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S Thompson

Publications and source records attributed to S Thompson.

At least 199 records · Page 11Linked to original sources

A-type potassium channel clusters revealed using a new statistical analysis of loose patch data.

The spatial distribution of ion channels over the surface of a neuron is an important determinant of its excitable properties. We introduce two measures of channel clustering for use in patch-clamp experiments: a normalized chi-squared statistic (eta) and the number of zero-channel patches in a data set (Z). These statistics were calculated for data sets describing the distribution of A-type potassium channels on neurons of the nudibranch Doriopsilla and measurements of Ca-dependent outward current channels on bullfrog hair cells, as well as simulated channel distributions. When channels are clustered, eta is approximately equal to the amount of current in a cluster. The analysis shows that somatic A-channels in the nudibranch are distributed in clusters of approximately 50 channels each. The clusters are < 2 microns wide and are separated, on average, by 3.2 microns. Outward current channels on hair cells occur in clusters of approximately 27 channels each, in agreement with the original analysis. Channel clustering may reflect properties of the insertion or regulation of channels in the membrane.

Animals↗

p53, c-erbB-2 and the epidermal growth factor receptor in the benign and malignant prostate.

Expression of the p53, the epidermal growth factor receptor (c-erbB-1) and c-erbB-2 protein was studied in 34 men with benign prostatic hyperplasia and 29 men with locally advanced prostate cancer by means of an immuno-histochemical method. Strong staining for p53 was found in five of 29 prostate cancers (17%; mean 21% +/- 7% of malignant cells stained in the positive tumours), but no staining was found in benign prostatic hyperplasia (p less than 0.05). On the other hand, the epithelium in benign glands was stained positively for c-erbB-2 in 18% (6/34) and for the epidermal growth factor receptor in 88% (30/34); whereas malignant epithelium stained strongly for c-erbB-2 in 21% (6/29) and for the epidermal growth factor receptor in only 17% (5/29). Prostate cancer was associated with a significant decrease in epidermal growth factor receptor staining (p less than 0.0001) and a significant increase in p53 staining (p less than 0.05). Most of the tumours were advanced and no significant relationship was observed between tumour stage and grade and expression of p53, the epidermal growth factor receptor or c-erbB-2. These findings demonstrate that altered expression of the epidermal growth factor receptor and p53 protein occurs in prostate cancer, but were not associated with other features of prognostic importance such as stage or grade.

Aged↗

A dynamic dual isotope radionuclear method of quantifying penile blood flow.

A new radionuclear method of quantifying arterial and venous blood flow of the penis is described. The technique is based on the simultaneous recording of the change in blood volume and venous outflow in the flaccid and erect states, which is produced pharmacologically. The change in penile blood volume is determined by measuring the change in the technetium-labeled red blood cell activity with time. Venous outflow is recorded with a xenon washout technique. The isotope data are used to compute arterial and venous flows with a complex computerized mathematical formula. Three basic blood flow patterns have been noted that distinguish normal patients from those with arterial insufficiency and venous leakage. The study is relatively easy and noninvasive to perform, and it appears to quantify penile blood flow accurately.

Adult↗

Social rehabilitation and return to work after cardiac transplantation--a multicenter survey.

As the medical results of heart transplantation steadily improve, the social rehabilitation of patients, in particular, their ability to return to some form of employment, is becoming increasingly important. Two-hundred fifty patients were therefore surveyed at 7 heart transplant centers (5 of which were Medicare certified) from different geographic regions in the U.S.A. Over all, 45% were employed, 36% were unemployed, 13% were medically disabled, and 6% were retired. Of those employed, 87% had returned to their previous employment, and only 13% had secured new employment. Of the unemployed, 16% had made job applications, and no fewer than 63% had no current plan to seek employment. Factors found to negatively influence a return to work included the following: (1) length of medical disability prior to transplantation; (2) a patient's self-perception of being physically unable to work; and (3) the potential loss of health insurance and/or disability income. At 2 centers, where there was a definite policy of not supporting a patient's claim for medical disability in the absence of an absolute indication, there were significantly increased numbers who (1) secured new employment and (2) planned to seek employment. More serious attention must be paid to aspects of employment if heart transplant recipients are to become fully productive members of the community.

Adult↗

Practical screening priorities for hearing impairment among children in developing countries.

Routine screening for hearing impairment in childhood is now widespread in industrial countries, although there is considerable controversy over the most efficient techniques and procedures. In most developing countries, however, routine screening programmes for hearing impairment do not currently exist. The problems involved in implementing screening programmes in developing and industrial countries are very different, and in selecting screening procedures for a particular population the following factors have to be taken into consideration: the environmental test conditions; the availability of resources for equipment and the training of testers; the local attitudes towards disability; the level of hearing impairment that may cause handicaps; and the major types of pathology causing hearing impairment. We suggest that in developing countries children should be screened at school entry using a simple field audiometer and that the external ear be inspected for the presence of a discharge. There is an urgent need to develop reliable and simple screening procedures for infants and young children; where possible, all children should be screened for severe or significant hearing impairment before the age of 2 years. No screening should, however, be implemented until appropriate follow-up services are available.

Acoustic Impedance Tests↗

A dual-radioisotope technique for the evaluation of penile blood flow during tumescence.

A technique is described for concomitant study of both arterial and venous penile blood flow during tumescence. Dual-isotope acquisition is started after labeling red cells in vivo with 99mTc. Xenon-133 in saline is then injected into the corpus cavernosum followed with vasoactive drugs to induce an erection. The resulting xenon and technetium time-activity curves are inputs for a one-compartment model. In 14 subjects, the average peak arterial flow rate (PAF) for normal males was calculated as 13.0 +/- 1.28 ml/min (avg +/- s.d.) compared to 16.1 +/- 5.14 and 5.02 +/- 1.78 ml/min for patients with venous leak (VL) or arterial insufficiency (AI), respectively. Peak venous flows (PVF) were 4.25 +/- 1.17, 12.1 +/- 3.75, and 3.78 +/- 1.00 ml/min for normal, VL and AL respectively. Al patients have significantly lower PAF than normal (p = 0.002) or VL patients (p = 0.018), and VL patients had significantly higher PVF than normal (p = 0.012) or Al (p = 0.018). The technique may be helpful in the study of impotence.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗