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Biomedical subjects

M Hassan

Publications and source records attributed to M Hassan.

At least 19 recordsLinked to original sources
PubMed2006

Speciation of 210Po and 210Pb in air particulates determined by sequential extraction.

Speciation of (210)Po and (210)Pb in air particulates of two Syrian phosphate sites with different climate conditions has been studied. The sites are the mines and Tartous port at the Mediterranean Sea. Air filters were collected during September 2000 until February 2002 and extracted chemically using different selective fluids in an attempt to identify the different forms of these two radionuclides. The results have shown that the inorganic and insoluble (210)Po and (210)Pb (attached to silica and soluble in mineral acids) portion was found to be high in both sites and reached a maximum value of 94% and 77% in the mine site and Tartous port site, respectively. In addition, only 24% of (210)Pb in air particulates was found to be associated with organic materials probably produced from the incomplete burning of fuel vehicle and similar activities. Moreover, the (210)Po/(210)Pb activity ratio in air particulates was higher than that in all samples at both sites and varied between 3.85 in November 2000 at Tartous port site and 20 in April 2001 at the mine area. These activity ratios were also higher than the natural levels. The (210)Po/(210)Pb activity ratio was also determined in each portion resulting from the selective extraction and found to be higher than that in most samples. The sources of (210)Po excess in these portions are discussed. Soil suspension, which is common in the dry climate dominant in the area, sea water spray and heating of phosphate ores were considered; polonium is more volatile than the lead compounds at even moderate temperature. Furthermore, variations in the chemical forms of (210)Po and (210)Pb during the year were also investigated. However, the results of this study can also be utilized for dose assessment to phosphate industry workers.

Air Pollutants, Radioactive↗
PubMed2006

Impact on the cytomegalovirus (CMV) viral load by CMV-specific T-cell immunity in recipients of allogeneic stem cell transplantation.

Patients experience cytomegalovirus (CMV) reactivation after stem cell transplantation (SCT) and need repeated courses of pre-emptive therapy. Analysis of CMV-specific immunity might help to assess the need for antiviral therapy. Forty-eight patients were studied during the first 3 months after SCT. Peripheral blood lymphocytes were stimulated by CMV antigen, and interferon (INF)-gamma production by CD3+ and CD4+ T cells was analysed. Results were correlated to transplant factors and CMV disease. Patients with INF-gamma production by CD3+ cells at 4 weeks after SCT had lower peak viral loads than patients with no such production (P=0.03). There was a similar tendency as regards CD4+ cells (P=0.09). Patients who underwent reduced-intensity conditioning (RIC) more frequently had CD3+ (48%) and CD4+ immunity (56%) 4 weeks after SCT compared with patients who received myeloablative conditioning (CD3+ 25%; CD4+ 35%). There was no effect of stem cell source, donor type or acute graft-versus-host disease. Three of 48 patients developed CMV disease and none of them had detectable INF-gamma production. CMV-specific T-cell response is associated with a lower rate of CMV replication. RIC results in improved T-cell reconstitution. Recovery of CMV-specific immunity might be delayed in patients with CMV disease. These observations suggest that detection of CMV-specific T-cells is useful in assessing the immunity against CMV.

Adolescent↗
PubMed2006

Bovine hypodermosis: prevalence and economic significance in southern Punjab, Pakistan.

Prevalence and economic losses of warble fly infestation (WFI) in cattle and buffaloes were recorded in Dera Ghazi Khan and Rajan Pur districts of southern Punjab (Pakistan). A total of 18,000 cattle and 9000 buffaloes were examined in the field and slaughter house. Only one species of Hypoderma, i.e. Hypoderma lineatum was recorded from this area. The prevalence of WFI was higher in slaughter house versus field, cattle versus buffaloes, males versus females, and young versus old animals in both the districts. The highest month-wise prevalence was recorded in December and the lowest in July. Organ-wise prevalence of WFI was highest in oesophagus followed in order by rumen and spleen. The economic losses based on the value of warbled and warble-free hides were estimated as Rs. 22.8 million per annum (currency exchange rate is Rs. 57.5=US 1 dollar).

Age Factors↗
PubMed2006

Screening for cervical carcinoma using visual inspection with acetic acid.

OBJECTIVE: To assess the performance of visual inspection with acetic acid (VIA) as a screening test for early detection of cervical carcinoma in the Dakahlia Governorate in Egypt. METHODS: Diluted acetic acid (5%) was applied to the cervix during routine gynecologic examination. Women with positive results were referred for colposcopy. Those with negative results were referred for colposcopy only when they had clinical indications. RESULTS: Among the 5,000 women who were screened using VIA, 409 were referred for colposcopy. Cervical intraepithelial neoplasia (CIN) was diagnosed in 151 (60%) of the 253 women with positive screening results and in 4 of the 156 women with negative screening results. There were 39 women with high-grade and 116 with low-grade CIN. The sensitivity and negative predictive value of the VIA screening test was 97%. Its positive predictive value was 60% for all grades of CIN and 90% for high-grade CIN. CONCLUSION: Visual inspection with acetic acid, although associated with a relatively high rate of false-positive results, is a valuable test for the screening of cervical carcinoma.

Acetic Acid↗
PubMed2006

Inhibition activities of Colchicum luteum baker on lipoxygenase and other enzymes.

In vitro enzymes inhibition activities of the crude methanolic extract and various fractions of Colchicum luteum Baker (Liliaceae) including chloroform, ethyl acetate, n-butanol and aqueous were carried out against actylcholinesterase, butyrylcholinesterase, lipoxygenase and urease enzymes. A significant enzyme inhibition activity (89%) is shown by the crude methanolic extract and its fractions against lipoxygenase, while low to significant activity (32-75%) was evident against butyrylcholinesterase. The crude methanolic extract and its various fractions demonstrated low activity (29-61%) against acetylcholinesterase and no activity against urease.

Acetylcholinesterase↗
PubMed2005

Identification of functional genes during Fas-mediated apoptosis using a randomly fragmented cDNA library.

We describe a general strategy for the identification of functional genes that, when downregulated, result in a selectable phenotype. This strategy is based on expression selection of cDNA fragments that counteract their cognate genes. A cDNA library containing random fragments expressed in human HepG2, A375 and CLS-354 cells was used to identify functional genes whose inhibition conferred resistance to Fas-induced apoptosis. Thirty-five clones were isolated, 28 of which were derived from unknown genes, that tagged 19 individual genes and 7 of which referred to known genes that tagged the apoptosis-related protein (APR)-1, -2 and indoleamine-pyrrole 2,3,-dioxygenase (IDO). The ability of APR-1-, -2- and IDO-derived antisense RNAs to induce resistance to Fas in HepG2, A375 and CLS-354 cells suggested that APR-1, -2 and IDO genes are involved in the machinery of Fas-mediated apoptosis. Our gene discovery strategy provides a generally applicable procedure to identify functional genes that interfere with apoptosis, and may therefore be clinically relevant for tumor therapy.

Antibodies↗
PubMed2005

Cell-mediated immune responses to influenza vaccination in healthy volunteers and allogeneic stem cell transplant recipients.

Influenza is one of the most common respiratory diseases in humans. The response to vaccination is frequently poor in immunosuppressed individuals. The aim of the present study was to develop an enzyme-linked immunospot (ELISPOT) assay for measuring of the specific T-cell response to influenza vaccination. In all, 18 healthy subjects and six stem cell transplantation (SCT) patients tested before and 4 weeks after influenza vaccination were included in the present study. Peripheral blood lymphocytes were stimulated with four influenza peptides; three based on sequences from the hemagglutinin and one from the M1 protein. The ELISPOT assay and the measurement of intracellular IFN-gamma production were used to determine the cell-mediated responses after stimulation with the peptides. Influenza vaccination elicited strong cell-mediated immune responses in the healthy controls to all four peptides with 3.2-6.9-fold increases in the number of IFN-gamma producing spots/10(6) cells. By intracellular staining, it was suggested that CD4+ cells mediated the responses to the hemagglutinin peptides. In contrast, there was no increase in the number of IFN-gamma producing cells response after vaccination in the six SCT patients. In conclusion, our results suggest that the ELISPOT assay might be used as a complement to serology for monitoring of future influenza vaccine studies in SCT patients.

Adult↗
PubMed2005

Cyclophosphamide induces mRNA, protein and enzyme activity of cytochrome P450 in rat.

The effects of cyclophosphamide (CPA) on CYP enzymes in vivo and its auto induction in rat were investigated in Wistar/Fu male rats at a single dose (40 or 200 mg kg(-1)) or as repeated dose of 200 mg kg(-1) CPA. After a single dose of CPA, mRNAs of CYPs 2B1, 2B2, 3A2, 2C11 were significantly induced up to 220-, 6.7-, 5.0- and 5.8-fold at the low dose CPA, and 4800-, 52-, 22- and 2.5-fold at the high dose. CYP2B1/2 and CYP3A proteins were increased by 4- and 2-fold (low dose) and by 28- and 1.7-fold (high dose). CYP2C11 protein levels were not altered. Microsomal activities of CYP2B, CYP3A and 2C11 were increased by 2-, 1.8- and 1.3-fold at low dose CPA, and 3.2-, 1.7- and 1.6-fold at high dose. A significant (p<0.05) decrease in CPA concentration and a significant (p<0.05) increase in 4-OH-CPA levels were observed with repeated administration of CPA. Acute induction effect on CYP2B1, 2B2, 2C11 and 3A2 and a substantial up regulation of CYP2B1 mRNA were observed after a single dose of CPA, auto induction was observed by repeated administration.

Animals↗
PubMed2005

Bacterial lipopolysaccharide both renders resistant mice susceptible to mercury-induced autoimmunity and exacerbates such autoimmunity in susceptible mice.

The initiation and severity of systemic autoimmune diseases are influenced by a variety of genetic and environmental factors, in particular bacterial infections and products. Here, we have employed bacterial lipopolysaccharide (LPS), which non-specifically activates the immune system, to explore the involvement of innate immunity in mercury-induced autoimmunity in mice. Following treatment of mouse strains resistant [DBA/2 (H-2(d))] or susceptible [SJL(H-2(s))] to such autoimmunity with mercuric chloride and/or LPS or with physiological saline alone (control), their immune/autoimmune responses were monitored. Resistant DBA/2 mice were rendered susceptible to mercury-induced autoimmunity by co-administration of LPS, exhibiting pronounced increases in the synthesis of IgG1 and IgE, high titres of IgG1 deposits in the kidneys and elevated circulating levels of IgG1 antibodies of different specificities. Furthermore, the percentages of the T cells isolated from the spleens of DBA/2 mice exposed to both mercury and LPS that produced pro-inflammatory cytokines were markedly increased by in vitro stimulation with phorbol myristate acetate (PMA) and ionomycin, which was not the case for splenic T cells isolated from mice receiving mercuric chloride, LPS or saline alone. In addition, exposure of susceptible SJL mice to mercury in combination with LPS aggravated the characteristic features of mercury-induced autoimmunity, including increased synthesis of IgG1 and IgE, the production of IgG1 anti-nucleolar antibodies (ANolA) and the formation of renal deposits of IgG1. In summary, our findings indicate that activation of the innate immune system plays a key role in both the induction and severity of chemically induced autoimmunity.

Animals↗
PubMed2004

Translocation (Y;22) resulting in the loss of SHOX and isolated short stature.

Chromosomal rearrangements involving both chromosome Y and chromosome 22 are rare, and may result in a number of different phenotypes. We report on a 4-year-old child with short stature and a dicentric chromosome with a deletion of the distal end of chromosome Yp. The pregnancy was uneventful, until intra-uterine growth retardation was noted. Prenatal karyotyping showed a (Y;22) translocation. No structural fetal abnormality was shown at ultrasound examination, and the pregnancy went to term. A growth-retarded boy with an otherwise normal physical examination was delivered at 39 weeks. At age 4, the child had short stature (-3 SD) without mental retardation. Radiological examination of the wrist was normal. A blood karyotype confirmed the chromosomal rearrangement previously seen on the amniotic fluid cells. C-banding showed a dicentric chromosome, and fluorescence in situ hybridization (FISH) with centromeric probes confirmed the presence of both chromosome Y and 22 centromeres on the derivative chromosome. The karyotype was thus 45,X,der(Y;22)(p11;q11)del(Y)(p11p11). Our patient's phenotype and chromosomal rearrangement prompted us to further investigate the distal Yp region. FISH using a subtelomeric probe showed a deletion of the distal Yp region. This technique also revealed that this chromosomal rearrangement resulted in the deletion of SHOX but not SRY. Although haploinsufficiency of SHOX may result in Léri-Weill Dyschondrosteosis, this diagnosis did not seem obvious in this young patient. This observation confirms the importance of FISH in the investigation of chromosomal abnormalities, and further delineates the phenotype of SHOX deleted patients.

Body Height↗
PubMed2004

Quantitative assessment of tumor vasculature and response to therapy in kaposi's sarcoma using functional noninvasive imaging.

Two noninvasive methods, thermography and laser Doppler imaging (LDI), were assessed for their ability to quantitatively assess parameters of vascularity in lesions of HIV-associated Kaposi's sarcoma (KS). Thermography and LDI images of a representative KS lesion were recorded in 16 patients and compared to normal skin either adjacent to the lesion or on the contralateral side. Eleven of the 16 patients had greater than 0.5 degrees C increased temperature and 12 of the 16 patients had increased flux (measured by LDI) as compared to normal skin. There was a strong correlation between these two parameters (R = 0.81, p < 0.001). In ten patients, measurements were obtained prior to therapy and after receiving a regimen of liposomal doxorubicin and interleukin-12. After 18 weeks of therapy, temperature and blood flow of the lesions were significantly reduced from the baseline (p = 0.004 and 0.002 respectively). These techniques hold promise to assess physiologic parameters in KS lesions and their changes with therapy.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Alteration of pharmacokinetics of cyclophosphamide and suppression of the cytochrome p450 genes by ciprofloxacin.

Recently, it has been reported that prophylactic administration of ciprofloxacin during cyclophosphamide (CY) conditioning was a high-risk factor for relapse in patients undergoing allogeneic BMT. In the present study, we investigated the possible mechanisms of this interaction in male Sprague-Dawley rats. The kinetics of CY and its active 4-OH-CY metabolite were determined, after 3 days pretreatment with ciprofloxacin (200 mg/kg) and compared to control rats without treatment. CY was administered as a high or low single intravenous dose (150 and 90 mg/kg, respectively). The expression of the CYP2B1, CYP2B2, CYP2C11, CYP3A1 and CYP3A2 genes was evaluated by SYBR Green I Dye real-time PCR for quantification of mRNA. The administration of ciprofloxacin resulted in a significant increase in the AUC (P=0.007) and a significant decrease in clearance (P=0.007) when CY was given as a high dose. In accordance, the metabolic ratio (AUC4-OH-CY/AUCCY) was significantly lower (P=0.007) compared to that found in the control group. Ciprofloxacin significantly suppressed gene expression of CYP2C11 (P=0.01) and CYP3A1 (P=0.04); however, no effect was observed on the gene expression of CYP3A2, CYP2B1 and CYP2B2. Our study revealed that ciprofloxacin interacts with CY and suppressed relevant cytochromes p450 at the transcriptional level. This study may have a great clinical impact when ciprofloxacin is used in therapy.

Animals↗
PubMed2003

The effect of metronidazole on busulfan pharmacokinetics in patients undergoing hematopoietic stem cell transplantation.

Busulfan (Bu) is an important component of some myeloablative regimens prior to stem cell transplantation (SCT). Over the last few years it has been shown that other drugs administered concomitantly can influence Bu pharmacokinetics. In the present study, we compared Bu concentrations (trough levels) in three groups of patients. Group A (n=5) received metronidazole as graft-versus-host disease prophylaxis during Bu treatment. Group B (n=9) received Bu only for 2 days followed by 2 days of Bu and metronidazole. Group C (n=10) was a control group that received Bu without metronidazole. The mean Bu levels for Group A receiving metronidazole during conditioning was significantly (P<0.001) higher (948+/-280 ng/ml), compared to those observed in the control group (507+/-75 ng/ml). In Group B, the administration of metronidazole resulted in a significant (P<0.001) increase in Bu levels (807+/-90 ng/ml) during the last 2 days, compared to 452+/-68 ng/ml during the first 2 days. In Group A, one patient died with multiorgan failure, three experienced veno-occlusive disease (VOD) and one developed hemorrhagic cystitis. Elevated liver transaminases (AST, ALT) and bilirubin were detected in all Group A patients. In Group B, six patients had elevated liver function tests but no VOD was observed. We conclude that metronidazole should not be administered simultaneously with Bu to avoid the high plasma levels of Bu, which may lead to severe toxicity and/or treatment related mortality.

Adolescent↗
PubMed2003

N-acetyl-L-cysteine does not affect the pharmacokinetics or myelosuppressive effect of busulfan during conditioning prior to allogeneic stem cell transplantation.

Busulfan is currently used as a main component in the conditioning regimen prior to allogeneic stem cell transplantation (SCT). Several studies have shown a correlation between exposure to busulfan and transplantation-related liver toxicity, such as venoocclusive disease (VOD) in patients undergoing SCT. Busulfan is metabolized mainly through glutathione (GSH). During high-dose therapy, busulfan may deplete hepatocellular levels of GSH. As part of the conditioning therapy, busulfan is usually followed by high doses of cyclophosphamide. The activation of cyclophosphamide yields a cytotoxic metabolite, 4-hydroxy cyclophosphamide, which is highly reactive and detoxified through GSH. According to recent studies using cell lines and animal models N-acetyl-L-cysteine (NAC), a GSH precursor, does not hamper the myeloablative effect of busulfan during conditioning. In the present study, we administered NAC during conditioning to 10 patients at risk of VOD due to pretransplant liver disorders or elevated liver enzymes. No side effects related to the NAC infusions were observed and busulfan concentrations were not affected. All patients became pancytopenic and engrafted with 100% donor cells. None of the patients developed VOD or liver failure. Increased liver enzymes during conditioning decreased or normalized in all patients. We suggest that NAC therapy is safe and does not impair the myeloablative effect of busulfan during conditioning prior to SCT.

Acetylcysteine↗
PubMed2003

Fractionated TBI correlates with less T cell mixed chimerism but increased risk of relapse compared to busulphan in patients with haematological malignancies after allogeneic stem cell transplantation.

We prospectively evaluated mixed chimerism (MC) in the T cell and myeloid lineages and its correlation to busulphan, single-dose total body irradiation (TBI) and fractionated TBI (fTBI) conditioning in 180 patients with haematological malignancies after allogeneic stem cell transplantation (SCT). In all patients receiving busulphan, the area under curve (AUC) was calculated. The incidence of MC in the T cell lineage was significantly lower in patients receiving fTBI (22%) compared to those given TBI (53%, P=0.02) or busulphan (47%, P<0.01). The incidence of myeloid MC did not differ between the three groups. The overall probability of acute graft-versus-host disease grades II-IV was significantly higher in patients with complete T cell donor chimerism (49%) compared to patients with T cell MC (23%, P<0.001). The incidence of T cell and myeloid MC after SCT did not differ between low (55%), medium (42%) and high (43%) AUC levels of busulphan during conditioning. Patients receiving fTBI had a significantly higher probability of relapse compared to busulphan-treated patients (44 vs l6%, P=0.01). In multivariate analysis adjusted for diagnosis, busulphan-treated patients showed both a better survival (P=0.04) and less probability of relapse (0.03) compared to TBI-treated patients.

Adolescent↗
PubMed2003

Role of polymorphic human CYP2B6 in cyclophosphamide bioactivation.

The role of polymorphic CYP2B6 in cyclophosphamide (CPA) bioactivation was investigated in human liver microsomes. A total of 67 human liver specimens were first genotyped with respect to the CYP2B6*5 and CYP2B6*6 variant alleles. CYP2B6 apoprotein levels in 55 liver microsomal preparations were assessed by immunoblotting. 4-Hydroxy-CPA and hydroxy-bupropion were quantified by using HPLC and LC-MS, respectively. 7-Ethoxy-4-trifluoromethyl coumarin O-deethylase activity was measured fluorometrically. The frequencies of CYP2B6*5 and CYP2B6*6 mutant alleles were 9.0 and 16.4%, respectively. CYP2B6 protein expression was detected in 80% of the samples, with a large variation (0.003-2.234, arbitrary units). There was a high correlation between CYP2B6 apoprotein content and CPA 4-hydroxylation (n=55, r=0.81, P<0.0001). When based on the CYP2B6 apoprotein levels, the *6 carriers had significantly higher CPA 4-hydroxylation (P<0.05). CPA 4-hydroxylation also correlated significantly with other CYP2B6-specific reactions (n=20, P<0.0001). V(max) and K(m) for CPA 4-hydroxylation in recombinant CYP2B6 enzyme were 338 nmol/min/nmol enzyme and 1.4 mM, respectively. CYP2B6 showed much higher in vitro intrinsic clearance than previously observed in recombinant CYP2C19 and CYP2C9 variants in yeast expression system. Our results demonstrate that the polymorphic CYP2B6 is a major enzyme in the bioactivation of CPA. Moreover, we identified a strong impact of CYP2B6*6 on CPA 4-hydroxylation.

Analysis of Variance↗
PubMed2003

[Imaging aspects of sphenoid during development].

To show the different steps of ossification and pneumatization of the sphenoid bone in children in order to emphasize normal anatomic variations. CT scanners and MRI studies of children up to 15 year old performed for various craniofacial conditions, without suspected involvement on cranial growth, are presented. The normal process of the ossification, of the closure of the synchondroses and of the pneumatization is demonstrated. Some examples of congenital abnormalities are also shown. The knowledge of these normal steps and variations is essential, in order to properly evaluate traumatic or congenital situations, but is also helpful for the diagnosis of bone dysplasias and bone marrow diseases (tumor or hematologic disorders).

Adolescent↗