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Biomedical subjects

S Naderi

Publications and source records attributed to S Naderi.

At least 19 recordsLinked to original sources

Degradation of cyclin D3 independent of Thr-283 phosphorylation.

Cyclin D3 has been shown to play a major role in the regulation of cell cycle progression in lymphocytes. It is therefore important to understand the mechanisms involved in the regulation of this protein. We have previously shown that both basal and cAMP-induced degradation of cyclin D3 in Reh cells is dependent on Thr-283 phosphorylation by glycogen synthase kinase-3beta (GSK-3beta). We now provide evidence of an alternative mechanism being involved in the regulation of cyclin D3 degradation. Treatment of lymphoid cells with okadaic acid (OA), an inhibitor of protein phosphatases 1 and 2A (PP1 and PP2A), induces rapid phosphorylation and proteasomal degradation of cyclin D3. This degradation is not inhibited by the GSK-3beta inhibitors lithium or Kenpaullone, or by substitution of Thr-283 with Ala on cyclin D3, indicating that cyclin D3 can be degraded independently of Thr-283 phosphorylation and GSK-3beta activity. Interestingly, in vitro experiments revealed that PP1, but not PP2A, was able to dephosphorylate cyclin D3 efficiently, and PP1 was found to associate with His-tagged cyclin D3. These results support the hypothesis that PP1 constitutively keeps cyclin D3 in a stable, dephosphorylated state, and that treatment of cells with OA leads to phosphorylation and degradation of cyclin D3 through inhibition of PP1.

Amino Acid Sequence↗

Surgical anatomy of the cervical sympathetic trunk.

Lack of knowledge of the anatomy of the cervical sympathetic trunk (CST) may complicate surgical procedures on the cervical spine. This study aims to define linear and angular relations of the CST with respect to consistent structures around it, including the number and size of the cervical ganglia, the distances between the CST and the longus colli muscle and the anterior tubercles of the transverse processes of cervical vertebrae. Morphometric parameters of the 24 CSTs of 12 adults were measured on both sides. The CST had superior, middle, and inferior (or cervicothoracic) ganglia in 20.8% of specimens; superior and inferior (or cervicothoracic) ganglia in 45.8%; superior, middle, vertebral, inferior, or cervicothoracic ganglia in 12.5%, and superior, vertebral, inferior or cervicothoracic ganglia in 20.8% of specimens. The superior ganglion was observed in all specimens, the middle ganglion and vertebral ganglion were each observed in 33.3%. There was no difference between the number of superior and vertebral ganglia between the right and left sides. The average distance between the CST and the medial border of the ipsilateral longus colli muscle (LCM) was 17.2 mm at C3 and 12.4 mm at C7. As the CSTs converged caudally, the LCMs diverged. The average distance between the anterior tubercles of transverse processes of the cervical vertebrae and the lateral borders of the ipsilateral CST was 3.4 mm at C4, 3.2 mm at C5, and 3.9 mm at C6. The presence of a vertebral ganglion and variations, such as the localization of the CST within the carotid sheath, are important. The anatomical landmarks described should assist the spinal surgeon to avoid injury of the CST.

Adult↗

A retrospective review of cervical corpectomy: indications, complications and outcome.

BACKGROUND: Cervical corpectomy is a common spinal surgery procedure used to decompress the spinal cord in numerous degenerative, traumatic and neoplastic conditions. The aim of this study was to investigate the indications, complications and outcomes in past cervical corpectomy cases at one centre. METHOD: 72 patients who underwent cervical corpectomy between February 1992 and June 2001 were retrospectively investigated. FINDINGS: The indications for this operation were degenerative spondylitic disease (26 cases; 36.1%), trauma (18 cases; 25%), tumour (11 cases; 15.3%), infection (10 cases; 13.9%), and ossification of the posterior longitudinal ligament (7 cases; 9.7%). Thirty-seven patients (51.4%) underwent one-level corpectomy, and 35 (48.6%) underwent two-level corpectomy. Autografts were used in 13 cases (18.1%) and allografts were used in 59 cases (81.9%). Anterior plate-screw fixation was performed in all cases. There were 31 postoperative complications in 15 (20.8%) patients. Twelve of the complications were surgical, 5 were graft-related, 7 were plating-related, and 7 were medical. Solid bony fusion was achieved in 65 (92.9%) of the 70 surviving patients. The mean follow-up time was 23.4 months. An overall favourable outcome was achieved in 88% of cases. CONCLUSION: The outcomes in this series indicate that cervical corpectomy is an effective method for treating traumatic lesions, degenerative disease, tumours and infectious processes involving the anterior and middle portions of the cervical spine.

Adult↗

Trigeminal root recording in normal trigeminal function.

Despite many investigations on the detection of trigeminal evoked potentials (TEP), there is still no consensus on a technique or interpretation of its components. In order to obtain clear TEP waveforms and analyze the origin of early components, we recorded TEP by the conventional far-field technique at the ipsilateral auricula as well as by near-field technique with a bipolar electrode at the trigeminal root just distal to the entry zone of its root. Trigeminal recordings were performed in nine patients with intrameatal vestibular schwannomas and in three with trigeminal neuralgia without trigeminal nerve deficits. In near-field recording at the trigeminal root, a triphasic response was recorded, with the first component occurring at 3.16 ms, 2.98 ms, and 4.16 ms following supraorbital, infraorbital, and mandibular nerve stimulation, respectively. Using conventional farfield TEP, the first component recorded at the trigeminal root occurred later than the first component in all other recordings. This suggests that the N2.0 component of far-field TEP is of extra-axial origin and the N5 component is of brainstem origin. The N13.0 component may be of cortical origin. We conclude that the N5.0 component and N5.0-N13.0 interpeak latency may be used as electrophysiological parameters of brainstem function during posterior fossa surgery.

Electric Stimulation↗

Brucellar spondylitis: MRI findings.

This study was carried out to identify the distinguishing features of brucellosis on magnetic resonance imaging (MRI). MRI examinations were performed in 14 patients with spinal brucellosis. A 1-T Magnetom (Erlangen, Siemens) was used to obtain T1-weighted (TR/TE 500/30) and T2-weighted (TR/TE 2000/80/20) spin echo sequences, in both sagittal and axial planes. Thirty-three percent of the vertebrae and 18 levels of disc were involved in the 14 brucellar spondylitis cases. Eleven patients (79.8%) with discitis revealed anterior superior vertebral body involvement. Fourteen (77.7%) of the levels with discitis displayed soft tissue swelling without presence of abscess formation. Seven facet joints of five patients with discitis displayed signal increase after contrast enhancement. Vertebral body signal changes without morphologic changes marked signal increase in the intervertebral disc on T2-weighted and contrast-enhanced sequences, and soft tissue involvement without abscess formation can be accepted as specific MRI features of brucellar spondylitis. The facet joint signal changes following contrast enhancement is another MRI sign of spinal brucellosis, which has not been mentioned so far.

Adolescent↗

Ossified thoracic spinal meningioma in childhood: a case report and review of the literature.

Spinal ossified meningiomas are extremely rare. This is a report of a study on a 15-year-old boy with thoracic spinal ossified meningioma. The meningioma was resected totally. Histopathological examination revealed a transitional meningioma (psammomatous+meningothelial). Immunohistochemically, Ki 67 antibody was applied but no positive staining was present. The surgical and pathological aspects of spinal ossified meningiomas were reviewed.

Adolescent↗

Role of retinoblastoma tumor suppressor protein in DNA damage response.

Growth arrest induced by DNA damage in mammalian cells requires the function of the retinoblastoma tumor suppressor protein (RB). RB-deficient cells cannot undergo G1, mid-S or G2 arrest following DNA damage, although they can activate the G2 checkpoint, which is reversible. RB-deficient cells are also hypersensitive to DNA damage-induced apoptosis. Induction of apoptosis in RB wild-type cells is associated with the loss of RB protein through cleavage by caspase. Two substitution mutations in exon 25 of the Rb gene have been created in the mouse germline to generate the Rb-MI allele that codes for a caspase-resistant RB protein. The RB-MI protein desensitizes cells to apoptosis. Taken together, these results suggest that RB plays a critical role in determining the cell fate following DNA damage. Growth arrest is dependent on RB and apoptosis is activated following RB degradation.

Animals↗

Spinal epidural gas after cardiac surgery.

The authors describe a patient with severe lower back and left leg pain in the early postoperative period after cardiac surgery. Radiologic examination revealed gas in the spinal epidural space at the level of L4-5. The pain could not be relieved with analgesics and the patient underwent lumber surgery after cardiac surgery. After decompression, the patient improved and was discharged with no symptoms.

Coronary Artery Bypass↗

Morphologic and radiologic anatomy of the occipital bone.

Several diseases may cause craniovertebral instability warranting occiput-cervical fusion. As occipital screw and rod constructs are becoming more popular, requiring that screws be placed either medially or laterally in the occipital bone, the need for clearer anatomical and computed tomography (CT)-confirmed data regarding the relative thickness of the occiput in its various localities has become more critical. In 18 cadaveric specimens, the occipital bone was divided into 35 measurable segments. Transversely, the occipital bone was divided into five lines starting at the level of the inion; horizontal lines then proceeded inferiorly in 1-cm segments, 1, 2, 3, and 4 cm below the level of inion. In a comparable fashion, the occipital bone was divided vertically, starting at the midline, and proceeding laterally also in 1-, 2-, and 3-cm segments. Anatomical measurements of thickness were directly performed using a Vernier caliper. Results were directly correlated with axial CT measurements of bony thickness. Anatomical and CT measurements closely correlated within the same specimen, but there was significant interspecimen variability. The marked differences in the occipital bone anatomy noted between specimens indicates that patients undergoing occipital screw placement for cranial-cervical instability would benefit from preoperative occipital CT evaluations.

Cadaver↗

Further cranial settling of the upper cervical spine following odontoidectomy. Report of two cases.

A variety of diseases may affect the craniovertebral junction and require a decompressive and fusion procedure. Craniovertebral junction instability is expected after a fusion procedure. The authors describe two patients with basilar invagination who underwent transoral odontoidectomy and occipitocervical fixation. Despite an uneventful immediate postoperative course, further cranial settling of the C-2 vertebral body (VB) was demonstrated. One patient experienced neurological deterioration and required a second decompressive procedure, whereas the second patient was asymptomatic and required no additional surgery. It was concluded that the odontoidectomy may have led to horizontal separation of the C-1 lateral masses, resulting in further cranial settling of the C-2 VB. Preservation of one aspect of the C-1 anterior arch minimizes C-1 lateral mass offset and, in turn, further cranial settling of the C-2 VB. In addition, a more rigid fixation of C-2 may minimize the possibility of horizontal separation of the C-1 lateral masses after transoral odontoidectomy.

Adult↗

cAMP-mediated growth inhibition of lymphoid cells in G1: rapid down-regulation of cyclin D3 at the level of translation.

cAMP is an important physiological mediator of lymphoid growth inhibition. The purpose of the present study was to establish the link between cAMP and the cell cycle machinery leading to inhibition of G1/S transition in human peripheral blood lymphocytes (PBL). To unravel immediate effects of cAMP on this part of the cell cycle machinery, lymphocytes were synchronized in mid to late G1 after stimulation with phytohemaglutenin (PHA) for 32 h. We report that addition of forskolin or cAMP analogues to the cells resulted in dephosphorylation of retinoblastoma protein commencing as early as 30 min. A rapid effect of forskolin was noted on the activity of cyclin-dependent kinase (cdk) 4, which decreased significantly within 30 min of treatment. The decrease in cdk4 activity was concurrent with reduced levels of cyclin D3 protein and a decrease in the fraction of cdk4 associated with cyclin D3. The down-regulation of cyclin D3 was at the level of translation, and this event was preceded by a pronounced inhibition of Akt/protein kinase B phosphorylation at Ser 473. Taken together, our data imply that cyclin D3 is a major effector of cAMP-mediated inhibition of cell cycle progression in PBL, and that cAMP exerts its effect on cyclin D3 expression at the level of translation.

8-Bromo Cyclic Adenosine Monophosphate↗

Co-induction of Mad1 and c-Myc in activated normal B lymphocytes.

The purpose of the present study was to examine the expression of the Myc network proteins c-Myc, Mad1 and Max in normal cells under different growth and differentiation conditions. A dominant view has been that Mad1 as a c-Myc antagonist plays a role in growth inhibition linked to differentiation. Of particular interest to us was therefore to study the regulation of Mad1 in cells undergoing differentiation in the absence of growth cessation. To do so we utilized normal B lymphocytes isolated from peripheral blood. The cells were induced to concomitant proliferation and differentiation by stimulation with a combination of anti-IgM antibodies (anti-mu) and the phorbol ester TPA. Thus, by 72 h of stimulation the percentage of plasmablasts increased from 3 to 17%, and the percentage of lymphocytes decreased from 89 to 27%. The most intriguing observation we made using this cell system was a pronounced coinduction of Mad1 and c-Myc. The levels of c-Myc and Mad1 mRNAs and proteins increased within 3 h of anti-mu stimulation, and the levels were further enhanced by TPA. Furthermore, the expressions of both c-Myc and Mad1 were reduced by forskolin, which also inhibited the anti-mu + TPA driven growth and differentiation of the B lymphocytes. The level of Max remained virtually unchanged. Taken together, our results indicate that a high level of Mad1 in normal human B cells is linked to differentiation and not to growth inhibition. Furthermore, the results demonstrate that Mad1 and c-Myc are not necessarily expressed in a reciprocal manner, which underlines an independent role of Mad1 unrelated to its function as a c-Myc antagonist.

B-Lymphocytes↗

RB-dependent S-phase response to DNA damage.

The retinoblastoma tumor suppressor protein (RB) is a potent inhibitor of cell proliferation. RB is expressed throughout the cell cycle, but its antiproliferative activity is neutralized by phosphorylation during the G(1)/S transition. RB plays an essential role in the G(1) arrest induced by a variety of growth inhibitory signals. In this report, RB is shown to also be required for an intra-S-phase response to DNA damage. Treatment with cisplatin, etoposide, or mitomycin C inhibited S-phase progression in Rb(+/+) but not in Rb(-/-) mouse embryo fibroblasts. Dephosphorylation of RB in S-phase cells temporally preceded the inhibition of DNA synthesis. This S-phase dephosphorylation of RB and subsequent inhibition of DNA replication was observed in p21(Cip1)-deficient cells. The induction of the RB-dependent intra-S-phase arrest persisted for days and correlated with a protection against DNA damage-induced cell death. These results demonstrate that RB plays a protective role in response to genotoxic stress by inhibiting cell cycle progression in G(1) and in S phase.

Animals↗

Cervical facet dislocation: techniques for ventral reduction and stabilization.

OBJECT: To demonstrate the safety and utility of one surgical approach, the authors reviewed their experience with the ventral surgical approach for decompression, reduction, and stabilization in 10 patients with either unilateral or bilateral cervical facet dislocation. METHODS: Six patients presented with unilateral cervical facet dislocation and four patients with bilateral cervical facet dislocation. There were six male and four female patients who ranged in age from 17 to 72 years (average 37.1 years). The level of facet dislocation was C4-5 in one, C5-6 in four, and C6-7 in five patients. Three patients presented with a complete spinal cord injury (SCI), three patients with an incomplete SCI, three with radicular symptoms or myeloradiculopathy, and one patient was neurologically intact. All patients underwent plain radiography, magnetic resonance imaging, and computerized tomography evaluation of the cervical spine. All patients had sustained significant ligamentous injury with minimum or no bone disruption. All patients underwent ventral decompressive surgery, reduction of the dislocation, and stabilization of the cervical spine. Techniques for performing ventral reduction of unilateral or bilateral cervical facet dislocation are described. Decompression, reduction, and stabilization of the cervical spine via the ventral approach was accomplished in all but one patient. This patient underwent a ventral decompressive procedure and an attempt at ventral reduction and subsequent dorsal reduction and fusion in which a lateral mass screw plate fixation system was used; this was followed by ventral placement of instrumentation and fusion. There were no surgery-related complications. Postoperative neurological status was unchanged in four patients and improved in six patients. No patient experienced neurological deterioration after undergoing this surgical approach. CONCLUSIONS: The authors conclude that a ventral surgical decompression, reduction, and stabilization procedure provides a safe and effective alternative for the treatment of patients with unilateral or bilateral cervical facet dislocation without significant bone disruption.

Adolescent↗

Lovastatin inhibits G1/S transition of normal human B-lymphocytes independent of apoptosis.

Lovastatin is a potent inhibitor of protein prenylation, and it has been reported to have pleiotropic cellular effects. In the present study we have elucidated the effects of lovastatin on cell cycle progression and apoptosis of normal human B-lymphocytes. When added to B-lymphocytes stimulated with anti-immunoglobulin (anti-mu) and SAC, lovastatin (20 microM) inhibited the cells in the late G1 phase of the cell cycle. Thus, no early activation parameters such as Ca(2+) flux or MYC induction were affected by lovastatin, whereas progression of cells into the second cell cycle as well as DNA synthesis was markedly reduced. We therefore examined the effects of lovastatin on components of the cell cycle machinery responsible for regulating the G1/S transition. We demonstrated that pRB phosphorylation, cdk2 activity needed for this phosphorylation, and the levels of cyclin A, D, and E were inhibited after 24 h of lovastatin treatment, while the levels of p27(Kip1) were elevated. There was no effect on p21(Cip1), cyclin D2, cdk4, and cdk6. These data are consistent with the cells being inhibited by lovastatin between 24 and 32 h into G1. Lovastatin added to stimulated B-cells in late G1 still inhibited the DNA synthesis by 60%, but at this point only minor effects were noted on the cell cycle machinery. We therefore looked for induced apoptosis as an explanation for reduced S-phase entry of the cells. However, despite the ability to enhance the apoptosis of unstimulated B-cells from 48 to 61% as judged by the TUNEL method, lovastatin only marginally affected apoptosis when administered to stimulated B-cells. Thus, it appears that accelerated apoptosis cannot account for the effect of lovastatin on cell cycle progression.

Apoptosis↗

Retinoic acid prevents phosphorylation of pRB in normal human B lymphocytes: regulation of cyclin E, cyclin A, and p21(Cip1).

The mechanisms underlying the growth-inhibitory effect of retinoids on normal human B lymphocytes are not well understood. We addressed this issue by examining the effect of retinoic acid on the cell cycle machinery involved in G1/S transition. When retinoic acid was administered to B cells stimulated into mid to late G1 by anti-IgM antibodies (anti-mu) and Staphylococcus aureus crude cell suspension (SAC), the phosphorylation of pRB required for S-phase entry was prevented in a time- and dose-dependent manner. Thus, 2-hour treatment with retinoic acid at the optimal concentration of 1 micromol/L prevented phosphorylation of pRB, and effects were noted at concentrations as low as 10 nmol/L. Based on our results, we suggest that the rapid effect of retinoic acid on pRB phosphorylation is due primarily to the reduced expression of cyclin E and cyclin A in late G1. This could lead to the diminished cyclin E- and cyclin A-associated kinase activities noted as early as 2 hours after addition of retinoic acid. Furthermore, our results imply that the transient induction of p21(Cip1) could also be involved. Thus, retinoic acid induced a rapid, but transient increased binding of p21(Cip1) to CDK2. The retinoic acid receptor (RAR) agonist TTNPB mimicked the key events affected by retinoic acid, such as pRB phosphorylation, cyclin E expression, and expression of p21(Cip1), whereas the RAR-selective antagonist Ro 41-5253 counteracted the effects of retinoic acid. This implies that retinoic acid mediates its growth-inhibitory effect on B lymphocytes via the nuclear receptors.

B-Lymphocytes↗