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Biomedical subjects

I J Jackson

Publications and source records attributed to I J Jackson.

At least 73 records · Page 4Linked to original sources
PubMed1992

Hypoxaemia and pain relief after upper abdominal surgery: comparison of i.m. and patient-controlled analgesia.

Forty patients recovering from upper abdominal surgery were allocated randomly to receive i.m. morphine 0.15 mg kg-1 as required or patient-controlled analgesia (PCA), with i.v. morphine 1 mg and a 5-min lock out time. Arterial oxygen saturation (SpO2) was measured continuously the night before and for 24 h immediately after surgery. A significantly greater proportion of patients in the PCA group (nine of 19) rated their analgesia as excellent compared with the i.m. group (two of 20) (P < 0.05). There was no significant difference in the incidence of postoperative hypoxaemia in the two treatment groups. Severe postoperative hypoxaemia (SpO2 < 85% for more than 6 min h-1) was seen in three patients receiving i.m. analgesia and one patient in the PCA group.

Abdomen↗
PubMed1992

Transdermal hyoscine with patient-controlled analgesia.

Transdermal hyoscine (Scopoderm TTS CIBA) was compared with placebo in 67 patients receiving postoperative analgesia via a patient-controlled analgesia system. All patients underwent an abdominal hysterectomy and had a standard anaesthetic. They were followed up in recovery and daily for 3 days postoperatively. Fewer patients in the hyoscine group suffered emetic sequelae in recovery and on the third postoperative day (p less than 0.05). The hyoscine group received half the number of supplementary antiemetic doses compared to placebo. However, despite transdermal hyoscine there was still a high (78%) incidence of nausea and vomiting. The only significant (p less than 0.05) increase in side effects attributable to hyoscine was a higher reported incidence of visual disturbance on the second day.

Adult↗
PubMed1992

Functional properties of cloned melanogenic proteins.

Several genes critical to the regulation of melanin production in mammals have recently been cloned and characterized. They map to the albino, brown, and slaty loci in mice, and encode proteins with similar structures and features, but with distinct catalytic capacities. The albino locus encodes tyrosinase, an enzyme with three distinct catalytic activities--tyrosine hydroxylase, 3,4-dihydroxyphenylalanine (DOPA) oxidase and DHI (5,6-dihydroxyindole) oxidase. The brown locus encodes TRP-1 (tyrosinase-related protein-1), which has the same, but greatly reduced, catalytic potential. The slaty locus encodes TRP-2, another tyrosinase related-protein, which has DOPAchrome tautomerase activity. In this study we have examined the enzymatic interactions of these proteins, and their regulation by a novel melanogenic inhibitor. We observed that tyrosinase activity is more stable in the presence of TRP-1 and/or TRP-2, but that the catalytic function of TRP-2 is not affected by the presence of TRP-1 or tyrosinase. Other factors also may influence melanogenesis and a unique melanogenic inhibitor suppresses tyrosinase and DOPAchrome tautomerase activities, but does not affect the spontaneous rate of DOPAchrome decarboxylation to DHI. The results demonstrate the catalytic functions of these proteins and how they stably interact within a melanogenic complex in the melanosome to regulate the quantity and quality of melanin synthesized by the melanocyte.

Animals↗
PubMed1992

TRP-2/DT, a new early melanoblast marker, shows that steel growth factor (c-kit ligand) is a survival factor.

We have used a probe derived from TRP-2/DT to detect migratory melanoblasts shortly after they emerge from the neural crest, as early as 10 days post coitum (dpc). TRP-2/DT expression is otherwise restricted to the presumptive pigmented retinal epithelium, the developing telencephalon and the endolymphatic duct. The pattern of steel and c-kit hybridisation in the developing brain differed from that of TRP-2. TRP-1 and tyrosinase probes also detected melanoblasts but were both expressed later in development than TRP-2. We used the TRP-2/DT probe to investigate the way that the Steel-dickie (Sld) mutation interferes with melanocyte development, and found that the membrane-bound steel growth factor which is missing in Sld/Sld mutants is necessary for the survival of melanoblasts but not for their early migration and initial differentiation.

Animals↗
PubMed1991

Production of mouse Hox-2.1 protein in Escherichia coli: characterisation of in vitro binding to DNA.

The developmentally regulated mouse Hox-2.1 gene encodes a homeodomain-containing (Hox) protein which is likely to function as a transcription factor. We expressed the DNA coding for full-length Hox-2.1 protein in a T7 promoter-containing vector in bacteria, which produced low levels of protein showing weak DNA-binding activity. Synthesis of a truncated polypeptide lacking all the sequence upstream from the homeodomain enabled us to produce greater amounts of protein and demonstrate its sequence-dependent DNA binding. The tetranucleotide ATTA is necessary for binding, but a single copy is not by itself sufficient. Flanking sequences are important; in particular a cytosine immediately 5' to the ATTA enhances binding.

Animals↗
PubMed1991

The tyrosinase-related protein-1 gene has a structure and promoter sequence very different from tyrosinase.

We have determined the exon structure of the mouse tyrosinase-related protein-1 (TRP-1) gene. The gene is only 15kb in length, but contains seven introns, in contrast to the tyrosinase gene which is almost 100kb long with only four introns. Only two introns are located in homologous positions in both genes. Intron I of TRP-1 has three alternative 5' splice sites clustered within 21bp, which all splice to the same 3' site. Intron V has a very unusual 5' splice site, which has the dinucleotide GC rather than the conventional GT. We show that as little as 370bp of 5'-flanking DNA is sufficient to direct cell-specific expression of the chloramphenicol acetyl transferase gene. The flanking DNA of TRP-1, unlike tyrosinase, does not contain a TATA box or a CCAAT box. Both mouse genes, however, share an 11bp sequence, also found in human tyrosinase, which we suggest may be a melanocyte-specific promoter element.

Animals↗
PubMed1991

The human homolog of the mouse brown gene maps to the short arm of chromosome 9 and extends the known region of homology with mouse chromosome 4.

The mouse brown locus encodes a tyrosinase-related protein, TRP-1. The human homolog of TRP-1 was recently cloned from a melanoma cDNA library and sequenced. We have made oligonucleotide primers corresponding to the human TRP1 3' untranslated region and used them to map the human TRP1 gene by species-specific PCR in human/rodent somatic cell hybrids. By this means, the human TRP1 gene has been mapped to the short arm of chromosome 9.

Animals↗
PubMed1991

The first year's experience of an acute pain service.

The benefits, risks and resource implications of providing an Acute Pain Service were assessed during the first year of the service. Six hundred and sixty patients recovering from major surgery were treated with patient-controlled analgesia (510 patients) or extradural infusion analgesia (150 patients). The results of a prospective outcome study showed that pain control was good: more than 60% of patients scored their pain as mild during the first 24 h. Only 10% of patients complained of severe postoperative pain. Eight patients developed potentially serious complications including respiratory depression and hypotension; the diagnosis and management of these problems on general wards is discussed. Retrospective analysis of the incidence of postoperative chest infection in surgical patients showed a marked reduction during the first year of the service (1.3% in 1988, 0.4% in 1989-90 (P less than 0.01].

Acute Disease↗
PubMed1991

Postoperative pain control. A survey of current practice.

A survey of postoperative analgesia in 195 anaesthetic departments in England and Wales was undertaken. The results showed that 64% of respondents were dissatisfied or very dissatisfied with the present situation. Large differences were demonstrated between what was regarded as the safest technique and what would form the ideal management of postoperative pain.

Analgesia, Epidural↗
PubMed1991

Minitracheotomy Seldinger--assessment of a new technique.

A multicentre, prospective study of 26 patients was undertaken for the assessment of insertion of minitracheotomy tubes by the Seldinger technique. The technique of insertion is described. There were two misplacements, three blockages of the inserting Tuohy needle with fat, and six cases of difficulty in passing the minitracheotomy tube.

Anesthesia, Local↗
PubMed1991

Evaluation of the Graseby PCAS. A clinical and laboratory study.

The Graseby patient-controlled analgesia system was evaluated in the laboratory and in clinical use. The problems encountered with eight examples used to treat 510 patients are reported. Laboratory performance revealed the unit to be accurate at infusion volumes of 1 and 2 ml.

Analgesia, Patient-Controlled↗
PubMed1991

Reverse genetics in the mouse and its application to the study of deafness.

Genetic variants of the laboratory mouse can serve as useful models for hereditary deafness syndromes in humans. Recessive mutations at the shaker-1 (sh-1) and whirler (wi) loci, in chromosomes 7 and 4, respectively, both result in circling behavior and a deafness syndrome. In sh-1 homozygotes this deafness is associated with neurophysiological abnormalities that may be accompanied by structural abnormalities of the inner ear. Radiation-induced deletion mutations are being used in a strategy of reverse genetics to identify the genes defined by these mutations. Genetic analyses have refined the position of sh-1 to a chromosomal interval between break points of deletions involving the closely linked albino (c) locus. A cDNA encoding olfactory marker protein (OMP) and the anonymous locus D7OR1 have also been mapped to this interval. These clones contribute to the physical map of the sh-1 region and could be important for accessing the sh-1 gene itself. Similarly, we have identified a radiation-induced deletion of the brown (b) locus that covers the wi locus and two that do not. Thus, the wi locus has been located within a chromosome 4 interval defined by structural rearrangements, which should likewise aid in identifying closely linked molecular clones.

Animals↗
PubMed1990

Identification of the albino mutation of mouse tyrosinase by analysis of an in vitro revertant.

From within an albino melanocyte line grown in vitro we identified and cloned cells that apparently had reverted to wild type. We sequenced a part of the tyrosinase gene, encompassing a candidate mutation, from wild-type, albino, and revertant cell DNAs. The revertant cells contain, on one chromosome, a perfect base reversion to the wild-type sequence of this candidate mutation, proving that this is the sole defect in the tyrosinase gene of albino mutant mice. The revertant cells readily regain the albino phenotype after freezing and thawing. Taking advantage of a Dde I restriction site created by the albino mutation, we demonstrated that the regained phenotype is due to allele loss involving the wild-type chromosome. The Dde I site also allowed us to show that all inbred albino mice carry the same mutation and so must be derived from the same progenitor.

Albinism↗
PubMed1990

Genetic and molecular analysis of chlorambucil-induced germ-line mutations in the mouse.

Eighteen variants recovered from specific locus mutation rate experiments involving the mutagen chlorambucil were subjected to several genetic and molecular analyses. Most mutations were found to be homozygous lethal. Because lethality is often presumptive evidence for multilocus-deletion events, 10 mutations were analyzed by Southern blot analysis with probes at, or closely linked to, several of the specific locus test markers, namely, albino (c), brown (b), and dilute (d). All eight mutations (two c; three b; two d; and one dilute-short ear [Df(d se)]) that arose in post-spermatogonial germ cells were deleted for DNA sequences. No evidence for deletion of two d-se region probes was obtained for the remaining two d mutations that arose in stem-cell spermatogonia. Six of the primary mutants also produced low litter sizes ("semisterility"). Karyotypic analysis has, to date, confirmed the presence of reciprocal translocations in four of the six. The high frequency of deletions and translocations among the mutations induced in post-spermatogonial stages by chlorambucil, combined with its overall high efficiency in inducing mutations in these stages, should make chlorambucil mutagenesis useful for generating experimentally valuable germ-line deletions throughout the mouse genome.

Animals↗
PubMed1990

The molecular basis of brown, an old mouse mutation, and of an induced revertant to wild type.

The murine b locus encodes the tyrosinase related protein, TRP-1, a putative membrane-bound, copper-containing enzyme having about 40% amino acid identity with tyrosinase. The protein is essential for production of black rather than brown hair pigment. We show that skin of mutant brown mice contains the same amount of TRP-1 mRNA as wild type. On sequencing the coding region of the mutant mRNA we find four nucleotide differences from the wild-type (Black) sequence. Two of these differences result in different amino acid residues encoded by the brown allele. By sequencing the TRP-1 gene from a mouse in which a reversion from brown to Black has been induced by ethylnitrosourea we are able to show that only one of these amino acid changes, which substitutes a tyrosine for a conserved cysteine, is the cause of the brown phenotype. This mutation is adjacent to another cysteine at which, in the analogous position in tyrosinase a mutation results in the albino phenotype. The sequence of the revertant is the first report of DNA sequence of an ethylnitrosourea-induced genetic change in mouse.

Amino Acid Sequence↗