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).

Molecular basis of a yeast prion species barrier.

The yeast [PSI+] factor is inherited by a prion mechanism involving self-propagating Sup35p aggregates. We find that Sup35p prion function is conserved among distantly related yeasts. As with mammalian prions, a species barrier inhibits prion induction between Sup35p from different yeast species.

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.

Quality of care by race and gender for congestive heart failure and pneumonia.

Background: Variations in the rates of major procedures by race and gender are well described, but few studies have assessed the quality of care by race and gender for basic hospital services.

Objective: To assess quality of care by race and gender.

Research Design: Retrospective review of medical records.

The effect of patients' preferences on racial differences in access to renal transplantation.

Background: In the United States, black patients undergo renal transplantation less often than white patients, but few studies have directly assessed the association between race and patients' preferences with respect to transplantation.

Methods: To assess preferences with respect to transplantation and experiences with medical care, we interviewed 1392 (82.9 percent) of 1679 eligible patients with end-stage renal disease (age range, 18 to 54 years) approximately 10 months after they had begun maintenance treatment with dialysis.

Academic health centers on the front lines: survival strategies in highly competitive markets.

The authors describe approaches that five academic health centers (AHCs) have taken to reduce costs, enhance quality, or improve their market positions since the onset of price competition and managed care. The five AHCs, all on the West Coast, were selected for study because they (1) are located in markets that had been highly competitive for the longest time; (2) are committed to all the major missions of AHCs; and (3) own or substantially control their major clinical teaching facilities. The study findings reflect the status of the five AHCs during the fall of 1998.

Income levels of bad-debt and free-care patients in Massachusetts hospitals.

This study disputes the common notion that many hospitalized patients whose expenses are written off to bad debt are able to pay their bills. By matching 1996 state tax returns to more than 350,000 bad-debt and free-care claims at seven Massachusetts hospitals, we found that most patients involved had incomes below the federal poverty level and thus were presumably eligible for either public programs or hospital-based free care. This suggests that hospitals and public officials need to investigate further why low-income, uninsured patients are not receiving benefits for which they are eligible.

MR imaging of intraventricular silicone: case report.

A 42-year-old man with human immunodeficiency viral infection developed cytomegaloviral retinitis that was complicated by retinal detachment and was treated with an intravitreous injection of silicone. Fifteen months later, magnetic resonance imaging revealed intraocular and intraventricular silicone. Signal intensity characteristics and chemical shifts of silicone in the two locations were identical.

Localization and characterization of speech arrest during transcranial magnetic stimulation.

Objective: To determine the anatomic and physiologic localization of speech arrest induced by repetitive transcranial magnetic stimulation (rTMS), and to examine the relationship of speech arrest to language function.

Methods: Ten normal, right-handed volunteers were tested in a battery of language tasks during rTMS. Four underwent mapping of speech arrest on a 1 cm grid over the left frontal region.

Upstream stimulatory factor regulates major histocompatibility complex class I gene expression: the U2DeltaE4 splice variant abrogates E-box activity.

The tissue-specific expression of major histocompatibility complex class I genes is determined by a series of upstream regulatory elements, many of which remain ill defined. We now report that a distal E-box element, located between bp -309 and -314 upstream of transcription initiation, acts as a cell type-specific enhancer of class I promoter activity. The class I E box is very active in a neuroblastoma cell line, CHP-126, but is relatively inactive in the HeLa epithelial cell line.

Current imaging techniques for head and neck tumors.

Modern head and neck imaging has led to advances in both the diagnosis and treatment of head and neck cancers. Both computed tomography (CT) and magnetic resonance imaging (MRI) studies provide important information about the location and extent of neoplasm, particularly with respect to the interface of tumor with bone, fat, muscles and other soft tissues, air, blood vessels, dura, and brain. Conventional angiography can be used to assess tumor blood supply and vascularity and to perform therapeutic embolization.

Hospital readmissions and quality of care.

Background: Readmission rates are often proposed as markers for quality of care. However, a consistent link between readmissions and quality has not been established.

Objective: To test the relation of readmission to quality and the utility of readmissions as hospital quality measures.

Imaging of a Stafne bone cavity: what MR adds and why a new name is needed.

Stafne bone cavities are asymptomatic radiolucencies seen at the angle of the mandible. Although plain films are often sufficient for diagnosis, confirmatory imaging is needed in atypical cases. We describe the MR imaging findings of a Stafne bone cavity, describe the contents, explain why a new name is needed, and discuss the relative merits of different radiologic techniques for establishing this diagnosis.

Market forces and unsponsored research in academic health centers.

Context: Increased competitive pressures on academic health centers may result in reduced discretionary funds from patient care revenues to support the performance of unsponsored research, including institutionally funded and faculty-supported activities.

Objective: To measure the amount and distribution of unsponsored research activities and their outcomes.

Design And Setting: Survey conducted in academic year 1996-1997 of 2336 research faculty in 117 medical schools.

Termination from Medicaid: how does it affect access, continuity of care, and willingness to purchase insurance?

Welfare reform has raised fears that Medicaid recipients will lose coverage, yet efforts to insure the poor via waiver programs may fall short. A telephone sample of 351 enrolled and terminated members of a Medicaid managed care plan based in community health centers were asked about insurance status, source of care, willingness to purchase new insurance, and access. Of terminated families, 78 percent had one member without insurance, 93 percent retained a regular source of care (vs.

The stability of preferences for life-sustaining care among persons with AIDS in the Boston Health Study.

Background: Clinicians recognize the importance of eliciting patient preferences for life-sustaining care, yet little is known about the stability of those preferences for patients with serious disease.

Objectives: To examine the stability of preferences for life-sustaining care among persons with AIDS and to assess factors associated with changes in preferences.

Design: Two patient surveys and medical record reviews, administered four months apart in 1990-1991.

Quality of care for two common illnesses in teaching and nonteaching hospitals.

Teaching hospitals are recognized for treating rare diseases, but their value in caring for common illnesses is less clear. To assess quality of care for congestive heart failure and pneumonia, we reviewed the medical records of Medicare beneficiaries in major teaching, other teaching, and nonteaching hospitals in four states. Overall quality was rated better in major and other teaching hospitals than in nonteaching hospitals by physician reviewers and explicit process criteria, but the results varied for different subsets of explicit measures.

Imaging of Bezold's abscess.

Objective: Our purpose was to describe the CT findings in patients with Bezold's abscesses.

Conclusion: Bezold's abscesses are rare complications of mastoiditis. In our series most were seen in adults and were associated with a history of cholesteatoma and mastoidectomy.

Clinical research in medical schools: seizing the opportunity.

Academic medical centers (AMCs) face challenges to the achievement of their potential in clinical research. These challenges include reduced support of research from clinical revenue, cultural impediments to clinical research within the traditional value system of research-intensive AMCs, and potential problems of patient access to clinical research in intensive managed care environments. This article considers options to strengthen clinical research that have been developed at some medical centers.

GroEL-GroES-mediated protein folding requires an intact central cavity.

The chaperonin GroEL is an oligomeric double ring structure that, together with the cochaperonin GroES, assists protein folding. Biochemical analyses indicate that folding occurs in a cis ternary complex in which substrate is sequestered within the GroEL central cavity underneath GroES. Recently, however, studies of GroEL "minichaperones" containing only the apical substrate binding subdomain have questioned the functional importance of substrate encapsulation within GroEL-GroES complexes.

HIV-1 tat binds TAFII250 and represses TAFII250-dependent transcription of major histocompatibility class I genes.

HIV Tat, a transactivator of viral transcription, represses transcription of major histocompatibility (MHC) class I genes. Repression depends exclusively on the C-terminal domain of Tat, although the mechanism of this repression has not been known. We now show that repression results from the interaction of Tat with the TAFII250 component of the general transcription factor, TFIID.