. Correlations were: MHAS (r = .34, P < .01), SS (r = .67, p < .01), AS (r = .54, p < .01), SOBS (r = -.41, p < .05), FS (r = -.56, P < .001) and the OHRI (r = .45, p < .001). Reliability was determined using Cronbachs, alpha and were: SS = .92, AS = .87, SOBS = .86, FS = .85 and OHRI = .88. Findings support the need for testing and evaluation of instruments measuring functional ability in diverse cardiovascular populations.

Activities of Daily Living↗
PubMed1993

Vascular adventitial cell expression of collagen I messenger ribonucleic acid in anti-glomerular basement membrane antibody-induced crescentic nephritis in the rabbit. A cellular source for interstitial collagen synthesis in inflammatory renal disease.

BACKGROUND: Scarring in the interstitial compartment of the renal cortex heralds a poor prognosis in many forms of renal injury, however, the mechanism through which glomerular inflammation leads to interstitial scarring is not understood. In a model of anti-GBM disease in the rabbit, development of crescentic glomerulonephritis is associated with marked interstitial fibrosis and decreased renal function. We previously demonstrated that collagen accumulation in the model was preceded by increases in collagen I and IV mRNA and that these changes were primarily extraglomerular at early time points when inflammation was predominantly intraglomerular. In order to identify the cellular origins of extraglomerular collagen synthesis in this model, in situ hybridization using an alpha 2(I) procollagen probe was performed. EXPERIMENTAL DESIGN: A 602 bp rabbit alpha 2(I) procollagen cDNA was cloned using a PCR strategy and sequenced. The nucleotide sequence of the coding region was 94% identical with the human alpha 2(I) procollagen sequence. Northern blots were performed to define conditions of specific hybridization of the anti-sense riboprobe. Tissue sections from normal rabbit kidneys and from kidneys 4, 5, 7, 10 and 14 days after injection of anti-GBM antibody were hybridized with 35S-labeled sense and anti-sense riboprobes. Cells containing alpha 2(I) mRNA were identified by autoradiography and mRNA abundance was quantitated by grain density. RESULTS: No specific hybridization was detected with the sense probe at any time. alpha 2(I) mRNA was undetectable with the anti-sense probe in normal kidney sections. In contrast, the anti-sense probe hybridized specifically at all time points after induction of anti-GBM disease. In agreement with previous filter hybridization studies, on day 4, when inflammation was predominantly intraglomerular, cells in the periarterial adventitial compartment of renal cortex hybridized strongly. At later time points, labeling was also present in the interstitial spaces, the periglomerular region, in Bowman's space and in the glomerular tuft itself. CONCLUSIONS: We conclude that perivascular adventitial cells are among the first to respond to glomerular inflammation and represent a pool of cells that subsequently contribute to interstitial and glomerular scarring.

Amino Acid Sequence↗
PubMed1992

Epidemiology of thrombocytopenia in HIV infection.

Thrombocytopenia is a known complication of human immunodeficiency virus Type-1 (HIV-1) infection, and more data need to be collected on its frequency, severity, and clinical sequelae. We determined the frequency of thrombocytopenia and its relationship to other HIV infection characteristics from a review of records of 1004 HIV-infected patients attending two outpatient clinics in Washington, D.C. The self-reported sources of HIV-1 exposure were male homosexual activity (68%), bisexual activity (10%), heterosexual activity (6%), and intravenous drug use (15%). Fifty-nine percent of the individuals were white, 37% were black and 94% were male. Fifteen percent had AIDS. Thrombocytopenia occurred more frequently in subjects with AIDS (21.2%) than in HIV-infected individuals who did not fit clinical criteria for AIDS (9.2%) (p less than 0.001). Patients with few CD4-positive cells and an advanced stage of disease were more likely to have low platelet counts: 30% with an absolute CD4 cell count lower than 200/mm3 vs 8% with CD4 counts between 200 and 500 (p less than 0.00001), and 18.5% with Stage IV disease compared to 7.6% in Stage II (p less than 0.001) had platelet counts less than 150,000/mm3. Thrombocytopenia was more frequent in white males and older subjects. Although subjects infected by heterosexual exposure had a lower frequency of thrombocytopenia, intravenous drug users and homosexual men exhibited similar frequencies of thrombocytopenia. Of all subjects with platelet counts less than 50,000/mm3, 40% reported bleeding and 1 died of an intracranial hemorrhage. Thrombocytopenia occurs frequently in HIV-infected people, primarily in those with AIDS, low CD4 cell numbers, and advanced stages of diseases.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Analysis of T cells and major histocompatibility complex class I and class II mRNA and protein content and distribution in antiglomerular basement membrane disease in the rabbit.

The major interacting components of the immune system, major histocompatibility complex (MHC) class I and class II proteins and T cells were analyzed in a model of anti-GBM (glomerular basement membrane) disease in the rabbit that progresses to develop cellular crescents and glomerular and interstitial fibrosis. Class I and II mRNA and protein were measured in isolated glomeruli and whole renal cortex using cDNA probes and monoclonal antibodies. The distribution of T cells and class I and II proteins was assessed by immunofluorescence. Normal glomeruli contained no T cells and were class II negative. By day 4, glomeruli contained MHC class I and II mRNA and protein and class II positive T cells. Although some animals had T cells in the periglomerular area, these cells were class II negative. By day 7 periglomerular T cells were largely class II positive (activated) and there was increased MHC class I and II mRNA and protein in whole renal cortex. Later T cells accumulated in the tubulo-interstitial compartment, which became diffusely positive for MHC classes I and II, but to a variable extent in different animals. Those with high class II mRNA expression also had detectable T cell antigen receptor mRNA by Northern analysis. The authors conclude 1) in this model there was a close association between mRNA abundance and protein expression for both MHC classes I and II in glomeruli and renal cortex as a whole; 2) in this model of glomerular injury there are three phases of activation. The first phase takes place in the glomerulus and is associated with accumulation of activated T cells and MHC class I and II protein in the glomerulus. Phase 2 is associated with the accumulation of periglomerular T cells and their becoming class II positive. There is subsequent dissemination (phase 3) of activated T cells and accumulation of class I and II mRNA and protein throughout the interstitial compartment. This spacial progression of glomerulocentric inflammation is likely associated with degree of injury and permanent loss of renal function.

Animals↗
PubMed1991

Transforming growth factor-beta production in anti-glomerular basement membrane disease in the rabbit.

The purpose of this study was to assay for the presence of collagen synthesis stimulatory activity in the kidney during immune-induced renal injury that results in severe fibrosis in both glomerular and interstitial compartments. A model of antiglomerular basement (anti-GBM) disease in the rabbit was induced on day 0 by the injection of anti-GBM antibody and renal cortex tissues were then sampled at various time points. Only conditioned media prepared from diseased renal cortical samples showed collagen synthesis stimulatory activity when tested on rabbit mesangial cells. The activity had an estimated molecular weight range of 16 to 25 kd and was neutralized by antibody to transforming growth factor-beta (TGF-beta). A standard assay for TGF-beta using a mink lung epithelial cell line confirmed the increase in TGF-beta activity in conditioned media of diseased cortex from day 7 and day 14 animals, which was not significantly activated by previous acidification. This suggests that most of the TGF-beta present in renal conditioned media was in the active form. The increase in renal cortical secretion of active TGF-beta was accompanied by increases in renal cortical TGF-beta mRNA content on days 4 and 7 after induction, with subsequent return to control levels. A similar increase in TGF-beta activity was present in nonacidified conditioned media of purified glomeruli from diseased days 7 and 14 animals, which was also accompanied by significant increases in TGF-beta mRNA. However with acidification no significant differences were noted between control and diseased samples, suggesting the presence of substantial latent TGF-beta activity in control glomerular conditioned media. These same control-conditioned media contained inhibitor activity for added exogenous TGF-beta. These results support the conclusion that the association between increased TGF-beta secretion and increased renal cortical collagen synthesis in this model is consistent with a role for this cytokine in directing fibrogenesis in the kidney.

Animals↗
PubMed1986

Antibody-induced receptor loss. Different fates for asialoglycoproteins and the asialoglycoprotein receptor in HepG2 cells.

The human asialoglycoprotein receptor (ASGP-R) is a membrane glycoprotein which participates in receptor-mediated endocytosis and delivery of its ligands to lysosomes for degradation. In order to examine the pathways and mechanisms responsible for the turnover and degradation of the ASGP-R we have followed the fate of the ASGP-R in HepG2 cells during exposure to anti-receptor antibody as well as inhibitors of lysosomal processing and receptor recycling. Incubation of cells at 37 degrees C with anti-ASGP-R antibody results in the rapid (t 1/2 30 min) loss of mature 46,000-Da ASGP-R (control, t 1/2 20 h). This process requires whole IgG, since Fab fragments do not induce loss of receptor. Furthermore, this antibody-induced loss is specific, since incubation with antibody to the transferrin receptor does not alter cellular ASGP-R content. Of note, weak bases (e.g. primaquine) abrogate this antibody-induced loss of ASGP-R. Inhibitors of lysosomal proteases (EC64 and leupeptin) do not alter this antibody-mediated loss. Furthermore, this effect occurs at 18 degrees C, a temperature at which delivery of ligand to the lysosome is blocked. Thus, the present observations suggest a unique pathway for antibody-induced ASGP-R loss which is distinct from the pathway of lysosomal delivery of ligand.

Antigen-Antibody Complex↗