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Biomedical subjects

A M Cross

Publications and source records attributed to A M Cross.

At least 19 recordsLinked to original sources
PubMed2003

Non-invasive ventilation in acute respiratory failure: a randomised comparison of continuous positive airway pressure and bi-level positive airway pressure.

OBJECTIVES: To determine whether there is a difference in required duration of non-invasive ventilation between continuous positive airway pressure (CPAP) and bi-level positive airway pressure (BiPAP) in the treatment of a heterogeneous group of emergency department (ED) patients suffering acute respiratory failure and the subgroup of patients with acute pulmonary oedema (APO). Secondary objectives were to compare complications, failure rate, disposition, length of stay parameters, and mortality between the treatments. METHODS: This prospective randomised trial was conducted in the emergency departments of three Australian teaching hospitals. Patients in acute respiratory failure were randomly assigned to receive CPAP or BiPAP in addition to standard therapy. Duration of non-invasive ventilation, complications, failure rate, disposition, length of stay (hospital and ICU), and mortality were measured. RESULTS: 101 patients were enrolled in the study (CPAP 51, BiPAP 50). The median duration of non-invasive ventilation with CPAP was 123 minutes (range 10-338) and 132 minutes (range 20-550) for BiPAP (p = 0.206, Mann-Whitney). For the subgroup suffering APO, 36 were randomised to CPAP and 35 to BiPAP. For this group the median duration of non-invasive ventilation for CPAP was 123 minutes (range 35-338) and 133 minutes (range 30-550) for BiPAP (p = 0.320, Mann-Whitney). CONCLUSIONS: These results suggest that there is no significant difference in the duration of non-invasive ventilation treatment between CPAP and BiPAP when used for the treatment of acute respiratory failure in the ED. There was also no significant difference between the groups in secondary end points.

Acute Disease↗
PubMed1998

Identification of residues within the herpes simplex virus type 1 origin-binding protein that contribute to sequence-specific DNA binding.

Gene UL9 of herpes simplex virus type 1 encodes an 851-amino-acid protein which is essential for viral DNA synthesis and functions as a sequence-specific origin-binding protein and DNA helicase. We generated monoclonal antibodies against purified UL9 protein and identified one such antibody (MAb 13924) that can block the interaction of the UL9 C-terminal DNA-binding domain (amino acids 534-851) with its recognition sequence. MAb 13924 interacted with immobilized peptides containing residues 780-786 of UL9. Although the corresponding region of the homologous protein encoded by varicell-azoster virus differs at only a single position it was not recognized by MAb 13924. Site-directed mutagenesis experiments confirmed that residues within this region contribute to the epitope recognized by MAb 13924 and may be involved in sequence-specific DNA binding. In addition, all eight lysine residues within the DNA-binding domain were separately changed to alanine and the DNA-binding properties of the mutated proteins were examined. The results showed that lysine residues that are located close to the peptide recognized by MAb 13924 or lie within the region of the DNA-binding domain most highly conserved among homologous alphaherpesvirus proteins play a role in sequence-specific DNA binding. Moreover, alteration of a lysine residue 18 amino acids from the recognized peptide prevented the interaction of MAb 13924 with the UL9 C-terminal DNA-binding domain. Three helical segments are predicted to occur within the region containing mutations that affect sequence-specific binding and interaction with MAb 13924.

Amino Acid Sequence↗
PubMed1996

The herpes simplex virus type 1 UL8 protein influences the intracellular localization of the UL52 but not the ICP8 or POL replication proteins in virus-infected cells.

We have developed a panel of 14 monoclonal antibodies (MAbs) to POL, the catalytic subunit of herpes simplex virus type 1 (HSV-1) DNA polymerase encoded by gene UL30, and one MAb to the UL52 protein, another of the seven proteins essential for replication of HSV DNA. The approximate locations of the epitopes of the polymerase-specific MAbs were identified using truncated polymerase molecules, and the antibodies were characterized in a number of immunological assays allowing eight different specificities to be recognized. These MAbs, together with a polyclonal antibody raised in rabbits against a third DNA replication protein, ICP8, were used to localize the respective proteins by immunofluorescence in cells infected with wild-type HSV-1 or the DNA replication-defective mutants ambUL8 or 2-2. In BHK cells infected with ambUL8, a mutant with an amber termination codon within the coding region of gene UL8, the UL52 protein did not enter the nucleus, although ICP8 and POL entered the nucleus in a normal fashion. The failure of the UL52 protein to be correctly transported to the nucleus was also observed in both HFL and Vero cells infected with ambUL8. In contrast, UL52 protein was transported to the nucleus in BHK cells infected with wild-type HSV-1 or with 2-2, a mutant lacking a functional UL9 protein.

Animals↗
PubMed1995

Recovery of left ventricular function in acute nonischemic congestive cardiomyopathy.

The extent and time course of recovery of left ventricular function were investigated in 29 patients with no previous symptoms who had acute nonischemic congestive cardiomyopathy and left ventricular ejection fraction of 0.22 +/- 0.07. Improvement in left ventricular ejection fraction by at least 0.05 was observed in 24 of the 29 patients and was achieved within 6 months after the initial evaluation. Progressive improvement was seen, with a maximum ejection fraction of 0.45 +/- 0.17 being achieved within approximately 18 months. The degree of ejection fraction recovery was not related to the initial clinical or hemodynamic variables. However, the extent of fibrosis detected on endomyocardial biopsy correlated inversely with subsequent changes in ejection fraction (r = -0.65, p = 0.0003). Thus significant recovery is likely after an acute episode of nonischemic cardiomyopathy and may be progressive during the first year. Recovery is related to the extent of myocardial fibrosis detected on endomyocardial biopsy but cannot be predicted from the initial clinical or hemodynamic presentation.

Acute Disease↗
PubMed1995

Oxygen deficit during exercise testing in heart failure. Relation to submaximal exercise tolerance.

Measurements of oxygen deficit during submaximal exercise were correlated with the anaerobic threshold (as measured by gas exchange analysis), peak work rate on a ramp protocol, and the ability to perform constant work rate exercise in 10 male patients with New York Heart Association class 2 congestive heart failure and 12 age- and gender-matched normal controls. All subjects performed a maximal ramp exercise test for measurement of the anaerobic threshold. In addition, several 15-min constant work rate exercise sessions were conducted to evaluate oxygen deficit, measured as the area between the "ideal" square curve of oxygen consumption at the onset of constant work rate exercise and the actual exponentially shaped curve. Since the oxygen deficit significantly correlated with the plateau oxygen consumption during the 25-W constant work rate exercise (r = 0.61, p = 0.002), the oxygen deficit was normalized by the rectangular area of 15-min oxygen consumption above baseline. This normalized value significantly correlated with the inverse of the anaerobic threshold (r = 0.81, p < 0.0001). The logarithm of the normalized oxygen deficit significantly correlated with the maximum ramp work rate (r = -0.86, p < 0.0001) and the highest constant work rate sustained for 15 min (r = -0.82, p < 0.0001). In addition, the time to reach plateau oxygen consumption for the 25-W exercise significantly correlated with the inverse of the anaerobic threshold (r = -0.78, p < 0.0001), the maximum ramp work rate (r = -0.76, p < 0.0001), and the highest constant work rate sustained for 15 min (r = -0.74, p < 0.0001). Thus, the oxygen deficit seen in patients with heart failure during constant work rate exercise results from abnormally slow oxygen uptake kinetics and correlates with exercise capacity as measured by anaerobic threshold (via gas exchange analysis) and maximal and submaximal exercise tolerance. Oxygen deficit warrants further evaluation as a submaximal index of functional capacity in patients with heart failure.

Adult↗
PubMed1994

Localization of the herpes simplex virus type 1 major capsid protein VP5 to the cell nucleus requires the abundant scaffolding protein VP22a.

The intracellular distributions of three herpes simplex virus type 1 (HSV-1) capsid proteins, VP23, VP5 and VP22a, were examined using vaccinia virus and plasmid expression systems. During infection of cells with HSV-1 wild-type virus, all three proteins were predominantly located in the nucleus, which is the site of capsid assembly. However, when expressed in the absence of any other HSV-1 proteins, although VP22a was found exclusively in the nucleus as expected, VP5 and VP23 were distributed throughout the cell. Thus nuclear localization is not an intrinsic property of these proteins but must be mediated by one or more HSV-1-induced proteins. Co-expression experiments demonstrated that VP5 was efficiently transported to the nucleus in the presence of VP22a, but the distribution of VP23 was unaffected by the presence of either or both of the other two proteins.

Biological Transport↗
PubMed1992

Rapid attachment of a helper T cell epitope to branched peptides by fragment condensation to give enhanced immunogenicity.

We describe a rapid method of fragment condensation to couple a helper T cell epitope, active in BALB/c mice, to the amino terminus of branched peptides (or 'multiple antigenic peptides', MAPs). The helper T cell epitope-MAP conjugate considerably enhanced the immunogenicity in BALB/c mice of branched peptides. The method of fragment condensation, whereby the helper T cell epitope portion of the immunogen is added as a 'cassette' in a one step addition process, is both faster and more convenient than continuous step-by-step addition of individual amino acids and is likely to be generally applicable. The method should be advantageous in the development of peptide based vaccines.

Amino Acid Sequence↗
PubMed1990

A single amino acid substitution in the large subunit of herpes simplex virus type 1 ribonucleotide reductase which prevents subunit association.

The herpes simplex virus type 1 temperature-sensitive (ts) mutant ts1207 does not induce detectable levels of ribonucleotide reductase activity at the non-permissive temperature (NPT, 39.5 degrees C). The ts lesion prevents the association of the enzyme's large (RR1) and small (RR2) subunits to give an active holoenzyme and maps within the gene specifying RR1. Here, it is shown that the ts mutant phenotype is due to the substitution of an asparagine for the wild-type (wt) serine at RR1 position 961, which is located within a region highly conserved between herpesviral and cellular RR1 subunit polypeptides. This ts1207 asparagine is predicted to alter a wt alpha-helix to a beta-strand. We have used synthetic oligopeptides, corresponding to the wt amino acid sequence of the mutation site, and antisera raised against them to determine whether this region is involved in subunit association. Neither the oligopeptides nor the antisera inhibit the enzyme activity, or the reconstituted activity formed by mixing intact RR2 and RR1 subunits present in partially purified extracts of cells infected at the NPT with ts1207 or ts1222 (an HSV-1 mutant with a lesion in the RR2 subunit), respectively. We infer from these results that the site of the mutation is unlikely to be positioned at the surface of RR1 and hence is probably not directly involved in subunit association. We suggest that the mutation site identifies an important RR1 region whose alteration in ts1207 changes the structure of a contact region(s) positioned at the RR1/RR2 interface.

Amino Acid Sequence↗
PubMed1989

Mapping of epitopes on the 65k DNA-binding protein of herpes simplex virus type 1.

Previously we have described the isolation of seven monoclonal antibodies (MAbs) and two polyvalent rabbit sera directed against the product of herpes simplex virus type 1 (HSV-1) gene UL42, a 65K DNA-binding protein (65KDBP) which is essential for HSV DNA replication and virus growth. We now report the synthesis of all 483 overlapping hexapeptides of this 488 amino acid protein and describe their use for the identification of epitopes recognized by these MAbs and polyvalent sera. MAb 6898, derived from one fusion, recognizes the peptides EDLDGA and DLDGAA which correspond to amino acids 363 to 369 of 65KDBP. MAbs Z4D4, Z6F3, Z1A8, Z10Cl, Z3H12 and Z1F11, derived from a second fusion, all recognize the peptides GDPEDL and DPEDLD which correspond to amino acids 360 to 366. As expected both polyvalent sera recognize several different epitopes.

Amino Acid Sequence↗
PubMed1988

The products of herpes simplex virus type 1 gene UL26 which are involved in DNA packaging are strongly associated with empty but not with full capsids.

We report on the properties of a family of related herpes simplex virus type 1 polypeptides (designated p40) of Mr around 40,000. The intracellular localization of these polypeptides has been examined using monoclonal antibodies and their association with viral capsids within the nuclei of infected cells has been demonstrated directly by immunoelectron microscopy. Specific DNA staining and the use of mutants defective for DNA packaging has revealed, in contrast to earlier findings, that p40 is present in empty capsids. Protein p40 is not present as a major component of full capsids or of mature virions indicating that it is transiently associated with capsids and that its removal from capsids is linked with the process of DNA packaging.

Capsid↗
PubMed1988

Herpes simplex virus immunoglobulin G Fc receptor activity depends on a complex of two viral glycoproteins, gE and gI.

Evidence was recently presented that herpes simplex virus type 1 (HSV-1) immunoglobulin G (IgG) Fc receptors are composed of a complex containing a previously described glycoprotein, gE, and a novel virus-induced polypeptide, provisionally named g70 (D. C. Johnson and V. Feenstra, J. Virol. 61:2208-2216, 1987). Using a monoclonal antibody designated 3104, which recognizes g70, in conjunction with antipeptide sera and virus mutants unable to express g70 or gE, we have mapped the gene encoding g70 to the US7 open reading frame of HSV-1 adjacent to the gE gene. Therefore, g70 appears to be identical to a recently described polypeptide which was named gI (R. Longnecker, S. Chatterjee, R. J. Whitley, and B. Roizman, Proc. Natl. Acad. Sci. USA 84:147-151, 1987). Under mildly denaturing conditions, monoclonal antibody 3104 precipitated both gI and gE from extracts of HSV-1-infected cells. In addition, rabbit IgG precipitated the gE-gI complex from extracts of cells transfected with a fragment of HSV-1 DNA containing the gI, gE, and US9 genes. Cells infected with mutant viruses which were unable to express gE or gI did not bind radiolabeled IgG; however, cells coinfected with two viruses, one unable to express gE and the other unable to express gI, bound levels of IgG approaching those observed with wild-type viruses. These results further support the hypothesis that gE and gI form a complex which binds IgG by the Fc domain and that neither polypeptide alone can bind IgG.

Animals↗
PubMed1987

Generation and properties of the glycoprotein E-related 32K/34K/35K and 55K/57K polypeptides encoded by herpes simplex virus type 1.

A hybridoma line was isolated which produced antibody reacting with polypeptides of apparent molecular weights 32,000, 34,000 and 35,000 (32K/34K/35K) and 55,000 and 57,000 (55K/57K). These were sulphated glycoproteins that have previously been found in the medium of herpes simplex virus type 1 (HSV-1)-infected cells. By tryptic peptide mapping and serological cross-reactions the polypeptides were shown to be related to HSV-1 glycoprotein E (gE-1) but they lacked the Fc binding function. The 32K/34K/35K and 55K/57K polypeptides were not found in the medium of HSV-1-infected cells incubated in serum-free medium. They could be generated in vitro from purified gE-1 in the presence of serum. It is likely that 32K/34K/35K and 55K/57K are derived from gE-1 by the action of serum proteases.

Animals↗
PubMed1976

The immunological properties of haptens coupled to thymus-independent carrier molecules. IV. The IgG response to dinitrophenylated Ficoll.

Dinitrophenylated polysucrose (DNP-Ficoll) elicits T cell-independent IgM anti-DNP antibody formation in mice. This antigen also elicits a heterogeneous IgG1 and IgG2 anti-DNP response, which is operationally as T-independent as the IgM response. However, a concomitant graft-versus-host reaction markedly enhances the IgG response (allogeneic effect). These results confirm those of others, indicating that a certain proportion of the precursors of IgG-producing cells can be triggered by some T-independent antigens. However, our results suggest that even with such antigens optimal triggering of IgG precursors requires T cell help.

Animals↗
PubMed1975

Effects of treating immune lymphocytes with a proteolytic enzyme (papain): reduction in immune potential and recovery after incubation.

Immune spleen cells were treated with papain, washed, and boosted with homologous antigen (4-hydroxy-3-iodo-5-nitrophenylacetic acid coupled to chicken globulin) for 1 hr at 4 degrees C. When transferred to irradiated mice, they produced up to 20-fold less anti-hapten antibody than non-papain-treated cells. The lymphocytes could recover their ability to respond if incubated at 37 degrees C after papain treatment but before antigen boosting. Incubation for 30 min at 37 degrees C gave complete or almost complete recovery. Although papain usually reduced the response, in 31% of experiments the reduction was not significant. Possible reasons for this variability are discussed.

Animals↗