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Biomedical subjects

G Wilson

Publications and source records attributed to G Wilson.

At least 91 records · Page 5Linked to original sources
PubMed1998

Mapping immunoreactive epitopes in the human peripheral nervous system using human monoclonal anti-GM1 ganglioside antibodies.

A series of monoclonal IgM anti-GM1 ganglioside antibodies has been cloned from peripheral blood lymphocytes of patients with multifocal motor neuropathy and Guillain-Barré syndrome. In solid-phase immunoassay, the antibodies react with GMI, and also in differing degrees to the structurally related glycolipids asialo-GM1 (GA1) and GD1b. Here we describe the binding patterns of six human anti-GM I antibodies to epitopes within the human nervous system. Antibodies were observed to bind to motor neurons and spinal grey matter, dorsal and ventral spinal roots, dorsal root ganglion neurons, nodes of Ranvier, neuromuscular junctions and skeletal muscle. The distribution of immunoreactive epitopes, which included sensory structures, extended beyond those sites conventionally regarded as pathologically affected in anti-GM1 antibody-associated motor nerve syndromes. This undermines a model of disease pathogenesis based solely on antigen distribution. Factors other than the presence or absence of antigen, such as the local ganglioside topography, antibody penetration into, and pathophysiological vulnerability of a particular site may also influence the clinicopathological outcome of anti-GM1 antibody-mediated autoimmune attack.

Antibodies, Monoclonal↗
PubMed1998

Atopic dermatitis and food hypersensitivity reactions.

OBJECTIVE: To determine the role of food hypersensitivity in atopic dermatitis and to determine whether patients with atopic dermatitis who had food hypersensitivity could be identified by screening prick skin tests using a limited number of food allergens. STUDY DESIGN: Patients with atopic dermatitis attending the Arkansas Children's Hospital Pediatric Allergy Clinic underwent allergy prick skin testing to a battery of food antigens. Patients with positive prick skin tests underwent double-blind, placebo-controlled food challenges. RESULTS: One-hundred sixty-five patients were enrolled and completed the study. Patients ranged in age from 4 months to 21.9 years (mean 48.9 months). Ninety-eight (60%) patients had at least one positive prick skin test. A total of 266 double-blind, placebo-controlled food challenges were performed. Sixty-four patients (38.7% of total) were interpreted as having a positive challenge. Seven foods (milk, egg, peanut, soy, wheat, cod/catfish, cashew) accounted for 89% of the positive challenges. By use of screening prick skin tests for these seven foods we could identify 99% of the food allergic patients correctly. CONCLUSIONS: This study confirms that most children with atopic dermatitis have food allergy that can be diagnosed by a prick skin test for the seven foods.

Adolescent↗
PubMed1998

Nucleotide-evoked calcium signals and anion secretion in equine cultured epithelia that express apical P2Y2 receptors and pyrimidine nucleotide receptors.

1. Experiments with a spontaneously transformed equine epithelial cell line showed that certain nucleotides increased intracellular free calcium ([Ca2+]i) in cells plated on glass coverslips. The rank order of potency was ATP UTP > 5-Br-UTP, whilst UDP and ADP were ineffective. The response thus appears to be mediated by P2Y2 receptors. 2. Nucleotides also increased short circuit current (Isc) in cells grown into epithelial monolayers and the rank order of potency was UDP> UTP > 5-Br-UTP > ATP > ADP. The increase in [Ca2+]i and the rise in ISC thus have different pharmacological properties. Cross-desensitization experiments indicated that, as well as P2Y2 receptors, the monolayer cultures express at least one additional receptor population that allowed nucleotides to increase ISC. 3. The UDP-evoked increase in ISC was essentially abolished in BAPTA-loaded epithelia suggesting that this response is dependent upon increased [Ca2+]i. Moreover, experiments in which ISC and [Ca2+]i were measured simultaneously showed that the UDP- and ADP-evoked increases in ISC were accompanied by increases in [Ca2+]i. 4. When grown under conditions which favour the development of a polarized phenotype, these epithelial cells thus appear to express [Ca2+]i-mobilizing receptors sensitive to UDP and ADP that are not present in non-polarized cells on coverslips.

Adenosine Diphosphate↗
PubMed1998

Comparison by contact lens cytology and clinical tests of three contact lens types.

PURPOSE: To determine if hydrogel lens materials from different FDA groups have different effects on the human ocular surface. METHODS: Contact lenses from Groups I and II, and Group IV were tested on 10 healthy adapted hydrogel contact lens wearers. For each comparison, the subject wore 2 new contact lenses for approximately 45 min. Lens movement was measured, and comfort evaluated using a subjective scale. After removal of the lenses, fluorescein staining and tear break-up time were measured. Cells were collected by contact lens cytology (CLC), and the size and number of cells harvested from each lens were determined. RESULTS: There were differences between lens groups in lens movement and comfort, but no differences in fluorescein staining or tear break-up time. CLC showed no differences in cell counts or cell size. There was no correlation between the results of CLC and the clinical tests for lens movement, lens comfort, tear break-up time, and fluorescein staining. CONCLUSIONS: With short durations of lens wear, differences in ionicity and water content have no effect upon the size and number of cells collected from a contact lens. This suggests that, in the short-term, the shedding of cells beneath a hydrogel lens is not affected by the choices of lens material.

Adult↗
PubMed1998

Letters from the radiation oncologist: do referring doctors give a damn?

Letters sent to referring and associated doctors by a radiation oncologist after consultation and treatment for 128 consecutive patients were reviewed. Overall, only 60% of information items previously identified as 'essential' were included in these letters. An anonymous survey of the referring doctors and general practitioners (GPs) for these 128 patients was conducted. A total of 93 of 103 respondents considered letter content to be satisfactory or very good, nine considered letter content to be only average and only one respondent considered content to be unsatisfactory. The possible reasons for high levels of satisfaction regarding correspondence by referring doctors and GPs in spite of the relatively low level of information content are explored.

Attitude of Health Personnel↗
PubMed1998

Adult ankle fractures--an increasing problem?

The epidemiology of ankle fractures is changing. Increasing longevity has resulted in the highest age-specific incidence of ankle fractures being in women between 75 and 84 years of age. The introduction of the AO classification has facilitated analysis of the commonest fracture types. This survey of 1,500 ankle fractures, seen in a 3-year period in the Edinburgh Orthopaedic Trauma Unit, shows that the commonest ankle fractures are the B1.1 and A1.2 lateral malleolar fractures. Isolated malleolar fractures accounted for two thirds of the series, with bimalleolar fractures occurring in one fourth of the patients and trimalleolar fractures in the remaining 7%. Open fractures occurred in 2%.

Adolescent↗
PubMed1997

Dimerization properties of human BAD. Identification of a BH-3 domain and analysis of its binding to mutant BCL-2 and BCL-XL proteins.

Bad, an inducer of programmed cell death, was recently isolated from a mouse cDNA library by its ability to bind to the anti-apoptotic protein BCL-2. Sequence analysis suggested that Bad was a member of the BCL-2 gene family that encodes both inducers and inhibitors of programmed cell death. To further analyze the role of BAD in the network of homo- and heterodimers formed by the BCL-2 family, we have cloned the human homologue of BAD and assessed its biological activity and its interactions with wild type and mutant BCL-2 family proteins. Our results indicate that the human BAD protein, like its mouse homologue, is able to induce apoptosis when transfected into mammalian cells. Furthermore, in yeast two-hybrid assays as well as quantitative in vitro interaction assays, human Bad interacted with BCL-2 and BCL-XL. Sequence alignments of human BAD revealed the presence of a BH-3 homology domain as seen in other BCL-2 family proteins. Peptides derived from this domain were able to completely inhibit the dimerization of BAD with BCL-XL. Thus, as previously shown for BAX, BAK, BCL-2, and BCL-XL, the BH3 domain of BAD is required for its dimerization with other BCL-2 family proteins. BAD was further analyzed for its ability to bind to various mutants of BCL-2 and BCL-XL that have lost the ability to bind BAX and BAK, some of which retain biological activity and some of which do not. Surprisingly, all of the mutated BCL-2 and BCL-XL proteins analyzed strongly interacted with human BAD. Our data thus indicate that mutations in BCL-2 and BCL-XL can differentially affect the heterodimeric binding of different death-promoting proteins and have implications concerning the relationship between heterodimerization and biological activity.

Amino Acid Sequence↗
PubMed1997

The Mars Pathfinder atmospheric structure investigation/meteorology (ASI/MET) experiment.

The Mars Pathfinder atmospheric structure investigation/meteorology (ASI/MET) experiment measured the vertical density, pressure, and temperature structure of the martian atmosphere from the surface to 160 km, and monitored surface meteorology and climate for 83 sols (1 sol = 1 martian day = 24.7 hours). The atmospheric structure and the weather record are similar to those observed by the Viking 1 lander (VL-1) at the same latitude, altitude, and season 21 years ago, but there are differences related to diurnal effects and the surface properties of the landing site. These include a cold nighttime upper atmosphere; atmospheric temperatures that are 10 to 12 degrees kelvin warmer near the surface; light slope-controlled winds; and dust devils, identified by their pressure, wind, and temperature signatures. The results are consistent with the warm, moderately dusty atmosphere seen by VL-1.

Atmosphere↗
PubMed1997

A gene for FG syndrome maps in the Xq12-q21.31 region.

FG syndrome is an X-linked recessive condition in which mental retardation is associated with congenital hypotonia, macrocephaly, characteristic face, and constipation. This syndrome was mapped by Zhu et al. [Cytogenet Cell Genet 1991;58:2091A] to Xq21.31-q22 by linkage analysis with a max lod score of 1.2 for the DXYS1X, DXS178, DXS101, and DXS94 loci and crossovers at DXS16 (Xp22.31) and DXS287 (Xq22.3). However, this mapping was only provisional and needed to be refined. In this paper, we report the results of a new linkage analysis performed on 10 families including that studied by Zhu et al. [1991]. Two-point analysis demonstrated linkage with DXS441 (Zmax = 3.39 at theta = 0.12) at Xq13. In addition, separate analysis of the lod scores obtained for the Xq13 markers suggested linkage exclusion for three families. Genetic heterogeneity was confirmed by analysis of the linkage results with the HOMOG program (max logL = 4.07, theta = 0, alpha = 0.65). Localization of one FG gene between DXS135 and DXS1066 was suggested by analysis of crossovers found in those three families which were assumed to be linked to Xq13 with a probability of 0.95 or more. This region could be reduced to the DXS135-DXS72 interval after combining our data with those from deletions previously described in males in the Xq13-q21 region.

Abnormalities, Multiple↗
PubMed1997

The lubricant of life: a proposal that solvent water promotes extremely fast conformational fluctuations in mobile heteropolypeptide structure.

Recent observations using the novel technique of Raman optical activity suggest that individual residues in unfolded proteins and in disordered loop regions of molten globule-like states cluster in the alpha-helix, beta-structure, and PPII-helix regions of the Ramachandran surface and that they "flicker" between these regions at rates approximately 10(12) s-1 at room temperature. It is proposed that these rapid motions, which occur on the same picosecond time scale as rearrangements of the hydrogen bond network in bulk water, are promoted by solvent water molecules via a repertoire of transient hydrated reverse turn conformations. Some implications of this proposal for protein folding and function are discussed.

Peptides↗
PubMed1997

Structural and functional complementation of an inactive Bcl-2 mutant by Bax truncation.

Interactions among proteins in the Bcl-2 family regulate the onset of programmed cell death. Previous work has shown that the death-inhibiting family members Bcl-2 and Bcl-xL form heterodimers with the death-promoting homologue Bax and that certain site-directed mutants of Bcl-2 and Bcl-xL lose both biological activity and the ability to bind Bax. To better understand the structural basis of heterodimer formation, we have used a yeast two-hybrid assay to screen for mutants of Bax that regain the ability to bind to these inactive Bcl-2(G145A) and Bcl-xL(G138A) mutants. This screen identified a series of C-terminally truncated Bax molecules that contain complete BH3 (Bcl-2 homology domain 3) domains but that have lost BH1 and BH2 sequences. These results indicate that while the Bcl-2 and Bcl-xL mutants fail to bind full-length Bax, they still retain a binding site for the critical BH3 domain. This suggests that conformational constraints in full-length Bax regulate its ability to bind to other Bcl-2 family members. Furthermore, we demonstrate that the normally inert Bcl-2(G145A) mutant effectively blocks apoptosis induced by a C-terminally truncated Bax molecule, but does not block apoptosis induced by wild-type Bax. This demonstrates that cell protection can be effected by directly binding pro-apoptotic members of the Bcl-2 family.

Amino Acid Sequence↗
PubMed1997

A common binding site mediates heterodimerization and homodimerization of Bcl-2 family members.

Bcl-2 inhibits apoptosis induced by a wide variety of stimuli. In contrast, the Bcl-2 homologue, Bax, antagonizes Bcl-2's death protecting function. Bcl-2 forms protein-protein homodimers with itself and heterodimers with Bax, and previous experiments have shown that point mutations in Bcl-2 can abrogate Bax binding while leaving homodimerization intact. These mutagenesis results can be interpreted to suggest that Bcl-2 has separate binding sites that are responsible for homodimer and heterodimer formation. Results from yeast two-hybrid studies have also suggested that homodimerization and heterodimerization reflect distinct modes of interaction. However, using quantitative plate binding assays, we now show that Bax as well as peptides derived from the BH3 domains of Bax and Bak block both Bcl-2/Bax binding and Bcl-2/Bcl-2 binding. Similar assays demonstrate that Bcl-xL can form both homodimers and heterodimers and that these interactions are also inhibited by Bax and the BH3-derived peptides. These results demonstrate that the same binding motifs are responsible for both homodimerization and heterodimerization of Bcl-2 family members.

Amino Acid Sequence↗
PubMed1997

Protection from procarbazine-induced testicular damage by hormonal pretreatment does not involve arrest of spermatogonial proliferation.

Hormone treatments that suppress sperm production enhance the recovery of spermatogenesis after gonadal exposure to various cytotoxic agents. It has generally been assumed that the mechanism of protection involved an arrest of spermatogonial kinetics. To test this hypothesis critically, we examined spermatogonial kinetics and numbers in rats in which the completion of spermatogenesis was suppressed with a 6-week testosterone plus 17beta-estradiol treatment that protected the testis from procarbazine-induced damage. Histological examination showed that the numbers of A-aligned, intermediate, and B spermatogonia and preleptotene spermatocytes and their mitoses were unaffected by testosterone plus 17beta-estradiol treatment. Flow cytometric analysis of bromodeoxyuridine-labeled cells showed that the percentage of diploid cells undergoing DNA synthesis, the progression of B spermatogonia and preleptotene spermatocytes through S-phase, the division of intermediate and B spermatogonia, the entry of intermediate spermatogonia into their next S-phase as type B cells, and the progression of cells through meiotic prophase were either unchanged or very slightly increased. Thus, changes in spermatogonial numbers or suppression of their proliferation cannot account for protection of spermatogenesis from exposure to cytotoxic agents.

Animals↗