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Biomedical subjects

H Soliman

Publications and source records attributed to H Soliman.

At least 37 records · Page 2Linked to original sources

Anti- and pro-apoptotic activities of baculovirus and Drosophila IAPs in an insect cell line.

The anti-apoptotic activities of two baculovirus IAPs, OpIAP and CpIAP, were directly compared with that of two Drosophila IAPs, DIAP1 and DIAP2, in the same insect cell line, SF-21 cells. Like OpIAP and CpIAP, DIAP1 inhibited actinomycin D-induced apoptosis and apoptosis induced by Doom. Removal of the RING finger of DIAP1 reduced but did not eliminate its anti-apoptotic activity. DIAP2 was unable to inhibit actinomycin-D induced apoptosis but was able to partially inhibit Doom-induced apoptosis. The baculoviral BIR and RING finger regions, when separated, were unable to block apoptosis induced by actinomycin D or Doom. Instead, the BIR regions of OpIAP and CpIAP as well as the RING finger regions of CpIAP and DIAP1 induced apoptosis. Thus, there were significant differences in the manner in which the different domains of the viral and cellular homologues of IAPs interacted with the components of the pathways regulating apoptosis in SF-21 cells.

Journal Article↗

Sandwich-type enzyme immunoassay for big endothelin-I in plasma: concentrations in healthy human subjects unaffected by sex or posture.

A sandwich-type enzyme immunoassay has been developed for measuring human big endothelin-1 (big ET-1) in human plasma and supernatant fluids from human cell cultures. Big ET-1 is the precursor of endothelin 1 (ET-1), the most potent vasoconstrictor known. A rabbit antibody raised against the big ET-1 COOH-terminus fragment was used as an immobilized antibody (anti-P16). The Fab' fragment of a monoclonal antibody (1B3) raised against the ET-1 loop fragment was used as the enzyme-labeled antibody, after being coupled to acetylcholinesterase. The lowest detectable value in the assay was 1.2 pg/mL (0.12 pg/well). The assay was highly specific for big ET-1, demonstrating no cross-reactivity with ET-1, <0.4% cross-reactivity with big endothelin-2 (big ET-2), and <0.1% with big endothelin-3 (big ET-3). We used this assay to evaluate the effect of two different postural positions (supine and standing) on plasma big ET-1 concentrations in 11 male and 11 female healthy subjects. Data analysis revealed that neither sex nor body position influenced plasma big ET-1 concentrations. This assay should thus permit the detection of possible variations in plasma concentrations of big ET-1 in certain pathologies and, in association with ET-1 assay, make possible in vitro study of endothelin-converting enzyme activity in cell models. Such studies could clarify the physiological and clinical roles of this family of peptides.

Adolescent↗

Screening cystoscopy and survival of spinal cord injured patients with squamous cell cancer of the bladder.

PURPOSE: Yearly cystoscopy has been advocated in spinal cord injured patients with chronic or recurrent urinary tract infections secondary to the increased risk of squamous cell cancer of the bladder. We examined the effectiveness of this protocol in our patients. MATERIALS AND METHODS: The medical records of all spinal cord injured patients with squamous cell cancer of the bladder between 1980 and 1996 were reviewed for the method of detection of the lesion. Screened patients (those presenting with chronic or recurrent urinary infections) were considered asymptomatic and were compared to symptomatic patients (those presenting with overt signs or symptoms of the bladder lesion) with respect to age, latency since spinal cord injury, treatment of neurogenic bladder, therapy, pathological stage and survival. RESULTS: Of 14 patients (9 symptomatic at presentation) 13 underwent cystoprostatectomy, while 1 presented with metastatic disease and was treated with supportive care only. Three symptomatic patients received adjuvant radiation therapy for positive lymph nodes or margins. Pathological stage was more advanced in the symptomatic group, including 7 patients (78%) with stage pT3a or pT3b (4 had positive lymph nodes), 1 with stage pT1N0M0 and 1 with stage pT2N0M0 cancer. In the asymptomatic group 3 patients had stage pT2N0M0, 1 had stage pT3aN0M0 and 1 had pT3bN0M0 disease. Overall and cancer specific survival rates for symptomatic patients were 44 and 50%, respectively, with a median of 40 months to death. In the asymptomatic group there was 1 noncancer related death, while the remaining patients were alive at a mean followup of 8.2 years. CONCLUSIONS: Cystoscopy to screen for squamous cell cancer of the bladder in spinal cord injured patients with chronic or recurrent urinary tract infection results in an earlier stage at diagnosis and appears to convey a survival advantage. Such a protocol should be strictly followed and careful prospective studies must be performed to ascertain if this will become significant.

Carcinoma, Squamous Cell↗

Convenient chromatographic prepurification step before measurement of urinary cortisol by radioimmunoassay.

We applied various prepurification protocols (extraction with different solvents, liquid/solid separation on bonded silica media, Celite, and Sephadex LH20 chromatography) with a range of commercially available RIA kits to measure cortisol in urine samples. We then compared the results with the concentrations measured by a HPLC method validated with reference to isotope dilution gas chromatography-mass spectrometry. We conclude that chromatography on a commercial, prepacked diol minicolumn (Waters Sep-Pak Vac RC) in combination with dichloromethane extraction is a convenient and very effective purification step before RIA of urinary cortisol in patients not receiving corticoid medication. We tested numerous steroids for interference and found that free polar cortisol derivatives (hydroxylated or hydrogenated) could only partially account for the overestimations routinely encountered when free urinary cortisol concentrations are measured by direct RIA.

Adult↗

Radioimmunoassay of cortisone in serum, urine, and saliva to assess the status of the cortisol-cortisone shuttle.

We have developed a new assay for cortisone (E) in serum, saliva, and urine involving Celite chromatography followed by RIA with 125I-labeled E and scintillation proximity assay. The chromatography step separates cortisol (F) from E, and in combination with their RIAs, permits assessment of the status of the F-E shuttle. We report the results of basal, postcorticotropin (ACTH), and postdexamethasone E and F concentrations and their circadian fluctuations in the serum, saliva, and urine of healthy volunteers. The serum and urine F/E ratios were increased in patients with ectopic ACTH secretion, whereas in adrenal adenoma and Cushing disease only the urinary ratio was increased. In chronic renal insufficiency this ratio was increased in serum (23.5 +/- 3.9) but diminished in saliva (0.38 +/- 0.11), and in apparent mineralocorticoid excess the ratios were high in serum (44.3 +/- 9.3) and urine (5.35 +/- 0.85) compared with those of healthy subjects (serum 9.8 +/- 3.5, urine 0.52 +/- 0.29, saliva 0.52 +/- 0.29).

11-beta-Hydroxysteroid Dehydrogenases↗

Unresolved issues in laparoscopic splenectomy.

BACKGROUND: Laparoscopy is now expanding to surgery of intra-abdominal solid organs such as splenectomy for hematologic diseases. The purpose of this study is to further demonstrate that laparoscopic splenectomy is feasible for the surgeon, teachable for the resident, and beneficial to the patient and to revise prior contraindications to this minimally invasive approach. METHODS: Thirty-three consecutive cases of laparoscopic splenectomy were performed between May 1992 and March 1996. The series included 21 females and 12 males with a median age of 42 years (range 19-79) and a median weight of 73 kg (range 36-115). Indications included: immune thrombocytopenic purpura (20), hemolytic anemia (5), hereditary spherocytosis (4), infarction with abscess (1), Hodgkin's lymphoma (1), Gaucher's disease (1), and AIDS-related thrombocytopenia (1). Dissection was predominately performed with a new surgical instrument, the harmonic shears, and main vessels were controlled with clips. RESULTS: Thirty-two (97%) of the cases were completed laparoscopically, with 1 (3%) conversion to control hilar bleeding. Four patients underwent simultaneous cholecystectomy. The median spleen size was 13 cm (range 8-28) and median weight was 256 g (range 40-2100). Median operating time was 242 minutes (range 85-515). Morbidity occurred in 2 (6%) patients: ileus and small bowel obstruction. Median hospital stay was 4 days (range 2-14). There was no mortality in our series. Median follow-up was 20 months (range 1-46) with no evidence of late surgical complication or recurrent disease. CONCLUSION: Laparoscopic splenectomy may be successful in cases previously considered contraindicated, particularly splenomegaly and splenic infarct with abscess. It is a procedure that can be learned under appropriate guidance in academic centers.

Adult↗

11 beta-Hydroxysteroid dehydrogenase deficit: a rare cause of arterial Hypertension. Diagnosis and therapeutic approach in two young brothers.

We report the clinical history and results of endocrine investigations in two brothers born to consanguineous parents, who presented with hypokalemia and arterial hypertension when they were aged 2 and 6 years. The hormonal serum assay results, including extremely low values for aldosterone and plasma renin activity, favored the existence of apparent mineralocorticoid excess. A diagnosis of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) deficiency was made, based on assays of the hydrogenated urinary metabolites of cortisol and cortisone, as well as of corticosterone and dehydrocorticosterone. Indeed we found a very low rate of urinary elimination of cortisone metabolites: tetrahydrogenated cortisone was reduced to between 0.10 and 30 mumol/24 h, which is 15-100 times lower than the normal rate; hexahydrogenated cortolones alpha and beta were found to be 7- to 20-fold lower than normal levels; and the 11-keto-17-ketosteroid derivatives of cortisone were also reduced. Urinary elimination of the cortisol-reduced metabolites 5 beta- and 5 alpha-tetrahydrogenated cortisol were slightly reduced or normal. These results argue in favor of a deficit in the enzyme 11 beta-HSD, which oxidizes cortisol into cortisone. A moderate defect in the conversion of cortisol into 5 beta-THF compared to normal conversion into 5 alpha-THF was also found. With respect to corticosterone metabolism, we demonstrated the presence of a defect in the oxidation of that steroid into dehydrocorticosterone, also due to the deficit in 11 beta-HSD. Arterial hypertension and hypokalemia were corrected by treatment with dexamethasone, concomitantly with correction of the low aldosterone and plasma renin activity levels. On the other hand, during this treatment, urinary concentrations of the metabolites of cortisol, cortisone and corticosterone were only moderately affected.

11-beta-Hydroxysteroid Dehydrogenases↗

Comparison of one-day versus two-day incubation of urine cultures.

The value of incubating urine cultures for 1 versus 2 days was evaluated prospectively for 1526 consecutive specimens. A total of 507 cultures (33.2%) were positive after 1 day; 41 (2.7%) showed different results after 2 days. Only yeasts and corynebacteria were detected more often with longer incubation. Patient charts were available for review from 27 of 41 late positives; in only three instances (11.1%) was action taken by physicians based on these results.

Colony Count, Microbial↗

Effect of oral isotretinoin treatment on skin androgen receptor levels in male acneic patients.

An oral daily dose (mean +/- SD, 0.75 +/- 0.05 mg/kg) of isotretinoin was administered for 3 months to six male patients with acne (scores of 4 and 5 according to Rosenfield). The therapy resulted in complete resolution of acne in four patients and improved acne significantly (score 1) in two patients. In accordance with recent findings, no change in serum testosterone and significant decreases in 5 alpha-dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol glucosiduronate, and androsterone glucosiduronate levels were observed after treatment. Androgen receptor status was investigated in back skin biopsies obtained in acne areas before and after 3 months of isotretinoin treatment. The treatment did not modify the binding affinity constant of skin androgen receptor (0.44 vs. 0.32 nmol/L), but it did induce a 2.6-fold decrease in its binding capacity constant (62 vs. 24 fmol/mg cytosolic protein), as assessed by Scatchard plot and confirmed immunologically by Western blot analysis. These data clearly showed that skin androgen receptor was sensitive to oral isotretinoin administration in acneic patients. The decrease in skin androgen receptor levels (this study) and the recently reported suppression of skin 5 alpha-dihydrotestosterone production by isotretinoin treatment appeared consistent with the involvement of androgen receptor and 5 alpha-dihydrotestosterone in the pathogenesis of acne. Indeed, sebum production is under androgen control, and an abnormal response of the pilosebaceous unit to androgens appears to be implicated in the pathogenesis of acne. These observations were consistent with the absence of sebum in complete androgen-insensitive patients and normal sebum production in male pseudohermaphrodites.

Acne Vulgaris↗

Blood and plasma 5-hydroxytryptamine levels in patients with cirrhosis.

Serotoninergic mechanisms are thought to play a role in portal hypertension. Because this biomine is metabolized by the liver, peripheral blood and plasma levels of 5-hydroxytryptamine and 5-hydroxyindole acetic acid (the main metabolite of 5-hydroxytryptamine) were measured in 30 patients with cirrhosis. Whole-blood 5-hydroxytryptamine levels were significantly lower in patients with cirrhosis (158 +/- 28 nM) than in age-matched controls (332 +/- 19 nM), and no correlation was found between these levels and the severity of cirrhosis. Unconjugated plasma 5-hydroxytryptamine levels, an indication of the active form of 5-hydroxytryptamine, were significantly higher in patients with cirrhosis than in controls (6.8 +/- 1.7 nM and 3.4 +/- 0.5 nM, respectively), and in patients with cirrhosis these levels were higher in Pugh grade A than in Pugh grade C patients. Conjugated-plasma 5-hydroxytryptamine levels were not significantly different between patients with cirrhosis (32.2 +/- 8.1 nmol/L) and controls (16.4 +/- 1.4 nmol/L). Plasma 5-hydroxyindole acetic acid was significantly lower in patients with cirrhosis than in controls (1.5 +/- 0.1 nmol/L and 2.3 +/- 0.1 nmol/L, respectively). In conclusion, this study shows that serotoninergic mechanisms are altered in patients with cirrhosis.

Hepatic Veins↗

The application of a new highly-sensitive radioimmunoassay for plasma 21-deoxycortisol to the detection of steroid-21-hydroxylase deficiency.

21-deoxycortisol (21-DF) is a steroid of strictly adrenal origin formed by the 11-hydroxylation of 17-hydroxyprogesterone. This metabolic pathway is minor in normal subjects, in whom basal plasma concentrations range from 0.03 to 0.63 nmol/L and from 0.865 to 1.50 nmol/L after adrenocorticotrophic hormone (ACTH; Synacthène Immédiat, Ciba/Geigy, France). However, this metabolic pathway becomes major in 21-hydroxylase-deficient patients: in those who have the classical form of congenital adrenal hyperplasia (CAH) basal plasma 21-DF levels can attain more than 144 nmol/L. The synthesis of two isomers, E and Z, of the 21-deoxycortisol-3-carboxymethyloxime (CMO) hapten enabled us to prepare the corresponding E and Z immunogens by coupling them to bovine serum albumin (BSA), as well as the corresponding iodinated E and Z 21-DF-3-CMO-histamine tracers. We developed a very sensitive radioimmunoassay for 21-DF in plasma by associating an anti-21-DF-3-CMO-BSA-E isomer antibody to an iodinated 21-DF histamine-Z isomer (standard curve IC 50 = 8 pg/tube). This plasma 21-DF radioimmunoassay allowed diagnosis of the classical form of CAH in untreated newborn (basal 21-DF levels greater than 144 nmol/L), as well as the late-onset form (post-ACTH 21-DF levels greater than 11.54 nmol/L), and also permitted detection of 21-hydroxylase-deficient heterozygotes of both forms of CAH among the general population (post-ACTH 21-DF levels between 2.02 and 9.52 nmol/L).

Adolescent↗

Evidence for decreased androgen 5 alpha-reduction in skin and liver of men with severe acne after 13-cis-retinoic acid treatment.

To investigate the effect of 13-cis-retinoic acid (13-cis-RA) treatment on androgen metabolism in men with severe nodulocystic acne, eight men with severe acne received an oral daily dose of 0.7 mg/kg 13-cis-RA over 3 months. Exploration of androgen metabolism in serum samples, 24-h urine collections, and skin biopsies obtained before and at the end of the treatment revealed no significant alterations in serum levels of either adrenal or gonadal androgens. However, the treatment did induce significant decreases in serum levels of the 5 alpha-reduced androgens: 5 alpha-dihydrotestosterone (P < 0.02), androsterone glucosiduronate (P < 0.04), and 5 alpha-androstan-3 alpha, 17 beta-diol glucosiduronate (P < 0.004). Unlike serum, the urinary 5 alpha-reduced metabolites 5 alpha-androstan-3 alpha, 17 beta-diol and androsterone did not vary significantly despite a decrease in the excretion of the latter. Moreover, a marginally significant increase in urinary excretion of etiocholanolone, very similar to the decrease in androsterone excretion, was observed. The ratio of androsterone to etiocholanolone decreased significantly (P < 0.004) after 13-cis-RA therapy and suggested a metabolic deviation from the androgen 5 alpha- to 5 beta-reduction pathway in the liver. The most pronounced effect was observed in skin biopsies, which lost 80% of their ability to form 5 alpha-dihydrotestosterone (P < 0.001). It is concluded that 13-cis-RA therapy in men with severe nodulocystic acne did not alter gonadal or adrenal functions, but it did induce 1) a highly significant decrease in 5 alpha-dihydrotestosterone formation by skin biopsies; 2) significant decreases in serum 5 alpha-dihydrotestosterone, androsterone glucosiduronate, and 5 alpha-androstan-3 alpha, 17 beta-diol glucosiduronate; and, finally, 3) deviation of the liver androgen 5 alpha- to 5 beta-reduction pathway. The effect of 13-cis-RA treatment on severe acne is consistent with the dramatic decrease in androgen 5 alpha-reduction observed mainly in the skin.

Acne Vulgaris↗

Hirsutism and acne in women: coordinated radioimmunoassays for eight relevant plasma steroids.

We developed and validated a coordinated set of RIAs for the following eight steroids in single small aliquots (< or = 1 mL) of plasma: androstenedione, dehydroepiandrosterone, 11-deoxycortisol, 21-deoxycortisol (21-DF), 11 beta-hydroxyandrostenedione, 17 alpha-hydroxypregnenolone (17-Hpreg), 17 alpha-hydroxyprogesterone, and testosterone. Samples were extracted and then chromatographed on celite microcolumns. Radioiodinated tracers were used for two of the assays (17-Hpreg and 21-DF). Tritiated tracers and scintillation proximity assay counting were used to give separation-free procedures for the other six assays, which considerably improved their practicability and reproducibility. The basal and postadrenocorticotropic hormone plasma values for these steroids in normal women sampled in the follicular phase are presented. Finally, the measurement of the eight steroids as a diagnostic method is evaluated with reference to data from 203 patients with hirsutism and (or) acne.

17-alpha-Hydroxypregnenolone↗

Impaired oxygenation of gastric mucosa in portal hypertension. The basis for increased susceptibility to injury.

Increased susceptibility to mucosal damage is a prominent feature of portal hypertensive gastropathy. Since the portal hypertensive gastric mucosa has extensive microvascular changes, we postulated that the increased sensitivity to mucosal damage could have an ischemic basis. We measured distribution of gastric serosal and mucosal oxygenation in a group of portal hypertensive and sham-operated rats, and then studied the effects of intragastric aspirin. In the basal state, gastric mucosa of portal hypertensive rats had significantly reduced oxygenation compared to controls (24 +/- 5 vs 45 +/- 7 mm Hg PO2, P less than 0.02), while serosal oxygenation was similar between the two groups. Intragastric aspirin produced significantly greater mucosal damage to portal hypertensive rats and mucosal oxygenation was almost one third that of sham-operated controls. Systemic arterial pressures and oxygenation were similar between the two groups. We conclude that there is impairment of gastric mucosal oxygenation and increased mucosal damage by aspirin in portal hypertensive rats compared with sham-operated controls. These results support our hypothesis that the increased sensitivity of the portal hypertensive mucosa to damage is a consequence of impaired mucosal oxygenation.

Animals↗

Improvement of the nutritional quality of Egyptian and Sudanese sorghum grains by the addition of phosphates.

1. Male broilers (0 to 35 d) were given foods with two types of yellow sorghum substituted for maize in isonutrient diets. Sorghum-based foods were also supplemented with extra phosphorus, to provide a total P of about 8 g/kg; the P being from either orthophosphoric acid or food grade dicalcium phosphate. 2. Both sorghums depressed growth and food:gain ratio and increased the incidence of locomotor disorder to about 0.50 (maize control = 0). Sorghum from Sudan, with higher concentrations of both tannin and phytate, caused more severe anti-nutritive effects than sorghum from Egypt. 3. Within the limits of statistical significance the growth depressing effect of sorghum was completely reversed by extra P. With the more toxic Sudanese sorghum this amelioration was numerically less than complete (growth = 0.94, maize control = 1). Locomotor disorders were also virtually, but not completely, eliminated by phosphorus treatment. 4. Treatment of sorghum by dry-mixing with dicalcium phosphate could form the basis of a simple and economic method for extending the use of high-tannin sorghum in poultry foods. The mode of action of the treatment remains to be determined.

Animal Feed↗

Circulating monoamine oxidase B and phenolsulfotransferase activities in essential hypertensive patients.

Circulating monoamine oxidase (MAO) and phenolsulfotransferase M and P (PST M, PST P) activities were determined in 24 untreated essential hypertensive patients and in 35 age-matched normotensive healthy controls. These enzymes are involved in the inactivation of monoamines and their metabolites. After lysis of blood, enzymatic activities were determined by radioenzymatic techniques using as substrates [14C]-beta-phenylethylamine for MAO, 3-methoxy-4-hydroxyphenylglycol for PST M and phenol for PST P. MAO activity measured by this method is fully accounted for by platelet MAO B activity. Women presented higher MAO activity than men. Significantly lower MAO-B activities were observed in hypertensive patients, both in men and in women, when compared to normotensive controls. Circulating PST activities, of which more than 80% is platelet-derived, were similar in hypertensive and normotensive subjects. These data suggest that the intracellular serotonin inactivation processes, through MAO and PST, cannot account for the reduction of platelet 5-HT content observed in essential hypertension.

Adult↗