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Biomedical subjects

M J Carter

Publications and source records attributed to M J Carter.

At least 37 records · Page 2Linked to original sources
PubMed2000

Poliovirus induces an early impairment of mitochondrial function by inhibiting succinate dehydrogenase activity.

Poliovirus infection of COS-1 and T47D cells caused a rapid decrease in total cell respiration, and this was attributed to an inhibition of mitochondrial respiration. The stimulation of mitochondrial respiration by pyruvate plus malate or succinate was impaired in saponin-permeabilised cells. However, this inhibition could be overcome by the addition of N,N,N',N'-tetramethyl-1, 4-phenylenediamine and ascorbate. The activity of succinate dehydrogenase was impaired in parallel with the inhibition of mitochondrial respiration during poliovirus infection. This shows that mitochondrial function is profoundly altered during poliovirus infection and that this occurs primarily through inhibition of electron flow at complex II of the mitochondrial respiratory chain.

Animals↗
PubMed2000

Survival analysis in percutaneous endoscopic gastrostomy feeding: a worse outcome in patients with dementia.

OBJECTIVE: Percutaneous endoscopic gastrostomy (PEG) feeding has been validated in specific clinical situations such as acute stroke with dysphagia and oropharyngeal malignancy. The perception that gastrostomy insertion is safe and technically simple has led to an increase in the demands for PEG insertion, encompassing clinical applications such as in patients with dementia, in whom its role has not been justified. The purpose of this study was to compare the mortality of patients with dementia who were fed by PEG to that of other subgroups of patients requiring gastrostomy feeding. METHODS: The study focused on a cohort of 361 consecutive patients requiring PEG feeding between August 1992 and July 1997 from two District General Hospitals (Rotherham District General Hospital and Doncaster Royal Infirmary) in South Yorkshire. A retrospective cohort survival analysis was performed using the Kaplan-Meier survival method and Cox proportional hazards analysis. RESULTS: In all patients requiring gastrostomy feeding there is a high initial mortality of 28% at 30 days. However, patients with dementia have a worse prognosis compared to other subgroups, with 54% having died at 1 month and 90% at 1 yr (log rank test p < 0.0001). This difference remained significant (log rank p < 0.0001) after adjusting for age at the time of PEG insertion. CONCLUSIONS: This is the first demonstration in the United Kingdom that the mortality of patients with dementia who are fed by gastrostomy is considerable. Consequently, we may wish to advise against gastrostomy feeding in selected patients within this clinical setting.

Aged↗
PubMed1999

Application of electronmicroscopy, enzyme immunoassay, and RT-PCR to monitor an outbreak of astrovirus type 1 in a paediatric bone marrow transplant unit.

During 1997, an extensive outbreak of astrovirus occurred in a unit where paediatric patients were being treated for leukaemias and inherited immune deficiency disorders. Prolonged shedding of virus for many months following infection was demonstrated in three patients who had undergone bone marrow transplantation. Comparison of reverse transcription-polymerase chain reaction (RT-PCR), enzyme immunoassay (EIA), and electronmicroscopy (EM) to monitor the outbreak showed that many subclinical infections, mainly in children aged > 3 years could only be detected by RT-PCR. Use of RT-PCR revealed that several patients were infected earlier and shed virus for longer than by using EM or EIA. The virus responsible for the outbreak was identified as HAstV-1 and was shown to have a sequence that differed from a strain obtained in 1988.

Astroviridae Infections↗
PubMed1999

Molecular epidemiology of childhood astrovirus infection in child care centers.

This study assessed the role of human astrovirus (HAstV) in outbreaks and sporadic cases of diarrhea among children attending child care centers (CCCs) and determined the infecting astrovirus antigenic types by reverse transcriptase-polymerase chain reaction (RT-PCR) and sequence analysis. Eight astrovirus outbreaks occurred in 6 CCCs. Of 179 children with diarrhea, 36 (20%) had astrovirus-associated diarrhea. Diarrhea stools obtained during diarrhea outbreaks were more likely to contain astrovirus (40/476) than were samples not associated with a diarrhea outbreak (14/452) (P<.001). Type-specific RT-PCR and DNA sequencing identified 5 outbreaks associated with HAstV-1 and 3 outbreaks with HAstV-2. Sequential outbreaks in 2 CCCs occurred with a different type in the same year. Phylogenetic analysis identified 6 clades of HAstV-1 and 2 clades of HAstV-2 during this 1-year surveillance. Astrovirus was a significant cause of diarrhea outbreaks, and 2 antigenic types were present in the community during 1 diarrhea season.

Animals↗
PubMed1999

Prevalence of antibodies to astrovirus types 1 and 3 in children and adolescents in Norfolk, Virginia.

OBJECTIVE: To determine the prevalence of antibody to human astrovirus types 1 (HAstV-1) and 3 (HAstV-3) in children. METHODS: Sera from children hospitalized in Norfolk, VA, for noninfectious conditions were collected for a 1-month period every 6 months from 1993 to 1996 and tested by enzyme immunoassay for antibody to HAstV-1 and HAstV-3 with the use of baculovirus-expressed recombinant capsid proteins as antigens. RESULTS: The seroprevalence of 393 infants and children to HAstV-1 decreased from 67% in infants <3 months of age to 7% by 6 to 8 months of age, consistent with loss of transplacental antibodies. Children acquired HAstV-1 antibody with a peak prevalence of 94% at 6 to 9 years of age (P < 0.001). Antibodies to HAstV-3 exhibited a lower prevalence, with 26% positive at <3 months, 0% at 6 to 11 months and 42% by 6 to 9 years of age. HAstV-1 seroprevalence in children O to 2 months of age decreased from 89% in November, 1993, to 40% in November, 1996 (P = 0.009). CONCLUSIONS: Astrovirus type-specific antibody prevalence can be measured by baculovirus-expressed capsid antigens in an enzyme immunoassay. Children developed antibody to HAstV-1 (94%) and to HAstV-3 (42%) by 6 to 9 years of age indicating frequent exposure to these enteric viruses in infancy and early childhood.

Adolescent↗
PubMed1999

The nucleotide sequence of sacbrood virus of the honey bee: an insect picorna-like virus.

We have determined the nucleotide sequence of sacbrood virus (SBV), which causes a fatal infection of honey bee larvae. The genomic RNA of SBV is longer than that of typical mammalian picornaviruses (8832 nucleotides) and contains a single, large open reading frame (179-8752) encoding a polyprotein of 2858 amino acids. Sequence comparison with other virus polyproteins revealed regions of similarity to characterized helicase, protease and RNA-dependent RNA polymerase domains; structural genes were located at the 5' terminus with non-structural genes at the 3' end. Picornavirus-like agents of insects have two distinct genomic organizations; some resemble mammalian picornaviruses with structural genes at the 5' end and non-structural genes at the 3' end, and others resemble caliciviruses in which this order is reversed; SBV thus belongs to the former type. Sequence comparison suggested that SBV is distantly related to infectious flacherie virus (IFV) of the silk worm, which possesses an RNA of similar size and gene order.

Amino Acid Sequence↗
PubMed1997

New monoclonal antibodies to oestrogen and progesterone receptors effective for paraffin section immunohistochemistry.

Assessment of oestrogen and progesterone receptors (ER and PgR) in breast cancer is widely used for the prediction of response to endocrine therapy and as a prognostic marker. Cytosolic assays have been replaced in many centres by immunochemical techniques, which have many advantages including applicability to small samples, simplicity, and cost-effectiveness. This study describes the generation and characterisation of two novel murine monoclonal antibodies recognizing ER and PgR, designated NCL-ER-6F11 and NCL-PGR respectively, which are effective in heat-treated formalin-fixed, paraffin-embedded tissue. The antibodies have been characterized by Western blotting and by immunohistochemistry on normal and pathological breast and other tissues. NCL-ER-6F11 has been shown to compare favourably with a currently available ER antibody. These antibodies may prove of value in the assessment of hormone receptor status in human breast cancer.

Antibodies, Monoclonal↗
PubMed1996

Extrahepatic secreted complement C3 contributes to circulating C3 levels in humans.

The majority of complement protein C3 is synthesized by the liver, but many other cell types produce small amounts of functionally active C3. The overall contribution of such extrahepatic C3 production to the total circulating C3 level is unknown. Bone marrow and extrahepatic C3 productions were quantified in bone marrow transplant (BMT) and liver transplant (LT) recipients, respectively, where a mismatch for the C3 allotypes distinguished by the mAb HAV 4-1 had occurred. In the BMT group, donor-derived C3 was detected by ELISA and immunoblotting techniques. It contributed to 0.1 to 2.6% of the total circulating C3 during the immediate post-BMT period in response to inflammatory stimuli. Cell culture and immunostaining techniques demonstrated that monocytes were the source of the C3. By 6 wk following BMT, donor-derived C3 levels had decreased to below the detection limit of the assays. By contrast in the LT group, total extrahepatic C3 levels were higher (3.1-5.7% of the total circulating C3) and remained stable for up to 1 yr post-LT. This study demonstrates that extrahepatic derived C3 forms a larger proportion of the circulating C3 levels than was considered previously and that in the resting state, most of this extrahepatically derived C3 comes from nonmyeloid sources. In addition, monocytes, which in the resting state contribute negligible amounts of C3, have the potential when stimulated to contribute significantly to the total systemic C3 pool. These findings highlight the importance of locally secreted complement proteins.

Antibodies, Monoclonal↗
PubMed1996

Organ-specific contribution to circulating C7 levels by the bone marrow and liver in humans.

Many cells types can produce complement component C7, although the major site of C7 synthesis is unknown. Conversion from recipient to donor allotype following organ transplantation has demonstrated the synthetic sites of several complement proteins, but in the case of C7 this was not possible until recently. A novel C7 polymorphism (C7 M/N) has been described based on the reactivity with the monoclonal antibody WU 4-15 which identifies in allotype of C7 (C7 M). Bone marrow and hepatic C7 production was quantified in bone marrow transplant and liver transplant recipients, respectively, where a mismatch for the C7 allotypes distinguished by the monoclonal antibody had occurred. In the bone marrow transplant group, one informative transplant was identified and donor-derived C7 was detected by enzyme-linked immunosorbent assay. It contributed to 18-27% of the total circulating C7 during the post-transplant phase and was increased during episodes of inflammation. In the liver transplant group, the hepatic contribution to the C7 levels were 30% and 52%, respectively, in two patients identified prospectively. A further three informative liver transplant patients were identified retrospectively and in these individuals, 56-62% of the circulating C7 was liver-derived. This study demonstrates that the majority of the circulating C7 is derived from the liver and bone marrow with a lesser contribution from other sources. These findings provide further support for the concept that locally secreted complement proteins have an important role in inflammation.

Base Sequence↗
PubMed1996

The molecular biology of astroviruses.

Astroviruses (genus Astrovirus) are assigned to a newly established virus family, the Astroviridae. The molecular biology of these agents reveals many features unique amongst the non-enveloped animal viruses and resembles that of members of certain plant virus families. In particular, their possession of a serine protease and use of ribosomal frameshifting to express the RNA polymerase are similar to the luteoviruses. Many aspects of the astrovirus replication strategy are still unclear, but replication may involve a nuclear step and non-structural proteins may influence host cell range.

Amino Acid Sequence↗
PubMed1996

Feline calicivirus strain differentiation using monoclonal antibody analysis in an enzyme-linked immuno-flow-assay.

Six monoclonal antibodies raised against feline calicivirus (FCV) strain F9 were used in an enzyme-linked immuno-flow-assay (ELIFA) to analyse 55 isolates of FCV. Forty seven field isolates were obtained from cats with acute oral/respiratory disease, chronic oral lesions, and from cats showing vaccine reactions, i.e. clinical signs of FCV infection shortly after vaccination. Eight reference strains including F9 and three vaccine strains based on F9 were also examined. All of the strains of F9, derived from various sources, reacted with all six of the monoclonal antibodies, whereas some of the field isolates did not react with any. In general, the field isolates showed a spectrum of reactivities and selected isolates could be distinguished. However, there were no clear cut differences between the clinical groups. Overall, the oral/respiratory group showed less reactivity with the monoclonals, suggesting they were less related to F9. Although the other groups appeared to be more closely related to F9, none of the isolates tested reacted with all six monoclonal antibodies.

Animals↗
PubMed1996

Seroprevalence of astrovirus types 1 and 6 in London, determined using recombinant virus antigen.

We have developed a microimmunofluorescence test (IF) which uses cells infected with a recombinant baculovirus which expresses the capsid proteins of astrovirus types 1 or 6. The IF test was sensitive and specific and the results for human astrovirus type 1 (HAst-1) were comparable to those obtained by immune electronmicroscopy and radioimmunoassay. Application of the test to a panel of 273 sera collected from patients and staff at two childrens hospitals in London showed that over 50% of the population were infected by HAst-1 between the age of 5 and 12 months rising to 90% by 5 years, whereas human astrovirus type 6 (HAst6) was relatively uncommon (10-30%) in all age groups.

Adult↗
PubMed1995

Prokaryotic expression and analysis of the antibody response to a Newcastle isolate of the core gene of hepatitis C.

The full length hepatitis C virus (HCV) core gene was isolated from a Newcastle strain and expressed in E. coli. A truncated HCV core gene which lacks the hydrophobic carboxyl-terminal sequence was also expressed. The truncated HCV core was expressed at higher levels with fewer cleavage products. Antibody reactivity to the recombinant HCV core antigen was analysed by ELISA and Western blotting in 60 HCV antibody-positive patients with a broad spectrum of liver disease. There was no significant difference between the presence of IgG to recombinant HCV core and reactivity to the core antigen in the RIBA-2 test. There was also no significant difference between the presence of IgG to recombinant core and diagnostic PCR as a marker for active liver inflammation.

Antigens, Viral↗
PubMed1995

Prevalence of human astrovirus serotype 4: capsid protein sequence and comparison with other strains.

Astrovirus serotype 4 has increased in relative prevalence in the Oxford, UK area in 1993. The structural gene of human astrovirus serotype 4 has been sequenced and the results indicate that this protein differs substantially from serotypes 1 and 2. In particular, conservation at the C terminus is greatly reduced. However, amino acid substitutions in this region show a strong conservation in character suggesting that structural or functional constraints operate in this region.

Amino Acid Sequence↗
PubMed1995

Caffeine enhances acetylcholine release in the hippocampus in vivo by a selective interaction with adenosine A1 receptors.

Caffeine is a commonly used drug that increases arousal, a condition associated with increased cholinergic activity in the mammalian cerebral cortex including the hippocampus. We have used the technique of microdialysis in association with microbore high-performance liquid chromatography to investigate the effects of caffeine on the extracellular levels of acetylcholine in the hippocampus of awake, freely moving rats. The oral administration of caffeine dose-dependently (3-30 mg/kg) increased the extracellular levels of acetylcholine. This increase was completely blocked when the microdialysis probe was perfused with the Na(+)-channel blocker tetrodotoxin, and strongly attenuated when a Ca(2+)-free Ringer solution was used. The effect of caffeine on hippocampal acetylcholine release was concentration-dependently counteracted by local perfusion of an A1 receptor agonist, N6-cyclopentyladenosine (0.1-1 mumol/liter), but not by the A2 receptor agonist, CGS 21680 (10 mumol/liter). Neither agonist affected base-line acetylcholine release at these concentrations. These results demonstrate that acetylcholine release in the hippocampus is under tonic inhibitory control of the endogenous neuromodulator adenosine, and that orally administered caffeine enhances action potential-dependent vesicular acetylcholine release by antagonism of local A1 receptors. Hence, the data provide a possible link between adenosine A1 receptors in the hippocampus, increased cholinergic activity and the psychostimulant effects of caffeine.

Acetylcholine↗
PubMed1994

Genomic organization and expression of astroviruses and caliciviruses.

Astroviruses and caliciviruses are two families defined initially by their characteristic morphology. Many of these viruses have been difficult to grow in culture. Molecular biology has now provided a valuable insight into the nature of these viruses, and in many respects knowledge of genome structure now outstrips that of more classical virological features. However these advances have allowed a more detailed approach to virus classification and have led to the establishment of the Astroviridae as a distinct virus family.

Amino Acid Sequence↗