Search PubMed⌕ Search

Biomedical subjects

G Brown

Publications and source records attributed to G Brown.

At least 361 records · Page 20Linked to original sources
PubMed1986

Control of human B-lymphocyte replication. I. Characterization of novel activation states that precede the entry of G0 B cells into cycle.

Tonsillar B lymphocytes of a particularly high buoyant density were prepared essentially free of contaminating monocytes and T cells. When exposed to anti-immunoglobulin, such cells initiated the hydrolysis of inositol phospholipids. This provides a postulated 'dual signal' for growth through the liberation of intracellular calcium stores and the activation of protein kinase C. Nevertheless, neither anti-immunoglobulin nor direct agonists of this bifurcating pathway (respectively, calcium ionophore and the phorbol ester TPA) were capable, when used alone, of driving cells out of G0 and into RNA synthesis. All three agents did, however, induce two activation antigens at the surface of G0 B cells, which included CD23, p45 and a lineage-unrestricted antigen identified by the monoclonal antibody BK.19.9. Cells that had been exposed to calcium ionophore, but not those activated with either TPA or anti-immunoglobulin, revealed further change indicated by an increased accessibility of their native DNA for the intercalating dye acridine orange. Cells receiving full mitogenic signals in the form of Staphylococcus aureus Cowan Strain I (SAC) or a combination of TPA and calcium ionophore showed the same initial sequelae but continued to enter the cell cycle and progress through to DNA synthesis. The observations identify two phases in the early activation of human B cells, both in terms of various temporal events, and the signals required to promote each activation state. before entering the proliferative cycle. Thus, the exit of human B cells from G0 appears subject to multiple controls that precede those associated with G1 and later phases of the cell cycle.

Antigens, Surface↗
PubMed1986

Control of human B-lymphocyte replication. II. Transforming Epstein-Barr virus exploits three distinct viral signals to undermine three separate control points in B-cell growth.

Highly purified resting (Go) B lymphocytes were monitored for their response to transforming Epstein-Barr virus (B95-8 strain), to a non-transforming mutant (P3HR-1) containing a deletion in the EBNA-2 coding region, and to inactivated virus of either type. All preparations induced an early appearance of two activation antigens, which included the CD23,p45 ("Blast-2') antigen. Thus, virus binding was sufficient for an initial activation step. Further change required an active viral genome. Infection with the P3HR-1 strain prompted the exit of cells out of Go but led to an arrest in the early G1 phase of the cycle. While initially showing sequels to activation indistinguishable from those observed with P3HR-1 virus, cells infected with B95-8 virus continued through G1 to express late activation antigens, enter S-phase and complete the replicative cycle. The addition of the phorbol ester TPA was found to compensate for the abortive cell cycle entry achieved with the P3HR-1 mutant, but could not supplement the minimal activation observed with inactivated virus. These findings demonstrate that the Epstein-Barr virus undermines three separate control points in the growth cycle of human B lymphocytes, and exploits three distinct viral signals to achieve this end.

Antigens, Viral↗
PubMed1985

Synergism between diacylglycerols and calcium ionophore in the induction of human B cell proliferation mimics the inositol lipid polyphosphate breakdown signals induced by crosslinking surface immunoglobulin.

Resting human tonsillar B cells were stimulated to divide by heat killed Staphylococcus aureus Cowan strain 1 which was shown to induce hydrolysis of phosphatidylinositol 4, 5-bisphosphate known to give rise to diacylglycerol and an increase in cytosolic free calcium. Addition of the diacylglycerols, 1-oleoyl-2 acetyl glycerol or sn-1, 2-dioctanoylglycerol, together with the calcium ionophore ionomycin to B cell cultures induced marked cell proliferation whereas these agents were ineffective when used alone. Both diacylglycerols were shown to compete with [3H] phorbol 12,13 dibutyrate in binding to protein kinase C. These data support the hypothesis that synergism between cytosolic calcium and endogenous diacylglycerol, which activates protein kinase C, is involved in signal transduction in the proliferation of human B cells.

B-Lymphocytes↗
PubMed1985

Topic analysis: an objective measure of the consultation and its application to computer assisted consultations.

A simple method has been developed to classify the verbal interaction during medical consultations in terms of the relative proportions of medical and social content and the initiator of conversational topics discussed. The method has been applied to video tape recordings of three doctors' consultations with and without a computer present to classify and compare the items discussed. Actual computer use has been shown to have a medical effect on the consultations (p less than 0.05) and to increase the proportion of topics initiated by the doctor (p less than 0.001). Although this was largely accounted for by the massive increase in doctor initiated medical items resulting directly from computer use, there was evidence that, for two of the doctors, these topics were replacing some of the normal social and patient initiated medical exchanges.

Diagnosis, Computer-Assisted↗
PubMed1985

Computer assisted screening: effect on the patient and his consultation.

The initial impact of computer assisted preventive screening in general practice consultations has been monitored. The technology has not been found stressful by patients, and the power of the consultation to alleviate low arousal has been increased by computer use. No appreciable increase in the durations of consultation was detected, despite an average computer initiated input of two minutes eight seconds. The computer has successfully prompted preventive screening and health education with a sixfold increase in the number of potentially relevant procedures being mentioned. The actual information presented by the computer has been shown to be crucial, with the terminal's mere presence an ineffective reminder. The computer terminal was used in 65% of the consultations for which it was available, which, if sustained, represents an effective screening programme for attending patients.

Arousal↗
PubMed1985

Reprioritization of hepatic plasma protein release in trauma and sepsis.

We studied the temporal pattern of seven hepatic synthesized plasma proteins in 26 severely injured patients beginning in the immediate posttrauma period. Clinical sepsis developed in ten patients between three and eight days after injury, and 16 patients had nonseptic courses. In the initial five days after injury, except for albumin, all acute-phase protein levels rose. However, if sepsis developed, C-reactive protein, fibrinogen, ceruloplasmin, and alpha 1-antitrypsin levels continued to be elevated after the initial five posttrauma days, while transferrin, albumin, and alpha 2-macroglobulin levels fell. This differential response became more extreme as sepsis progressed. Covariance analysis of the regression of the five true acute-phase hepatic proteins on C-reactive protein showed that, when sepsis occurred after major traumatic injury, the C-reactive protein rise was associated with a significant reprioritization of hepatic acute-phase plasma protein release. This reprioritization response seems to be both a predictor of sepsis as well as a measure of the adequacy of the host response to trauma and sepsis.

Acute-Phase Proteins↗
PubMed1985

Severe illness caused by the products of bacterial metabolism in a child with a short gut.

An 8-year-old boy with a short gut had six episodes of metabolic acidosis and neurological dysfunction over a 1 month period. The neurological features consisted of a depressed conscious state, confusion, aggressive behaviour, slurred speech and ataxia. The organic acid profile of urine demonstrated increased amounts of lactic, 3-hydroxypropionic, 3-hydroxyisobutyric, 2-hydroxyisocaproic, phenyllactic, 4-hydroxyphenylacetic and 4-hydroxyphenyllactic acids. Of the lactic acid 99% was D-lactic acid. The anaerobic gut flora consisted almost entirely of Lactobacilli in unusually large numbers. A course of vancomycin prevented further episodes. A urinary organic acid profile may be diagnostic when a person with a short gut develops metabolic acidosis or an unusual encephalopathy and bacterial metabolites should be considered in other patients with unusual combinations of organic acids in the urine.

Acidosis↗
PubMed1985

Environmental deprivation and transient elevation of sweat electrolytes.

We report five children who had transient elevations in sweat electrolyte values in association with environmental deprivation. The high electrolyte values were not always associated with malnutrition, and normalized more rapidly than weight. The reason for these abnormalities is unknown. In as much as elevated sweat electrolytes are rarely associated with environmental deprivation, repeat studies are recommended before diagnosing cystic fibrosis in such children.

Child, Preschool↗
PubMed1985

Serum-mediated depression of neutrophil chemiluminescence following blunt trauma.

To investigate one possible mechanism responsible for decreased neutrophil bactericidal activity following trauma, the chemiluminescence response of normal neutrophils was measured following incubation in nonseptic and septic serum from 19 blunt trauma patients. Incubation of normal neutrophils in septic patients' sera (61 studies) resulted in a marked decrease in the chemiluminescence response (36 +/- 26% of control), compared to incubation in nonseptic sera (92 studies, 80 +/- 53% of control; p less than 0.005). This difference between nonseptic and septic serum was apparent immediately after injury, prior to the development of sepsis (47 +/- 4% versus 77 +/- 12%; p less than 0.05). The depression of the CL response was due to a suppressive factor present in septic patients' sera. This factor was nondialyzable and was present in high performance liquid chromatography (HPLC) fractions containing protein of molecular weight 50 to 100,000. Removal of albumin using Affigel-blue did not remove the suppressive factor. In contrast to the suppressive effect of septic trauma serum, septic patients' neutrophils had a normal chemiluminescence response after their isolation and washing. We conclude that trauma results in the generation of a serum factor that suppresses neutrophil chemiluminescence and that is present in greater amounts in patients who eventually become septic. This factor may be responsible for the decreased bactericidal activity and depressed host defense following injury.

Adult↗
PubMed1985

A combination of calcium ionophore and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) stimulates the growth of purified resting B cells.

In this study we investigated whether the calcium ionophores A23187 and ionomycin can act synergistically with the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) to stimulate the growth of resting B lymphocytes purified from human tonsil cells. Ionomycin, A23187, and TPA added separately to cultures at doses of 0.4-1.6 micrograms/ml, 0.2-0.8 micrograms/ml, and 0.05-0.25 ng/ml respectively, did not induce DNA synthesis in resting B lymphocytes. In contrast, calcium ionophores at concentrations of 0.4-1.6 micrograms/ml ionomycin and 0.2-0.8 micrograms/ml A23187, in the presence of 0.05-4 ng/ml TPA, induced marked DNA synthesis and B-cell proliferation, as shown by analyses of incorporation of [3H]thymidine, growth kinetics, and the percentage of cells in the S and G2 + M phases of the cell cycle. These results show that the synergistic effects of calcium ionophores and TPA can bypass the requirement for antigen and exogenous growth factors in B-cell activation. These observations are similar to those obtained from studies of T lymphocytes by other workers.

B-Lymphocytes↗
PubMed1985

Effect of neuraminidase on the expression of the 3-fucosyl-N-acetyllactosamine antigen in human tissues.

The monoclonal antibody AGF4.48 detects the 3-fucosyl-N-acetyllactosamine carbohydrate structure and reacts with a variety of human tissues, as shown by an immunoperoxidase method on paraffin sections of formalin fixed material. The intensity and distribution of the immunoperoxidase reactivity were affected by treatment of sections with neuraminidase. In some sites, such as bone marrow, brain, breast, and pituitary, the reaction was more intense after neuraminidase treatment. In several organs, including kidney, oesophagus, pancreas, submandibular gland, and uterus, the reaction was more widespread after neuraminidase treatment. Other organs, such as liver, lung, lymph node, skin, and uterine tube, showed an altered distribution of reactivity with AGF4.48 after sections were treated with neuraminidase. These results show that the 3-fucosyl-N-acetyllactosamine antigen is cryptic in many tissues. The antigen is masked to a variable extent in different tissues by neuraminic acid residues and can be revealed by the simple procedure of pretreating sections with neuraminidase. The value of using AGF4.48 antibody in combination with the enzyme neuraminidase to show accessible and cryptic antigen is that this reveals distinctive patterns of sialylation within various normal tissues. Whether similar patterns occur in disease will be of particular interest.

Antibodies, Monoclonal↗
PubMed1985

A monoclonal antibody identifies a 215 000-dalton nuclear envelope protein restricted to certain cell types.

The monoclonal antibody, AGF2.3, was isolated from mice immunised with the human promyeloid cell line HL60. By immunofluorescence and immunoelectron microscopy the antibody was shown to bind to the nuclear envelope in uninduced HL60 cells. Immunofluorescent staining was reduced to very low levels in HL60 cells induced to mature to monocytes or neutrophils by addition of 12-0-tetradecanoylphorbol-13-acetate or dimethyl sulfoxide respectively. Blood neutrophils did not express the antigen. Weak immunofluorescent staining of cell nuclei was observed in peripheral blood lymphocytes and in sections of normal human kidney, tonsil and skin epithelium. The AGF2.3 antigen was strongly expressed on the nuclei of 21/21 haemopoietic cell lines and 21/25 permanent non-haemopoietic cell lines representing various cell types. In contrast, the antigen was not expressed by any of six primary (untransformed) cell cultures. These included fibroblasts, endothelial cells and keratinocytes. The antigen was expressed in the Q10 SV-40 transformed cell line derived from a non-expressing primary fibroblast culture. AGF2.3 antibody precipitated a protein with an apparent subunit molecular weight of approximately 215 kDa from Triton X-100 extracts of HL60 and HeLa cells labelled with 35S-methionine. This protein was not detectable in extracts of primary skin fibroblasts prepared in parallel. We conclude that AGF2.3 antibody recognises a previously undescribed protein associated with the nuclear envelope which is expressed at high levels in most transformed cell lines but which is weakly expressed or absent in normal tissues and primary cell cultures.

Animals↗