Search PubMed⌕ Search

Biomedical subjects

D L Brown

Publications and source records attributed to D L Brown.

At least 307 records · Page 17Linked to original sources
PubMed1984

Changes in distribution of nuclear matrix antigens during the mitotic cell cycle.

We examined the distribution of nonlamin nuclear matrix antigens during the mitotic cell cycle in mouse 3T3 fibroblasts. Four monoclonal antibodies produced against isolated nuclear matrices were used to characterize antigens by the immunoblotting of isolated nuclear matrix preparations, and were used to localize the antigens by indirect immunofluorescence. For comparison, lamins and histones were localized using human autoimmune antibodies. At interphase, the monoclonal antibodies recognized non-nucleolar and nonheterochromatin nuclear components. Antibody P1 stained the nuclear periphery homogeneously, with some small invaginations toward the interior of the nucleus. Antibody I1 detected an antigen distributed as fine granules throughout the nuclear interior. Monoclonals PI1 and PI2 stained both the nuclear periphery and interior, with some characteristic differences. During mitosis, P1 and I1 were chromosome-associated, whereas PI1 and PI2 dispersed in the cytoplasm. Antibody P1 heavily stained the periphery of the chromosome mass, and we suggest that the antigen may play a role in maintaining interphase and mitotic chromosome order. With antibody I1, bright granules were distributed along the chromosomes and there was also some diffuse internal staining. The antigen to I1 may be involved in chromatin/chromosome higher-order organization throughout the cell cycle. Antibodies PI1 and PI2 were redistributed independently during prophase, and dispersed into the cytoplasm during prometaphase. Antibody PI2 also detected antigen associated with the spindle poles.

Animals↗
PubMed1984

Methylmethacrylate and atrioventricular conduction in dogs.

The effect of intravenous methylmethacrylate (MMA) on atrioventricular conduction times was studied in dogs, utilizing His-bundle electrograms. Dogs were anesthetized with halothane or enflurane; then MMA in a dose causing minimal to profound hemodynamic changes was administered and His-bundle electrograms, and arterial, pulmonary artery, and central venous pressures were recorded. This experimental model did not demonstrate a prolongation of atrioventricular conduction intervals which could be implicated as etiologic in MMA-induced dysrhythmias.

Anesthesia, Inhalation↗
PubMed1984

Changes in organization and microtubule assembly activity of the centrosome during lymphocyte stimulation.

Changes in the organization of centrosomes in mouse splenic T lymphocytes stimulated by concanavalin A (con A) were examined by electron microscopy of serial sections. In both resting and stimulated lymphocytes the single centrosome consists of a pair of centrioles, satellite bodies, and pericentriolar material. In resting cell centrosomes the satellite bodies are preferentially associated with, and appear to be attached by short stalks to, one of the centrioles. The satellite bodies are the primary sites of microtubule termination in the resting cell centrosome. During stimulation by con A there is a several-fold increase in microtubule content. This is correlated with an overall increase in centrosome size, an apparent increase in the size and in the number of satellite bodies, and a redistribution of satellite bodies to occupy a position between the two centrioles. Increased numbers of microtubules are detected terminating on the satellite bodies and in the pericentriolar material of the stimulated cell centrosome. Microtubule assembly from centrosomes in vitro was assessed by electron microscopy using detergent-permeabilized lymphocytes that had been pretreated to remove endogenous microtubules and supplied with purified bovine brain tubulin. These studies indicate that satellite bodies are major sites of microtubule assembly in both resting and stimulated cell centrosomes and show that the centrosomes of stimulated cells assemble more microtubules in vitro than resting cell centrosomes. This parallels the increase in microtubule content in intact lymphocytes stimulated by con A and suggests that the changes in centrosome organization and microtubule assembly capacity that occur during stimulation are causally related.

Animals↗
PubMed1984

Cardiovascular neurons of brain stem with projections to spinal cord.

In urethan-anesthetized rats a portion of the rostral ventrolateral medulla, the intermediate portion of the nucleus paragigantocellularis lateralis, was explored electrophysiologically for spinally projecting cardiovascular neurons. Spinal projections were demonstrated for 48 of 300 units tested for antidromic activation following spinal cord stimulation. The cardiovascular nature of units was tested by monitoring unit activity during transient changes in arterial pressure. A total of 47 cardiovascular neurons were identified; of these, 43 showed activities inversely correlated with arterial pressure and changes in activity closely coupled in time to arterial pressure changes. At high arterial pressures these neurons also displayed activities phasically linked to the cardiac cycle. Of these 43 neurons, 13 projected to or through the thoracic cord and 5 to or through the cervical cord. Axonal conduction velocities averaged 4.7 m/s. A second type of cardiovascular neuron (4 units of 47) was found that increased activity as arterial pressure increased. Three of these neurons projected to the cord. These results provide evidence for tonically active, baroreceptor-inhibited neurons with axonal projections to the thoracic spinal cord.

Animals↗
PubMed1984

Anti-heart antibodies in cardiac allograft recipients.

Serum antibodies reactive with rat cardiac and skeletal muscle were found by indirect immunofluorescence in 11 of 16 heart transplant patients receiving heterologous antithymocyte globulin and 1 of 5 patients receiving cyclosporin A. These antibodies appeared de novo following transplantation and were present for variable lengths of time. Antibodies reactive with rat liver, stomach and kidney were also found in several patients, 9 out of 16 patients receiving equine globulin had antibodies directed against components of the microvasculature, including endothelial, smooth muscle and vessel wall connective tissue. Analysis of antibody kinetics and acute cardiac rejection did not reveal any well-defined associations, though anti-heart antibodies were present in 4 of 6 patients who died from acute rejection.

Acute Disease↗
PubMed1983

Increases in microtubule assembly and in tubulin content in mitogenically stimulated mouse splenic T lymphocytes.

We have examined the changes in the microtubule and tubulin contents in populations of mouse splenic T lymphocytes stimulated by the mitogen concanavalin A. Indirect immunofluorescence staining with antiserum to tubulin indicated that a more extensive microtubule network was assembled from the centrosome in those cells which had increased in size in response to the mitogen. Direct counts of microtubules from electron micrographs of the centrosome regions of cells showed approximately a 2-fold increase in microtubule number in 48 h stimulated populations and up to a 5-fold increase in the large, fully stimulated, blast cells. Determinations of tubulin and actin contents were made by the measurement of peptides specific to those proteins. As a percentage of total cell protein both of these cytoskeletal proteins increased during the first 24 h of stimulation. Tubulin increased 50% by 24 h and remained high in populations stimulated for 48 h. The tubulin content per cell increased 2.5-fold, from 0.20 to 0.51 microgram/10(6) cells, in the 48 h stimulated population. An increase in tubulin content was also seen following the stimulation of nude mouse B lymphocyte populations and of total splenic lymphocyte populations. Our results show that during lymphocyte stimulation there is a large increase in the numbers of microtubules assembled which is correlated with, and appears dependent on, a similar large increase in the cellular tubulin content.

Actins↗
PubMed1983

Serial analysis of circulating immune complexes, complement, and antithymocyte globulin antibodies in heart transplant recipients.

Thirteen heart transplant patients receiving heterologous antithymocyte globulin were examined serially for the presence of circulating immune complexes, activation of complement, and antibodies to antithymocyte globulin. Using three independent assays, all patients were found to develop immune complexes at some time following transplantation, mostly as a consequence of antithymocyte globulin administration and infection. Simultaneous analysis of endogenous complement levels revealed C3 and C4 hypocomplementaemia in 28 and 44% of the samples, respectively. However, no correlation was evident between immune complex or complement levels and cardiac rejection assessed histologically in 64 endomyocardial biopsies. Serial analysis of antibodies to equine and rabbit antithymocyte globulin by solid-phase radioimmunoassay showed that 8 of 10 patients had significantly elevated values. Evidence was also obtained which indicated a substantial degree of cross-reactivity between the antibodies to these heterologous proteins. The results demonstrate a complex interplay of immune reactants relating to transplantation, infection, and immunosuppression therapy.

Adult↗
PubMed1983

Respiratory complications of achondroplasia.

Nine patients with achondroplasia who were seen over a three-year period developed significant respiratory complications. Eight had sleep-disordered breathing, including obstructive sleep apnea in five, for which two required tracheostomy. Of the seven patients with significant hypoxemia, five had clinical evidence of cor pulmonale and recurrent pulmonary infiltrates. Two patients died, one with autopsy findings of compression of the medulla at the level of the foramen magnum and one with respiratory and cardiac failure. Appropriate therapy for our patients depended on recognition of the mechanisms that led to the respiratory complications, including (1) chest deformity, (2) upper airway obstruction and sleep-disordered breathing, (3) neurologic complications, and (4) coincidental chronic pulmonary conditions such as asthma.

Achondroplasia↗
PubMed1983

Nuclear bodies in mouse splenic lymphocytes: II - Cytochemistry and autoradiography during stimulation by concanavalin A.

Nuclear bodies (NB) are poorly understood nucleoplasmic structures frequently observed in many animal cell types. Murine lymphocytes mitogenically stimulated with concanavalin A contain 5 types of NB. In order to examine the origin and function of the NB we have carried out cell fractionation and have performed cytochemistry, immunocytochemistry and autoradiography at the electron microscope level. Regressive staining for RNP showed that simple NB (types I and II) and the shells of complex NB (types III, IVa and V) consist of a non-chromatinic fibrillar material which is most likely proteinaceous. Projections of this material from the NB surface appear to link the NB to nucleoplasmic fibrogranular elements. The fibrillar, filamentous and granular components of the cores of complex NB were largely RNP and in some instances closely resembled fibrogranular areas in the nucleoplasm. Chromatin masses were seen occasionally in the cores. All NB types remained unstained after nucleolus-specific silver nitrate staining, and were also not stained by a centromere-specific antibody. Autoradiography was performed along long-term labelling with 3H-uridine, 3H-thymidine or 3H-leucine. The NB were not labelled by any of the precursors, indicating that macromolecular synthesis does not play a major role in NB evolution in these cells. By fractionation, we showed that NB co-isolated with the nuclear matrix, and were linked to the fibrogranular nuclear matrix component by projections from the surface of the NB. A possible role of NB in RNA processing is discussed.

Animals↗
PubMed1983

Terminal phalangeal sclerosis in sickle cell disease.

Hand films of 100 patients with sickle cell disease were analyzed in order to establish the type, distribution, and incidence of terminal phalangeal sclerosis. Fifty hand films from patients with no known sickle cell disease matched for age and race were also studied. Twenty-four of 100 patients with sickle cell disease, with 14 less than 20 years old, showed clear evidence of terminal phalangeal sclerosis, while only 10% of the controls were positive. The incidence was significantly different from the control group (chi 2 = 4.1949, d.f. = 1, p less than 0.05) suggesting that terminal phalangeal sclerosis is a significant finding in a young patient with sickle cell disease.

Adolescent↗
PubMed1983

Acute responses to blunt head trauma. Experimental model and gross pathology.

This study of blunt craniocerebral trauma describes an experimental model that involves delivery of forceful blows to the resting movable skulls of anesthetized cats. Injuries inflicted by this method included skull fractures in 81% of cases, epidural hemorrhages in 50%, subdural hemorrhages in 80%, subarachnoid hemorrhages in 100%, and brain contusions in 84%. In the majority of instances the subdural and epidural hemorrhages were thin films of blood that did not compress or distort the subjacent brain. The distribution of cerebral contusions was restricted to the cerebral parenchyma beneath the locus of cranial impact except for contusions associated with skull fractures. This experimental model recapitulates clinically realistic human cranial trauma and produces pathological lesions suitable for investigation of the pathophysiology of blunt head trauma.

Animals↗
PubMed1983

Guidelines can resolve turf battles between local and corporate boards.

The relationship of a local board that is a member of a multihospital system with the corporate board of the system is a confusing one for trustees. This article provides a model for the distribution of power between corporate and local boards of hospitals that are owned or leased by a multihospital corporation.

Community-Institutional Relations↗