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Biomedical subjects

R S Ross

Publications and source records attributed to R S Ross.

At least 37 records · Page 2Linked to original sources

Immunodominant B-cell domains of hepatitis C virus envelope proteins E1 and E2 identified during early and late time points of infection.

BACKGROUND/AIMS: We characterized immunoreactive B-cell domains of hepatitis C virus (HCV) envelope proteins E1 and E2 by a peptide ELISA using sera of patients who were infected by the same isolate of HCV (HCV-AD78). METHODS: Fifty-four overlapping peptides which corresponded to the sequence of E1 and E2 of isolate HCV-AD78 were used to detect specific antibodies. Three groups of HCV-AD78 related sera were analyzed. Two groups were from sera obtained at early time points of infection (months 4-15) from patients who later resolved infection (group A), or who later developed chronic disease (group B). Group C sera were from later time points of chronic disease. As a control, sera of chronic HCV patients who did not have HCV-AD78 infection were also analyzed (group D). RESULTS: In group A, 25 of the 54 peptides produced OD405 above the cut-off, whereas 17 peptides produced such values in group B. Only 10 and 3 peptides yielded such values in groups C and D, respectively. The overall prevalence of antibodies against peptides was high in the early phase of infection (means of 28.7+/-14.8% and 25.9+/-14.5% in groups A and B, respectively). At later time points of chronic infection (group C), the overall prevalence was lower (mean 18.6+/-15.4%). Group D sera produced the lowest overall prevalence (mean 13.2+/-14.1%). Three peptides, covering aa271-290, aa481-500 and aa551-570, were recognized significantly more frequently (p<0.05) by group A sera than group B sera. CONCLUSIONS: We conclude that more linear epitopes of the HCV envelope are recognized with a high prevalence of antibodies, as was suggested previously. However, most B-cell domains of the HCV envelope induce a similarly high antibody response in patients who resolve infection or develop chronic disease.

Adult↗

Detection of TT virus DNA in specimens other than blood.

BACKGROUND: Recently, a new infective agent of humans, TT virus (TTV), was identified. Very high prevalence rates of TTV in different population groups, including apparently healthy individuals, were reported for several countries. OBJECTIVES, STUDY DESIGN: In order to investigate whether or not non-parenteral transmission routes can contribute to TTV spread, we have tested saliva, urine, and stool samples from eight TT viraemic individuals for the presence of TTV DNA by polymerase chain reaction. RESULTS: TTT DNA was detected in saliva of five subjects and stools of four patients. None of the urine samples contained TTV DNA. Viral titres in saliva were close to those found in serum. In feces, TTV DNA could only be detected in low concentrations. CONCLUSIONS: Our findings on the presence of TTV DNA in saliva and stool suggest that TTV might be transmitted non-parenterally.

DNA Virus Infections↗

Comparison of bending stiffness of six different colours of copolymer polypropylene.

This paper compares the bending stiffness of 5 different colours of copolymer polypropylene (CCP) with that of natural copolymer polypropylene (NCP). Flesh coloured and natural sheets are supplied thicker than other pigmented sheet. The bending stiffness of a specimen may be defined as EI, i.e. the product of E, Young's modulus of elasticity and I, the 2nd moment of area. Strips of "as supplied" (AS) and "post-draped" (PD) specimen were clamped and subjected to bending to assess the effect of pigmentation on bending characteristics. The gradient of the graph of bending deflection delta versus bending moment enables EI to be estimated. The process of thermoforming polypropylene reduces EI, the bending stiffness. However, the manual draping and vacuum procedure introduces so many variables that it is difficult to quantify the effect of pigmentation. The E of a bent specimen may be estimated from the gradient of the graph of deltaI versus bending moment. In the case of AS sheet, the effect of pigmentation on E is inconclusive. PD specimens indicate a significant reduction in E due to thermoforming. This was verified by an electron-microscope study of AS and PD specimens. Draping an ankle-foot orthosis (AFO) results in a non-uniform wall thickness. The results of this study with respect to the effects of pigmentation on the bending stiffness of AFOs are inconclusive. More detailed studies require to be completed in order to confirm which factors are responsible for this non-uniformity in wall thickness and consequent variation in bending stiffness.

Biomechanical Phenomena↗

Primary bilateral adrenal lymphoma.

Primary adrenal lymphoma is a rare primary neoplastic disease of the adrenal glands, with up to 65 cases reported in the literature over the past 40 years. The increasing use and sophistication of medical diagnostic imaging has allowed this disease to be diagnosed more frequently premortem, presenting more opportunity for treatment. The true incidence of these neoplasms is not known, nor is it clear why historical autopsy series have not reported this neoplasm more frequently, and why its existence has been documented more recently with advanced diagnostic imaging. This review has presented our new case, and reviewed 5 more in the literature, bringing the total number of cases to over 70. Accumulation of more cases and the experience treating these cases is needed to develop a better picture of diagnostic procedures and treatment regimens that have maximum efficacy.

Adrenal Gland Neoplasms↗

High prevalence of TT virus infection in Brazilian blood donors.

A recent report has described the molecular cloning and characterization of a novel, single-stranded DNA virus, named TT virus (TTV), which was present in the sera of Japanese patients with posttransfusion hepatitis of unknown etiology [Okamoto et al. (1998) Hepatology Research 10:1-16]. Using a nested polymerase chain reaction assay, sera from Brazilian patients with acute non A-C hepatitis and blood donors were examined for the presence of TTV DNA sequences. Thirty-seven of 52 (71%) patients with acute non A-C hepatitis and 45 of 72 (62%) blood donors were found to have TTV sequences in their sera. Such a high proportion in blood donors indicated that TTV infection is common in the general Brazilian population. Partial nucleotide sequences (326 bases in open reading frame 1) from seven isolates were determined. By phylogenetic analysis, four TTV strains were classified into the genomic subgroup G1a described previously. The three others belonged to subgroup G1b. Sequence homologies between strains belonging to a same subgroup were 92.9-99.1%, whereas homologies of 85.9-90.2% were calculated between isolates from different subgroups.

Adolescent↗

Beta1 integrins participate in the hypertrophic response of rat ventricular myocytes.

Multiple signaling pathways have been implicated in the hypertrophic response of ventricular myocytes, yet the importance of cell-matrix interactions has not been extensively examined. Integrins are cell-surface molecules that link the extracellular matrix to the cellular cytoskeleton. They can function as cell signaling molecules and transducers of mechanical information in noncardiac cells. Given these properties and their abundance in cardiac cells, we evaluated the hypothesis that beta1 integrin function is involved in the alpha1-adrenergic mediated hypertrophic response of neonatal rat ventricular myocytes. The hypertrophic response of this model required interaction with extracellular matrix proteins. Specificity of these results was confirmed by demonstrating that ventricular myocytes plated onto an anti-beta1 integrin antibody supported the hypertrophic gene response. Adenovirus-mediated overexpression of beta1 integrin augmented the myocyte hypertrophic response when assessed by protein synthesis and atrial natriuretic factor production, a marker gene of hypertrophic induction. DNA synthesis was not altered by integrin overexpression. Transfection of cultured cardiac myocytes with either the ubiquitously expressed beta1A integrin or the cardiac/skeletal muscle-specific beta1 isoform (beta1D) activated reporter expression from both the atrial natriuretic factor and myosin light chain-2 ventricular promoters, genetic markers of ventricular cell hypertrophy. Finally, suppression of integrin signaling by overexpression of free beta1 integrin cytoplasmic domains inhibited the adrenergically mediated atrial natriuretic factor response. These findings show that integrin ligation and signaling are involved in the cardiac hypertrophic response pathway.

Adenoviridae↗

Distinct prevalence of antibodies to the E2 protein of GB virus C/hepatitis G virus in different parts of the world.

Since the identification of the new human virus, GB virus C (GBV-C)/hepatitis G-virus (HGV), in 1995/1996, reverse transcription polymerase chain reaction remained the sole available diagnostic tool for GBV-C/HGV infection. Recently, a serologic test based on the detection of antibodies to the putative envelope protein 2 (anti-E2) has been introduced. We used this assay for a seroepidemiological survey including 3,314 healthy individuals from different parts of the world, 123 patients from Germany who were suspected to have an increased risk of acquiring GBV-C/HGV infection, 128 multiple organ donors, and 90 GBV-C/HGV RNA positive persons. In European countries, anti-E2 seropositivity ranged from 10.9% (Germany) to 15.3% (Austria). In South Africa (20.3%) and Brazil (19.5%), even higher anti-E2 prevalence rates were recorded. In Asian countries like Bhutan (3.9%), Malaysia (6.3%), and the Philippines (2.7%), anti-E2 positivity was significantly lower. GBV-C/HGV anti-E2 prevalence in potential "risk groups," i.e., patients on hemodialysis and renal transplant recipients, did not vary significantly from anti-E2 seroprevalence in German blood donors. Anti-E2 and GBV-C/HGV RNA were found to be mutually exclusive, confirming the notion that anti-E2 has to be considered as a marker of past infection.

Antibodies, Viral↗

Lack of evidence for an association between TTV infection and severe liver disease.

BACKGROUND: In 1997 a new human virus, TTV, was identified. The clinical significance of the TTV infection, however, remains unknown. OBJECTIVE: Establishment of the prevalence of TTV DNA in different population groups in Germany and the assessment of the possible clinical significance of TTV infection. STUDY DESIGN: Detection of the TTV DNA by PCR in blood donors, patients with end-stage liver disease, and multiple transfused patients with haemotological disorders. RESULTS: TTV DNA was detected in 16 of 122 (13.1%) volunteer blood donors, in 34 of 77 (44.2%) patients with end-stage liver disease, and in 21 of 38 (55.3%) multiple transfused patients. There was no difference in the prevalence of the TTV DNA in end-stage liver disease patients with regard to sex, age, presence of HCV and HBV infection markers, and etiology of liver disease. Phylogenetic analysis of the amplified DNA fragments from 12 randomly selected TTV infected subjects demonstrated that in Germany at least two putative TTV genotypes and four subtypes are circulating. CONCLUSIONS: (i) TTV is widely spread in German population; (ii) one of the possible ways of its transmission is blood transfusion; (iii) TTV infection most probably does not generally lead to the development of the end-stage liver disease.

Adult↗

Antibodies to the E2 protein of GB virus C/hepatitis G virus: low prevalence in Asian countries.

Epidemiological investigations of GB virus C (GBV-C)/hepatitis G virus (HGV), an infectious agent discovered in 1995/1996, are facilitated by a recently developed immunoassay for the detection of antibodies to the viral envelope 2 protein (anti-E2). We used this assay to establish GBV-C/HGV prevalence in seven European, African, and Asian countries. A total of 1579 serum samples from healthy adults lacking prior exposure to known parenteral risk factors was screened. Anti-E2 positivity ranged from 13.6% (Italy) to 7.7% (Mauritius) in the European and African countries investigated. Anti-E2 prevalence was exceedingly low in the Philippines and Sri Lanka. This observation might be attributable to socio-economical and demographic factors.

Adult↗

Sequence variability in the putative coding region of TT virus: evidence for two rather than several major types.

Recently a new human virus, TT virus (TTV) was identified in the serum of a patient with post-transfusion hepatitis of unknown aetiology. Comparative sequence analysis of a 222 nt fragment of ORF 1 of TTV was performed to assess the genomic variability of this virus. Phylogenetic analysis of the nucleotide sequences of 76 TTV isolates collected in 17 countries segregated them into two major groups: TTV 1 and TTV 2. The TTV 1 group comprised two distinct subgroups, which corresponded to previously described TTV subtypes 1a and 1b. The TTV 2 group was separated into four main branches, two of which included sequences previously provisionally attributed as TTV types 2 and 3. Bootstrap resampling, however, did not support the reliability of this grouping, suggesting that the isolates in the TTV 2 group should be considered as subtypes of a single type rather than different TTV types.

Base Sequence↗

GB virus C infection in patients who underwent liver transplantation.

To elucidate the impact of an infection with the recently discovered GB virus C (GBV-C) on the clinical course after orthotopic liver transplantation (OLT), we studied eight patients who were GBV-C RNA positive after transplantation. Five individuals had been viraemic before transplantation, three became GBV-C RNA positive thereafter. A control group comprised eight patients without pre- or post-transplant GBV-C infection. GBV-C RNA was detected by reverse-transcription followed by nested polymerase-chain-reaction (PCR) with primers corresponding to the NS5 genome region. Nested PCR products were sequenced directly. The five patients infected with GBV-C before transplantation remained GBV-C RNA positive throughout the time of observation. Pre- and post-transplant GBV-C RNA titres were almost identical. Phylogenetic analysis revealed a very close relationship between the pre- and post-transplant viral nucleotide sequences indicating persistent GBV-C infection. No signs of hepatitis could be detected after transplantation in all GBV-C infected patients. However, four out of eight GBV-C RNA positive patients had a clinical course complicated by severe cholestasis, which was not observed in the control group. Although GBV-C infection does not lead to an increase in the rate of post-transplant hepatitis, it might be associated with severe unexplained cholestatic courses after OLT.

Adult↗

[Not Available].

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Chemistry, Clinical↗

An HF-1a/HF-1b/MEF-2 combinatorial element confers cardiac ventricular specificity and established an anterior-posterior gradient of expression.

The molecular determinants that direct gene expression to the ventricles of the heart are for the most part unknown. Additionally, little data is available on how the anterior/posterior axis of the heart tube is determined and whether the left and right atrial and ventricular chambers are assigned as part of this process. Utilizing myosin light chain-2 ventricular promoter/beta-galactosidase reporter transgenes, we have determined the minimal cis-acting sequences required for ventricular-specific gene expression. In multiple independent transgenic mouse lines, we found that both a 250 base pair myosin light chain-2 ventricular promoter fragment, as well as a dimerized 28 bp sub-element (HF-1) containing binding sites for HF1a and HF1b/MEF2 factors, directed ventricular-specific reporter expression from as early as the endogenous gene, at day 7.5-8.0 post coitum. While the endogenous gene is expressed uniformly throughout both ventricles, the transgenes were expressed in a right ventricular/conotruncal dominant fashion, suggesting that they contain only a subset of the elements which respond to positional information in the developing heart tube. Expression of the transgene was cell autonomous and its temporospatial characteristics not affected by mouse strain/methylation state of the genome. To determine whether ventricular-specific expression of the transgene was dependent upon regulatory genes required for correct ventricular differentiation, the 250 base pair transgene was bred into both retinoid X receptoralpha and Nkx2-5 null backgrounds. The transgene was expressed in both mutant backgrounds, despite the absence of endogenous myosin light chain-2 ventricular transcript in Nkx2-5 null embryos. Ventricular specification, as judged by transgene expression, appeared to occur normally in both mutants. Thus, the HF-1 element, directs chamber-specific transcription of a transgene reporter independently of retinoid X receptoralpha and Nkx2-5, and defines a minimal combinatorial pathway for ventricular chamber gene expression. The patterned expression of this transgene may provide a model system in which to investigate the cues that dictate anterior-posterior (right ventricle/left ventricle) gradients during mammalian heart development.

Animals↗

[Not Available].

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Chemistry, Clinical↗

Molecular and physiological alterations in murine ventricular dysfunction.

The present study reports the development and characterization of a murine model of right ventricular dysfunction following graded constriction in the pulmonary artery via microsurgical approaches. To analyze in vivo ventricular function, a technique of x-ray contrast microangiography was developed to allow the quantitative analysis of ventricular volumes and of ejection fraction in normal and pressure-overloaded right ventricle. Severe, chronic pulmonary arterial banding for 14 days resulted in right ventricular dilatation and dysfunction, associated with right atrial enlargement, and angiographic evidence of tricuspid regurgitation. These effects were dependent on the extent of hemodynamic overload, since more moderate pulmonary arterial constriction resulted in hypertrophy with maintenance of right ventricular function. With severe pulmonary artery constriction, the murine right ventricle displays a failing heart phenotype including chamber dilation with reduced function that resembles right ventricular dysfunction in man during chronic pulmonary arterial hypertension. Northern and immunoblot analyses demonstrate a marked down-regulation of phospholamban mRNA and its corresponding protein with both levels of constriction, while a less pronounced but significant depression of sarcoplasmic reticulum Ca(2+)-ATPase protein was observed with severe overload, suggesting that this pattern is an early genetic marker of ventricular dysfunction. By coupling mouse genetics with this murine model and the ability to assess cardiac function in vivo, one should be able to test the role of the down-regulation of phospholamban and other defined alterations in the cardiac muscle gene program in the onset of the failing heart phenotype.

Adenosine Triphosphatases↗