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Biomedical subjects

K M Wilson

Publications and source records attributed to K M Wilson.

At least 55 records · Page 3Linked to original sources

Age differences in the formation of equivalence classes.

In order to investigate the relationship between stimulus equivalence class formation and age differences, two groups of elderly (ages 62-81) and young (ages 19-22) adult men and women mastered a series of simple and conditional discriminations. Subsequently, they were administered a test for the emergence of equivalence relations. There was a significant age difference in the emergence of equivalence relations, with the elderly subjects less likely to demonstrate equivalence relations. Measures of response latencies evidenced a general slowing of behavior for the elderly group across tasks. There were no gender or Age by Gender interactions. Possible explanations for the age differences are discussed.

Adult↗

Altered p53 in microdissected, metachronous, premalignant and malignant oral lesions from the same patients.

Aims-To determine whether mutant p53 alleles harboured by malignant tumours of the oral cavity were also present in previous premalignant lesions at the same site.Methods-Paraffin embedded tumour specimens along with their premalignant counterparts were analysed for p53 alterations using immunohistochemistry, microdissection, polymerase chain reaction amplification, and DNA sequencing.Results-Malignant lesions from five of eight patients showed overexpression of p53 protein by immunohistochemistry. Upon DNA sequencing, two of these five specimens had p53 mutations. Of the five patients whose cancers showed p53 overexpression by immunohistochemistry, three had previous premalignant lesions that also had immunohistochemically detectable p53 protein. However, DNA sequencing showed that none of these three had mutations in the p53 gene. The remaining five premalignant lesions had no immunohistochemically detectable p53 protein.Conclusions-Some premalignant lesions have increased p53 protein which can be detected by staining with antibody to p53. This staining is not caused by mutations in p53 that are found in subsequent tumours at the same site.

Journal Article↗

Thyroplasty using a silicone elastomer implant.

Silicone has been used in a variety of forms as a replacement for soft tissue for more than three decades in the United States. The safety of this practice has come under scrutiny recently as our knowledge of the local, systemic, and immune effects of silicone has expanded. Contrary to what was once thought, silicone is not biologically inert. Silicone elastomer, however, has not been implicated in the development of systemic immune disease or carcinogenesis. The evidence to date supports the continued use of silicone elastomer implants in the larynx. It is clear, however, that continued investigation into the basic biologic properties and mechanisms of the host-silicone implant interaction is warranted.

Humans↗

Simplified conjugation chemistry for coupling peptides to F(ab') fragments: autologous red cell agglutination assay for HIV-1 antibodies.

The rapid whole blood test, developed for the detection of circulating antibodies to human immunodeficiency virus type 1 (HIV-1), is based on agglutination of autologous red blood cells using an anti-human glycophorin antibody conjugated to the HIV-1 immunodominant epitope of gp41 (579-613). A simplified procedure for preparing antibody-peptide conjugates for use in the autologous red cell agglutination test is described. F(ab')2 fragments of the anti-glycophorin antibody were prepared by pepsin digestion and reduced to F(ab') fragments with the use of tri-n-butylphosphine (TBP). This permitted the simultaneous reduction of the F(ab') fragments and coupling of a bromoacetyl derivative of the synthetic immunodominant peptide gp41 (579-613) [Cys-Acm 598, Lys-BrAc 604] containing epsilon-bromoacetyl-lysine at residue 604 to the resultant F(ab') fragment. Conjugation to the F(ab') fragment resulted in a stable thio-ether linkage between the peptide Lys-604 and the inter heavy chain cysteines of the F(ab'). The resultant F(ab')-peptide conjugate was comparable to the previously described disulfide coupled conjugate when used in the autologous red cell agglutination test. This simplified conjugation chemistry may also be useful for the development of reagents for FACS analysis as well as targetted vaccines.

Amino Acid Sequence↗

The effect of perioperative blood transfusion on survival in head and neck cancer.

This Head and Neck Intergroup analysis was undertaken to evaluate further previously reported observations linking blood transfusions, which were given to patients with head and neck cancer, to a worse prognosis. This study population represents those patients registered to the Head and Neck Intergroup Trial 0034 for previously untreated resectable squamous cell carcinoma. Additional transfusion data were obtained by one of us (D.E.S.) on 217 patients and added to the Head and Neck Intergroup data set, providing an opportunity for assessing the impact of survival by other variables. The study group was separated using 13 variables. Analysis demonstrated that transfusion did not significantly decrease the locoregional control (P = .60). Multivariate analysis indicated that T stage (P = .015), N stage (P = .004), treatment received (P = .004), and Karnofsky Performance Scale (P = .031) were the only factors that did significantly influence survival. This multivariate analysis controlling for these variables demonstrated no significant effect on survival for those patients receiving transfusion during surgery (P = .55) or after surgery (P = .39). This study of 217 patients, controlled for other variables, does not demonstrate any significant negative relation between blood transfusions and either locoregional control or survival.

Activities of Daily Living↗

Autologous red cell agglutination test for antibodies to feline immunodeficiency virus.

The T-lymphotropic lentivirus, feline immunodeficiency virus (FIV) is now recognised as a major viral pathogen affecting domestic cat populations worldwide. A rapid, autologous red cell agglutination test for antibodies to FIV has been developed. A synthetic peptide analog corresponding to the immunodominant epitope within the FIV transmembrane glycoprotein gp40 residues (680-715) KVEAMEKFLYTAFAMQELGC (Acm)NQNQFFK(BrAc)KIPLELWTR was conjugated to an anti-feline erythrocyte antibody using a thio-ether linkage. Within 3 min of adding this reagent to 20 microliters of whole blood, circulating antibody to the peptide epitope caused agglutination of the red blood cells. The performance of this simple test is comparable with the two commercially available enzyme immunoassay (EIA) kits and an EIA based on this peptide. A variant of the gp40 (680-715) peptide corresponding to the FIV, PPR strain gp40 (678-716) sequence was also synthesised and no difference in reactivity was observed in an EIA on 211 seropositive samples, indicating that the peptide-based test may be applicable to other known strains of the virus.

Amino Acid Sequence↗

Double incision open technique for carpal tunnel release: an alternative to endoscopic release.

I prospectively evaluated the results of 30 consecutive patients with bilateral carpal tunnel release using two techniques. The first release was performed with a standard incision while the opposite hand underwent release by a double incision open technique. Postoperatively, subjective complaints of pain, grip strength, pinch strength, and pillar tenderness were evaluated at 1, 2, 4, 6, and 10 weeks. All patients expressed complete relief of preoperative numbness in both hands. The improvement in pinch and grip strength and lack of pillar tenderness in the hands that underwent the double incision open technique closely matched the reported results of endoscopic carpal tunnel release. There were no complications with either technique.

Adolescent↗

Kinetics of the autologous red cell agglutination test.

The kinetics of the autologous red cell agglutination test for detecting circulating antibodies to HIV-1 were studied. Two monoclonal anti-red blood cell antibodies (1C3/86 and 10F7MN) were used to construct Fab-peptide conjugates for the test. Both antibodies recognize glycophorin alpha on the surface of erythrocytes by immunoprecipitation or immunoblotting techniques. The number of binding sites, association and dissociation constants of 1C3/86 Fab and 10F7MN Fab' fragments were determined (n = 4.80 X 10(5) sites/erythrocyte, Ka = 0.43 X 10(7) M-1, Kd = 23 X 10(-8) M for 1C3/86, n = 4.66 X 10(5) sites/erythrocyte, Ka = 1.05 X 10(7) M-1, Kd = 9.5 X 10(-8) M for 10F7MN. The binding studies were performed under the same conditions as the autologous red blood cell agglutination test. When 0.9 microgram of anti-glycophorin Fab was added to 10 microliters of blood 0.25 microgram of 1C3/86 Fab was bound whereas 0.29 microgram for 10F7MN Fab' was bound. Antibody binding reached a plateau after 2 min and once bound did not exchange with unbound Fab over the time scale of the test. The binding of the anti-peptide antibody (cross-linking antibody) was also complete within 2 min. Addition of approximately 0.1 microgram of anti-peptide antibody gave half a maximal agglutination score. This is equivalent to 10 micrograms/ml circulating antibody. Under the agglutination test conditions, Fab-peptide conjugate was bound to 14% of available glycophorin molecules. Half maximal agglutination occurred when approximately 1.1% of the bound Fab-peptide conjugates were cross-linked. A maximum agglutination score of four occurred in the presence of 1 microgram of anti-peptide antibody equivalent to 100 micrograms/ml circulating antibody whereas an agglutination score of 1+ was elicited by only 0.32 microgram anti-peptide antibody and involved the cross-linking of approximately 160 glycophorin molecules per red cell.

Antibodies↗

Distal forearm regional block anesthesia for carpal tunnel release.

A technique of nerve block in the distal forearm is described for use in carpal tunnel release operations. In 70 operations, the extremities of 52 patients have been successfully anesthetized in this manner without complication. This simple anesthetic technique is recommended for use by the hand surgeon.

Carpal Tunnel Syndrome↗

Cell-surface expression of human histocompatibility leucocyte antigen (HLA) class II-associated invariant chain (CD74) does not always correlate with cell-surface expression of HLA class II molecules.

The human histocompatibility leucocyte antigen (HLA) class II-associated invariant chain comprises at least four polypeptides. One of these is expressed as a membrane-bound subunit and has been designated as CD74. We investigated the expression of CD74 on B- and T-cell types utilizing monoclonal antibodies (mAb) specific for the c-terminus of CD74. All B cells tested expressed CD74 regardless of their HLA phenotypes. High and low CD74 expressors were provisionally assigned based on quantitative variations found in some haplotypes. A mutant cell with selective deletions of class II loci DR and DQ but with retention of DP and additional class II heterodimers synthesize normal amounts of CD74. In contrast, however, a mutant with a total class II deletion had diminished expression of CD74, suggesting that at least one of the class II isotypes is essential for full constitutive expression of CD74. Major histocompatibility complex (MHC) class II negative T-cell lines and CD3+ T cell isolated from peripheral blood did not express CD74. However, allostimulated T cells which express de novo induced class II determinants also did not express CD74. Taken together, these results show that CD74 is expressed on B cells and unexpectedly is not synthesized on de novo-induced class II positive T-cell clones.

Antigens, Differentiation, B-Lymphocyte↗

Hyperhydrating effect of acute administration of angiotensin II in rats.

Water intake, urine output, and fluid exchange (water intake less urine output) were measured in rats at hourly intervals for 7 hours and at 24 hours following acute administration of angiotensin II (AII, 200 micrograms/kg SC). AII induced the expected abrupt increase in water intake and a more gradual increase in urine output. The change in fluid exchange (fluid exchange of the AII-treated group less fluid exchange of controls) became positive within the first hour after treatment with AII, decreased linearly with time, and reached 0 at approximately 10 to 12 hours after treatment with AII. When AII was administered intracerebroventricularly (50 ng), similar results were observed. In this case, the change in fluid exchange (delta F) reached 0 in about 6 hours. Imposition of a water load (1% of body weight, IP) on the group receiving AII SC failed to affect the time required for delta F to reach 0 if the water load was disregarded. However, inclusion of the load as a part of intake extended the time the rats remained in positive fluid balance beyond that of the nonloaded, AII-treated control group. In the case of the larger water load (3% of body weight, IP), delta F returned to that of controls in about 4 to 5 hours if the water load was disregarded. However, inclusion of the load as part of intake extended the period of hyperhydration well beyond that of both the nonloaded, AII-treated group and the AII-treated group given the 1% load.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Observations using antiendotoxin antibody (E5) as adjuvant therapy in humans with suspected, serious, gram-negative sepsis.

OBJECTIVE: To evaluate the safety and efficacy of E5 (Xomen-E5), a murine monoclonal immunoglobulin M antibody, in reducing mortality in patients with serious Gram-negative infections. Phase II, single-site study. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Surgical, neurosurgical and medical ICUs, comprising approximately 30 beds in a multidisciplinary university hospital. PATIENTS: Patients with clinical evidence of serious infection admitted to the ICU for monitoring of vital signs and for intensive care nursing. Of the 39 patients enrolled in the study, 23 had documented Gram-negative infection. METHODS: Patients suspected of having life-threatening Gram-negative infections received one of two doses of E5 or placebo. Safety and efficacy were assessed by survival on days 3, 7, and 21, appearance of adverse reactions, development of antimurine antibodies, and effects on BP, urine output, WBC count, and temperature. MEASUREMENTS AND MAIN RESULTS: Mortality rate from Gram-negative infection 3 days after the last drug (or placebo) infusion was two (22%) of nine deaths in the placebo group compared with 0 of nine for E5 2.5 mg/kg and 0 of five for E5 7.5 mg/kg. At 21 days after therapy, three patients treated with E5 had died. Only one of these three deaths resulted from infection. Eight of 15 E5 patients tested had immunoglobulin G antimurine antibodies by 3 wks after therapy began, but all were asymptomatic. CONCLUSIONS: E5 was well tolerated and may have the potential to reduce early morbidity and the mortality rate in seriously ill patients with Gram-negative infections. Results from larger phase III studies are needed to confirm these findings.

Acute Disease↗

Rapid whole blood assay for HIV-1 seropositivity using an Fab-peptide conjugate.

A rapid whole blood test has been developed for circulating antibodies to human immunodeficiency virus type 1 (HIV-1), based on agglutination of autologous red blood cells. Evaluation of the test revealed that 100% of seropositive HIV-1 patients (both asymptomatic and AIDS cases) were detected (n = 94) with a specificity of 99.5% in healthy blood donors (n = 596). The assay uses an Fab fragment of a monoclonal antibody specifically directed against glycophorin (a transmembrane glycoprotein present on the surface of human red blood cells). This anti-red blood cell Fab is conjugated via the inter-heavy chain cysteines to a synthetic peptide corresponding to the immunodominant epitope of the HIV-1 viral coat protein gp41 (579-613). Addition of this reagent to 10 microliters of whole blood results in the Fab-peptide conjugate coating the red blood cells with peptide. In the presence of circulating antibodies to the HIV-1 peptide, red cell agglutination occurs within 2 min. The sensitivity and specificity of this reagent indicate that it is appropriate for use as a rapid diagnostic test for HIV-1 seropositivity.

Agglutination Tests↗

Synergistic interactions between alpha 1- and alpha 2-adrenergic receptors in activating 3H-inositol phosphate formation in primary glial cell cultures.

Norepinephrine (NE)-stimulated 3H-inositol phosphate (3H-InsP) formation in primary glial cell cultures is thought to be due to alpha 1-adrenergic receptor activation. Surprisingly, the alpha 1-selective agonists phenylephrine and methoxamine showed only 12-21% of the intrinsic activity of NE in activating this response. Although the alpha 2-selective agonist UK 14,304 was itself inactive, inclusion of UK 14,304 increased the response to the alpha 1-selective agonists by about threefold. This increase was concentration-dependent and occurred at all time points examined. 6-Fluoro-NE and alpha-methyl-NE mimicked the effect of NE in glial cultures, although with lower potencies. However, several partial agonists were ineffective in activating this response, in both the presence and absence of UK 14,304. Synergistic interactions were not observed for alpha 1-mediated responses in slices of rat cerebral cortex, either for formation of 3H-InsPs or potentiation of isoproterenol- or adenosine-stimulated cyclic AMP accumulation. Both UK 14,304 and phenylephrine inhibited NE-stimulated 3H-InsP formation in concentrations similar to those necessary to activate this response directly. These results suggest that NE activates 3H-InsP formation in primary glial cultures by synergistic actions on both alpha 1- and alpha 2-adrenergic receptors. The agonists UK 14,304 and phenylephrine also can act to inhibit the response to NE competitively.

Adrenergic alpha-Agonists↗

Bioinequivalence of four 100 mg oral aspirin formulations in healthy volunteers.

The single dose pharmacokinetics of 4 commercially available 100 mg oral aspirin formulations were studied in 6 healthy men and 6 healthy women. Two of the formulations were rapid release ('Cardiprin' 100, 'Platelin') and the other 2 were enteric coated formulations ('Astrix' 100, 'Cartia'). There were marked differences in the plasma concentration-time profiles between the rapid release and the enteric coated formulations. There were no significant differences (p greater than 0.05) in the mean time to achieve maximum aspirin concentrations between 'Cardiprin' 100 (0.48 h) and 'Platelin' (0.35 h), but this was significantly prolonged (p less than 0.001) for 'Astrix' 100 (3.73 h) and even more prolonged for 'Cartia' (6.84 h). Similar between-formulation differences were seen in the areas under the plasma concentration-time curves, for which the rank order was 'Cardiprin' 100 (1.60 mg/L.h) = 'Platelin' (1.54 mg/L.h) greater than 'Astrix' 100 (0.73 mg/L.h) greater than 'Cartia' (0.56 mg/L.h). For 'Cardiprin' 100, 'Platelin' and 'Astrix' 100 plasma aspirin concentrations were below 5 micrograms/L by 7 h after ingestion, whereas for 'Cartia' aspirin was detectable for up to 16 h, giving the appearance of sustained release. The enteric coated formulations produced the greatest variability in the plasma aspirin concentration vs time profiles. The urinary recovery of salicylate was greater than 80% of the administered dose for all 4 formulations. The clinical significance of the marked pharmacokinetic differences observed with these 4 low-dose aspirin formulations is not known.

Administration, Oral↗

Randomized, double-blind phase II study of anti-endotoxin antibody (E5) as adjuvant therapy in humans with serious gram-negative infections.

Xomen-E5 (E5) is a murine monoclonal IgM antibody (MAb) that binds to the lipid A epitope of endotoxin. The MAb was developed by immunization against the J5 mutant of Escherichia coli. Prior studies in humans have shown safety and T1/2 of 18.4 hours. In this double blind study patients suspected to have life threatening gram-negative infections were randomized to receive 2 doses, 24 hours apart, of placebo (P), 2.5 mg/kg E5, or 7.5 mg/kg E5. Overall 23 patients had a documented serious gram-negative infection and received at least one dose of study drug. Mortality 3 days after last infusion was 2 of 9 for P, 0 of 9 for 2.5 mg/kg, and 0 of 5 for 7.5 mg/kg. By 21 days after therapy one E5 treated patient had died. Wheezes occurred in one E5 treated patient. Eight of 15 E5 patients treated had IgG anti-murine antibodies by 3 weeks after therapy. These data suggest the need to pursue studies designed to verify that E5 reduced mortality and morbidity in seriously ill patients with gram-negative infections.

Antibodies, Monoclonal↗