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A Saleh

Publications and source records attributed to A Saleh.

At least 37 records · Page 2Linked to original sources

Changes in T cell subsets, interleukin-6 and C-reactive protein after laparoscopic and open colorectal resection for malignancy.

BACKGROUND: Attenuation of the immune response to surgery, as demonstrated with the laparoscopic approach to cholecystectomy, has potential benefits in patients undergoing laparoscopic colonic resection for malignancy. We aimed to study the perioperative immune response in patients undergoing laparoscopically assisted and open surgery for colorectal cancer. METHODS: This study involved 23 patients undergoing laparoscopically assisted (n = 13) and open surgery (n = 10). Interleukin-6 (IL-6) C-reactive protein (CRP), the total lymphocyte count, and the CD3, CD4, CD8, CD16, and CD19 lymphocyte subpopulations were assayed preoperatively and at 4, 8, 10, 24, 48, and 168 h postoperatively. RESULTS: Significant rises in IL-6 and CRP were demonstrated within 4 and 24 h, respectively (p < 0.001) in both groups. However, no significant difference between the groups was seen. Significant decreases in total lymphocyte count and all T cell subsets were demonstrated in both groups, beginning at 4 h (p < 0.01). However, no significant difference between the groups was seen. All parameters, excluding CRP, had returned to baseline by 7 days postoperatively in both groups. CONCLUSIONS: Patients with malignancy exhibit significant perioperative immune disturbance with laparoscopically assisted and open surgery. The current data do not provide justification for the laparoscopically assisted approach on grounds of immune preservation.

Aged↗

Class I MHC-binding characteristics of the 129/J Ly49 repertoire.

The Ly49 family of NK cell receptors and its MHC-binding characteristics have only been well characterized in C57BL/6 (B6) mice. Previous studies have shown that 129/J mice express unique Ly49 genes that are not found in the B6 strain. Screening of a 129/J cDNA library led to the discovery of 10 distinct full-length Ly49-related coding sequences (Ly49e, g, i, o, p, r, s, t, u, and v). Although 129/J mice share identical class I MHC (K(b) and D(b)) transcripts with B6 mice, only one Ly49 is identical in the two strains (Ly49E). In addition to the previously characterized Ly49P, two new activating Ly49 proteins were discovered, Ly49R and U. The MHC specificity of the total 129/J Ly49 repertoire was evaluated with soluble class I MHC tetramers and found to be distinct compared with the B6 Ly49 repertoire. Ly49V bound to many types of class I MHC, suggesting that Ly49V(+) NK cells may monitor host cells for a global down-regulation in MHC levels. An activating receptor, Ly49R, was shown to bind soluble class I molecules to a moderate degree, a result not previously observed for other activating Ly49 proteins. Furthermore, tetramer-binding results were confirmed functionally with cytotoxicity assays using sorted 129/J NK cells. This study shows that the Ly49 repertoire and its MHC-binding characteristics can be very different among inbred mouse strains. Ly49 divergence should be considered when using 129-derived embryonic stem cells for the production of gene-targeted mice, especially when an immune or NK-derived phenotype is under scrutiny.

Alleles↗

A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis.

X-linked inhibitor-of-apoptosis protein (XIAP) interacts with caspase-9 and inhibits its activity, whereas Smac (also known as DIABLO) relieves this inhibition through interaction with XIAP. Here we show that XIAP associates with the active caspase-9-Apaf-1 holoenzyme complex through binding to the amino terminus of the linker peptide on the small subunit of caspase-9, which becomes exposed after proteolytic processing of procaspase-9 at Asp315. Supporting this observation, point mutations that abrogate the proteolytic processing but not the catalytic activity of caspase-9, or deletion of the linker peptide, prevented caspase-9 association with XIAP and its concomitant inhibition. We note that the N-terminal four residues of caspase-9 linker peptide share significant homology with the N-terminal tetra-peptide in mature Smac and in the Drosophila proteins Hid/Grim/Reaper, defining a conserved class of IAP-binding motifs. Consistent with this finding, binding of the caspase-9 linker peptide and Smac to the BIR3 domain of XIAP is mutually exclusive, suggesting that Smac potentiates caspase-9 activity by disrupting the interaction of the linker peptide of caspase-9 with BIR3. Our studies reveal a mechanism in which binding to the BIR3 domain by two conserved peptides, one from Smac and the other one from caspase-9, has opposing effects on caspase activity and apoptosis.

Amino Acid Motifs↗

Effects of laparoscopic ovarian drilling on adrenal steroids in polycystic ovary syndrome patients with and without hyperinsulinemia.

OBJECTIVE: To evaluate adrenal steroid responses to ACTH stimulation and insulin responses to oral glucose tolerance test (OGTT) in clomiphene-citrate-resistant anovulatory women with polycystic ovary syndrome (PCOS) before and after laparoscopic ovarian drilling. DESIGN: Prospective study. SETTING: Healthy participants in a university teaching hospital. PATIENT(S): Twenty clomiphene-citrate-resistant anovulatory women with PCOS. INTERVENTION(S): Laparoscopic ovarian drilling. MAIN OUTCOME MEASURE(S): Adrenal steroid responses to ACTH stimulation and insulin responses to OGTT before and after ovarian drilling. RESULT(S): Fourteen of 20 women completed the study. There was a correlation between body mass index and basal insulin levels before ovarian drilling. This correlation was lost after surgery. Area-under-the-curve glucose and insulin values before surgery in women with hyperinsulinemia (1,033.3 +/- 112.7 mmol/L and 141,919 +/- 26,177 pmol/L, respectively) were significantly higher than in those with normoinsulinemia (777.1 +/- 77.2 mmol/L and 69,867 +/- 19,390 pmol/L respectively, P<.05). There was a significant difference in insulin and glucose responses before and after ovarian drilling in women with hyperinsulinemia. No difference was found in women with normoinsulinemia. There was no significant difference in adrenal steroid responses to ACTH stimulation before and after ovarian drilling. CONCLUSION(S): PCOS women with hyperinsulinemia respond differently to laparoscopic ovarian drilling than do those with normoinsulinemia. Among women with hyperinsulinemia, surgery decreases glucose and insulin responses to OGTT. Regardless of the insulin level, laparoscopic ovarian drilling does not influence adrenal steroid dynamics.

Adrenocorticotropic Hormone↗

Estimation of antithyroid drug dose in Graves' disease: value of quantification of thyroid blood flow with color duplex sonography.

The purpose of this study was to evaluate if there is an association between the antithyroid drug dose that is needed to establish euthyroidism and thyroid blood flow measurements. A total of 23 Graves' disease patients with euthyroidism taking antithyroid drug therapy were enlisted to undergo spectral duplex sonography of the thyroid arteries and color-flow mapping of the thyroid gland. Color pixel density (CPD) was calculated with computer assistance from the color-flow maps. There was a strong correlation between the CPD and methimazole dose (rp = 0.79). Methimazole maintenance dosage could be predicted from CPD values with a coefficient of determination of 0.62. In conclusion, CPD measurements could be a useful tool for the clinical endocrinologist to estimate the antithyroid drug dose that is needed to maintain euthyroidism.

Adult↗

Effects of local bupivacaine instillation on pain after laparoscopy.

STUDY OBJECTIVE: To evaluate the effect of preincisional and intraperitoneal bupivacaine administration on immediate and late pain after operative laparoscopy. DESIGN: Randomized study (Canadian Task Force classification I). SETTING: University teaching hospital. PATIENTS: One hundred fifty women undergoing laparoscopy for various gynecologic indications. INTERVENTION: A dose of 0.5% bupivacaine 10 ml (50 mg) was injected into cannula sites before incisions and another 10 ml diluted with 100 ml saline into the peritoneal cavity at completion of the procedure. Equal amount of physiologic saline was used in controls. MEASUREMENTS AND MAIN RESULTS: Modified McGill pain intensity scores and amount of analgesic required in the recovery room and within 24 hours postoperatively were evaluated. Of 150 women, 142 completed the study (71 bupivacaine group, 71 controls). Groups did not differ significantly in body mass index, duration of surgery, return to consciousness, and analgesic requirement during 3-hour observation in the recovery room and 24 hours after discharge. Pain scores were highest 30 minutes after the procedure in both groups. At that time the pain score in the bupivacaine group was lower than that in the control group (1.8 +/- 0.2 vs 2.3 +/- 0.2, p <0.05). Beyond that time, the groups did not differ in pain scores and analgesic requirements. CONCLUSION: Postoperative pain is the highest within 30 minutes after laparoscopy. Local instillation of bupivacaine before incision and intraperitoneally was effective in reducing pain immediately after operative laparoscopy, but the effect was not seen beyond 30 minutes.

Anesthetics, Local↗

[Does tissue harmonic imaging allow early determination of postoperative thyroid volume?].

AIM: Therapy for endemic goitre after surgical resection depends on the residual thyroid volume. Post-operative changes have been known to impair the fundamental sonographic evaluation of residual thyroid tissue. It was our aim to determine whether THI is a feasible method for thyroid volumetry after surgery. METHODS: 48 patients underwent thyroidectomy, hemithyroidectomy, near total resection, or partial resection of the thyroid gland. In all patients THI of the neck was performed 4 (mean; range: 2-7 days) days after surgery using an Elegra sonographic device (Siemens, Erlangen, Germany) with a transmitted frequency of 3.4 MHz and received frequency of 6.8 MHz. The examiner was blinded to the patient's diagnosis and the type of surgery. The residual tissue volume measured by means of THI and intra-operative volumetry were both compared to sonographic volumetry 12 weeks after surgery, the latter serving as the gold standard. Accuracy of THI and intraoperative volumetry were tested for significant differences using a paired t-test. RESULTS: Volumetry by the surgeon was available in 26 patients (54%). The men error of THI volumetry was 2.4 ml (SD: 3.3 ml; maximum: 17 ml). The mean error of intraoperative volumetry was 1.4 ml (SD: 1.9 ml; maximum: 6 ml). The mean difference between THI and intraoperative volumetry was 1 ml (SD: 2.7 ml; maximum: 7 ml; p = 0.085). CONCLUSIONS: THI permits early volumetry of the residual tissue after thyroid surgery comparable with the intraoperative volumetry. Thus, THI may be helpful in guiding the substitution of thyroid hormones.

Adult↗

[Real-time compound imaging: improved visibility of puncture needles and localization wires as compared to single-line ultrasonography].

AIM: To compare the visibility of biopsy needles and localization wires using real-time compound imaging (SonoCT) and single-line ultrasound (SLU). METHODS: 14-18 G biopsy needles and 5 different localization wires with and without puncture needle were placed into cadaverous muscle in 4 different angulations (0, 12, 18 and 25 degrees). Sonography was performed with an ATL HDI 5000 sonography device with a 5-12 MHz linear array using single-line ultrasound and compound imaging with 3 and 9 frames (Comp3 and Comp9) from different viewing angles. Images of the needles were obtained in the longitudinal plane without changing depth, focus position, and gain settings between the measurements. The mean grey values of the needle (gv_n) and of the background (gv_b) were obtained from histograms. Contrast was calculated using the equation (gv_n-gv_b)/gv_b + gv_n). Mean contrast in single-line and compound images was compared for each angulation using a Student t-test. RESULTS: The mean contrast at 0 degree was 0.686 in single-line ultrasound. This was significantly higher than in Comp3 (0.62) and Comp9 (0.633) (p < 0.05) images. At 12 degrees no significant differences could be observed. At 18 degrees image contrast was significantly higher in compound images with 0.493 (Comp3) and 0.498 (Comp9), compared to SLU (0.433) (p < 0.05). At 25 degrees the difference between compound images (Comp3: 0.394; Comp9: 0.402) and SLU (0.306) was greatest (p < 0.0001). CONCLUSION: At 0 degree and 12 degrees visibility is very good for all tested materials. For steeper angulations contrast was partly critical in SLU and significantly enhanced with compound imaging. Thus, SonoCT may be useful to increase precision of ultrasound-guided percutaneous interventions.

Animals↗

Circulating filarial antigens for monitoring the efficacy of ivermectin in treatment of filariasis.

Seventy-three asymptomatic bancroftian filariasis patients with positive microfilaria in their blood films were included. The patients were randomly divided into 2 groups: ivermectin group (50 cases) given 2 doses each of 100 ug/kg body weight, 3 months apart, and 23 cases had 2 doses of placebo. The study was run blindly for one year. The initial mean microfilaria (MF) count was 111/ml. At 3 months after ivermectin therapy, mean MF became 7.8/ml and 24% of ivermectin treated cases had no detectable MF (P <0.05). At 6, 9 and 12 months, the mean MF count became 4.1, 6.5 and 11/ml with amicrofilaria in 54%, 42% and 40% of treated cases respectively (P <0.05). On the other hand, no statistically significant change in the mean MF count in placebo group was detected. The routine laboratory investigations were unchanged or slightly improved at 3 and 6 months. Side effects after the first dose of ivermectin were mild fever in 16% and weakness in 20%. None was recorded after the second dose. Circulating filarial antigens could be detected in 66% of cases before treatment, as all cases with high microfilaremia had positive antigenemia. The mean antigen level started to decline significantly after 9 months post treatment. At the end of the study (one-year), all negative microfilaremic cases had negative antigen levels, indicating that detection of antigen in-patients sera is a very good indicator of cure and efficacy of the drug.

Adolescent↗

Negative regulation of cytochrome c-mediated oligomerization of Apaf-1 and activation of procaspase-9 by heat shock protein 90.

The release of cytochrome c from mitochondria results in the formation of an Apaf-1-caspase-9 apoptosome and induces the apoptotic protease cascade by activation of procaspase-3. The present studies demonstrate that heat shock protein 90 (Hsp90) forms a cytosolic complex with Apaf-1 and thereby inhibits the formation of the active complex. Immunodepletion of Hsp90 depletes Apaf-1 and thereby inhibits cytochrome c-mediated activation of caspase-9. Addition of purified Apaf-1 to Hsp90-depleted cytosolic extracts restores cytochrome c-mediated activation of procaspase-9. We also show that Hsp90 inhibits cytochrome c-mediated oligomerization of Apaf-1 and thereby activation of procaspase-9. Furthermore, treatment of cells with diverse DNA-damaging agents dissociates the Hsp90-Apaf-1 complex and relieves the inhibition of procaspase-9 activation. These findings provide the first evidence for a negative cytosolic regulator of cytochrome c-dependent apoptosis and for involvement of a chaperone in the caspase cascade.

Amino Acid Sequence↗

Extraintestinal polyps in Peutz-Jeghers syndrome: presentation of four cases and review of the literature. Deutsche Peutz-Jeghers-Studiengruppe.

Peutz-Jeghers syndrome (PJS) is a rare hereditary disorder characterized by hamartomatous polyps in the gastrointestinal tract and typical pigment lesions. Extraintestinal polyps have rarely been reported. Possible sites include the respiratory tract, urogenital tract, and gallbladder. We here describe four cases of extraintestinal polyps in PJS patients and review the literature on the need for operative therapy of extraintestinal polyps in PJS. Three nonrelated patients were examined who had PJS and polyps in the gallbladder; the fourth patient had PJS and recurrent choanal polyps. Surgery has so far been performed only for symptomatic polyps: one laparoscopic cholecystectomy and removal of the choanal polyps for recurrent infections of the respiratory tract. The remaining two patients reported no symptoms from the extraintestinal polyps. No malignant transformation was found in these patients, nor has such been reported in the literature on PJS. The frequent observation of this manifestation in our patients raises the question of clinical management: Is prophylactic surgery indicated? Since malignant transformation of PJS polyps in the intestine is extremely rare we see no reason for operative therapy as long as the polyps are small and asymptomatic. Regular sonographic controls are recommended since the risk of malignant transformation cannot be ruled out at present.

Adult↗

Effects of laparoscopic ovarian drilling on serum vascular endothelial growth factor and on insulin responses to the oral glucose tolerance test in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the serum vascular endothelial growth factor concentrations and insulin responses to the oral glucose tolerance test before and after laparoscopic ovarian drilling in women with PCOS. DESIGN: Prospective study. SETTING: University teaching center. PATIENT(S): Twenty-seven women with clomiphene citrate-resistant polycystic ovary syndrome. INTERVENTION(S): Laparoscopic ovarian drilling. MAIN OUTCOME MEASURE(S): VEGF levels and insulin responses to OGTT before and after ovarian drilling. RESULT(S): No difference was found in VEGF levels in women with PCOS before (6.0 +/- 1.2 ng/mL) and after ovarian drilling (5.5 +/- 1.2 ng/mL). VEGF levels before and after ovarian drilling in women who conceived were, respectively, 5.9 +/- 1.0 and 5.1 +/- 0.9 ng/mL and in those who did not conceive were 6.0 +/- 1.3 and 5.7 +/- 1.2 ng/mL. No correlation was found between baseline serum insulin and VEGF levels. VEGF concentrations in women with normal ovaries (4.5 +/- 1.7 ng/mL) were significantly lower than in women with PCOS. There was no difference in glucose and insulin responses to OGTT before and after ovarian drilling. CONCLUSION(S): VEGF levels in women with PCOS are higher than in normal women, and ovarian drilling does not affect these levels. The procedure does not change insulin responses to OGTT.

Analysis of Variance↗

A randomized study of the effect of 10 minutes of bed rest after intrauterine insemination.

OBJECTIVE: To evaluate the effects of 10 minutes of bed rest after intrauterine insemination (IUI) on the pregnancy rate. DESIGN: Prospective randomized study. SETTING: University teaching hospital. PATIENT(S): One hundred sixteen couples with unexplained infertility. INTERVENTION(S): Patients were prospectively randomized either to immediate mobilization after IUI (group I) or to remain in a supine position for 10 minutes after the procedure (group II). MAIN OUTCOME MEASURE(S): Cumulative pregnancy rate. RESULT(S): Ninety-five couples were included in the analysis. Group I consisted of 40 couples (90 cycles), and group II consisted of 55 couples (120 cycles). The pregnancy rate per couple in group I (4 of 40 [10%]) was significantly lower than in group II (16 of 55 [29%]). The pregnancy rate per cycle in group I (4.4%) was also lower than in group II (13. 3%). With use of life-table analysis, the cumulative probability of pregnancy in group II was significantly higher than in group I. CONCLUSION(S): A 10-minute interval of bed rest after IUI has a positive effect on the pregnancy rate. We recommend that mandatory bed rest for 10 minutes after IUI should be adopted into a standard practice.

Adult↗

Negative regulation of the Apaf-1 apoptosome by Hsp70.

Release of cytochrome c from mitochondria by apoptotic signals induces ATP/dATP-dependent formation of the oligomeric Apaf-1-caspase-9 apoptosome. Here we show that the documented anti-apoptotic effect of the principal heat-shock protein, Hsp70, is mediated through its direct association with the caspase-recruitment domain (CARD) of Apaf-1 and through inhibition of apoptosome formation. The interaction between Hsp70 and Apaf-1 prevents oligomerization of Apaf-1 and association of Apaf-1 with procaspase-9. On the basis of these results, we propose that resistance to apoptosis exhibited by stressed cells and some tumours, which constitutively express high levels of Hsp70, may be due in part to modulation of Apaf-1 function by Hsp70.

Adenosine Triphosphate↗

Characterization of a diadenosine tetraphosphate-receptor distinct from the ATP-purinoceptor in human tracheal gland cells.

Human submucosal tracheal glands are now believed to play a major role in the physiopathology of cystic fibrosis, a genetic disease in which ATP is used as a therapeutic agent. However, actions of ATP on tracheal gland cells are not well known. ATP binds to P2 receptors and induced secretory leucocyte protease inhibitor (SLPI) secretion through formation of cyclic adenosine monophosphate and mobilization of intracellular [Ca(2+)]. Since diadenosine polyphosphates (ApnA) are also endogenous effectors of P2 receptors, we investigated their effects in a cell line (MM39) of human tracheal gland cells. Diadenosine tetraphosphates (Ap4A) induced significant stimulation (+50+/-12%) of SLPI secretion and to a similar extent to that of ATP (+65+/-10%). No significant effects were observed with diadenosine triphosphate (Ap3A), diadenosine pentaphosphate (Ap5A), ADP and 2-methylthio-adenosine triphosphate (2-MeS-ATP). Since Ap4A was weakly hydrolyzed (<2% of total), and the hydrolysis product was only inosine which is ineffective on cells, this Ap4A effect was not due to Ap4A hydrolysis in ATP and adenosine monophosphate (AMP). A mixture of Ap4A and ATP elicited only partial additive effects on SLPI secretion. ADP was shown to be a potent antagonist of ATP and Ap4A receptors, with IC(50)s of 0.8 and 2 microM, respectively. 2-MeS-ATP also showed antagonistic properties with IC(50)s of 20 and 30 microM for ATP- and Ap4A-receptors, respectively. Single cell intracellular calcium ([Ca(2+)](i)) measurements showed similar transient increases of [Ca(2+)](i) after ATP or Ap4A challenges. ATP desensitized the cell [Ca(2+)](i) responses to ATP and Ap4A, and Ap4A also desensitized the cell response to Ap4A. Nevertheless, Ap4A did not desensitize the cell [Ca(2+)](i) responses to ATP. In conclusion, both P2Y2-ATP-receptors and Ap4A-P2D-receptors seem to be present in tracheal gland cells. Ap4A may only bind to P2D-receptors whilst ATP may bind to both Ap4A- and ATP-receptors.

Adenosine Diphosphate↗

Cytochrome c and dATP-mediated oligomerization of Apaf-1 is a prerequisite for procaspase-9 activation.

To elucidate the mechanism of activation of procaspase-9 by Apaf-1, we produced recombinant full-length Apaf-1 and purified it to complete homogeneity. Here we show using gel filtration that full-length Apaf-1 exists as a monomer that can be transformed to an oligomeric complex made of at least eight subunits after binding to cytochrome c and dATP. Apaf-1 binds to cytochrome c in the absence of dATP but does not form the oligomeric complex. However, when dATP is added to the cytochrome c-bound Apaf-1 complex, complete oligomerization occurs, suggesting that oligomerization is driven by hydrolysis of dATP. This was supported by the observation that ATP, but not the nonhydrolyzable adenosine 5'-O-(thiotriphosphate), can induce oligomerization of the Apaf-1-cytochrome c complex. Like the spontaneously oligomerizing Apaf-530, which lacks its WD-40 domain, the oligomeric full-length Apaf-1-cytochrome c complex can bind and process procaspase-9 in the absence of additional dATP or cytochrome c. However, unlike the truncated Apaf-530 complex, the full-length Apaf-1 complex can release the mature caspase-9 after processing. Once released, mature caspase-9 can process procaspase-3, setting into motion the caspase cascade. These observations indicate that cytochrome c and dATP are required for oligomerization of Apaf-1 and suggest that the WD-40 domain plays an important role in oligomerization of full-length Apaf-1 and the release of mature caspase-9 from the Apaf-1 oligomeric complex.

Apoptotic Protease-Activating Factor 1↗

Venous incompetence in erectile dysfunction: evaluation with color-coded duplex sonography and cavernosometry/-graphy.

The purpose of this study was to assess the accuracy of multi-parameter measurements with color-coded duplex sonography (CCDS) for the diagnosis of venous leakage in patients with erectile dysfunction. Sixty patients with repeated unsatisfactory reactions after intracavernous injection of vasoactive substances underwent CCDS. Following intracavernous injection of prostaglandin E1, peak systolic velocity (PSV), enddiastolic velocity (EDV), time averaged velocity (TAV), resistance index (RI), and pulsatility index (PI) were measured in the cavernous arteries over 30 min (one measurement per minute). The results were compared with independent measurements based on dynamic pharmaco-cavernosometry/cavernosography (DPCC). Dynamic pharmaco-cavernosometry/cavernosography revealed venous leakage in 33 patients. Of 48 patients with normal PSV ( > 25 cm/s), 25 had veno-occlusive dysfunction and the remainder presented normal venous function. No statistically significant differences between these groups were found in EDV, RI, and PI measurements. In contrast, differences in TAV were significant between patients with (mean 9.4 +/- 4.6 cm/s) and without venous leakage (mean 5.5 +/- 2.2 cm/s; p = 0.001). Analysis of relative frequencies revealed a broad overlap of EDV, TAV, RI, and PI measurements between both groups. Sensitivities and specificities determined from receiver-operating-characteristic curves were > 80 % and > 50% for a TAV threshold of 5 cm/s, and an RI threshold of 1.0. Measurements of EDV, TAV, RI, and PI in patients with repeated unsatisfactory reactions on intracavernous prostaglandin injection are poor predictors of venous leakage and should not replace DPCC in the investigation of vasculogenic impotence.

Adult↗