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Biomedical subjects

G Wild

Publications and source records attributed to G Wild.

At least 73 records · Page 4Linked to original sources

Human T-cell mediated response to homologous lens antigen.

T-Cell response to a suspension of homologous whole lens antigen was investigated in three groups: (1) adults with normal eyes; (2) patients with mature and hypermature cataract with an intact lens capsule; and (3) patients, who had had extracapsular cataract surgery or lens injury, some of whom had clinical evidence of severe lens-induced inflammation. The results show that sensitized T-cells occur only in some patients in the third group. To our knowledge, this is the first direct evidence of a difference in the response to T-cells to lens antigen released from mature and hypermature lenses, and to lens antigen exposed by lens injury or extracapsular cataract surgery. The test may be useful to confirm clinical suspicion of delayed hypersensitivity to lens antigen in patients with severe sterile purulent inflammation or milder delayed sterile non-purulent inflammation following lens injury or extracapsular surgery, in the absence of histological proof.

Adult↗

Scalloped valvulae conniventes: an endoscopic marker of celiac sprue.

The finding, in a patient with celiac sprue, of a characteristic change at endoscopy (scalloping of the valvulae conniventes, event on close inspection, but forming only a mosaic pattern from a distance) led to an endoscopic survey designed to define its incidence. In a series of 28 sequential patients found to have microscopic changes characteristic of sprue on biopsy, distinctive endoscopic changes were found in 22 (in 6 of 9 with sprue in relapse, and 16 of 19 presenting with initial symptoms). The finding of the distinctive appearance provides an endoscopically recognizable pattern that can be associated with sprue. It also provides the potential for early recognition of the process in patients in whom the diagnosis might otherwise have been delayed due to a lack of substantial evolution of the usually associated symptom complex.

Biopsy↗

Immunological abnormalities 17 years after accidental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Eighteen workers were reviewed 17 years after accidental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin). Clinical assessment showed that they were in good health. A study of several biochemical and immunological parameters in these subjects and in 15 carefully matched controls showed no difference in serum concentrations of hepatic enzymes between exposed workers and controls. Although mean serum concentrations of cholesterol and triglyceride were higher in exposed subjects than in controls, the results did not reach statistical significance. Antinuclear antibodies and immune complexes were detected significantly more frequently in the peripheral blood of workers exposed to dioxin. There was no significant difference between exposed workers and controls in the number of T lymphocytes, B lymphocytes, and helper and suppressor T cell counts in peripheral blood, but the number of natural killer cells identified by the monoclonal antibody Leu-7 was significantly higher in workers exposed to dioxin.

Accidents, Occupational↗

Polymorphic keratins in human epidermis.

Human epidermal keratins from many different individuals were identified and compared by both high-resolution 1- and 2-dimensional gel electrophoresis and immunoblotting. While the polypeptide patterns obtained for keratin-enriched cytoskeletal preparations could be considered typical of normal interfollicular epidermis, they also disclosed variations, among the individuals, concerning some of the constituent protein subunits. Three sets of interindividually varying keratins could be distinguished owing to their distinct, though small, differences in electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gels and their similar or identical charge characteristics upon nonequilibrium pH gradient electrophoresis: the basic keratins 1a and 1b as well as 5a and 5b and the acidic keratins 10a and 10b. Of each set either a doublet, showing a marked 1:1 ratio of polypeptides, or the one or the other variant protein was detected together with keratin 14, which did not display any variation in a series of 148 individual tissue samples tested. Thus, the keratin composition of human epidermis could be summarized in the formula: (1a v 1b) + (5a v 5b) + (10a v 10b) + 14. The systematic appearance of the variants suggested that each protein within a set is the product of an independent allele. In support of this hypothesis we have found that the same variant is expressed in other epithelia of a given individual. Moreover, the frequency of any of the keratins in our sampling concurred with the frequency predicted by the Hardy-Weinberg relation for the distribution of alleles in a population, as did the frequency distribution of particular keratin patterns.

Alleles↗

Total and allergen-specific IgE in relation to allergic response pattern following bone marrow transplantation.

Total and allergen-specific serum IgE were measured in relation to allergic response pattern before and after bone marrow transplant (BMT) in seven sibling donor/recipient pairs. Two non-atopic recipients developed persistently raised total serum IgE levels but no apparent allergic response after BMT from non-atopic donors; three non-atopic recipients showed raised total serum IgE after BMT, with allergen-specific IgE to the same allergens as their respective atopic donors. A penicillin-tolerant recipient showed clinical sensitivity and specific IgE to penicillin after BMT from a penicillin-sensitive donor, but with this case both donor and recipient showed raised serum IgE levels. One atopic recipient showed decreased total IgE after BMT from a mildly atopic donor. These allergic response patterns could occur as a result of repopulation in the recipient with IgE-specific T lymphocytes having similar regulatory influences as in the donor. The pattern of acquired responses would also be consistent with reconstitution by primed B lymphocytes of donor origin.

Adolescent↗

The early diagnosis of impending coagulopathies following surgery and multiple trauma.

Blood coagulation problems, either disseminated intravascular coagulation (DIC) or adult respiratory distress syndrome (ARDS) are frequent complications during the recovery of the polytraumatized surgical patient or accident victims. The key to their successful control lies in prompt recognition and aggressive treatment of the disease as soon as it appears. Unfortunately their onset is not usually well defined clinically and success in handling usually depends upon clinical expertise in recognising "high risk" situations coupled with measurements in the haematological laboratory of changes in plasma coagulation factors. It is suggested in this communication that a relatively simple examination of plasma complement profiles in the high risk, intensive care patient, may not only provide early warning of the onset of a coagulopathy but also distinguish the type. Simple tests are described, based on the assessment of plasma complement C5 levels, which have a high predictive value for the onset of ARDS, a disease with few early clinical manifestations and notably lacking in early changes in haematological parameters. In prospective trials complement tests correctly identified 18 patients who later developed ARDS but were no more effective than haematological tests in the identification of 24 patients who subsequently developed DIC.

Blood Protein Electrophoresis↗

Skin testing in the investigation of reactions to intravenous anaesthetic drugs. A prospective trial of atracurium and tubocurarine.

Intradermal skin testing is widely used to determine the causative drugs of presumed anaphylactic anaesthetic reactions. This paper sets out to evaluate the usefulness of skin tests, both intradermal and prick testing, in the prediction of anaesthetic reactions. The muscle relaxant drugs tubocurarine and atracurium were chosen for study since they are known to produce a high incidence of minor histaminoid reactions. A trial was conducted in 22 female patients about to undergo elective gynaecological surgery for non-malignant conditions. In intradermal tests, positive wheal and flare reactions to one or other relaxant (diluted 1 in 1,000) occurred in 17 patients and reactions to both drugs in 11 patients. Despite this high incidence of positive reactions, none of the patients had received either drug previously, a view confirmed by the negative results of prick testing. Likewise, when anaesthetized for surgery using atracurium or tubocurarine allocated randomly, the minor histaminoid manifestations observed showed no correlation whatsoever with the intradermal tests results. The results of the trial, combined with external reports to this centre, indicate that intradermal testing of anaesthetic drugs, particularly muscle relaxants, produces a high incidence of false positive results. This probably reflects their pharmacological activity rather than antigenicity. It is recommended, therefore, that skin testing should be reserved for situations in which there are strong indications from laboratory tests, backed by case history, of immune sensitization.

Adult↗

pH and protease control of acrosomal content stasis and release during the guinea pig sperm acrosome reaction.

The purpose of this study was to examine how trypsin inhibitors affect the guinea pig sperm acrosome reaction in vitro. Using spermatozoa pretreated with lysophosphatidyl choline, we found that both naturally occurring high molecular weight and the smaller synthetic trypsin inhibitor p-aminobenzamidine (PAB) delayed the onset of the acrosome reaction as monitored by light microscopy. Examination with electron microscopy revealed that acrosomal matrix dispersal rather than membrane fusion was affected. Despite the morphologic delay in acrosomal content release, PAB unexpectedly permitted 96% of soluble acrosomal antigen to be released into the supernatant. In addition, total acrosin release in the presence of PAB was 74% of control, with the vast majority as latent rather than active enzyme. A morphologically intact but membrane-free target of acrosomal matrix (AM), which is sensitive to trypsin inhibitor, was partially purified using Triton-x-100 at pH 5.2. AM remained morphologically stable at pH 5.2; however, shift up to pH 7 resulted in rapid dissolution within several minutes as monitored by light and electron microscopy and light scattering. Trypsin inhibitor prevented dispersion of AM at pH 7. The results suggest that, during the acrosome reaction, one distinct region of the acrosomal contents disperses after membrane vesiculation in a pH and trypsin inhibitor-insensitive fashion while a pH sensitive trypsin-like activity (acrosin?) disperses another discrete region of acrosomal matrix.

Acrosin↗

Allergy, plasma IgE level and anaphylactoid response: a hypothesis.

Any simple test predictive of immediate hypersensitivity-like (anaphylactoid) response to anaesthetic agents would be clinically useful. Possession of the traits of allergy or atopy, and of raised plasma IgE levels, all easily established, have previously been reported as predisposing factors. The usefulness of such observations has been limited by the fact that many reactions are not immune and do not involve IgE antibodies. This hypothesis suggests how IgE levels may be widely predictive of other reaction mechanisms and partially explains some of the divergent views on the mechanisms of anaphylactoid response which occur in the literature.

Adult↗

Reference ranges for serum alpha 1 antitrypsin.

References ranges for serum alpha 1 antitrypsin at various ages have been constructed using specific protein calibration material (SPS-01). Median values and 5th-95th centile ranges for alpha 1 antitrypsin in cord blood are equivalent to those of the adult. The median concentration falls during the first 6 months of age to rise again to adult values by 12 months. Concentrations in early school age are higher than in normal adults.

Adolescent↗

Influence of colchicine and vinblastine on the intracellular migration of secretory and membrane glycoproteins: II. Inhibition of secretion of thyroglobulin in rat thyroid follicular cells as visualized by radioautography after 3H-fucose injection.

Young (40 gm) rats were given a single intravenous injection of colchicine (4.0 mg) or vinblastine (2.0 mg). At 10 min after colchicine and 30 min after vinblastine administration, the rats were injected with 3H-fucose. Control rats received 3H-fucose only. All rats were sacrificed 90 min after 3H-fucose injection and their tissues processed for radioautography. In thyroid follicular cells of control animals, at this time interval, 57% of the total label was associated with colloid and secretory vesicles in the apical cytoplasm while 27% was localized in the Golgi apparatus and neighboring vesicles. In experimental animals, the proportion of label in colloid and apical vesicles was reduced by more than 69% after colchicine and more than 83% after vinblastine treatment. The proportion of label in the Golgi region, on the other hand, increased by more than 125% after colchicine and more than 179% after vinblastine treatment. Within the Golgi region, the great majority of the label was associated with secretory vesicles which accumulated adjacent to the trans face of the Golgi stacks. It is concluded that the drugs do not interfere with passage of newly synthesized thyroglobulin from the Golgi saccules to nearby secretory vesicles, but do inhibit intracellular migration of these vesicles to the cell apex. In most cells the number of vesicles in the apical cytoplasm diminished, but this was not always the case, suggesting that exocytosis may also be partially inhibited. The loss of microtubules in drug-treated cells suggests that the microtubules may be necessary for intracellular transport of thyroglobulin.

Animals↗

Influence of colchicine and vinblastine on the intracellular migration of secretory and membrane glycoproteins: III. Inhibition of intracellular migration of membrane glycoproteins in rat intestinal columnar cells and hepatocytes as visualized by light and electron-microscope radioautography after 3H-fucose injection.

In the first paper of this series (Bennett et al., 1984), light-microscope radioautographic studies showed that colchicine or vinblastine inhibited intracellular migration of glycoproteins out of the Golgi region in a variety of cell types. In the present work, the effects of these drugs on migration of membrane glycoproteins have been examined at the ultrastructural level in duodenal villous columnar cells and hepatocytes. Young (40 gm) rats were given a single intravenous injection of colchicine (4.0 mg) or vinblastine (2.0 mg). At 10 min after colchicine and 30 min after vinblastine administration, the rats were injected with 3H-fucose. Control rats received 3H-fucose only. All rats were sacrificed 90 min after 3H-fucose injection and their tissues processed for radioautography. In duodenal villous columnar cells, 3H-fucose labeling of the apical plasma membrane was reduced by 51% after colchicine and by 67% after vinblastine treatment; but there was little change in labeling of the lateral plasma membrane. Labeling of the Golgi apparatus increased. This suggests that labeled glycoproteins destined for the apical plasma membrane were inhibited from leaving the Golgi region, while migration to the lateral plasma membrane was not impaired. In hepatocytes, labeling of the sinusoidal plasma membrane was reduced by 83% after colchicine and by 85% after vinblastine treatment. Labeling of the lateral plasma membrane also decreased, although not so dramatically. Labeling of the Golgi apparatus and neighboring secretory vesicles increased. This indicates that the drugs inhibited migration of membrane glycoproteins from the Golgi region to the various portions of the plasma membrane. Accumulation of secretory vesicles at the sinusoidal front suggests that exocytosis may also have been partially inhibited. In both cell types, microtubules almost completely disappeared after drug treatment. Microtubules may, therefore, be necessary for intracellular transport of membrane glycoproteins, although the possibility of a direct action of these drugs on Golgi or plasma membranes must also be considered.

Animals↗

[Psychosocial situation of married couples prior to artificial insemination with donor sperm].

57 couples who attended our outpatient department for artificial insemination with donor sperm (AID) had a detailed semistandardized interview prior to treatment. The Giessen Test was used as personality test, as well as a questionnaire concerning the sexual and partner relationship. We found that it was the woman who had to bear the major part of the intrapsychic burden and who primarily suffered because of the problem which was actually caused by male sterility. However, 54 of 57 couples had no psychological difficulties to overcome the sterility problem. These couples developed individual and partnership strategies to deal with the burden of unwanted childlessness. They preferred AID rather than adoption, because for the woman this alternative offers the chance of real parenthood. AID seems to provide a medico-technical solution for couples with sterility problems: the reproductive process at the biological level was regarded as distinctly separated from their future role as parents which they considered to be a social task.

Adult↗

Genetic control of antisperm autoantibody response in vasectomized guinea pigs.

About 50% of vasectomized and none of sham-operated outbred Hartley GP develop autoantibodies to TSDA, surface antigens on sperm, spermatids, and residual bodies detectable by a sensitive quantitative cellular radioimmunobinding assay. A similar study of anti-TSDA antibody responses on different strains of GP demonstrates that Strain 13 GP are high responders and PLLhr guinea pigs are nonresponders, whereas the responses of Strain 2 and PLLlr GP are intermediate. Furthermore, 100% of vasectomized F1 GP between Strain 13 females and PLLhr males produce anti-TSDA antibody. Of the vasectomized back-cross GP between the F1 and PLLhr, 46% produce anti-TSDA antibody, 54% do not. These data provide strong evidence that autoimmune antibody response to sperm surface antigens in vasectomized GP is controlled by a single dominant autosomal or X-linked gene. Antisera from vasectomized Strain 13, F1, and back-cross GP are found to react with 3 major polypeptides (MW 63, 37, and 22 kd) on sperm surface that can be radioiodinated and extracted by NP-40.

Animals↗