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Biomedical subjects

S Thompson

Publications and source records attributed to S Thompson.

At least 217 records · Page 12Linked to original sources
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↗
PubMed1989

Mechanistic studies on beta-ketoacyl thiolase from Zoogloea ramigera: identification of the active-site nucleophile as Cys89, its mutation to Ser89, and kinetic and thermodynamic characterization of wild-type and mutant enzymes.

Thiolase proceeds via covalent catalysis involving an acetyl-S-enzyme. The active-site thiol nucleophile is identified as Cys89 by acetylation with [14C]acetyl-CoA, rapid denaturation, tryptic digestion, and sequencing of the labeled peptide. The native acetyl enzyme is labile to hydrolytic decomposition with t 1/2 of 2 min at pH 7, 25 degrees C. Cys89 has been converted to the alternate nucleophile Ser89 by mutagenesis and the C89S enzyme overproduced, purified, and assessed for activity. The Ser89 enzyme retains 1% of the Vmax of the Cys89 enzyme in the direction of acetoacetyl-CoA thiolytic cleavage and 0.05% of the Vmax in the condensation of two acetyl-CoA molecules. A covalent acetyl-O-enzyme intermediate is detected on incubation with [14C]acetyl-CoA and isolation of the labeled Ser89-containing tryptic peptide. Comparisons of the Cys89 and Ser89 enzymes have been made for kinetic and thermodynamic stability of the acetyl enzyme intermediates both by isolation and by analysis of [32P]CoASH/acetyl-CoA partial reactions and for rate-limiting steps in catalysis with trideuterioacetyl-CoA.

Acetyl-CoA C-Acyltransferase↗
PubMed1989

A multiwell lectin-binding assay using lotus tetragonolobus for measuring different glycosylated forms of haptoglobin.

Using the fucose-specific lectin, Lotus tetragonolobus, we recently isolated abnormally-glycosylated forms of haptoglobin (FHp) that are useful for monitoring cancer patients and for detecting active disease in rheumatoid arthritis. FHp is detected by electrophoresis and silver staining. In order to use FHp clinically, a better assay is required. A lectin-binding assay (LBA) is described, in which FHp is captured by lotus bound to multi-well plates, and the amount captured is measured by an enzyme-labelled antibody system. The LBA results correlate with those obtained with electrophoresis. The method also gives good precision and low background values. In the presence of 1 mol/l fucose the bound-FHp was reduced by between 60-100%. This confirms that the method is detecting abnormally-fucosylated forms of haptoglobin. This approach opens up exciting possibilities for investigating large numbers of pathological sera and it suggests that other combinations of lectin and antibody may be worth investigating in the future.

Arthritis, Rheumatoid↗
PubMed1989

Germ line transmission and expression of a corrected HPRT gene produced by gene targeting in embryonic stem cells.

The deletion mutation in the HPRT-deficient mouse embryonic stem (ES) cell line E14TG2a has been corrected by gene targeting. The presence of plasmid sequences in the correcting vector DNA did not affect the frequency of correction. We have characterized three different HPRT gene structures in correctants. Cells from one corrected clone have been introduced into mouse blastocysts, and germ line transmission of the ES cell-derived corrected gene has been achieved. The corrected gene has the same pattern of expression as the wild-type gene, with the characteristic elevated level of expression in brain tissue. Hence, we have demonstrated the feasibility of introducing targeted modifications into the mouse germ line by homologous recombination in ES cells.

Animals↗
PubMed1989

A pharmacokinetic study of granisetron (BRL 43694A), a selective 5-HT3 receptor antagonist: correlation with anti-emetic response.

As part of an open dose-ranging study, the pharmacokinetics of granisetron (BRL 43694A), a selective 5-HT3 receptor antagonist given by the i.v. route, was studied in 18 patients receiving highly emetogenic cytotoxic drugs, predominantly cisplatin, either alone or in combination with other cytostatic agents. All patients received 30-min infusions of granisetron at a dose of 40 micrograms/kg. Nine showed complete absence of the gastrointestinal side effects normally associated with cisplatin, and in the majority of the remaining patients, the onset and severity of nausea was significantly modified. No acute side effects were observed at this dose and the drug was well tolerated in all cases. Peak plasma concentrations and area under the curve (AUC) values for granisetron showed considerable inter-patient variation. Higher plasma levels of granisetron were observed at 5 h in responding patients compared with those in whom the drug was ineffective in controlling emesis (P less than 0.05). AUC values were higher in responding patients, but this difference was not statistically significant. There was apparently no defined plasma concentration threshold for the drug's anti-emetic effect in these patients. Granisetron seems to be an effective and safe anti-emetic in patients receiving cytotoxic chemotherapy. Further exploration of its dose scheduling and pharmacokinetic profile is warranted.

Adult↗
PubMed1989

Measurement of nonuniform current densities and current kinetics in Aplysia neurons using a large patch method.

A large patch electrode was used to measure local currents from the cell bodies of Aplysia neurons that were voltage-clamped by a two-microelectrode method. Patch currents recorded at the soma cap, antipodal to the origin of the axon, and whole-cell currents were recorded simultaneously and normalized to membrane capacitance. The patch electrode could be reused and moved to different locations which allowed currents from adjacent patches on a single cell to be compared. The results show that the current density at the soma cap is smaller than the average current density in the cell body for three components of membrane current: the inward Na current (INa), the delayed outward current (Iout), and the transient outward current (IA). Of these three classes of ionic currents, IA is found to reach the highest relative density at the soma cap. Current density varies between adjacent patches on the same cell, suggesting that ion channels occur in clusters. The kinetics of Iout, and on rare occasions IA, were also found to vary between patches. Possible sources of error inherent to this combination of voltage clamp techniques were identified and the maximum amplitudes of the errors estimated. Procedures necessary to reduce errors to acceptable levels are described in an appendix.

Action Potentials↗
PubMed1989

Glycine tRNA mutants with normal anticodon loop size cause -1 frameshifting.

Mutations in the acceptor stem, the 5-methyluridine-pseudouridine-cytidine (TFC) arm, and the anticodon of Salmonella tRNA2Gly can cause -1 frameshifting. The potential for standard base pairing between acceptor stem positions 1 and 72 is disrupted in the mutant sufS627. This disruption may interfere with the interaction of the tRNA with elongation factor-Tu.GTP or an as-yet-unspecified domain of the ribosome. The potential for standard base pairing in part of the TFC stem is disrupted in mutant sufS625. The nearly universal C-61 base of the TFC stem is altered in mutant sufS617, and the TFC loop is extended in mutant sufS605. These changes are expected to interfere with the stability of the TFC loop and its interaction with the D arm. The mutation in mutant sufS605, and possibly other mutants, alters nucleoside modification in the D arm. Three mutants, sufS601, sufS607, and sufS609, have a cytidine substituted for the modified uridine at position 34, the first anticodon position. None of the alterations grossly disrupts in-frame triplet decoding by the mutant tRNAs. The results show that -1 frameshifting in vivo can be caused by tRNAs with normal anticodon loop size and suggest that alternative conformational states of the mutant tRNAs may allow them to read a codon in frame or to shift reading frame.

Anticodon↗
PubMed1989

ELISPOT: a new approach to studying the dynamics of virus-immune system interaction for diagnosis and monitoring of HIV infection.

A new approach to detect and enumerate HIV-specific antibody-secreting cells (ASC) in the peripheral blood was developed using the enzyme-linked immunospot (ELISPOT) methodology. ASC to an HIV envelope recombinant protein were demonstrated in 75% of 16 adults and 72% of 21 children with untreated AIDS or ARC and in 63% of 34 asymptomatically infected adults but in none of the 51 HIV antibody-negative individuals. Only 1 of the 13 adults receiving AZT therapy yielded a positive reaction, and 27% of the 30 infants born to seropositive mothers were found to have HIV-ASC. The number of HIV-ASC in positive individuals varied from 8 to 202 per 10(6) circulating mononuclear cells. The reactivity was specifically inhibited by soluble HIV antigen and was abrogated by cycloheximide, indicating that the observed reaction was the result of de novo synthesis of HIV-specific antibodies. Nonspecific polyclonal B cell activation was unlikely to be responsible for the results observed as no reactivity was found to a common antigen, tetanus toxoid. Since circulating antigen-specific ASC reflect persistent or recent antigenic stimulation, our findings indicate that this new approach could provide a dynamic perspective of the natural course of virus-immune system interactions in individuals infected with HIV, as well as in those undergoing prophylactic or therapeutic interventions.

AIDS-Related Complex↗