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Biomedical subjects

C H Thompson

Publications and source records attributed to C H Thompson.

At least 127 records · Page 7Linked to original sources
PubMed1985

Brain glutamate decarboxylase and cholinergic enzyme activities in scrapie.

C57BL/6J mice, age 6-8 weeks were inoculated intracerebrally with brain homogenate from mice previously infected with the 139A strain of scrapie; control mice were identically treated with brain homogenate from non-infected normal mice. The activities of choline acetyltransferase (CAT), acetyl cholinesterase (AChE), and glutamic acid decarboxylase (GAD) were determined in the forebrain and hindbrain of these animals after 67, 126 and 151 days post-inoculation. There were no significant differences in the activities of CAT and GAD between scrapie and control mice at early, middle or late stages of the disease in the scrapie-infected animals; there was an about 20% decline in AChE activity in the scrapie brain.

Acetylcholinesterase↗
PubMed1985

Optimised growth of human epidermal cells in vitro without the use of a feeder layer or collagen substrate.

A culture method has been developed which enables a reasonably large quantity of human epidermal cells to be grown in vitro without the use of irradiated 3T3 feeder layers or collagen substrates. These cultures become confluent within 2 or 3 weeks of initiation, and may be sub-cultured several times over their 16-week average lifespan provided that the calcium levels in the cultured medium are controlled. Some of the potential uses of these cultures are briefly discussed.

Calcium↗
PubMed1985

Monoclonal antibodies to bovine alpha-crystallin.

Monoclonal antibodies to bovine alpha-crystallin have been produced using hybridoma technology. Five selected hybridoma clones were maintained as ascites tumours in mice and gram quantities of the antibodies were purified from the ascites fluids by affinity chromatography on alpha m-crystallin covalently bound to Sepharose CL-2B. Preliminary characterization studies suggest that the antibodies are pure and monospecific. The antibodies could be divided into two groups on the basis of their reactivities towards iodinated alpha-crystallin, their ability to bind to Protein A-Sepharose, their immunoglobulin subclass, their immunoelectrophoretic patterns and their abilities to react with chicken and opossum alpha-crystallin. The availability of these monoclonal antibodies will greatly facilitate studies on the surface topography of alpha-crystallin.

Amino Acids↗
PubMed1985

Occurrence of tumors among litters of BALB/c female mice.

In the application of statistical techniques to tumor incidence data it is generally assumed that animals respond independently with regard to tumor occurrence, with littermates being no more alike than are animals from different litters. Data for nine different types of tumors from the large ED01 study conducted at the National Center for Toxicological Research were used to compare tumor prevalence rates among litters with the tumor rates expected under the assumption of homogeneity of tumor rates among litters. These data did not provide sufficient evidence to reject the assumption of homogeneity of tumor prevalence rates among litters of inbred female BALB/c mice for either spontaneously occurring tumors or bladder tumors produced by exposure to 2-acetylaminofluorene (CAS: 53-96-3). However, there does appear to be a difference in liver tumor prevalence rates among litters at 24 months of age. Thus litter effects are a factor that should be considered in the assignment of animals to treatment groups in carcinogenesis studies.

2-Acetylaminofluorene↗
PubMed1984

Immunoscintigraphy for detection of lymph node metastases from breast cancer.

A radiolabelled monoclonal antibody that reacts with human breast cancer was injected into the web space of each hand in eight women with breast cancer, and the axillae were scanned 16-24 h later. Scans were positive in seven axillae with palpable lymph nodes and in two axillae with impalpable lymph nodes (metastases later confirmed by needle aspiration). The scan was negative in one axilla with a palpable mass, and here no tumour cells were obtained on needle aspiration. In a man with axillary lymphoma, no specific binding of antibody was observed. This technique could lead to earlier and more precise diagnosis of lymph node metastasis in patients with breast cancer.

Adult↗
PubMed1984

Alzheimer paired helical filaments: bulk isolation, solubility, and protein composition.

A method has been developed for the bulk isolation of Alzheimer neurofibrillary tangles (ANT) of paired helical filaments (PHF) from histopathologically confirmed cases of Alzheimer disease/senile dementia of the Alzheimer type (AD/SDAT). The fresh or frozen autopsied cerebral cortex affected with Alzheimer neurofibrillary changes is dissociated by homogenization and sieving through nylon bolting cloth and the ANT are separated by a combination of sucrose discontinuous density gradient centrifugation, glass bead column chromatography, and sodium dodecyl sulfate (SDS) treatment. The isolated ANT produce red-green birefringence when viewed through polarized light after staining with Congo red. Ultrastructurally, the isolated PHF are well preserved and have the dimensions of the PHF seen in situ. Two major Populations of ANT which exist in different proportions in AD/SDAT brains are identified on the basis of their solubility in SDS. The ANT I and the ANT II are soluble and insoluble respectively on treatment with 2% SDS at room temperature for 5 min. Solubilization of the ANT II requires several repeated extractions with a solution containing 10% each of SDS and beta-mercaptoethanol (BME) at 100 degrees C for 10 min. Sonication of the ANT II greatly facilitates their solubilization. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of the isolated ANT reveals the presence of two major polypeptides with molecular weights (MW) of 62,000 and 57,000, several minor polypeptides with MW below 57,000, and a significant amount of material not entering the stacking and the resolving gels. Re-electrophoresis of polypeptides extracted from various areas of the resolving gel or of the material which does not enter the gel generates the same polypeptide profile as on the first gel, suggesting that the PHF material which does not enter the gel may result from the reaggregation of the polypeptides that enter the resolving gel. None of the polypeptides that enter the resolving gel. None of the polpeptides observed in the isolated PHF comigrate in the SDS-PAGE with any of the neurofilament polypeptides, tubulin, actin, or myosin.

Actins↗
PubMed1984

Effect of propafenone in patients with stable ventricular arrhythmias.

Thirty patients with clinically significant ventricular ectopy were treated with propafenone, a new potent antiarrhythmic agent with membrane stabilizing action. Patients had a minimum mean of greater than 30 ventricular premature beats per hour documented by continuous 48-hour ambulatory ECG recording. Twenty-five patients qualified as responders, defined as greater than 85% reduction of ventricular ectopy compared to baseline, and completed a double-blind placebo-crossover phase. Significant reduction in single ventricular ectopy per hour, paired ventricular ectopy per hour, and ventricular tachycardia beats per hour were observed. Almost total abolition of ventricular tachycardia and paired ventricular ectopy was achieved. Side effects were minimal and well tolerated. A significant prolongation of the PR interval occurred. QRS prolongation and prolongation of the corrected QT interval was observed in some patients, with new left bundle branch block developing in two patients. Long-term efficacy and safety studies will be necessary to determine the ultimate role of this new agent in the selection of antiarrhythmic therapy, but these initial results are encouraging.

Adult↗
PubMed1984

Tumor immunotherapy in the mouse with the use of 131I-labeled monoclonal antibodies.

This report describes the use of 131I-labeled monoclonal antibodies in two experimental models for tumor immunotherapy. In vitro treatment of the radiation-induced murine thymoma ITT-1-75NS with radiolabeled anti-Ly-2.1 significantly impaired subsequent tumor growth in vivo. However, in vivo treatment of this tumor, which previously had been injected into C57BL/6 mice, was unsuccessful. By contrast, in vitro treatment of a human colorectal tumor cell line (COLO 205) with 131I-labeled 250-30.6--a monoclonal antibody directed against a secretory component of normal and malignant gastrointestinal epithelium--completely inhibited subsequent tumor growth in BALB/c nude (nu/nu) mice. Furthermore, in vivo treatment of preexisting human colorectal tumor xenografts significantly impaired progressive tumor growth. Although some tumor inhibition was also produced by unlabeled 250-30.6 antibody, this response was considerably amplified by treatment with [131I]-labeled 250-30.6 (P less than .05), suggesting that in vivo treatment of human tumors with the use of 131I-labeled monoclonal antibodies may be clinically beneficial. The antithyroid drug propylthiouracil was used to reduce dehalogenation of the radiolabeled immunoglobulins in an attempt to improve their therapeutic efficacy.

Animals↗
PubMed1983

The definition of an MB related specificity by a monoclonal antibody.

A number of monoclonal antibodies have been described that react with monomorphic and polymorphic Ia-like specificities on human B cells, but it is not clear whether these react with HLA-DR encoded molecules or with the products of other closely linked genes within the MHC, such as MB, MT, or DC 1 antigens. A monoclonal antibody is described herein (MC-26.1) which detects a new Ia-like specificity as shown by B-cell reactivity, chemistry, family studies, including recombinant family and coprecipitation studies. The latter studies showed that specificity detected by the MC-26.1 antibody coprecipitated with determinants detected by conventional anti-MB3 and MT3, but not with HLA-DR4 antisera. The determinant was polymorphic but not related to any of the known MB or MT specificities. However, cross-reactions were demonstrated by the variability of reaction on different individuals. Coprecipitation studies indicate that the antigen defined by MC-26.1 coprecipitates with MB and MT specificities suggesting that the antibody defines a new specificity on the MB3 and MT3 molecules.

Animals↗
PubMed1983

Monoclonal antibodies to human colon and colorectal carcinoma.

A series of monoclonal antibodies was produced by immunizing mice with fresh carcinoma of the colon and with the cell line HT-29. These antibodies could be classified into 3 different groups: (a) those which were HT-29 specific and reacted with no other cell line or fresh colon carcinoma samples; (b) antibodies which reacted with HT-29 and were also reactive with a number of other in vitro cell lines; and (c) antibodies which appeared to be specific for carcinoma of the colon cell lines in that they reacted selectively with colon carcinoma cell lines and not with carcinoma lines derived from other tissues. It was clearly shown by immunoperoxidase staining of both normal and neoplastic cells of the gastrointestinal mucosa, from stomach to colon, that these antibodies were not tumour-specific. Indeed, one antibody (250-30.6) has a remarkable specificity for secretory epithelium of any tissue whether it be found in the gastrointestinal tract, respiratory system or urinary system. We question the existence of tumour-specific antigens detected by monoclonal antisera described thus far, and comment on the remarkable specificity of some of the sera produced, emphasized by the secretory cell-specific antibody described herein.

Animals↗
PubMed1983

Hu Ly-M3--a human leukocyte antigen.

A monoclonal antibody, 5-4.8, was produced against human peripheral blood lymphocytes and it appears to be leukocyte-specific in that it reacts with a common determinant (called Hu Ly-m3) present on the peripheral blood T, B and null lymphocytes of 40 individuals. The antibody also reacts with thymocytes, spleen cells, and bone marrow cells (30%) and weakly with granulocytes and platelets--but not with heart, liver, or kidney. Affinity to lentil-lectin and molecular weight analysis demonstrated that Hu Ly-m3 is a glycoprotein consisting of a single chain of 47,000 daltons which is not HLA because it is not present on all cells; because it is present on the surface of the phenotypically HLA- Daudi cell line; and because soluble HLA antigens did not inhibit the binding of the 5-4.8 antibody.

Animals↗
PubMed1983

Tumour visualisation using a radiolabelled monoclonal antibody.

A radiolabelled monoclonal antibody was injected intravenously into two patients with disseminated carcinoma of the colon and serial scintigrams were then obtained on three consecutive days. In addition to the "specific" antibody image, blood pool and conventional liver scans were also obtained. After computer-based subtraction discrete hepatic metastases could be demonstrated in both patients, while in the second patient, the primary colonic tumour was also visualised for the first time. The study demonstrates the specific localisation of primary and secondary carcinoma of the colon with a radiolabelled monoclonal anti-tumour antibody and offers an improved method of specifically detecting tumours in man.

Adenocarcinoma↗
PubMed1983

A human breast tissue-associated antigen detected by a monoclonal antibody.

Two monoclonal antibodies were produced in mice immunized with the human breast carcinoma cell line MCF-7. One antibody (24-17.1) reacted with MCF-7 and other breast tumor cell lines and detected an antigen of Mr 95,000. This antigen was not breast-specific because other tumor cell lines were also reactive. The second antibody (24-17.2) detected an antigen of Mr 100,000 (initially appearing to be specific for breast tissue and possibly for breast carcinomas) which was present on 10 of 10 malignant breast lines and absent from 41 of 43 other cell lines of differing origins. The antigen could not be detected by absorption or a direct test on normal tissues (liver, kidney, heart, spleen) or on lymphocytes. In addition, the 24-17.2 antibody reacted absorptively with 12 of 13 fresh breast carcinoma samples but not with fresh colon carcinoma samples. The 100,000-Mr antigen detected by the 24-17.2 antibody appeared to be distinct from the other components of normal breast, such as casein, lactalbumin, or milk fat globulin protein. This evidence indicated that the 24-17.2 antibody detected a human breast carcinoma-associated antigen (HBCAA). However, further histologic studies were used to determine the cellular distribution of the HBCAA, which was found on malignant breast epithelium, the epithelium of gynecomastia, and in lesser amounts and differently distributed on normal breast epithelium. The antigen was also found in several other tissues; nonetheless, the anti-HBCAA could be detected in increased amounts in the sera of patients with breast cancer.

Antibodies, Monoclonal↗
PubMed1983

Localization of human colorectal tumor xenografts in the nude mouse with the use of radiolabeled monoclonal antibody.

For the evaluation of the clinical usefulness of monoclonal antibodies as diagnostic or therapeutic reagents, tumor localization must be clearly demonstrated in an experimental model. In this report, nude mice carrying two human tumor xenografts--a colon carcinoma (Colo 205) and a melanoma (Colo 239)--were given ip injections of radiolabeled monoclonal antibodies. Monoclonal antibody 250-30.6, which reacted specifically with the colon carcinoma but not with the melanoma, was labeled with 125I, while a second monoclonal antibody of similar immunoglobulin subclass, but unreactive with either cell type, was labeled with 131I. Both antibodies were injected simultaneously, and either the mice were scanned with a gamma camera or their tissues were removed and the localization of radiolabeled antibody was calculated with the use of localization index (LI)--the ratio of the tissue to blood distribution for each isotope. The studies showed that specific localization had occurred, there being a colon tumor LI of 6 at 2 days. Tumors of 150-300 mg (mean diameter, 6 mm) and with an LI as low as 1.5 could be successfully imaged after computer-assisted background subtraction. This study demonstrated that relatively small human tumor xenografts in the nude mouse can be specifically detected with the use of paired monoclonal antibodies, each labeled with a different isotope.

Animals↗
PubMed1982

Correlation of left ventricular wall motion abnormalities with ventricular arrhythmias in patients with coronary artery disease.

We studied 71 patients with 12-hour Holter monitoring to determine if the incidence and complexity of ventricular arrhythmias in symptomatic coronary artery disease patients were related to the extent of left ventricular dysfunction. Their average age was 51 years, and each had cardiac catheterization within 3 months of study. Thirty-six patients had left ventricular aneurysms, 10 had normal left ventricular angiograms and 25 had left ventricular hypokinesis or akinesis without dyskinesis. The patients with aneurysms had significantly more heart failure, prior infarction, cardiomegaly and impaired ejection fractions. The mean premature ventricular contractions per hour for the aneurysm patients was 34 +/- 52, 3 +/- 5 for those with normal left ventricles, and 11 +/- 24 in the remainder. Complex premature ventricular contraction were noted in 50% of the aneurysm patients, in 10% of the patients with normal left ventricles and in 23% of the patients with hypokinesis or akinesis. Ventricular arrhythmias increase with greater left ventricular wall motion abnormality in patients with symptomatic coronary artery disease.

Adult↗
PubMed1982

The role of buffer anions and protons in secretion by the rabbit mandibular salivary gland.

1. The role of extracellular HCO3- and H+ in the formation of primary saliva and its subsequent modification by the glandular ducts has been investigated in the isolated perfused mandibular salivary gland of the rabbit. 2. Variation of extracellular HCO3- concentration between 12.5 and 50.0 mmol/l was without effect on salivary flow rate or on Na+ and K+ excretion, even though salivary HCO3- (and Cl-) content altered with changes in the extracellular concentration of the two anions. 3. Complete replacement of perfusate HCO3- by Cl- reduced fluid secretion by 34% and almost abolished ductal Na+ absorption. However, when extracellular pH was controlled by replacing HCO3- with the hydrophilic HEPES buffer, fluid secretion but not ductal Na+ absorption was restored to normal. 4. Complete replacement of exogenous HCO3- with acetate increased fluid secretion by 110% and also stimulated ductal Na+ absorption. This effect did not appear to be related to changes in cell pH and remains unexplained. Acetate entered the saliva in concentrations comparable to those seen for HCO3- in control experiments. 5. Salivary secretion showed an almost linear dependence on extracellular pH, rising from 14% of control (pH 7.4) levels at pH 6.2 to 130% at pH 7.8. Ductal Na+ absorption showed similar pH dependence. 6. Carbonic anhydrase inhibitors did not affect fluid secretion rates (except when supramaximal doses of ACh were used to evoke secretion) but they did cause a large reduction in salivary HCO3- output. In glands perfused with acetate rather than HCO3-, carbonic anhydrase inhibitors had no effect on excretion of fluid, acetate or metabolically derived HCO3-. Duct perfusion studies suggested that the effect of the inhibitors on HCO3- output was at the site of primary secretion rather than at the ductal site of HCO3- transport.

Animals↗
PubMed1982

Acebutolol therapy for ventricular arrhythmia. A randomized placebo-controlled double-blind multicenter study.

The safety and efficacy of acebutolol in suppressing ventricular ectopy was evaluated in 60 males (average 59 years) using 24-hour Holter recordings and a double-blind, randomized, crossover protocol. Acebutolol, 200 mg and 400 mg thrice daily, was compared with placebo. Only patients who had a mean of at least 30 ventricular premature complexes (VPCs) per hour on three 24-hour control Holter recordings were included. Analysis of Holter recordings revealed greater than 70% reduction in VPCs/hour from control levels during acebutolol therapy in over 50% of the 60 patients; dose-related reduction in the mean number of single and paired VPCs and ventricular tachycardia episodes (p less than 0.05) by acebutolol; and significant, asymptomatic reduction in resting heart rate and blood pressure. All side effects were transient. Acebutolol was discontinued because of side effects in one patient only.

Acebutolol↗