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Biomedical subjects

P Tomlinson

Publications and source records attributed to P Tomlinson.

At least 19 recordsLinked to original sources
PubMed1992

Expression of major histocompatibility complex class I antigens at low levels in the thymus induces T cell tolerance via a non-deletional mechanism.

Transgenic CBA (H-2k haplotype) mice expressing the H-2 Kb major histocompatibility complex (MHC) class I gene under control of transcriptional promoter elements from a milk protein gene display high-level H-2 Kb transcription in lactating mammary glands and low-level transcription in skin and thymus of male and virgin female transgenic mice. However, H-2 Kb antigen could be detected only in lactating mammary gland epithelial cells by immunohistological methods. All transgenic mice are tolerant of H-2 Kb since they fail to reject skin grafts from mice expressing H-2 Kb molecules. Furthermore, anti-H-2 Kb cytotoxic responses could not be generated using responder T cells from transgenic mice but T cells from the same mice proliferated, in the presence of interleukin-2, in response to stimulator cells expressing H-2 Kb. Tolerance to H-2 Kb is induced in the thymus since CBA mice grafted with thymus tissue from transgenic mice fail to reject H-2 Kb disparate skin grafts. However, experiments with double-transgenic mice also expressing a T cell receptor with anti-H-2 Kb specificity reveal that tolerance induction is not brought about by elimination of thymocytes bearing H-2 Kb-reactive receptors. Instead, a non-deletional mechanism which results in down-modulation of both CD8 and T cell receptor expression in peripheral T cells correlates with the induction of tolerance in these mice. These data reveal that extremely low levels of self-antigen expression in the thymus are sufficient to induce tolerance via non-deletional mechanisms.

Animals↗
PubMed1992

A comparison of height, weight and head circumference of primary school children living in deprived and non-deprived circumstances.

Heights, weights and head circumferences were obtained from two groups of primary school children: 1016 children from throughout Oxfordshire, a rural county with few areas of deprivation, and 219 children from an economically deprived part of the city of Newcastle on Tyne. Compared to Tanner and Whitehouse standards, Oxfordshire children were significantly taller, but not heavier, while the Newcastle children were significantly shorter and markedly lighter. Mean head circumference values were lower in the Newcastle than the Oxfordshire children. Existing national growth standards are outdated when applied to children in acceptably advantaged circumstances while impoverished children still fall below these standard in a pattern suggestive of under nutrition.

Body Height↗
PubMed1990

Prediction of acute renal failure after birth asphyxia.

Twenty-one babies of 34-41 weeks' gestational age with birth asphyxia (5 minute Apgar score less than or equal to 5 or umbilical artery pH less than or equal to 7.2) were studied during the first two days of life to find out whether the urinary excretion of tubular markers of renal function is of value in the early diagnosis of acute renal failure. Urinary retinol binding protein, myoglobin, and N-acetyl-beta-D-glucosaminidase (NAG), expressed as a ratio with urinary creatinine, were measured and excretion profiles repeated at 3-6 days in 15 infants and at 7-14 days in 11 infants. Plasma creatinine concentration, creatinine clearance, plasma myoglobin concentration, and fractional sodium excretion were measured where possible in asphyxiated infants. Control data were obtained from 50 healthy infants: 28 gave urine samples alone, 17 urine and blood, and five blood alone. Normal urinary values were derived from 17, 25, and three infants, respectively, for the three time periods. The number of control samples was limited for ethical reasons. Four asphyxiated infants had acute renal failure (group 1), four had tubular dysfunction without glomerular disturbance (group 2) and 13 had normal renal function (group 3). Group 1 were clearly identified by greatly increased urinary retinol binding protein (greater than 27,000 micrograms/mmol creatinine) and myoglobin (greater than 1500 micrograms/mmol creatinine) excretion measured in the first two days of life. In control infants the range of excretion of retinol binding protein within the same time period was 3 to 967 micrograms/mmol creatinine and urinary myoglobin was undetectable. Excretion of NAG failed to discriminate between groups 1 and 2. Acute renal failure occurred only in infants who had heavy myoglobinaemia. Tubular dysfunction in group 2 was transient and not accompanied by plasma electrolyte disturbances. We conclude that measurement of urinary excretion of retinol binding protein or myoglobin after birth is helpful in the early diagnosis of acute renal failure.

Acetylglucosaminidase↗
PubMed1988

Meningococcal serogroups in New South Wales, 1977-1987.

Data are presented on serogroups of meningococci (Neisseria meningitidis) that were submitted to Westmead Hospital and The Children's Hospital, Camperdown, from patients in Sydney and in rural areas of New South Wales, from January 1, 1977 to December 31, 1987. One hundred and ten organisms that were isolated from cerebrospinal fluid or from blood were examined. All organisms were isolated from sporadic cases of meningococcal disease. Patients in the zero-to-two-years' age-group were affected most commonly, but 36.3% of isolates were from older children and adults. The distribution of serogroups was as follows: serogroup B, 43.6; serogroup A, 28.2%; serogroup C, 10.0%; serogroup W135, 8.2%; serogroup Y, 4.5%; and serogroup Z, 0.9%. The isolates that were serogrouped by us represented approximately half the cases of meningococcal meningitis that were notified in New South Wales during this period. Serogrouping of meningococcal isolates is very important in order to follow epidemiological trends in the disease and to monitor the serogroups that cause outbreaks, where vaccination of contacts may be indicated. Our laboratories are prepared to receive isolates for serogrouping and antibiotic sensitivity testing from across New South Wales.

Adolescent↗
PubMed1988

Overtransfusion as a possible cause of split skin graft loss.

A child who underwent burns surgery received excessive transfusion of red blood cells during operation and subsequently suffered severe skin graft and donor site loss. The possible causes are discussed and hyperviscosity is suggested to be the most probable.

Graft Survival↗
PubMed1988

Identification and expression of a human cytomegalovirus glycoprotein with homology to the Epstein-Barr virus BXLF2 product, varicella-zoster virus gpIII, and herpes simplex virus type 1 glycoprotein H.

An open reading frame with the characteristics of a glycoprotein-coding sequence was identified by nucleotide sequencing of human cytomegalovirus (HCMV) genomic DNA. The predicted amino acid sequence was homologous with glycoprotein H of herpes simplex virus type 1 and the homologous protein of Epstein-Barr virus (BXLF2 gene product) and varicella-zoster virus (gpIII). Recombinant vaccinia viruses that expressed this gene were constructed. A glycoprotein of approximately 86 kilodaltons was immunoprecipitated from cells infected with the recombinant viruses and from HCMV-infected cells with a monoclonal antibody that efficiently neutralized HCMV infectivity. In HCMV-infected MRC5 cells, this glycoprotein was present on nuclear and cytoplasmic membranes, but in recombinant vaccinia virus-infected cells it accumulated predominantly on the nuclear membrane.

Amino Acid Sequence↗
PubMed1987

Large-scale rearrangement of homologous regions in the genomes of HCMV and EBV.

The 20,349-bp sequence of the human cytomegalovirus (HCMV) HindIII F fragment has revealed eight open reading frames with homology to herpes simplex virus (HSV) and/or Epstein-Barr virus (EBV). With respect to EBV, these homologous genes can be divided into two blocks: one block contains three genes, including the DNA polymerase and glycoprotein B, and the other block contains five genes of unknown function. Although the relative organisation of genes within each block is identical in HCMV and EBV, the relative position of each block within the two genomes differs: in HCMV the two blocks are present directly adjacent to each other, whereas in EBV they are found 92 kb apart. This suggests that a genetic rearrangement has occurred in this region. Transcription analysis of the glycoprotein B gene is presented and the evolutionary relationship between the genomes of HCMV, EBV, and HSV is discussed.

Amino Acid Sequence↗
PubMed1987

Sequence and transcription analysis of the human cytomegalovirus DNA polymerase gene.

DNA sequence analysis has revealed that the gene coding for the human cytomegalovirus (HCMV) DNA polymerase is present within the long unique region of the virus genome. Identification is based on extensive amino acid homology between the predicted HCMV open reading frame HFLF2 and the DNA polymerase of herpes simplex virus type 1. We present here a 5280-base-pair DNA sequence containing the HCMV pol gene, along with the analysis of transcripts encoded within this region. Since HCMV pol also shows homology to the predicted Epstein-Barr virus pol, we were able to analyze the extent of homology between the DNA polymerases of three distantly related herpesviruses, HCMV, Epstein-Barr virus, and herpes simplex virus. The comparison shows that these DNA polymerases exhibit considerable amino acid homology and highlights a number of highly conserved regions; two such regions show homology to sequences within the adenovirus type 2 DNA polymerase. The HCMV pol gene is flanked by open reading frames with homology to those of other herpesviruses; upstream, there is a reading frame homologous to the glycoprotein B gene of herpes simplex virus type 1 and Epstein-Barr virus, and downstream there is a reading frame homologous to BFLF2 of Epstein-Barr virus.

Amino Acid Sequence↗
PubMed1987

Primary structure and transcription of the genes coding for the two virion phosphoproteins pp65 and pp71 of human cytomegalovirus.

Human cytomegalovirus contains a phosphorylated matrix protein of 65,000 apparent molecular weight (65K phosphoprotein; pp65) and a related phosphoprotein of 71,000 molecular weight (pp71). The 65K phosphoprotein is usually by far the most abundant structural component found in culture-grown purified virus particles. This study describes the precise mapping of the genes for both polypeptides, giving the entire nucleotide sequences and the exact positions of the respective transcripts. The 65K phosphoprotein is coded for by the 5'-terminal part of an abundant 4-kilobase (kb) mRNA. The 71K phosphoprotein corresponds to the single translational reading frame of a rare nonspliced 1.9-kb mRNA that is coterminal with the 4-kb transcript. The promoter for 4-kb mRNA appears to be unusual in structure; it does not contain a characteristic TATA sequence. The expression of antigenic epitopes from pp65 may allow improved serodiagnosis of human cytomegalovirus infections.

Amino Acid Sequence↗
PubMed1986

Reversed-phase high-performance liquid chromatographic assay for the determination of potency and impurities in tazadolene succinate bulk drug and capsules.

A reversed-phase assay based on high-performance liquid chromatography with a water-acetonitrile-tetrahydrofuran (THF)-triethylamine (TEA)-perchloric acid (pH 2.5) mobile phase and a Zorbax C8 column has been validated for the determination of the purity of tazadolene succinate (I) [E-(+/-)-1-(2-benzylidenecyclohexyl)azetidine succinate, U-53996H] bulk drug, the potency of tazadolene succinate hard-filled capsule formulations and impurity levels in bulk drug. The system resolves E- and Z-isomers and other structurally related molecules. Retention of these compounds is mainly dependent on the amount of acetonitrile and THF in the mobile phase. An amine must be present in the mobile phase to bring about elution of I. The potency assay utilizes testosterone as internal standard. Potency assays exhibited relative standard deviations (R.S.D.) of less than 1%. Quantitative recovery from hard-filled capsules (HFC) is obtained by using a simple extraction procedure. Potential process impurities, potential degradation products, and formulation excipients are resolved. The assay is linear for tazadolene succinate concentrations equivalent to 50-150% of the assay concentration. Impurities can be quantitated to levels equivalent to about 0.1% by weight with R.S.D. less than 5%. The estimated limit of detection for I is about 2 ng for a 20 microliters injection.

Analgesics↗
PubMed1986

Identification of the human cytomegalovirus glycoprotein B gene and induction of neutralizing antibodies via its expression in recombinant vaccinia virus.

A human cytomegalovirus (HCMV) glycoprotein gene with homology to glycoprotein B (gB) of herpes simplex virus and Epstein-Barr virus and gpII of varicella zoster virus has been identified by nucleotide sequencing. The gene has been expressed in recombinant vaccinia virus and the gene product recognized by monoclonal antibodies and human immune sera. Rabbits immunized with the recombinant vaccinia virus produced antibodies that immunoprecipitate gB from HCMV-infected cells and neutralize HCMV infectivity in vitro. These data demonstrate a role for this protein in future HCMV vaccines.

Amino Acid Sequence↗
PubMed1986

Evaluation of lysis filtration as an adjunct to conventional blood culture.

A lysis filtration system was used in conjunction with conventional broth culture for 1112 blood cultures. The system, which entailed collection of 5 ml of blood into bottles containing 50 ml isotonic phosphate buffer, Tween 20, and Rhozyme with subsequent filtration using a 0.45 micron Millipore field monitor, was simple and economical to use. Positive results were obtained earlier than those obtained with conventional broth cultures, and almost twice as many fungi and yeasts were isolated. Some fastidious organisms such as Haemophilus influenzae and Streptococcus pneumoniae however, were not recovered from the lysis system, and contaminants in lysis cultures were three times as common as in conventional culture. The number of positive cultures was also adversely influenced by incubation of the blood lysis mixture overnight before filtration. We conclude that this lysis filtration system is useful as an adjunct to conventional broth culture in selected patients in cases in which filtration can be carried out soon after collection.

Bacteria↗
PubMed1984

Is the antimicrobial removal device a cost-effective addition to conventional blood cultures?

Two hundred and thirty-four blood cultures from 140 patients receiving antibiotics were processed using the antimicrobial removal device (ARD) in parallel with conventional blood cultures. One hundred and seventy cultures were obtained from patients suspected to have bacteraemia and 64 from patients known to have a positive conventional blood culture within the preceding three days. A total of 38 (16.2%) ARD-processed cultures were positive, compared with 21 (8.9%) conventional cultures (p less than 0.0001, Fisher's exact test). No instances of positive conventional cultures and negative ARD-processed cultures were identified. Thirty-three of 38 ARD-processed cultures became positive within 24 h, compared with 14 parallel conventional cultures (p less than 0.0001 Fisher's exact test). Although the yield and rapidity of isolation of bacteria from blood were improved by ARD processing, in only one of 140 patients did this information alter treatment. As the use of an ARD is associated with a sixfold increase in the cost of blood cultures, we conclude that, in our hands, general use of the device in patients receiving antibiotics is not cost-effective. Considerable care should be taken in selecting patients for ARD-processing of blood cultures.

Anti-Bacterial Agents↗
PubMed1982

Systemic Haemophilus influenzae infection in childhood.

Forty-nine children who had systemic Haemophilus infection and were treated at the Westmead Centre, Sydney, over a two-year period are described. The majority (29 of 49 children) were aged two years or less. Epiglottis and meningitis accounted for 77% of these infections. All H. influenzae isolates associated with clinical disease were of the capsular type b. Eight per cent (four of 50) of H. influenzae infections were caused by beta-lactamase producing strains. There was no geographic clustering or seasonal variation. There was no mortality. Major morbidity included two patients who had epiglottis and required tracheostomy, and two patients who had meningitis developed bilateral profound sensorineural deafness. No secondary cases were detected in household contacts of 21 patients with H. influenzae meningitis during the study period. Epiglottis frequently occurs in very young children. The rapid response to antibiotic treatment suggests that early cases of epiglottis may be undiagnosed, but treated with antibiotic agents in the community.

Anti-Bacterial Agents↗