Biomedical subjects

A R Rosenberg

Publications and source records attributed to A R Rosenberg.

At least 19 recordsLinked to original sources

PubMed2006

Low density lipoprotein receptor transcripts correlates with liver hepatitis C virus RNA in patients with alcohol consumption.

Alcohol consumption has a major impact on the natural history of chronic hepatitis C virus (HCV) infection, although the underlying mechanisms are still debated. We designed a clinical study to evaluate the impact of alcohol abuse on both viral load and expression of low-density lipoprotein receptor (LDLR) and CD81 expression. Thirty-eight consecutive HCV-infected patients were enrolled. Group 1 (n = 18), < or =10 g alcohol/day, group 2 (n = 8), < or =30 g alcohol/day, group 3 (n = 12), >or =30 g alcohol/day. Receptors expression was measured by flow cytometry analysis in peripheral blood mononuclear cells (PBMC) and by specific real-time retrotranscription polymerase chain reaction (RT-PCR) in the liver. Serum viral load was evaluated by quantification of both HCV genomic RNA and total core antigen. The hepatic viral load was assessed by real-time RT-PCR. Serum HCV-RNA and total core antigen were significantly correlated, and were higher, albeit not significantly, in group 3 than in group 1. Alcohol consumption had no effect on expression of HCV putative receptors in PBMC, except for CD81, which was upregulated on monocytes in group 2. In the liver, viral load and levels of LDLR transcripts were significantly higher in group 3 than in group 1. Remarkably, a significant positive correlation was found between LDLR transcripts and HCV-RNA (r2 = 0.83, P < 10(-3)). Finally, in vitro experiments suggested that the effect of ethanol on LDLR expression was indirectly mediated by both tumour necrosis factor-alpha and interleukin-1beta. In conclusion, this study is the first to support a role for LDLR in the natural infection by HCV in man.

Adult↗

PubMed2005

Isotonic is better than hypotonic saline for intravenous rehydration of children with gastroenteritis: a prospective randomised study.

AIMS: To determine whether the risk of hyponatraemia in children with gastroenteritis receiving intravenous (IV) fluids is decreased by the use of 0.9% saline. METHODS: A prospective randomised study was carried out in a tertiary paediatric hospital. A total of 102 children with gastroenteritis were randomised to receive either 0.9% saline + 2.5% dextrose (NS) or 0.45% saline + 2.5% dextrose (N/2) at a rate determined by their treating physician according to hospital guidelines and clinical judgement. Plasma electrolytes, osmolality, and plasma glucose were measured before (T(0)) and 4 hours after (T(4)) starting IV fluids, and subsequently if clinically indicated. Electrolytes and osmolality were measured in urine samples. Results were analysed according to whether children were hyponatraemic (plasma sodium <135 mmol/l) or normonatraemic at T(0). RESULTS: At T(0), mean (SD) plasma sodium was 135 (3.3) mmol/l (range 124-142), with 37/102 (36%) hyponatraemic. At T(4), mean plasma sodium in children receiving N/2 remained unchanged in those initially hyponatraemic (n = 16), but fell 2.3 (2.2) mmol/l in the normonatraemic group. In contrast, among children receiving NS, mean plasma sodium was 2.4 (2.0) mmol/l higher in those hyponatraemic at baseline (n = 21) and unchanged in the initially normonatraemic children. In 16 children who were still receiving IV fluids at 24 hours, 3/8 receiving N/2 were hyponatraemic compared with 0/8 receiving NS. No child became hypernatraemic. CONCLUSIONS: In gastroenteritis treated with intravenous fluids, normal saline is preferable to hypotonic saline because it protects against hyponatraemia without causing hypernatraemia.

Anthropometry↗

PubMed2004

BK viral infection in an Australian pediatric renal transplant population.

BK virus (BKV) is recognized as a significant cause of renal allograft dysfunction in adults, and there is growing awareness of its importance in the pediatric population. Eighteen pediatric renal transplant recipients and 18 age-matched controls were prospectively studied. Anti-BKV immunoglobulin G (IgG) and IgM titres were assayed in all subjects at entry to the study. Polymerase chain reaction (PCR) for BKV DNA was performed on urine and serum at entry, and prospectively tested again at 4, 8 and 12 months. Mean age +/- s.d. of transplant recipients and controls was 14.6 +/- 3.3 and 13.9 +/- 0.33 yr respectively [not significant (NS)]. Transplant patients were studied at a mean time of 5.6 +/- 4.2 yr post-transplant. 56% of transplant patients and 39% of controls were seropositive (+ve BKV IgG) (NS). Plasma BKV PCR was positive in one transplant patient (who also had positive urine PCR) and in none of the controls. The prevalence of positive urine PCR in transplant patients was greater than in controls (33% vs. 0%, p = 0.02). Positive urine BKV PCR was more commonly found in patients treated with mycophenolate than azathioprine (p = 0.04). We conclude that the prevalence of BKV seropositivity and viral activation in this Australian pediatric renal transplant population is similar to that reported in adult and pediatric populations in other countries. BK viruria was more common in children with greater immunosuppression, suggesting that this group is at higher risk of BKV induced nephropathy.

Adolescent↗

PubMed2003

HBV associated nephrotic syndrome: resolution with oral lamivudine.

A 6 year old boy presenting with a five month history of fever, lethargy, and anorexia, was found to have hepatitis B associated membranous glomerulonephropathy and nephrotic syndrome. After two months treatment with oral lamivudine, his proteinuria cleared and serum albumin and aminotransferases normalised, associated with disappearance of hepatitis B e antigen (HBeAg) and appearance of anti-HBeAg antibodies. After 12 months, without side effects, lamivudine was discontinued. He remains well 11 months off treatment.

Administration, Oral↗

PubMed2001

HTLV-1 structural proteins.

HTLV-1 structural proteins do not appear to ensure virus transmission as efficiently as most other retrovirus structural proteins do, whereas all other retroviruses can be transmitted via either free virions or cell-to-cell contacts, infection by HTLV-1 by free virions is very inefficient, and effective infection requires the presence of HTLV-1 infected cells. This characteristic feature of HTLV-1 provides a unique tool which can be used to analyse retrovirus cellular transmission in the absence of simultaneous cell-free infection. Here we summarise what is known about HTLV-1 structural proteins and identify the questions about these proteins which remain to be answered.

Amino Acid Sequence↗

PubMed2001

The diagnosis and management of neonatal urinary ascites.

Urinary ascites in a newborn infant is unusual and most commonly indicates a disruption to the integrity of the urinary tract. The following report describes a case of urinary ascites, probably due to bladder rupture caused by umbilical artery catheterization, associated with hyponatremia, hyperkalemia and elevated serum creatinine. This unusual biochemical profile is characteristic of urinary 'autodialysis' and was corrected by bladder drainage.

Anuria↗

PubMed2001

Perception of fear, distress and pain by parents of children undergoing a micturating cystourethrogram: a prospective study.

OBJECTIVES: To investigate whether parents' expectations of their child's fear, distress or pain during a micturating cystourethrogram (MCU) are realized. METHODOLOGY: Prospective study in which parents were asked to fill out two questionnaires using a visual analogue scale, one before (pre) and the other after the MCU procedure (post), was conducted at a tertiary level paediatric hospital in Sydney, Australia. The questionnaires were designed to compare the parents' anticipated and experienced anxiety about their child's procedure and their perception of fear, distress and pain in their child during and after the procedure. The parents' satisfaction with information provided to them on the procedure was also recorded. Twenty-five parents participated in the study. RESULTS: There were significant differences between anticipated and experienced parental anxiety. Parents' reporting of fear, distress and pain in their child during the MCU and after the procedure was lower than they had anticipated. There was a significant correlation between the parents' anxiety and their perception of severity of their child's fear (r = 0.52, P = 0.009), distress (r = 0.48, P = 0.017) and pain (r = 0.50, P = 0.01) during the procedure, but less so with the child's distress after the procedure (r = 0.39, P = 0.059). The parents were satisfied with the information given to them regarding the MCU procedure. CONCLUSIONS: Parents' perception of their child's fear, distress and pain during the MCU, as well as distress following the MCU, was not as severe as they had anticipated. Parental anxiety is an important factor in the perception of fear, distress and pain in children during and after the procedure.

Anxiety↗

PubMed2000

Interaction of CD82 tetraspanin proteins with HTLV-1 envelope glycoproteins inhibits cell-to-cell fusion and virus transmission.

The entry of retroviruses into their target cell involves interactions between the virus envelope glycoproteins and their cellular receptors, as well as accessory ligand-receptor interactions involving adhesion molecules that can also participate in fusion. We have studied the contribution of CD82 proteins to the transmission of the human T-cell leukemia virus type 1 (HTLV-1), which is greatly dependent on cell-to-cell contacts. CD82 proteins belong to a class of cell surface molecules, the tetraspanins, that can act as molecular facilitators in cellular adhesion processes. The coexpression of CD82 proteins with HTLV-1 envelope glycoproteins resulted in marked inhibition of syncytium formation, whereas CD82 proteins had no effect on syncytium formation induced by human immunodeficiency virus type 1 (HIV-1) envelope proteins. The presence of CD82 proteins also inhibited cell-to-cell transmission of HTLV-1. Coimmunoprecipitation and cocapping experiments showed that CD82 associates with HTLV-1 envelope glycoproteins, both within the cell and at the cell surface. Finally, whereas the intracellular maturation of HTLV-1 glycoproteins was not modified by the presence of CD82 proteins, HTLV-1 protein coproduction delayed the intracellular maturation of CD82 proteins. There thus seems to be a reciprocal interaction between virus and cell proteins, and the cellular proteins involved in adhesion modulate retrovirus transmission both positively, as shown in other systems, and negatively, as shown here.

Animals↗

PubMed2000

Low incidence of new renal scars after ureteral reimplantation for vesicoureteral reflux in children: a prospective study.

PURPOSE: The major aim of treating vesicoureteral reflux in children is the prevention of renal scars. Dimercapto-succinic acid (DMSA) is the modality of choice for detecting renal scars. We documented the incidence of new renal scarring and measured changes in differential renal function after ureteral reimplantation using DMSA studies. MATERIALS AND METHODS: We evaluated 45 boys and 98 girls with a median age of 2 years who had vesicoureteral reflux and underwent ureteral reimplantation. DMSA scans were done preoperatively and at a median of 3.4 years postoperatively. Maximal reflux grade was III in 84 children (59%), IV in 27 (19%) and V in 6 (4%). RESULTS: Preoperatively DMSA studies showed scarred or contracted kidneys in 106 of the 143 patients (74%). After reimplantation mean change in differential function was 2.5%. New scars developed in 3 children (2%). We noted greater than 6% decrease in relative differential function without new scarring in 7 cases (5%). CONCLUSIONS: The incidence of new renal scars in our study using DMSA was lower than that in previous series using excretory urography and imaging. Surgical correction of vesicoureteral reflux may offer better protection of kidneys in childhood than previously believed.

Adolescent↗

PubMed1999

Early assembly step of a retroviral envelope glycoprotein: analysis using a dominant negative assay.

As for most integral membrane proteins, the intracellular transport of retroviral envelope glycoproteins depends on proper folding and oligomeric assembly in the ER. In this study, we considered the hypothesis that a panel of 22 transport-defective mutants of the human T cell leukemia virus type 1 envelope glycoprotein might be defective in ER assembly. Upon cell cotransfection with wild-type envelope, however, the vast majority of these transport-defective mutants (21 of 22) exerted a specific trans-dominant negative effect. This effect was due to random dimerization of the mutated and wild-type glycoproteins that prevented the intracellular transport of the latter. This unexpected result suggests that association of glycoprotein monomers precedes the completion of folding. The only mutation that impaired this early assembly was located at the NH2 terminus of the protein. COOH-terminally truncated, soluble forms of the glycoprotein were also trans-dominant negative provided that their NH2 terminus was intact. The leucine zipper-like domain, although involved in oligomerization of the envelope glycoproteins at the cell surface, did not contribute to their intracellular assembly. We propose that, at a step subsequent to translation, but preceding complete folding of the monomers, glycoproteins assemble via their NH2-terminal domains, which, in turn, permits their cooperative folding.

Amino Acid Substitution↗

PubMed1999

Recurrent bacteremia with enteric pathogens in recessive polycystic kidney disease.

Eight children with autosomal recessive polycystic kidney disease (ARPKD) and recurrent bacteremia with enteric pathogens are described. Typical clinical features of bacterial cholangitis were absent, although in five patients histological and/or microbiological data indicated that the bacteremic episodes originated in the biliary tree. Bacteremia with enteric pathogens or recurrent culture-negative febrile illness in a child with ARPKD should raise suspicion of cholangitis, even in the absence of typical clinical findings.

Bacteremia↗

PubMed1999

Consensus on renal cortical scintigraphy in children with urinary tract infection. Scientific Committee of Radionuclides in Nephrourology.

A questionnaire related to cortical scintigraphy in children with urinary tract infection was submitted to 30 experts. A wide consensus was reached on several issues related to planar images: 99mTc dimercapto succinic acid (DMSA) appears as the most appropriate tracer for renal imaging; dynamic tracers are considered to be inferior, in particular 99mTc diethylenetriaminepentaacetate, which is not recommended. The general opinion is that DMSA scintigraphy is not feasible with a minimal dose below 15 MBq, whereas the maximum dose should not be higher than 110 MBq. The dose schedule generally is based on body surface area, and sedation is only exceptionally given to children. Images are obtained 2 to 3 hours after injection, preferably with high resolution collimators; pinhole images are used by only half of the experts. Posterior and posterior oblique views are used by most of the experts, and the posterior view is acquired in supine positions. At least 200.000 kcounts or 5 minute acquisition is required for nonzoomed images. As a quality control, experts check the presence of blurred or double outlines on the DMSA images. Color images are not used and experts report on film or directly on the computer screen. As far as normal DMSA images are concerned, most experts agree on several normal variants. Hydronephrosis is not a contraindication for DMSA scintigraphy but constitutes a pitfall. Differential renal function generally is measured, but no consensus is reached whether or not background should be subtracted. Most of the experts consider 45% as the lowest normal value. A consensus is reached on some scintigraphic aspects that are likely to improve and on some others that probably represent persistent sequelae. There is a wide consensus for the systematic use of DMSA scintigraphy for detection of renal sequelae, whereas only 58% of the experts are systematically performing this examination during the acute phase of infection.

Child↗

PubMed1999

Survivors of neonatal extracorporeal membrane oxygenation at school age: unusual findings on intelligence testing.

Data are presented on 17 children who received extracorporeal membrane oxygenation (ECMO) in the neonatal period for persistent pulmonary hypertension (PPHN). These children are being followed as part of a larger program of follow-up research on children who have been treated for PPHN with several treatment methods. On intelligence testing at ages 5 to 8 years, these 17 children had unusual patterns of results. A higher-than-predicted percentage of the ECMO survivors had discrepancies between their Verbal and Performance IQ and a much-higher-than-predicted percentage had areas of unusual strength or weakness on their IQ subtest scores. Also, there was a significant correlation between the amount of time a child received ECMO and the child's Performance IQ: the longer the child received ECMO, the higher the Performance IQ. While findings of unusual weaknesses or deficits on intelligence testing at school age in children who have been severely ill in the neonatal period are not unusual, findings of high scores and areas of strength are not easily explained, particularly when these findings seem to relate to an invasive treatment like ECMO. Similar findings have been reported in two other small studies, which suggest that the impact of ECMO on the developing infant brain may not be purely detrimental.

Child↗

PubMed1999

The Y-S-L-I tyrosine-based motif in the cytoplasmic domain of the human T-cell leukemia virus type 1 envelope is essential for cell-to-cell transmission.

The human T-cell leukemia virus type 1 (HTLV-1) transmembrane glycoprotein has a 24-amino-acid cytoplasmic domain whose function in the viral life cycle is poorly understood. We introduced premature-stop mutations and 18 single-amino-acid substitutions into this domain and studied their effects on cell-to-cell transmission of the virus. The results show that the cytoplasmic domain is absolutely required for cell-to-cell transmission of HTLV-1, through amino acids which cluster in a Y-S-L-I tyrosine-based motif. The transmission defect in two motif mutants did not result from a defect in glycoprotein incorporation or fusion. It appears that the Y-S-L-I tyrosine-based motif of the HTLV-1 glycoprotein cytoplasmic domain has multiple functions, including involvement in virus transmission at a postfusion step.

Amino Acid Motifs↗

PubMed1999

Multiple functions for the basic amino acids of the human T-cell leukemia virus type 1 matrix protein in viral transmission.

We studied the involvement of the human T-cell leukemia virus type 1 (HTLV-1) Gag matrix protein in the cell-to-cell transmission of the virus using missense mutations of the basic amino acids. These basic amino acids are clustered at the N terminus of the protein in other retroviruses and are responsible for targeting the Gag proteins to the plasma membrane. In the HTLV-bovine leukemia virus genus of retroviruses, the basic amino acids are distributed throughout the matrix protein sequence. The HTLV-1 matrix protein contains 11 such residues. A wild-type phenotype was obtained only for mutant viruses with mutations at one of two positions in the matrix protein. The phenotypes of the other nine mutant viruses showed that the basic amino acids are involved at various steps of the replication cycle, including some after membrane targeting. Most of these nine mutations allowed normal synthesis, transport, and cleavage of the Gag precursor, but particle release was greatly affected for seven of them. In addition, four mutated proteins with correct particle release and envelope glycoprotein incorporation did not however permit cell-to-cell transmission of HTLV-1. Thus, particle release, although required, is not sufficient for the cell-to-cell transmission of HTLV-1, and the basic residues of the matrix protein are involved in steps that occur after viral particle release.

Amino Acid Sequence↗

PubMed1998

Identification of exposed epitopes on the envelope glycoproteins of human T-cell lymphotropic virus type I (HTLV-I)

Several lines of evidence underscore the important role of the humoral response specific for HTLV-I envelope protein in the protection against viral infection. One approach to producing efficient immunogens is to synthesize peptides corresponding to the primary amino-acid sequence of neutralizing epitopes found in the external sub-unit gp46. In this study, we have selected synthetic peptides overlapping the major linear neutralizing determinants described earlier and used them as immunogens in rabbits and mice. All rabbit polyclonal anti-sera raised against peptides recognized epitopes in a denaturated context as well as MAbs raised against the HB peptide (aa287-311). By contrast, synthetic peptides O (aa89-110), HH (aa190-209), T (aa190-212) and HB (aa287-311) have generated antibodies efficiently binding their epitopes in a native context, suggesting that these domains are well exposed both at the heterodimer and at the oligomer surface. None of the antibodies induced by synthetic peptides show in vitro neutralizing properties, even those with a good capacity to bind the native form of HTLV-I envelope proteins.

Amino Acid Sequence↗

PubMed1998

Analysis of functional conservation in the surface and transmembrane glycoprotein subunits of human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2.

Human T-cell leukemia virus types 1 and 2 (HTLV-1 and HTLV-2) are closely related retroviruses with nucleotide sequences that are 65% identical. To determine whether their envelope glycoproteins function similarly and to define the molecular determinants of HTLV-2 envelope-mediated functions, we have used pseudotyped viruses and have introduced mutations into regions of the HTLV-2 glycoproteins homologous to those known to be important for HTLV-1 glycoprotein functions. The envelopes of the two viruses could be exchanged with no loss of infectivity, suggesting that the glycoproteins function in broadly similar ways. However, comparative analysis of the HTLV-1 and HTLV-2 glycoproteins showed subtle differences in the structure-function relationships of the two surface glycoprotein (SU) subunits, even though they recognize the same receptor. Indeed, mutations introduced at equivalent positions in the two SU glycoproteins resulted in different phenotypes in the two viruses. The scenario is the opposite for the transmembrane glycoprotein (TM) subunits, in which the functional domains of the two viruses are strictly conserved, confirming the involvement of the TM ectodomain in postfusion events required for full infectivity of the HTLVs. Thus, although they recognize the same receptor, the HTLV-1 and HTLV-2 SU subunits have slightly different ways of transducing the conformational information that primes a common fusion mechanism effected by similar TM subunits.

Amino Acid Sequence↗

PubMed1997

A novel human T-leukemia virus type 1 cell-to-cell transmission assay permits definition of SU glycoprotein amino acids important for infectivity.

Human T-leukemia virus type 1 (HTLV-1) envelope glycoproteins play a major role in viral transmission, which in the case of this virus occurs almost exclusively via cell-to-cell contact. Until very recently, the lack of an HTLV-1 infectivity assay precluded the determination of the HTLV-1 protein domains required for infectivity. Here, we describe an assay which allows the quantitative evaluation of HTLV-1 cell-to-cell transmission in a single round of infection. Using this assay, we demonstrate that in this system, cell-to-cell transmission is at least 100 times more efficient than transmission with free viral particles. We have examined 46 surface (SU) glycoprotein mutants in order to define the amino acids of the HTLV-1 SU glycoprotein required for full infectivity. We demonstrate that these amino acids are distributed along the entire length of the SU glycoprotein, including the N-terminus and C-terminus regions, which have not been previously defined as being important for HTLV-1 glycoprotein function. For most of the mutated glycoproteins, the capacity to mediate cell-to-cell transmission is correlated with the ability to induce formation of syncytia. This result indicates that the fusion capacity is the main factor responsible for infectivity mediated by the HTLV-1 SU envelope glycoprotein, as is the case for other retroviral glycoproteins. However, other factors must also intervene, since two of the mutated glycoproteins were correctly fusogenic but could not mediate cell-to-cell transmission. Existence of this phenotype shows that capacity for fusion is not sufficient to confer infectivity, even in cell-to-cell transmission, and could suggest that postfusion events involve the SU.

Animals↗