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Biomedical subjects

J Weissman

Publications and source records attributed to J Weissman.

At least 19 recordsLinked to original sources
PubMed2003

Use of basiliximab with mycophenolate mofetil in kidney transplantation.

INTRODUCTION: Randomized, placebo-controlled studies have determined that administration of basiliximab (chimeric IL-2 receptor antagonist) decreases the acute rejection rate in kidney transplantation when used in combination with cyclosporine, azathioprine, and steroids. We report our experience using basiliximab with mycophenolate mofetil, a calcineurin inhibitor, and steroids in kidney transplantation. METHODS: We retrospectively analyzed 127 patients who received their first kidney transplant between September 1, 1998, and December 30, 2000, including 59 who received basiliximab (22 living and 37 cadaveric donor recipients) and the 68 that did not receive this antibody (31 living and 37 cadaveric donor recipients). The groups were demographically comparable for risk factors such as race, peak of panel-reactive antibody, delayed graft function, donor age, and cold ischemia time. The analysis assessed serum creatinine levels, acute rejection, cytomegalovirus infection, and posttransplant lymphoproliferative disease incidence as well as patient and graft survival at 6 months. RESULTS: Serum creatinine levels were 3 +/- 3.1 and 2.6 +/- 2.5 mg/dL (P =.346) at discharge, 1.5 +/- 0.6 and 1.7 +/- 1.1 mg/dL (P =.098) at 1 month, and 1.5 +/- 0.7 and 1.6 +/- 0.7 mg/dL (P =.454) at 6 months posttransplantation for patients treated with versus without basiliximab, respectively. Only one episode of acute rejection was seen among patients treated with basiliximab within 1 month posttransplantation versus three episodes among patients treated without basiliximab (P =.382). Three patients (5.1%) treated with basiliximab and two patients (2.9%) treated without basiliximab developed acute rejection within 6 months posttransplantation (P =.536). Patient and graft survivals at 6 months posttransplantation were not significantly different between patients treated with versus without basiliximab (100% and 100% versus 100% and 98.3%, respectively). There was no increased incidence of cytomegalovirus infection with the use of basiliximab (5.1% vs 5.9%, P =.844). There was only one case of posttransplant lymphoproliferative disease within 6 months posttransplantation in a patient treated without basiliximab. CONCLUSION: These data suggest that the routine addition of basiliximab to a mycophenolate mofetil-based regimens does not appear to be warranted. A larger prospective randomized study with longer follow-up is needed to confirm these results.

Adult↗
PubMed2001

The Sar1 GTPase coordinates biosynthetic cargo selection with endoplasmic reticulum export site assembly.

Cargo selection and export from the endoplasmic reticulum is mediated by the COPII coat machinery that includes the small GTPase Sar1 and the Sec23/24 and Sec13/31 complexes. We have analyzed the sequential events regulated by purified Sar1 and COPII coat complexes during synchronized export of cargo from the ER in vitro. We find that activation of Sar1 alone, in the absence of other cytosolic components, leads to the formation of ER-derived tubular domains that resemble ER transitional elements that initiate cargo selection. These Sar1-generated tubular domains were shown to be transient, functional intermediates in ER to Golgi transport in vitro. By following cargo export in live cells, we show that ER export in vivo is also characterized by the formation of dynamic tubular structures. Our results demonstrate an unanticipated and novel role for Sar1 in linking cargo selection with ER morphogenesis through the generation of transitional tubular ER export sites.

Animals↗
PubMed2001

Prevalence of short-segment Barrett's epithelium.

BACKGROUND/AIMS: The incidence of adenocarcinoma of the oesophagus has increased. Its major risk factor is Barrett's epithelium of which the sine qua non is microscopically diagnosed intestinal metaplasia. Short segment Barrett's epithelium may often be overlooked during routine endoscopy. In routine biopsies taken from normal-appearing mucosa of the distal oesophagus, the reported rates of short segment Barrett's epithelium in the distal oesophagus reached 36%. We compared these rates with the results obtained in a community hospital in Israel. METHODS: Consecutive patients undergoing oesophagogastroduodenoscopy were enrolled. Biopsy specimens taken from cardia, oesophagogastric junction and 2 cm above the oesophagogastric junction were stained with haematoxylin & eosin and Alcian blue. RESULTS: There were 112 study patients (mean age +/- SD 48. 9+/-18.3 years, 51.8% males). Nine (8.04%) patients had intestinal metaplasia (according to specimen from 2 cm above oesophagogastric junction), and symptoms of gastro-oesophageal reflux were found in only four (44.4%) of them. Of these nine patients, six (6.66%) had normal-appearing mucosa and three (3.33%) had macroscopic Barrett's epithelium. Alcian blue staining revealed two patients with intestinal metaplasia that haematoxylin & eosin staining had missed. CONCLUSION: We found an 8% prevalence of intestinal metaplasia compared to 18-36% reported in the literature. We also determined that the added advantage of routine biopsy was 5.4%.

Adenocarcinoma↗
PubMed2000

Stage-specific assays to study biosynthetic cargo selection and role of SNAREs in export from the endoplasmic reticulum and delivery to the Golgi.

To analyze the role of coat protein type II (COPII) coat components and targeting and fusion factors in selective export from the endoplasmic reticulum (ER) and transport to the Golgi, we have developed three novel, stage-specific assays. Cargo selection can be measured using a "stage 1 cargo capture assay," in which ER microsomes are incubated in the presence of glutathione S-transferase (GST)-tagged Sar1 GTPase and purified Sec23/24 components to follow recruitment of biosynthetic cargo to prebudding complexes. This cargo recruitment assay can be followed by two sequential assays that measure separately the budding of COPII-coated vesicles from ER microsomes (stage 2) and, finally, delivery of cargo-containing vesicles to the Golgi (stage 3). We show how these assays provide a means to identify the snap receptor (SNARE) protein rBet1 as an essential component that is not required for vesicle formation, but is required for vesicle targeting and fusion during ER-to-Golgi transport. In general, these assays provide an approach to characterize the biochemical basis for the recruitment of a wide variety of biosynthetic cargo proteins to COPII vesicles and the role of different transport components in the early secretory pathway of mammalian cells.

Biological Transport↗
PubMed1999

Origin of the West Nile virus responsible for an outbreak of encephalitis in the northeastern United States.

In late summer 1999, an outbreak of human encephalitis occurred in the northeastern United States that was concurrent with extensive mortality in crows (Corvus species) as well as the deaths of several exotic birds at a zoological park in the same area. Complete genome sequencing of a flavivirus isolated from the brain of a dead Chilean flamingo (Phoenicopterus chilensis), together with partial sequence analysis of envelope glycoprotein (E-glycoprotein) genes amplified from several other species including mosquitoes and two fatal human cases, revealed that West Nile (WN) virus circulated in natural transmission cycles and was responsible for the human disease. Antigenic mapping with E-glycoprotein-specific monoclonal antibodies and E-glycoprotein phylogenetic analysis confirmed these viruses as WN. This North American WN virus was most closely related to a WN virus isolated from a dead goose in Israel in 1998.

Amino Acid Sequence↗
PubMed1998

Cargo selection by the COPII budding machinery during export from the ER.

Cargo is selectively exported from the ER in COPII vesicles. To analyze the role of COPII in selective transport from the ER, we have purified components of the mammalian COPII complex from rat liver cytosol and then analyzed their role in cargo selection and ER export. The purified mammalian Sec23-24 complex is composed of an 85-kD (Sec23) protein and a 120-kD (Sec24) protein. Although the Sec23-24 complex or the monomeric Sec23 subunit were found to be the minimal cytosolic components recruited to membranes after the activation of Sar1, the addition of the mammalian Sec13-31 complex is required to complete budding. To define possible protein interactions between cargo and coat components, we recruited either glutathione-S-transferase (GST)-tagged Sar1 or GST- Sec23 to ER microsomes. Subsequently, we solubilized and reisolated the tagged subunits using glutathione-Sepharose beads to probe for interactions with cargo. We find that activated Sar1 in combination with either Sec23 or the Sec23-24 complex is necessary and sufficient to recover with high efficiency the type 1 transmembrane cargo protein vesicular stomatitis virus glycoprotein in a detergent-soluble prebudding protein complex that excludes ER resident proteins. Supplementing these minimal cargo recruitment conditions with the mammalian Sec13-31 complex leads to export of the selected cargo into COPII vesicles. The ability of cargo to interact with a partial COPII coat demonstrates that these proteins initiate cargo sorting on the ER membrane before budding and establishes the role of GTPase-dependent coat recruitment in cargo selection.

Animals↗
PubMed1998

Relationship between health status and utility measures in older claudicants.

The purpose of this study was to examine the relationship between health status and health utility measures in 34 older claudicants and to determine which attributes of health status were significant predictors of health state valuation/preference. The MOS SF-36 was used to assess health status and the rating scale and multiattribute Health Utility Index (HUI) were used to assess utility scores. With regard to health status, the bodily pain and physical functioning subscales contributed the most to reductions in quality of life (QoL) with mean subscale scores substantially lower than reported population norms. Patients rated their health status approximately one-third below a state of perfect health on both utility measures. Moderate correlations were observed between the MOS SF-36 subscale scores and the HUI and rating scale scores. In multivariable regression models, physical functioning and mental health were the best predictors of HUI scores, whereas general health and vitality were the best predictors of rating scale scores. Approximately 50% of the variance in utility scores was explained by these attributes. This study provides further documentation that bodily pain and reductions in physical function contribute to reductions in QoL in older patients with intermittent claudication. Other attributes of health status, however, notably psychological distress, were predictive of patients' preference for health states. Recognized constructs of physical and mental health explained the substantial variation in the utility/preference assessment in this population. Furthermore, these data are consistent with those reported in the Dutch Iliac Stent Trial.

Aged↗
PubMed1997

An impact evaluation of project SNAPP: an AIDS and pregnancy prevention middle school program.

OBJECTIVES: A theory-based curriculum designed to delay the onset of intercourse and increase use of condoms was implemented in the classrooms of six Los Angeles middle schools. METHODS: The curriculum activities were very interactive, emphasized skill building, and were implemented by well trained peer educators, including young HIV-positive males and teen mothers. To evaluate the impact of the curriculum, 102 classrooms of students were randomly assigned to receive either the existing curriculum or the existing curriculum plus the intervention curriculum. Students completed confidential questionnaires before program implementation, five months later, and 17 months later. A total of 1,657 students completed both the baseline and 17-month follow-up questionnaires. RESULTS: Analyses of these data revealed that the curriculum significantly increased knowledge, significantly improved only two out of 21 attitudes or beliefs, and did not significantly change sexual or contraceptive behaviors. CONCLUSIONS: Well implemented programs that are based on upon theory, use interactive activities, and utilize well-trained peer educators do not always change important sexual attitudes and behaviors among middle school youth.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Uncompensated hospital care. Will it be there if we need it?

The debates over health care system reform continue, but they rarely mention the enduring need for free or reduced-cost hospital care as a safety net for uninsured and underinsured individuals. Policy changes on numerous fronts threaten the ability or willingness of hospitals to provide uncompensated care. These changes include the decline of Hill-Burton funds, the closings or mergers of not-for-profit and public hospitals, the dominance of competitive forces, and the redirection of funds intended for disproportionate share hospitals or uncompensated pools. Federal and state governments lack coordinated approaches toward uncompensated care, and health system reforms may not have the expected effects on reducing hospitals' burden of paying for services to indigents. Furthermore, measurement of uncompensated care is inconsistent. In light of the persistent growth in the number of persons with inadequate health insurance coverage and the central role that uncompensated care will continue to play in ensuring access to care for the poor and uninsured, these policies need to be reexamined. Guidelines for policy based on past experience are presented herein.

Cost Allocation↗
PubMed1995

Skull base tumor volume and surgical margins: a pilot study.

The relationship between preoperative assessment of tumor volume and oncologic adequacy of surgical margins was studied retrospectively. Our hypothesis was that the risk of inadequate, or positive, margins would rise with increasing tumor volume and that this would adversely affect survival. We anticipated that limitations of surgical approaches used until 1988 would be reflected in an increasing proportion of positive margins with increasing tumor volume. We conducted a pilot study of 25 patients with malignant tumors of the anterolateral cranial base operated on at the University of Pittsburgh Center for Cranial Base Surgery between 1987 and 1988. Preoperative computed tomography assessment of tumor volume was performed in all patients, and correlation between tumor volume, surgical margins, and survival was examined. Follow-up interval averaged 31.7 months. Twelve histologic tumor types were represented, with squamous cell carcinoma the most common (eight patients [32%]). Tumor volume ranged from 0.9 to 390 cc, with a median of 48 cc. Based on a median split of tumor volumes, patients were classified as high volume (more than 48 cc) or low volume (less than 48 cc). Of patients in the high volume group, 92% were found to have positive surgical margins, whereas only 50% of patients in the low volume group had positive margins. Analysis of the effect of tumor volume and surgical margins on survival was limited by sample size constraints, but both high-tumor volume and positive margins tended to reduce patient survival (0.07 < p 0.10).

Journal Article↗
PubMed1995

Iodoacetate-induced skeletal muscle contracture: changes in ADP, calcium, phosphate, and pH.

The effects of iodoacetic acid (IAA) and ischemic contraction were studied in rat extensor digitorum longus muscles. Ischemic stimulation of IAA-treated muscles produced contracture. We measured total muscle water content, distribution of water between intracellular and extracellular spaces, creatine concentration ([Cr]), creatine phosphate concentration ([PCr]), [ATP], [Pi], intracellular pH, and intracellular Ca2+ concentration ([Ca2+]i) at the onset of contracture. [ADP] was calculated from the equilibrium of the creatine kinase reaction using the measured values of [ATP], [PCr], [Cr], and pH. At the onset of contracture there was a 75% reduction of [PCr], a 12-fold increase in [ADP], and an 11-fold increase in [Ca2+]i compared with unstimulated IAA-treated muscles. [ATP] was not depleted at contracture compared with unstimulated IAA-treated muscles, and [Pi] increased less in muscles at contracture compared with stimulated control muscles. The persistent tension in contractures probably resulted from increased [Ca2+]i combined with increased myofibrillar Ca2+ sensitivity due to elevated [ADP] and relatively reduced intracellular acidification and [Pi].

Adenosine Diphosphate↗
PubMed1995

Experimental acidemia and muscle cell pH in chronic acidosis and renal failure.

To test whether muscle intracellular pH (pHi) decreases when extracellular pH falls, 31P-nuclear magnetic resonance was utilized in rats made acidotic by infusion of HCl, gavage-feeding NH4Cl, or induction of chronic renal failure (CRF). A 2- or 4-h HCl infusion did not lower muscle pHi, even though serum bicarbonate fell to 5 mM. With chronic acidemia, blood pH was 7.15 +/- 0.01 vs. 7.38 +/- 0.02 in pair-fed controls, and muscle pHi was 7.09 +/- 0.01 and 7.14 +/- 0.02, respectively (P < 0.01). pHi in muscle of CRF rats (7.16 +/- 0.01) did not differ from sham-operated, pair-fed controls (7.19 +/- 0.01) despite a blood pH of 7.23 +/- 0.05 in CRF vs. 7.39 +/- 0.01 in controls. Because ion transport is abnormal in CRF, we examined whether recovery of pHi is impaired when muscles of six CRF and control rats were exercised to tetany by stimulation of the sciatic nerve. Neither pHi nor the recovery of pHi differed between CRF and control rats. We conclude that pHi is maintained in muscle in uremia and that signals other than changing pHi must be necessary to disrupt metabolism.

Acidosis↗
PubMed1994

Utilization of formal and informal home care by AIDS patients in Boston: a comparison of intravenous drug users and homosexual males.

The assumption that intravenous (i.v.) drug users have weaker informal support networks than homosexual men has led to opposing policy recommendations: one emphasizes outreach and more formal (paid) home care for i.v. drug users, whereas the other maintains that formal home care programs are less effective for this risk group due to the lack of informal (unpaid) caregivers to coordinate efforts. Data from interviews with a sample of 231 persons with AIDS in the Boston area were used to compare the use of formal and informal home care between the two largest risk groups, homosexual men and i.v. drug users. Multivariate regression analysis was also employed to adjust estimates and to determine the significance of population characteristics in explaining utilization differences. IV drug users received about twice as much formal and informal home care as homosexual men. Controlling for functional status, income and assets, insurance and potential caregiver supply, i.v. drug users obtained significantly fewer formal home care services, but more informal care. Overall, i.v. drug users received a greater number of adjusted home care hours. These findings cast doubt upon the previous assumptions of the literature and suggest that members of both risk groups are appropriate candidates for formal home care services.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Health-related quality of life in persons with acquired immune deficiency syndrome.

Assessing health-related quality of life in persons infected with human immunodeficiency virus (HIV) is extremely important, but most available scales are too long, contain items that are not relevant for such persons, or do not assess important signs and symptoms of HIV infection. This study presents a new set of scales for assessing the symptoms and functioning of persons infected with HIV and reports data on their reliability and validity collected in face-to-face interviews with 189 patients receiving primary care. This study also assesses the associations among systems, functional impairment, and global health assessments. The scales are easy to administer, are reliable, and serve as valid measures of quality of life. Fatigue, functional status, and average severity of all symptoms were the best predictors of overall perceived health status. Psychological well-being and perceived health status were the best predictors of overall perceived health status. Psychological well-being and perceived health status were the strongest correlates of life satisfaction. When assessing the health-related quality of life of persons infected with HIV, this study recommends utilizing a comprehensive set of measures that allows one to examine both discrete symptoms and the more diffuse impact of illness on functioning, mental health, and quality of life.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Response time of pulse oximeters assessed using acute decompression.

In human volunteers, the response times of 11 pulse oximeters to a 10% step reduction in arterial oxygen saturation were measured using an acute decompression technique. When finger probes were used, nine oximeters had similar response times and two were significantly slower (P less than 0.05). The ear probe response time was similar on six oximeters assessed, and faster than the finger probes. The response times of the oximeters to an acute increase in arterial saturation were tested by suddenly changing the inspired gas from air to 100% oxygen at an ambient pressure of 380 mm Hg. For ear probes, the response times were similar for all oximeters; for finger probes, three fast-responding and three slow-responding oximeters were identified (P less than 0.05). A faster response could be elicited by placing the probes on the thumb (P less than 0.05). We conclude that if a rapid indication of changes in arterial saturation is required, pulse oximeters with ear probes should be used. If finger probes are used, they should be placed on the thumb. The oximeter used will influence the response time if finger probes are used, but it will have little effect if ear probes are used.

Adult↗