S. Amr - Academia.edu (original) (raw)

Papers by S. Amr

Estradiol-17j3 dehydrogenase (E2DH) activity was measured in the endometrium of immature and of m... more Estradiol-17j3 dehydrogenase (E2DH) activity was measured in the endometrium of immature and of mature rat uteri at different times of the estrous cycle and during the first 10 days of pregnancy. E2DH activity is not detected in immature or castrated mature rats. During the estrous cycle, E2DH activity is 565 Â±103 pmol/mg protein/h (mean Â±SEM, n = 7) at proestrus; 479 Â±80

Endocrinology, 1987

The beta-subunit of hCG was digested with trypsin to produce a modified form of the subunit for s... more The beta-subunit of hCG was digested with trypsin to produce a modified form of the subunit for structure-function and immunological studies. After digestion of hCG beta with trypsin, the residual disulfide-linked core was isolated and found to be lacking the carboxy-terminal peptide (residues 115-145) and to contain bond cleavages between residues 2-3, 43-44, 74-75, and 95-96. The locations of these bond cleavages within the disulfide-bridged core were identified by isolation of the following peptides after reduction and S-carboxymethylation of the trypsin beta-core: beta 1-43, beta 3-43, beta 44-74, beta 44-95, beta 75-95, and beta 96-114. The circular dichroic spectrum of the tryptic beta-core over the wavelength region of about 200-320 nm was similar to that of the native subunit. In addition, the tryptic beta-core retained nearly full immunopotency in both polyclonal and monoclonal competitive RIAs and could combine with complementary native alpha-subunit. The hybrid, composed ...

... AND BIOPHYSICAL RESEARCH COMMUNICATIONS Pages 146151 SIALSC ACID RESIDUES OF TH trSUBUNIT ARE... more ... AND BIOPHYSICAL RESEARCH COMMUNICATIONS Pages 146151 SIALSC ACID RESIDUES OF TH trSUBUNIT ARE REQUIRED FCR THE THYROIRCPIC ACTIVITY OF HCG Sania Amr, Yasuyuki ... Amir, SM, Sullivan, R. and Ingbar, SH (1981) Endocrinology 109, 12031211. ...

We have characterized the distribution, metabolism and excretion of hCG and its subunits in norma... more We have characterized the distribution, metabolism and excretion of hCG and its subunits in normal human subjects. The initial apparent volume of distribution was the same for hCG, hCG beta, and hCG alpha. Their disappearance curves fit a two-component exponential model, and calculations indicated that both the rapid and slow phase half-times of hCG are approximately 10-fold greater than those of hCG beta and 30-fold greater than those of hCG alpha. Despite the more rapid metabolic clearance rates of the subunits, their renal clearance is 2- to 3-fold less than that of hCG. Thus, renal clearance accounts for less than 1% of the metabolic disposal of the subunits, whereas it represents a major fraction (20-25%) of the metabolic disposal of hCG. After injection of the isolated beta subunit of hCG, two forms were excreted in the urine. One was intact hCG beta and the other was a discrete fragment of the hCG beta which appears to lack the hCG beta carboxyterminal peptide immunologic det...

EstradioI-17@3 dehydrogenase (E2DH) activity in rat endometrium is undetectable in the cas trated... more EstradioI-17@3 dehydrogenase (E2DH) activity in rat endometrium is undetectable in the cas trated rat but can be induced by E2 stimulation. When E2 is given alone for 3 days, the E2DH activity induced is linearly related to the logarithm of the dose administered (r = 0.90, P<0.005). Administration of progesterone (P) with the third E2 injection decreases the enzyme activity but a linear relationship is still observed with the logarithm of the dose of E2 administered (r = 0.77, P<0.O05).P aloneisnotabletoinduceE2DH activity. However,when P isadministered for3days and E2 is added with the last P injection, the effect of this single dose of E2 is magnified. A time lag is observed between E2 administration and the induction of E2DH activity when the dose of E2 is 0.1 jig. When the single dose of E2 is increased to 2 jig, the time lag is shortened. After induc tion in these conditions, P alone is able to maintain E2DH activity. These data indicate that changes in the enzyme activit...

Journal of Biological Chemistry

In order to further characterize chemical, physicochemical, and immunochemical properties, as wel... more In order to further characterize chemical, physicochemical, and immunochemical properties, as well as structure-function relationships, of the common alpha subunit of human glycoprotein hormones, a tryptic core was prepared from the alpha subunit of human choriogonadotropin. The core was purified in greater than 80% yield using gel permeation and anion-exchange chromatography, and, following reduction and S-carboxymethylation, the constituent peptides were purified by gel permeation and high performance liquid chromatography. The disulfide-bridged peptides comprising the alpha core were identified as residues 1-35 and residues 52-91 by amino acid composition and amino acid carboxyl sequence analyses of the reduced, S-carboxymethylated peptides. The alpha tryptic core contained both N-asparagine carbohydrate moieties, but was devoid of residues 36-51 and the carboxyl-terminal serine at position 92. The small peptides cleaved from residues 36-51, a known potential O-glycosylation region of the alpha subunit, were purified and identified. The tryptic core retained full immunopotency relative to the intact subunit in the binding to polyclonal and monoclonal antibodies directed against the alpha subunit. The region consisting of residues 36-51 is not part of the epitope recognized by these antibodies. With antisera generated to the reduced, S-carboxymethylated subunit, peptide 1-35, but not 52-91, was immunoreactive. This finding is consistent with the known dominant antigenicity of the amino-terminal region in the reduced, S-carboxymethylated molecule. The core exhibited no appreciable interaction with the complementary beta subunit, and, not surprisingly, was unable to compete with intact hormone binding in a radioreceptor assay using rat testicular homogenates. Circular dichroic spectroscopy was used to probe gross features of tertiary structure (240-300 nm) and secondary structure (190-240 nm). The tryptic core and each of the two constituent peptides exhibited spectra above 240 nm that resembled that of the reduced, S-carboxymethylated subunit more than that of the native material, thus suggesting a significant loss of tertiary structure in the core and isolated peptides. This finding is unexpected in consideration of the full retention of immunopotency by the alpha core although consistent with failure of the core to combine with intact complementary beta subunit. The intact subunit as well as the isolated constituent peptides exhibit little if any helicity in aqueous solution. Interestingly, the reduced, S-carboxymethylated chain and peptide 52-91 displayed helicity in 80% trifluoroethanol, a helicogenic solvent.

American Journal of Physiology-Endocrinology and Metabolism

We investigated the function of thyrotrophs in rat pituitaries that were transplanted under the r... more We investigated the function of thyrotrophs in rat pituitaries that were transplanted under the renal capsule of 3-wk-old male Sprague-Dawley rats, which were either intact or hypophysectomized. Groups of 12 animals were implanted with osmotic minipumps that delivered a constant infusion of either thyrotropin-releasing hormone (TRH; 1 mg X kg-1 X day-1) or normal saline for 1 wk. In hypophysectomized rats, TRH infusion led to the appearance of substantial amounts of biologically active serum TSH and prevented the hypothyroidism that occurred in the control group. However, TRH did not change the transplant contents of DNA, immunoactive TSH, and mRNA levels for TSH subunits. Comparison of sellar and renal pituitary tissues, obtained from intact rats after 1 wk of either saline or TRH infusion, showed that removal of the pituitary from hypothalamic influence resulted in a 90% depletion of the thyrotroph TSH content. TRH infusion depleted only 63% of the TSH content of sellar thyrotroph...

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism

We compared the effects of |n~a]ipid and dextrose infusion on plasma lecithin:cholesterol acy|tra... more We compared the effects of |n~a]ipid and dextrose infusion on plasma lecithin:cholesterol acy|transferase (LCAT), p|asma ||p|d profiles and ||po|ytic activity. We used 5-week-old male Sprague-Dawley rats which were given tota| parentera| nutrition (TPN) with either llntralipid (3 g/kg body weight) or an equicaioric amount of 25% dextrose in the presence or absence of hepar|n (1 or l0 IU/ml of TPN). 40 rain after the end of 4 h of infusion, plasma LCAT activity wa~ significantly decreased (P< 0.00D, wMle total choleseero| and free fatty acid |evels were significantly (P < 0.05) increased in rats given Intrafipid as compared to those given dextrose. We found associations (P < 0.005) between LCAT activ|ty and total cholesterol and between LCAT and free fatty acid levels; the coefficients of negative correla~on were 0.543 and 0.607, respectively. Concom|tanfly to the increment |n plasma total cholesterol levels, there was a decrease in the high-density |ipoproteln (HDL) cholestero| fraction; the iat~er, which was 40% of the total plasma cholesterol |n control and dextrose-infused rats, declined to 9% in rats Oven lntralipid. Administration of beparin during |ntra]ipid infusion, even up to 10 H.J/ml of TPN, did not affect any of these changes. After dex~ose infusion, the values of all thr~e pa_~meters were sim||ar to those of the control group. Plasma |ipolytic activity was not significantly different between ra:~ given infus|on (Intra|ipid or dextrose) and contro|s. However, in the presence of heparin, plasma lipolytic activity increased similarly in both infused groups. These data indicate that in young rats, |nt~alipid infusion leads to an |ncrease in plasma total cholesterol and free fat~ acid levels, which correlates with a decrease in LCAT activity; the concurrent decrease in HDL cholesterol |eve|s might account, in part, for the loss of LCAT activity. The aehninistrafion of beparin results in an elevation of plasma Hpolytic activity; however, it does not prevent the hypercholesterolemia, nor the decline in LCAT activity associated with Intralipid infusion.

The Journal of biological chemistry, Jan 15, 1986

The American journal of physiology, 1986

Annales d'endocrinologie, 1984

We have observed unusual forms of human choriogonadotropin (hCG) in the urine of patients with ge... more We have observed unusual forms of human choriogonadotropin (hCG) in the urine of patients with gestational trophoblastic neoplasia. These molecules were of two types: Carboxyterminal fragments of hCG beta-subunit and desialylated forms of hCG. Substantial amounts of these materials were found in the urines of 83% and 50%, respectively, of the patients (n = 12) studied. In contrast, negligible quantities were found in the urine of 14 healthy pregnant women. Also, these unusual forms were not detectable in normal controls given an infusion of hCG. These findings indicate that these forms have clinical potential for diagnosing gestational trophoblastic neoplasia and differentiating it from normal pregnancy.

Urologic Oncology: Seminars and Original Investigations, 2012

Pediatric Cardiology, 2001

The true incidence of myocarditis in children is difficult to estimate because many mild cases go... more The true incidence of myocarditis in children is difficult to estimate because many mild cases go undetected. This study describes an unusual cluster of myocarditis cases that occurred in young children living in the greater Baltimore area between May and October 1997. A search of multiple comprehensive databases and interviews with area pediatric cardiologists were conducted to identify unreported cases and determine the background rate of myocarditis in the area. Seven cases of myocarditis were found as well as two with a similar clinical picture and myocardial fibrosis on tissue examination. Six case patients with active myocarditis and one child with fibrosis died. The case children were predominantly black (eight of nine) and male (seven of nine), with no identifiable risk factors. The disease was characterized by a fulminant course with malignant arrhythmias. The greatest number of pediatric myocarditis deaths reported in 1 year prior to 1997 was three. Myocardial tissues were examined using immunohistochemistry, in situ hybridization, and polymerase chain reaction but no etiologic agent was identified. This outbreak is unusual because of both the number of cases and the fulminant course of the disease in this group of children.

The Journal of Clinical Endocrinology & Metabolism, 1986

... Bioactivity *. PAOLO BECK-PECCOZ , PISCITELLI PISCITELLI , SANIA AMR , MARIA BALLABIO , MONIQ... more ... Bioactivity *. PAOLO BECK-PECCOZ , PISCITELLI PISCITELLI , SANIA AMR , MARIA BALLABIO , MONIQUE BASSETTI , GIULIANA GIANNATTASIO , ANNA SPADA , MARINA NISSIM , BRUCE D. WEINTRAUB and GIOVANNI FAGLIA ...

International Journal of Radiation Biology and Related Studies in Physics, Chemistry and Medicine, 1977

Hormone and Metabolic Research, 1981

Thyroid-stimulating hormone (TSH) in tumor and serum of mice with thyrotropic tumors was studied ... more Thyroid-stimulating hormone (TSH) in tumor and serum of mice with thyrotropic tumors was studied by radioimmunoassay (RIA), radioreceptor assay (RRA) and thyroid adenylate cyclase assay (ACA). In unfractionated samples, serum TSH displayed significantly higher ACA/RIA (0.69 +/- 0.10) and ACA/RRA ratios (0.79 +/- 0.04) than TSH in tumor extracts (0.45 +/- 0.05 and 0.31 +/- 0.01, respectively). After gel chromatography, both tumor and serum TSH activity measured in RIA and RRA eluted in broad, heterogeneous peaks with an apparent molecular weight range of 26,000 - 44,000 daltons. The ACA activity of tumor TSH eluted in 2 sharp peaks (26,000 and 44,000) while that of serum TSH eluted in 3 peaks (26,000, 33,000 and 44,000). The ACA/RIA and ACA/RRA ratios varied greatly among the chromatography fractions, the lowest ratios being detected in the tumor TSH of 33,000 daltons (0.02 for each) and the highest ratios in both tumor and serum TSH of 26,000 (ACA/RIA = 1.60 - 1.90, ACA/RRA = 1.12 - 1.20). Since previous biosynthetic studies have suggested that such heterogeneous forms of mouse tumor TSH differ solely in carbohydrate content, our data suggest that the biologic activity of TSH may be modulated by its glycosylation.

Endocrinology, 1986

To investigate whether TRH regulates TSH production through a pre- or posttranslational mechanism... more To investigate whether TRH regulates TSH production through a pre- or posttranslational mechanism, we determined the pituitary levels of mRNAs for alpha-subunit and TSH beta in male Sprague-Dawley rats given TRH in the presence or absence of thyroid hormones, with or without hypothalamic influence. In normal rats, serum TSH increased 6-fold after a single sc injection of TRH (7 micrograms/kg BW), but the levels of mRNA for both TSH subunits did not differ from the control values. Infusion of TRH, achieved by osmotic minipumps that were implanted sc, increased serum TSH for 3 days. Conversely, the pituitary content of TSH dropped to and remained 35% of that in the controls. In these normal rats, throughout the TRH infusion, the pituitary levels of mRNA for the TSH subunits did not differ from those in the controls. Thyroidectomy increased, by 27 and 75 times, the normal levels of mRNAs for alpha and TSH beta, respectively. TRH, given either as a single injection or a 3-day infusion, did not further elevate these levels. We then studied thyroidectomized animals whose pituitaries were transplanted under their renal capsules. These pituitaries responded to TRH infusion by releasing TSH. T4 injection inhibited this response significantly, but not completely. In spite of this evidence of normal responsiveness to TRH, infusion of TRH for a week did not increase the level of mRNAs for either TSH subunit in transplanted pituitaries. We conclude that in the presence or absence of thyroid hormones, with or without concurrent hypothalamic influence, TRH did not affect rat pituitary level of mRNA for either TSH subunit despite persistent high levels of serum TSH. Therefore, TRH does not regulate TSH production through a pretranslational mechanism. Although a translational regulation cannot be completely excluded, the present data, in conjunction with previous findings, support the hypothesis that TRH regulates TSH production primarily by stimulating both posttranslational carbohydrate processing and secretion of this hormone.

Cancer Epidemiology Biomarkers & Prevention, 2012

Background: We investigated associations between tobacco exposure, history of schistosomiasis, an... more Background: We investigated associations between tobacco exposure, history of schistosomiasis, and bladder cancer risk in Egypt. Methods: We analyzed data from a case-control study (1,886 newly diagnosed and histologically confirmed cases and 2,716 age-, gender-, and residence-matched, population-based controls). Using logistic regression, we estimated the covariate-adjusted ORs and 95% confidence interval (CI) of the associations. Results: Among men, cigarette smoking was associated with an increased risk of urothelial carcinoma (OR ¼ 1.8; 95% CI, 1.4-2.2) but not squamous cell carcinoma (SCC); smoking both water pipes and cigarettes was associated with an even greater risk for urothelial carcinoma (OR ¼ 2.9; 95% CI, 2.1-3.9) and a statistically significant risk for SCC (OR ¼ 1.8; 95% CI, 1.2-2.6). Among nonsmoking men and women, environmental tobacco smoke exposure was associated with an increased risk of urothelial carcinoma. History of schistosomiasis was associated with increased risk of both urothelial carcinoma (OR ¼ 1.9; 95% CI, 1.2-2.9) and SCC (OR ¼ 1.9; 95% CI, 1.2-3.0) in women and to a lesser extent (OR ¼ 1.4; 95% CI, 1.2-1.7 and OR ¼ 1.4; 95% CI, 1.1-1.7, for urothelial carcinoma and SCC, respectively) in men. Conclusions: The results suggest that schistosomiasis and tobacco smoking increase the risk of both SCC and urothelial carcinoma. Impact: This study provides new evidence for associations between bladder cancer subtypes and schistosomiasis and suggests that smoking both cigarettes and water pipes increases the risk for SCC and urothelial carcinoma in Egyptian men. Cancer Epidemiol Biomarkers Prev; 21(3); 537-46. Ó2011 AACR.