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P Anderson

Publications and source records attributed to P Anderson.

At least 325 records · Page 18Linked to original sources
PubMed1990

Functions of the myosin ATP and actin binding sites are required for C. elegans thick filament assembly.

We have determined the positions and sequences of 31 dominant mutations affecting a C. elegans muscle myosin heavy chain gene. These mutations alter thick filament structure in heterozygotes by interfering with the ability of wild-type myosin to assemble into stable thick filaments. These assembly-disruptive mutations are missense alleles affecting the globular head of myosin. The most strongly dominant alleles alter highly conserved residues of the myosin ATP binding site, indicating that functions of the myosin ATPase are important for thick filament assembly. Other alleles alter the site at which myosin binds actin.

Actin Cytoskeleton↗
PubMed1990

Splicing of a C. elegans myosin pre-mRNA in a human nuclear extract.

Splicing of mammalian introns requires that the intron possess at least 80 nucleotides. This length requirement presumably reflects the constraints of accommodating multiple snRNPs simultaneously in the same intron. In the free-living nematode, C. elegans, introns typically are 45 to 55 nucleotides in length. In this report, we determine whether C. elegans introns can obviate the mammalian length requirement by virtue of their structure or sequence. We demonstrate that a 53 nucleotide intron from the unc-54 gene of C. elegans does not undergo splicing in a mammalian (HeLa) nuclear extract. However, insertion of 31 nucleotides of foreign, prokaryotic sequence into the same intron results in efficient splicing. The observed splicing proceeds by the same two-step mechanism observed with mammalian introns, and exploits the same 3' and 5' splice sites as are used in C. elegans. The branch point used lies in the inserted sequence. We conclude that C. elegans splicing components are either fewer in number or smaller than their mammalian counterparts.

Animals↗
PubMed1990

Fc gamma receptor type III (CD16) is included in the zeta NK receptor complex expressed by human natural killer cells.

We recently reported that CD3- natural killer (NK) cells express the zeta chain of the T-cell receptor complex (zeta NK) in association with higher molecular weight structures whose expression differs between individual NK cell clones. Because NK cell cytolytic activity is known to be triggered by perturbation of the type III Fc gamma receptor (CD16), we sought to determine whether this activating molecule is included in the zeta NK molecular complex. Biochemical evidence for a physical association between CD16 and zeta NK was obtained by comparing immunoprecipitates formed using monoclonal antibodies reactive with each of these molecules by SDS/polyacrylamide gel electrophoresis, immunoblotting, and peptide mapping. In both clonal and polyclonal populations of CD3- NK cells, CD16 and zeta NK specifically associated with one another. Functional evidence for a specific association between CD16 and zeta NK in intact cells was obtained by demonstrating a coordinate down-modulation of both of these molecules induced by either phorbol 12-myristate 13-acetate or monoclonal antibodies reactive with CD16. Our results suggest that Fc gamma receptor type III (CD16) is included in the zeta NK complex and that this complex is likely to play an important role in NK cell activation.

Antibodies, Monoclonal↗
PubMed1990

Is alcohol a carcinogenic risk?

Consumption of alcoholic beverages has been implicated as a risk factor for the development of various cancers including oesophageal, oral, pharyngeal, laryngeal, liver and breast cancers. This article is a commentary on an earlier paper entitled 'Alcohol: a carcinogenic risk?' which challenges some of the evidence relating alcoholic beverage consumption to risk for these cancers. In the course of commenting on this paper, evidence is reviewed which shows a relationship between these cancers and consumption of alcoholic beverages, which is often found to be dose-related.

Alcoholic Beverages↗
PubMed1990

Nifedipine as an antihypertensive drug in patients with renal failure--pharmacokinetics and effects.

Pharmacokinetics and pharmacodynamics of nifedipine were studied in 12 patients with renal failure and hypertension, after a single dose and during an 18-week treatment period. The plasma concentrations of nifedipine and its first pyridine metabolite were measured by gas chromatography mass spectrometry. The oral plasma clearance of nifedipine was 1189 +/- 876 ml min-1, and the mean plasma half-life (t1/2) was 5.99 +/- 3.05 h. The pyridine metabolite was not retained. Plasma concentrations of nifedipine were found to be significantly correlated with the effects on blood pressure, forearm blood flow and peripheral resistance, and these effects did not vary with the degree of renal failure. Normotension was achieved in eight of the nine patients observed over a period of 4 months with doses in the range 20-40 mg, administered twice daily. The mean Cr-EDTA clearance remained unchanged during the study (initial value 31.4 +/- 12.3 ml min-1; final value 32.7 +/- 14.4 ml min-1), and in three patients it increased. Nifedipine induces a slight increase in metabolic rate in patients with renal failure, but it is not necessary to modify the dose. It is effective in lowering blood pressure, has mild side-effects and may improve renal function in some patients.

Adult↗
PubMed1990

Multiple mechanisms in serum factor-induced resistance of Haemophilus influenzae type b to antibody.

Incubation of Haemophilus influenzae type b at less than or equal to 10(7) CFU/ml with serum ultrafiltrate induces a phenotypic conversion in which complement-mediated bactericidal activity by somatic antibodies decreases while killing by capsular antibody is unchanged. Conversion had been shown to occur in a capsule-deficient (b-) mutant of strain Eag (thus appearing independent of capsulation), to include an increase in lipopolysaccharide content, and to be inhibited by chloramphenicol or puromycin. In the present study, in several strains not previously examined, conversion was not inhibited by the drugs and the corresponding b- mutants did not convert. Incubation in ultrafiltrate was also found to increase capsulation, as detected by radioassay, only 1.6-fold in Eag but 4.5-fold in DL26, the strain with the largest increase in resistance; moreover, complement-mediated opsonization by capsular antibody was greatly decreased. Thus, multiple mechanisms, capsule dependent as well as independent, appear to contribute to the serum factor-induced resistance of H. influenzae type b to antibody.

Antibodies, Bacterial↗
PubMed1990

Automated measurement of two indicators of human selenium status, and applicability to population studies.

We developed an automated system consisting of a centrifugal analyzer and an atomic absorption spectrophotometer with Zeeman background correction to produce a profile of the concentrations of selenium and the selenium-dependent enzyme glutathione peroxidase (EC 1.11.1.9) in serum and whole blood, for use in epidemiological surveys in Northern Ireland. No pretreatment of samples other than dilution is required, and at least 35 subjects can be screened within 24 h of venesection. For selenium in serum the between-run CV was 5.7% and 4.4% within run. For selenium in whole blood the CV was 5.9% between runs, 5.7% within run. The within-run CV for glutathione peroxidase was 0.92% for serum, 1.18% for blood; the between-run CV was 8.3% for serum. To illustrate the use of the system, we present the profile of selenium and glutathione peroxidase in serum and whole blood from 100 adults 25 to 64 years old.

Adult↗
PubMed1989

Monoclonal antibodies reactive with the T cell receptor zeta chain: production and characterization using a new method.

We have developed a novel method for the production and characterization of monoclonal antibodies reactive with lineage-restricted intracellular Ag. Using this technique, we have produced a panel of antibodies that react specifically with permeabilized T lymphocytes but not with permeabilized B lymphocytes or native T cells. One of these antibodies, designated TIA-2, was found to react with greater than 98% of peripheral blood T lymphocytes. Immunoblotting experiments showed TIA-2 to recognize a 32 kd protein that was reduced to 16 kDa in the presence of 2-mercaptoethanol. Immunoprecipitates analyzed on non-reducing/reducing diagonal polyacrylamide gels showed the homodimeric structure recognized by TIA-2 to be associated with additional structures whose pattern closely resembled that of the T cell receptor complex. When immunoprecipitates formed using antibodies reactive with CD3 epsilon were immunoblotted with TIA-2, the homodimeric TCR zeta chain was specifically recognized. Using TIA-2 as a TCR zeta specific reagent, we show that whole cell expression of this TCR subunit is dramatically reduced following exposure to mAb reactive with CD3. mAb reactive with activating epitopes of CD2 were also capable of down-modulating the expression of TCR zeta, but to a lesser degree. Exposure to Con A or IL-2, on the other hand, did not reduce the whole cell expression of TCR zeta. Given the central importance of TCR zeta in the expression of a functionally competent Ag receptor, its reduced expression in response to certain activating stimuli is likely to play an important role in regulating T cell responsiveness.

Animals↗
PubMed1989

CD3-negative natural killer cells express zeta TCR as part of a novel molecular complex.

Natural killer (NK) cells are large granular lymphocytes capable of killing tumour cells in a non-MHC restricted manner. NK cells do not express cell-surface CD3, or any known target recognition structure analogous to the T cell antigen receptor (TCR) heterodimers (alpha beta or gamma delta). Consistent with their lack of expression of a CD3-TCR complex, NK cells do not require prior sensitization or antigen presentation by accessory cells to specifically recognize their tumour targets. Although NK cells do not express CD3-TCR, they do express CD2, the target of an alternative activation pathway which is functional in both T cells and NK cells. In T cells, this alternative activation pathway utilizes some component of the CD3-TCR complex as a transducer molecule that is required for mitogenesis. The fact that NK cells are activated by this alternative pathway suggested that they might express a related subunit of the CD3-TCR complex capable of transducing the CD2-mediated signal. Here we show that human NK cells express the zeta-chain of the TCR complex in association with additional structures not included in CD3-TCR.

Antibodies, Monoclonal↗
PubMed1989

Multiple carpo-metacarpal dislocations.

Ten patients with closed multiple carpo-metacarpal dislocations have been reviewed. Closed manipulation was found to be successful if performed within two days of the injury. Plaster cast immobilisation supplemented by percutaneous Kirschner wire fixation is recommended to maintain the reduction, due to the unstable nature of the dislocation. Early appropriate treatment of these injuries carries a good prognosis.

Bone Wires↗
PubMed1989

Sources of low-molecular-weight host factors that phenotypically increase the resistance of Haemophilus influenzae type b to bacteriolysis: non-identity with a factor active in gonococci.

Both gonococci and Haemophilus influenzae type b (Hib) in response to incubation with low-molecular-weight components of blood are converted to a relative resistance to killing by antibody and complement in vitro. Recently, cytidine 5'-mono-phospho-N-acetylneuraminic acid (a sialyl donor present in mammalian tissues) was found to convert gonococci. Here we report that this compound was inactive in Hib. In further contrast, the Hib-converting activity of serum was not retained by 500-M, filters, not sensitive to pH 2, and not active in the presence of growth media. Thus the phenotypic resistance in Hib and gonococci appear to have a different metabolic basis. The low-Mr serum factors active in Hib remain to be identified. Filtrates of human nasopharyngeal washes were also active, further suggesting that the converted form resembles the phenotype of Hib in vivo.

Blood Bactericidal Activity↗
PubMed1989

The Tc3 family of transposable genetic elements in Caenorhabditis elegans.

We describe genetic and molecular properties of Tc3, a family of transposable elements in Caenorhabditis elegans. About 15 Tc3 elements are present in the genomes of several different wild-type varieties of C. elegans, but Tc3 transposition and excision are not detected in these strains. Tc3 transposition and excision occur at high frequencies, however, in strain TR679, a mutant identified because of its highly active Tc1 elements. In TR679, Tc3 is responsible for several spontaneous mutations affecting the unc-22 gene. Tc3-induced mutations are unstable, and revertants result from precise or nearly precise excision of Tc3. Although Tc3 is very active in TR679, it is not detectably active in several other mutator mutants, all of which exhibit high levels of Tc1 activity. Tc3 is 2.5 kilobases long, and except for sequences near its inverted repeat termini, it is unrelated to Tc1. The termini of Tc3 are inverted repeats of at least 70 base pairs; the terminal 8 nucleotides of Tc3 are identical to 8 of the terminal 9 nucleotides of Tc1.

Animals↗
PubMed1989

A new kind of informational suppression in the nematode Caenorhabditis elegans.

Independent reversions of mutations affecting three different Caenorhabditis elegans genes have each yielded representatives of the same set of extragenic suppressors. Mutations at any one of six loci act as allele-specific recessive suppressors of certain allels of unc-54 (a myosin heavy chain gene), lin-29 (a heterochronic gene), and tra-2 (a sex determination gene). The same mutations also suppress certain alleles of another sex determination gene, tra-1, and of a morphogenetic gene, dpy-5. In addition to their suppression phenotype, the suppressor mutations cause abnormal morphogenesis of the male bursa and the hermaphrodite vulva. We name these genes smg-1 through smg-6 (suppressor with morphogenetic effect on genitalia), in order to distinguish them from mab (male abnormal) genes that can mutate to produce abnormal genitalia but which do not act as suppressors (smg-1 and smg-2 are new names for two previously described genes, mab-1 and mab-11). The patterns of suppression, and the interactions between the different smg genes, are described and discussed. In general, suppression is recessive and incomplete, and at least some of the suppressed mutations are hypomorphic in nature. A suppressible allele of unc-54 contains a deletion in the 3' noncoding region of the gene; the protein coding region of the gene is apparently unaffected. This suggests that the smg suppressors affect a process other than translation, for example mRNA processing, transport, or stability.

Alleles↗
PubMed1989

Haemophilus influenzae b polysaccharide revaccination: a continued role for the unconjugated vaccine.

In a study of the issue of revaccination with Haemophilus influenzae b polysaccharide vaccine, 36 children who had been vaccinated with polysaccharide vaccine at age 18 to 20 months were stratified according to their 3-week postvaccination anticapsular antibody concentration determined by radioantigen binding assay, then sequentially assigned to one of three groups so as to have comparable distributions of peak antibody concentrations. These children were revaccinated with polysaccharide vaccine at 24 to 27, 30 to 33, or 36 to 39 months of age. The post-reimmunization geometric mean antibody concentrations in these three groups were 3.1, 3.0 and 7.8 micrograms/ml, respectively, and the percentages rising to greater than 1 microgram/ml were 75, 80 and 93%. The geometric means and antibody response rates were nearly identical to age-matched control groups not previously vaccinated. Thus there was no evidence of priming (memory induction) or of tolerance induction by the early (18 months old) primary vaccination.

Age Factors↗
PubMed1989

Health authority policies for the prevention of alcohol problems.

Although national policy has a major influence in preventing alcohol problems, much can be done at a local level. In addition national policy can either be made or at least influenced from the local level, and local communities are well placed to change attitudes and influence key processes, thus creating a climate for appropriate national debates and policy developments. This paper addresses why a local policy is needed for the prevention of alcohol problems, and then considers a number of the components of such a policy, how such a policy might be implemented, and how such a policy might be evaluated.

Alcoholism↗