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Biomedical subjects

S Naderi

Publications and source records attributed to S Naderi.

At least 37 records · Page 2Linked to original sources
PubMed1999

Mad1 expression in the absence of differentiation: effect of cAMP on the B-lymphoid cell line Reh.

The protein Mad1 heterodimerizes with Max to form an E-box binding complex able to interfere with the transcriptional and transforming activities of c-Myc. Downregulation of c-Myc accompanied by induction of Mad1 upon differentiation has fueled the notion that Mad1 may play a role in the cessation of proliferation associated with the differentiation process. Since studies on Mad1 expression have so far been limited to cells undergoing differentiation, it was of interest to examine Mad1 expression in a cell system unable to differentiate. To do so, we utilized the leukemia-derived B-precursor cell line, Reh, and studied the expressions of Mad1, c-Myc, Mxil, and Max during cAMP-mediated growth inhibition of these cells. Thus, the adenylate cyclase activator forskolin induced growth inhibition of the cells in the G1 phase of the cell cycle. This growth inhibition was associated with transient increased expression of Mad1 concomitant with transient downregulation of c-Myc. The Mad1 protein levels essentially paralleled those of mRNA, with peak levels at 4 h of forskolin treatment. By coimmunoprecipitation we detected increased binding of Mad1 to Max in forskolin-treated cells, indicating that the changes in Mad1 protein levels had functional implications. By continually treating Reh cells with forskolin for 72 h, we observed a sustained elevated expression of Mad1 concomitant with downregulated c-Myc expression, still without changing the differentiation profile of the Reh cells. Interestingly, we showed that other known cell cycle regulatory proteins also were transiently regulated by forskolin. To this extent, following forskolin treatment of Reh cells, cyclin E-cdk2 activity was transiently reduced concomitant with dephosphorylation of pRB. We suggest that the early changes in Mad1 and the cell cycle regulatory proteins initiate a chain of events resulting in permanent growth arrest. Thus, the increased expression of Mad1 in the absence of differentiation indicates that Mad1 expression in Reh cells is linked to growth arrest per se.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗
PubMed1999

Activation of the cAMP signaling pathway increases apoptosis in human B-precursor cells and is associated with downregulation of Mcl-1 expression.

During B- and T-cell ontogeny, extensive apoptosis occurs at distinct stages of development. Agents that increase intracellular levels of cAMP induce apoptosis in thymocytes and mature B cells, prompting us to investigate the role of cAMP signaling in human CD10+ B-precursor cells. We show for the first time that forskolin (which increases intracellular levels of cAMP) increases apoptosis in the CD10- cells in a dose-dependent manner (19%-94% with 0-1,000 microM forskolin after 48 hours incubation, IC50 = 150 microM). High levels of apoptosis were also obtained by exposing the cells to the cAMP analogue 8-chlorophenylthio-cAMP (8-CPT-cAMP). Specific involvement of cAMP-dependent protein kinase (PKA) was demonstrated by the ability of a cAMP antagonist, Rp-isomer of 8-bromo-adenosine- 3', 5'- monophosphorothioate (Rp-8-Br-cAMPS), to reverse the apoptosis increasing effect of the complementary cAMP agonist, Sp-8-Br-cAMPS. Furthermore, we investigated the expression of Bcl-2 family proteins. We found that treatment of the cells with forskolin or 8-CPT-cAMP for 48 hours resulted in a fourfold decline in the expression of Mcl-1 (n = 6, P = 0.002) compared to control cells. The expression of Bcl-2, Bcl-xL, or Bax was largely unaffected. Mature peripheral blood B cells showed a smaller increase in the percentage of apoptotic cells in response to 8-CPT-cAMP (1.3-fold, n = 6, P = 0.045) compared to B-precursor cells, and a smaller decrease in Mcl-1 levels (1.5-fold, n = 4, P = 0.014). Taken together, these findings show that cAMP is important in the regulation of apoptosis in B-progenitor and mature B cells and suggest that cAMP-increased apoptosis could be mediated, at least in part, by a decrease in Mcl-1 levels.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

CD2-mediated CD59 stimulation in keratinocytes results in secretion of IL-1alpha, IL-6, and GM-CSF: implications for the interaction of keratinocytes with intraepidermal T lymphocytes.

Normal epidermal keratinocytes are here shown to express membrane-associated complement inhibitory protein CD59 in vitro that protects keratinocytes from damage by complement because preincubation with blocking antibodies to CD59 renders the cells susceptible to complement mediated lysis. CD59 expression in keratinocytes is constitutive and not modulated by inflammatory cytokines, phorbol myristate acetate (PMA), and a number of other agents tested. Antibody mediated cross-linking of CD59, however, revealed an additional function of CD59: keratinocytes in vitro are activated to secrete the cytokines IL-1alpha, IL-6, and GM-CSF. CD59 mediated induction of these cytokines is regulated at the transcriptional level. Binding of keratinocytes to HL60 cells that express CD59 ligand CD2 induced the same pattern of secreted cytokines whereas binding to CD2-negative HL60 cells did not. Induction of cytokine secretion was completely blocked by preincubation of keratinocytes with both anti-CD58 and anti-CD59 antibodies together. The results demonstrate that CD2-mediated CD59 stimulation in human keratinocytes leads to synthesis of a particular set of cytokines implying a potential activation pathway in the interaction of keratinocytes with intraepithelial CD2+ T cells.

Antibodies, Blocking↗
PubMed1999

Findings and outcome of revision lumbar disc surgery.

One hundred fourteen patients (64 men, 50 women) with prior lumbar disc surgery underwent a reexploration for intractable back and/or leg pain. The finding in revision surgery included disc herniation in 89 cases (78%), epidural fibrosis in 14 cases (12.2%), adhesive arachnoiditis in 4 cases (3.5%), isolated lateral spinal stenosis in 3 cases (2.6%), and iatrogenic instability in 4 cases (3.5%). Review of operative reports of patients who underwent a first operation in our institute revealed that seven cases (12.5%) had a second laminotomy without a discectomy in addition to the previous laminotomy and discectomy performed in the same session. Fifty-six of the patients with disc hemiation in revision surgery had a true recurrence. Disc hemiation was protruded in 38 cases (42.8%), extruded in 44 cases (49.4%), and sequestrated in 7 cases (7.8%). The outcome was assessed using Prolo's functional and economic scale. According to Prolo's scale, a good outcome was detected in 79 cases (69.2%), moderate in 22 (19.2%), and a poor outcome was detected in 13 cases (11.4%). The best outcome was achieved in patients with disc hemiation. It is concluded that recurrent disc disease is the most important cause of reexploration. This fact dictates a careful preoperative workup and discectomy in the first intervention. The likelihood of occurrence of disc herniation in the negative laminotomy level (i.e., laminotomy without discectomy procedure) also requires a careful preoperative radiologic workup before lumbar disc surgery.

Adult↗
PubMed1999

Surgical treatment of sacral perineural cysts. A case report.

Most of the perineural cysts (Tarlov's cysts) are asymptomatic. They are usually diagnosed incidentally, and a specific treatment is not necessary. They should be operated on, only if they produce progressive or disabling symptoms and/or sign clearly attributable to them. Several reports have been made regarding their sign and symptom, neurological and radiological features. This is a report emphasizing on their surgical indication and surgical treatment. We reported a 48 year-old woman who underwent surgery because of the symptomatic perineural cyst. It is concluded that the total excision of the perineural cyst is not necessary and a partial resection with a resultant reduction in the cyst size results in a favourable outcome.

Female↗
PubMed1998

Biomechanical comparison of C1-C2 posterior fixations. Cable, graft, and screw combinations.

STUDY DESIGN: Four combinations of cable-graft-screw fixation at C1-C2 were compared biomechanically in vitro using nondestructive flexibility testing. Each specimen was instrumented successively using each fixation combination. OBJECTIVES: To determine the relative amounts of movement at C1-C2 after instrumentation with various combinations of one or two transarticular screws and a posterior cable-secured graft. Also to determine the role of each component of the construct in resisting different types of loading. SUMMARY OF BACKGROUND DATA: Spinal stiffness increases after instrumentation with two transarticular screws plus a posterior wire-graft compared with a wire-graft alone. Other C1-C2 cable-graft-screw combinations have not been tested. METHODS: Eight human cadaveric occiput-C3 specimens were loaded nondestructively with pure moments, and nonconstrained motion at C1-C2 was measured. The instrumented states tested were a C1-C2 interposition graft attached with multistranded cable; a cable-graft plus one transarticular screw; two transarticular screws alone; and a cable-graft plus two transarticular screws. RESULTS: The transarticular screws prevented lateral bending and axial rotation better than the posterior cable-graft. The cable-graft prevented flexion and extension better than the screws. Increasing the number of fixation points often significantly decreased the rotation and translation (paired t test; P < 0.05). Axes of rotation shifted from their normal location toward the hardware. CONCLUSIONS: It is mechanically advantageous to include as many fixation points as possible when atlantoaxial instability is treated surgically.

Adult↗
PubMed1998

Degenerative spondylolisthesis: when to fuse?

This article reviews four reports that have addressed the efficacy of spinal instrumentation to enhance spinal fusion in patients with degenerative spondylolisthesis. These papers serve to highlight some of the common problems with interpreting and applying the clinical findings of such studies: small, nonuniform patient selection; variable instrumentation techniques; relatively brief follow-up periods (usually less than 5 years); lack of a uniform scale for clinical assessment of patients; and lack of consensus on the definition and clinical documentation of motion segment instability.

Journal Article↗
PubMed1998

Cervical spondylotic myelopathy: surgical results and factors affecting prognosis.

OBJECTIVE: A variety of factors may affect surgical outcome in patients with cervical spondylotic myelopathy. The aim of this study is to determine these factors on the basis of preoperative radiological and clinical data. METHODS: To assess the factors affecting postoperative outcome after surgery for cervical spondylotic myelopathy, the clinical and radiological data of 27 patients with cervical spondylotic myelopathy were reviewed. Functional and neurological statuses were assessed using the Japanese Orthopaedic Association (JOA) scale modified by Benzel. In all patients, the effect of age, symptom duration, cervical curvature, presence or absence of preoperative high signal intensity within the spinal cord as revealed by T2-weighted magnetic resonance imaging, and diameters of the spinal canal and vertebral body on pre- and postoperative neurological statuses were investigated. Plain radiographs were obtained for all patients, magnetic resonance images for 21 patients (77.8%), computed tomographic scans for 13 patients (48.1%), myelograms for 6 patients (22.2%), and computed tomographic myelograms for 4 patients (14.8%). There were five patients with a JOA score of 10, six patients with a JOA score of 11, six patients with a JOA score of 12, four patients with a JOA score of 13, four patients with a JOA score of 14, one patient with a JOA score of 15, and one patient with a JOA score of 16. All patients underwent cervical laminectomies. The mean follow-up period was 54.1 months. The final neurological examinations revealed improvement in the JOA scores of 85.1 % of the patients. RESULTS: Statistical analysis of all patients revealed mean JOA scores of 12.185 +/- 1.618 and 14.370 +/- 2.15 before surgery and at final examination, respectively. The difference between the preoperative JOA score and the final JOA score was determined to be statistically significant (P < 0.0001). Statistical analyses also showed better neurological improvement in patients younger than 60 years and in patients with normal preoperative cervical lordosis. Although patients without preoperative high signal intensity of the spinal cord showed a better improvement rate than did patients with preoperative high signal intensity, the determined difference was statistically insignificant. CONCLUSION: It can be concluded that age and abnormal cervical curvature predict less postoperative neurological improvement. The presence of preoperative high signal intensity within the spinal cord may also reflect less neurological improvement.

Adult↗
PubMed1996

Cervical spondylotic myelopathy: surgical decision making.

Cervical spondylotic myelopathy can produce a variety of clinical signs and symptoms secondary to neural compromise and biomechanical involvement of the spine. The surgical treatment of cervical spondylotic myelopathy remains a controversial issue after many years of study, evolution, and refinement. Several ventral, dorsal, or combined approaches have been defined. The complications associated with ventral approaches and the concerns about kyphosis following dorsal approaches led to the development of a variety of laminoplasty procedures. This paper reviews the biomechanical basis of cervical spondylotic myelopathy and its effect on choosing the appropriate surgical approach.

Journal Article↗
PubMed1996

Cervical spondylotic myelopathy treated with corpectomy: technique and results in 44 patients.

Forty-four patients with cervical spondylotic myelopathy who underwent a ventral surgical approach were evaluated with respect to the results of surgery. The neurological status of the patients was categorized according to the modified Japanese Orthopedic Association scale (0-18). Three patients had a functional score of 8, one patient 9, five patients 10, five patients 11, seven patients 12, seven patients 13, seven patients 14, and nine patients had a functional score of 15, preoperatively. Twenty-three patients underwent a one-level corpectomy, 15 patients a two-level corpectomy, and six patients underwent a three-level corpectomy. Forty-one (93.1%) of the 44 patients underwent ventral cervical plate fixation. Complications among the 44 patients included graft- and instrumentation-related complications in seven cases, iliac crest donor-site infection in three cases, and respiratory complications in three cases. The follow-up periods ranged between 7 and 60 months (mean 42.3 months). Overall, the fusion rate was 97.72%. Three patients showed no functional change (6.8%), two patients were worse (4.5%), and 39 patients (88.6%) showed functional improvement in their score between +1 and +6 points (mean 2.16 points). There was no statistically significant difference in the functional improvement score in patients younger or older than 60 years old. The mean improvement in the functional score was found to be +2.857 +/- 1.352, +2.400 +/- 1.454, and +0.5000 +/- 1.871 following one-level corpectomy, two-level, and three-level corpectomies, respectively. There were statistically significant differences in the neurological improvement observed between patients with one-level corpectomy and three-level corpectomy (p < 0.01), as well as between those with two-level and three-level corpectomy (p < 0.05). There was no statistically significant difference in the neurological outcome between patients with one-level and two-level corpectomy (p > 0.05). The results of this study demonstrate a high rate of solid bone fusion and a high rate of functional (neurological) improvement. Five patients underwent reoperation, predominantly for instrumentation failure. The use of instrumentation dictates careful consideration of the risk/benefit ratio associated with its use in each case.

Journal Article↗
PubMed1995

Preferential association of membrane phospholipids with the human erythrocyte hexose transporter.

This study reports the results of an investigation to determine to what extent the influence of membrane lipids on the human erythrocyte sugar transporter protein activity (Caruthers, A. and Melchior, D.L. (1988) Annu. Rev. Physiol. 50, 257-271) is related to lipid/protein associations in the membrane bilayer. Differential scanning calorimetry was carried out on the human erythrocyte transport protein reconstituted into artificial bilayers formed from preselected lipids. it was found that the transport protein displays a preferential and in some cases strongly preferential affinity for specific lipid types. This association is a function of lipid head group, backbone and hydrocarbon chain length. It appears that the affinity of the transport protein for various lipids can correlate with the lipid's ability to influence transporter activity. This study further suggests that certain lipids (in this case sphingomyelin) can induce an oligomeric association of HEST monomers in the bilayer.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1995

Peptide presentation by bacteriophage P4.

This article focuses on bacteriophage P4 as a potential peptide display phage by exploring the possibility of using the P4 capsid decoration component, Psu, as a peptide carrier protein. Psu is non-essential for P4 growth but it enhances the stability of the P4 capsid by binding to its exterior. We have constructed a unique SacI cloning site in the beginning of the psu gene. This site changes the third amino acid of Psu from Ser to Leu. This substitution does not destroy the binding of Psu to the P4 capsid. A synthetic oligonucleotide encoding a 10-amino acid peptide whose sequence is part of the human p62c-myc protein, has been inserted into the SacI site. The Psuc-myc shows full capsid binding activity and reacts with monoclonal antibodies directed against the c-myc peptide. These results pave the way for the further development of a peptide display system based on bacteriophage P4.

Amino Acid Sequence↗
PubMed1994

Contribution of hepatic cytochrome P450 systems to the generation of reactive oxygen species.

The rate of generation of reactive oxygen species (ROS) in hepatic microsomes was assayed using a fluorescent probe. This rate was stimulated in a manner proportional to the concentration of NADPH present. NADH could not be substituted for NADPH, and an inhibitor of mixed-function oxidases (SKF 525A) blocked stimulation by NADPH. This suggested the involvement of cytochrome P450 oxidase systems in ROS formation. Low molecular weight iron salts may not have been involved in the stimulated ROS formation since deferoxamine failed to eliminate the oxidative response to NADPH. Catalase only partially inhibited, and glutathione peroxidase did not significantly inhibit this response, implying that hydrogen peroxide does not play a key role. However, since NADPH-enhanced generation of reactive oxygen species was totally prevented by superoxide dismutase, superoxide was an obligatory intermediate. The presence of toluene, ethanol or phenobarbital did not enhance the production of NADPH-effected reactive oxygen species; free radical production was maximal in the absence of substrates subject to oxidation by cytochrome P450 enzymes. Hepatic cytochrome P450 oxidases are likely to contribute significantly to overall ROS formation, even under basal conditions where mixed-function oxidases are not induced.

Animals↗
PubMed1994

The formation of reactive oxygen species in a fraction of rat brain by metabolism of nitric oxide.

The potential of nitric oxide for the induction of reactive oxygen species (ROS) has been evaluated in a cerebral synaptosomal fraction. Nitric oxide (NO) was generated using S-nitroso-N-acetylpenicillamine (SNAP). NO stimulated ROS production, assayed using a fluorescent probe. This stimulation was largely inhibited by superoxide dismutase but not by catalase, implying that superoxide anion but not hydrogen peroxide, was a critical intermediate. An iron chelator, deferoxamine or hydroxyl radical scavengers failed to prevent stimulation of ROS by SNAP. This suggests the possibility of formation of a novel class of short-lived active oxygen species by NO.

Animals↗
PubMed1994

Evaluation of cerebral vasospasm in patients with subarachnoid hemorrhage using single photon emission computed tomography.

Cerebral vasospasm (CVS) occurs as a result of the breakdown in cerebral autoregulation mechanisms. Because cerebral vasospasm can occur after subarachnoid hemorrhage (SAH), it is important to evaluate borderline perfusion. Evaluation of borderline vascular insufficiency is important to reduce ischemic complications. In this study 25 patients with SAH were investigated by somatosensory evoked potentials (SEP), computed tomography (CT), digital subtraction angiography (DSA) and single photon emission computed tomography (SPECT) in order to predict borderline ischemic areas. Clinical grades were also correlated with these investigations. Thirteen patients had symptomatic vasospasm and 15 patients had angiographic vasospasm. SPECT showed hypoperfusion in 22 out of 25 patients. CT predicted CVS in 8 of these 22 patients. Our study shows that brain perfusion SPECT is a non-traumatic, non-invasive, non-allergic, inexpensive method for the prediction of cerebral vasospasm. We conclude that brain SPECT with Tc-99m HM-PAO is an accessible technique that can demonstrate varying degrees of regional tissue hypoperfusion in patients with delayed ischemic deficits due to CVS following SAH.

Adolescent↗