PubMed Health⌕ Search

Biomedical subjects

J K Chamberlain

Publications and source records attributed to J K Chamberlain.

16 recordsLinked to original sources
PubMed2001

Electromagnetic fields used clinically to improve bone healing also impact lymphocyte proliferation in vitro.

An important aspect of medical device development is the need to understand how a device produces a specific biological effect. The focus can then be on optimizing that effect by device modification and repeated testing. Several reports from this lab have targeted programmed cell death, or apoptosis, as a cellular pathway that is induced by exposure of transformed leukemic T-cells in culture to specific frequency and intensity electromagnetic fields (EMFs). An EMF delivery device capable of selectively inducing T-cell apoptosis in human tissues could be used to enhance healing by limiting the production of molecules that promote inflammatory disorders such as psoriasis and tendonitis. In the present study, we examined the normal T-cell response to EMF exposure in vitro. In the peripheral blood, 70-80% of the lymphocytes are T-cells, and thus is a rich source of normal cells that match the transformed T-cells used in other experiments (Jurkat cells). We isolated lymphocytes from the peripheral blood of humans and rats, cultured them in nutritive medium and exposed them to either a complex 1.8 mT pulsed EMF (Electrobiology, Inc.), a 0.1 mT, 60 Hz power frequency EMF or a 0.2 mT, 100 Hz sinusoidal EMF. Control lymphocytes were cultured similarly, without field exposure. Lymphocytes were then treated with T-cell mitogens and evaluated for proliferative capacity after an additional 72 hours culture. Results indicate that T-cell proliferation is modulated by in vitro exposure to defined EMFs. The potential use of an EMF delivery device capable of selectively inducing such T-cell effects is discussed.

Animals↗
PubMed2000

Experiments showing that electromagnetic fields can be used to treat inflammatory diseases.

While it is well known that electromagnetic fields (EMFs) can induce repair of non-healing bone fractures, EMF therapy remains confined to orthopedic clinics mainly because the biological and physical mechanisms underlying the therapy are unknown. However, it is generally believed that non-invasive, EMF therapy might have a broad, albeit currently unrecognized clinical potential. In support of this view, we report that 0.1 mT, 60 Hz EMFs induce a 20% mean-increase in anti-CD3 binding to T cell receptors (TcRs) of Jurkat cells, a T lymphocyte cell line. Additionally, we show that 60 Hz sinusoidal EMFs and a commercial bone healing EMF modulate signal transduction pathways that regulate lymphocyte proliferation and that are normally triggered by activating the Jurkat TcR. Similar EMF effects are shown in human peripheral blood lymphocytes (hPBLs), exposed to EMFs in culture and in rat PBLs, when donor animals are exposed to a bone healing field (21 days, 4 hr/day). Although we do not yet satisfactorily understand the differences we obtain in cell and animal based experiments, our findings clearly demonstrate that EMFs can regulate lymphocyte proliferation in vitro and in vivo. Since T cells are key modulators of inflammation, the development of EMF based therapeutic devices to regulate their activity can be expected to provide important tools to treat numerous human inflammatory diseases such as psoriasis and arthritis.

Animals↗
PubMed1988

Effects of housing and muricidal behavior on serotonergic receptors and interactions with novel anxiolytic drugs.

Mouse killing by rats represents a predatory behavior that can be modified by drugs from several different therapeutic classes and by environmental conditions. Buspirone and gepirone, non-benzodiazepine anxiolytics that stimulate serotonergic receptors (5HT1a) and inhibit isolation-induced intraspecies aggression, were tested for inhibition of muricidal behavior by isolated rats. Neither buspirone (3.0 mg/kg s.c.) nor gepirone (from 5.0 to 40 mg/kg) inhibited muricide. Additional rats were housed, either aggregated or isolated, and tested for muricidal behavior 9 times over 5 weeks to establish which animals were muricidal: thus, there were 4 groups of rats: muricidal or non-muricidal under either isolated or aggregated housing condition. [3H]-Spiperone was used to determine striatal D2 receptor Bmax and Kd and prefrontal cortex D2 and 5HT2 receptor binding. There were no changes across the four groups. Binding of [3H]-5-hydroxytryptamine (5HT) to 5HT1a receptors decreased in septum of both groups of isolated rats and binding to 5HT1b receptors decreased 50% in hippocampus of isolated and aggregated muricidal rats. Binding of [3H]-5HT to either receptor was unchanged in amygdaloid area and hypothalamus across all groups. Thus, stimulating pre- and postsynaptic 5HT1a receptors does not alter muricidal behavior and changes in 5HT1 receptor binding occurs in limited areas. Whether this limited change in hippocampal 5HT1b binding is important for establishing muricidal behavior is unclear; however the direction of the change is consistent with reports that decreased serotonergic activity increases predatory behavior.

Animals↗
PubMed1987

Endotoxin: a twofold effect on bone marrow ultrastructure.

Ultrastructural studies of mouse bone marrow reveal that reduction of the marrow-blood barrier precedes the two waves of leukocytosis which follow endotoxin administration. These ultrastructural changes include a decrease in adventitial cover of the marrow sinus wall, an increase in sinus circumference, and a decrease in endothelial cell overlap. The marrow-blood barrier changes which precede the first wave of leukocytosis are transient and are associated with depletion of marrow granulocytes. The changes that precede the second wave of leukocytosis 5 to 6 days later are more sustained and are associated with marked granulocyte hyperplasia. We suggest that endotoxin has two effects on marrow ultrastructure: (1) an early, direct effect on the sinus wall and (2) a later, indirect effect associated with granulocyte proliferation. The late effect may be mediated through endotoxin induced release of colony stimulating factor. Both effects diminish the normal marrow-blood barrier and appear to facilitate cell release from the marrow.

Animals↗
PubMed1986

Regional [3H]testosterone uptake in the brain of isolated non-aggressive mice.

Male mice which are housed individually develop a characteristic aggressive, 'fighting' behavior. A small percentage of mice so isolated fail to become aggressive and in fact, behaviorally are strikingly different in that they develop a 'timid' behavior. Isolation-induced aggression is an androgen-dependent behavior and androgen-sensitive neurons have been identified in mouse brain, mainly in the limbic system. When intact isolated aggressive mice and isolated and aggregated non-aggressive mice were injected with radioactive testosterone and sacrificed after 30 min no remarkable differences in uptake of radioactive testosterone occurred in various brain areas. However, in castrated animals the uptake of testosterone was greatly enhanced in the isolated non-fighters whereas testosterone uptake in the isolated fighters and aggregated non-fighters was in the range of the intact animals. This study represents, for the first time, a documented hormonal difference between isolated aggressive and non-aggressive animals.

Aggression↗
PubMed1984

Histofluorescent identification of indoleamine-concentrating brain loci associated with intraspecies, reflexive biting and locomotor behavior in olfactory-bulbectomized mice.

The histofluorescent identification of indoleamine (serotonin)-concentrating neurons and the changes induced by olfactory bulbectomy (Obx) were correlated with reflexive biting and locomotor behavioral activities in grouped male mice. Between 2 and 35 days post-Obx, an increase in the number and fluorescent-intensity of indoleamine-containing neurons was identified in the olfactory tubercle, lateral olfactory tract (bed neurons) and piriform cortex. Neurons in the nucleus accumbens and anterior olfactory nucleus also demonstrated increased histofluorescence by Day 35 post-Obx as compared with controls, but to a lesser extent than observed in the other olfactory loci. The increase in serotonin concentration was inversely related to locomotor activity and directly correlated to biting behavior in Obx mice. These results demonstrate that the development of this type of intraspecies aggression is temporally correlated with an enhanced serotonin histofluorescence in specific forebrain, olfactory regions in mice.

Animals↗
PubMed1978

Parasinusoidal location of megakaryocytes in marrow: a determinant of platelet release.

Megakaryocytopoiesis occurs in the hematopoietic (extravascular) compartment of marrow. Thus, platelets must traverse the wall of the vascular sinuses of marrow to enter the circulation. We have examined mouse and rat marrow, fixed by rapid immersion so as to maintain anatomical relationships as close to the natural state as possible. Quantitative transmission electron microscopy (TEM) of random transections of femurs established that megakaryocytes reside less than 1 mu from a marrow sinus wall with a probability unlikely to be the result of chance (P less than 0.001). An intimate relationship exists between the megakaryocyte periphery and the abluminal surface of the endothelial lining cell. At the time of platelet release megakaryocyte cytoplasm invaginates and penetrates the endothelial lining cell. The penetrating cytoplasm is detached and enters the marrow circulation. From their dimensions in comparison to circulating platelets, the released cytoplasm represents a packet of platelets that undergoes further fragmentation in the circulation. The parasinusoidal location of megakaryocytes and the process of sinus-wall penetration and platelet delivery was observed by TEM and scanning electron microscopy. These studies provided quantitative support for a specific anatomical arrangement of megakaryocytes in marrow. Moreover, the process of platelet release appears to be a physiological form of metastasis with invasion of vascular walls and vascular spread of cells, that are in this case amitotic.

Animals↗
PubMed1977

The regulation of the release of granulocytes from normal marrow.

Figure 16 synthesizes the various aspects of marrow egress. The central anatomical relationship of the hematopoietic compartment to vascular sinus is shown above. The hatched blocks represent the sinus wall, capable of developing narrow migration channels. In the marrow, immature granulocytes alter their biophysical characteristics by developing motility, nuclear and cytoplasmic deformability and surfaces which facilitate egress. Humoral factors contribute to proliferation and maturation. Also, other humoral agents, releasing factors, may act on mature cells, for example, as cytoattractants, and on the sinus wall to reduce its adventitial cover and thereby to enhance egress. In the sinus, flow or discharge of sinus contents may be regulated by humoral agents or neural messages which may affect terminal sphincters or other structures. Although the marrow in situ is a difficult organ to study, future innovations are to be expected and our understanding of the delicate balance between hematopoietic cells, stroma and vasculature will be enhanced. Corrections of inferential errors due in part to the semi-quantitative and qualitative nature of much of our current data should be expected.

Animals↗
PubMed1976

Isolation of variant lymphoma cells with reduced growth requirements for extracellular calcium and magnesium and enhanced oncogenicity.

By exposing an established cell line of malignant mouse lymphocytic cells (L5178Y) to a culture environment low in calcium and magnesium, we have isolated and maintained in continuous culture a variant population with reduced growth requirements for the cations. The variant cells are larger, have enhanced aggregability, tend to form dispersed colonies in semisolid medium, and have increased oncogenicity. Variants and their progenitors share similar morphology, maximum proliferative rate, and stability of phenotype. The significance of these findings is discussed and an analogy suggested between the selective influence of calcium and magnesium deprivation in vitro and the evolution of thymic dysplasias in divalent cation-deprived rodents.

Animals↗
PubMed1975

Bone marrow sinus cell packing: a determinant of cell release.

Ultrastructural studies of erythropoietin effects on the bone marrow of control and hypertransfused (65 hct) mice revealed a decrease in adventitial cell cover of the sinus apertures in erythropoietin-treated animals. A more striking finding, however, was the marked inhibition of erythropoietin-induced reticulocytosis by hypertransfusion itself. Hypertransfusion of the erythropoietin-treated animals appeared to decrease the reticulocyte response by inhibiting reticulocyte response by marrow cords in addition to inhibiting erythroid proliferation. This inhibition of reticulocyte response was associated with clustering of reticulocytes around the marrow sinuses which were packed with red cells. Acute lowering of the hematocrit of erythropoietin-treated, hypertransfused animals to normal at the time of maximal reticulocyte response in control animals resulted in more than a twofold increase in reticulocytosis with 2 hr. It is suggested that (1) elevated levels of erythropoietin are associated with a diminution of the normal marrow-peripheral blood barrier, thereby contributing to the premature release of marrow elements and (2) the hematocrit is an important determinant of cell release from the marrow into the peripheral circulation.

Animals↗
PubMed1975

Contrasting splenic mechanisms in the blood clearance of red blood cells and colloidal particles.

We have studied the blood clearance and organ uptake of colloidal particles and of antibody-coated and chemically treated Na2 51Cr O4-labeled erythrocytes (RBC) in mice. Hepatic and splenic uptake of both colloidal particles and autologous RBC coated with rabbit antibody were reduced significantly following pretreatment of animals with cortisone acetate. Hepatic removal of RBC previously treated in vitro with N-ethyl-maleimide (NEM) or phenylhydrazine-HCl (PHZ) was similarly depressed by pretreatment with cortisone. In contrast, the splenic uptake of NEM- and PHZ-altered erythrocytes was unaffected by cortisone. Scanning and transmission electron microscopic examination of perfused spleens from PHZ-injected animals demonstrated extensive mechanical trapping of Heinz body-containing RBC in sinus wall apertures, whereas little erythrophagocytosis was observed. These studies suggested that, while clearance of inert particulate matter and of antibody-coated RBC from the blood occurred primarily by a cortisone-suppressible, presumably phagocytic process in the spleen, chemically altered RBC were removed primarily by a cortisone-insensitive filtration process in the splenic microvasculature.

Animals↗
PubMedDate not supplied

Regional CNS densities of serotonin and dopamine receptors in high alcohol-drinking (HAD) and low alcohol-drinking (LAD) rats.

The densities of subtypes of serotonin (5-HT) and dopamine (DA) receptors were determined in the CNS of male alcohol-naive HAD and LAD lines of rats. Autoradiographic studies were undertaken to measure the densities of (a) 5-HT1A sites labelled with 2 nM [3H]8-OH DPAT, (b) 5-HT2A sites labelled with 2 nM [3H] ketanserin, (c) D1 sites labelled with 1 nM [3H]SCH23390, and (d) D2 sites labelled with 20 nM [3H]sulpiride. Membrane binding, using tissue combined from the olfactory bulb, olfactory tubercle, and nucleus accumbens, was carried out to determine Kd and Bmax values for the binding of 0.25-8.0 nM [3H]7-OH DPAT to D3 sites. Among the 14 regions measured for densities of 5-HT1A sites, no interline differences were found in the cerebral cortical regions or in the septal nuclei; however, within the hippocampus, 15-20% lower binding of [3H]8-OH DPAT was observed in the posterior dorsal CA3 and dentate gyrus of the HAD line. There were no interline differences in any of the 10 regions examined for [3H]ketanserin binding to 5-HT2A sites, or in the densities of D1 and D2 sites in the mesolimbic and nigrostriatal DA systems, except for a 35% higher density of D2 sites in the substantia nigra pars compacta of the HAD line. There were no interline differences in the Kd or Bmax values for [3H]7-OH DPAT binding to D3 sites. Overall, these results indicate that no marked interline differences are evident in the densities of 5-HT1A, 5-HT2A, D1, D2, and D3 receptors within the mesolimbic system that could be associated with the disparate alcohol drinking behaviors of the HAD and LAD rats.

8-Hydroxy-2-(di-n-propylamino)tetralin↗