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Biomedical subjects

J Westman

Publications and source records attributed to J Westman.

At least 55 records · Page 3Linked to original sources
PubMed1998

Sterol 27-hydroxylase- and apoAI/phospholipid-mediated efflux of cholesterol from cholesterol-laden macrophages: evidence for an inverse relation between the two mechanisms.

Cholesterol-laden, human monocyte-derived macrophages were found to contain 27-hydroxycholesterol in proportion to their content of cholesterol ester. In accordance with previous work with human lung alveolar macrophages, there was a significant efflux of 27-hydroxycholesterol and 3beta-hydroxy-5-cholestenoic acid from the cultured cells. The efflux of 27-hydroxycholesterol was proportional to the cellular content of this steroid. Incubation of cholesterol-laden macrophages with reconstituted discoidal complexes made from apolipoprotein A-I and phospholipids resulted in a decrease in total cellular cholesterol, an increase in the efflux of free cholesterol, and a concomitant decrease in the total production and efflux of 27-oxygenated steroids, in particular, 3beta-hydroxy-5-cholestenoic acid. Reconstituted discoidal complexes with the Milano variant of apolipoprotein A-I gave virtually identical results, whereas high density lipoprotein was less efficient. These results suggest that cultured cholesterol-laden cells can export some of their excess cholesterol in the form of 27-hydroxycholesterol, 3beta-hydroxy-5-cholestenoic acid, and free cholesterol. In the presence of exogenous cholesterol acceptors, export of free cholesterol becomes more effective, resulting in less cholesterol exported via the 27-hydroxylase pathway. The balance between the two mechanisms for removal of cholesterol from macrophages may be of importance for formation of foam cells and development of atherosclerosis.

Apolipoprotein A-I↗
PubMed1997

Involvement of nitric oxide in the pathophysiology of acute heat stress in the rat. Influence of a new antioxidant compound H-290/51.

The possibility that nitric oxide (NO) is involved in the pathophysiology of brain injury caused by heat stress (HS) was examined using immunohistochemistry of a constitutive isoform of neuronal nitric oxide synthase (c-NOS) in a rat model. In addition, to discover the role of oxidative stress in inducing c-NOS activity in HS, the effect of a new antioxidant H-290/51 on HS-induced expression of c-NOS immunoreactivity was examined. Subjection of conscious young animals to a 4-h HS in a biological oxygen demand (BOD) incubator at 38 degrees C resulted in marked upregulation of c-NOS in the cerebral cortex and hippocampus of stressed rats compared to normal rats kept at room temperature (21 +/- 1 degrees C). The c-NOS immunoreactivity was found in distorted neurons located in the edematous regions not normally showing c-NOS activity. Pretreatment with H-290/51 significantly attenuated the upregulation of c-NOS in animals subjected to HS, and the signs of neuronal distortion and edema were less pronounced. These results suggest that HS has the capacity to induce upregulation of c-NOS, and these effects can be reduced by prior treatment with H-290/51, indicating a possible neuroprotective effect of antioxidants in thermal brain injury.

Animals↗
PubMed1997

Topical application of insulin like growth factor-1 reduces edema and upregulation of neuronal nitric oxide synthase following trauma to the rat spinal cord.

The neuroprotective effects of insulin like growth factor-1 (IGF-1) on spinal cord injury induced edema formation, cell changes and profound upregulation of constitutive isoform of neuronal nitric oxide synthase (cNOS) was examined in a rat model. A focal spinal cord injury produced by making a lesion (about 2 mm deep and 5 mm long) of the right dorsal horn of the T10-11 segment resulted in a marked edema formation, cell injury and upregulation of cNOS following 5 h after trauma. In separate groups application of IGF-1 (0.1 microgram/microliter) topically on the exposed spinal cord (T10-11) starting from 30 min before injury (20 microliter), immediately before injury followed by 30 min, 60 min and thereafter every 1 h after injury until sacrifice resulted in significant attenuation of edema formation and cell changes. Immunohistochemistry showed a less pronounced expression of cNOS in the T9 and T12 segments of the cord in IGF treated rats compared to untreated traumatised controls. These results for the first time show that IGF treatment is neuroprotective and this effects of the IGF appears to be mediated via inhibition of NOS upregulation.

Administration, Topical↗
PubMed1997

Prostaglandins modulate constitutive isoform of heat shock protein (72 kD) response following trauma to the rat spinal cord.

The influence of prostaglandins on the constitutive isoform of heat shock protein (HSP 72 kD) response following a focal trauma to the rat spinal cord was examined using immunohistochemistry. A focal trauma to the spinal cord by making a longitudinal incision into the right dorsal (about 2 mm deep and 5 mm long) of the T10-11 segments, markedly enhanced the upregulation of HSP immunoreactivity in the traumatised as well as in the perifocal T9 and T12 segments. This upregulation of HSP was significantly reduced by pretreatment with indomethacin (10 mg/kg, i.p., 30 min before injury) an inhibitor of prostaglandin synthesis. These results show that blockade of PG synthesis prior to trauma has an inhibitory influence on the upregulation of HSP response, not reported earlier.

Animals↗
PubMed1997

Topical application of 5-HT antibodies reduces edema and cell changes following trauma of the rat spinal cord.

Involvement of serotonin in the early microvascular reactions and cell changes following trauma of the spinal cord was examined using topical application of serotonin antibodies to the traumatised cord in a rat model. A focal trauma of the spinal cord was produced by making an incision into the right dorsal horn of the T10-11 segments (about 2 mm deep and 5 mm long); the animals were allowed to survive 5 h after injury. Monoclonal 5-HT antibodies (1:20) were applied (25 microliters in 10 sec) to the traumatised spinal cord 2 min after injury. There was a significant reduction in the breakdown of the blood-spinal cord barrier, edema formation, and cell changes in the traumatised rats which received 5-HT antiserum compared to the injured rats given saline. These results show that 5-HT is an important mediator involved in the early pathophysiological responses of spinal cord injury.

Administration, Topical↗
PubMed1997

Benzodiazepine receptors influence spinal cord evoked potentials and edema following trauma to the rat spinal cord.

The possibility that diazepam will influence spinal cord evoked potentials (SCEP), edema formation and cell changes following spinal cord injury (SCI) was examined in a rat model. The SCI was produced in equithesin anaesthetised animals by making a longitudinal incision (about 2 mm deep and 5 mm long) in the right dorsal horn of the T10-11 segments. The SCEP were recorded from the epidural space of the T9 segment after stimulation of the right tibial and sural nerves. The SCEP consisted of a small positive peak followed by a broad and high negative peak. Infliction of trauma to the rats resulted in an immediate and pronounced decrease of the maximal negative peak (MNP) amplitude. The spinal cord edema and cell changes were markedly pronounced 5 h after injury. Pretreatment with diazepam attenuated the early SCEP changes induced by the trauma and reduced the later development of edema and cell injury. These results suggest that benzodiazepine receptors are involved in trauma induced alterations in SCEP changes, edema formation and cell injury, not reported earlier.

Animals↗
PubMed1997

Role of neurochemicals in brain edema and cell changes following hyperthermic brain injury in the rat.

The involvement of three potent neurochemical mediators of the edema formation such as serotonin, prostaglandins and opioids in the pathophysiology of hyperthermic brain injury was examined in a rat model using a pharmacological approach. Hyperthermic brain injury was induced in conscious young rats by exposing them to heat stress at 38 degrees C for 4 h. In these rats the blood-brain barrier (BBB) permeability, brain edema, cerebral blood flow (CBF), heat shock protein 72 kD (HSP) response and cell changes were examined. Pretreatment with ketanserin (a serotonin-2 receptor antagonist), indomethacin (prostaglandin synthesis inhibitor) and naloxone (opioid receptor antagonist) in separate groups of rats reduced hyperthermia and HSP response following heat stress and significantly attenuated changes in the BBB permeability, brain edema, CBF and cell reaction. These results suggest that the pathophysiology of hyperthermic brain injury is a complex mechanisms and several neurochemicals are involved in the brain pathology caused by heat stress.

Animals↗
PubMed1997

Acute heat stress induces edema and nitric oxide synthase upregulation and down-regulates mRNA levels of the NMDAR1, NMDAR2A and NMDAR2B subunits in the rat hippocampus.

The influence of heat stress on constitutive isoform of neuronal nitric oxide synthase (cNOS) and NMDA receptor gene expression in hippocampus was examined in a rat model. Subjection of animals to 4 h heat stress at 38 degrees C resulted in a marked upregulation of cNOS in the hippocampus accompanied with a marked general expansion and edematous cell changes. On the other hand NMDA receptor messenger RNA encoding NMDAR1, NMDAR2A and NMDAR2B subunits showed a marked downregulation in the hippocampus of heat stressed rats compared to the controls. Our results show that upregulation of cNOS is instrumental in heat stress associated edema and cell injury. Furthermore, an increased production of NO as evident with upregulation of cNOS appears to be a key factor in the downregulation of NMDA receptor gene expression in heat stress.

Acute Disease↗
PubMed1996

A new method for transcutaneous coaxial neuroendoscopy.

A new method of direct endoscopy of the subarachnoid space and a major part of the ventricles of the human central nervous system is presented. The technique was developed on more than 100 human bodies with the help of a bronchoscope. Percutaneous entry into the subarachnoidal space is performed from the dorsal side between vertebrae L5 and S1. The endoscope can be moved along the spinal cord on both the dorsal and the ventral side. From the dorsal side of spinal cord the cerebello-medullary cistern can be reached. The fourth ventricle is entered through the median aperture and then the third ventricle through the cerebral aqueduct. From the ventral side of the spinal cord the posterior cranial fossa is reached and the large arteries and the cranial nerves can be inspected. The main conclusion of the present report is that the subarachnoid space seems to be large enough for a coaxial exploration with a 3-5 mm diameter fibroscope if the investigator possesses a good knowledge of the subarachnoid anatomy. The technique provides new approaches in research and possibilities of clinical investigations and therapy.

Cadaver↗
PubMed1996

Involvement of nitric oxide in acute spinal cord injury: an immunocytochemical study using light and electron microscopy in the rat.

The possibility that nitric oxide participates in the pathophysiology of spinal cord injury was examined using a constitutive isoform of neuronal nitric oxide synthase immunoreactivity in a rat model. Spinal cord trauma was produced by making an incision into the right dorsal horn of the T10-11 segments. Five h after trauma, a marked upregulation of NOS-immunostained neurons was seen in the perifocal T9 and T12 segments of the cord. The immunolabelling was most pronounced in the dorsal horn of the ipsilateral side. Topical application of an antiserum to nitric oxide synthase (NOS) 2 min after injury prevented the trauma-induced upregulation of NOS-immunoreactivity. In contrast, application of preabsorbed serum or L-NAME, an inhibitor to NOS, was ineffective in reducing the induction of NOS-immunoreactivity. Trauma caused a marked expansion of the cord and resulted in marked cell changes. This expansion and cell reaction was significantly reduced following application of NOS antiserum but it was not seen after application of preabsorbed antiserum or L-NAME. Our results for the first time show that a focal trauma to the spinal cord has the capacity to upregulate neuronal NOS immunoreactivity and that application of NOS antiserum has a neuro protective effect. This indicates that nitric oxide is somehow involved in the pathogenesis of secondary injuries after spinal cord trauma.

Amino Acid Sequence↗
PubMed1995

Probable involvement of serotonin in the increased permeability of the blood-brain barrier by forced swimming. An experimental study using Evans blue and 131I-sodium tracers in the rat.

The possibility that endogenous serotonin (5-hydroxytryptamine, 5-HT) participates in alteration of the blood-brain barrier (BBB) following short-term forced swimming (FS) exercise was examined in a rat model. Subjection of conscious young (age 8-9 weeks, 80-90 g) animals to continuous FS (at a water temperature of 30 +/- 1 degrees C) for 30 min, increased the permeability of the BBB to Evans blue albumin (EBA) and 131I-sodium in six and nine brain regions, respectively. The EBA staining was noted in posterior cingulate cortex, parietal, occipital cortices, cerebellar vermis, medial lateral cerebellar cortices and dorsal surface of hippocampus. In addition to these brain regions, the BBB permeability to 131I-sodium was further extended to caudate nucleus, thalamus and hypothalamus. This effect of FS on the BBB permeability was absent in adult (age 24-30 weeks, 300-400 g) animals. Measurement of 5-HT showed a profound increase of plasma and brain in young rats by 180% and 250%, respectively, from the control group. Adult animals showed only a minor increase in brain and plasma 5-HT levels. In young animals, pretreatment with p-CPA (a 5-HT synthesis inhibitor) and indomethacin (a prostaglandin synthesis inhibitor) prevented the FS induced increase in BBB permeability and 5-HT levels. Destruction of serotonergic neurons with 5,7-dihydroxytryptamine (5,7-DHT) reduced the breakdown of the BBB and attenuated the brain 5-HT level without affecting the plasma 5-HT. Cyproheptadine, ketanserin (5-HT2 receptor antagonists) and vinblastine (a vesicular transport inhibitor) prevented the increased permeability of the BBB alone. The plasma and brain 5-HT continued to remain high. These observations suggest that (i) 5-HT plays an important role in the breakdown of BBB permeability in FS, (ii) this effect of 5-HT on BBB permeability is mediated by 5-HT2 receptors, and (iii) FS induced increase in BBB permeability is age dependent.

5,7-Dihydroxytryptamine↗
PubMed1995

FGF binding and FGF receptor activation by synthetic heparan-derived di- and trisaccharides.

Fibroblast growth factors (FGFs) require a polysaccharide cofactor, heparin or heparan sulfate (HS), for receptor binding and activation. To probe the molecular mechanism by which heparin or HS (heparin/HS) activates FGF, small nonsulfated oligosaccharides found within heparin/HS were assayed for activity. These synthetic and isomerically pure compounds can activate the FGF signaling pathway. The crystal structures of complexes between FGF and these heparin/HS oligosaccharides reveal several binding sites on FGF and constrain possible mechanisms by which heparin/HS can activate the FGF receptor. These studies establish a framework for the molecular design of compounds capable of modulating FGF activity.

Animals↗
PubMed1995

A serotonin synthesis inhibitor, p-chlorophenylalanine reduces the heat shock protein response following trauma to the spinal cord: an immunohistochemical and ultrastructural study in the rat.

The influence of the serotonin synthesis inhibitor, p-CPA on the expression of the heat shock protein (70 kDa), which occurs around an injury to the rat spinal cord, was examined by immunohistochemistry. A longitudinal incision was made into the right dorsal horn at the T10-11 level. Five hours later samples were removed from the T9 and T12 segments. Samples from untreated traumatised animals showed signs of edema and many distorted neurons, particularly in the ipsilateral grey matter. Neurons of the same regions showed a profound increase in HSP-70 immunostaining compared with intact controls. At ultrastructural level, the immunoreactivity was detected in neuronal cytoplasm attached to the surface of organelles including endoplasmic reticulum, in the nucleus and in dendrites. Other groups of rats were given p-CPA before injury to reduce the synthesis of serotonin and to minimise its stores in the cord. The HSP-immunostaining in neurons of the T9 and T12 segments of the spinal cord was virtually lacking in the drug treated animals. The signs of edema and the structural changes of these segments were markedly reduced. The results show that inhibition of serotonin synthesis prior to the traumatic insult has an inhibitory influence on HSP response occurring in neurons around the site of injury to the spinal cord, not reported earlier.

Animals↗
PubMed1995

In vitro reverse cholesterol transport from THP-1-derived macrophage-like cells with synthetic HDL particles consisting of proapolipoprotein A1 or apolipoprotein A1 and phosphatidylcholine.

The human monocytic leukaemia cell line THP-1 was induced to differentiate to macrophage-like cells by the addition of phorbol myristoyl acetate (PMA). Subsequently, the cells were enriched in cholesterol and these cholesterol laden cells were used to study the capability of reconstituted discoidal complexes (RDCs), consisting of either human apolipoprotein A1 (apo A1) or recombinant human proapolipoprotein A1 (proapo A1) and phosphatidylcholine (PC), to promote cholesterol efflux. RDCs containing apo A1 and proapo A1 were both effective in the mobilization of intracellular cholesterol, whether this was measured by intracellular cholesterol mass or by the appearance of radiolabelled cholesterol in the supernatant. Using the radiolabelling technique, the activity was saturable and followed Michaelis-Menten kinetics. For both types of complexes and for native HDL the maximum rate of cholesterol removed was approximately 0.5 nmol h-1 per 10(6) cells. For RDCs of proapo A1 and apo A1 and for native HDL the Km values were 3.7, 2.9 and 64.8 micrograms ml-1 respectively. A significant in vitro cholesterol efflux could only be achieved with protein-lipid complexes; no significant export was observed with either free proapo A1 or multilamellar PC liposomes without apolipoprotein. Both RDCs were found to be more active in the mobilization of intracellular cholesterol than HDL isolated from human plasma. The combined results demonstrate that synthetic complexes consisting either of apo A1 or proapo A1 and PC are both active in the in vitro reverse transport of cholesterol.

Apolipoprotein A-I↗
PubMed1994

Role of serotonin and prostaglandins in brain edema induced by heat stress. An experimental study in the young rat.

The possibility that serotonin and prostaglandins participate in edema formation following heat stress (HS) was examined in young rats. Exposure of conscious young animals (8-9 weeks old) to heat at 38 degrees C in a biological oxygen demand (BOD) incubator (relative humidity 50-55%; wind velocity 20-25 cm/s) for 4 h resulted in marked increase in the whole brain water content (about 3%) as compared to animals kept at room temperature (21 degrees C). A marked extravasation of Evans blue and 131I-sodium occurred in the brain of heat exposed animals as compared to normal animals. Morphological examination using electron microscopy of selected brain regions of heat stressed animals showed profound cell changes. Thus perivascular edema, swollen neuronal and glial cells, membrane damage, vesiculation of myelin, axonal swelling and synaptic damage was frequent in this group of untreated animals. Pretreatment with ketanserin (a selective serotonin2 receptor antagonist) or indomethacin (an inhibitor of prostaglandin synthesis) markedly reduced edema formation after 4 h HS in young animals. These heat stressed animals had considerably less extravasation of protein tracers as compared to the untreated group. Cell changes and edema at the ultrastructural level were mainly absent. Our results suggest that serotonin and prostaglandins are involved in heat stress induced breakdown of the BBB permeability, edema formation, and cell damage.

Animals↗