Biomedical subjects

L Dragovic

Publications and source records attributed to L Dragovic.

11 recordsLinked to original sources

PubMed1994

Expression of immunologically relevant endothelial cell activation antigens on isolated central nervous system microvessels from patients with multiple sclerosis.

Activation of the vascular endothelium is thought to be an important facet of inflammation, thrombosis, and vasculitis. Activated endothelial cells express a number of immunologically relevant surface markers not expressed by normal endothelial cells. Many of these surface antigens are thought to augment adhesion reactions and migration. Our results show that endothelial activation may play a central role in the pathogenesis of multiple sclerosis (MS). Normal human central nervous system microvessels isolated from autopsy material do not express endothelial cell activation markers, including the adhesion proteins vascular cell adhesion molecule-1 (VCAM-1) and endothelial cell leukocyte adhesion molecule-1 (E-selectin/ELAM-1). They exhibit little to no constitutive expression of immunoreactive intercellular adhesion molecule-1 (ICAM-1) or the urokinase plasminogen activator receptor. Control microvessels exhibit no major histocompatibility complex (MHC) class II antigen. MS microvessels express significant levels of MHC class II antigens, ICAM-1, VCAM-1, and urokinase plasminogen activator receptor. E-selectin was expressed by 3 of 5 MS brains tested. Histologically unaffected areas of MS brain expressed less VCAM-1, ICAM-1, and E-selectin than did microvessels from periplaque zones. However, MHC class II antigens and urokinase plasminogen activator receptor were increased in areas exhibiting little to no evidence of leukocyte infiltration. When microvessels were examined for dual expression of activation markers, we found that in periplaque areas, 50% of microvessels coexpressed HLA-DR and VCAM-1, 28% of microvessels coexpressed HLA-DR and urokinase plasminogen activator receptor, and 43% of microvessels coexpressed HLA-DR and ICAM-1.

Adolescent↗

PubMed1993

Expression of endothelial cell activation antigens in microvessels from patients with multiple sclerosis.

Although the mechanisms governing EC activation are not well understood, evidence points to a role for locally released cytokines from activated leukocytes. We propose that the sequence of events that result in EC activation are important in perivascular leukocyte infiltration into the CNS seen in MS. In the present study we examined expression of EC activation antigens on cerebral microvessels from patients with MS using immunofluorescence staining and quantitation by laser cytometry. Normal human microvessels do not express MHC class II antigens (Ags), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), or the urokinase plasminogen activator receptor (uPA-R). They express low levels of transferrin receptors and express factor VIII. Microvessels prepared from MS brain with plaque involvement expressed decreased factor VIII and increased transferrin receptors (tfR). Expression of the adhesion molecules VCAM-1, and ICAM-1 were found on 80% of isolated microvessels. HLA-DR Ags were expressed on 40-60% of microvessels, and the uPA-R was expressed on 50% of MS microvessels examined. MHC class II Ags co-express with VCAM-1 and ICAM-1 more frequently than with the uPA-R. Results indicate that activation of EC in MS is likely to be an important factor in disease pathology.

Antigens, Surface↗

PubMed1992

Selective deep hypothermia of the spinal cord prevents paraplegia after aortic cross-clamping in the dog model.

We tested, in the dog, the hypothesis that selective deep hypothermia (19 degrees to 12 degrees C) of the spinal cord protects it from the ischemia that follows double aortic cross-clamping. The extracorporal perfusion system consisted of heat exchanger and a pump, infusing saline solution at 5 degrees C into the subarachnoid space (L-6) and draining it through the cisterna magna. After 30 minutes this system cools a normally perfused spinal cord to a stable temperature gradient of 13 degrees C (inflow) to 18 degrees C (outflow). Proximal and distal intrathecal, proximal and distal aortic, and central venous pressures were continuously recorded. Rectal temperature was maintained between 36.5 degrees C and 38.5 degrees C. Eight control dogs had cross-clamping of the aorta below the left subclavian artery and above the diaphragm without cord hypothermia. Nine experimental dogs had cord hypothermia initiated 50 minutes before systemic heparinization (100 U/kg) and double cross-clamping of the aorta. Cross-clamping was maintained for 45 minutes. The aorta was then unclamped, heparin was reversed, cord cooling was discontinued, and the dura was closed. Hindlimb function of animals was graded by use of Tarlov's scale at recovery and 24 hours later. The dogs were then killed, and the cords were removed and fixed for microscopy. All control animals were paraplegic and had histologic confirmation of spinal cord infarction. All experimental animals had intact hindlimb function and normal appearing cords on histologic examination. A two-tailed Fisher's exact test (chi square) shows this difference to be significant to p = 0.00004. In the dog selective deep hypothermia of the cord avoids the ischemic injury induced by aortic cross-clamping that results in paraplegia. The implications of these findings in thoracoabdominal aortic clamping in humans is discussed.

Animals↗

PubMed1992

Microsurgical anatomy of the lower basilar artery.

This study was designed to study the microvascular anatomy of the basilar artery between the superior cerebellar artery and the vertebrobasilar junction (i.e. the lower basilar artery). Twenty unfixed brains were injected with silicone rubber solution and studied with a Zeiss OPMI microscope. The length of this segment of the basilar artery was 28.1 + 1.35 mm and its course was straight in 9 (45%) brains, curved in 7 (35%) and tortuous in 4 (20%). The total number of perforators found in 20 brains was 340 with an average of 17 per brain. Of these, 118 (34.7%) were median and 222 (65.2%) were lateral. Median branches had a mean length of 5.8 + 1.25 mm, whereas left and right lateral branches had a mean length of 16 + 1.25 mm and 16 + 1.58 mm respectively.

Autopsy↗

PubMed1992

Variability of the territories of the major cerebral arteries.

Recent morphological and functional studies on the circle of Willis suggest that the areas of supply of the six major cerebral arteries show a considerable variation in distribution, in contrast to the relatively consistent pattern generally accepted; therefore, the cortical and intracerebral distribution of the territories of these arteries was investigated in 25 unfixed human brains obtained at routine autopsy. The six major cerebral arteries were simultaneously injected under the same pressure with different-colored Araldite F mixtures under standardized conditions to obtain the most realistic territorial distribution. The cortical boundaries were examined and recorded in relation to the cerebral gyri and sulci, and the territories of the anterior, middle, and posterior cerebral arteries were analyzed and compared. The intracerebral distribution of these territories was investigated after the injected brains were cut in parallel slices. The variability of the territories of these arteries was much larger than generally described in the literature. Twenty-six variations in the territory of the anterior cerebral artery, 17 variations in the area of the middle cerebral artery, and 22 variations in the area of the posterior cerebral artery were found in the cortex of 50 hemispheres. Intracerebrally, the anterior, middle, and posterior cerebral arteries contributed in varying degrees to the blood supply of the lobar white matter, the internal capsule, the caudate nucleus, and the lentiform nucleus. The large variation in the area in which the cortical and intracerebral boundaries between these territories was located was demonstrated by illustrating the minimum and maximum extent of each. The results are compared with prior findings, and their implications for both experimental model studies and clinical practice are discussed.

Adolescent↗

PubMed1991

The anterior cavernous sinus space.

The anterior cavernous sinus space is the venous space anterior to the cavernous carotid artery. It is tetrahedral in shape with the anterior apex at the superior orbital fissure. The superomedial wall is formed by the base of the anterior clinoid process. The inferomedial wall is formed by the sphenoid bone. The lateral wall consists of two layers of dura with the oculomotor, trochlear, ophthalmic and abducens nerves in the inner layer. Medially, the posterior wall consists of the cavernous carotid artery. Laterally, it communicates with the lateral cavernous sinus space. Paraclinoid and carotid cave aneurysms may occupy this space and its microanatomy is important in the surgery of these aneurysms.

Carotid Arteries↗

PubMed1991

Characterization of herpes simplex virus type 2 latency-associated transcription in human sacral ganglia and in cell culture.

The ability of herpes simplex virus type 2 (HSV-2) to establish latency in and reactivate from sacral dorsal root sensory ganglia is the basis for recurrent genital herpes. The expression of HSV-2 genes in latently infected human sacral ganglia was investigated by in situ hybridization. Hybridizations with a probe from the long repeat region of HSV-2 revealed strong nuclear signals overlying neurons in sacral ganglia from five of nine individuals. The RNA detected overlaps with the transcript for infected cell protein O but in the opposite, or "anti-sense," orientation. These observations mimic those made previously with HSV-1 in human trigeminal ganglia and confirm the recent findings during latency in HSV-2-infected mice and guinea pigs. Northern hybridization of RNA from infected Vero cells showed that an HSV-2 latency-associated transcript was similar in size to the larger (1.85 kb) latency transcript of HSV-1. Thus, HSV-1 and HSV-2 latency in human sensory ganglia are similar, if not identical, in terms of their cellular localization and pattern of transcription.

Adult↗

PubMed1991

Anatomy of the sympathetic pathways in the carotid canal.

The sympathetic fibers in the carotid canal were studied in 30 unfixed specimens from human cadavers. Thirty petrous internal carotid arteries were injected with red silicone rubber, and the course of the sympathetic fibers was examined after removal of the inferior and superior wall of the carotid canal. The internal carotid artery was removed completely, leaving the sympathetic fibers intact as much as possible. Instead of a plexus-like configuration of the sympathetic fibers around the petrous carotid artery in all specimens, an anterosuperior group and a posteroinferior group of sympathetic fibers were found together, and both closed on the inferior-anterior side of the terminal portion of the horizontal part of the carotid canal. Seventy-three percent of the anterosuperior group of sympathetic fibers consisted of one large bundle, and 27% consisted of two smaller bundles. The majority of the posteroinferior group of sympathetic fibers consisted only of one bundle (93%). In 60% of the specimens, the majority of sympathetic fibers in the carotid canal were found in the anterosuperior group, 20% were found in the posteroinferior group, and in 20%, there was an equal distribution. The formation of the petrous bone and the related structures of the skull base play an important role in the configuration of these groups of sympathetic fibers. This study shows that, in cases of operative intervention in the carotid canal, the anterosuperior group of sympathetic fibers may be encountered. Damage to this bundle may result in sympathicoparesis, as it often contains the most sympathetic fibers. This group of sympathetic fibers can be easily separated from the internal carotid artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Carotid Artery, Internal↗

PubMed1991

Microvascular anatomy of foramen caecum medullae oblongatae.

The foramen caecum (FC) is a triangular-shaped fossa situated in the midline on the base of the brain stem, at the pontomedullary junction. Although this area is known to have a very high concentration of brainstem perforating vessels, its microvascular anatomy has not been studied in detail. The purpose of this study was to detail the microvasculature of this territory. Twenty unfixed brains were injected with silicone rubber solution and dissected under a microscope equipped with a camera. The origin, course, outer diameter, and branching pattern of the perforators were examined. The total number of perforators found in the 20 brains was 287, with an average (+/- standard deviation) of 14.35 +/- 1.24 perforators per brain (range seven to 28). Their origin was as follows: right vertebral artery in 52 perforators (18.11%); left vertebral artery in 35 (12.19%); basilar artery below the anterior inferior cerebellar artery (AICA) in 139 (48.43%); basilar artery above the AICA in 46 (16.02%); AICA in 10 (3.48%); and anterior spinal artery in five (1.74%). Most of the perforators arose as sub-branches of larger trunks; their average outer diameter was 0.16 +/- 0.006 mm while that of trunks was 0.35 +/- 0.02 mm. These anatomical data are important for those wishing 1) to study the pathophysiology of vascular insults to this area caused by atheromas, thrombi, and emboli; 2) to plan vertebrobasilar aneurysm surgery; 3) to plan surgery for vertebrobasilar insufficiency; and 4) to study foramen magnum neoplasms.

Arteriovenous Anastomosis↗

PubMed1990

Circadian rhythms of human pineal melatonin, related indoles, and beta adrenoreceptors: post-mortem evaluation.

Human pineal glands obtained from 77 post-mortem sources from various age groups and times of death were used to examine the 24-hour cycle of serotonin (5-HT), melatonin, N-acetylserotonin (NAS), and beta adrenoceptor density. Pineal glands were divided sagittally and a single half was used to measure 5-HT, NAS, and melatonin concentrations, while the remaining half from the same gland was employed to assess changes in the density of beta adrenoceptors on partially purified membranes. The results show that density of pineal beta adrenoceptors was relatively constant between midnight and 18.00 h and became significantly higher between 18.00 and 20.00 h as measured by ligand saturation binding experiments using (125-I) iodocyanopindolol. The receptor affinity of all of the samples assayed remained in relatively narrow range near 58 pM and only changes in the relative receptor density were apparent. The up-regulation of receptors coincided with an increase in the concentration of 5-HT that began to rise between 16.00 and 20.00 h and became maximal between 20.00 and midnight. NAS, the immediate precursor of melatonin, was also at maximal levels between 20.00 h and midnight. Both 5-HT and NAS began declining after midnight and this change corresponded to the maximal pineal gland concentration of melatonin between midnight and 4.00 h. It is therefore suggested that the up-regulation of beta adrenoceptors noted during the late afternoon and early evening hours corresponds to the increased synthesis of 5-HT and the subsequent conversion to NAS. These events are followed by the highest accumulation of melatonin after midnight and represent the synthesis of melatonin from its precursor NAS in a sequential pattern.

Adolescent↗

PubMed1985

Neurotoxicity of Adriamycin and misonidazole in the mouse.

The neurotoxicity of the anticancer drug adriamycin was investigated in the peripheral nerve of the mouse. Injection of adriamycin into the sciatic nerve resulted in biochemical and morphologic signs of severe axonal degeneration. The biochemical evidence was based on marked increases in lysosomal enzyme activity. Acid protease and N-acetylglucosaminidase remained elevated for more than 70 days after injecting the drug. In contrast, local injection of the radiation-sensitizing drug misonidazole into the peripheral nerve failed to increase lysosomal enzyme activity.

Animals↗