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Biomedical subjects

J Green

Publications and source records attributed to J Green.

At least 379 records · Page 21Linked to original sources

How accurate are hospital discharge data for evaluating effectiveness of care?

Demand for quality of care data has led to publication of adjusted mortality rates of hospitals and physicians. Yet the accuracy of databases used for this purpose is questionable, raising the possibility that consumer-oriented profiles of providers could be misleading. A stratified random sample of discharge abstract records of Medicare-aged patients hospitalized in California were audited by the state's health data agency. The results of the audit were analyzed to determine the effect that coding errors have on expected death rates assigned to hospitals as risk-adjustment measures in the annual Medicare hospital mortality report. Discharge abstracts of Medicare-aged patients contained many errors among coded risk factors used to calculate expected death rates. Comorbidities and transfers from nursing homes were seriously underreported and 'urgency of admission' was often miscoded. Hospitals differed with respect to error rates (P < .0001); these varying levels of miscoding caused measurement errors that ranged in size from 0.2 to 2.2 expected 30-day deaths per 100 admissions (10th vs. 90th percentile). Detailed knowledge of the limitations of claims data can help analysts minimize the impact of coding error. Beyond this, quality control of data used for outcomes research needs strengthening.

Abstracting and Indexing↗

Properties of FNR proteins substituted at each of the five cysteine residues.

FNR is a transcriptional regulator controlling the expression of a number of Escherichia coli genes in response to anoxia. It is structurally-related to CRP (the cyclic AMP receptor protein) except for the presence of a cysteine-rich N-terminal extension, which may form part of an iron-binding, redox-sensing domain in FNR. Site-directed substitution has previously shown that four of the cysteine residues (C20, C23, C29 and C122) are essential for FNR function, whereas the fifth (C16) is not. The FNR protein exists in two forms separable by non-reducing SDS-PAGE, and in studies with altered FNR proteins containing single substitutions at each of the five cysteine residues it was concluded that the faster-migrating form (FNR(27)), possesses an intramolecular disulphide bond linking C122 to one of the cysteines near the N-terminus. FNR(27) was more abundant in aerobic cells but the physiological significance of this was not established. Footprint studies indicated that FNR proteins lacking essential cysteine residues are impaired in their ability to protect FNR sites in the ndh promoter. The non-essential cysteine residue (C16) was identified as the source of the most reactive sulphydryl group and all of the inactive proteins exhibited different sulphydryl reactivities. The iron content of the C122A-substituted protein was much reduced but those of the other proteins were less affected. Electrospray mass spectrometry confirmed the accuracy of the gene-derived amino acid composition of FNR with a mutant protein and it showed that a fraction of the wild-type protein may carry a 78 Da substituent which could not be removed with dithiothreitol or beta-mercaptoethanol.

Aerobiosis↗

Solid-phase synthesis of [Ala1,3,11,15]-endothelin-1 by a modified double-coupling procedure.

[Ala1,3,11,15]-Endothelin-1, a linear analogue of endothelin-1 in which alanines replace the cystine residues, has been prepared by solid-phase synthesis in approximately 17% yield. Fmoc amino acids were coupled using an economical modified double-coupling (symmetrical anhydride followed by O-benzotriazolyl ester) procedure under fully automated conditions. Conditions for synthesis and purification were closely monitored and should be applicable to other endothelin analogues.

Amino Acid Sequence↗

Ultrasound during pregnancy: a discussion. Interview by Max Allen.

Prenatal screening by ultrasound is increasing in the United States. In 1990, 52 percent of mothers who had live births received ultrasound, compared with 48 percent in 1989 (Monthly Vital Stat Rep 1993; 42:2(S):6). A recent multicenter, randomized study of 15,151 low-risk pregnant women, conducted by the Routine Antenatal Diagnostic Imaging With Ultrasound (RADIUS) Study Group, reported no significant differences in pregnancy outcomes between women who received no ultrasound scan and women who received two scans during pregnancy (N Engl J Med 1993; 329:821-827). Ewigman et al concluded, "The adoption of routine ultrasound screening in the United States would add considerably to the cost of care in pregnancy, with no improvement in perinatal outcome."

Australia↗

Norwalk-like viruses: demonstration of genomic diversity by polymerase chain reaction.

A reverse transcription-polymerase chain reaction (RT-PCR) amplification procedure was developed for the detection of Norwalk-like viruses in fecal specimens. Ninety-nine fecal specimens collected in the United Kingdom and containing small round-structured virus particles as determined by electron microscopy were tested. They came from 50 outbreaks and 16 sporadic cases of viral gastroenteritis. RT-PCR products of the appropriate size for Norwalk virus RNA were detected in 15 specimens from three outbreaks, suggesting that viruses closely related to Norwalk virus have not been circulating widely in the United Kingdom in recent years. From four isolates, the RT-PCR amplification products of two genomic regions were sequenced and the degree of genomic variation was compared. DNA sequencing of the PCR products revealed strong similarities among strains from the United Kingdom (approximately 97% for both regions amplified) but significant differences from Norwalk virus (67 to 78%). All of the viruses detected by RT-PCR were classified as serotype UK2 by solid-phase immune electron microscopy or enzyme-linked immunosorbent assay. These findings provide evidence of a genomic relationship between Norwalk virus and serotype UK2 small round-structured viruses.

Base Sequence↗

Psychosocial issues raised by a familial ovarian cancer register.

A Familial Ovarian Cancer Register has been established which has recruited primarily through media publicity. In depth semi-structured interviews were carried out with 20 women who had volunteered in order to explore (1) knowledge about the disease, (2) motivations for contacting the Register, and (3) expectations. We found that interviewees were generally well informed about the symptoms of the disease as a result of their relatives' experiences. There was, nevertheless, a need for information which the Register was seen as potentially fulfilling, although most subjects gave altruistic reasons for volunteering. Only one interviewee said that the publicity about the Register had made her more anxious. Most said that their anxieties had not been affected either way by the Register. Subjects did not have a clear idea of what being on the Register would mean, although there was an expectation of screening for early signs of the disease. Many interviewees had models of familial disease which did not follow mendelian genetics. This has implications for the targetting of education and screening programmes. Other psychosocial issues raised by a register of this kind are discussed, many of which require continuing monitoring to ensure that the psychological costs do not outweight the benefits.

Adult↗

Adjustment to the psychological and social sequelae of recurrent genital herpes simplex infection.

OBJECTIVE: To investigate whether adverse psychological consequences and impaired sexual and interpersonal functioning are present in individuals suffering from recurrent genital herpes simplex infection (HSV). DESIGN: A questionnaire-based study completed by subjects defined as having more than one episode of HSV infection. SUBJECTS: Completed questionnaires were returned from 90 subjects; 40 from the department of genitourinary medicine at our hospital and 50 from members of the Herpes Association. RESULTS: Stress and being physically run-down were identified as provoking factors by the majority of individuals (78% and 56% respectively). The frequency of sexual activity was not different when comparing rates before and after infection (p < 0.001) and the majority of subjects had told partners of their infection. Women reported significantly greater disturbances in several psychological variables and reported a greater decrement in their general health. However, overall there were no differences in the psychological sequelae following herpes infection. CONCLUSIONS: The study suggests that, given time, most people are able to adjust psychologically to having recurrent herpes infection. However, for a minority of subjects this is not the case and these individuals may require psychotherapeutic intervention.

Adaptation, Psychological↗

1,25-Dihydroxyvitamin D3 inhibits Na(+)-dependent phosphate transport in osteoblastic cells.

In the present work we investigated the influence of vitamin D3 metabolites on Na(+)-dependent phosphate (Pi) transport in the clonal osteoblastic cell line UMR-106. The vitamin D3 metabolite 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] dose-dependently inhibited Pi transport with a half-maximal concentration of approximately 5 x 10(-11) M. The effect of 1,25(OH)2D3 was first observed after 8 h of preincubation period. Inhibition of phosphate uptake was relatively specific for the 1,25(OH)2D3 analogue of vitamin D3. The potency order was 1,25(OH)2D3 >> 24,25-dihydroxyvitamin D3 > 25-[3H]hydroxyvitamin D3. Kinetically, 1,25(OH)2D3 decreased the maximal velocity of the phosphate uptake system, whereas the affinity for phosphate was unaffected. Activation of protein kinase C (PKC) in UMR-106 cells stimulated Na(+)-dependent Pi transport. Nonetheless, the inhibitory effect of 1,25(OH)2D3 on Pi transport was not related to downregulation of PKC. Chemical determination of intracellular Pi showed a 50% reduction after 24-h preincubation with 10(-8) M 1,25(OH)2D3. We conclude that 1,25(OH)2D3 inhibits Na(+)-dependent phosphate transport in osteoblastic cells. This in turn leads to intracellular Pi depletion. The physiological implication of this phenomenon on the effects of vitamin D on osteoblasts in situ is discussed.

Biological Transport↗

Acute phosphate depletion inhibits the Na+/H+ antiporter in a cultured renal cell line.

We studied the effect of acute Pi depletion on the regulation of intracellular pH (pHi) in the OK opossum kidney cell line by using the pH-sensitive dye 2'7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF). Cell recovery from an NH4Cl acid load in HCO3-free buffer disclosed an Na(+)-dependent component blocked by amiloride and a smaller Na(+)-independent component that increased on exposure of the cells to a high-K+ buffer. After 24-h incubation of the cells in phosphate-free medium, pHi recovery by the Na+/H+ exchanger was markedly inhibited, whereas the Na(+)-independent pHi recovery was not affected. The inhibition of Na+/H+ exchange was reversible on correction of cellular Pi deficit. A similar phenomenon was observed when cellular Pi depletion was induced by acute exposure (min) to fructose. Pi depletion shifted the pHi dependence of the exchanger and also reduced its maximal activity. Time-course studies revealed that the effect of Pi depletion could not be attributed to attenuation of Na(+)-K(+)-adenosinetriphosphatase activity and resultant diminution of the transmembrane gradient for the Na+ influx. We conclude that acute Pi depletion in cultured proximal tubular cells leads to reversible inhibition of the Na+/H+ exchanger. This in vitro finding may relate to the in vivo observation of impaired HCO3 reabsorption and bicarbonaturia in acute Pi depletion.

Ammonium Chloride↗

The pulmonary response of white and black adults to six concentrations of ozone.

Many early studies of respiratory responsiveness to ozone (O3) were done on healthy, young, white males. The purpose of this study was to determine whether gender or race differences in O3 response exist among white and black, males and females, and to develop concentration-response curves for each of the gender-race groups. Three hundred seventy-two subjects (n > 90 in each gender-race group), ages 18 to 35 yr, were exposed once for 2.33 h to 0.0 (purified air), 0.12, 0.18, 0.24, 0.30, or 0.40 ppm O3. Each exposure was preceded by baseline pulmonary function tests and a symptom questionnaire. The first 2 h of exposure included alternating 15-min periods of rest and exercise on a motorized treadmill producing a minute ventilation (VE) of 25 L/min/m2 body surface area (BSA). After exposure, subjects completed a set of pulmonary function tests and a symptom questionnaire. Lung function and symptom responses were expressed as percent change from baseline and analyzed using a nonparametric two factor analysis of variance. Three primary variables were analyzed: FEV1, specific airway resistance (SRaw), and cough. Statistical analysis demonstrated no significant differences in response to O3 among the individual gender-race groups. For the group as a whole, changes in the variables FEV1, SRaw, and cough were first noted at 0.12, 0.18, and 0.18 ppm O3, respectively. Adjusted for exercise difference, concentration-response curves for FEV1 and cough among white males were consistent with previous reports (1).

Adolescent↗

Effects of N-terminal, midregion, and C-terminal parathyroid hormone-related peptides on adenosine 3',5'-monophosphate and cytoplasmic free calcium in rat aortic smooth muscle cells and UMR-106 osteoblast-like cells.

N-Terminal analogs of PTH-related protein (PTHrP) and PTH bind to a common receptor and exhibit similar biological properties. However, recent studies suggest that certain midregion and C-terminal PTHrP peptides have activities distinct from those of PTH in the placenta and in osteoclasts, respectively. In this study we determined the biological activities of full-length recombinant PTHrP-(1-141) and several synthetic N-terminal, midregion, and C-terminal PTHrP fragments in two PTHrP-producing cell types. Peptides were tested for their ability to stimulate cAMP production and raise intracellular free calcium ([Ca2+]i) in primary rat aortic smooth muscle cells (VSMC) and UMR-106 rat osteoblast-like (UMR) cells. In UMR cells PTHrP-(1-34)NH2, PTHrP-(1-141), and bovine PTH-(1-34) all increased cAMP (approximately 50 fold) and [Ca2+]i (180 nM). By contrast, in VSMC, these N-terminal peptides increased cAMP (3-fold) but had no detectable effect on [Ca2+]i. PTHrP-(1-34) and PTHrP-(1-141) significantly blunted the angiotensin II-induced rise in cAMP (but not the calcium signal) consistent with the concept that PTHrP opposes angiotensin II activity in VSMC. PTHrP-(67-86)NH2, PTHrP-(107-138)NH2, and PTHrP-(107-111)NH2 had no effect on either cAMP or [Ca2+]i in either cell type. VSMC and UMR-106 cells both expressed a 2.5-kilobase PTH/PTHrP receptor messenger RNA (mRNA) transcript. However, high affinity specific binding of 125I-labeled [Tyr36] PTHrP-(1-36)NH2 was detected in UMR cells but not in VSMC. We conclude that the PTH-like, N terminus of the PTHrP molecule is critical in induction of cAMP and [Ca2+]i pathways in UMR cells, and for cAMP stimulation in VSMC. In addition, PTHrP, like other established vasodilators, signals in VSMC mainly (if not exclusively) by increasing the production of cAMP.

Animals↗

Discordant expression of CD28 ligands, BB-1, and B7 on keratinocytes in vitro and psoriatic cells in vivo.

The process for optimal T-cell activation requires not only engagement of the T-cell receptor/CD3 complex, but also the delivery of additional co-stimulatory signals that synergize with the primary response mediated through the T-cell receptor. Thus, the regulated expression of ligands for such co-stimulatory molecules can be critical in determining whether a cell can effectively activate T cells following the presentation of a foreign antigen. The CD28 antigen has recently been shown to mediate such co-stimulatory signals by interacting with the B7/BB-1 molecule expressed on activated B cells and monocytes. We show in this study that activated keratinocytes, both in vitro and in vivo display a discordance in expression between B7 and BB-1 based on differential monoclonal antibody (MAb) reactivity. Activated keratinocytes in vitro, as well as psoriatic keratinocytes and epithelial cells in the thymus, are reactive with the BB-1 MAb but not anti-B7 MAbs. These BB-1 positive cells fail to express detectable B7 messenger RNA by Northern blot analysis. Furthermore, keratinocytes bind specifically to CD28-transfected COS7 cells, and this binding is inhibited by anti-CD28 and anti-BB-1 but not B7 MAbs. These studies suggest: 1) that the MAb against BB-1 binds a functional epitope on a molecule distinct from B7 as detected on activated keratinocytes in vitro and in vivo and 2) that keratinocytes in skin and epithelial cells in thymus can express cell-surface molecules that might mediate T-cell co-stimulation via CD28.

Antibodies, Monoclonal↗