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Biomedical subjects

A M Hall

Publications and source records attributed to A M Hall.

At least 19 recordsLinked to original sources
PubMed2001

Mouse fatty acid transport protein 4 (FATP4): characterization of the gene and functional assessment as a very long chain acyl-CoA synthetase.

FATP4 (SLC27A4) is a member of the fatty acid transport protein (FATP) family, a group of evolutionarily conserved proteins that are involved in cellular uptake and metabolism of long and very long chain fatty acids. We cloned and characterized the murine FATP4 gene and its cDNA. From database analysis we identified the human FATP4 genomic sequence. The FATP4 gene was assigned to mouse chromosome 2 band B, syntenic to the region 9q34 encompassing the human gene. The open reading frame was determined to be 1929 bp in length, encoding a polypeptide of 643 amino acids. Within the coding region, the exon-intron structures of the murine FATP4 gene and its human counterpart are identical, revealing a high similarity to the FATP1 gene. The overall amino acid identity between the deduced murine and human FATP4 polypeptides is 92.2%, and between the murine FATP1 and FATP4 polypeptides is 60.3%. Northern analysis showed that FATP4 mRNA was expressed most abundantly in small intestine, brain, kidney, liver, skin and heart. Transfection of FATP4 cDNA into COS1 cells resulted in a 2-fold increase in palmitoyl-CoA synthetase (C16:0) and a 5-fold increase in lignoceroyl-CoA synthetase (C24:0) activity from membrane extracts, indicating that the FATP4 gene encodes an acyl-CoA synthetase with substrate specificity biased towards very long chain fatty acids.

Amino Acid Sequence↗
PubMed2001

Tooth notations.

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Classification↗
PubMed2000

Measurement of T-helper cytokines secreted by cord blood mononuclear cells in response to allergens.

It has been proposed that in utero factors may predispose towards the development of childhood atopy. To test this hypothesis, it will be necessary to measure T-helper cell (Th) cytokines secreted by human cord blood mononuclear cells (CBMC) stimulated by allergens. However, to date, it has proven impossible to measure allergen-specific CBMC secretion of the key Th cytokine interleukin-4 (IL-4) using conventional sandwich ELISA techniques. We report for the first time the successful measurement of IL-4 secreted by CBMC stimulated by the allergens timothy grass pollen and house dust mite extract. The method is an adaptation of a novel cell-based ELISA (celELISA), which demonstrated an increased (up to 20-fold) sensitivity to detect IL-4. The method is simple, precise, is no more costly than a conventional ELISA, and can identify individuals in a general population whose CBMC exhibit different cytokine biases in response to allergens. The frequency distribution of IL-4 and interferon-gamma (IFN-gamma) CBMC responses to allergens in the general population approximates to a log-normal distribution, which will permit the application of linear regression techniques in the identification of in utero factors which influence Th bias.

Allergens↗
PubMed1999

Sequences of European wheat mosaic virus and oat golden stripe virus and genome analysis of the genus furovirus.

The complete nucleotide sequences of both RNAs of oat golden stripe virus (OGSV) and a wheat-infecting furovirus isolate from France, previously thought to be soil-borne wheat mosaic virus (SBWMV), have been determined. Both viruses had a similar genomic organisation to SBWMV and Chinese wheat mosaic virus, the two other furoviruses previously sequenced but had <70% nucleotides identical to them. The French isolate has been named European wheat mosaic virus (EWMV). Phylogenetic analyses supported the recognition of these isolates as distinct viruses in the genus Furovirus. Analysis of the coat protein readthrough domain on RNA2 of all furoviruses strongly predicts two mutually compatible conserved transmembrane domains that may be significant for fungus transmission. The second of these regions is eliminated by a deletion in the isolate of OGSV studied. Leaky opal (UGA) stop codons occur on both RNAs of all four furoviruses characterised and, in common with most other leaky opal codons identified in plant viruses, they are followed by a CGG codon.

Amino Acid Sequence↗
PubMed1999

The frequency of breast screening in older women.

Increasing age is the main risk of breast cancer in women. Screening mammograms are effective in women aged over 65 years for the early detection of breast cancer. Older women's health beliefs affect their use of mammogram screening and they tend not to take advantage of screening opportunities. Nurses must discuss the benefits of screening mammograms with their older clients.

Aged↗
PubMed1998

Attentional focus of students with hyperactivity during a word-search task.

Mirrors have been used to focus attention to aspects of the self (e.g., to known strategies, standards). We hypothesized that this could be important for students with hyperactivity/inattention, who typically direct attention outward to external novelty. In this study, we administered a partially solvable word puzzle to 43 middle school students, with and without hyperactivity/inattention, in the presence and absence of a mirror, counterbalanced for condition and form order. Differences between students with hyperactivity/inattention and comparisons in accuracy were found only in the no mirror condition. Furthermore, the beneficial effect of the mirror for children with hyperactivity/inattention was most pronounced for those who looked at the mirror. Findings were interpreted in terms of their potential to remedy the production deficits of these children.

Adolescent↗
PubMed1998

Merlin, the neurofibromatosis type 2 gene product, and beta1 integrin associate in isolated and differentiating Schwann cells.

Neurofibromatosis type 2, a disease characterized by the formation of multiple nervous system tumors, especially schwannomas, is caused by mutation in the gene-encoding merlin/schwannomin. The molecular mechanism by which merlin functions as a tumor suppressor is unknown, but is hypothesized to involve plasma membrane and cytoskeleton interaction. Several merlin antibodies were used to study merlin expression, localization, and protein association in primary cultures of rat sensory neurons, Schwann cells (SCs), and SCs grown with neurons (SC/N cultures) before and during differentiation into myelinating cells. Western blot analysis revealed that neurons predominantly expressed a 68-kD protein, but SCs expressed two additional 88- and 120-kD related proteins. Extensive immunological characterization demonstrated that the 88-kD protein shared three domains with the 68-kD merlin protein. Western blot analysis of soluble and insoluble culture fractions demonstrated that the majority of merlin and related proteins were soluble in isolated SCs and undifferentiated SC/N cultures, but became insoluble in myelinating SC/N cultures. Double immunofluorescence staining suggested that merlin translocated from the perinuclear cytoplasm in undifferentiated SCs to the subplasmalemma in differentiating SCs and partially colocalized with beta1 integrin. Finally, beta1 integrin antibody coimmunoprecipitated 68-kD merlin from isolated SC and undifferentiated SC/N cultures, but predominantly the 88-kD protein from differentiating SC/N cultures. Together, these results provide evidence that merlin interacts with beta1 integrin and that merlin localization changes from a cytosolic to cytoskeletal compartment during SC differentiation.

Animals↗
PubMed1997

Identification of T-cell epitopes on the Rhesus polypeptides in autoimmune hemolytic anemia.

We have shown previously that the Rhesus (Rh) polypeptides are the commonest targets for pathogenic anti-red blood cell (RBC) autoantibodies in patients with autoimmune hemolytic anemia (AIHA). The aim of the current work was to determine whether activated T cells from such patients also mount recall responses to epitopes on these proteins. Two panels of overlapping 15-mer peptides, corresponding to the sequences of the 30-kD Rh proteins associated with expression of the D and Cc/Ee blood group antigens, were synthesized and screened for the ability to stimulate the in vitro proliferation of mononuclear cells from the peripheral blood or spleen of nine AIHA cases. Culture conditions were chosen that favor recall proliferation by previously activated T cells, rather than primary responses. In seven of the patients, including all four cases with autoantibody to the Rh proteins, two or more peptides elicited proliferation, but cells from eight of nine patients with other anemias and seven of nine healthy donors failed to respond to the panels. Multiple peptides were also stimulatory in two positive control donors who had been alloimmunized with Rh D-positive RBCs. Six different profiles of peptides elicited responses in the AIHA patients, and this variation may reflect the different HLA types in the group. Stimulatory peptides were identified throughout domains shared between, or specific to, each of the related 30-kD Rh proteins, but T cells that responded to nonconserved regions did not cross-react with the alternative sequences. Anti-major histocompatibility complex class II antibodies blocked the responses and depletion experiments confirmed that the proliferating mononuclear cells were T cells. Notably, splenic T cells that proliferated against multiple Rh peptides also responded to intact RBCs. We propose that pathogenic autoantibody production in many cases of AIHA is driven by the activation of T-helper cells specific for previously cryptic epitopes on the Rh proteins.

Adult↗
PubMed1997

Multidrug-resistance modulators from Stephania japonica.

An alkaloidal extract of the vines of Stephania japonica showed multidrug-resistance-reversing activity as demonstrated by the bicinchoninic acid assay. Two known bisbenzylisoquinoline alkaloids, isotrilobine (1) and trilobine (2), were isolated by bioassay-directed fractionation and separation. Isotrilobine (1) was shown to be as active as verapamil (3) in reversing doxorubicin resistance in human breast cancer cells.

Antineoplastic Agents, Phytogenic↗
PubMed1996

Bicinchoninic acid protein assay in the determination of adriamycin cytotoxicity modulated by the MDR glycoprotein.

The development of simultaneous resistance to structurally unrelated drugs in cancer cells is a major obstacle to effective cancer chemotherapy. This multidrug-resistance (MDR) phenomenon is largely attributed to overexpression of a 170 kD glycoprotein, which serves as a transmembrane efflux pump in extruding a variety of natural anticancer drugs such as vinblastine, doxorubicin, and taxol from cancer cells. It is desirable, therefore, to discover compounds that can block the efflux mechanism and thus reverse drug resistance. The bicinchoninic acid protein assay has been adapted for use in a microtiter plate, into an easy, indirect method for screening MDR efflux blockers in plant extracts. This spectrophotometric assay is used to determine the enhancement of adriamycin cytotoxicity against resistant cancer cells by plant extracts or pure compounds indirectly. We have shown that the optical density measured (amount of cellular protein present) correlates with the number of viable cells and that fluorescence of Adriamycin associated with the cell correlates with the concentrations of Adriamycin added to the media. In addition, the relative efficacy of MDR reversal by various alkaloids has been determined.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Central and peripheral dopamine D1/DA1 receptor modulation of gastric secretion and experimental gastric mucosal injury.

1. Dopamine D1 (central)/DA1 (peripheral) receptors are believed to influence gastrointestinal function and pathology. 2. When given i.c.v. or i.p., an agonist (SKF38393) and an antagonist (SCH23390) of this DA receptor subtype inhibit and enhance, respectively, gastric secretion and gastric mucosal injury. 3. When given both i.c.v. and i.p., their respective effects in the gut were amplified. 4. Antagonist or agonist given i.p., blocked the corresponding protective and worsening effect of the agonist or antagonist given i.c.v. 5. Both central and peripheral D1/DA1 receptors modulate gastric function and response to injury.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1994

Clozapine, a dopamine DA4 receptor antagonist, reduces gastric acid secretion and stress-induced gastric mucosal injury.

Dopamine and its agonists modulate a variety of gastrointestinal functions. In light of the increasing attention directed toward novel dopamine receptors and compounds that are active at these sites, we examined the effects of a dopamine D4 antagonist and putative antipsychotic, clozapine, in a model of conscious basal gastric acid secretion and in a model of stress-induced gastric mucosal injury. At a dose of 10.0 mg/kg i.p., clozapine significantly inhibited basal gastric acid secretion by 84% relative to vehicle. Lower doses (2.5 and 5.0 mg/kg) were inactive. Doses of 2.5, 5.0 and 7.5 mg/kg i.p. all significantly reduced restraint stress-induced gastric mucosal injury in rats. The highest dose inhibited gastric lesions by 70% relative to vehicle. We conclude that dopamine D4 receptors, present in high concentrations in mesolimbic brain regions, modulate gastric function and pathology in addition to mesolimbic D1 receptors, whose role in gastrointestinal function is already established.

Animals↗
PubMed1994

Central nervous system and gut interactions: dopamine and experimental gastroduodenal lesions.

There is increasing evidence for brain regulation of gastroduodenal function and pathological responses. This laboratory has demonstrated a significant role for dopamine (DA) as a modulator of gastrointestinal function and disease. Using models of both acute (ethanol restraint stress; cysteamine) and chronic (iodoacetamide-induced gastritis) gastroduodenal mucosal injury, as well as tests of gastric secretory function (conscious basal gastric acid secretion; pylorus ligation; ex vivo gastric chamber), we have shown that DA, particularly DA1/D1 receptor agonists are powerful gastroprotective agents. This action is demonstrable upon peripheral administration as well as central (particularly intramesolimbic) administration. DA1/D1 agonists such as SKF38393 and SKF75670C reduce experimental gastric mucosal injury and secretion while antagonists of these receptors, including SCH23390, worsen experimental gastroduodenal lesions and augment secretion. That there exists a significant central component to DA-induced gastroprotection is demonstrated by data showing that rats assessed as anxiety prone, develop a greater degree of experimentally induced gastric damage, require greater amounts of DA agonists for 50% gastroprotection and respond to exogenous stress challenge with greater central DA turnover and loss, relative to rats assessed as low in anxiety. Very recently, we showed that dopamine D4 receptor blockade by clozapine and activation of dopamine D3 receptors by 7-hydroxy-N, N-di-n-propyl-2-aminotetralin (7-OHDPAT) are also associated with antiscretory and gastroprotective effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Use of a polypropylene mesh in fixing a chronic intracerebroventricular cannula.

Surgical implantation of an intracerebroventricular cannula allows investigators to determine the effects of central administration of compounds on physiological/pathological events taking place in the periphery. Attempts to examine the influence of repeated, chronic drug administration on gastrointestinal function have been hampered by the tendency of cannulae to become dislodged and lost during the course of such studies. We describe herein the insertion of surgical polypropylene mesh between the skull and the fixative during surgical implantation of an intracerebroventricular (i.c.v.) cannula. This inexpensive addition to a standard surgical procedure extends the period of time during which the cannula remains viable for i.c.v. drug administration. Extending the active life of the cannula, in turn, allows the investigator to reduce the number of animals used.

Animals↗
PubMed1992

Brain-gut relationships: gastric mucosal defense is also important.

Growing recognition that there exists a functionally important brain-gut axis has prompted several research groups to examine more closely the role of central nervous system factors in gastric mucosal injury. Less attention has been directed toward brain regulation of defensive factors in the gut. Toward that end, we have been characterizing a growing role for dopamine as an important mediator of gastric defense. New data suggest that dopamine, and other substances including many peptides as well as interleukin, act not only to reduce aggressive elements which promote gastric mucosal injury (gastric acid, pepsin, gastrin, leukotrienes) but also to augment defensive factors which retard ulcerogenesis (mucus, bicarbonate, prostaglandins, free radical scavenging enzymes, vasodilators/relaxers). Increasing attention should be directed toward the often-neglected defensive aspect of gastric mucosal ulcerogenesis and protection.

Animals↗
PubMed1991

Integrating the community into geriatric case management: public health interventions.

Gatekeepers, or nontraditional referral sources, have proven to be an effective means of case finding and outreach for the mental health needs of isolated senior citizens. A two-year project administered by the Public Health Division of the Health Services Department in a San Francisco Bay Area county found the gatekeeper concept to be an effective means of case finding in the public health setting. Program statistics showed similar profiles of individuals referred by gatekeepers and other referral sources except that gatekeepers referred more individuals living alone.

Aged↗