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Biomedical subjects

S Nazarian

Publications and source records attributed to S Nazarian.

18 recordsLinked to original sources

Immunosuppressant PG490 (triptolide) inhibits T-cell interleukin-2 expression at the level of purine-box/nuclear factor of activated T-cells and NF-kappaB transcriptional activation.

PG490 (triptolide) is a diterpene triepoxide with potent immunosuppressive and antiinflammatory properties. PG490 inhibits interleukin(IL)-2 expression by normal human peripheral blood lymphocytes stimulated with phorbol 12-myristate 13-acetate (PMA) and antibody to CD3 (IC50 of 10 ng/ml), and with PMA and ionomycin (Iono, IC50 of 40 ng/ml). In Jurkat T-cells, PG490 inhibits PMA/Iono-stimulated IL-2 transcription. PG490 inhibits the induction of DNA binding activity at the purine-box/antigen receptor response element (ARRE)/nuclear factor of activated T-cells (NF-AT) target sequence but not at the NF-kappaB site. PG490 can completely inhibit transcriptional activation at the purine-box/ARRE/NF-AT and NF-kappaB target DNA sequences triggered by all stimuli examined (PMA, PMA/Iono, tumor necrosis factor-alpha). PG490 also inhibits PMA-stimulated activation of a chimeric transcription factor in which the C-terminal TA1 transactivation domain of NF-kappaB p65 is fused to the DNA binding domain of GAL4. In 16HBE human bronchial epithelial cells, IL-8 expression is regulated predominantly by NF-kappaB, and PG490 but not cyclosporin A can completely inhibit expression of IL-8. The mechanism of PG490 inhibition of cytokine gene expression differs from cyclosporin A and involves nuclear inhibition of transcriptional activation of NF-kappaB and the purine-box regulator operating at the ARRE/NF-AT site at a step after specific DNA binding.

Binding Sites↗

Improved radiolabeled substrates for soluble epoxide hydrolase.

Two rapid assays for the soluble epoxide hydrolase (sEH) are described. First, a sensitive radiometric assay based on thin-layer chromatography of [(14)C]-cis-9,10-epoxystearic acid and its corresponding diol ((14)C]-9,10-dihydroxystearic acid) is described. The cis fatty acid oxide exhibits higher specific activity of hydration with sEH from mouse, rat, human, and potato compared to trans-stilbene oxide (TSO). The K(m) and V(max) obtained for [(14)C]-cis-9,10-epoxystearic acid with mouse sEH are 11.0 microM and 3460 nmol/min/mg protein, respectively. [(14)C]-cis-9,10- Epoxystearic acid might more closely mimic the structures of natural substrates for sEH. Second, [2-(3)H]-trans-1,3-diphenyl-propene oxide ([(3)H]-tDPPO) and [2-(3)H]-cis-1,3-diphenylpropene oxide ([(3)H]-cDPPO) were synthesized and rapid radiometric assays for epoxide hydrolases (EHs) were developed by differential partitioning of the epoxide into iso-octane and its corresponding diol into aqueous phase containing methanol. It was shown that sEHs from mouse, rat, human, and potato rapidly hydrolyze [(3)H]-tDPPO and in comparison to TSO have 20-,49-,28-, and 7-fold higher rates, respectively. Mouse sEH hydrates [(3)H]-tDPPO at 26,200 nmol/min/mg protein, and a K(m)p4 of 2.80 microM is observed.

Animals↗

A comprehensive classification of thoracic and lumbar injuries.

In view of the current level of knowledge and the numerous treatment possibilities, none of the existing classification systems of thoracic and lumbar injuries is completely satisfactory. As a result of more than a decade of consideration of the subject matter and a review of 1445 consecutive thoracolumbar injuries, a comprehensive classification of thoracic and lumbar injuries is proposed. The classification is primarily based on pathomorphological criteria. Categories are established according to the main mechanism of injury, pathomorphological uniformity, and in consideration of prognostic aspects regarding healing potential. The classification reflects a progressive scale of morphological damage by which the degree of instability is determined. The severity of the injury in terms of instability is expressed by its ranking within the classification system. A simple grid, the 3-3-3 scheme of the AO fracture classification, was used in grouping the injuries. This grid consists of three types: A, B, and C. Every type has three groups, each of which contains three subgroups with specifications. The types have a fundamental injury pattern which is determined by the three most important mechanisms acting on the spine: compression, distraction, and axial torque. Type A (vertebral body compression) focuses on injury patterns of the vertebral body. Type B injuries (anterior and posterior element injuries with distraction) are characterized by transverse disruption either anteriorly or posteriorly. Type C lesions (anterior and posterior element injuries with rotation) describe injury patterns resulting from axial torque. The latter are most often superimposed on either type A or type B lesions. Morphological criteria are predominantly used for further subdivision of the injuries. Severity progresses from type A through type C as well as within the types, groups, and further subdivisions. The 1445 cases were analyzed with regard to the level of the main injury, the frequency of types and groups, and the incidence of neurological deficit. Most injuries occurred around the thoracolumbar junction. The upper and lower end of the thoracolumbar spine and the T10 level were most infrequently injured. Type A fractures were found in 66.1%, type B in 14.5%, and type C in 19.4% of the cases. Stable type A1 fractures accounted for 34.7% of the total. Some injury patterns are typical for certain sections of the thoracolumbar spine and others for age groups. The neurological deficit, ranging from complete paraplegia to a single root lesion, was evaluated in 1212 cases.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗

Epiphysiodesis of the first metatarsal with cancellous allograft.

The authors describe a technique for an isolated epiphysiodesis of the first metatarsal with a cancellous allograft for the correction of juvenile hallux abducto valgus deformity. The procedure requires no incision. It is a benign, safe, and effective way of correcting the deformity.

Bone Transplantation↗

[Anatomic basis of the harvest of abdominal organs for organ transplants].

The abdominal organs removals, with a view to transplants, are complex surgical operations which require a perfect knowledge of visceral vascular anatomy. The common point of these removals is the "birenal en bloc excision", whose we have codified the development. This removal has induced us to revise many points of surgical anatomy and particulary: the connections between the liver and the right kidney; the importance of the mesoduodenum; the relative orientations of the portal vein and inferior vena cava axis; the ureteral vascularisation; the topography and the number of renal arteries; the connections between renal arteries orifices and superior mesenteric arterial orifice. When we have to remove, besides the kidneys, the liver or the pancreas or even the small intestine, surgical problems are the same, but then, the dissections concern also the celiac axis and the superior mesenteric artery. These multiple removals raise also many questions to the anatomist, the most interesting concerning: the multiple hepatic arteries; the connections between celiac branches of the abdominal aorta. All these notions are envisaged not only by the light of the anatomical preparations but also by reference to the clinical experience of the authors.

Abdomen↗

Anatomic basis of the transgluteal approach to the hip.

In order to define the technical modalities of the so-called transgluteal approach to the hip, the authors studied the structure and topography of the anatomic features encountered in this approach. The gluteus medius, gluteus minimus and vastus lateralis muscles are anatomically continuous by way of their tendinous fibers. The gluteus minimus muscle winds over the cranial and then anterolateral aspect of the capsule, to which it is bound by fibrous tracts and tendinous expansions; its terminal tendon blends its fibers with the anterior part of the tendon of the gluteus medius and enters into continuity with the superficial tendinous fibers of the anterior part of the vastus lateralis. The zone of junction of the three muscle structures is closely bound to the anterior aspect of greater trochanter. The caudal neurovascular trunk of the space between the gluteus medius and vastus lateralis is situated at a distance of 3 to 5 cm from the greater trochanter. The practical surgical implications are discussed, particularly as regards the methods of dissecting the anterior margin of the transgluteal incision, exposure of the capsule and preservation of the neurovascular pedicle, with reference to concepts published previously in studies elsewhere.

Buttocks↗

[Classification of injuries of the cervical spine].

Recent advances and the technical options that have lately become available in the surgical treatment of spinal injuries mean that clear definition of the indications is essential. Precise observation and classification of each injury to the cervical spine are of paramount importance for this purpose, to allow the comparison of proposed methods of treatment and of the results obtained with them. There are a number of classification systems for injuries to the cervical spine, none of which, however, is generally accepted. These classification systems are based on different criteria, such as nature of the accident at which the injury was sustained, neurologic deficits, morphological criteria, the concept of instability, and implications for treatment and prognosis. These criteria, however, hardly allow the classification of most of the injuries affecting the upper and those affecting the lower cervical spine in a single system. Therefore, the authors propose a system of their own, which draws on the principles of classification suggested by the ASIF for fractures of the extremities. According to this proposed new system, injuries are divided into those of the upper and those of the lower cervical spine, and each of these two main groups is further divided into three subgroups. In the case of the lower cervical spine, injuries are classed according as whether they affect the anterior or the posterior section of the spine more, or both to the same degree. Beyond this, injuries are subdivided with reference to whether they affect primarily bone, bone and ligament equally, or primarily ligament. Further subdivision by severity and implications for treatment allows more detailed differentiation. This classification system is based on the analysis of over 200 cases of injury to the cervical spine treated by the authors and of cases from the literature.

Axis, Cervical Vertebra↗

Anatomical basis of intervertebral disc puncture with chemonucleolysis.

Transparietal puncture of the lumbar intervertebral discs is done to achieve enzymatic nucleolysis. This technique requires firm understanding of the morphology and topography of the anatomical structures traversed by the needle as well as those to be avoided. Vertebral disc puncture with chemonucleolysis has been done by the author for four years. The aim of this study was to identify the parameters allowing facilitation of this procedure, thereby leading to a decreased X-ray exposure. To achieve this goal an analytical study of the target structure and its neurovascular, osseous and visceral relations was carried out. The results of this study led to practical conclusions regarding especially the parameters of disc puncture, their preoperative identification and the risks encountered in case of erroneous puncture.

Chymopapain↗

Normal CT anatomy of the spine. Anatomo-radiological correlations.

To analyse the anatomo-radiological correlation of the spine and spinal cord, 22 formalized, frozen anatomical specimens corresponding to different regions of the spinal column (8 cervical, 5 dorsal, and 9 lumbar) were studied by CT scans on axial, sagittal and coronal planes and by contact radiography after they were cut into anatomical slices in order to clarify the normal CT anatomy of the spinal column. The results obtained from CT patient scans, performed exclusively on the axial plane, were compared with those obtained from the anatomical specimens (both CT and contrast radiography). High resolution CT programs were used, enabling us to obtain better individualization of the normal structures contained in the spinal column. Direct sagittal and coronal sections were performed on the specimens in order to get further anatomo-radiological information. Enhanced CT studies of the specimens were also available because of the air already present in the subarachnoid spaces. Excellent visualization was obtained of bone structures, soft tissue and the spinal cord. High CT resolution of the spine appears to be an excellent neuroradiological procedure to study the spine and spinal cord. A metrizamide CT scan is, however, necessary when a normal unenhanced CT scan is insufficient for diagnosis and when the spinal cord is not clearly visible, as often happens at the cervical level. Clinical findings are certainly very useful to ascertain the exact CT level and to limit the radiation exposure.

Cervical Vertebrae↗

Lumbar stenosis surgery: the experience of the orthopaedic surgeon.

Between 1974 and 1989 350 patients were submitted to surgery for the treatment of stenosis of the lumbar canal; in 280 of these cases a minimum two-year follow-up was obtained. In all of the cases there was significant stenosis of the spinal canal, which was furthermore secondary to hypertrophy of the facet joints of degenerative nature. In 67% of the cases neurogenic claudication was present; in 57% there was monolateral radiculopathy, in 43% bilateral radiculopathy. The lesions extended from L4 to S1 in 39.2% of the cases, L3 to S1 in 36.3%, L5 to S1 in 8.5%, L2 to S1 in 7.2%, L4 to L5 in 4.6%, and L3 to L4 in 2.1%. Radiological diagnosis was confirmed by myelography and CT scan. Surgery involved laminectomy leaving intact at least 6 mm of the posterior facet joints in order to avoid destabilizing the spine; moreover, the anteromedial portion of the joint osteophytes was removed in order to release the lateral recess and, when necessary, decompression was extended to the intervertebral foramen. During the first years of our experience fusion of the posterior joints with osteosynthesis using plates and pedicular screws was associated with decompression in 43% of the cases. Thereafter, fusion was performed in only 17% of the cases. From a subjective point of view the results obtained in radiculopathies were satisfactory in only 87% of the cases, objectively in 72%. The results obtained with treatment of lumbar pain was better in patients in whom lumbosacral fusion was associated as compared to cases treated with laminectomy alone (85% vs. 65%). Complications were rare and mild.

Adult↗

Correlative anatomic and CT study of the lumbar lateral recess.

The lumbosacral nerve roots and their relation to the lateral recess in the lumbar region were studied by computed tomography both in anatomic specimens from six cadavers and in vivo in 100 patients with or without disk herniation. The anatomic and tomodensitometric correlations are discussed. The normal morphology and contents of the lumbar spinal canal can be used as a guide to radiologic diagnostic exploration, which in turn can indicate the etiology and extent of lumbar sciatica and the course of treatment.

Diagnosis, Differential↗