Search PubMed⌕ Search

Biomedical subjects

S Jones

Publications and source records attributed to S Jones.

At least 343 records · Page 19Linked to original sources
PubMed1995

Similar but nonidentical amino acid residues on vascular cell adhesion molecule-1 are involved in the interaction with alpha 4 beta 1 and alpha 4 beta 7 under different activity states.

The integrin receptors alpha 4 beta 1 and alpha 4 beta 7 both bind to vascular cell adhesion molecule-1 (VCAM-1). Here, we report that the amino acid residue requirements for murine VCAM-1 adhesion to murine alpha 4 beta 1 (WEHI 231) and alpha 4 beta 7 (38C13/beta 7-transfectant) positive cells are strikingly similar but nonidentical under multiple adhesion activity states. By site-directed mutagenesis of domain 1 of VCAM-1, the amino acid residues on the loop between beta strands C and D (R36, Q38, I39, D40, P42) and on the adjacent antiparallel beta strand F (L70 and T72) were required for basal level adhesion to both alpha 4 beta 1-positive and alpha 4 beta 7-positive cells. Mutation at two other sites, N44 (loop between beta strands C and D) and E66 (loop between beta strands E and F), specifically reduced alpha 4 beta 7-positive cell adhesion, but not alpha 4 beta 1-positive cell adhesion. Mutation H85A augmented alpha 4 beta 7 binding but not alpha 4 beta 1 binding. These apparent differences relate to the higher intrinsic activity state of alpha 4 beta 1 on WEHI 231 than on alpha 4 beta 7 (38C13/beta 7-transfectant). In contrast, under higher adhesion activity states induced by either MnCl2 or truncation of the beta 7 cytoplasmic tail, mutation of either amino acid residue D40 or L70 completely blocked cell adhesion without evidence of structural perturbation of VCAM-1. These results suggested that the two structurally discontinuous amino acid residues, the negatively charged D40 and the hydrophobic L70 adjacently located on domain 1 of VCAM-1, are essential for interaction under multiple activity states with both alpha 4 beta 1 and alpha 4 beta 7 integrin receptors.

Amino Acid Sequence↗
PubMed1995

Exon scanning for mutations of the NF2 gene in pediatric ependymomas, rhabdoid tumors and meningiomas.

Deletions of chromosome 22 have been identified in 3 types of childhood primary brain tumor: meningiomas, rhabdoid or atypical teratoid tumors (ATT) and ependymomas. This implicates the involvement of tumor suppressor genes on chromosome 22 in the genesis of these rare tumors. One such candidate tumor suppressor gene is the recently cloned neurofibromatosis 2 (NF2) locus. The purpose of our study was to determine the frequency of germ-line and somatic NF2 mutations in a selected group of brain tumors in children. Using single-strand conformation polymorphism (SSCP) assays we screened 17 exons of the NF2 gene in 13 pediatric brain tumors and 9 matched normal blood DNA samples. Tumors included 3 meningiomas, 2 rhabdoid or ATTs, 7 ependymomas and 1 malignant tumor of glial lineage. In addition, lymphoblastoid cell lines from 3 patients with rhabdoid/ATT in whom no tumor tissue was available were analyzed for germ-line mutations. Migration shifts were not detected in any of the normal DNA samples analyzed. Of the 13 tumors screened by SSCP, 1 meningioma with monosomy 22 produced a migration shift in exon 13. DNA sequencing of exon 13 revealed a deletion of a single guanine nucleotide (base 1397) in codon 466, causing a frame shift. While not all mutations might have been picked up by this technique, the data suggest that, similar to adult sporadic meningiomas, some pediatric meningiomas may result from somatic mutations in the NF2 gene. For rhabdoid tumors and ependymomas it appears that a locus distinct from NF2 might be responsible for tumorigenesis.

Base Sequence↗
PubMed1995

Putting Yiamouyiannis into perspective.

Few names crop up so often in the context of water fluoridation as that of John Yiamouyiannis, an American who has campaigned hard to stop this public health measure not only in the United States but in other countries such as Britain. During 1993, Yiamouyiannis was given considerable air time by the BBC, appearing on its prestigious You and yours and Nature programmes where he denigrated the efforts of local health authorities to reduce tooth decay by means of fluoridating their water supplies. His dramatic claims about fluoridation--in particular, that it increases people's risk of dying of cancer--must understandably alarm those who take them at face value. So just who is John Yiamouyiannis? And do his allegations hold up? This review of his career is based on publicly documented records and statements.

Fluoridation↗
PubMed1995

Evaluation of an autologous red cell agglutination test, VetRED FIV, for the presence of FIV antibody in cats.

A commercially available whole blood agglutination test, VetRED FIV, used for the detection of antibodies to feline immunodeficiency virus (FIV), was evaluated. The test is based on the use of a synthetic peptide conjugated to a non-agglutinating anti-feline red blood cell monoclonal antibody. The amino acid sequence of the synthetic peptide was derived from the predicted sequence of the transmembrane protein of FIV. The sensitivity and specificity of VetRED FIV was 100% when 34 known FIV-positive and 15 known FIV-negative cats were tested. These cats were part of studies on experimentally induced FIV infection, with their FIV status confirmed by virus isolation. Further, VetRED FIV was compared with another commercially available test for FIV antibody, PetChek in a field trial on 548 feline blood samples received by a diagnostic laboratory. Of the test results 94.2% (516/548) were in agreement: 112 were positive by VetRED FIV and PetChek; 404 were negative by both tests and 32 were discordant. These 5.8% discordant samples producing VetRED FIV-positive/PetChek-negative or VetRED FIV-negative/PetChek-positive were further assessed by Western blot assay. In the field trial, the sensitivity and specificity of VetRED FIV was 97% and 97%, respectively, comparable to the 98% sensitivity and 99% specificity for PetChek. The results from the trial also confirm the relatively high overall prevalence of FIV in Australian cats predominantly among mature male cats in the 9-12 year age group. Given the simplicity of the VetRED FIV procedure, it is concluded that VetRED FIV is a useful addition to the available commercial tests for FIV infection.

Animals↗
PubMed1995

Bradykinin excites rat sympathetic neurons by inhibition of M current through a mechanism involving B2 receptors and G alpha q/11.

Bradykinin (BK) is a peptide mediator released in inflammation that potently excites sympathetic neurons. We have studied the mechanism of this excitation in dissociated rat sympathetic neurons and found that at low nanomolar (EC50 = 0.9 nM) concentrations, BK inhibited the M-type K+ current IK(M). Studies with the selective antagonist Hoe140 revealed that this effect was mediated via the B2 receptor subtype, and mRNA encoding this receptor was identified in these neurons by RT-PCR. IK(M) inhibition was unaffected by Pertussis toxin or microinjection of antibodies to G alpha o but was selectively inhibited by microinjection of antibodies to G alpha q/11. Thus, BK is the most potent M current inhibitor yet described in mammalian neurons, and BK inhibition of M current is mediated by a G protein pathway similar to that activated by muscarinic acetylcholine receptors.

Animals↗
PubMed1995

Alpha-actinin in nemaline bodies in congenital nemaline myopathy: immunological confirmation by light and electron microscopy.

To elucidate the protein composition of the nemaline bodies present in the muscle fibres of patients with congenital nemaline myopathy (CNM), we studied muscle biopsies with monoclonal antibodies against alpha-actinin and desmin in combination with a modified Gomori trichrome method. Electron microscopy of immunolabelled resin embedded sections was used for cytochemical localisation of alpha-actinin and desmin. Light microscopy of sections immunolabelled for alpha-actinin showed a cross-striation of the muscle fibres corresponding to the Z band pattern, focal thickening of the Z bands and additional reactivity with a granular pattern corresponding to the presence of nemaline bodies. Labelling of desmin did not show a similar pattern. Electron microscopy confirmed the presence of alpha-actinin in the nemaline bodies and Z bands, whereas desmin was only found in intermediate filaments around the Z bands. Western blots showed single, sharp alpha-actinin bands indistinguishable from normal. Our results provide direct evidence for the presence of alpha-actinin in nemaline bodies and a lack of quantitative or qualitative differences between the alpha-actinin of normal and CNM muscle.

Actinin↗
PubMed1995

The economic costs of alcohol-related absenteeism and reduced productivity among the working population of New Zealand.

Lost productivity accounts for a significant proportion of the total cost of alcohol. This study quantifies the costs associated with alcohol consumption using survey data collected from four alcohol surveys conducted in Auckland between November 1990 to May 1992. The total sample size was 4662, of which 2638 were drinkers in paid employment. A computer-assisted telephone interviewing system was used to interview a random sample that closely matched the Auckland population. Respondents gave information about their typical alcohol consumption and frequency of absences from paid employment which were a result of their drinking. They also gave a report of the number of times in the past 12 months when they felt their work had been impaired as a result of their drinking. The cost of absenteeism was recorded as the number of times a respondent reported time away from work multiplied by gross income. Estimates of reduced work efficiency were derived from US figures, which estimated a 25% reduction in work performance among heavy alcohol users; 3.7% of the sample reported alcohol-related absences and 12% reported reduced efficiency days. There was a significant difference in both the number and cost of absentee and reduced efficiency days reported between the top 10% and the bottom 10% drinkers. A conservative estimate of alcohol-related lost productivity among the working population of New Zealand (with a population of 3.4 million and a per capita absolute alcohol consumption of 9.7 litres) was found to be $57 million per year.

Absenteeism↗
PubMed1995

Requirement of nucleotide exchange factor for Ypt1 GTPase mediated protein transport.

Small GTPases of the rab family are involved in the regulation of vesicular transport. It is believed that cycling between the GTP- and GDP-bound forms, and accessory factors regulating this cycling are crucial for rab function. However, an essential role for rab nucleotide exchange factors has not yet been demonstrated. In this report we show the requirement of nucleotide exchange factor activity for Ypt1 GTPase mediated protein transport. The Ypt1 protein, a member of the rab family, plays a role in targeting vesicles to the acceptor compartment and is essential for the first two steps of the yeast secretory pathway. We use two YPT1 dominant mutations that contain alterations in a highly conserved GTP-binding domain, N121I and D124N. YPT1-D124N is a novel mutation that encodes a protein with nucleotide specificity modified from guanine to xanthine. This provides a tool for the study of an individual rab GTPase in crude extracts: a xanthosine triphosphate (XTP)-dependent conditional dominant mutation. Both mutations confer growth inhibition and a block in protein secretion when expressed in vivo. The purified mutant proteins do not bind either GDP or GTP. Moreover, they completely inhibit the ability of the exchange factor to stimulate nucleotide exchange for wild type Ypt1 protein, and are potent inhibitors of ER to Golgi transport in vitro at the vesicle targeting step. The inhibitory effects of the Ypt1-D124N mutant protein on both nucleotide exchange activity and protein transport in vitro can be relieved by XTP, indicating that it is the nucleotide-free form of the mutant protein that is inhibitory. These results suggest that the dominant mutant proteins inhibit protein transport by sequestering the exchange factor from the wild type Ypt1 protein, and that this factor has an essential role in vesicular transport.

Alleles↗
PubMed1995

Similar patterns of simian immunodeficiency virus env sequences are found in the blood and lymphoid tissues of chronically infected macaques.

Two cynomolgus macaques were infected with a genetically complex challenge stock of simian immunodeficiency virus (SIVmac251-32H). One animal developed SIV-induced disease and was sacrificed at 16 months postinfection. The second remained healthy until it too was sacrificed at 20 months postinfection. The polymerase chain reaction (PCR) was used to amplify env gp120-coding sequences from provirus present in samples of blood, spleen, and inguinal lymph node taken from both animals on the day of sacrifice. The proviral burden present in each of the tissue samples was also determined using a quantitative PCR assay. The proviral burdens in the blood, spleen, and inguinal lymph node of the healthy animal (I225) were similar. This was not the case for animal I227, in which the burden in the inguinal lymph node was much higher than for blood or spleen. Phenogram analysis of the hypervariable V1 region of env revealed that the diversity of nucleotide sequences recovered from each tissue of both macaques were similar and overlapping. Some selected amino acid differences were observed that were specific for a tissue or one of the macaques. However, the results do not suggest that the overall evolution of env in provirus populations recovered from lymphoid tissues is distinct from that recovered from the blood.

Amino Acid Sequence↗
PubMed1995

Aniridia-associated cytogenetic rearrangements suggest that a position effect may cause the mutant phenotype.

Current evidence suggests that aniridia (absence of iris) is caused by loss of function of one copy of the PAX6 gene, which maps to 11p13. We present the further characterisation of two aniridia pedigrees in which the disease segregates with chromosomal rearrangements which involve 11p13 but do not disrupt the PAX6 gene. We have isolated three human YAC clones which encompass the PAX6 locus and we have used these to show that in both cases the chromosomal breakpoint is at least 85 kb distal of the 3' end of PAX6. In addition, the open reading frame of PAX6 is apparently free of mutations. We propose that the PAX6 gene on the rearranged chromosome 11 is in an inappropriate chromatin environment for normal expression and therefore that a 'position effect' is the underlying mechanism of disease in these families.

Aniridia↗
PubMed1995

Case report: congenital absence of the left pulmonary artery accompanied by ipsilateral emphysema and adenocarcinoma.

Unilateral absence of the left pulmonary artery is a rare congenital anomaly that may remain unrecognized until adulthood, in which case it may lead to inappropriate diagnosis and management. The authors describe a case in which a patient came to their institution with dyspnea and a chest roentgenogram showing a prominent right pulmonary artery, right aortic arch, and a left lung mass accompanied by ipsilateral volume loss. Although the initial evaluation suggested a differential diagnosis that included thromboembolic pulmonary disease and vascular compression by tumor, further workup revealed unilateral absence of the left pulmonary artery accompanied by left lung hypoplasia, and interestingly, ipsilateral emphysema and adenocarcinoma. The embryologic factors responsible for this abnormality and how it may potentially affect the development of emphysema and adenocarcinoma are discussed.

Adenocarcinoma↗
PubMed1995

Carbapenem antibiotic production in Erwinia carotovora is regulated by CarR, a homologue of the LuxR transcriptional activator.

Strain GS101 of Erwinia carotovora makes the carbapenem antibiotic, 1-carbapen-2-em-3-carboxylic acid. Mutants defective in antibiotic production can be assigned to two groups, group 1 and group 2. Group 2 mutants are defective in the carl gene encoding a protein responsible for synthesis of the Lux autoinducer N-(3-oxohexanoyl)-L-homoserine lactone (OHHL), which is required to induce carbapenem synthesis in strain GS101. In this paper we describe the molecular genetic analysis of the group 1 mutants which we presumed were defective in the carbapenem biosynthesis (car) genes. We isolated a cosmid (cWU142) that complemented the group 1 mutants of strain GS101. A small (1.03 kb) subclone of cWU142 complemented most of the group 1 mutants, and the sequence revealed that the relevant gene (carR) encodes a homologue of the Vibrio fischeri LuxR protein. A disproportionately high frequency of carR mutants arose in strain GS101 and this was due to carR acting as a 'hot spot' target for secondary transposition of a Tn5 element in this strain. The CarR protein joins a rapidly growing list of homologues, found in taxonomically unrelated bacteria, which act as positive transcriptional activators of genes encoding diverse metabolic functions, including bioluminescence, exoenzyme virulence factor synthesis, cell division, plasmid conjugation, rhizosphere-specific gene induction, surfactant synthesis and antibiotic production. Most of these LuxR-type regulators have been shown to depend, for their function, on N-acyl homoserine lactones, which act as chemical signals enabling co-ordination of gene expression with cell density.

Amino Acid Sequence↗
PubMed1995

Long-term community-based attachments: the Cambridge course.

This paper reports on the establishment of the Cambridge Community-based Clinical Course and places on record details of the organization, goals and teaching arrangements of the course. It also identifies the main questions which are being addressed in the course and which must be answered before it will be clear whether such attachments are generally viable.

Community Medicine↗