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Biomedical subjects

M A Jensen

Publications and source records attributed to M A Jensen.

At least 37 records · Page 2Linked to original sources
PubMed1993

Interferon beta decreases T cell activation and interferon gamma production in multiple sclerosis.

Interferons (IFN) are biological molecules with anti-viral, anti-proliferative and immunomodulatory actions. There is evidence that IFN-gamma increases the frequency of exacerbations of multiple sclerosis (MS) whereas IFN-beta may reduce their frequency. Here we present evidence that IFN-beta significantly decreases concanavalin A (Con A)-induced proliferation of peripheral blood mononuclear cells (PBMC) of MS patients and healthy individuals. Similar results were obtained when PBMC were activated through the T cell receptor (TcR) by anti-CD3 monoclonal antibody or independently of it by phorbol ester and Ca2+ ionophore. These effects of IFN-beta were also noted when IFN-gamma and IFN-beta were added together. Furthermore, IFN-beta decreased proliferation when added to cells that were already pre-activated. Activated CD4+ and CD8+ T cells were downregulated to approximately the same extent. Analysis of cytokine production showed that IFN-gamma production by Con A activated PBMC was increased in MS when compared to controls. IFN-beta significantly decreased IFN-gamma production in MS patients and control individuals. Con A activated cultures treated with IFN-beta showed decreased IL2R expression and accumulation of IL2. These results show that IFN-beta decreases T cell activation and IFN-gamma production in vitro, effects that may be beneficial in MS.

Adult↗
PubMed1993

Astrocyte cytolysis by MHC class II-specific mouse T cell clones.

The brain is "immunologically privileged," in part because class I and II MHC antigens are not normally present on glia or neurons. However, under certain conditions such as transplantation, glial cells express MHC proteins at levels sufficient for glia to become targets of immune responses. Cultured astrocytes expressing very low levels of MHC class I protein are killed efficiently by MHC class I antigen-specific CTL. Mouse brain allografts, however, are rejected by CD4+ T cells that are likely to be class II MHC-specific. The level of expression of MHC class II antigen needed to trigger specific killing of astrocytes by CD4+ T cells, independent of exogenous antigen, has not been studied. We examined the role of glial class II MHC in the lysis of cultured neonatal mouse astrocytes by an alloreactive murine CD4+ CTL alone. IFN-gamma induced functionally relevant increases in MHC class II antigen on target cells. Astrocytes were lysed by the CD4+ clone only when class II MHC antigens reached levels readily detectable by flow cytometry. MHC class II expression and lysis increased when astrocytes were coincubated with IFN-gamma and TNF-alpha. Conversely, lysis decreased when class II expression was downregulated by IFN-alpha/beta or dbcAMP. Cytolysis by CD4+ clones was blocked by antibodies to CD4 and LFA-1 on T cells, and to ICAM-1 and class II molecules on astrocytes. The role of LFA-1 in CD4+ cell-mediated lysis was greater than that of LFA-1/ICAM-1 in CD8+ T cell-mediated lysis. CD4+ cells may lyse activated astrocytes when the immune privilege of the brain is compromised as in transplantation, tumors, and inflammatory diseases.

Animals↗
PubMed1993

Effect of PCR conditions on the formation of heteroduplex and single-stranded DNA products in the amplification of bacterial ribosomal DNA spacer regions.

PCR amplifications of 16S/23S rDNA spacer regions were carried out from conserved 16S and 23S sequences for genomic DNA samples from strains representing 16 bacterial species (12 genera). Multiple products were produced containing conserved homologous sequences at the 3' and 5' ends, separated by highly variable internal spacer sequences. These products cross-hybridized forming heteroduplex DNA structures containing double-stranded ends surrounding an internal single-stranded loop. Single-stranded DNA was also produced in the amplification of rDNA spacer sequences. Fragments comprising the nonhomoduplex DNA components were identified by their susceptibility to removal by digestion with a single-stranded endonuclease. The relative formation of heteroduplex and single-stranded DNA was reduced by reaction conditions favoring primer/template annealing, for example, higher ionic strength, higher primer concentration, and lower annealing temperature, as well as by decreasing the number of amplification cycles. Heteroduplex and single-stranded DNA structures were also generated by denaturing and reannealing spacer amplification products in the absence of polymerase activity. Whereas heteroduplex and single-stranded DNA structures provide additional information that is helpful in distinguishing between species of bacteria that produce similar homoduplex products, the mobility of heteroduplex and single-stranded DNA structures DNA structures is extremely sensitive to electrophoretic conditions.

Base Sequence↗
PubMed1993

Rapid identification of bacteria on the basis of polymerase chain reaction-amplified ribosomal DNA spacer polymorphisms.

To facilitate genus and species level identification of a broad range of bacteria without the requirement of presumptive identification, we have developed a unified set of primers and polymerase chain reaction conditions to amplify spacer regions between the 16S and 23S genes in the prokaryotic rRNA genetic loci. Spacer regions within these loci show a significant level of length and sequence polymorphism across both genus and species lines. A generic pair of priming sequences was selected for the amplification of these polymorphisms from highly conserved sequences in the 16S and 23S genes occurring adjacent to these polymorphic regions. This single set of primers and reaction conditions was used for the amplification of 16S-23S spacer regions for over 300 strains of bacteria belonging to eight genera and 28 species or serotypes, including Listeria, Staphylococcus, and Salmonella species and additional species related to these pathogenic organisms. When the spacer amplification products were resolved by electrophoresis, the resulting patterns could be used to distinguish all of the species of bacteria within the test group. Unique elements in the amplification product patterns generally clustered at the species level, although some genus-specific characteristics were also observed. On the basis of the results obtained with our test group of 300 bacterial strains, amplification of the 16S-23S ribosomal spacer region is a suitable process for generating a data base for use in a polymerase chain reaction-based identification method, which can be comprehensively applied to the bacterial kingdom.

Base Sequence↗
PubMed1992

Contrasting effects of alpha, beta, and gamma interferons on nonspecific suppressor function in multiple sclerosis.

Interferons are biological molecules with antiviral, antiproliferative, and immunomodulatory actions. Interferon alpha (IFN-alpha) and -beta are potentially useful in the treatment of multiple sclerosis (MS). IFN-gamma, in contrast, increases the frequency of exacerbations of MS. In this study, we compared the effect of recombinant human IFN-alpha, -beta, and -gamma on suppressor function in patients with MS. Nonspecific suppressor cell function, measured in a concanavalin A suppressor assay, was significantly decreased in 16 patients with progressive MS (mean percent suppression +/- SEM, 14.4 +/- 5.5 in patients with MS, 33.5 +/- 4.8 in 16 normal subjects; p less than 0.001). Recombinant human IFN-beta augmented suppressor function in MS to 45.4 +/- 5.1% (p less than 0.001) and in control subjects to 56.8 +/- 3.8% (p less than 0.001). Similarly, recombinant human IFN-alpha improved suppression in MS to 43.0 +/- 5.6% (p less than 0.001) and in control subjects to 51.1 +/- 5.9% (p less than 0.001). In contrast, recombinant human IFN-gamma had no effect on suppressor function in patients with MS and in control subjects. This study shows that IFN-alpha and -beta augment deficient suppressor function in MS, whereas IFN-gamma has no effect on suppressor function in the progressive phase of the disease.

Adult↗
PubMed1992

Preferential increase of IL-2R+ CD4+ T cells and CD45RB- CD4+ T cells in the central nervous system in experimental allergic encephalomyelitis.

We examined lymphocytes isolated from the spinal cord (SC), peripheral blood (PB) and lymph nodes (LN) draining the immunization site of Lewis rats with acute experimental allergic encephalomyelitis (EAE). Cells were analysed for T cell subset markers CD4 (mAb W3/25) and CD8 (mAb OX8), for IL-2R (mAb OX39), and for high molecular mass leukocyte common antigen (LCA, CD45RB) expression (mAb OX22). T cells expressing high (CD45RB+) or low (CD45RB-) molecular mass LCA are of different maturational stages and/or separate lineages. CD4+ T cells were more predominant in SC than in PB and LN; CD8+ T cells were scarce in SC but common in PB and LN. Activated CD4+ T cells (IL-2R+) were common in the SC and LN but infrequent in blood. CD4+ T cells that were CD45RB+ were scarce in the SC. In contrast, the majority of CD4+ T cells in the PB and LN were CD45RB+. The preferential accumulation of IL-2R+ CD4+ T cells and of CD45RB- CD4+ T cells in the central nervous system (CNS) indicates that a selective mechanism directs cell egress into CNS lesions in EAE.

Animals↗
PubMed1991

Improvements in the chain-termination method of DNA sequencing through the use of 7-deaza-2'-deoxyadenosine.

Significant improvements in the quality of DNA sequencing data have been shown when deoxyadenosine triphosphate (dATP) is replaced by 7-deaza-2'-deoxyadenosine triphosphate (c7dATP). The use of c7dATP in conjunction with 7-deaza-2'-deoxyguanosine triphosphate (c7dGTP) further decreases anomalies in electrophoretic mobility which are caused by compressions involving G and/or A residues. This effect is observed for both isotope-based and fluorescence-based sequencing approaches. Replacing dATP with c7dATP also results in a higher degree of uniformity in the frequency of chain termination reactions, when such terminations involve the incorporation of fluorescence-labeled dideoxynucleotides by T7 polymerase. These improvements in the gel-resolution and distribution of chain-terminated DNA products result in higher accuracy in both manual and automated base assignment.

Adenosine Triphosphate↗
PubMed1990

Interferon beta augments suppressor cell function in multiple sclerosis.

Suppressor cell function has been previously reported to be decreased in patients with progressive multiple sclerosis (MS). The abnormality could not be corrected in vitro and was present even after patients were treated with immunosuppressive agents. We now report that interferon beta augments suppressor cell function in vitro in progressive MS. Nonspecific suppressor cell function as measured in a concanavalin A (Con A) suppressor assay was reduced in 24 MS patients (mean percent suppression, 19.6 +/- 2.2) when compared to 19 normal subjects (mean percent suppression, 35.0 +/- 3.3). The data are highly significant (p less than 0.001). When recombinant human interferon beta (10(3) units/ml) was added to lymphocyte cultures with Con A, suppressor activity improved significantly. The mean percent suppression improved from 19.6 +/- 2.2 to 37.8 +/- 2.6 in MS (p less than 0.001) and from 35.0 +/- 3.3 to 46.2 +/- 3.5 (p less than 0.025) in control subjects. This study shows that recombinant interferon beta improves suppressor function in humans, an effect that is particularly significant in progressive MS.

Adult↗
PubMed1987

A system for rapid DNA sequencing with fluorescent chain-terminating dideoxynucleotides.

A DNA sequencing system based on the use of a novel set of four chain-terminating dideoxynucleotides, each carrying a different chemically tuned succinylfluorescein dye distinguished by its fluorescent emission is described. Avian myeloblastosis virus reverse transcriptase is used in a modified dideoxy DNA sequencing protocol to produce a complete set of fluorescence-tagged fragments in one reaction mixture. These DNA fragments are resolved by polyacrylamide gel electrophoresis in one sequencing lane and are identified by a fluorescence detection system specifically matched to the emission characteristics of this dye set. A scanning system allows multiple samples to be run simultaneously and computer-based automatic base sequence identifications to be made. The sequence analysis of M13 phage DNA made with this system is described.

Automation↗
PubMed1987

Psychotropic drug use with successful and unsuccessful community placed developmentally disabled groups.

While psychotropic drug use data have been reported for public residential facilities (PRF) and community residential facilities (CRF), no data have been reported for individuals discharged from PRFs and CRFs, especially with respect to how such usage relates to successful and unsuccessful placement. This study reports psychotropic drug use at the time of PRF discharge, at CRFs for successful placements, upon PRF readmission for unsuccessful placements, and factors related to successful and unsuccessful CRF placements.

Adult↗
PubMed1986

The AHEC library program and consortia development in California.

A brief history of the first Area Health Education Center (AHEC) Library Program in California is presented, with a description of methodology and results. The goals of this program were to develop and improve hospital library resources and services, to train hospital library personnel, and to promote resource sharing in a medically underserved area. The health sciences library consortium that evolved became a model for the ten other library consortia in the state. Based on AHEC's twelve years' experience with consortia, from 1973 to 1985, recommendations are made as to size, composition, leadership, outside funding, group participation, publicity, and linkages.

Area Health Education Centers↗
PubMed1984

Nicotinamide adenine dinucleotide (NAD+). Formal potential of the NA+/NAD couple and NAD dimerization rate.

The rate constant, kd, for the dimerization of the free radical (NAD), produced on the initial one-electron reduction of NAD+, was measured by double potential-step chronoamperometry, fast-scan cyclic voltammetry (cathodic-anodic peak current ratio) and slow-scan cyclic voltammetry (peak potential shift) for a medium in which neither NAD+ nor its reduction products are adsorbed at the solution/electrode interface. All three methods give concordant values of kd (approx. 3 X 10(7) M-1 X s-1), which are in reasonable accord with the values determined by pulse radiolysis but are considerably greater than values previously determined electrochemically. For the NAD+/NAD couple, the heterogeneous rate constant (ks,h) exceeds 1 cm X s-1 at 25 degrees C and the formal potential (E0c) vs. sce is -1.155 V at 25 degrees C and -1.149 V at 1 degree C at pH 9.1, with an uncertainty of about +/- 0.005 V.

Calorimetry↗
PubMed1979

Effects of response-contingent clock stimuli on behavior maintained by intravenous codeine in the rhesus monkey.

Response-contingent brief presentations of clock stimuli differentially correlated with food availability altered rates of codeine-maintained lever pressing. Rhesus monkeys performed under a two lever multiple schedule: Multiple fixed interval clock 5 min variable interval 2 min. Different colored lights were presented during successive 75 sec period of the fixed-interval clock component. Lever pressing under the FI Clock schedule was maintained by presentation of 1 g Noyes pellets, and lever pressing under the VI schedule by 0.05 mg/kg infusions of codeine PO4. Characteristic schedule-controlled performance developed in both schedule components. When the clock stimulus from the first or the final period of the FI Clock schedule was presented contingent upon completion of a short fixed ratio of responses during the variable-interval schedule component, the first clock stimulus decreased and the final clock stimulus increased rates of codeine-maintained lever pressing. Neither the first nor the final clock stimulus altered the frequency of codeine injection. The effect of each clock stimulus was accentuated by increasing the duration of stimulus presentation and by decreasing the response requirement for stimulus illumination. These rate-altering effects of the clock stimuli were most pronounced when different reinforcers were presented in the two components of the multiple schedule when either food or intravenous codeine injection was available under both components of the multiple schedule, response-contingent clock stimulus presentation did not alter response rates under the VI schedule.

Animals↗
PubMed1977

Visual complaints and binocular function in bilaterally aphakic persons with cataract glasses.

Seventy-one consecutive patients who underwent operation for senile cataract in both eyes during the period 1969-1973 were examined and questioned about visual complaints an average of 18 months after being fitted with cataract spectacles. In the distance situation none had complaints, either reported spontaneously or after questioning. Except for a few immobile patients, all could manage on their own in the street and on stairs. In the near situation 16 of the 71 patients had permanent alternating or intermittent exotropia which, however, gave rise to diplopic complaints in only two. The diplopia in these two patients disappeared after the glasses had been decentered. On questioning, complaints of diplopia could be elicited in another 5 patients. Investigation of sensory binocular function using Titmus' sterotest showed that 35 of the 71 patients could manage the test at the level 40 inches/arc. Division of the material into two groups by duration of monocular visual function during the development of the cataract and during the period between the operations on the two eyes, disclosed that this factor was of no importance to the postoperative motor and sensory binocular function.

Aged↗