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Biomedical subjects

D L Brown

Publications and source records attributed to D L Brown.

At least 343 records · Page 19Linked to original sources
PubMed1981

Cribside neurosonography: real-time sonography for intracranial investigation of the neonate.

A prospective study was made of 94 real-time sonographic sector scans of 56 neonates in a 6 month period. The examinations were performed using the anterior fontanelle as an acoustic window. In 17 cases, computed tomography (CT) head scans were available for comparison. In no case did the CT and sonographic examination disagree as to the size of the lateral ventricles. Abnormalities detected by sonography include ventriculomegaly, intracerebral hematomas, a congenital glioma, and several cystic lesions. Sonographic sector scanning produces excellent, detailed images of dilated lateral and third ventricles, uses no ionizing radiation, is less expensive than CT, and can be performed in the isolette, minimizing the risk of hypoxia and hypothermia. At Methodist Hospital Graduate Medical Center, sonography has replaced CT as the initial method of investigation of ventricular size. CT plays a complementary role in the evaluation of the posterior fossa, intracranial hemorrhage, and mass lesions.

Cerebral Arteries↗
PubMed1981

In vivo generation and clearance of soluble immune complexes containing IgM antibodies in normal and decomplemented rabbits.

Soluble immune complexes containing IgM antibodies (IgM.IC) were generated in vivo utilizing a passive induction model, whereby purified antibodies were injected into rabbits with circulating radiolabelled bovine serum albumin (BSA) as antigen. A triphasic response was obtained consisting of an initial rapid elimination of TCA-precipitable antigen in the first 30 min, followed by a progressive diminution in the clearance velocity as antigen from the tissues moved back into the circulation to re-equilibrate, and subsequent elimination of the antigen at a rate close to that of free BSA. The dynamics of IC formation and disappearance were studied by a combination of Farr assay and solid-phase C1q binding. The results show that the rate of clearance decreased as the complexes progressively moved into antigen excess, and that the decrease in the proportion of complexed antigen was mirrored by a similar decrease in the ability of the complexes to bind C1q. Depletion of complement by treatment with cobra venom factor did not inhibit the clearance of the antigen, but may have inhibited solubilization of the complexes in vivo. Tissue localization experiments indicated that the liver is the organ predominantly involved in the uptake and catabolism of in vivo-generated IgM.IC. These results show that the clearance velocity of soluble IgM.IC is critically dependent on the antigen/antibody ratio, and that clearance is mediated via a C3b-independent mechanism in the RES.

Animals↗
PubMed1981

Relationship of microtubule organization in lymphocyte to the capping of immunoglobulin.

We have used a double fluorescence staining procedure to examine the distribution of antitubulin-staining structures in mouse splenic lymphocytes induced to patch and cap surface immunoglobulin by treatment with antiimmunoglobulin antibodies. A well organized network of fibers, extending from a single microtubule organizing center (MTOC) associated with the centriole pair, was detected by antitubulin staining at all stages of the capping process. In lymphocytes possessing as intact network, the cap was formed and internalized over the region of the cytoplasm containing the organizing center, Golgi apparatus, and most other organelles. In contrast, in lymphocytes which had been subjected to a colchicine treatment sufficient to completely disassemble networks prior to cap induction, no relationship was detected by immunofluorescence between the position of the centrioles (a marker for the MTOC) and the location of the surface cap. Electron microscopic observation of colchicine-treated cells, induced to cap by ferritin-conjugated anti-Ig, revealed extensive disorganization of cytoplasmic organelles and exclusion of organelles from the region of underlying the cap. These results indicate a role for the microtubule network of lymphocytes in maintaining cytoplasmic polarity and in specifying the site of Ig cap formation.

Animals↗
PubMed1981

Sudden unexpected death from primary pulmonary hypertension.

Five cases of sudden unexpected death from primary pulmonary hypertension (PPH) are reviewed. Right ventricular myocardial hypertrophy and a dilated pulmonary conus may be the only findings at the initial gross examination. Characteristic microscopic changes in the lungs are primarily those of plexiform vascular lesions. The pathophysiology and morphologic alterations of PPH are discussed, and the association of this entity with collagen vascular diseases and mixed connective tissue disease is emphasized. It is concluded that PPH is an unusual cause of sudden unexpected death and its diagnosis may be difficult because prior signs or symptoms may be absent. The increased familial incidence of PPH underscores the necessity of considering this entity in cases of sudden unexpected death of obscure cause.

Adult↗
PubMed1981

Clearance kinetics of soluble pre-formed immune complexes containing IgM antibodies in normal and decomplemented rabbits.

The clearance kinetics of homologous soluble pre-formed 125I-BSA/IgM anti-BSA immune complexes (IgM . IC) injected into the blood was studied in the rabbit. IgM . IC close to equivalence were cleared with a greater velocity than those in x 5 or x 10 antigen excess. Clearance of BSA specifically bound to antibody, was measured by the Farr assay and found to exhibit an exponential mode of elimination suggesting a selective removal of large over small lattice complexes or free antigen. The role of C3 in the clearance of IgM . IC was examined by treating rabbits with cobra venom factor (CVF). While more variation was noted in CVF-treated rabbits, no statistically significant differences could be detected between C3-depleted and control animals. It is, therefore, concluded that soluble preformed IgM . IC are cleared from the rabbit circulation by a C3b-independent mechanism. This finding for soluble IC is clearly different from the clearance of IgM-coated red cells from the circulation, which has previously shown to be highly C3b-dependent.

Animals↗
PubMed1980

Lidocaine toxicity.

Lidocaine is recognized as a first line drug for ventricular arrhythmias and has recently been used in acute myocardial infarction as prophylaxis against ventricular fibrillation. A 68-year-old man was erroneously given 2 gm of lidocaine by intravenous push and sustained a cardiac arrest. He was treated supportively and had complete recovery. We discuss complications of therapeutic and excessive doses of lidocaine and outline measures for treatment of massive lidocaine overdose.

Aged↗
PubMed1980

The use of C1q, conglutinin and low affinity rabbit IgM antibody to human Fc in a ligand coctail radioassay for detecting and characterizing immune complexes in pathological sera.

A ligand radioassay for the detection of IC which utilizes C1q, bovine conglutinin and low affinity rabbit IgM anti-human Fc in a reagent coctail, is presented. IC are first isolated from serum by precipitation in polyethylene glycol, then analysed for their ability to react with the ligand coctail. Dual-label studies with 125I and 131I-tagged ligands, designed to determine whether the ligands bound independently to IC, indicate that the binding of each ligand to IC is not significantly affected by the presence of the other two ligands. The results of assaying pathological sera for IC by the ligand coctail radioassay correlate well with the results of three other assays. The assay system is also flexible enough to allow other low affinity IgM reagents to be used which could potentially cover the whole range of immunoglobulin classes occurring in pathological IC.

Antibody Affinity↗
PubMed1979

Nitrous acid mutagenesis of duplex DNA as a three-component system.

Purified native Hemophilus influenzae DNA is relatively insusceptible to nitrous acid (NA) mutagenesis in vitro, but is readily mutated following denaturation. NA mutagenicity for duplex DNA is significantly increased in the presence of various alcohols, glycols, phenols or primary amines. Phenol-extracted DNA contains dissociable contaminants of low molecular weight that enhance NA mutagenesis. Enhancement of NA mutagenesis by phenol and by spermine is due to the formation of unstable molecular species. We propose that reactive organic nitroso compounds are formed which then serve as delivery vehicles to promote mutagenicity of native DNA, perhaps via transnitrosation reactions. Similar reactions probably occur in vivo to promote NA-induced base substitution (but not frameshift) mutations in Salmonella typhimurium and in Escherichia coli. The possible significance of these observations to carcinogenesis is discussed.

DNA, Bacterial↗
PubMed1979

Aryl-monoalkyl and cyclic triazenes: direct-acting mutagens.

An aryl-monoalkyl triazene, methyl-p-tolyl triazene (MTT) and a cyclic triazene (delta2-triazoline) are direct-acting mutagens for Salmonella typhimurium bacteria and for cell-free Hemophilus influenzae DNA. MTT causes reversion of the hisG46 base-substitution mutation, but no reversion of the hisD3052 frameshift mutation. Induced mutation frequency is not strongly influenced by modifications in the genetic background of the S. typhimurium Ames tester strains, but is mildly enhanced by the addition of a pool of amino acids to the plating medium and is strongly enhanced by liquid preincubation before plating.

Base Sequence↗
PubMed1979

Purification of cytoplasmic tubulin and microtubule organizing center proteins functioning in microtubule initiation from the alga Polytomella.

Cytoplasmic tubulin and the microtubule organizing centers (MTOCs) for the cytoskeletal microtubule system of the flagellate Polytomella have been isolated. The isolated MTOCs serve as sites for the in vitro assembly of the purified tubulin protein. The major proteins (four polypeptides of molecular weights 190,000-210,000) functioning in this assembly have been extracted from the MTOCs and purified. Kinetic studies and experiments with in vivo 35S-labeled MTOC proteins (or 35S-labeled tubulin) demonstrate that these proteins function specifically in microtubule initiation and do not contribute to microtubule elongation. The results indicate that microtubule assembly in vivo is controlled by microtubule initiating proteins associated with the organelles termed MTOCs.

Carrier Proteins↗
PubMed1979

Microtubules, colchicine, and lymphocyte blastogenesis.

We have studied the time course of disassembly of microtubules of resting and stimulated mouse lymphocytes caused by the drug colchicine, as well as the effect of this compound on DNA and RNA synthesis of human and mouse lymphocytes. Fine-structure studies with the electron microscope showed a great increase in number of microtubules resulting from stimulation of mouse lymphocytes by the mitogenic lectin Con A. The presence of a network of microtubules was demonstrated in resting lymphocytes by use of the technique of immunofluorescence; this technique was not effective for the study of the microtubules of stimulated lymphocytes in the blast stage. The disappearance of microtubular networks in some cells (approximately 25%) was caused by the protocol of colchicine treatment used in many laboratories (30 min at 10(6) M); a 6- to 8-h treatment was required to cause all cells to lose their microtubules. It is indicated in these findings that there is need for extreme caution in implicating microtubule disruption as the cause of certain colchicine effects, such as that on the Con A-induced inhibition of receptor-ligand migration. The addition of colchicine to stimulated cells at varying times of culture caused marked inhibition of DNA synthesis provided that sufficient time (approximately 20 h for maximum inhibition) elapsed between addition of the drug to the stimulated culture and assay of DNA synthesis. Our data on the time course of inhibition of DNA synthesis by alpha-methyl mannoside (alpha MM) and by colchicine do not exclude the possibility that the latter compound may act partially by affecting the commitment of stimulated lymphocytes to DNA synthesis but they show that it can inhibit well after commitment is complete. The later the time of assay of thymidine incorporation, the more disparate were the curves relating the effects of alpha MM and colchicine to DNA synthesis of human cells. In the case of mouse splenic lymphocytes, there was no resemblance between the time course of the alpha MM and of the colchicine effects. Synthesis of RNA after 12 h of culture of stimulated human lymphocytes was also sensitive to colchicine.

Animals↗
PubMed1979

Detection of immune complexes by a new assay, the polyethylene glycol precipitation-complement consumption test (PEG-CC).

A new assay for the detection of circulating immune complexes, the polyethylene glycol precipitation-complement consumption assay (PEG-CC), is described. The test is both simple and sensitive, and exhibits a high degree of specificity. Immune complexes are first isolated from serum by precipitation in 2.5% polyethylene glycol (PEG) and concentrated. They are then assayed functionally by measuring their ability to fix complement using a sensitive kinetic assay for total haemolytic complement. The test can detect aggregated IgG in serum at concentrations around 6.0 micrograms/ml (about 2.0 micrograms absolute. Using DNA-anti-DNA and ovalbumin-anti-ovalbumin immune complexes prepared in vitro, antigen concentrations less than 0.5 micrograms/ml can be detected. Interference by endogenous complement, polyanions and other factors in test sera has been virtually eliminted by the design of the assay. The increased specificity of the PEG-CC test for immune complexes, should prove useful in the diagnosis and monitoring of immune complex-mediated diseases.

Animals↗