Biomedical subjects
S Mahmoud
Publications and source records attributed to S Mahmoud.
Oesophageal perforation: a dangerous but potentially curable condition.
A series of three cases of oesophageal perforation are described. All three presented differently and the X-ray findings were different in the three patients.
Effect of adamantylamide dipeptide on reinfection resistance after primary infection eradication in experimental Schistosomiasis mansoni.
The immunomodulatory effect of adamantylamide dipeptide (AdDP) was tested in Schistosoma mansoni-infected challenged mice and infected praziquantel-treated (2 x 500 mg/kg) challenged animals. In AdDP-treated mice, the drug was given 58 days post infection of mice with 120 S. mansoni cercariae, challenged with 240 cercariae one day after treatment, while in praziquantel-treated mice, the drug was given 44 days post infection, two weeks post treatment (58 days post infection) they were given AdDP in the same dose and one day later challenged with the same cercarial load. AdDP increased the resistance against reinfection (90.3% vs. 83.5% in infected challenged control). The significant increase in resistance against reinfection was accompanied by significant increase in the percentage of lymphocytes forming EAC rosettes. Mice cured of their primary infection by praziquantel showed a significant reduction in percent resistance, hepatic granuloma size and intragranulomal Thy+ 1,2 and Lyt+ 1 T cells. In mice treated with both praziquantel and AdDP, resistance to reinfection was significantly higher than in mice treated with praziquantel only (89.29% vs. 62.13%) reaching a level comparable to that recorded in infected-challenged controls. Meanwhile granuloma size was not significantly different from that in the infected-challenged controls with a significant rise in Lyt+ 1 T cells. Data may suggest a role for granuloma as a mechanical obstacle and/or as a T cell-mediated reaction in maintenance of resistance to reinfection. A role for B lymphocytes should be considered as the rise of percent resistance to reinfection in mice treated with AdDP alone was accompanied by a significant increase in the percentage of B lymphocytes forming EAC rosettes. Moreover, findings may suggest the use of AdDP together with specific chemotherapy in endemic areas where reinfection and repeated treatment with its consequences are of common occurrence.
Age-related changes in tissue content of malondialdehyde-modified proteins.
One of the possible mechanisms of the age-related modifications of proteins is the result of reaction with malondialdehyde (MDA), a lipid peroxidation byproduct. To determine the effect of age on the extent of MDA derivatization of proteins in plasma and various tissues, male Fisher 344 rats at 4, 12 and 26 months of age were studied. Protein electrophoresis and immunoblotting was carried out using a specific antiserum against MDA-protein complexes. The concentration of MDA-proteins in plasma (mean +/- SD of optical density in 50 micrograms protein) was 201.6 +/- 47.7 in 4 month old rats, 197.4 +/- 67 in 12 month old rats and 101.4 +/- 22.7 in 26 month old rats (P < 0.01). The MDA protein content of testicle, liver and heart was increased in 12 month old rats compared to 4 and 26 months old rats. There were no age-related differences in MDA-protein content of lung, brain, and kidney. Because of the interindividual variability of MDA-protein profiles within an age group distinct age-related changes in the distribution of various MDA protein bands could not be documented.
Tissue-specific distribution of malondialdehyde modified proteins in diabetes mellitus.
A potential mechanism of diabetes-related tissue damage is modification of various proteins by lipid peroxidation by-products such as malondialdehyde (MDA). To determine the extent of MDA derivatization of various proteins in diabetes mellitus, Western blots were carried out using a specific anti-MDA antiserum to study proteins in plasma and various tissues of control and streptozotocin (STZ)-induced diabetic rats. The concentration of MDA-proteins was highest in plasma compared to other tissues tested. Diabetes was associated with a reduction in MDA-protein content of plasma, lung and liver while in the heart, testicle, cerebrum and kidney the MDA-protein concentration was not altered. Insulin treatment of diabetic rats normalized MDA-protein content of plasma but not in the lung or liver. A large interindividual variability in various protein species was observed within a group. This was partly attributed to polymerization of MDA-proteins. It is concluded that although diabetes is associated with increased lipid peroxidation the content of MDA-proteins in plasma and in some tissues is decreased.
[Psi 13,14] bombesin analogues inhibit growth of small cell lung cancerin vitro and in vivo.
Bombesin/gastrin releasing peptide (BN/GRP) functions as an autocrine growth factor in small cell lung cancer (SCLC). Previously, this autocrine growth cycle was disrupted by a monoclonal antibody which binds to the carboxyl terminal of BN and neutralizes the peptide so that it is unable to interact with the BN/GRP receptor. Here a series of BN analogues were synthesized which have a reduced peptide bond near the carboxyl terminal. The analogues inhibited specific binding of 125I-GRP to SCLC cell line NCI-H345 in a dose-dependent manner and the analogue [D-Nal6, Psi13,14, Phe14] BN6-14 was approximately 6-fold more potent than was (Psi13,14, Leu14)BN with a 50% inhibition concentration value of 5 nM. [DNal6, Psi13,14, Phe14]BN6-14 and [Psi13,14, Leu14]BN had no effect on the cytosolic Ca2+ levels but antagonized the increase in cytosolic Ca2+ caused by 10 nM BN. [Psi13,14, Leu14]BN (1 microM) inhibited the growth of SCLC in vitro using a clonogenic assay by approximately 70% Also, injection of [Psi13,14, Leu14]BN (10 micrograms, s.c.) inhibited the growth of SCLC xenografts in nude mice in vivo by approximately 50%. These data suggest that the autocrine growth cycle of BN/GRP in SCLC may also be disrupted by peptide antagonists which bind to the BN receptor.
Small cell lung cancer bombesin receptors are antagonized by reduced peptide bond analogues.
The potency of 3 reduced peptide bond analogues of bombesin (BN) was investigated using small cell lung cancer (SCLC) cell lines. (Psi13,14, Leu14)BN, (Psi9,10, Leu14)BN and (Psi12,13, Leu14)BN inhibited specific binding of 125I-GRP with IC50 values of 15, 90, and 600 nM. (Psi13,14, Leu14)BN and (Psi9,10, Leu14)BN did not elevate cytosolic Ca2+ levels but antagonized the increase in cytosolic Ca2+ caused by BN. (Psi13,14, Leu14)BN antagonized the clonal growth of SCLC cells caused by BN. These data indicate that reduced peptide bond analogues may disrupt the autocrine growth cycle of SCLC cells by functioning as BN receptor antagonists.
Indium-111 monoclonal anti-myosin antibody in assessing skeletal muscle damage in trauma.
Accurate assessment of the severity of soft tissue damage particularly skeletal muscle associated with fractures in trauma patients is important in determining the plan of management and prognosis. We used Indium-111 labelled anti-myosin to determine the extent of skeletal muscle injury in five patients involved in traumatic accidents. We found abnormal uptake in all 20 sites of muscle injury in four patients, 13 at the sites of fractures and seven away from fracture sites. There was good correlation between the degree of uptake and the extent of muscle injury. No uptake was seen in a case with no fracture and no muscle injury. At surgery this case proved to be haemarthrosis of the left knee. Indium-111 anti-myosin scanning is a potentially sensitive and useful technique in assessing extent of acute muscle injury in trauma patients.
Human glioblastoma cell lines have neuropeptide receptors for bombesin/gastrin-releasing peptide.
Bombesin/gastrin-releasing peptide receptors were characterized in human glioblastoma cell lines. [125I]Gastrin-releasing peptide or ([125I]Tyr4)bombesin bound with high affinity to these cell lines. Binding to cell line U-118 was time dependent, reversible, and specific. ([125I]Tyr4)Bombesin bound with high affinity (Kd = 1.6 nM) to a single class of sites (Bmax = 30,000/cell). The C-terminal of bombesin- or gastrin-releasing peptide was essential for high-affinity binding. Bombesin- or gastrin-releasing peptide elevated the cytosolic Ca2+ levels in a dose-dependent manner. Because gastrin-releasing peptide, but not gastrin-releasing peptide, increased the cytosolic Ca2+ levels, the C-terminal but not the N-terminal of GRP is essential for biological activity. These data indicate that biologically active bombesin receptors are present in human glioblastoma cell lines.
A false positive I-131 MIBG due to dilated renal pelvis: a case report.
A case of false positive I-131 MIBG imaging for detection of pheochromocytoma is presented. There was an area of increased tracer uptake in the left renal region that showed steadily reducing activity over a period of three days. This raised the suspicion of a dilated renal pelvis, which was later confirmed by Tc-99m DTPA imaging. It is advisable in cases of ambiguous I-131 MIBG imaging to use Tc-99m DTPA rather than Tc-99m DMSA for localizing the kidneys and renal pelvis.
Neuropeptides elevate cytosolic calcium in small-cell lung cancer cells.
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Bombesin-like peptides elevate cytosolic calcium in small cell lung cancer cells.
The ability of bombesin-like peptides to elevate intracellular Ca2+ levels in small cell lung cancer cells was investigated using the fluorescent Ca2+ indicator Fura 2. Nanomolar concentrations of bombesin elevated cytosolic Ca2+ levels in the absence or presence of extracellular Ca2+. Potent bombesin receptor agonists, such as gastrin releasing peptide (GRP) or (GRP)14-27 elevated cytosolic Ca2+ levels whereas inactive compounds such as (D-Trp8)bombesin or (GRP)1-16 did not. Furthermore, the bombesin receptor antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11) substance P (30 microM) had no effect on the Ca2+ levels by itself but antagonized the increase in Ca2+ caused by 10 nM or 100 nM bombesin. These data suggest that bombesin receptors may regulate the release of Ca2+ from intracellular organelles in small cell lung cancer cells.
The combination of 17 alpha-hydroxyprogesterone and 11-epicortisol prevents the delayed feedback effect of natural and synthetic glucocorticoids.
Subcutaneous injection of 400 micrograms/100 g body weight of corticosterone (B) 2 h previously in male rats prevented the stress response, as assessed by the ability of adrenal glands removed from these animals to produce endogenous B. Two injections of a combination of 17 alpha-hydroxyprogesterone and 11-epicortisol, the first given 30 min before and the second with the B, were able to block this inhibitory effect on the stress response. Neither of the steroids alone was effective in this regard. The combination was also effective against the early delayed feedback effects of 400 micrograms/100 g body weight cortisol, prednisolone or beclomethasone dipropionate in the same system. The minimum effective dose for reversal of feedback by B or beclomethasone dipropionate (2 mg/100 g body weight of each antagonist) was lower than that required for the same effect against prednisolone or cortisol (5 mg/100 g body weight). Previous injection of B also abolished the ability of anterior pituitary gland fragments to respond to corticotropin-releasing factors (CRFs) added in vitro, an effect which was not abolished by the injection of the combination of putative antagonistic steroids. From experiments designed to measure the ability of 17 alpha-hydroxyprogesterone and 11-epicortisol to compete with 3H-corticosterone in binding to macromolecular components in hypothalamic, hippocampal and pituitary cytosolic preparations, it was deduced that the competition seen in the hypothalamic and hippocampal, rather than the pituitary, preparations was in better accord with the effect seen on the stress response.(ABSTRACT TRUNCATED AT 250 WORDS)
Diurnal variations in responsiveness of the hypothalamo-pituitary-adrenocortical axis of the rat.
Hypothalami, anterior pituitary gland segments and adrenal glands were removed from female Wistar-derived rats decapitated at various times of the day. Blood and tissue hormone concentrations were measured and the tissues challenged with appropriate stimuli in vitro. Both bioactive and immunoreactive corticotrophin-releasing factor (CRF) content of the hypothalami were significantly higher in the evening than in the morning, as was the basal release of bioactive CRF in vitro. The response of the hypothalami to serotonin or acetylcholine added in vitro did not change with time of day. Basal bioactive and immunoreactive adrenocorticotrophin (ACTH) release from the anterior pituitary gland was significantly increased in the evening, as was the response to synthetic ovine CRF in vitro. Plasma ACTH concentrations in intact rats given crude CRF (hypothalamic extract) in vivo were higher in the evening at all times after injection tested, but this difference was markedly reduced in animals with mediobasal hypothalamic lesions. Corticosterone released basally from adrenal glands in vitro was significantly increased in the evening and the response to added ACTH 1-24 was slightly enhanced. For adrenal glands removed from lesioned rats, the pattern was reversed, corticosterone release in vitro being lower in the evening for all doses of ACTH added. Similarly in vivo, in intact rats given ACTH 1-24, plasma corticosterone concentrations and corticosterone release in vitro from adrenal glands removed after the injection were higher in the evening. After the placement of basal hypothalamic lesions, the situation was reversed, the response to ACTH administration in vivo being greater in the morning.(ABSTRACT TRUNCATED AT 250 WORDS)
Application of orthogonal functions to spectrophotometric analysis of the preservatives benzylalcohol, phenol and parabens in aqueous cyanocobalamin solutions.
The orthogonal polynomials P3 and P2, 12 and 8 points, at 2 nm intervals over certain wavelength ranges were used for the spectrophotometric analysis of benzylalcohol, phenol or parabens in aqueous cyanocobalamin solutions. The 12 point-methods proved to be more sensitive and direct and to have sufficient accuracy and precision.
The characteristics of post tur blood loss: a preliminary study.
Peroperative and postoperative blood loss was studied in 20 patients. Both peroperative and postoperative blood loss was found to correlate together (p less than 0.05) and with the weight of resected tissue (p less than 0.05). The characteristics of the postoperative blood loss demonstrated a strong negative correlation with time, and calculation of the t50 showed that a 50% reduction in postoperative blood loss occurred within 16 h.
Schistosomiasis mansoni in an Egyptian village in the Nile Delta.
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Relative importance of corticosteroid negative-feedback at the hypothalamus and anterior pituitary gland [proceedings].
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