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Biomedical subjects

D Falcone

Publications and source records attributed to D Falcone.

17 recordsLinked to original sources
PubMed2000

Nucleotide-dependent binding of the GTPase domain of the signal recognition particle receptor beta-subunit to the alpha-subunit.

The signal recognition particle (SRP) receptor (SR) is a heterodimer of two polypeptides (SRalpha and SRbeta) that each contain a GTP-binding domain. The GTP-binding domain in the peripheral membrane SRalpha subunit has a well defined role in regulating targeting of SRP-ribosome-nascent chain complexes to the translocon. The only well established function for the transmembrane SRbeta subunit is anchoring SRalpha on the endoplasmic reticulum membrane. Deletion of the amino-terminal transmembrane domain of SRbeta did not affect receptor dimerization, but revealed a cryptic translocation signal that overlaps the GTPase domain. We demonstrate that the domain of SRalpha that binds SRbeta does so by binding directly to the nucleotide-bound form of the GTPase domain of SRbeta. An SRbeta mutant containing an amino acid substitution that allows the GTPase domain to bind XTP dimerized with SRalpha most efficiently in the presence of XTP or XDP, but not ATP. Our results suggest an additional level of regulation of SRP receptor function based on regulated dissociation of the receptor subunits.

Amino Acid Sequence↗
PubMed1999

Negatively charged residues in the IgM stop-transfer effector sequence regulate transmembrane polypeptide integration.

A non-hydrophobic sequence that contributes to the biogenesis of a transmembrane protein is termed a stop-transfer effector (STE). To examine the mechanism of STE-mediated stop-transfer, a series of fusion proteins were constructed containing variants of a putative STE from murine IgM fused to an otherwise translocated hydrophobic sequence. Unexpectedly, the fraction of molecules adopting transmembrane topology was insensitive to many amino acid substitutions within the STE sequence but varied directly with the number of negative charges. Furthermore, when present at the amino terminus of a reporter, mutants were observed that adopted type I (amino terminus lumenal) and type II (amino terminus cytoplasmic) transmembrane topologies, demonstrating that the STE sequence can be located at either side of the endoplasmic reticulum membrane. Our results suggest that recognition of a broad structural feature formed primarily by negatively charged residues within the STE halts translocation and triggers membrane integration, even when the negative charges end up on the cytoplasmic side of the membrane. Since functional STE sequences photocross-link to two membrane proteins not previously identified at the translocon, these unique proteins are presumably involved in recognizing STE sequences and/or facilitating STE function.

Amino Acid Sequence↗
PubMed1999

QOL and outcomes research in prostate cancer patients with low socioeconomic status.

The VA Cancer of the Prostate Outcomes Study (VA CaPOS) is collecting quality-of-life (QOL) information from prostate cancer patients, spouses, and physicians at six VA medical centers. Currently, 601 men with prostate cancer are included in the study, most of whom are of low socioeconomic status and over half of whom are African-American. Quality-of-life responses were most favorable for newly diagnosed patients, intermediate for those with stable metastatic disease, and poorest for those with progressive metastatic disease. Patients could not provide reliable estimates of their own preferences for future QOL states but responded reliably to questions phrased as a comparison of the preferences of two hypothetical patients. High out-of-pocket costs for hormonal therapies, lack of health insurance, and a belief that the non-VA system offered poorer services were the most common reasons for patient transferral to the VA system. Satisfaction with medical care was generally high. While African-American patients were more likely to have advanced prostate cancer at diagnosis, after adjustment for differences in health literacy, race was no longer a significant predictor of advanced disease. The VA CaPOS provides useful information on health status and patient satisfaction of VA prostate cancer patients. Long-term evaluations are needed to detect clinically meaningful QOL information as the disease progresses.

Adult↗
PubMed1996

The cotranslational integration of membrane proteins into the phospholipid bilayer is a multistep process.

During the cotranslational integration of a nascent protein into the endoplasmic reticulum membrane, the transmembrane (TM) sequence moves out of an aqueous pore formed by Sec61alpha, TRAM, and other proteins and into the nonpolar lipid bilayer. Photocross-linking reveals that this movement involves the sequential passage of the TM domain through three different proteinaceous environments: one adjacent to Sec61alpha and TRAM and two adjacent to TRAM that place different restrictions on TM domain movement. In addition, the TM sequence is not allowed to diffuse into the bilayer from the final TRAM-proximal site until translation terminates. Cotranslational integration is therefore linked to translation and occurs via an ordered multistep pathway at an endoplasmic reticulum site that is multilayered both structurally and functionally.

Cross-Linking Reagents↗
PubMed1995

Ca(2+)-ATPase inhibitor, cyclopiazonic acid, releases Ca2+ from intracellular stores in RBL-2H3 mast cells and activates a Ca2+ influx pathway that is permeable to sodium and manganese.

Cyclopiazonic acid has been reported to inhibit the Ca(2+)-ATPase of intracellular calcium stores in some nonexcitable cell types, such as myeloid cells and lymphocytes. The present study examines the effects of cyclopiazonic acid on rat basophilic leukemia (RBL) cells, a mucosal mast cell line. Addition of cyclopiazonic acid to fura-2-loaded RBL cells evoked a biphasic increase in free ionized intracellular calcium. Release of stored calcium accounted for the first phase of this response. The second phase was determined to be calcium entering through an influx pathway activated by cyclopiazonic acid. The influx pathway was selective for calcium, but was somewhat permeable to manganese. However, in a Ca(2+)-free solution containing EGTA, sodium ions permeated freely. This influx pathway appears to be identical to that which is activated by antigen, the physiological stimulus to the cells. Cyclopiazonic acid also induced secretion when combined with the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate, which activates protein kinase C.

Animals↗
PubMed1994

Access to long-term care: race as a barrier.

Race continues to impede access to health services, for acute as well as long-term care. Whites, for example, use disproportionately more days of nursing home care than nonwhites, not simply because they are more likely to be private payers and, therefore, are preferred over nonwhites: the difference in utilization persists even among those whose nursing home stays are covered by Medicare. Using data from a study of patients awaiting alternative placement in North Carolina acute care general hospitals in 1991, this article examines racial differences in discharge delay, that is, in the time between when a patient is medically ready for discharge to another form of care and when he or she actually is discharged. Logistic regression and ordinary least squares are used heuristically to identify patient characteristics associated with delay, and two-way analyses of variance are used to document the independent effect of race. The results indicate that race has substantial independent explanatory power. This finding is reinforced by the analysis of variance with controls for the patient's payment source for long-term care, chronic condition or special care requirements, demographic attributes, family cooperativeness, whether the patient had a behavior problem that impeded the discharge planning process, and whether there was a financial problem in arranging for the patient's discharge. The inescapable conclusion is that nursing homes discriminate on the basis of race in admitting patients. This practice is patently objectionable; it also is costly to hospitals, thus to society, since hospitals bear the direct costs of delayed discharges and hospitals do not keep costs to themselves. While research is needed to determine whether the North Carolina findings are replicable in other states, past research suggests that the problem is not confined to this state.

Black or African American↗
PubMed1994

Medicaid in Oklahoma.

Medicaid expenditures in Oklahoma increased 98.2% from 1986 through 1991 while those of the United States went up 111.0%. Of this increase, 21.6% was due to inpatient care and 25.9% to nursing home care. With respect to beneficiaries, 34.9% of the increase was attributable to the aged and 31.4% to the disabled. AFDC recipients accounted for only 19.1% of the increase.

Health Expenditures↗
PubMed1991

Both the 5' untranslated region and the sequences surrounding the start site contribute to efficient initiation of translation in vitro.

The role of RNA sequences in the 5' leader region between the cap site and initiating AUG in mediating translation was examined in vitro. Hybrid mRNAs were synthesized in which the cognate leader sequence was replaced with either optimized or compromised leader sequences, and translational efficiency was measured for six different coding regions. Translation was most efficient with a leader containing the 5' untranslated region from Xenopus beta-globin and an optimized initiation sequence. Compared with the cognate leaders, this hybrid was observed to increase translation of the various coding regions as much as 300-fold. The translational efficiencies of the different coding regions also varied substantially. In contrast to earlier suggestions that increased leader efficiency results from higher affinity of the leader for a limiting factor, our experiments suggest that increased translation from the beta-globin hybrid leader sequence results from more rapid initiation of translation.

Animals↗
PubMed1991

Waiting for placement: an exploratory analysis of determinants of delayed discharges of elderly hospital patients.

This article examines the causes of delayed hospital discharge for 3,111 patients waiting for alternative placement in 80 North Carolina acute care general hospitals during May 1989. Almost all of the patients were elderly: their average age was 77. Delay is defined as the period between the day a patient was judged medically ready for discharge by a discharge planner and the day the patient was discharged (or May 31 if unplaced). The average delay was 16.7 days. The policy-relevant patient characteristics associated with delay are requirement for heavy care, race, source of reimbursement, and whether or not there was a financial problem in arranging discharge. The patient's age and whether or not a problem with behavior or family cooperativeness was noted also were predictors. Along with patient characteristics, hospital features such as bed size, occupancy rate, and total revenues were correlated with delay. Local nursing and rest home (domiciliary) bed supply were insignificant predictors, possibly because of their limited variance: the number of nursing home beds in all North Carolina counties is below the national mean; the number of rest home beds exceeds it. The conclusion reached is that the delay problem warrants more intensive analysis, particularly regarding financial problems encountered at discharge, and race. Guidelines for such an endeavor are provided. Further, there is a need to recognize the increasing preponderance of a new type of heavy care patient via more appropriate reimbursement levels and "transitional care" services.

Aged↗
PubMed1988

The shadow price of pluralism: the use of tax expenditures to subsidize hospital care in the United States.

During the 1980s, and particularly during the past year, controversy has arisen over the propriety of the not-for-profit hospital's tax-exempt status. In addressing the issue, policy analysts and activists have focused attention on the comparative efficiency and effectiveness of not-for-profit and for-profit hospitals' provision of social benefit, variously conceived and quantified. We review the results of current research carried out within that focus and suggest that the findings are inconclusive and the focus misplaced. A more profitable avenue of inquiry would be to explore the extent to which the dominance of tax-subsidized not-for-profit hospitals is a societally preferred means of achieving the provision of a level of access to quality care that otherwise would require a large direct government subsidy.

Economics, Hospital↗
PubMed1979

Opioid effects on computer-derived sleep and EEG parameters in nondependent human addicts.

After one adaptation night, intramuscular doses of methadone (7.5, 15, 30 mg/70 kg), morphine (10 or 20 mg/70 kg), or placebo were given to seven male nondependent opiate addicts at weekly intervals in a randomized cross-over design. After three adaptation nights, heroin (3, 6, 12 mg/70 kg) was compared with morphine and placebo by means of a similar design in seven other subjects. Using electroencephalogram (EEG) bisector analysis, tape recordings of sleep were analyzed for two beta, three alpha, three theta, and two delta EEG patterns, as well as for detections of sleep spindles, K-complexes, eye movements, body movements, average electromyogram (EMG), and calculation of seven sleep-waking stages. All three opioids produce a dose-related arousal: they increase EMG and EEG measures of muscle activity, as well as body movements and EEG alpha, while decreasing EEG theta and spindling. These opioids also increase measures of waking state and decrease measures of spindle sleep and REM sleep. Although the 1974 version of the EEG bisector analysis is not exactly comparable to visual analysis, in this design it defined significant drug effects on sleep and EEG. Distinctive bisector analysis patterns are positively correlated with each sleep--waking stage.

Adult↗
PubMed1976

The policy effectiveness of health services research: a reconsideration.

It has often been asserted that health services research (HSR) has been either epiphenomenal or entirely ineffectual in influencing the formation of policy. In this examination of the HSR-policy relationship that assertion is contested; the authors conclude that there has been a relationship between HSR and policy, at least public policy. A diagrammatic framework is presented to describe the HSR-policy nexus in an attempt to facilitate an understanding of how future efforts in the conduct of HSR might be most effective.

Communication↗