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PubMed1998

The human Nramp2 gene: characterization of the gene structure, alternative splicing, promoter region and polymorphisms.

Nramp2 is a gene encoding a transmembrane protein that is important in metal transport, in particular iron. Mutations in nramp2 have been shown to be associated with microcytic anemia in mk/mk mice and defective iron transport in Belgrade rats. Nramp2 contains a classical iron responsive element in the 3' untranslated region that confers iron dependent mRNA stabilization. In this report, we describe a splice variant form of human nramp2 that has the carboxyl terminal 18 amino acids substituted with 25 novel amino acids and has a new 3' untranslated region lacking a classical iron-responsive element. This splice form of nramp2, nramp2 non-IRE, was found to be derived from splicing of an additional exon into the terminal coding exon. The nramp2 gene is comprised of 17 exons and spans more than 36 kb. It contains an additional 5' exon and intron (exon and intron 1) and an additional 3' exon (exon 17) and intron (intron 16) as compared to nramp1, a homologous gene. The additional exons and introns account for much of the difference in length between nramp2 (> 36 kb) and nramp1 (12 kb). The exon-intron borders of nramp2 exons 3-15 are homologous to nramp1 exons 2-14. The nramp2 5' regulatory region contains two CCAAT boxes but lacks a TATA box. The 5' regulatory region of nramp2 also contains five potential metal response elements (MRE's) that are similar to the MRE's found in the metallothionein-IIA gene, three potential SP1 binding sites and a single gamma-interferon regulatory element. Five single nucleotide mutations or polymorphisms were identified within the nramp2 gene. One of these, 1303C-->A, occurs in the coding region of nramp2 and results in an amino acid change from leucine to isolecine. A polymorphism, 1254T/C, also occurs in the coding region of nramp2 but does not cause an amino acid change. The other 3 polymorphisms are within introns (IVS2 + 11A/G, IVS4 + 44C/A, and IVS6 + 538G/Gdel). In addition, a polymorphic microsatellite TATATCTATATATC (TA)6-7 (CA)10-11 CCCCCTATA (TATC)3 (TCTG)5 TCCG (TCTA)6 was identified in intron 3. Analysis of cDNA derived by direct amplification of reversed transcribed RNA or cDNA clones isolated from a library provide evidence of skipping of exons 10 and 12 of nramp2. Deletion of either of these exons would result in a sequence that remains in frame yet would generate a protein that would lack transmembrane spanning region 7 or 8 respectively. The deletion of a single transmembrane domain would have severe topological consequences. The coding region of the nramp2 gene of hemochromatosis patients with or without mutations in the hemochromatosis gene, HFE, were examined and found to be normal. One hemochromatosis patient, with a normal HFE genotype, was heterozygous for the 1303C-->A mutation. Furthermore, in an examination of hemochromatosis patients with mutant HFE and normal HFE genes, we did not observe a linkage disequilibrium of either group with a particular nramp2 haplotype. These data suggest that mutations in nramp2 are not commonly associated with hemochromatosis.

Amino Acid Sequence↗

PubMed1988

Amino acid substitution at position 226 of the hemagglutinin molecule of influenza (H1N1) virus affects receptor binding activity but not fusion activity.

The receptor binding site of the hemagglutinin (HA) molecule of type A influenza virus A/USSR/90/77 (H1N1) has been studied. Site-specific mutagenesis has been used to introduce base changes into the sequence that codes for the amino acid residue at position 226 on the HA molecule, and mutant sequences replaced the wild-type sequence of the HA gene of the SV40-HA recombinant virus (SVHA). Mutant HA proteins were expressed in African green monkey kidney cells and analyzed for receptor binding and fusion activities. Two mutant HA proteins containing single amino acid substitutions of Asn and Met for Gln at position 226 retained their receptor binding activity, but others with amino acid substitutions Glu, His, Leu, Val, and Thr for Gln at position 226 lost this activity. All the mutant proteins retained their fusion activity. On the other hand, another four mutants containing single amino acid substitutions at positions other than 226 retained the receptor binding and fusion activities, despite the drastic change in charge or polarity to the respective amino acids. These results suggest that amino acid residue 226 of the H1 subtype of HA is critical for receptor binding activity of the HA protein. Our results also show that the lack of receptor binding activity of the HA protein does not affect fusion activity.

Amino Acids↗

PubMed2005

Candidate gene screening for posterior polymorphous dystrophy.

PURPOSE: To perform candidate gene screening for posterior polymorphous corneal dystrophy (PPCD). The initial 3 genes chosen, ID1, BCL2L1, and VSX1, lie within the region on chromosome 20 to which the PPCD gene has been linked, and mutations in VSX1 have previously been identified in patients with PPCD. METHODS: DNA extraction, PCR amplification, and direct sequencing of the VSX1, BCL2L1, and ID1 genes were performed in 14 affected patients (12 families) as well as in unaffected family members and healthy control subjects. RESULTS: No coding region mutations in the BCL2L1 or ID1 genes were identified in affected patients. In the VSX1 gene, the previously identified Gly160Asp missense change was not present in any of our 12 probands, and the Asp144Glu mutation was identified in 1 affected patient as well as 1 unaffected control individual. Additionally, 2 synonymous substitutions were identified, Ala182Ala (8 affected patients from 8 families) and Gly239Gly (1 affected patient and 1 unaffected patient from the same family). In the ID1 gene, the synonymous substitution Gly216Gly was observed in 2 affected patients (2 families) who also demonstrated a single nucleotide change in both the 5'UTR (2129T>C) and 3'UTR (3267A>G). Another 5'UTR change, 2177T>C, was identified in 1 affected patient and his unaffected parent, both of whom also demonstrated the 2129T>C and 3267A>G changes. CONCLUSIONS: None of the 12 probands with PPCD demonstrated the previously described Gly160Asp mutation within the VSX1 gene. The Asp144Glu missense change, present in an affected patient as well as an unaffected control individual, appears to be a rare polymorphism, not a disease-causing mutation. No coding region changes were identified in the ID1 or BCL2L1 genes. Therefore, although we report a number of novel polymorphisms in the VSX1 and ID1 genes, the failure to identify any sequence variants that sort with the disease phenotype suggests that other genetic factors are involved in PPCD.

Corneal Dystrophies, Hereditary↗

PubMed2001

Temporal representation of iterated rippled noise as a function of delay and sound level in the ventral cochlear nucleus.

The discharge patterns of single units in the ventral cochlear nucleus (VCN) of anesthetized guinea pigs were examined in response to iterated rippled noise (IRN) as a function of the IRN delay (which determines the IRN pitch) and the IRN sound level. Delays were varied over five octaves in half-octave steps, and sound levels were varied over a 30- or 50-dB range in steps of 5 dB. Neural responses were analyzed in terms of first-order and all-order inter-spike intervals (ISIs). The IRN quasi-periodicity was preserved in the all-order ISIs for most units independent of unit type or best frequency (BF). A deterioration of the temporal all-order code was found, however, when the neural response was influenced by inhibition. The IRN quasi-periodicity was also preserved in first-order ISIs for a limited range of IRN delays and levels. Sustained Chopper units (CS) in the VCN responded with very regular ISIs when the IRN delay corresponded to the unit's chopping period; i.e., the unit showed an increased proportion of intervals corresponding to the IRN delay (interval enhancement) relative to an equal-level, white-noise stimulation. This interval enhancement has a band-pass characteristic with a peak corresponding to the chopping period. Moreover, for CS units in rate saturation, the chopping period, and thus the interval enhancement to the IRN, did not vary with level. Units classified as onset-chopper also show a band-pass interval enhancement to the IRN stimuli; however, they show more level-dependent changes than CS units. Primary-like (PL) units also show level-dependent changes in their ability to code the IRN pitch in first-order intervals. The range of delays where PL units showed interval enhancement was broader and extended to shorter delays. Based on these findings, it is suggested that CS units may play an important role in pitch processing in that they transform a higher-order interval code into a first-order interval place code. Their limited dynamic range together with the preservation of the temporal stimulus features in saturation may serve as a physiological basis for the perceived level independence of pitch.

Action Potentials↗

PubMed2001

Screening for mutations in the steroidogenic acute regulatory protein and steroidogenic factor-1 genes, and in CYP11A and dosage-sensitive sex reversal-adrenal hypoplasia gene on the X chromosome, gene-1 (DAX-1), in hyperandrogenic hirsute women.

Abstract Abnormalities in adrenal and/or ovarian steroidogenesis are found in most patients with hirsutism. The rate-limiting step in the synthesis of steroids in the ovary and the adrenal is the conversion of cholesterol into pregnenolone by cholesterol side-chain cleavage enzyme (P450scc), encoded by the gene CYP11A, after cholesterol is introduced into the mitochondria by the steroidogenic acute regulatory protein (StAR). DAX-1 is a repressor of StAR gene expression, and steroidogenic factor-1 (SF-1) is a regulator of CYP11A, DAX-1, and StAR gene. Mutations in any of these factors resulting in gain of function, or loss of repression, of StAR or P450scc might contribute to the steroidogenic abnormalities present in hirsute patients. In the present study we have screened, using heteroduplex analysis, the genes encoding StAR and SF-1 as well as DAX-1 and CYP11A for mutations in genomic DNA from 19 women presenting with hirsutism and increased serum androgen levels. When variants were found, analysis was extended to a larger group of hyperandrogenic patients and nonaffected women. Two variants were identified in the SF-1 gene. A G-->C change in exon 6, resulting in an Arg(365)Pro mutation, was found in 1 of 45 patients, but not in controls. Also, a Gly(146)Ala missense mutation, resulting from a G-->C change in exon 4, was found in 2 of 48 patients and in 2 of 50 nonaffected individuals. We identified a C-->T base pair change at position -33 of the StAR gene. Three of 48 patients and 3 of 43 controls presented this variant. No mutations were found in coding regions of the StAR gene. Analysis of CYP11A-coding regions identified a G-->A change in exon 3, resulting in a Val(179)Ile missense mutation. This mutation was found in 1 of 29 patients studied and was not present in 50 controls. Finally, analysis of DAX-1 showed no variant in any of the women studied. In conclusion, mutations in StAR, SF-1, CYP11A, and DAX-1 are seldom found in hirsute patients and do not explain the steroidogenic abnormalities found in these women.

Adrenal Glands↗

PubMed1995

Hospital discharge register data in the assessment of trends in acute myocardial infarction. FINMONICA AMI Register Study Team.

We evaluated the reliability hospital discharge register data in the assessment of acute myocardial infarction trends. In the FINMONICA study areas, trends in age standarized attack rates for the years 1983-90 were calculated independently from two sources: the nationwide Finnish hospital discharge register and the FINMONICA acute myocardial infarction register. The trends were compared by a statistical regression model. The trends obtained from the hospital discharge register were very similar to the trends obtained from the FINMONICA acute myocardial infarction register. The attack rates differed significantly, however, and the change in the International Classification of Diseases version from version 8 to version 9 brought on a change in the attack rates obtained from the hospital discharge register. Thus, hospital discharge register data can be used to assess acute myocardial infarction trends in the community. However, modifications of the International Classification of Diseases codes (new versions of the classification) and changes in the clinical use of the codes for coronary heart disease can have an impact on the attack rates obtained from the hospital discharge register, and the reliability of the hospital discharge register data should be regularly assessed.

Adult↗

PubMed1992

SSCP and segregation analysis of the human type X collagen gene (COL10A1) in heritable forms of chondrodysplasia.

Type X collagen is a homotrimeric, short chain, nonfibrillar collagen that is expressed exclusively by hypertrophic chondrocytes at the sites of endochondral ossification. The distribution and pattern of expression of the type X collagen gene (COL10A1) suggests that mutations altering the structure and synthesis of the protein may be responsible for causing heritable forms of chondrodysplasia. We investigated whether mutations within the human COL10A1 gene were responsible for causing the disorders achondroplasia, hypochondroplasia, pseudoachondroplasia, and thanatophoric dysplasia, by analyzing the coding regions of the gene by using PCR and the single-stranded conformational polymorphism technique. By this approach, seven sequence changes were identified within and flanking the coding regions of the gene of the affected persons. We demonstrated that six of these sequence changes were not responsible for causing these forms of chondrodysplasia but were polymorphic in nature. The sequence changes were used to demonstrate discordant segregation between the COL10A1 locus and achondroplasia and pseudoachondroplasia, in nuclear families. This lack of segregation suggests that mutations within or near the COL10A1 locus are not responsible for these disorders. The seventh sequence change resulted in a valine-to-methionine substitution in the carboxyl-terminal domain of the molecule and was identified in only two hypochondroplasic individuals from a single family. Segregation analysis in this family was inconclusive, and the significance of this substitution remains uncertain.

Base Sequence↗

PubMed1998

Association of a common polymorphism in the factor XIII gene with myocardial infarction.

Factor XIII when activated by thrombin, crosslinks fibrin, however its role in thrombotic disorders is unknown. A common point mutation (G-->T) in exon 2 of the A-subunit gene which codes for an amino acid change three amino acids from the thrombin activation site (Factor XIIIVal34Leu) is a candidate for a role in the pathogenesis of acute myocardial infarction. Factor XIII genotype frequencies were determined in a case-control study of 398 caucasian patients and 196 healthy controls. Patients had undergone angiography for investigation of coronary artery disease and were evaluated for a history of myocardial infarction. The prevalence of the mutation was lower in patients with myocardial infarction than without (32% vs. 50%), p = 0.0009 and than in controls (32% vs. 48%), p = 0.005. Patients possessing the mutation with a history of myocardial infarction had higher PAI-1 concentrations (mean, 27.9 vs. 16.7 ng/ml, p = 0.004) and the PAI-1 4G/4G genotype was commoner (43% vs. 26%, p = 0.03). There was no difference in PAI-1 4G/4G genotype (33% vs. 32%) and PAI-1 levels (mean, 21.0 vs. 20.9 ng/ml) in patients possessing wild type with MI compared to those without MI. These results indicate that the G-->T mutation coding for factor XIIIVal34Leu is protective against myocardial infarction and suggest a mechanism whereby elevated levels of PAI-1 may contribute to vascular risk.

Case-Control Studies↗

PubMed1991

Use of PCR amplification of cDNA to study mechanisms of human cell mutagenesis and malignant transformation.

PCR is widely employed to amplify short segments of genomic DNA to determine if a specific change has occurred. But some investigators need to sequence the entire coding region of mammalian genes to determine what specific changes have occurred. In 1989, we [Yang et al: Gene 83:347-354] described a method to copy mRNA of the hypoxanthine (guanine) phosphoribosyl transferase (HPRT) gene directly from the lysate of a clone of 6-thioguanine-resistant mutant diploid human fibroblasts without the need for RNA extraction or DNA template purification. To avoid detecting random changes introduced by polymerases, 100 to 500 cells from an individual clone, each containing the identical mutation, are lysed and the cDNA is amplified 10(10)-to 10(11)-fold to obtain 5 to 10 micrograms of DNA. The consensus sequence of the cDNA is determined by direct nucleotide sequencing. Using this method, we have investigated the kinds of mutations induced by carcinogens in the coding region of the HPRT gene and their location in the gene and examined the role of DNA repair in this process. Normal repair-proficient human cells and cells deficient in DNA repair were exposed to mutagens in exponential growth or synchronized and exposed at the beginning of S phase or in G1 phase several hr prior to DNA replication. The kinds and location of mutations in the HPRT gene were determined and knowledge of the nature of the DNA lesions formed by the various mutagens allowed assignment of the DNA strand in which the premutagenic lesion that gave rise to the mutation had been located. Related assays involving PCR have been used to determine the nature of mutations in the coding region of the H-, N-, or K-ras genes of tumor-derived malignant human cells and to determine whether or not such cells express specific growth factor genes.

Cell Transformation, Neoplastic↗

PubMed1992

Time course of the in vivo effects of thyroid hormone on cardiac gene expression.

The rate of response to thyroid hormone on cardiac growth, heart rate, and the relative changes in messenger RNA (mRNA) coding for alpha- and beta-myosin heavy chain (MHC), slow sarcoplasmic reticulum calcium-adenosine triphosphatase, and thyroid hormone receptors in ventricular tissue of hypothyroid rats was investigated. Hypothyroid rats had significantly smaller hearts, with slower heart rates and expressed no alpha-MHC mRNA as analyzed by an S1 nuclease protection assay when compared to euthyroid animals that expressed 79% alpha-MHC. Twelve hours after treating hypothyroid rats with 20 micrograms of L-T4, detectable levels of alpha-MHC mRNA were present and the shift to alpha-MHC mRNA was complete by 72 h of treatment. Northern blot analysis showed that hypothyroidism resulted in a 60% decrease in the level of sarcoplasmic reticulum calcium-adenosine triphosphatase mRNA which increased after 12 h of T4 administration and was 2.5-fold (P less than 0.05) greater than euthyroid levels after 72 h. In contrast, thyroid hormone receptor mRNA levels measured in poly(A)+ RNA were elevated in hypothyroid rats and decreased to euthyroid levels within 24 h after thyroid hormone treatment. These changes in cardiac gene expression occurred simultaneously with changes in both cardiac size and heart rate. The current studies characterize the coordinated changes and the time course for gene expression that occur in the hypothyroid heart after acute T4 administration.

Animals↗

PubMed1993

The detection and characterization of multiple hemagglutinin-esterase (HE)-defective viruses in the mouse brain during subacute demyelination induced by mouse hepatitis virus.

It has previously been shown that passive immunization with antibodies specific for the hemagglutinin-esterase (HE) protein of mouse hepatitis virus (MHV) prevents acute lethal encephalitis, resulting in a subacute and chronic demyelination in mice infected with JHM(2), an isolate of the neurotropic JHM strain of MHV. To determine possible genetic changes occurring during infection, viruses were isolated from the brain of infected mice at various time points after infection and examined for the patterns of their structural proteins. The results showed that the sizes and expression levels of the viral spike, membrane, and nucleocapsid proteins were constant among 161 virus isolates throughout the infection. In contrast, most of the viruses isolated later in infection did not synthesize HE protein. This finding suggests that the HE gene expression is extremely variable and is preferentially lost during prolonged viral infections. In contrast, when viruses were passaged in tissue culture, no significant accumulation of HE protein-defective mutants was observed, suggesting that the accumulation of HE protein-defective mutants in infected animals was most likely the result of the positive selection for these mutants during the subacute and chronic infection. The genetic defects of HE gene in these mutants were characterized by cloning, sequencing, and in vitro translation of HE genes. Most of the mutations in the HE protein-defective mutants consisted of deletions of various lengths at different sites within the HE-coding region, resulting in the change of the reading frame and early termination. However, most of the truncated HE proteins were not detected in the infected cells. Since viruses from different mice exhibited different types of defects, the HE mutations probably occurred de novo in the brain. These results demonstrated the exceptionally rapid selection of HE-defective mutants during viral infection of mice and suggest that their selection may be related to the neuropathogenicity or persistence of MHV.

Animals↗

PubMed1999

Molecular and cellular adaptations to carbohydrate and fat intake.

Adaptation to carbohydrate and fat intake involves changes in a number of biochemical parameters at the cellular level. A change in the concentration of fat or carbohydrate in the blood acts directly to influence metabolic pathways by altering the flux of intermediates into cells. This in turn alters the concentration of hormones and other signaling molecules and changes the rate of expression of genes coding for key regulatory proteins or enzymes in metabolic pathways. These effects occur at different rates and in a tissue-specific manner in response to diet. A key metabolic adaptation involves changes in the level of expression of genes coding for proteins of critical importance in energy metabolism; this is largely due to an altered rate of transcription of selected genes under the control of hormones and/or carbohydrate and lipid. The mediators of this effect are transcription factors, that is, nuclear proteins which integrate the effects of hormones and substrates with the transcription process by binding to response elements in the promoters of regulated genes and interacting with the transcription machinery at the TATA box, thereby altering the activity of RNA polymerase II. In this review we will outline the hierarchy of cellular adaptations to diet and will emphasize the latest concepts of gene regulation in response to metabolites and hormones. In particular, we will review the role of the various transcription factors involved in the regulated expression of the gene for the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.132), a key gluconeogenic enzyme.

Adaptation, Physiological↗

PubMedDate not supplied

Defense style and the perception of asthma.

Approximately 15% of patients with bronchial asthma are unable to sense marked changes in airway obstruction. We have investigated the hypothesis that inability to sense changes in the severity of bronchial asthma varies with insensitivity to emotional arousal, which in turn is associated with repressive defense styles. Nine asthmatic patients were studied comparing actual changes in peak flow rate using a coded peak flow meter and in arousal during a stress-inducing psycholinguistic protocol with perceived changes. Our hypotheses were confirmed. Ability to perceive changes in asthma could be predicted from performance on the psycholinguistic stress test (Spearman's rho = +0.733, p less than 0.01). Repressors performed significantly worse on the asthma perception task (Spearman's rho = -0.650, p less than 0.05). The results suggest a role for defense pathology in the psychomaintenance of asthma.

Adult↗

PubMed2006

Use of physiological constraints to identify quantitative design principles for gene expression in yeast adaptation to heat shock.

BACKGROUND: Understanding the relationship between gene expression changes, enzyme activity shifts, and the corresponding physiological adaptive response of organisms to environmental cues is crucial in explaining how cells cope with stress. For example, adaptation of yeast to heat shock involves a characteristic profile of changes to the expression levels of genes coding for enzymes of the glycolytic pathway and some of its branches. The experimental determination of changes in gene expression profiles provides a descriptive picture of the adaptive response to stress. However, it does not explain why a particular profile is selected for any given response. RESULTS: We used mathematical models and analysis of in silico gene expression profiles (GEPs) to understand how changes in gene expression correlate to an efficient response of yeast cells to heat shock. An exhaustive set of GEPs, matched with the corresponding set of enzyme activities, was simulated and analyzed. The effectiveness of each profile in the response to heat shock was evaluated according to relevant physiological and functional criteria. The small subset of GEPs that lead to effective physiological responses after heat shock was identified as the result of the tuning of several evolutionary criteria. The experimentally observed transcriptional changes in response to heat shock belong to this set and can be explained by quantitative design principles at the physiological level that ultimately constrain changes in gene expression. CONCLUSION: Our theoretical approach suggests a method for understanding the combined effect of changes in the expression of multiple genes on the activity of metabolic pathways, and consequently on the adaptation of cellular metabolism to heat shock. This method identifies quantitative design principles that facilitate understating the response of the cell to stress.

Adaptation, Physiological↗

PubMed1997

On wearing two hats: role conflict in serving as both psychotherapist and expert witness.

OBJECTIVE: This article explores the clinical, legal, and ethical problems that typically occur when a psychotherapist serves as both a treating clinician and forensic evaluator (or expert witness) in the same case. METHOD: The professional literature, ethics codes, opinion surveys, and the changing economic and institutional contexts of psychotherapy are reviewed in order to identify obstacles to widespread recognition of this straightforward ethical issue. The processes of psychotherapy and forensic evaluation are then analyzed so as to reveal fundamental incompatibilities between the psychotherapist's clinical and legal functions. RESULTS: Attempting to treat and evaluate the same person typically creates an irreconcilable role conflict. This role conflict manifests itself in different conceptions of truth and causation, different forms of alliance, different types of assessment, and different ethical guidelines. CONCLUSIONS: Although circumstances sometimes compel a practitioner to assume the dual role of treater and evaluator, the problems that surround this practice argue for its avoidance whenever possible.

Attitude of Health Personnel↗

PubMed1993

The status of high-energy photon and electron beam dosimetry five years after the implementation of the IAEA Code of Practice in the Nordic countries.

The status of the dosimetry of high-energy photon and electron beams is analysed, taking into account the main developments in the field since the implementation of the IAEA Code of Practice in the Nordic countries. In electron beam dosimetry, energy-range relationships are discussed; Monte-Carlo results with different codes are compared with the experimentally derived empirical expression used in most protocols. Updated calculations of water-to-air stopping-power ratios following the changes in the Monte-Carlo code used to compute actual Sw,air values are compared with the data included in most dosimetry protocols. The validity of the commonly used procedure to select stopping-power ratios for a clinical beam from the mean energy at the phantom surface and the depth of measurement, is analysed for 'realistic' electron beams. In photon beam dosimetry, calculated correction factors including the effect of the wall plus waterproofing sleeve and existing data on the shift of the effective point of measurement of an ionization chamber, are discussed. New calculations of medium-to-air stopping-power ratios and their correlation with the quality of the beam obtained from the convolution of Monte-Carlo kernels are presented together with their possible practical implications in dosimetry. Trends in Primary Standard Dosimetry Laboratories towards implementing calibrations in terms of absorbed dose to water are presented, emphasizing controversial proposals for the specification of photon beam qualities. Plane-parallel ionization chambers are discussed regarding aspects that affect determinations of absorbed dose, either through the different methods used for the calibration of these chambers or by means of correction factors. Recent studies on the effect of the central electrode in Farmer-type cylindrical chambers are described.

Monte Carlo Method↗

PubMed1995

Revenue enhancement through total quality management/continuous quality improvement (TQM/CQI) in outpatient coding and billing.

To survive and thrive, rural hospitals are seeking enhanced revenues. This study focuses on outpatient laboratory and radiology coding and billing accuracy in a nonrandom sample of seven rural hospitals in a Western state. Information was gathered on (1) procedures incorrectly coded, (2) potential revenue increases from correct coding and billing, (3) barriers to implementing changes, and (4) perceived audit value. The identified major source of potential revenue enhancement was increased fees from private payers. Correct coding and billing to Medicare and Medicaid offered the potential of additional revenue. Participating administrators appreciated the validation of coding and billing practices and identification of potential enhanced revenues. Five of seven hospitals (71.4%) selectively implemented recommended changes. Complete compliance with recommended changes was limited by barriers of tradition, competition, and reimbursement, which must be overcome to realize successful implementation. Joint Commission on Accreditation of Healthcare Organization's (JCAHO) new Total Quality Management/Continuous Quality Improvement (TQM/CQI) emphasis provides an opportunity for revenue enhancement through coding/billing assessments and interdepartmental focus and coordination.

American Hospital Association↗

PubMed2003

In vitro characterization of a human calcitonin receptor gene polymorphism.

Calcitonin is a 32 amino acid peptide hormone that inhibits bone resorption by stimulating calcitonin receptors (CTR) located on the surfaces of osteoclasts. A polymorphism at nucleotide 1340 of the human calcitonin receptor gene (CALCR) lies within the coding region and has the potential to change the amino acid at codon 447 from leucine to proline. In the present study, we scanned the coding region, portions of the 5'-flanking and 3'-flanking sequences, and the intron-exon boundaries of the human CALCR gene for additional polymorphisms, and determined the frequency of the codon 447 polymorphism in several ethnic groups. Because a leucine to proline change has the potential for significant structural alteration, receptor genes encoding either leucine or proline at residue 447 were transiently expressed in COS-7 cells to determine the binding and functional consequences of this polymorphism. Our complete polymorphism scan of the CALCR gene identified 11 polymorphic sites in the gene and confirmed the presence of the previously identified nucleotide T1340C (codon 447) polymorphism. Ten of the 11 polymorphisms were single nucleotide polymorphisms (SNPs). For the codon 447 polymorphism, the prevalence of the TT genotype (leucine) was 59% in Caucasians, 27% in African-Americans, 0% in Asians, and 20% in Hispanics. The presence of this SNP appears to have no statistically significant difference with the receptor's ability to bind calcitonin or signal when activated with the hormone.

Analysis of Variance↗