Biomedical subjects

M H Mostafa

Publications and source records attributed to M H Mostafa.

At least 19 recordsLinked to original sources

PubMed2004

The human chorionic gonadotropin molecule from patients with trophoblastic diseases has a high thyrotropic activity but is less active in the ovary.

To examine the pathogenesis of hyperthyroidism in women with trophoblastic diseases, the biological activity of human chorionic gonadotropin (hCG) molecules in women with normal pregnancy (n = 85) and in women with trophoblastic diseases (vesicular mole, n = 30; and choriocarcinoma, n = 12) was compared. Hyperthyroidism (thyroid stimulating hormone (TSH) < 0.3 mIU/l) was observed more frequently in women with trophoblastic diseases. All the sera were then subjected to Chinese hamster ovary cells transfected with the human TSH receptor (CHO-hTSHr cells) and cAMP production was compared. Sera from the women with choriocarcinoma showed the highest cAMP production. Interestingly, significant correlation between serum hCG level and cAMP production in CHO-hTSHr cells was observed only in women with trophoblastic disease. All the sera were then applied to CHO cells transfected with hCG/luteinizing hormone (LH) receptor (CHO-hCG/LHr cells). In contrast to the findings with the TSH receptor, sera from the women with normal pregnancy showed the highest cAMP production in these cells. Correlation between serum hCG level and cAMP production in CHO-hCG/LHr cells was significant only in normal pregnancy. These results indicate that the hCG molecule from women with trophoblastic diseases displays enhanced thyrotropic activity.

Adolescent↗

PubMed2003

Changes in expression and activity of glutathione S-transferase in different organs of schistosoma haematobium-infected hamster.

Schistosomiasis is a major health problem in many subtropical developing countries, causing a number of serious pathologies, including bladder cancer. Most of the toxic compounds formed as a result of these infestations are derived either exogenously or formed endogenously and can be conjugated with glutathione (GSH) via glutathione S-transferase (GST). The present study investigates the effect of Schistosma haematobium infection on the activity of GST and glutathione reductase (GR) and levels of glutathione and free radicals (measured as thiobarbituric acid reactive substances) in different organs of the male hamster. The total activity of GST was increased in several organs; in kidney by 50 and 46% at 6 and 10 weeks postinfection, respectively, and in bladder tissues by 169, 23, and 130% at 2, 4, and 6 weeks postinfection, respectively. In support of this, the expression of GST isozymes was also induced in kidney and bladder tissues at early stages (2, 4, and 6 weeks) and reduced at the later stages of infection (8 and 10 weeks). In contrast, the expression of these isozymes was decreased in the spleen and liver at 2, 4, 6, 8, and 10 weeks postinfection. Also, such activity was decreased in lungs by 74 and 78% and in bladders by 65 and 72% at 8 and 10 weeks postinfection, respectively. GSH levels increased in lungs by 95, 40, and 56% at 2, 4, and 6 weeks and in spleen by 26 and 74% at 4 and 6 weeks, respectively, but decreased at later stages of S. haematobium infection in these organs. The depletion of GSH levels also occurred in bladders by 72 and 54% at 8 and 10 weeks postinfection, respectively. The activity of GR was increased in the livers, lungs, and kidneys of the S. haematobium-infected hamster. TBARS also increased in the lung by 14, 65, 53, 828, and 624% and in the kidney by 64, 29, 87, 190, and 111%, and in the bladder by 216, 23, 1468, 528, and 1025% at 2, 4, 6, 8, and 10 weeks postinfection, respectively. This study indicates that low GST expression and high levels of free radicals could provide new evidence for damage to the bladder and other organs as a result of S. haematobium infection.

Animals↗

PubMed2002

Immunological and biological activity of different commercial preparations of human chorionic gonadotropin.

In vitro immunological and biological activity of four commercially available preparations of human chorionic gonadotropin (hCG) for clinical use (Predalon(R): hCG-A, Primogonyl(R): hCG-B, Choragon(R): hCG-C and Pregnisin(R): hCG-D) were examined. The methods used include immunoassay, cAMP production in Chinese hamster ovary (CHO) cells and structural analysis of hCG with high performance liquid chromatography (HPLC). There were remarkable differences in immunological activities among preparations. hCG-D had the highest concentration of free hCGbeta. In CHO cells, production of cAMP with hCG-C was significantly higher than that with other preparations. Analyses in HPLC showed similar pattern in hCG-C and a standard preparation of hCG (CR 123). The highest immunological activity in hCG-A could be attributed to the presence of nicked form of hCG in this preparation. Various hCG components in preparation may explain these differences.

Animals↗

PubMed2002

Changes in the expression of cytochrome P450 isozymes and related carcinogen metabolizing enzyme activities in Schistosoma mansoni-infected mice.

Mixed-function oxidase enzymes metabolize most xenobiotic agents. Western blotting was used to investigate the effect of Schistosoma mansoni infection on the expression of various cytochrome P450 (CYP) isozymes and specific enzyme assays to study related metabolic functions in mouse liver microsomes. Male BK-TO mice were infected with 200 cercariae per mouse and their livers were assayed at 6, 15, 30 and 45 days post-infection (p.i.) and compared with appropriately matched controls. The expression of each of the CYP isozymes (1A1, 2B1/2, 2C6, and 4A) was either unaffected or transiently increased up to 30 days post-infection. By 45 days, a significant loss of signal was observed, particularly for CYP 1A1 and 2B1 /2 where no signal could be detected. Evidence supporting these findings was obtained from enzyme assays specific for particular CYP isozymes. The activity of ethoxyresorufin O-deethylase (CYP 1A1) was reduced by 97% and that of pentoxyresorufin O-depentylase (CYP 2B1 /2) by 96% at 45 days p.i. Similarly, the activity of ethoxycoumarin hydroxylase was progressively reduced over the period under study. It is believed that N-nitrosamines are activated principally by N-nitrosodimethylamine N-demethylase I which was significantly increased at both 30 and 45 days p.i. To further investigate metabolic competency following S. mansoni infection, the in vitro binding of benzo(a)pyrene metabolites to DNA was measured, using isolated liver microsomes to activate benzo(a)pyrene. Benzo(a)-pyrene-DNA adduct formation was markedly increased at 6,15 and 30 days with a maximum at 15 days, but decreased at 45 days p.i. It was concluded that S. mansoni infection changes the expression of different CYP isozymes and also the activity of phase I drug-metabolizing enzymes at different periods of infection and may thus change the liver's capacity to activate or detoxify many endogenous and exogenous compounds. Such alterations may also change the therapeutic actions of drugs that are primarily metabolized by the P450 system, when administered to patients with schistosomiasis.

Animals↗

PubMed2002

Human chorionic gonadotropin exhibits normal biological activity in patients with recurrent pregnancy loss.

To test the hypothesis that the structural abnormality of human chorionic gonadotropin (hCG) may induce recurrent pregnancy loss, we examined the biological activity of hCG in pregnant women with a history of repeated miscarriages (n = 44). Pregnant women without a history of miscarriage (n = 85) were included as controls. Serum hCG, estradiol (E2) and progesterone levels were found to be significantly lower in the pregnancy loss group. There was no difference in serum thyroid hormone levels. Sera from both groups of women were then incubated with Chinese hamster ovary (CHO) cells transfected with hCG/luteinizing hormone receptor (CHO-hCG/LHr) or human thyroid stimulating hormone receptor (CHO-hTSHr). Biological response to hCG in women with recurrent pregnancy loss was identical to that of women in the control group in both CHO-hCG/LHr and CHO-hTSHr cells. When sera were subjected to high performance liquid chromatography, no difference in hydrophobicity was observed between control and patients groups. The structure of the hCG molecule and its biological activity in women with a history of recurrent pregnancy loss are apparently not different from those in women with normal pregnancy. Lower serum progesterone and E2 levels in the patient group can be explained by lower serum hCG levels in these women. Intrinsic gonadotropic and thyrotropic activities of the hCG molecule appear to play no major role in recurrent pregnancy loss.

Abortion, Habitual↗

PubMed2001

Different levels of Schistosoma mansoni infection increased the mutagenicity of benzo(a)pyrene, the activity of aryl hydrocarbon hydroxylase and the formation of hepatic microsomal hydrogen peroxide.

The present study investigates the influence of different levels of Schistosoma mansoni infection (60, 120, 180, 300, 600 cercariae per mice) after 33 days on the activity of aryl hydrocarbon hydroxylase (AHH) and the formation of hepatic hydrogen peroxide (H(2)O(2)) during the metabolic activation of benzo(a)pyrene [B(a)p]. Also, it shows the mutagenic effect of B(a)p at different levels of S. mansoni infection using Salmonella typhimurium TA 98 and TA 102 as a tester strains. High levels of H(2)O(2) production (222 nmol/mg protein) and AHH activity (240 pmol 3-OH B(a)p per mg protein) were seen at 300 cercariae per mice. Increasing histidine revertant colonies at TA98 and TA102 were detected at different levels of S. mansoni infection. These data clearly demonstrate that S. mansoni infection changes the mutagenicity of B(a)p, AHH activity, as well as enhancing the formation of hepatic H(2)O(2) generated during the metabolic activation of B(a)p in infected mice.

Animals↗

PubMed2000

Enhanced alkaline protease production in addition to alpha-amylase via constructing a Bacillus subtilis strain.

Bacillus subtilis Bios11 strain was previously isolated and identified. This strain naturally produces a high level of alpha-amylase. The multicopy (pS1) plasmid that carries the complete alkaline protease aprA gene was introduced to this host strain by transformation. The newly constructed strain was found to express the aprA gene and produces a high level of alkaline protease. The level of alpha-amylase production was not affected compared with the parent strain. The pS1 plasmid in the new host was proved to be segregationally and structurally stable, and the multicopy aprA gene was expressed at the stationary phase. This expression did not affect growth rate and sporulation frequency. Moreover, the level of alpha-amylase was maintained. Both alkaline protease and alpha-amylase enzymes were purified using a single-step affinity chromatography column. The use of the newly constructed strain would be valuable to the enzyme industry and would promote recycling of some food-processing wastes.

Bacillus subtilis↗

PubMed1999

Unique properties of purified, Escherichia coli-expressed constitutive cytochrome P4504A5.

Cytochromes P450 of the 4A family metabolize a variety of fatty acids, prostaglandins, and eicosanoids mainly at the terminal carbon (omega-hydroxylation) and, to a lesser extent, at the penultimate carbon [(omega-1)-hydroxylation]. In the present study, cytochrome P4504A5 (4A5) has been successfully expressed in Escherichia coli, with an average yield of enzyme of approximately 80 nmol/liter of cells. Spectroscopic characterization of the purified enzyme, using electron paramagnetic resonance and absolute and substrate-perturbed optical difference spectroscopy, showed that the heme of resting 4A5 is primarily low spin, but is converted primarily to high spin by substrate binding. The kcat and Km values for laurate omega-hydroxylation were 41 min-1 and 8.5 microM, respectively, in the absence of cytochrome b5, and 138 min-1 and 38 microM, respectively, in the presence of cytochrome b5. Hydroxylation of palmitate was dependent on the presence of cytochrome b5; kcat and Km values were 48 min-1 and 122 microM, respectively. Hydroxylation of arachidonic acid was barely detectable and was unchanged by the addition of cytochrome b5.

Cytochrome P-450 CYP4A↗

PubMed1999

Relationship between schistosomiasis and bladder cancer.

Carcinoma of the urinary bladder is the most common malignancy in the Middle East and parts of Africa where schistosomiasis is a widespread problem. Much evidence supports the association between schistosomiasis and bladder cancer: this includes the geographical correlation between the two conditions, the distinctive patterns of gender and age at diagnosis, the clinicopathological identity of schistosome-associated bladder cancer, and extensive evidence in experimentally infected animals. Multiple factors have been suggested as causative agents in schistosome-associated bladder carcinogenesis. Of these, N-nitroso compounds appear to be of particular importance since they were found at high levels in the urine of patients with schistosomiasis-associated bladder cancer. Various strains of bacteria that can mediate nitrosation reactions leading to the formation of N-nitrosamines have been identified in the urine of subjects with schistosomiasis at higher intensities of infection than in normal subjects. In experimental schistosomiasis, the activities of carcinogen-metabolizing enzymes are increased soon after infection but are reduced again during the later chronic stages of the disease. Not only could this prolong the period of exposure to activated N-nitrosamines, but also inflammatory cells, stimulated as a result of the infection, may induce the endogenous synthesis of N-nitrosamines as well as generating oxygen radicals. Higher than normal levels of host cell DNA damage are therefore anticipated, and they have indeed been observed in the case of alkylation damage, together with an inefficiency in the capacity of relevant enzymes to repair this damaged DNA. In experimental schistosomiasis, it was also found that endogenous levels of host cell DNA damage were related to the intensity of infection. All of these factors could contribute to an increased risk of bladder cancer in patients with schistosomiasis, and in particular, the gene changes observed may have potential for use as biomarkers in the early detection of bladder cancer that may assist in alleviating the problem.

Animals↗

PubMed1998

Salivary nitrate, nitrite and nitrate reductase activity in relation to risk of oral cancer in Egypt.

It has been suggested that nitrate and nitrite may play a role in the etiology of human oral cancer. We investigated whether salivary nitrate and nitrite and the activity of nitrate reductase (NRase) may affect the risk of oral cancer in Egypt, an area with high levels of environmental nitrosating agents. Levels of salivary nitrite (8.3 +/- 1.0 micrograms/ml) and nitrate (44 +/- 3.7 micrograms/ml) and activity of NRase (74 +/- 10 nmol/ml/min) were significantly (P < 0.05) higher in oral cancer patients (n = 42) compared to control Egyptian healthy individuals (n = 40, nitrite = 5.3 +/- 0.3 micrograms/ml, nitrate = 27 +/- 1.2 micrograms/ml, and NRase activity = 46 +/- 4 nmol/ml/min). The adjusted odds ratio (OR) and the 95% confidence intervals (C.I.) for risk of oral cancer, categorized by the levels of salivary nitrate and nitrite and NRase activity, showed a higher cancer risk associated with nitrite > 7.5 micrograms/ml (OR: 3.0, C.I.: 1.0-9.3), nitrite > 40 micrograms/ml (OR: 4.3, C.I.: 1.4-13.3) and NRase activity > 50 nmol/ml/min (OR: 2.9, C.I.: 1.1-7.4). Our findings suggest that increased consumption of dietary nitrate and nitrite is associated with elevated levels of salivary nitrite. Together with the increased activity of salivary NRase, these observations may explain, at least in part, the role of nitrate and nitrite in the development of oral cancer in individuals from an area with a high burden of N-nitroso precursors.

Adult↗

PubMed1996

N-nitroso compounds induce changes in carcinogen-metabolizing enzymes.

The bioactivation of N-nitrosoamines and polycyclic aromatic hydrocarbons (PAH) is mediated by the mixed function oxidase system, which includes dimethylnitrosamine N-demethylase I (DMN-dI), arylhydrocarbon hydroxylase (AHH), cytochrome P-450, cytochrome b5 and NADPH-cytochrome c reductase of liver microsomes. The present study shows the influence of N-nitroso compounds on the activities of the above-mentioned enzymes. Single-dose treatment (20 mg/kg body weight) of male mice with ethylbutylnitrosamine, propylbutylnitrosamine, or dibutylnitrosamine: increased (1) the activity of DMN-dI by 108%, 104%, 51%, respectively; (2) the cytochrome P-450 content by 106%, 72%, 51%, respectively; (3) the activity of AHH by 95%, 106%, 80% respectively; (4) the cytochrome b5 content by 164%, 97%, 94% respectively; and (5) decreased the activity of NADPH-cytochrome c reductase by 55%, 50% and 45%, respectively. Methylpropylnitrosamine decreased the activity of DMN-dI by 44% and the P-450 content by 50%. Diphenylnitrosamine also decreased cytochrome P-450 by 54%, AHH activity by 64% but increased the activity of DMN-dI by 42%, the cytochrome b5 content by 159% and NADPH-cytochrome c reductase activity by 57%. It seems from this study that the activity of AHH is dependent on P-450 content but DMN-dI is not since the compounds that increased or decreased the activity of AHH had parallel effects on P-450 content. Also, the extent to which the altered activities of DMN-dI, P-450, AHH, cytochrome b5 and NADPH-cytochrome c reductase depends on the type of alkyl groups linked to the nitroso group.

Animals↗

PubMed1996

N-nitrosamines and their effects on the level of glutathione, glutathione reductase and glutathione S-transferase activities in the liver of male mice.

The present study investigates the influence of different chemical structure of N-nitroso compounds on the hepatic level of reduced glutathione (GSH), glutathione reductase (GSH-R) and glutathione S-transferase (GST) activities in the liver of male Balb/C mice after treatment with 20 mg/kg body weight of each compound for 1 h as a single dose. The level of reduced glutathione decreased significantly between 37 and 70% after the treatment of male mice with ethylbutylnitrosamine (-37%), diphenylnitrosamine (-50%), propylbutylnitrosamine (-52%), diethylnitrosamine (-54%), ethylmethylnitrosamine (-55%), and dibutylnitrosamine (-70%), whereas, methylpropylnitrosamine increased the level of GSH by 71%. All the N-nitrosamine compounds tested increased the activity of glutathione reductase except ethylmethylnitrosamine had no effect. The activity of glutathione S-transferase activity was inhibited after treatment of the male mice with diphenylnitrosamine (-60%), dibutylnitrosamine (-60%), and methylpropylnitrosamine (-81%), while, ethylmethylnitrosamine and ethylbutylnitrosamine had no effect on such activity. On the other hand, diethylnitrosamine increased the activity of glutathione S-transferase by 50%. It can be postulated from this study that the chemical structure of N-nitrosamines plays a significant role in the alteration of GSH level and GSH metabolizing enzymes, since the substitution of different groups on the nitroso group was found to be capable of causing an alteration in such activities.

Animals↗

PubMed1995

Marine algae that display anti-tumorigenic activity against Agrobacterium tumefaciens.

Thirty-five extracts representing different seasonal growths of 17 marine algal species collected from the Alexandria coast were tested for anti-tumorigenic activity against Agrobacterium tumefaciens galls on potato discs. Eleven extracts (nine species) displayed > 20% inhibition of tumor initiation, with three of these (Codium tomentosum, winter; Jania rubens, summer; Padina pavonia, winter) displaying relatively high activity. Bacterial viability tests showed that the inhibitory effects were directly due to anti-tumorigenesis rather than an indirect result of anti-bacterial activity.

Agrobacterium tumefaciens↗

PubMed1995

Changes in nocturnal pineal indoleamine metabolism in rats treated with parathion are prevented by beta-adrenergic antagonist administration.

Parathion, an organophosphorous insecticide, was previously shown to enhance the nighttime rise in pineal N-acetyltransferase (NAT) activity and serum melatonin levels. The purpose of the present study was to test whether parathion acts on the pineal gland by means of a beta-adrenergic receptor mechanism. Whereas parathion (total dose 6.5 mg/kg body wt over 6 days) by itself significantly augmented nocturnal pineal NAT activity and serum melatonin levels in otherwise untreated rats, the insecticide was ineffective in reference to this enzyme when it was given in conjunction with the beta-adrenergic receptor antagonist propranolol (20 mg/kg body wt, 1 h before lights off). The augmentation of NAT activity by parathion also caused significant reductions in pineal serotonin (5-HT); again, this response was blocked by propranolol treatment. Neither pineal hydroxyindole-O-methyltransferase (HIOMT) activity nor pineal levels of 5-hydroxytryptophan or hydroxyindole acetic acid (5-HIAA) were significantly changed as a result of either parathion or propranolol treatment. The results are consistent with the idea that parathion influences pineal 5-HT metabolism either at the level of the beta-adrenergic receptor or via the sympathetic innervation to the pineal gland.

Animals↗

PubMed1995

Role of schistosomiasis in human bladder cancer: evidence of association, aetiological factors, and basic mechanisms of carcinogenesis.

Several epidemiological, clinical and experimental studies have been carried out to determine whether there is an aetiological role for schistosomiasis in the multi-stage process of bladder carcinogenesis. Lines of evidence supporting the association between bladder cancer and schistosomiasis include indications from the geographical correlation between the two conditions, the distinctive patterns of gender and age at diagnosis, the clinicopathological identity of schistosome-associated bladder cancer and the extensive experimental evidence in infected laboratory animals. Although the causative role of schistosomiasis is now accepted, various associated factors have been proposed in the induction of this particular type of cancer. While all may contribute to the carcinogenic process taking place in the infected bladder, none of these has yet been confirmed. Most attention has been directed at theories proposing possible roles for urinary chemical carcinogens, particularly tryptophan metabolites, N-nitroso compounds and of beta-glucuronidase, as factors that are primarily involved in the initiation of bladder carcinogenesis in areas endemic for schistosomiasis.

Adult↗

PubMed1995

Night-time rise in rat pineal N-acetyltransferase due to carbaryl administration is reduced by propranolol treatment.

The purpose of the present study was to examine the effects of administration of sublethal doses of carbaryl on nighttime rat pineal melatonin synthesis in the presence and absence of propranolol, a beta-adrenergic receptor antagonist. Two groups of adult male albino rats were administered orally N-methyl-l-naphthylcarbamate (carbaryl) (8.33 mg/kg BW daily in corn oil) for six successive days; another two groups received corn oil only. On the last day of carbaryl treatment, half of the animals received an intraperitoneal injection of propranolol (20 mg/kg body weight, one hour before lights off). The other two groups were given a saline injection. Four hours after darkness onset, pineal N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) activities as well as pineal concentrations of 5-hydroxytryptophan (5HTP), serotonin (5HT), 5-hydroxyindole acetic acid (5HIAA) and pineal and serum melatonin levels were measured. Nocturnal NAT activity was increased due to carbaryl administration but the pesticide was ineffective in stimulating NAT activity in rats treated with propranolol. Pineal 5HT was decreased due to carbaryl administration but 5HTP and 5HIAA levels were unaffected. Pineal and serum melatonin levels were decreased due to propranolol treatment. The results indicate that carbaryl may influence pineal NAT activity by a mechanism that involves beta-adrenergic neural transmission.

Animals↗

PubMed1994

High level of expression and stability of the cloned alkaline protease (aprA) gene in Bacillus subtilis.

Gene expression and plasmid stability of the cloned alkaline protease (aprA) gene in Bacillus subtilis were investigated. B. subtilis cells harboring the multicopy aprA gene were grown on sporulation medium and the activity of the alkaline protease was monitored throughout the cultivation time. Results presented indicate that the expression of the aprA gene occurred late during the stationary phase and the plasmid that carries the aprA gene was segregationally and structurally stable.

Bacillus subtilis↗

PubMed1994

O6-alkylguanine-DNA alkyltransferase activity in schistosomiasis-associated human bladder cancer.

O6-Alkylguanine-DNA-alkyltransferase (ATase) activity was measured in extracts of 55 bladder tissue samples (46 tumour and nine uninvolved mucosal tissue) from Egyptian patients with schistosome-associated bladder carcinoma. Activity varied from 2.0 to 16.2 fmole ATase/microgram DNA (mean +/- S.D.; 5.6 +/- 4.0) or from 28 to 351 fmole ATase/mg (117 +/- 71). ATase levels in schistosome-associated bladder cancer tissues (5.6 +/- 4.0 fmole ATase/microgram DNA) tended to be lower than those observed in normal human bladder mucosal tissue (8.5 +/- 4.4 fmole ATase/microgram DNA). In a previous study (Badawi et al., Carcinogenesis, 1992, 13, 877-881) DNA-alkylation damage (O6-methyldeoxyguanosine) was found in 44/46 of these schistosome-associated bladder cancer samples at levels ranging from 0.012 to 0.485 mumole O6-MedG/mole deoxyguanosine. We now report an inverse correlation between the levels of methylation damage and ATase activity (r = -0.67; P < 0.001). These observations encourage further investigations of the possible role of environmental alkylating agents in the aetiology of early bladder cancer associated with schistosomiasis.

DNA, Neoplasm↗