PubMed Health⌕ Search

Biomedical subjects

J R Jensen

Publications and source records attributed to J R Jensen.

At least 19 recordsLinked to original sources
PubMed2006

Slc11a1 (formerly NRAMP1) gene modulates both acute inflammatory reactions and pristane-induced arthritis in mice.

Mice selected for the maximum acute inflammatory reaction (AIRmax) are highly susceptible to pristane-induced arthritis (PIA), whereas mice selected for the minimum response (AIRmin) are resistant. These lines show distinct patterns of leukocyte infiltration and R and S allele frequency disequilibrium of the solute carrier family 11a member 1 (Slc11a1) gene. In order to study the interactions of the Slc11a1 R and S alleles with the inflammation modulating Quantitative Trait Loci (QTL) during PIA development, homozygous AIRmax(RR), AIRmax(SS), AIRmin(RR) and AIRmin(SS) lines were produced by genotype-assisted breedings. These mice received two intraperitoneal injections of 0.5 ml pristane at 60-day intervals, and the subsequent development of arthritis was assessed for 210 days. Cytokine-secreting cell profiles were investigated using enzyme-linked immunospot. Arthritis incidence in AIRmax(RR) mice reached 29%, whereas PIA incidence in AIRmax(SS) mice was 70% by day 180. AIRmin(RR) mice were resistant, whereas 13.3% of AIRmin(SS) mice became arthritic. The presence of the defective S allele also increased arthritis severity, although acute inflammation was higher in mice bearing the R allele. A predominant Th0/Th2-type response in Slc11a1(SS) mice was observed. These results indicate that Slc11a1 is a strong candidate for the QTL modulating acute inflammation and for PIA.

Alleles↗
PubMed2006

Involvement of antibody production quantitative trait loci in the susceptibility to pristane-induced arthritis in the mouse.

Mice obtained by bidirectional selective breeding for high (HIII) or low (LIII) antibody (Ab) production are resistant or extremely susceptible to pristane-induced arthritis (PIA), respectively. Several quantitative trait loci regulating Ab production (Ab QTL) have been mapped in these lines, which were used to investigate the influence of these Ab QTL in PIA. Parental HIII and LIII mice and their F1 and F2 intercrosses were injected twice with pristane, and arthritis was observed for 200 days. In LIII mice PIA was more severe and incidence was 100% at day 105, while F1 and F2 mice showed intermediate values. HIII mice were totally resistant. Microsatellite polymorphisms of Ab QTL were analysed and D3Mit100 alleles cosegregated significantly with PIA incidence, severity and onset in F2 intercross mice, while the other four markers showed suggestive values. Results indicate colocalization of QTL for Ab production and PIA susceptibility. Moreover, the different cytokine and IgG isotype profiles observed in HIII and LIII lines after PIA induction are useful to candidate genes endowed with the regulation of the Ab production and arthritis phenotypes.

Animals↗
PubMed2001

Stimulated secondary emission from semiconductor microcavities.

We find strong influence of final-state stimulation on the time-resolved light emission dynamics from semiconductor microcavities after pulsed excitation allowing angle-resonant polariton-polariton scattering on the lower-polariton branch. The polariton dynamics can be controlled by injection of final-state polaritons at densities below a polariton saturation density of 5x10(8) cm(-2). A bosonic enhancement factor in the dynamics of up to 700 is evaluated.

Journal Article↗
PubMed2000

Regulating actin dynamics in neuronal growth cones by ADF/cofilin and rho family GTPases.

Growth cone motility and navigation in response to extracellular signals are regulated by actin dynamics. To better understand actin involvement in these processes we determined how and in what form actin reaches growth cones, and once there, how actin assembly is regulated. A continuous supply of actin is maintained at the axon tip by slow transport, the mobile component consisting of an unassembled form of actin. Actin is co-transported with actin-binding proteins, including ADF and cofilin, structurally related proteins essential for rapid turnover of actin filaments in vivo. ADF and cofilin activity is regulated through phosphorylation by LIM kinases, downstream effectors of the Rho family of GTPases, Cdc42, Rac and Rho. Attractive and repulsive extracellular guidance cues might locally alter actin dynamics by binding specific GTPase-linked receptors, activating LIM kinases, and subsequently modulating the activity of ADF/cofilin. ADF is enriched in growth cones and is required for neurite outgrowth. In addition, signals that influence growth cone behavior alter ADF/cofilin phosphorylation, and overexpression of ADF enhances neurite outgrowth. Growth promoting effects of laminin are mimicked by expression of constitutively active Cdc42 and blocked by expression of the dominant negative Cdc42. Repulsive effects of myelin and sema3D on growth cones are blocked by expression of constitutively active Rac1 and dominant negative Rac1, respectively. Thus a series of complex pathways must exist for regulating effectors of actin dynamics. The bifurcating nature of the ADF/cofilin phosphorylation pathway may provide the integration necessary for this complex regulation.

Actin Depolymerizing Factors↗
PubMed1999

Macrophages interact with enriched populations of distinct T lymphocyte subsets for the induction of severe destructive Lyme arthritis.

Severe destructive Lyme arthritis was detected in the hind paws of hamsters infused with enriched populations of either CD4+ or CD4- T lymphocytes along with macrophages exposed in vitro to formalin-inactivated Borrelia burgdorferi and then infected with the Lyme spirochete. Swelling was detected 4 days after infection, increased rapidly, peaked on day 8 of infection, and gradually decreased. Similarly, severe destructive arthritis was induced in hamsters infused with enriched populations of unfractionated T lymphocytes and macrophages exposed to spirochetes after infection with B. burgdorferi. Histopathological examination affirmed that hamsters infused with CD4+, CD4-, or unfractionated T lymphocytes and macrophages exposed to B. burgdorferi-induced arthritis. In addition, macrophages exposed in vitro to B. burgdorferi demonstrated both conventional and coiling phagocytosis, suggesting a mechanism by which CD4+ and CD4- T lymphocytes induce arthritis, respectively. These findings demonstrate that both CD4+ and CD4- subpopulations of T lymphocytes are capable of interacting with macrophages for the induction of severe destructive Lyme arthritis.

Animals↗
PubMed1998

Inhibition of the production of anti-OspA borreliacidal antibody with T cells from hamsters vaccinated against Borrelia burgdorferi.

The serious morbidity associated with Lyme borreliosis has focused considerable effort on the development of a comprehensive vaccine for protection against infection with Borrelia burgdorferi. Induction of borreliacidal antibody by vaccination or infection has been shown to correlate with protection of humans and animals against infection with the Lyme spirochete. In this report, we showed that high levels of borreliacidal antibody (titer of 1,280) were produced in vitro when T and B cells from hamsters 14 days after vaccination were incubated with macrophages and B. burgdorferi. By contrast, T and B cells from hamsters 7 or 21 days after vaccination failed to initiate production of borreliacidal activity. Furthermore, the T cells from hamsters 7 or 21 days after vaccination inhibited the in vitro production of borreliacidal antibody when cocultured with T and B cells obtained from hamsters 14 days after vaccination. When cell-free supernatants from the suspensions of T and B cells from hamsters 14 days after vaccination were absorbed with recombinant OspA, they lost nearly all borreliacidal activity. The removal of anti-OspA antibody resulted in a decrease in borreliacidal titer from 1,280 to less than 4. These results demonstrate that T cells from vaccinated animals can prevent a sustained production of protective borreliacidal antibody.

Animals↗
PubMed1997

Macrophages and enriched populations of T lymphocytes interact synergistically for the induction of severe, destructive Lyme arthritis.

Hamsters receiving both macrophages exposed to Formalin-inactivated Borrelia burgdorferi (Mphi-FBb) and enriched populations of either immune or naive T lymphocytes developed severe swelling of the hind paws when infected with B. burgdorferi. Swelling was detected 6 days after infection, peaked on day 10, and gradually decreased. Swelling was also observed in the hind paws of hamsters infused with only Mphi-FBb or only enriched populations of either immune or naive T lymphocytes after infection with B. burgdorferi. However, the swelling detected in these hamsters was less severe and of shorter duration. In addition, hamsters receiving both macrophages not exposed to Formalin-inactivated B. burgdorferi (Mphi-NFBb) and enriched populations of either immune or naive T lymphocytes failed to develop severe swelling after infection with B. burgdorferi. No swelling was also observed in hamsters infused with both Mphi-FBb and enriched populations of immune T lymphocytes and then inoculated with spirochetal growth medium. We further showed that macrophages and enriched populations of T lymphocytes did not interact synergistically for controlling B. burgdorferi infection, as spirochetes were readily recovered from the tissues of all cell transfer recipients infected with B. burgdorferi. These findings demonstrate that hamsters infused with both Mphi-FBb and enriched populations of either immune or naive T lymphocytes develop a more fulminate arthritis after infection with B. burgdorferi than recipients infused with either cell type alone. These findings suggest that macrophages and T lymphocytes interact synergistically for the induction of severe, destructive Lyme arthritis.

Animals↗
PubMed1996

Characterization of the protective borreliacidal antibody response in humans and hamsters after vaccination with a Borrelia burgdorferi outer surface protein A vaccine.

Significant borreliacidal antibody was induced in volunteers and hamsters 60 days after primary and secondary vaccination with high concentrations of recombinant outer surface protein A (rOspA). However, the borreliacidal antibody response waned rapidly. Only 1 person had detectable cidal activity 180 days after vaccination. Similarly, the borreliacidal antibody response waned rapidly in hamsters by week 10 of vaccination. By contrast, the total anti-rOspA antibody response remained elevated in volunteers and hamsters. When isolates of Borrelia burgdorferi sensu lato were incubated in sera from vaccinated humans or hamsters, only the vaccine-specific isolate was killed. These results were confirmed by challenging rOspA-vaccinated hamsters with different isolates of B. burgdorferi sensu lato. The results showed that monitoring total rOspA antibody is inappropriate for evaluating the efficacy of an rOspA vaccine. The rOspA vaccine must be improved to yield comprehensive protection and maintain sustained levels of protective borreliacidal antibodies.

Adolescent↗
PubMed1992

The initial stages of neural regeneration are dependent upon intracellular calcium levels.

The earliest events of neuronal regeneration require resealing of the neurite's membrane after injury and the subsequent formation of a new growth cone. We have investigated these activities in vitro employing the large identified neurons of the snail Helisoma. Regeneration was elicited by transection of neurite processes and assessed by studying the formation of new growth cones from the proximal neurite stumps. Under normal conditions new growth cones formed rapidly in 100% of the preparations. This formation appeared to follow, however, a large rise in intracellular calcium and did not start until after the cells homeostatic machinery had re-established near baseline calcium levels. To test the hypothesis that elevated intracellular calcium levels delayed or inhibited growth cone formation, transections were performed after experimentally increasing intracellular calcium concentrations to different levels by either depolarization or by calcium ionophores. Under these conditions, regeneration was significantly retarded in a fashion dependent upon the intracellular calcium concentration. Another change in the extracellular milieu, namely lowering of the extracellular calcium concentration, also significantly retarded growth cone formation. Under these conditions neurons appeared unable to reseal their cut ends and eventually died. Taken together, these studies demonstrate the importance of both the extracellular and intracellular milieu at times immediately following neurite transection in determining whether or not the earliest stages of neuronal regeneration will occur.

Animals↗
PubMed1991

FCCP releases Ca2+ from a non-mitochondrial store in an identified Helisoma neuron.

The proton ionophore FCCP was evaluated for use as a selective blocker of mitochondrial Ca2+ sequestration in identified Helisoma neurons in vitro. By use of the Ca2+ indicator fura-2, it was found that application of FCCP evoked a gradual increase in cell body [Ca2+]i that reached a level approximately 3-fold higher than baseline after 60 min. Moreover, FCCP released Ca2+ even when added after mitochondrial stores of Ca2+ had previously been emptied by an alternate method. From these and other experiments, it is concluded that FCCP, in addition to its recognized effect on mitochondrial Ca2+ sequestration, also releases Ca2+ from a non-mitochondrial store and is, therefore, unsuitable for use in an intact neuron to selectively inactivate mitochondrial Ca2+ uptake.

Animals↗
PubMed1991

A comparison of calcium homeostasis in isolated and attached growth cones of the snail Helisoma.

This study examines the capability of growth cones from identified neurons of the snail Helisoma trivolvis to perform calcium homeostasis. Calcium influx into the cytoplasm was eliminated or increased experimentally to alter [Ca]i, and the compensatory response of the growth cone was measured with the fluorescent calcium indicator Fura-2. Growth cones compensated for both increases and decreases in calcium influx by restoring [Ca]i towards basal levels under both types of challenges. The intrinsic ability of growth cones to control [Ca]i was examined in physically isolated growth cones. Isolated growth cones demonstrated essentially identical calcium homeostatic properties to their intact counterparts, indicating that mechanisms governing calcium homeostasis exist intrinsically in the growth cone. Such independence may add significantly to the growth cone's potential to locally interpret and respond to stimuli encountered en route to its appropriate target.

Animals↗
PubMed1989

Allosteric activation of brain mitochondrial Ca2+ uptake by spermine and by Ca2+: developmental changes.

Kinetic analysis of 45Ca2+ uptake by rat brain mitochondria in Ca2+ - 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid buffers indicated that spermine both increased the apparent affinity for Ca2+ and decreased the cooperativity of uptake. Both effects are consistent with an allosteric activation of uptake by spermine. The stimulating effect of spermine on 45Ca2+ uptake was maximal with mitochondria from postnatal day 10 animals and then steadily decreased with increasing age to reach adult values by approximately 30 postnatal days; this was observed independently of the substrates used to fuel mitochondria. Mitochondrial Ca2+ buffering was also analyzed by use of a Ca2+-selective electrode. Addition of a large bolus of Ca2+ produced a decrease in the subsequent equilibrium extramitochondrial Ca2+ concentration (or a "rebound overshoot") under some conditions. It is proposed that this effect is the result of an allosteric activation of Ca2+ uptake by Ca2+. This effect was slowly reversible, or hysteretic, and was blocked by spermine. The overshoot was increased in the presence of higher concentrations of Mg2+ and was absent when mitochondria were incubated with 0.3 mM Mg2+. It was maximal in mitochondria prepared from early postnatal brain, and changes in the magnitude of the effect during development paralleled those obtained with spermine stimulation of 45Ca2+ uptake. The data suggest that spermine produces an allosteric activation of Ca2+ uptake by binding to the same regulatory sites that are involved in the Ca2+-induced activation. The results as a whole suggest that spermine could modulate mitochondrial buffering of the intracellular Ca2+ concentration in brain, particularly during the early postnatal period.

Aging↗
PubMed1989

Allosteric activation of brain mitochondrial Ca2+ uptake by spermine and by Ca2+: brain regional differences.

Analysis of the initial rates of 45Ca2+ uptake by rat brain mitochondria in Ca2+-1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid buffers indicated that nontelencephalic mitochondria exhibited both a much less pronounced stimulatory effect of spermine and significantly more hyperbolic kinetics of Ca2+ uptake than telencephalic mitochondria. Nontelencephalic mitochondria were also markedly less susceptible to a Ca2+-induced hysteretic allosteric activation of the Ca2+ uniporter. A new Ca2+ loading procedure, which strikingly illustrates differences in mitochondrial Ca2+ buffering characteristics, is also described. In this procedure, low concentrations of Ca2+ (1, 2, or 5 microM) were repetitively added to mitochondria every 30 s while changes in free Ca2+ concentration were recorded. Spermine induced a marked attenuation of the rise in free Ca2+ level under these conditions. Steady-state rates of Ca2+ uptake were determined by a quantitative analysis of the buffering of repetitive Ca2+ additions, and, again, brain regional differences were qualitatively similar to those observed in the initial rate kinetics; Ca2+ uptake by nontelencephalic mitochondria in the steady state was markedly less responsive to stimulation by spermine and appeared to have a more hyperbolic dependence on Ca2+ in the absence of spermine. These results also suggest that there is a lag time in the activation of the uniporter by Ca2+, in addition to the hysteresis that has previously been observed in the deactivation of the uniporter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Polyamines stimulate mitochondrial calcium transport in rat brain.

The effects of the polyamines spermine and spermidine on rat brain mitochondrial calcium transport were examined using a variety of techniques for measuring the kinetics of calcium uptake and the buffering capabilities of isolated mitochondria. Spermine both increased the rate of calcium accumulation and decreased the set-point to which isolated mitochondria buffer free calcium concentration. In the presence of physiological concentrations of sodium and magnesium, spermine lowered the extramitochondrial calcium level to approximately 0.3 microM, a value close to the resting intracellular calcium concentration. The effect of polyamines was concentration dependent, with a half-maximal effect of spermine observed at approximately 0.1-0.4 mM (respiratory substrate dependent), whereas spermidine was approximately 10 times less potent. Calcium transport by hippocampal mitochondria was stimulated markedly more by spermine than was calcium transport by mitochondria isolated from brainstem. The stimulatory effect of spermine was not due to an increase in the transport of respiratory substrates inside the mitochondria nor to an effect on the enzymes using these respiratory substrates. An examination of the effect of spermine on the kinetics of calcium uptake indicated that spermine increased calcium uptake maximally at low calcium concentrations. Beyond that level, the stimulatory effect of spermine decreases, and spermine can even inhibit calcium uptake. These results are in good agreement with previous reports on the effects of polyamines on calcium transport in mitochondria from peripheral tissue. They support the hypothesis that spermine increases the rate of calcium uptake by mitochondria by increasing the affinity of the uniporter for calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Salt and peroxide compared with conventional oral hygiene. I. Clinical results.

The purposes of this 2-year longitudinal study were to: compare the clinical effectiveness of patient applied sodium bicarbonate, hydrogen peroxide, and sodium chloride (S/P) to the use of conventional oral hygiene methods and to investigate the motivational effect of using phase-contrast microscopy in teaching effective oral hygiene. Initially, 972 subjects were screened for signs of periodontitis. From these, 347 with early to moderate periodontitis were selected and each was randomly assigned to one of four home treatment regimens after scaling and root planing. The four treatment regimens included: conventional oral hygiene procedures, conventional oral hygiene procedures plus phase-contrast demonstration of subgingival microbial forms for oral hygiene motivation, S/P oral hygiene, and S/P oral hygiene plus phase-contrast demonstration of subgingival microbial forms for oral hygiene motivation. Plaque, bleeding, gingival inflammation, probing depth, and clinical attachment level were recorded at baseline, 8, 16, and 24 months. Subjects were recalled for reinforcement of oral hygiene and periodontal prophylaxis at various intervals. Data were analyzed based on disease severity, location of index sites and compliance. The results indicated that both conventional oral hygiene procedures and the S/P regimen were effective in reducing clinical signs of disease when combined with professional care. There were no differences between the two regimens in clinical effectiveness and trends favoring microscopic viewing of subgingival plaque for motivational purposes were not statistically significant.

Adult↗
PubMed1987

Salt and peroxide compared with conventional oral hygiene. II. Microbial results.

This study was designed to investigate the effect of conventional oral hygiene (n = 116 subjects) versus a salt and peroxide oral hygiene regimen (n = 115 subjects) on subgingival microorganisms. Subgingival plaque for microscopic evaluation was obtained from eight index tooth sites in each of 231 adult subjects. Microbial forms were microscopically identified at baseline, 8, 16, and 24 months. For both oral hygiene groups, cocci were increased (P less than 0.05) and motile rods were decreased (P less than 0.05) at 8 months and returned to baseline by 16 months. Spirochetes were decreased (P less than 0.05) and remained low through 24 months in both oral hygiene groups. The frequency of agreement between clinical (bleeding) and microbial (greater than or equal to 15% spirochetes or motile rods or greater than or equal to 20% spirochetes + motile rods) criteria for instrumentation was 59.8%. It was also found that fewer total instrumentations for test subjects were observed when microbiological criteria were used as compared with clinical criteria. The greater number of instrumentations based on clinical criteria was highly significant (P less than or equal to 0.001). A significant change in microbial signs associated with peridontal disease may be obtained with either a conventional oral hygiene or a salt and peroxide oral hygiene home care regimen.

Adult↗
PubMed1986

Natural and concanavalin A-induced cytotoxic activity towards continuously growing B lymphocytes derived from patients with cutaneous T-cell lymphoma.

Continuously growing T- and B-cell lines were derived from peripheral blood, affected skin, and lymph nodes of patients with mycosis fungoides (MF) and Sézary syndrome (SS). Two lymphoblastoid cell lines (MF-13 and SS-2) were Epstein-Barr virus (EBV)-transformed B cells evaluated by surface immunoglobulin, lack of E-rosette formation, positive EBV nuclear antibody test, and secretion of IgM antibody in a plaque-forming cell assay. Analysis of the natural-killer-cell activity using peripheral blood lymphocytes from patients with MF and healthy control persons towards MF-13 and SS-2 target cells suggested resistance to lysis even in tests supplemented with 1,000 IU/ml human gamma-interferon. However, the cell lines were not per se completely resistant to lysis because lymphocytes from control persons showed significant cytotoxicity in an 18-h assay supplemented with 2 micrograms/ml concanavalin A.

Adult↗