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Biomedical subjects

K Dalton

Publications and source records attributed to K Dalton.

At least 19 recordsLinked to original sources
PubMed2005

The glycosylation pattern of baculovirus expressed envelope protein E2 affects its ability to prevent infection with bovine viral diarrhoea virus.

We have investigated the role of glycosylation of the envelope glycoprotein E2 of bovine viral diarrhoea virus (BVDV), produced in insect cells, in BVDV infection. When amino acids predicated to code for the C-terminal N-linked glycosylation site were mutated the resulting protein was less efficient than wild type protein at preventing infection of susceptible cells with BVDV. In addition, mutational analysis showed that a further two predicted N-terminal N-linked glycosylation sites of E2 are required for efficient production of recombinant protein.

Animals↗
PubMed2001

cis-acting sequences required for coronavirus infectious bronchitis virus defective-RNA replication and packaging.

The parts of the RNA genome of infectious bronchitis virus (IBV) required for replication and packaging of the RNA were investigated using deletion mutagenesis of a defective RNA (D-RNA) CD-61 (6.1 kb) containing a chloramphenicol acetyltransferase reporter gene. A D-RNA with the first 544, but not as few as 338, nucleotides (nt) of the 5' terminus was replicated; the 5' untranslated region (UTR) comprises 528 nt. Region I of the 3' UTR, adjacent to the nucleocapsid protein gene, comprised 212 nt and could be removed without impairment of replication or packaging of D-RNAs. A D-RNA with the final 338 nt, including the 293 nt in the highly conserved region II of the 3' UTR, was replicated. Thus, the 5'-terminal 544 nt and 3'-terminal 338 nt contained the necessary signals for RNA replication. Phylogenetic analysis of 19 strains of IBV and 3 strains of turkey coronavirus predicted a conserved stem-loop structure at the 5' end of region II of the 3' UTR. Removal of the predicted stem-loop structure abolished replication of the D-RNAs. D-RNAs in which replicase gene 1b-derived sequences had been removed or replaced with all the downstream genes were replicated well but were rescued poorly, suggesting inefficient packaging. However, no specific part of the 1b gene was required for efficient packaging.

3' Untranslated Regions↗
PubMed2001

A longitudinal study of the effects of graduate medical education on hospital operating costs.

OBJECTIVE: To examine the effect of graduate medical education sponsorship on hospital operating costs over a seven-year period, to test for a longitudinal association between teaching intensity and cost, and to determine whether the indirect medical education (IME) payment adjustments made under Medicare's Prospective Payment System are appropriate. DATA SOURCES: Medicare cost and payment data from the Hospital Cost Report Information System and other related HCFA files, from FFY 1989 through 1995. The study population consists of all short-stay hospitals (approximately 5,000) participating in Medicare and receiving case payments by diagnosis-related groups. STUDY DESIGN: The original cost functions used to develop indirect medical education payment adjustments under PPS are re-estimated with panel data. Specification changes are included based on findings from critiques of the original hospital cost model. Additional variations on the model are explored to test for differences by hospital status, to control for the effect of additional disproportionate share and outlier payments, and to isolate the effects of improved case-mix measurement on model results. PRINCIPAL FINDINGS: Fixed effects regression produces no evidence of a significant within-hospital association between increased sponsorship of medical residents and increased cost per case. In models designed to capture a cross-sectional association, operating costs are positively related to teaching activity, but the association shows a decline in strength over time. In all years, the strength of the association is significantly greater among hospitals eligible for disproportionate share adjustments and among major teaching hospitals. Controlling for secular trends of increased teaching intensity results in a pattern of declining cross-sectional teaching coefficients that supports a theory that observed teaching effects are the result of unmeasured case severity. CONCLUSIONS: A significant but declining cost differential is observed between teaching and nonteaching hospitals. The association appears to be related to hospital and patient characteristics that cannot be controlled using currently available case-mix and wage indices. Longitudinal models do not provide evidence to support a payment adjustment formula that allows individual hospitals to recompute their IME adjustment rates as their teaching ratios rise or fall from year to year. Cross-sectional findings suggest that re-estimations of the teaching effect may be appropriate when significant improvements occur in Medicare case-mix measurement.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed2000

Oestrogens and progestogens for preventing and treating postnatal depression.

BACKGROUND: Postnatal depression, with a prevalence of at least 10%, is probably the most common complication of the puerperium. A deficiency or imbalance of sex hormones has repeatedly been suggested as a cause. OBJECTIVES: The objective of this review was to evaluate the role of oestrogens and progestogens in the prevention and treatment of postnatal depression. SEARCH STRATEGY: The register of clinical trials maintained and updated by the Cochrane Pregnancy and Childbirth Group. SELECTION CRITERIA: All trials were considered in which pregnant or postpartum women (up to 18 months) were randomised to receive postpartum oestrogen or progestogen or placebo for the treatment or prevention of postnatal depression. DATA COLLECTION AND ANALYSIS: Two published randomised placebo controlled trials were identified for inclusion in the analyses for this review. One study was excluded. MAIN RESULTS: Depot norethisterone enanthate given within 48 hours of delivery and lasting 8-12 weeks was associated with significantly higher postpartum depression scores than placebo. Oestrogen therapy in severely depressed women was associated with a greater improvement in depression scores than placebo. REVIEWER'S CONCLUSIONS: There is no place for synthetic progestogens in the prevention of treatment of postnatal depression. Long-acting norethisterone enanthate is associated with an increased risk of postnatal depression. It and other long-acting progestogen contraceptives should be used with caution in the postnatal period, especially in women with a history of depression. The role of progesterone in the prevention and treatment of postnatal depression has yet to be evaluated in a randomised placebo-controlled trial. Oestrogen therapy may be of modest value at a late stage of severe postnatal depression. Its role in the prevention of recurrent postnatal depression has not been evaluated. Further research on its value is unlikely for ethical reasons.

Depression, Postpartum↗
PubMed2000

Revisiting Rogowski and Newhouse on the indirect costs of teaching: a note on functional form and retransformation in Medicare's payment formulas.

In 1992 Rogowski and Newhouse identified errors in functional form and retransformation in the econometric model that underlies Medicare's payments to teaching hospitals. We re-estimate their model and expand on their work, with data from the following decade. We find: (1) the functional form imposed by Health Care Financing Administration's original specification of the teaching variable is supported by the data; (2) there is no evidence of a threshold effect when the teaching intensity variable is appropriately specified; (3) there is no longer evidence of heteroscedasticity across teaching hospital types, consequently there is no need to incorporate re-transformation factors into the payment formula. We attribute the differences in our findings to secular changes in the hospital industry and improvements in variable measurement.

Cost Allocation↗
PubMed2000

Leader switching occurs during the rescue of defective RNAs by heterologous strains of the coronavirus infectious bronchitis virus.

A defective RNA (D-RNA), CD-61, derived from the Beaudette strain of the avian coronavirus infectious bronchitis virus (IBV), was rescued (replicated and packaged) using four heterologous strains of IBV as helper virus. Sequence analysis of the genomic RNA from the four heterologous IBV strains (M41, H120, HV10 and D207) identified nucleotide differences of up to 17% within the leader sequence and up to 4.3% within the whole of the adjacent 5' untranslated region (UTR). Analysis of the 5' ends of the rescued D-RNAs showed that the Beaudette leader sequence, present on the initial CD-61, had been replaced with the corresponding leader sequence from the helper IBV strain but the adjacent 5' UTR sequence of the rescued D-RNAs corresponded to the original CD-61 Beaudette sequence. These results demonstrated that the phenomenon of leader switching previously identified for the coronaviruses murine hepatitis virus and bovine coronavirus (BCoV) also occurred during the replication of IBV D-RNAs. Three predicted stem-loop structures were identified within the 5' UTR of IBV. Stem-loop I showed a high degree of covariance amongst the IBV strains providing phylogenetic evidence that this structure exists and is potentially involved in replication, supporting previous observations that a BCoV stem-loop homologue was essential for replication of BCoV defective interfering RNAs.

5' Untranslated Regions↗
PubMed2000

Expression of reporter genes from the defective RNA CD-61 of the coronavirus infectious bronchitis virus.

The defective RNA (D-RNA) CD-61, derived from the Beaudette strain of the avian coronavirus infectious bronchitis virus (IBV), was used as an RNA vector for the expression of two reporter genes, luciferase and chloramphenicol acetyltransferase (CAT). D-RNAs expressing the CAT gene were demonstrated to be capable of producing CAT protein in a helper-dependent expression system to about 1.6 microgram per 10(6) cells. The reporter genes were expressed from two different sites within the CD-61 sequence and expression was not affected by interruption of the CD-61-specific ORF. Expression of the reporter genes was under the control of a transcription-associated sequence (TAS) derived from the Beaudette gene 5, normally used for the transcription of IBV subgenomic mRNA 5. The Beaudette gene 5 TAS is composed of two tandem repeats of the IBV canonical consensus sequence involved in the acquisition of a leader sequence during the discontinuous transcription of IBV subgenomic mRNAs. It is demonstrated that only one canonical sequence is required for expression of mRNA 5 or for the expression of an mRNA from a D-RNA and that either sequence can function as an acceptor site for acquisition of the leader sequence.

Animals↗
PubMed2000

The role of critical access hospital status in mitigating the effects of new prospective payment systems under Medicare.

This article examines rural hospitals that potentially qualify as critical access hospitals (CAH) and identifies facilities at substantial financial risk as a result of Medicare's expansion of prospective payment systems (PPS) to nonacute settings. Using Health Care Financing Administration (HCFA) cost reports from the federal year ending Sept. 30, 1996, combined with county-level sociodemographic data from the Area Resource File (ARF), characteristics of potential CAHs were identified and their finances analyzed to determine whether they could benefit from the cost-based reimbursement rules applicable to CAH status. Rural hospitals were identified as potential CAHs if they met a combination of federal and state criteria for necessary providers. Rural facilities were classified as "at risk" if they had poor financial ratios in conjunction with high levels of dependence on outpatient, home-care or skilled nursing services. Almost 30 percent of all rural hospitals were identified as potential CAHs. Ninety percent of potential CAH facilities were identified as "at risk" by at least one of five possible risk criteria, and one-third were identified by at least three. Of those classified "at risk," 48 percent might not benefit from conversion to CAH because their inpatient Medicare reimbursement would likely be less under CAH payment rules than under their current PPS payment rules. Many potential CAHs were doing well under inpatient PPS because they were sole community hospitals (SCH) and were therefore eligible for special adjustments to the PPS rates. The Rural Hospital Flexibility Act would be more beneficial to the population of isolated rural hospitals if those eligible for both CAH and SCH status were given the option of retaining their SCH inpatient payment arrangements while still qualifying for outpatient cost-based reimbursement.

Costs and Cost Analysis↗
PubMed2000

Medicare graduate medical education funding and rural hospitals.

To assess the importance of medical residents to rural hospitals, and to predict the possible effect of reductions in Medicare graduate medical education (GME) payments, data from Medicare hospital cost reports and from a telephone survey of rural hospitals with residency programs are analyzed. In prospective payment system year 11, 70 rural hospitals received more than $80 million in Medicare GME payments. The presence of rural training programs enhanced staff physician recruitment and retention and led to increased numbers of physicians settling in communities surrounding the facilities. Many survey respondents felt that elimination of GME funds would results in downsizing or outright elimination of their training programs. The results support the contention that rural training programs are important to hospitals and their surrounding communities and provide an essential component of the physician supply pipeline to rural areas.

Education, Medical, Graduate↗
PubMed1998

Sequence elements involved in the rescue of IBV defective RNA CD-91.

Deletion mutagenesis has been used to identify essential regions for rescue of coronavirus defective RNAs (D-RNAs). Using this technique on a cloned IBV D-RNA CD-91, we have identified a region potentially important in its rescue. Comparing the sequence of D-RNAs rescued with those not rescued we have deduced that a 72 base region corresponding to base number 13,824 to 13,896 in the viral genome is required for rescue. This may be an IBV D-RNA packaging signal or a cis-acting element involved in replication. Further experiments and modification of our techniques will be required to differentiate between the two processes.

Animals↗
PubMed1998

Rescue of IBV D-RNA by heterologous helper virus strains.

Coronavirus defective RNA (D-RNA) vectors could be developed to deliver selected genes for the production of recombinant coronavirus vaccines. An IBV D-RNA, CD-61, derived from a naturally occurring IBV Beaudette D-RNA, CD-91, is being developed as a D-RNA vector for IBV. In order to use CD-61 as a vector it will require rescue by heterologous strains in addition to Beaudette. Rescue will be determined by recognition of replication and packaging signals within the D-RNA by the helper virus. The 5' and 3' UTRs are believed to contain sequences involved in replication and transcription. The 5' and 3' UTRs of six strains of IBV have been sequenced and experiments performed using six strains of helper virus for rescue of CD-61 to determine whether rescue correlates with sequence conservation within the 5' and 3' UTRs. Results indicate that all strains of helper virus rescued the D-RNA to varying degrees. Sequence comparisons show a high degree of sequence identity in the UTRs, but enough strain differences exist to be used as markers. The 5' and 3' UTRs of the D-RNAs rescued by the heterologous strains were also sequenced and leader switching between the helper virus and the Beaudette leader on the D-RNAs was observed.

3' Untranslated Regions↗
PubMed1998

Utilising a defective IBV RNA for heterologous gene expression with potential prophylactic application.

Based on the natural ability of coronaviruses to undergo homologous RNA recombination, we are working to produce infectious bronchitis virus (IBV) recombinants using RNA generated from recombinant fowlpox viruses (FPV). The aim is to replace the spike (S) gene of an existing IBV vaccine strain with the S gene of a heterologous strain. CD-61 is an IBV defective RNA (D-RNA) derived from a naturally occurring IBV D-RNA (CD-91). CD-61 D-RNA is being investigated as an RNA vector for the expression of heterologous genes. T7-derived RNA transcripts of CD-61 can be replicated and passaged in the presence of helper virus, following electroporation into IBV-infected cells. CD-61 cDNA was modified by the addition of the hepatitis delta virus ribozyme plus T7 terminator downstream of the 3'UTR. This allowed the synthesis of discreet RNA transcripts. The complete cassette was cloned into an FPV transfer vector (pEFL10) for generating recombinant fowlpox viruses. FPV/CD-61 recombinants will be assessed for D-RNA production in IBV-infected cells. The luciferase reporter gene sequence has been inserted into the modified CD-61, under the control of the IBV transcription associated sequence (TAS) from gene 5. Luciferase has been successfully expressed from CD-61 in helper virus-infected cells.

Animals↗
PubMed1995

Effect of oral corticosterone administration on locomotor development of neonatal and juvenile rats.

In order to simulate the elevated corticosteroid levels to which offspring of stressed women may be subjected, rat pups were treated daily with two levels of oral corticosterone from the 2nd to the 15th postnatal day. The rat pups were subjected to swimming tests from their 8th postnatal day to examine their neuromuscular development and learning abilities. The locomotor performance of corticosterone-treated groups was similar to that of controls but its development was delayed, which demonstrates that even relatively low levels of corticosterone have a significant negative influence on the maturation and learning ability of neonatal rat pups. This indicates that the glucocorticoid levels to which suckling neonates (for example, children of women suffering from stress) might be exposed could modify the complex integrated neuromuscular adaptive mechanisms involved in normal locomotor development.

Animals↗