Biomedical subjects

L L Jones

Publications and source records attributed to L L Jones.

At least 19 recordsLinked to original sources

PubMed1999

Molecular signals for glial activation: pro- and anti-inflammatory cytokines in the injured brain.

Injury to the central nervous system leads to cellular changes not only in the affected neurons but also in adjacent glial cells. This neuroglial activation is a consistent feature in almost all forms of brain pathology and appears to reflect an evolutionarily-conserved program which plays an important role for the repair of the injured nervous system. Recent work in mice that are genetically-deficient for different cytokines (M-CSF, IL-6, TNF-alpha, TGF-beta 1) has begun to shed light on the molecular signals that regulate this cellular response. Here, the availability of cytokine-deficient animals with reduced or abolished neuroglial activation provides a direct approach to determine the function of the different components of the cellular response leading to repair and regeneration following neural trauma.

Animals↗

PubMed1999

Neuroglial activation repertoire in the injured brain: graded response, molecular mechanisms and cues to physiological function.

Damage to the central nervous system (CNS) leads to cellular changes not only in the affected neurons but also in adjacent glial cells and endothelia, and frequently, to a recruitment of cells of the immune system. These cellular changes form a graded response which is a consistent feature in almost all forms of brain pathology. It appears to reflect an evolutionarily conserved program which plays an important role in the protection against infectious pathogens and the repair of the injured nervous system. Moreover, recent work in mice that are genetically deficient for different cytokines (MCSF, IL1, IL6, TNFalpha, TGFbeta1) has begun to shed light on the molecular signals that regulate this cellular response. Here we will review this work and the insights it provides about the biological function of the neuroglial activation in the injured brain.

Animals↗

PubMed1998

Immune surveillance in the injured nervous system: T-lymphocytes invade the axotomized mouse facial motor nucleus and aggregate around sites of neuronal degeneration.

Although the CNS is an established immune-privileged site, it is under surveillance by the immune system, particularly under pathological conditions. In the current study we examined the lymphocyte infiltration, a key component of this neuroimmune surveillance, into the axotomized facial motor nucleus and analyzed the changes in proinflammatory cytokines and the blood-brain barrier. Peripheral nerve transection led to a rapid influx of CD3-, CD11a (alphaL, LFA1alpha)- and CD44-immunoreactive T-cells into the axotomized mouse facial motor nucleus, with a first, low-level plateau 2-4 d after injury, and a second, much stronger increase at 14 d. These T-cells frequently formed aggregates and exhibited typical cleaved lymphocyte nuclei at the EM level. Immunohistochemical colocalization with thrombospondin (TSP), a marker for phagocytotic microglia, revealed aggregation of the T-cells around microglia removing neuronal debris. The massive influx of lymphocytes at day 14 was also accompanied by the synthesis of mRNA encoding IL1beta, TNFalpha, and IFN-gamma. There was no infiltration by the neutrophil granulocytes, and the intravenous injection of horseradish peroxidase also showed an intact blood-brain barrier. However, mice with severe combined immunodeficiency (SCID), which lack differentiated T- and B-cells, still exhibited infiltration with CD11a-positive cells. These CD11a-positive cells also aggregated around phagocytotic microglial nodules. In summary, there is a site-selective infiltration of activated T-cells into the mouse CNS during the retrograde reaction to axotomy. The striking aggregation of these lymphocytes around neuronal debris and phagocytotic microglia suggests an important role for the immune surveillance during neuronal cell death in the injured nervous system.

Animals↗

PubMed1998

Transforming growth factor beta's 1, 2 and 3 inhibit proliferation of ramified microglia on an astrocyte monolayer.

The transforming growth factor beta's (TGFbeta) are a multipotent family of cytokines with strong immunosuppressive and neurotrophic effects. In the current study, we examined the effect of the TGFbeta's 1, 2 and 3 on the proliferation of ramified microglia cultured on top of a confluent astrocyte monolayer. All three TGFbeta isoforms inhibited proliferation. PCR analysis also showed the presence of mRNA for the TGFbeta receptors type I and II and for all 3 TGFbeta isoforms in microglia, astrocytes and in co-cultures. Moreover, removal of this endogenous TGFbeta activity with antibodies against TGFbeta1 and TGFbeta3 strongly stimulated microglial proliferation. These inhibitory effects on the proliferation of ramified microglia suggest that TGFbeta's may play an important role in the regulation of the microglial population under normal conditions and after injury or disease in the central nervous system.

Activin Receptors, Type I↗

PubMed1998

Symptoms of patients with myasthenia gravis receiving treatment.

The symptoms of myasthenia gravis (MG) are often simply classified as excessive fatigue rather than evaluated as different signs of disease progression. The purpose of this study was to evaluate the medical symptoms of patients with MG who had been under treatment for many years. Patients diagnosed with MG were compared to healthy controls. A survey questionnaire was used and differences were evaluated using non-parametric statistics. Health care givers should be aware of these differences in order to facilitate early appropriate treatment, to decrease disability, and to increase the quality of life.

Humans↗

PubMed1997

Impaired neuroglial activation in interleukin-6 deficient mice.

Astrocyte activation is a ubiquitous hallmark of the damaged brain and has been suggested to play an important regulatory role in the activation, survival, and regeneration of adjacent neurons, microglia, and oligodendrocytes. Little is known, however, about the endogenous signals that lead to this activation of astrocytes. Here we examined the regulation of interleukin 6 (IL6), a proinflammatory cytokine, its receptors, and the effects of IL6-deficiency in a model of traumatic central nervous system injury in the axotomized mouse facial motor nucleus. Facial nerve transection led to a massive but transient upregulation of IL6 mRNA in the disconnected motor nucleus, while IL6-receptor subunits were constitutively expressed on motoneurons and astrocytes. Absence of IL6 in genetically IL6-deficient mice led to massive reduction in the number of activated GFAP-positive astrocytes, a more moderate decrease in microglial activation and proliferation, and an increase in the late neuronal response to axotomy. These results emphasize the role of IL6 in the global regulation of neurons, astrocytes, and microglia and their activation in the injured nervous system.

Animals↗

PubMed1997

Population control of microglia: does apoptosis play a role?

Brain lesions, even of the most subtle type, are accompanied by the activation of microglia, the main immune cells of the brain. Microglial cells dramatically increase in number through proliferation and adhere to the injured neurons, where they displace the synaptic input. After proliferation, microglia gradually migrate into the nearby parenchyma and appear to decrease in number. Here we examined the possible involvement of apoptosis in the regulation of the microglial cell number using Terminal transferase mediated d-UTP Nick End-Labelling (TUNEL). In vitro, cell death is a common phenomenon in microglial cell cultures, and is enhanced by the withdrawal of the mitogen, granulocyte-macrophage colony stimulating factor. In vivo, application of the TUNEL-reaction revealed TUNEL-positive microglia beginning at day 4, with a peak 7 days after transection of the facial nerve. Surprisingly, TUNEL-labelling in vivo was localized on the outer side of the nuclear membrane and in the microglial cytoplasm, with very little staining within the nucleus itself. These TUNEL-labelled cells also lacked other classic morphological signs of apoptosis, like membrane blebbing, chromatin condensation and apoptotic bodies. These data suggest that the regulation of post-mitotic microglia is not mediated by the classic pathway of apoptosis.

Animals↗

PubMed1997

Regulation of CD44 in the regenerating mouse facial motor nucleus.

CD44 is a cell adhesion molecule which plays an important role in cell movement and adhesion, e.g. in lymphocyte homing and tumour metastasis. Here we studied the expression of CD44 mRNA and protein immunoreactivity in the facial nucleus after nerve injury and during the ensuing regeneration. Transection of the facial nerve led to a strong up-regulation of CD44, peaking 4 days after injury on the motoneurons of the axotomized facial nucleus. Use of the polymerase chain reaction confirmed the de novo expression of CD44 and detected only the standard haematopoietic CD44 isoform. Western blotting also detected the 76 kDa protein subtype, in line with the predicted size of the haematopoietic CD44 variant. At the ultrastructural level, CD44 immunoreactivity was restricted to the surface of the neuronal perikarya, their dendrites and axons. It was not seen in the adjacent activated astrocytes, microglia or vascular endothelia. This study shows strong up-regulation of the cell adhesion molecule CD44 on the regenerating motoneurons in the axotomized facial nucleus. These data suggest that CD44 may play a role in neurite outgrowth, in synaptic stripping or in the adhesion of activated glial cells to the perikaryal surface of the axotomized motoneurons.

Alternative Splicing↗

PubMed1997

Procurement coordinator support group.

This article describes a support group for procurement coordinators. The group was initiated to help coordinators assist grieving donor families and to cope with their own reactions to stressful events. The theory underlying support groups is presented as a guide to understanding the purpose and process of the group. Issues of concern to coordinators are discussed along with strategies for facilitating group discussions and reducing stress.

Adaptation, Psychological↗

PubMed1996

Regulation of thrombospondin in the regenerating mouse facial motor nucleus.

Thrombospondin (TSP) is a multifunctional extracellular matrix protein that plays a role in neuronal migration and axonal outgrowth in the developing central nervous system. In the current study we have examined the localization and regulation of TSP immunoreactivity (TSP-IR) during neuronal regeneration in the axotomized facial motor nucleus using Western blotting and light and electron microscopy. Transection of the facial nerve led to a gradual increase in TSP-IR in the regenerating motoneurons, peaking 4-7 days after injury (DAI). In addition to regenerating neurons, axotomy also caused a rapid upregulation of TSP-IR on activated microglia throughout the facial nucleus, with a maximum of 2-3 DAI, and a second increase at 14-21 DAI on microglial aggregates surrounding degenerating motoneurons and in neuronophagic microglia. In summary, injury leads to the induction of thrombospondin on axotomized neurons and activated microglia, peaking at the times of maximal posttraumatic microglial proliferation and during neuronal phagocytosis. Since thrombospondin is a multimodal extracellular matrix protein with a variety of cell attachment sites, thrombospondin might serve to link microglia and injured neurons, followed by microglial proliferation and removal of the neuronal debris.

Animals↗

PubMed1995

The impact of exit-site care and catheter design on the incidence of catheter-related infections.

The optimal approach to catheter exit-site care and catheter design in terms of catheter-related infections (e.g., exit-site infections, peritonitis) in children remains elusive. We retrospectively compared the incidence of exit-site infections and peritonitis in 33 pediatric peritoneal dialysis patients who used one of three exit-site care/catheter combinations. The catheters used were single-cuffed, curled Tenckhoff (T), and double-cuffed Swan neck (SN). Exit-site care included either povidone-iodine (PI) or chlorhexidine (CHL) as cleansing agents. Our data suggest that the use of chlorhexidine versus povidone-iodine is associated with a significant decrease (p < 0.05) in the frequency of catheter exit-site infections in children. The use of the Swan-neck double-cuffed catheter does not appear to have any further impact on the frequency of exit-site infections. Neither the use of chlorhexidine nor Swan neck catheters had an effect on our peritonitis rate. Our review suggests that a prospective evaluation of a chlorhexidine-based exit-site care regimen in children should be encouraged.

Anti-Infective Agents, Local↗

PubMed1993

Early and rapid de novo synthesis of Alzheimer beta A4-amyloid precursor protein (APP) in activated microglia.

Upon acute activation, microglia, the immuneffector cells of the brain parenchyma, express the amyloid precursor protein (APP) that is otherwise prominent in pathological structures related to Alzheimer's disease. In this disease complex amyloid-bearing neuritic plaques contain beta A4-amyloid protein, the APP, and numerous inflammatory proteins. The accompanying activation of microglia has mostly been viewed as a secondary reaction to amyloid deposits. Activation of microglia was performed in a graded fashion. Transection of peripheral nerves such as the facial or sciatic nerve causes a microglial reaction within hours in the nucleus of origin or in projection areas of the CNS. A predominantly glial up-regulation of APP mRNA and protein could be detected as early as 6 h post lesion not only at the site of affected neuronal cell bodies but also in corresponding projection areas. Its time course suggests rapid transneuronal signalling to glial cells in the projection area. Light and electron microscopy demonstrate that microglia, which are cells of mononuclear phagocyte lineage and comprise up to 20% of all glial cells, are the dominant source for non-neuronal APP expression. Ultrastructurally, brain perivascular cells within the basal lamina constitutively express APP and thus are a possible source of vascular amyloid. Additionally, microglia express leukocyte-derived (L)-APP mRNA and protein that have recently been described in mononuclear cells of the immune system. Increased L-APP expression may serve as a potential marker for glial/microglial activation. Such immune-mediated amyloidogenesis initiated by microglia might have implications for the treatment of neurodegenerative diseases.

Amyloid beta-Protein Precursor↗

PubMed1992

The benefits and costs of caregiving and care receiving for daughters and mothers.

In accordance with social exchange theory (Thibaut and Kelley, 1959), this study examined the outcomes of caregiving for elderly mothers and their caregiving daughters (N = 141 pairs). Data were gathered through face-to-face interviews. Principal components factor analyses revealed three factors for mothers: Helplessness, Feeling Loved, and Anger; and three factors for daughters: Insufficient Time, Frustration, and Anxiety. Block regressions with an initial block of demographic variables and a second block of situational variables were performed to determine the relative influence of these two sets of independent variables on caregiving outcomes. The regressions revealed limited influence of demographic variables and significant influence of situational variables. Of particular importance for daughters is the role of perceived intimacy with the mother: Daughters with better relationships experience fewer caregiving costs. Mothers' health plays a critical role in the outcomes of care receiving: Mothers in poorer health experience greater helplessness and are less likely to feel loved.

Aged↗

PubMed1990

Effects of short-term training on cardiac function during prolonged exercise.

To determine the relationship between the training-induced increases in plasma volume (PV) and alterations in cardiac performance during prolonged submaximal cycle exercise, seven male subjects were studied prior to and following a short-term (3 d) training period (2 h.d-1 at 65% VO2max). Mean (range) VO2max was 3.42 l.min-1 (2.96-3.87). Training resulted in a 20% increase (P less than 0.05) in plasma volume (PV) and a 12% increase (P less than 0.05) in total blood volume (TBV). In contrast, training had no effect (P greater than 0.05) in altering exercise VO2, VCO2, VE BTPS, or RER. Cardiac output (Q) was higher (P less than 0.05) posttraining at all exercise sampling times (30, 60, 90, and 120 min). The elevations in Q were accompanied by an average decrease (P less than 0.05) in stroke volume (SV) of 22 ml. Arteriovenous O2 (a-v O2) difference was depressed (P less than 0.05) during exercise following the training. Although elevations (P less than 0.05) in core temperature (degrees C) occurred during the exercise, the training-induced PV increases did not affect thermoregulatory behavior. These results indicate that an early adaptive response to exercise training is an elevation in Q, an increase in SV, and a reduction in HR. These effects persist during prolonged exercise in spite of the progressive increase in body heat content. It is proposed that the increase in Q serves primarily to increase muscle blood flow and maintain arterial O2 delivery, while the altered cardiodynamic behavior serves to increase cardiac reserve, providing a greater tolerance to prolonged heavy exercise.

Adult↗

PubMed1989

Autonomy and decision making between single older women and their caregiving daughters.

We examined perceptions of decisional autonomy and decision-making processes among 64 elderly, single mothers and their caregiving daughters. Mothers were highly involved in decisions affecting their lives, ranging from daily care to major health decisions; daughters were particularly influential over major health, financial and housing decisions. Mothers' level of personal care dependency was negatively associated with both mothers' and daughters' confidence in the mothers' decision-making abilities.

Adult↗

PubMed1989

Muscle energetics during prolonged cycling after exercise hypervolemia.

This study examined the question of whether increases in plasma volume (hypervolemia) induced through exercise affect muscle substrate utilization and muscle bioenergetics during prolonged heavy effort. Six untrained males (19-24 yr) were studied before and after 3 consecutive days of cycling (2 h/day at 65% of peak O2 consumption) performed in a cool environment (22-23 degrees C, 25-35% relative humidity). This protocol resulted in a 21.2% increase in plasma volume (P less than 0.05). During exercise no difference was found in the blood concentrations of glucose, lactate, and plasma free fatty acids at either 30, 60, 90, or 120 min of exercise before and after the hypervolemia. In contrast, blood alanine was higher (P less than 0.05) during both rest and exercise with hypervolemia. Measurement of muscle samples extracted by biopsy from the vastus lateralis muscle at rest and at 60 and 120 min of exercise indicated no effect of training on high-energy phosphate metabolism (ATP, ADP, creatine phosphate, creatine) or on selected glycolytic intermediate concentrations (glucose 1-phosphate, glucose 6-phosphate, fructose 6-phosphate, lactate). In contrast, training resulted in higher (P less than 0.05) muscle glucose and muscle glycogen concentrations. These changes were accompanied by blunting of the exercise-induced increase (P less than 0.05) in both blood epinephrine and norepinephrine concentrations. Plasma glucagon and serum insulin were not affected by the training. The results indicate that exercise-induced hypervolemia did not alter muscle energy homeostasis. The reduction in muscle glycogen utilization appears to be an early adaptive response to training mediated either by an increase in blood glucose utilization or a decrease in anaerobic glycolysis.

Adult↗

PubMed1987

Training-induced hypervolemia: lack of an effect on oxygen utilization during exercise.

To investigate the effect of training-induced increases in plasma volume on maximal aerobic power, 8 male subjects (age 19 to 24 yr) underwent a 4-d training program (2 h X d-1) at an estimated 71% maximal aerobic power. Following training, plasma volume measured using 131I-human serum albumin increased by 20.3% (P less than 0.01) whereas red cell volume remained unchanged and total blood volume increased by 12.3% (P less than 0.01). During progressive sub-maximal cycle exercise, oxygen consumption, carbon dioxide production, ventilation, and blood lactate concentration remained unchanged following the training whereas heart rate was significantly elevated (P less than 0.05). Significant post-training elevations were also noted in carbon dioxide production (P less than 0.05), blood lactate (P less than 0.01), and peak power output (P less than 0.05) during maximal exercise. Maximal aerobic power and ventilation were not altered. It is concluded that hypervolemia induced by short-term exercise training does not affect oxygen consumption either during sub-maximal or maximal exercise.

Adult↗

PubMed1986

Mechanistic aspects of ingested chlorine dioxide on thyroid function: impact of oxidants on iodide metabolism.

Toxicological studies dealing with recent findings of health effects of drinking water disinfectants are reviewed. Experiments with monkeys and rodents indicate that the biological activity of ingested disinfectants is expressed via their chemical interaction with the mucosal epithelia, secretory products, and nutritional contents of the alimentary tract. Evidence exists that a principal partner of this redox interaction is the iodide of nutritional origin that is ubiquitous in the gastrointestinal tract. Thus the observation that subchronic exposure to chlorine dioxide (ClO2) in drinking water decreases serum thyroxine levels in mammalian species can be best explained with changes produced in the chemical form of the bioavailable iodide. Ongoing and previously reported mechanistic studies indicate that oxidizing agents such as chlorine-based disinfectants oxidize the basal iodide content of the gastrointestinal tract. The resulting reactive iodine species readily attaches to organic matter by covalent bonding. Evidence suggests that the extent to which such iodinated organics are formed is proportional to the magnitude of the electromotive force and stoichiometry of the redox couple between iodide and the disinfectant. Because the extent of thyroid uptake of the bioavailable iodide does not decrease during ClO2 ingestion, it seems that ClO2 does not cause iodide deficiency of sufficient magnitude to account for the decrease in hormonogenesis. Absorption of one or more of iodinated molecules, e.g., nutrients, hormones, or cellular constituents of the alimentary tract having thyromimetic or thyroid inhibitory properties, is a better hypothesis for the effects seen.

Animals↗