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Biomedical subjects

G Freeman

Publications and source records attributed to G Freeman.

At least 55 records · Page 3Linked to original sources
PubMed1989

Expression and regulation of CD5 on in vitro activated human B cells.

The T cell-associated antigen CD5 has been shown to play an important role in the regulation of T cell activation. Monoclonal antibodies directed against CD5 upregulate helper function, and induce interleukin 2 (IL2) production by mature T cells as well as thymocytes. CD5 is also expressed on subsets of B cells associated with autoantibody production, and CD5+ B cells are present in increased numbers in patients with rheumatoid arthritis and systemic lupus erythematosis. More recently CD5 has been found to be present on human B lymphocytes following in vitro activation with phorbol myristate acetate. To date a similar functional role for CD5 has not to date been demonstrated for B cells. In this study we have shown that structurally similar CD5 molecules are present on activated B cells and T cells. In addition, CD5 on both stimulated B cells and T cells is phosphorylated, which may be important in the function of CD5 following activation. CD5 protein or mRNA was not detected on unstimulated splenic B cells depleted of any CD5+ cells. To investigate the control of CD5 expression, we examined a series of cytokines either alone or in combination for their effect on the induction of CD5. CD5 expression was specifically inhibited by IL4 but not by the other cytokines tested. This inhibition was very specific as IL4 did not inhibit the expression of other B cell activation antigens including CD25, B5, T9 and CD23 as well as the pan-B cell antigen CD20. The addition of other cytokines did not increase or reverse the inhibition of CD5 expression by IL4. This inhibition was demonstrated by immunofluorescence and flow cytometric analysis. Immunoprecipitation studies of 125I-labeled activated B cells demonstrated that there was a decrease in cell surface CD5 protein, and not simply inhibition of expression of a particular epitope. Northern blot analysis demonstrated that the expression of CD5 mRNA was markedly inhibited in the presence of IL4, whereas the induction of the protooncogene c-myb was unaffected. This suggests that IL4 inhibits CD5 protein expression on activated B cells by reducing the amount of CD5 mRNA transcription or increasing the degradation of CD5 mRNA. The role of the T cell-derived lymphokine IL4 in regulating CD5 expression may be important in the disease states characterized by increased numbers of CD5+ B cells.

Antigens, Differentiation↗
PubMed1989

Cytosolic-free calcium and neurotransmitter release with decreased availability of glucose or oxygen.

Exposing brain slices to reduced oxygen tensions or impairing their ability to utilize oxygen with KCN decreases acetylcholine (ACh) but increases dopamine (DA) and glutamate in the medium at the end of a release incubation. To determine if these changes are due to alterations in the presynaptic terminals, release from isolated nerve endings (i.e. synaptosomes) was determined during histotoxic hypoxia (KCN). KCN reduced potassium-stimulated synaptosomal ACh release and increased dopamine and glutamate release. Since several lines of evidence suggest that altered calcium homeostasis underlies these changes in release, the effects of reducing medium calcium concentrations from 2.3 to 0.1-mM were determined. In low calcium medium, KCN still increased dopamine and glutamate release, but had no effect on ACh release. Hypoxia increased cytosolic-free calcium in both the normal and low calcium medium, although the elevation was less in the low calcium medium. Thus, the effects of histotoxic hypoxia on cytosolic free calcium concentration paralleled those on glutamate and dopamine release. Reducing the glucose concentration of the medium also increased cytosolic-free calcium. The data are consistent with the hypothesis that hypoxia and hypoglycemia increase cytosolic-free calcium, which stimulates the release of dopamine and glutamate, whose excessive release may lead to subsequent cellular damage postsynaptically.

Animals↗
PubMed1989

Studies of in vitro activated CD5+ B cells.

Human B lymphocytes undergo distinct phenotypic changes following activation with antigen and polyclonal mitogens. Increasing interest has focused on the unique subpopulation of B cells that expresses the CD5 antigen. In this study, we examined the signals that induce the expression of CD5 on normal splenic B cells. Only 12-O-tetradecanoylphorbol-13-acetate (TPA) induced CD5 expression on highly purified splenic B cells, whereas anti-immunoglobulin (anti-Ig), Epstein-Barr virus, anti-CD20, recombinant interleukin-1 (rIL-1), rIL-2, rIL-4, recombinant interferon-gamma (rINF-gamma), and B-cell growth factor all failed to induce CD5 expression. The expression of CD5 was detected on the cell surface by 48 hours and decreased by 96 hours. Dual-fluorochrome analysis demonstrated that the CD5+ B cells coexpressed the B-cell activation antigens B5, IL-2 receptor, and CD23, thereby providing phenotypic evidence that this B-cell subpopulation is activated. In vitro studies of dual-fluorochrome-sorted, TPA-stimulated splenic B cells demonstrated significantly greater tritiated thymidine incorporation and Ig secretion by the CD20+ CD5- cells than by the CD20+ CD5+ subset. These phenotypic and functional studies are consistent with the notion that TPA-induced CD5+ B cells are a subset of in vitro activated B lymphocytes.

Antigens, CD20↗
PubMed1988

Pre-exposure of human B cells to recombinant IL-1 enhances subsequent proliferation.

The reported effects of the monocyte-derived cytokine IL-1 on human B lymphocytes are both varied and controversial. IL-1 has been reported to augment both proliferation and Ig secretion of previously activated human B cells. In the present study highly purified splenic B cells were cultured with rIL-1 before, simultaneously with, and after the addition of the polyclonal B cell mitogen, anti-Ig. rIL-1 had no significant effect on B cell proliferation when added simultaneously with or after B cell activation with anti-Ig. However, incubation of splenic B cells with rIL-1 for 24 h before stimulation with anti-Ig appeared to enhance mitogenesis. With the observation that rIL-1 exerted effects on resting B cells, the effect of rIL-1 on several events which accompany B cell activation was examined. rIL-1 failed to stimulate RNA synthesis, effect increases in cell size or intracellular Ca2+ levels, or lead to the hyperexpression of MHC class II or B cell activation Ag. These studies suggest that rIL-1 does not activate B cells but primes them to respond to subsequent activation.

Antibodies, Anti-Idiotypic↗
PubMed1988

Interventions among primary-care practitioners to improve care for preventable complications of diabetes.

The National Diabetes Advisory Board recommends that diabetes prevention and control programs focus on the preventable complications of diabetes, i.e., visual impairment, lower-extremity problems, renal problems, ketoacidosis, and adverse outcomes of pregnancy. The Florida Diabetes Control Program chose to focus its efforts on the first three of these complications at the federal- and state-funded primary-care programs in Florida because these programs had access to targeted, public-sector patients and because of fiscal restraints that make the care provider the logical source of entry to the health-care system. This study sought to document the current level of care for complications of diabetes in primary-care settings, provide state-of-the-art professional education along with patient education, and evaluate changes in practice habits. Three intervention and three control primary-care centers were selected. Medical records in each center were reviewed over a 2-yr period. At intervention sites, retinopathy referrals increased from 9 to 43% (P less than .001), urinalyses increased from 69 to 94% (P less than .001), and examinations of lower extremities increased from 66 to 94% (P less than .001). There were no such changes in the control sites. Hypertension was diagnosed in nearly two-thirds of patients, and a last blood pressure of greater than 140 mmHg systolic or greater than 90 mmHg diastolic was present in 64% of the intervention group at yr 1 and declined to 56% at yr 2 (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1988

[The depression ward--a review of the current status].

New therapeutic concepts are usually developed and realised step by step. Over the past years changes occurred mainly in two ways. There is a trend to reduce the size of the psychiatric hospital as such and/or to section off certain areas by introducing specialised units. From the experience with the so called "Affective Disorder Units" or "Mood Clinics" developed the concept of a Depression Unit, first introduced in Europe for research purposes at the Psychiatric University Hospital in Basle in 1968. In Germany the first Depression Unit was established at the PLK Weissenau in 1976. Similar units followed over the years at the PLK Reichenau, Weinsberg, the BKH Günzburg, the Landesklinik Nordschwarzwald Hirsau/Calw and the Rheinische Landesklinik Bedburg-Hau, other hospitals are planning them. Existing units are described in terms of their structural organisation, staffing situation and the service they provide. The concept of the Depression Unit according to criteria laid down agreed upon in the literature is summed up, and emotional atmosphere, structural organisation, activation, and individual therapeutic measures, discussed. Advantages are mentioned such as better understanding of patients, allowing them to let go and be cared for, aimed regression, the effects of being taken along, improved communication, and a way of dealing with suicidal thoughts and depressive behavior that reduces anxiety. Disadvantages such as the danger of spoiling patients or inducing a sense of resignation both in patients and staff are discussed.

Depressive Disorder↗
PubMed1987

B7, a B-cell-restricted antigen that identifies preactivated B cells.

After activation with antigen or mitogen, a number of cell surface proteins appear that are not expressed on resting B cells. To date, a number of B lineage restricted and associated activation antigens have been reported that appear at distinct intervals after in vitro activation. In this report, we describe a new B lineage restricted activation antigen (B7) that appears within 24 hr of in vitro stimulation. The expression of B7 antigen, which is detected on a minor subpopulation of B cells isolated from peripheral blood and lymphoid tissues, is strongly induced following stimulation with either anti-immunoglobulin or Epstein-Barr virus. In contrast, B7 was not detected on resting or activated T cells or monocytes. The B7 antigen was expressed on a subset of B cell lines and B cell neoplasms, but was not detected on leukemias and lymphomas of T cell or myeloid origin. B7 was distinguished from other B cell restricted and associated activation antigens by its unique pattern of expression on a variety of hemopoietic cell lines. The biochemical characterization of B7, that it is a single chain protein of 60 kDa, further distinguishes it from other B cell activation antigens. The functional importance of the B7 antigen was demonstrated when splenic B cells were fractionated into the B7+ and B7- populations. The peak of proliferation in response to anti-Ig, appeared earlier within the B7+ population. These studies suggest that B7 antigen identifies a subpopulation of B cells that are preactivated or primed in vivo, and have an accelerated response to subsequent activation via cross-linking of surface Ig.

Animals↗
PubMed1987

The effects of concurrent vocalization on foot and hand motor performance: a test of the functional distance hypothesis.

The effects of concurrent vocalization on hand and foot motor performance were examined in two dual-task experiments as a test of the functional distance hypothesis. No interference effects were found with either hand or foot tapping under two difficulty levels of verbal activity. There was no evidence of differential or asymmetrical interference patterns despite the differential functional and anatomical distances of these motor centers from the speech centers. Consequently, the data provided no support for the functional distance hypothesis.

Adolescent↗
PubMed1986

Measles virus haemagglutinin gene: cloning, complete nucleotide sequence analysis and expression in COS cells.

A measles virus (Hallé strain) cDNA library was prepared by cloning virus-induced mRNA directly into the expression vector PCD. Clones corresponding to the measles virus haemagglutinin (HA) gene were isolated and one, PCD-HA-15, which corresponded to the complete mRNA sequence, was further characterized. After transfection into COS-7 cells, measles virus HA antigen was detected by immunofluorescence. The [35S]methionine-labelled HA protein from transfected cells was immunoprecipitated by both polyclonal and monoclonal measles virus antibodies. Analysis by SDS-polyacrylamide gel electrophoresis revealed that the PCD-HA-15 protein migrated in a manner identical to the virus-induced HA. Nucleotide sequence analysis established that the gene contained 1949 nucleotides [exclusive of poly(A)] and coded for a protein containing 617 amino acids. A single hydrophobic domain likely to represent the transmembrane region was identified at the N-terminus. A second overlapping reading frame coded for a protein containing 70 amino acids. This contained a short hydrophobic region (16 amino acids) and had two potential N-glycosylation sites. Comparison of the HA gene of the Hallé strain with the published sequence of the Edmonston strain showed that there was a high degree of conservation (99.3%).

Amino Acid Sequence↗
PubMed1985

Cloning of Ly-5 cDNA.

A notable feature of Ly-5, among immunogenetic systems that identify glycoproteins of the cell surface and define the surface phenotype of cells according to their lineage, is that the Ly-5 locus specifies a range of molecular isoforms that distinguish cells of different stages and branches of hematopoietic development. The composition of the Ly-5 locus is of much interest in regard to how these isoforms are constructed and differentially regulated according to cell lineage. We describe here a cDNA clone, pLy-5-68, that identifies Ly-5. The Ly-5 specificity of the pLy-5-68 clone was first indicated by a restriction fragment length polymorphism (RFLP), which in Southern blotting distinguishes genomic DNA of C57BL/6 (B6) mice (Ly-5a) from that of B6-Ly-5b congeneic mice whose genome is the same as B6 except for the segment of chromosome 1 that bears Ly-5b. For the following reasons it is unlikely that pLy-5-68 represents a gene linked to Ly-5 that was carried over with Ly-5b during serial backcrossing to make the B6-Ly-5b congeneic strain. In all mouse strains tested, the serological Ly-5 allotype (Ly-5.1 vs. Ly-5.2) accorded with the RFLP pattern. Cells of the ST/bJ mouse strain have unique Ly-5 serological reactions and ST/bJ DNA gives a unique (third) RFLP pattern (Ly-5c) with pLy-5-68. All Ly-5+ cell types reacted positively with pLy-5-68 in RNA transfer blotting, and all Ly-5- cell types tested did not. The difference in size of mRNA reactive with pLy-5-68 in cells expressing the 200-kDa Ly-5 isoform as compared with cells expressing the 220-kDa Ly-5 isoform corresponded with the difference in size of the protein components of those isoforms.

Amino Acid Sequence↗
PubMed1985

Biaxial mechanical properties of the pericardium in normal and volume overload dogs.

The two-dimensional mechanical properties of the pericardium from dogs with a normal or chronically enlarged heart were studied in vitro. A 3.0-cm-square piece of the pericardium overlying the right and/or left ventricle was excised. An approximately 1.0-cm-square target was marked at the center, and its dimension was measured electrooptically. When immersed in physiological saline at 37 degrees C, the specimen was stretched and unloaded sinusoidally in one direction while force in the transverse direction was held constant. The tension-stretch relationship was highly reproducible and was insensitive to strain rate in the range of 0.002-0.1 Hz. Hysteresis was present. The pericardium was mostly anisotropic; however, the direction of maximal compliance varied among dogs. The elastic properties of the pericardium overlying the left and right ventricles were the same in most cases. Substantial stress relaxation was observed; in contrast, insignificant creep developed over 30 min. In five dogs with chronic cardiac dilatation due to an infrarenal aortocaval shunt, the tension-stretch curves were shifted significantly to the right (i.e., greater deformation at the same tension level). However, the pericardial viscoelastic properties and thickness were unchanged. In other words, chronic cardiac dilatation resulted in a more compliant pericardium.

Animals↗
PubMed1985

The inhibition of bovine lens aldose reductase by Clinoril, its absorption into the human red cell and its effect on human red cell aldose reductase activity.

The protein aldose reductase has been implicated in cataract in diabetes and galactosaemia. Recently it has been suggested that a number of non-steroidal anti-inflammatory agents have inhibitory activity against aldose reductase activity, and therefore might be used to prevent diabetic complications including cataract. Steady state kinetic experiments show that Clinoril (Sulindac sulphoxide) acts as a non-competitive inhibitor of NADPH oxidation with purified bovine lens aldose reductase, with an action that may involve binding to more than one site on the protein. As a preliminary to studying the effect on human lens and cataract, a double-masked, placebo-controlled study using random allocation into parallel groups was conducted on 20 volunteers to determine the penetration of Clinoril (Sulindac) and its metabolites into normal human red cells, and the effect of the drug on red cell NADPH-oxidising activity. It was found that while Clinoril, the sulphoxide form of the drug, and its metabolites the sulphone and the sulphide could be detected in the appropriate plasma samples (up to 36 micrograms of the sulphone/ml of plasma), very little could be detected in the red cells. There was no significant effect on red cell NADPH-oxidising activity.

Absorption↗
PubMed1985

Priority given by doctors to continuity of care.

The attitude of 297 general practitioners in the Wessex region to continuity of care was assessed by postal questionnaire; there were 280 complete replies (94% response). One-third of the doctors were asked to define continuity of care; the remaining two-thirds were asked to rank six priorities of practice organization one of which concerned continuity of care. In addition, all doctors were asked whether they used a personal or combined list. A wide variety of definitions for continuity of care was offered but the majority of doctors (61%) specified care by one doctor. Personal continuity was rated highest by significantly more doctors in large practices (list size of 10 000 or more) than in small practices and doctors in large practices were also more likely to use personal lists.

Attitude to Health↗
PubMed1984

Ocular infection with orf virus.

Orf virus infection of the pericanthal eyelid skin and conjunctiva was diagnosed by electron microscopy. Orf is a paravaccinia virus responsible for contagious pustular dermatitis in sheep and goats. It occasionally affects humans. The patient was a farmwife who had recently handled lambs. She had a raised ulcerating lesion at the inner canthus, follicular conjunctivitis, and lymphadenopathy. Treatment with 35% idoxuridine in dimethylsulfoxide on the skin and 0.5% idoxuridine ointment on the conjunctiva led to resolution after three weeks.

Adult↗
PubMed1984

Exercise induced "Mobitz type II" second degree AV block in a patient with chronic bifascicular block (right bundle branch block and left anterior hemiblock).

A 55 year old healthy man with chronic bifascicular block (right bundle branch block and left anterior hemiblock) had a near syncopal episode. A treadmill test showed exercise induced Mobitz type II AV block manifested clinically by paradoxical slowing of the heart rate and decreased blood pressure. True His Purkinje block and pseudo AV block due to His extrasystoles were documented by an electrophysiological study.

Blood Pressure↗