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Biomedical subjects

N Williams

Publications and source records attributed to N Williams.

At least 163 records · Page 9Linked to original sources
PubMed1997

Purification, cloning, and expression of two closely related Trypanosoma brucei nucleic acid binding proteins.

Nucleic acid binding proteins in the trypanosomatid family are of particular interest because of several unusual molecular phenomena discovered in these organisms. We have purified two closely related proteins, p34 and p37, from the procyclic from of T. brucei using high salt extraction and single-stranded-DNA (ssDNA) agarose chromatography. Antibodies raised against the p34 protein showed crossreactivity with p37, suggesting relatedness. High performance liquid chromatography analysis and microsequencing of tryptic peptides derived from p34 and p37 showed that the primary structures of the two proteins are nearly identical. We have cloned and sequenced the two genes encoding these two proteins. Protein sequences predicted from the cDNAs confirm the relatedness of the two proteins but also indicate the presence of an 18 amino acid insertion unique to one of the two proteins as well as several minor differences resulting from single amino acid changes. Three sequence motifs have been identified in both proteins: an N-terminal alanine, proline, and lysine rich domain, one and a half internal RNA-binding domains, and a C-terminal KKDX repeat region. Both proteins preferentially bind to heterogenous RNA and ssDNA versus double-stranded DNA and homopolymers. Both recombinant proteins have been expressed in E. coli and show properties indistinguishable from those observed with native p34/p37.

Amino Acid Sequence↗
PubMed1997

Association of the angiotensin I converting enzyme gene deletion polymorphism with early onset of ESRF in PKD1 adult polycystic kidney disease.

To determine the effect of the ACE gene insertion/deletion (I/D) polymorphism, angiotensinogen gene M235T polymorphism and the angiotensin 1 receptor gene A1166C polymorphism on the age of onset of end-stage renal failure (ESRF) in PKD1 adult autosomal-dominant polycystic kidney disease (ADPKD), 189 individuals from 46 families with PKD1 were genotyped for each polymorphism. Of the 189 patients 52 (28%) reached ESRF at an average age of 48 +/- 1 year. In patients genotyped for the ACE gene insertion/deletion polymorphism the frequencies of the DD, ID and II genotypes were similar to those expected from Hardy Weinberg equilibrium. In patients with ESRF there was an excess of patients homozygous for the deletion allele (DD: 48% chi2 = 9.97 (1df) P = 0.002). Cumulative renal survival was significantly reduced among those with DD genotype compared to ID and II genotypes. The estimated mean renal survival (95% confidence intervals) were: DD, 52 years [48, 57]; II, 59 years [54, 63]; ID, 64 years [56, 72]; chi2 = 6.13 (1df) P = 0.013, DD versus ID/II. The mean age of renal failure was significantly younger in the DD genotype compared to ID and II genotypes (DD, ID, and II: 44 +/- 2, 49 +/- 2 and 54 +/- 3 years, respectively; P < 0.05 DD vs. ID, P < 0.05 DD vs. II). Ten of the eleven patients who reached ESRF before the age of 40 were homozygous for the deletion allele. The relative risk for ESRF below the age 40 for DD genotype was 17. For all ages there was an overall increased risk of 1.4 for ESRF with the DD genotype. There was no interaction between age of onset of ESRF and either the angiotensinogen M235T allele or angiotensin 1 receptor A1166C polymorphism. This study strongly suggests that PKD 1 patients homozygous for the deletion allele of the ACE gene are at increased risk of developing ESRF at a early age.

Adult↗
PubMed1997

A prospective evaluation of central venous blood flow using Doppler ultrasound in patients with a long-term central venous catheter.

Using Doppler ultrasound, we prospectively evaluated the relationship between central venous blood flow and the development of central venous thrombosis in ten patients with a long term central line. The presence of turbulent blood flow around the catheter was followed by the development of central venous thrombosis in two patients but neither had subsequent clinical sequelae. More surprisingly, however, normal blood flow was demonstrated in eight patients, two of whom subsequently developed intravascular thrombi.

Adolescent↗
PubMed1997

Maternal psychological issues in the experience of breastfeeding.

This paper describes various situations wherein psychological etiologies of breastfeeding failure were discovered after exhausting the usual means of assisting the new mother. This discussion involves a look at possibilities of why and when to consider emotional difficulties and when to provide referrals for assistance.

Adaptation, Psychological↗
PubMed1997

Radiological confirmation of intraperitoneal free gas.

Although subdiaphragmatic gas on an erect chest or abdominal radiograph usually indicates the presence of a gastrointestinal perforation, this sign is present in only 60-80% of cases. Other less well known radiographic signs of perforation that may nonetheless be of utmost importance in diagnosis are described. The presence of such signs may then prompt further diagnostic procedures or surgical intervention as appropriate.

Humans↗
PubMed1997

Neutropenic colitis: a continuing surgical challenge.

BACKGROUND: Neutropenic colitis is a clinicopathological syndrome characteristically seen as a complication of chemotherapy for haematological malignancy. This review explores the pathogenesis of the condition and appraises the options for management. METHODS: A Medline search was carried out and all relevant papers were reviewed. RESULTS: There are many case reports but few published series, so experience is mainly anecdotal. Both medical and surgical management have been successful; it is not possible to compare treatment groups formally. CONCLUSION: The greater use of aggressive multiagent chemotherapy regimens may increase the frequency with which the condition is encountered. Heightened awareness of neutropenic colitis may prompt diagnosis and a better understanding of the pathophysiology may help guide clinical management.

Colitis↗
PubMed1997

The relative population sizes of megakaryocytic cells in mouse bone marrow as determined by mpl ligand responsiveness.

The relative population sizes of mpl ligand-responsive megakaryocytic cells were investigated, and all megakaryocytes grown in culture were assessed. Three groups were analyzed: 1) immature cells with the ability to form single mature megakaryocytes; 2) cells with the ability to divide once before forming megakaryocytes (doublets); and 3) progenitor cells with the ability to form colonies, i.e., to undergo both cytokinesis and maturation. Immature cells forming single megakaryocytes proved most sensitive to the mpl ligand. Committed megakaryocyte progenitors required approximately 30 times more mpl ligand to achieve maximum growth than did the immature megakaryocyte population. Similar numbers of committed megakaryocyte progenitors responded to interleukin (IL)-3 and to mpl ligand. The amplification potential of these progenitor cells responding to each growth factor was assessed by measuring the number of megakaryocytes per colony. In response to mpl ligand progenitor, cells generated smaller colonies, with most cell divisions completed at a signifcantly earlier time point compared with progenitor cells responding to IL-3. The growth of more primitive megakaryocyte progenitors was best achieved in combination with other growth factors, notably IL-3; mpl ligand alone was ineffective in this regard. A novel finding was the significant number of megakaryocytes that grew in culture as closely coupled pairs (doublets). Data reported indicate that doublet formation may be a result of detection and stimulation of immature megakaryocytes rather than the diminished mpl ligand responsiveness of a proportion of megakaryocyte progenitors. By combining the number of mpl ligand-responsive cells forming single megakaryocytes with those forming megakaryocyte doublets, it is estimated that the size of the immature megakaryocyte pool greatly exceeds previous calculations. Thus we conclude that the immature megakaryocyte population is significantly larger than previously estimated and that these cells are the most sensitive to mpl ligand. Accordingly, these cells are potentially crucial in bone marrow responsiveness to mpl ligand that results from acute thrombocytopenia, being capable not only of endomitosis and maturation but perhaps of cell division as well.

Animals↗
PubMed1997

Managing back pain in general practice--is osteopathy the new paradigm?

Back pain is a common problem in general practice, and is of enormous economic importance. A recent report urges general practitioners (GPs) to refer early for manual therapies, such as osteopathy. The key concept to understanding osteopathic principles is somatic dysfunction. This is a disorder of function, rather than pathology, of the musculoskeletal and related systems. Its characteristic features are asymmetry of anatomical landmarks, asymmetry of joint movement, tissue texture changes, and tenderness. The scientific basis of the tissue texture changes and tenderness can be explained in terms of the 'facilitated segment', but the cause of movement asymmetry remains elusive. Randomized controlled trials provide some support for the use of osteopathic treatment in acute low back pain. It is proposed that somatic dysfunction is the new paradigm for non-specific back pain.

Back Pain↗
PubMed1996

The ATP synthase of Trypanosoma brucei is developmentally regulated by an inhibitor peptide.

The Trypanosoma brucei ATP synthase, like those of other organisms, is composed of two moieties, the membrane bound F0 and the catalytic F1 with each of these parts comprised of multiple subunits. In addition, an endogenous inhibitor peptide of the ATP synthase has been identified from a variety of sources. Previous reports have suggested that the Trypanosoma brucei ATPase may not possess such an inhibitor. Recently, we have isolated an inhibitor peptide fraction from the procyclic form of Trypanosoma brucei by modification of a previously published procedure. This fraction is composed of two dominant polypeptides with estimated molecular weights of 14,000 and 12,000 and an additional polypeptide of 15,000 that may or may not be functionally required. Antibodies raised to the smallest polypeptide showed strong cross reactivity with the other two polypeptides, suggesting that they are related. Antibodies to rat liver inhibitor peptide show cross reactivity with the same polypeptides in crude fractions. The inhibitor peptide fraction strongly suppresses the ATPase activity of membrane bound ATPase in a Mg(2+)-dependent manner and is cold and heat stable. Using antibodies to the smallest polypeptide and rat liver inhibitor peptide we have shown in crude extracts from the three experimental life cycle stages of T. brucei that the inhibitor peptide(s) is developmentally regulated to a modest extent. The pattern of regulation is opposite of the pattern seen for the ATP synthase complex. This suggests that the ATP synthase is stringently controlled in T. brucei in a unique way.

Animals↗