Biomedical subjects
Publications and source records attributed to K Thompson.
This report of a patient with an interstitial deletion 18q and review of previously described cases suggest a clinically recognizable syndrome. The phenotype appears to result from a microdeletion of part of 18q12.2 or q12.3, or a deletion of parts of both bands.
Evidence suggests that endothelial cell layer heparan sulfate proteoglycans include a variety of different sized molecules which most likely contain different protein cores. In the present report, approximately half of endothelial cell surface associated heparan sulfate proteoglycan is shown to be releasable with soluble heparin. The remaining cell surface heparan sulfate proteoglycan, as well as extracellular matrix heparan sulfate proteoglycan, cannot be removed from the cells with heparin. The heparin nonreleasable cell surface proteoglycan can be released by membrane disrupting agents and is able to intercalate into liposomes. When the heparin releasable and nonreleasable cell surface heparan sulfate proteoglycans are compared, differences in proteoglycan size are also evident. Furthermore, the intact heparin releasable heparan sulfate proteoglycan is closer in size to proteoglycans isolated from the extracellular matrix and from growth medium than to that which is heparin nonreleasable. These data indicate that cultured porcine aortic endothelial cells contain at least two distinct types of cell surface heparan sulfate proteoglycans, one of which appears to be associated with the cells through its glycosaminoglycan chains. The other (which is more tightly associated) is probably linked via a membrane intercalated protein core.
The effects of benzodiazepine (triazolam 0.25 and 0.50 mg) on different aspects of cognitive function were assessed. Triazolam impaired free recall and recognition of information presented after drug administration. In contrast to these impairments in explicit memory, a memory function that did not require conscious awareness was not altered by triazolam. Similarly, triazolam did not affect subjects' abilities to access semantic memory.
Standard microscopic suture vasovasostomy represents a challenge to many urologists. It is technically demanding, and requires two to five hours of operative time. In an attempt to decrease the technical demand and the time requirement, we report the use of a microvascular anastomotic clip and compare this microclip to a standard eight-suture nonstented technique and a six-suture stented technique using a hollow, absorbable 0.5-mm polyglycolic acid stent. The control group with suture required an average of 38.5 minutes per anastomosis for the nonstented group and twenty-two minutes for the stented group. The clip group required 7.6 minutes for the unstented vasovasostomy and 6.5 minutes for the stented vasovasostomy. We obtained a 91 percent patency rate for the stented clip group and 100 percent patency for the unstented clip group. In a rat vasovasostomy, the operative time as well as the inherent technical demand were significantly reduced.
A simple, continuous spectrophotometric assay for dihydrofolate reductase (DHFR) activity was adapted for determination of drug-resistant enzyme activity expressed from transfected genes in cells containing drug-sensitive enzyme. Methotrexate inhibition characteristics in this assay system were assessed for the murine wild-type (WT) enzyme as well as variant genes encoding amino acid substitutions at codon positions 22 (arg22) or 31 (trp31) expressed in DHFR-deficient Chinese hamster ovary (CHO) cells and in mouse 3T3 cells. Methotrexate concentrations were thus identified which maximized inhibition of the wild-type enzyme while maintaining substantial arg22 or trp31 activity. Mixing experiments were conducted to determine the minimum amount of drug-resistant enzyme distinguishable from a constant amount of wild-type enzyme in the presence of methotrexate. Mixtures of enzymes from a variety of sources (WT, arg22, or trp31 expressed in CHO or 3T3 cells) demonstrated a detection limit of 0.03 to 0.06 nmol/min. Assay of methotrexate-resistant arg22 DHFR appeared to be limited by the low level of activity associated with this enzyme variant, whereas assay of the trp31 variant was limited by enzyme inhibition at lower concentrations of methotrexate. The assay was thus applicable to two quite diverse DHFR variants and may be useful for assaying the expression of other drug-resistant DHFR genes as well after introduction into cells containing drug-sensitive enzyme.
A manpower database for nurses employed by the Department of Health and Social Services (DHSS) in Northern Ireland is used to identify the qualified nurses not currently employed by the DHSS, i.e. the limbo stock, and describe this stock in terms of age, sex, length of previous service, grade and location. This information is invaluable for manpower planners who must decide on how many vacancies can be filled by recruitment from the limbo stock, as opposed to training new nurses. Such a methodology provides a valuable tool for the nurse manpower planner.
The heavy and light chain nucleotide sequences of 17 monoreactive and polyreactive rheumatoid factors largely derived from the inflamed synovial tissue of two patients with rheumatoid arthritis are described. Some of these sequences have been the subject of a previous report from our laboratories. Additionally, a few rheumatoid factors from the peripheral blood of patients with systemic lupus erythematosus and Sjogren's syndrome as well as a normal individual are included. A review of our previous results as well as the new data provided within this paper lead to the following major conclusions: (1) Rheumatoid factors and polyreactive antibodies derive from a diverse array of VH and VL gene segments; (2) While many rheumatoid factors and polyreactive antibodies are direct or nearly direct copies of germline genes, some show clear evidence of somatic mutation; (3) The CDR3 of all of these antibodies is extraordinarily diverse in length and composition. Certain 'restrictions' do appear in this very large sample: (a) the polyreactive antibodies are exclusively lambda, and (b) there seems to be a preponderance of a particular subset of VH3 genes beyond that one would expect based on random utilization.
Inhibition of IGF-I action by circulating IGF-I receptor autoantibodies is a potential mechanism of IGF-I resistance in growing children. To define the prevalence of IGF-I receptor antibodies in short-statured children, we have examined serum and plasma samples from a well-characterized group of 34 short, prepubertal, growth hormone-sufficient children and three growth hormone-deficient children. IGF-I receptor purified from human placental membranes was radioiodinated by the solid phase radioiodination method. Serum from a patient with severe insulin resistance immunoprecipitated 28.9-44.7% of the 125I-labeled IGF-I receptor. The ranges (mean +/- 3 SD) of 125I-labeled IGF-I receptor immunoprecipitated by 1:10 diluted and by undiluted nonimmune human serum were 1.99 +/- 0.63% and 4.42 +/- 1.32%, respectively. Immunoprecipitation of the 125I-labeled IGF-I receptor by eight samples from six children was greater than 3 SD above the mean when assayed at a 1:10 dilution. Nevertheless, when assayed undiluted, only one of these samples immunoprecipitated slightly more 125I-labeled IGF-I receptor than nonimmune serum. We conclude from these data that immunoprecipitating autoantibodies to the IGF-I receptor are not commonly present in short-statured children.
OBJECTIVE: To determine whether arrest disorders result in increased neurologic abnormalities in infancy or childhood. METHODS: Four hundred thirteen infants with arrest disorders as defined by Friedman criteria were matched to a similar population without arrest disorders. The median length of follow-up was 6 years for the study infants and 5.07 years for the controls. The numbers of children with abnormalities in the groups with and without arrest disorders, as well as the specific abnormalities encountered, were stratified by method of delivery. RESULTS: Thirty neurologic abnormalities were found in the arrest group and 37 in the control group; thus, the null hypotheses could not be rejected. In addition, although the control group was not followed as long as the study population, the diagnosis of abnormalities was more frequent in the later years in the controls. This suggests that had the follow-ups been equal, there would have been stronger proof that arrest by itself was not associated with infant brain damage. CONCLUSION: Our study confirms that labor diagnoses of prolonged active phase, protractions or arrests, and failure to descend are not associated with increased neurologic abnormalities. Delivery by cesarean or vaginal birth and use of oxytocin are not factors in the etiology of major brain damage.
BACKGROUND: Infected pseudocysts, pancreatic abscesses, and infected pancreatic necroses have been proposed as distinct clinical entities in terms of treatment and outcome. To evaluate this classification, we reviewed the clinical course and bacteriologic findings of pancreatic infections. METHODS: Of 1299 patients with pancreatitis or a related complication admitted over a 7-year period, 64 (4.9%) with culture-documented secondary pancreatic infections were reviewed with regard to cause, clinical course, bacteriologic findings, and outcomes. RESULTS: Group I consisted of 23 patients with infected pseudocysts; group II, 20 patients with pancreatic abscesses; and group III, 21 patients with infected pancreatic necrosis. The causes were alcohol in 36%, biliary tract disease in 30%, and postoperative in 16%, with no significant difference between groups. Patients in group I had abdominal pain or a mass without accompanying signs of sepsis, whereas patients in groups II and III had sepsis. In group I, 15 patients were treated with internal drainage, four with percutaneous drainage, and four with external drainage. In group II, three had percutaneous drainage, 15 operative drainage, and two open packing. In group III, 19 patients had operative drainage and two had open packing. Morbidity occurred in 26% of patients in group I, 40% in group II, and 90% in group III (p less than 0.001). Mortality rates were 9% in group I, 25% in group II, and 48% in group III (p less than 0.01). Enteric organisms were present in 66% of isolates, with no difference between groups, suggesting a common mode of infection. CONCLUSIONS: Despite similar bacteriologic findings, infected pseudocysts, pancreatic abscesses, and infected pancreatic necroses have significantly different presentations, clinical courses, and outcomes, confirming that they are distinct entities. This distinction is important when therapeutic outcomes are compared.
Rheumatoid factors (RF) are present in the plasma of patients with rheumatoid arthritis (RA) although the site of synthesis of most of these antibodies is within the synovium. This report primary concerns RF of the IgM isotype. While a few of the RF derive from patients with systemic lupus erythematosus or from normal individuals, the remaining derive from the inflamed synovial tissue of patients with RA. Two RF are encoded by members of the VH1 gene family, 8 from the VH3 family and 2 from the VH4 family. Two polyreactive antibodies derive from the VH3 family and 2 come from the VH4 family. This distribution is not fundamentally different from the distributions seen in a large array of autoantibodies and antibodies to external antigens. Similarly, the light chains derive from most of the known kappa and lambda VL families. It is hard to escape the preliminary conclusion that gene segments from virtually any light chain variable region can contribute to RF or polyreactive antibody structures. Most IgM RF and polyreactive antibodies are direct copies of germline genes in one of their polypeptide chains or at most are 2 nucleotides away in one of their chains from a known germline gene.
We have recently found that association of the two alpha beta dimers of the insulin-like growth factor I (IGF I) receptor is required for formation of a high-affinity binding site for IGF I [Tollefsen, S. E., & Thompson, K. (1988) J. Biol. Chem. 263, 16267-16273]. To determine the structural requirements for IGF I activated kinase activity, we have examined the effect of dissociation of the two alpha beta dimers of the IGF I receptor on beta subunit autophosphorylation. The alpha beta dimers formed after treatment with 2 mM dithiothreitol (DTT) at pH 8.75 for 5 min were separated from IGF I receptor remaining as tetramers after DTT treatment by fast protein liquid chromatography on a Superose 6 gel filtration column. Purification of the alpha beta dimers was confirmed by Western blot analysis using 125I-labeled alpha IR-3, a monoclonal antibody to the IGF I receptor. Autophosphorylation of the IGF I receptor (alpha beta)2 tetramer, treated without DTT or remaining after DTT treatment, is stimulated 1.6-2.9-fold by IGF I. In contrast, autophosphorylation of the alpha beta dimers incubated in the presence or absence of IGF I (100 ng/mL) does not occur. Both IGF I receptor dimers and tetramers exhibit similar kinase activities using the synthetic substrate Arg-Arg-Leu-Ile-Glu-Asp-Ala-Glu-Tyr-Ala-Ala-Arg-Gly, indicating that the failure to detect autophosphorylation of the IGF I receptor dimers does not result from inactivation of the kinase by DTT treatment. We conclude that autophosphorylation of the IGF I receptor depends upon the interaction of the two alpha beta dimers.
A gene encoding beta-glucanase activity from Bacillus amyloliquefaciens was subcloned in both orientations into plasmid shuttle vector pSA3. In only one orientation could a co-integrate be generated with the conjugative plasmid pVA797. The plasmid co-integrate was conjugated into Lactobacillus helveticus strain CNRZ450, where it was stably maintained without antibiotic selection and exhibited beta-glucanase activity. This method of introducing cloned DNA into thermophilic lactobacilli will facilitate the study of heterologous gene expression in non-transformable species.
We examined script and lexical retrieval in patients with probable Dementia-Alzheimer's Type (DAT), Depressed patients, and normal controls. DAT patient breakdown in script production was structurally similar to their impaired lexical retrieval such that script events of low frequency and low centrality value were lost first. DAT patients also produced more events that fell outside the script boundary as well as more event-order errors. Four cases with DAT were identified on the basis of Z scores whose script production was at least 2 SDs greater than their lexical production or vice versa. This finding suggests that it may be possible to dissociate script and lexical knowledge and production processes. The findings lend partial support for a model of knowledge representation that includes parallel and partially redundant memory networks that are distinctly distributed in the brain.
A manpower database for nurses employed by the Department of Health and Social Services in Northern Ireland has been developed. This database contains information on all nurses employed between March 1977 and July 1988 and consists of data on all posts held in this period, including breaks in service. The authors show how these data may be used to analyse the durations of spells in post and spells out of service prior to departure to a number of destinations for the sister and staff nurse grades. The results are presented in a graphical format which enables us to evaluate the relative proportion of departures to each destination and at what stage in service these departures are likely to occur. Such a methodology provides a valuable tool for the nurse manpower planner, and utilizes personnel data which are routinely collected by most health authorities.
This study assessed validity and reliability of the Health Knowledge Inventory-Alpha (HKI-Alpha) in a sample of high school seniors. The HKI-Alpha, a general health knowledge test, consists of 110 multiple choice items covering 11 health content areas. All seniors attending one of four high schools completed HKI-Alpha twice, one week apart. A secondary sample of college students also was tested. Descriptive analysis revealed the test discriminated among examinees and avoided ceiling and floor effects. Test-retest reliability was .81 (n = 355). Internal consistency reliability (KR20) was .85 (n = 418). A sample of college students scored significantly higher than the high school students, demonstrating construct validity. Other estimates of content validity, criterion-related validity, and construct validity were high.
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To better understand the structural basis for rheumatoid factor activity, the nucleotide sequence of the light chain variable regions of nine human monospecific IgM rheumatoid factors were analyzed. Rheumatoid factors were isolated from three patients with rheumatoid arthritis, a patient with systemic lupus erythematosus, and a normal individual. The VL gene segments used by these rheumatoid factors are not as restricted as previous work on mixed cryoglobulin rheumatoid factors had suggested. Each of the different VK families is represented and there are two examples where a V lambda gene segment is used. Molecules with structures similar to those of the Wa and Po CRI, characteristic of mixed cryoglobulin rheumatoid factors, are not common among these rheumatoid factors isolated from patients with rheumatoid arthritis. While there are clear examples of rheumatoid factors that are direct copies of germline genes, most of the sequence data suggest that the processes of antigenic selection and somatic mutation contribute significantly to the generation of monospecific rheumatoid factors in patients with autoimmune disease.