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S Thompson

Publications and source records attributed to S Thompson.

At least 37 records · Page 2Linked to original sources
PubMed1991

Demonstration that CFTR is a chloride channel by alteration of its anion selectivity.

Expression of the cystic fibrosis transmembrane conductance regulator (CFTR) generates adenosine 3',5'-monophosphate (cAMP)-regulated chloride channels, indicating that CFTR is either a chloride channel or a chloride channel regulator. To distinguish between these possibilities, basic amino acids in the putative transmembrane domains were mutated. The sequence of anion selectivity of cAMP-regulated channels in cells containing either endogenous or recombinant CFTR was bromide greater than chloride greater than iodide greater than fluoride. Mutation of the lysines at positions 95 or 335 to acidic amino acids converted the selectivity sequence to iodide greater than bromide greater than chloride greater than fluoride. These data indicate that CFTR is a cAMP-regulated chloride channel and that lysines 95 and 335 determine anion selectivity.

Amino Acid Sequence↗
PubMed1991

The role of oil and agalactosyl IgG in the induction of arthritis in rodent models.

The proportion of agalactosyl IgG [Gal(O)] is raised in human rheumatoid arthritis and tuberculosis. We report here that injection of pristane into the peritoneal cavities of mice on days 0 and 50, which is known to induce plasmacytomas and arthritis, also induced a rise in the proportion of Gal(O), correlating with a simultaneous rise in the level of IgG antibody binding to the 65-kDa heat-shock protein of Mycobacterium bovis (hsp65). Arthritis developed in a proportion of those CBA/Igb mice with the highest percentage of Gal(O). Pretreatment with 50 micrograms of recombinant mycobacterial hsp65 intraperitoneal (i.p.) on day -10, or with 500 rad irradiation on day -2 before the first of the two injections of pristane reduced the incidence of arthritis from 24% in control animals, to 5.3% and 0.4%, respectively. The reduced incidence of disease correlated with smaller rises in the % Gal(O) at 50-75 days, although levels at 150-200 days were not affected. The arthritogenic effect of oil was not confined to the pristane model, since a single i.p. injection of oil 21 days before immunizing DBA/1 mice with type II collagen reduced the mean day of onset of this arthritis, [which we have previously shown to correlate with raised % Gal(O)], from 38 to 15 days (p less than 0.001). One interpretation is that an autoimmunogenic stimulus, given when % Gal(O) is raised, is more likely to evoke disease. Since oil granulomata are known to secrete interleukin 6, which has B cell-regulatory properties and is secreted by rheumatoid synovial cells, we tested sera from interleukin 6-transgenic mice, and found a strikingly raised percentage of Gal(O). We suggest, therefore, that the role of oil in the induction of arthritis is the dysregulation of cytokine release of which a raised percentage of Gal(O) may be a direct or indirect consequence, associated with an increased susceptibility to autoimmunogenic stimuli.

Animals↗
PubMed1991

Abnormally-fucosylated haptoglobin: a cancer marker for tumour burden but not gross liver metastasis.

A previous study has shown that there are high levels of an abnormally-fucosylated form of haptoglobin (FHp) in the blood of cancer patients (Thompson & Turner, 1987b). In this study, we investigated the expression of this substance in serial blood specimens from women with ovarian or breast cancer who were undergoing cytotoxic chemotherapy. The level of FHp was related to patient response to therapy status, this latter index being an indirect determination of tumour burden. FHp levels did not correlate with gross liver metastasis (as shown by CT scans or the blood levels of liver enzymes). This conclusion was further supported by results from patients with hepatocellular cancer. FHp was elevated in most of these patients, but the pattern of change did not correlate with variations in the level of the hepatoma marker, alpha-foetoprotein. It seems likely that FHp is produced by the liver. Primary and secondary tumours could release substances, such as cytokines, which interfere with fucose metabolism in the liver.

Adult↗
PubMed1991

Influence of infusion pumps on the pharmacologic response to nitroprusside.

OBJECTIVE: To compare the relationship between variability in nitroprusside delivery from five infusion pumps and the resulting variability in mean arterial pressure (MAP). DESIGN: Randomized, crossover study design. SETTING: A pediatric ICU in a university hospital. PATIENTS: Informed parental consent was obtained for six patients who were hemodynamically stable and receiving a continuous nitroprusside infusion for a clinical application. Subjects ranged in age from 11 months to 9 yr. INTERVENTIONS: All of the subjects were administered nitroprusside using selected infusion pumps, which included Abbott (Micro), 3M/AVI (210), IMED (965), IVAC (565), and Kendall McGaw (MicroRate). MEASUREMENTS AND MAIN RESULTS: After an initial equilibration interval for each device, MAP was measured and recorded at 10-sec intervals for greater than or equal to 90-min intervals using a computerized data collection technique. Variation in nitroprusside administration (flow continuity) for each infusion pump was determined in vitro using a computerized gravimetric technique. Variation in both MAP and flow continuity was mathematically expressed as the coefficient of variance (CV) of the measured values for each of the respective infusion pumps. For the Abbott, IMED, 3M/AVI, IVAC, and Kendall McGaw, infusion pumps, mean +/- SD continuity CV values were 85 +/- 31%, 39 +/- 26%, 19 +/- 8%, 17 +/- 3%, and 12 +/- 3%, respectively, and MAP CV values were 18 +/- 21%, 15 +/- 11%, 8 +/- 2%, and 16 +/- 10%, respectively. CONCLUSIONS: An apparent direct relationship between MAP variability and flow continuity was observed. We speculate that variation in effect of potent short-acting drugs may, in part, be due to infusion pump operation.

Blood Pressure↗
PubMed1991

Identification and regulation of the cystic fibrosis transmembrane conductance regulator-generated chloride channel.

Cystic fibrosis transmembrane conductance regulator (CFTR) generates cAMP-regulated Cl- channels; mutations in CFTR cause defective Cl- channel function in cystic fibrosis epithelia. We used the patch-clamp technique to determine the single channel properties of Cl- channels in cell expressing recombinant CFTR. In cell-attached patches, an increase in cellular cAMP reversibly activated low conductance Cl- channels. cAMP-dependent regulation is due to phosphorylation, because the catalytic subunit of cAMP-dependent protein kinase plus ATP reversibly activated the channel in excised, cell-free patches of membrane. In symmetrical Cl- solutions, the channel had a channel conductance of 10.4 +/- 0.2 (n = 7) pS and a linear current-voltage relation. The channel was more permeable to Cl- than to I- and showed no appreciable time-dependent voltage effects. These biophysical properties are consistent with macroscopic studies of Cl- channels in single cells expressing CFTR and in the apical membrane of secretory epithelia. Identification of the single channel characteristics of CFTR-generated channels allows further studies of their regulation and the mechanism of ion permeation.

Adenosine Triphosphate↗
PubMed1991

Clinical and pathologic correlation of endometrial cavity fluid detected by ultrasound in the postmenopausal patient.

A registry of ultrasound procedures spanning nearly 5 years was searched retrospectively to discover cases of endometrial cavity fluid collections in postmenopausal women. Twenty cases were identified; all medical records were available for review. One patient was lost to follow-up. Seventeen patients had surgical procedures: 11 had only a D&C, and six had a primary evaluation of laparotomy with removal of the uterus and adnexa. Five women had cancer (two ovarian, one tubal, one endometrial, and one cervical); eight women had benign gynecologic conditions, including uterine fibroids (five), ovarian serous cystadenoma (two), and cervical dysplasia (one). There were two cases of apparent subclinical pyometra. Five women had endometrial pathology consistent with prescribed hormone therapy for breast cancer (four) or endometrial hyperplasia (one).

Aged↗
PubMed1991

Complications associated with needle localization biopsy of the breast.

A review of 144 consecutive needle localization biopsies of the breast (NLBB) was performed to assess complications associated with this procedure. Thirty-four complications occurred in 27 patients. There were 11 wound infections associated with NLBB. During this time period, there were 1,583 clean general surgical operations performed, other than biopsy of the breast, yielding an over-all wound infection rate of 1.2 per cent (p less than 0.001). A trend was noted, suggesting that use of drains may have contributed to wound infection versus no drainage (25 versus 5 per cent, respectively). Electrocautery burns requiring local wound care occurred during seven biopsies and four of these patients subsequently had a wound infection develop. Four lesions required more than one excision to remove the abnormal mammary tissue, and in four, there was a failure to remove the lesion at the first operation. Fifty-three localization procedures were performed using methylene blue. In this group, only one patient required more than one biopsy to remove the abnormal mammary tissue, and there were no failures with this technique. Also, a smaller mean volume of tissue was removed in this group versus the standard NLBB (30.2 +/- 3.0 versus 53.3 +/- 4.6 cubic millimeters, respectively) (p less than 0.01). Four cardiovascular complications occurred, requiring overnight admission. All of these patients were more than 65 years old and had the procedure performed while under general anesthesia. Patient age, type of anesthesia, resident versus attending surgeon and length of procedure had no independent effect on local complication rate.

Aged↗
PubMed1990

Serum alpha-1-proteinase inhibitor with abnormal properties in ovarian cancer.

It was previously reported that sera from ovarian cancer patients contained abnormal forms of alpha-1-proteinase inhibitor (API) that predicted unresponsiveness to chemotherapy. These molecules were detected by extracting the sera with the fucose-specific lectin, lotus tetragonolobus, and analysing the extracts by electrophoresis. In a new study of ovarian cancer, we report that API cannot be extracted by lotus from fresh sera, unless the specimens are subjected to repeated cycles of freezing and thawing. Furthermore, increases in lotus-extractable API in the pretreated sera are also associated with a poor response to chemotherapy. This would suggest that lotus is extracting the same molecules in both studies. It seems likely that the discrepancy between the two studies is due to the length of time the specimens were stored prior to analysis. We present evidence suggesting that the API extracted by lotus is present in serum as soluble complexes, the detailed composition of which is unclear. The change in the properties of API in cancer may be very important with respect to tumour spread.

Adenocarcinoma, Mucinous↗
PubMed1990

National surveillance of antimicrobial resistance in Neisseria gonorrhoeae. The Gonococcal Isolate Surveillance Project.

The Gonococcal Isolate Surveillance Project is a national sentinel surveillance system to estimate levels and monitor trends of antimicrobial resistance in prospectively collected isolates of Neisseria gonorrhoeae. Of 6204 isolates evaluated from 21 clinic sites between September 1987 and December 1988, 21% met at least one of the surveillance criteria for resistance to penicillin, tetracycline, cefoxitin, or spectinomycin; 2.2% were penicillinase-producing N gonorrhoeae; 1.0% had high-level plasmid-mediated tetracycline resistance; and 16.8% of the isolates without plasmid-mediated resistance had chromosomally mediated resistance (defined as a minimum inhibitory concentration greater than or equal to 2 micrograms/mL) to penicillin, tetracycline, or cefoxitin. Three isolates were resistant to spectinomycin. All isolates were susceptible to ceftriaxone. Resistant isolates were identified from all participating centers. Patient demographic and behavioral characteristics were not predictive of infections caused by resistant organisms. These results demonstrate the wide distribution of antimicrobial-resistant N gonorrhoeae and support recent changes in Centers for Disease Control therapy recommendations for gonococcal infections that no longer recommend tetracycline and penicillin as first-line therapies.

Adolescent↗
PubMed1990

The role of EF-Tu and other translation components in determining translocation step size.

The two EF-Tu encoding genes, tufA and tufB, of Salmonella typhimurium have been sequenced. Nearly all the differences from their Escherichia coli counterparts are third position changes which do not alter the encoded amino acids. Unexpectedly, most of the changes in one Salmonella tuf gene are paralleled by changes in the other tuf gene perhaps due to gene repair despite the distance separating the genes. Three mutants which cause mis-framing, have their substitutions at codon 375. Explanations for mutants which cause mis-framing are considered and the mechanism of normal reading frame maintenance discussed.

Escherichia coli↗
PubMed1990

Errors in force estimation can be explained by tendon organ desensitization.

Here we report observations on the sense of muscle tension in human subjects and compare them with responses of tendon organs in cat hindlimb muscles. Human subjects learned under visual guidance to estimate a 4% maximum voluntary contraction (m.v.c.) of elbow flexors of one arm. When they were able to reproduce this force reliably without visual feedback, they repeated the estimation immediately after a 5 second m.v.c. or a 5 second period of relaxation. In a second experiment the 4% m.v.c. was generated under visual control with one arm, and matched with the other, test arm, without visual feedback. The matching task was then repeated after test arm conditioning. In both experiments subjects reported an accurate match using significantly more than the reference force ("overmatched") after an m.v.c. The overmatching was greatest during the first 5 second period following the conditioning contraction, and during the subsequent 20 seconds it gradually declined to near reference levels. The size of the matching error was directly proportional to the duration of the conditioning contraction. In the first experiment extension of the arm immediately following conditioning increased the error, in the second it slightly decreased it, although tension continued to be overmatched. In a series of experiments on the soleus muscle of anaesthetised cats responses of tendon organs to 10% of maximum contraction were seen to drop sharply when preceded by a conditioning maximum contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Obstructive sleep apnea and obesity.

OSA affects approximately 1 per cent of the adult male population and is more common among obese patients. The mechanism for the relationship between obesity and OSA may be mechanical obstruction or hypoxemia. Patients with obesity often have other medical problems that can exacerbate or complicate OSA. The physician should look for other problems such as diabetes, hypertension, and coronary disease while evaluating an obese patient with OSA. Weight loss is important either as a primary therapy or in conjunction with surgical treatment of OSA. Weight loss methods include behavior modification with diet, very low calorie diets with behavior modification, and bariatric surgery. In morbidly obese patients, more dramatic means such as bariatric surgery or very low calorie diets seem to be preferable because of the significant reduction in the length of time it takes for patients to lose weight. Because of a tendency for obese patients to regain weight, it is important to follow the patients long term to prevent the regaining of weight.

Behavior Therapy↗
PubMed1989

A preliminary study of serum class II levels in healthy individuals and bone-marrow transplant patients.

A double-determinant ELISA has been developed to measure class II major histocompatibility complex molecules in blood from healthy individuals and patients who received either an allogeneic or an autologous bone-marrow transplant. Levels were higher in pre-transplant patients than in healthy individuals, and in the majority of patients, these levels rose even higher at 4 weeks post-transplantation. At later times after transplantation, it was difficult to draw firm conclusions, because the number of values available were too limited. Nevertheless, in the autologous group with no graft-versus-host disease (GVHD), levels were consistently lower at 6 months and one year; in the allogeneic group these long-term levels varied. As class II antigens are expressed on skin and rectal epithelia in GVHD, this study suggests that serial measurement of serum class II levels may be useful for monitoring GVHD in bone-marrow transplantation.

Adult↗
PubMed1989

Abnormally-fucosylated serum haptoglobins in patients with inflammatory joint disease.

The fucosylation of haptoglobins is altered in rheumatoid arthritis. In order to investigate the clinical usefulness of this finding, serum levels of abnormally-fucosylated haptoglobins (FHp) have been assessed in defined and matched groups of patients with different inflammatory joint diseases. FHp was elevated in 16/17 patients with active rheumatoid arthritis (RA); 1/20 patients with inactive rheumatoid arthritis; 1/11 patients with osteoarthritis; and 4/10 patients with seronegative polyarthritis. Raised FHp levels, therefore, are not disease-specific. There was no relationship between the duration of RA and the FHp level. The FHp expression in RA was also compared with other biochemical indices of disease activity. The degree of correlation between FHp and articular index, joint score and early-morning stiffness was very similar to that obtained for C reactive protein (CRP), and better than that obtained for erythrocyte sedimentation rate and haemoglobin. FHp, however, gives fewer false-positives than CRP in cases of inactive disease. until FHp can be measured more easily and cheaply, CRP estimation is still the biochemical test of choice in RA.

Adult↗