Dr. Syed Abdul Aziz

Publications

• 1.84

  Impact points

  Efficacy of high-dose intra-dermal hepatitis B virus vaccine in previous vaccination non-responders with chronic liver disease.

  S Dhillon, C Moore, S D Li, A Aziz, A Kakar, A Dosanjh, A Beesla, L Murphy, D H Van Thiel

  Digestive diseases and sciences. 12/2011; 57(1):215-20.

  Hepatitis B virus (HBV) vaccination is essential in chronic liver disease (CLD), because it can help prevent acute-on-chronic disease, which has potentially fatal complications. Unfortunately, this group has a significant proportion of HBV vaccination non-responders. A variety of intra-muscular (IM)... [more] Hepatitis B virus (HBV) vaccination is essential in chronic liver disease (CLD), because it can help prevent acute-on-chronic disease, which has potentially fatal complications. Unfortunately, this group has a significant proportion of HBV vaccination non-responders. A variety of intra-muscular (IM) vaccination methods have been used in an attempt to remedy this poor-response, but with limited success. Herein is reported the safety and efficacy of high-dose intra-dermal (ID) HBV vaccination in CLD individuals who had failed previous IM standard and boost-dosing regimens. Forty-eight CLD individuals, known HBcAb negative, who had failed both a three-dose schedule of 40 μg IM vaccination, and boost dosing of either 40 or 80 μg IM, were identified, of which 42 completed the vaccination course. Each received a 40 μg ID total dose (20 μg per arm) during their clinic visits until a response was documented or a maximum of three doses had been administered. HBsAb titer ≥ 10 mIU/ml was regarded as an immunologic response; the intention was to achieve an optimum response of ≥ 100 mIU/ml. Twenty-nine of forty-two (69%) individuals had an immunologic response, with 15 (51%) of the responders having the optimum response. No changes in serologic data occurred. No serious dermatologic reactions were observed. No differences between those who responded and those who did not were observed with regard to the presence of cirrhosis, diabetes mellitus, or chronic kidney disease. High-dose ID HBV vaccination of previous CLD non-responders to the standard IM regimen with boost dosing is both safe and efficacious, and should be considered for all such groups.
• 1.83

  Impact points

  Toxicologic and immunologic effects of perinatal exposure to the brominated diphenyl ether (BDE) mixture DE-71 in the Sprague-Dawley rat.

  Genevieve S Bondy, David E Lefebvre, Syed Aziz, Wendy Cherry, Laurie Coady, Ellen Maclellan, Cheryl Armstrong, Michael Barker, Gerard Cooke, Dean Gaertner, Doug L Arnold, Rekha Mehta, Paul R Rowsell

  Environmental toxicology. 05/2011;

  Brominated diphenyl ethers (BDEs) are persistent environmental contaminants found in human blood, tissues, and milk. To assess the impact of the commercial BDE mixture DE-71 on the developing immune system in relation to hepatic and thyroid changes, adult (F0) rats were exposed to DE-71 by gavage at... [more] Brominated diphenyl ethers (BDEs) are persistent environmental contaminants found in human blood, tissues, and milk. To assess the impact of the commercial BDE mixture DE-71 on the developing immune system in relation to hepatic and thyroid changes, adult (F0) rats were exposed to DE-71 by gavage at doses of 0, 0.5, 5, or 25 mg/kg body weight (bw)/d for 21 weeks. F0 rats were bred and exposure continued through gestation, lactation and postweaning. F1 pups were weaned and exposed to DE-71 by gavage from postnatal day (PND) 22 to 42. On PND 42, half of the F1 rats were assessed for toxicologic changes. The remaining F1 rats were challenged with the T-dependent antigen keyhole limpet hemocyanin (KLH) and immune function was assessed on PND 56. Dose-dependent increases in total BDE concentrations were detected in the liver and adipose of all F0 and F1 rats. In F0 rats, increased liver weight, hepatocellular hypertrophy, and decreased serum thyroxine (T4) were characteristic of DE-71 exposure. In F1 rats perinatal DE-71 exposure caused a nondose-dependent increase in body weight and dose-dependent increases in liver weight and hepatocellular hypertrophy. Serum T3 and T4 levels were decreased. In spleen from DE-71 exposed rats the area occupied by B cells declined while the area occupied by T cells increased; however, cellular and humoral immune responses to KLH challenge were not altered. Thus hepatic and thyroid changes in rats exposed perinatally to DE-71 were associated with altered splenic lymphocyte populations, an effect which has been linked to hypothyroidism. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2011.
• 1.44

  Impact points

  Public health impact of hearing impairment and disability.

  M N Kotby, S Tawfik, A Aziz, H Taha

  Folia phoniatrica et logopaedica : official organ of the International Association of Logopedics and Phoniatrics (IALP). 02/2008; 60(2):58-63.

  This presentation of the public health impact of hearing impairment highlights the important elements of interaction between the disability and community. OBJECTIVES: Retrospective study to identify the size of the problem of hearing loss, illustrating not only the magnitude but also the serious eff... [more] This presentation of the public health impact of hearing impairment highlights the important elements of interaction between the disability and community. OBJECTIVES: Retrospective study to identify the size of the problem of hearing loss, illustrating not only the magnitude but also the serious effect of the lack of reliable data concerning this matter. It highlights the challenges met within a mid-economy community regarding the handling of the impact of the disability. The Egyptian data is given as an example of the situation in a mid-economy community. STUDY DESIGN: A brief introduction of some epidemiological factors of hearing impairment is presented including the size of the problem in Egypt. Data of the neonatal hearing screening program of the Audiology Unit, Ain Shams University, is presented. The impact of the disability is then discussed in relation to the age of onset and the degree and type of hearing loss. This is followed by the description of the nature and effect of the disability in the different age groups. A discussion of the various factors that may modify the capability of the community to deal with such disability follows. This includes various economic indices with their possible limitations on the part of the community. Such a briefing illustrates the challenges met in the rehabilitation of the deaf and the hearing-impaired in a developing mid-economy country. The broad lines of the management of the problem both at the prophylactic as well as the rehabilitative levels are discussed. A final remark on recommendations and possible future development in a developing country is presented.
• 1.72

  Impact points

  Immunomodulatory effects of dietary potassium perfluorooctane sulfonate (PFOS) exposure in adult Sprague-Dawley rats.

  David E Lefebvre, Ivan Curran, Cheryl Armstrong, Laurie Coady, Monique Parenteau, Virginia Liston, Michael Barker, Syed Aziz, Kathryn Rutherford, Pascale Bellon-Gagnon, Jacintha Shenton, Rekha Mehta, Genevieve Bondy

  Journal of toxicology and environmental health. Part A. 02/2008; 71(23):1516-25.

  Perfluorooctanesulfonate (PFOS) is a stable and environmentally persistent metabolic or degradation product of perfluorooctanyl compounds that were manufactured for a variety of industrial and consumer applications. PFOS itself was sold for use as a surfactant. The structurally related contaminants ... [more] Perfluorooctanesulfonate (PFOS) is a stable and environmentally persistent metabolic or degradation product of perfluorooctanyl compounds that were manufactured for a variety of industrial and consumer applications. PFOS itself was sold for use as a surfactant. The structurally related contaminants perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDA), and N-ethyl perfluorooctane sulfonamide (N-EtPFOSA) were shown to suppress immune responses in laboratory rodents. Relatively low doses of PFOS were found to be immunosuppressive in mice. To assess effects of PFOS on the rat immune system at doses known to alter hepatic function, changes in the morphology and function of immune tissues and cells were measured in adult rats exposed to PFOS in their diet for 28 d at levels ranging from 2 to 100 mg PFOS/kg diet (corresponding to approximately 0.14 to 7.58 mg/kg body weight [bw]/d) and compared to those receiving control diet. Body weight reductions were significant in male and female rats exposed to 50 and 100 mg PFOS/kg diet. Liver/body weight was significantly increased in females exposed to 2 mg PFOS/kg diet and in males exposed to 20 mg PFOS/kg diet. Female rats exposed to 100 mg PFOS/kg diet exhibited a significant increase in spleen weight relative to body weight; these changes lacked a histologic correlate and were not observed in males. While thymus weights relative to body weights were not affected, numbers of apoptotic lymphocytes rose in thymus with increasing dietary PFOS. There was a significant dose-related increase in total peripheral blood lymphocyte numbers in female but not male rats. In both genders the percentages of cells within lymphocyte subclasses were altered. There was a significant trend toward increasing T and T-helper (Th) cells and decreasing B cells with higher PFOS dose. Serum total immunoglobulin (Ig) G1 levels were significantly reduced in males exposed to 2 and 20 mg PFOS/kg diet. The ability of male and female rats to mount delayed-type hypersensitivity (DTH) responses to the T-cell-dependent antigen keyhole limpet hemocyanin (KLH) was not altered by PFOS. There was a significant trend toward elevated KLH-specific IgG in serum from male rats exposed to increasing levels of PFOS in diet. Splenic T- and B-cell proliferation in response to ex vivo mitogen exposure was unaffected by exposure to dietary PFOS. In conclusion, changes in immune parameters in rat did not manifest as functional alterations in response to immune challenge with KLH and may be secondary to hepatic-mediated effects of PFOS in this model.
• 3.35

  Impact points

  Efficacy of repeated high-dose hepatitis B vaccine (80 microg) in patients with chronic liver disease.

  A Aziz, S Aziz, D S Li, L Murphy, N Leone, M Kennedy, S Dhillon, D H Van Thiel

  Journal of viral hepatitis. 04/2006; 13(4):217-21.

  Patients with chronic liver disease (CLD) respond poorly to standard hepatitis B (HBV) vaccine given as sequential 20 microg IM shots because of an overall impaired immune response. Many of these patients go on to liver transplantation and are at risk of acquiring recurrent or de novo HBV infection.... [more] Patients with chronic liver disease (CLD) respond poorly to standard hepatitis B (HBV) vaccine given as sequential 20 microg IM shots because of an overall impaired immune response. Many of these patients go on to liver transplantation and are at risk of acquiring recurrent or de novo HBV infection. To evaluate the efficacy and safety of high-dose (80 microg) IM HBV vaccination in patients with CLD who had previously failed to respond to a standard three-dose schedule of 40 microg IM vaccine given monthly. A retrospective review was undertaken at our institution of 79 patients with CLD who were treated with high-dose (80 microg) HBV vaccinations. All had previously failed a three-dose course of 40 microg HBV vaccine. An HBV vaccine response was defined as an anti-HBs titer greater than 100 mIU/ml. Liver enzymes, creatinine, age, prothrombin time, total vaccine dose, and MELD score were recorded. No adverse events were reported. Seventy-two per cent (57/79) of the subjects had an adequate response after receiving a mean total dose of 220 mug vaccine (range 80-800 microg). Twenty-eight per cent (22/79) of the subjects did not respond after receiving a mean total dose of 420 microg vaccine (range 240-720 microg). Non-responders had more severe hepatic disease defined as a higher mean total bilirubin level (p = 0.003) and a lower mean albumin level (p < 0.05). Age, prothrombin time, MELD score, and creatinine were not statistically significant between the responders and non-responders. Repeated high-dose (80 microg) HBV vaccination, in patients who do not respond to standard HBV vaccine doses, is safe and effective in the majority of patients with CLD.
• 5.75

  Impact points

  Novel association of RP1 gene mutations with autosomal recessive retinitis pigmentosa.

  S Khaliq, A Abid, M Ismail, A Hameed, A Mohyuddin, P Lall, A Aziz, K Anwar, S Q Mehdi

  Journal of medical genetics. 06/2005; 42(5):436-8.
• 5.75

  Impact points

  Evidence of RPGRIP1 gene mutations associated with recessive cone-rod dystrophy.

  A Hameed, A Abid, A Aziz, M Ismail, S Q Mehdi, S Khaliq

  Journal of medical genetics. 09/2003; 40(8):616-9.
• 1.08

  Impact points

  Case control study of novel prognostic markers and disease outcome in pregnancy/lactation-associated breast carcinoma.

  Syed Aziz, Shahid Pervez, Shaista Khan, Tariq Siddiqui, Naila Kayani, Muhammad Israr, Mohammed Rahbar

  Pathology, research and practice. 01/2003; 199(1):15-21.

  A case control study of pregnancy/lactation associated breast carcinoma (PAC) was conducted on 24 test cases with two controls per case, matching age, tumor grade, tumor size and axillary lymph nodes status. During seven years of this study, 6% of all patients with breast cancer had PAC. In this stu... [more] A case control study of pregnancy/lactation associated breast carcinoma (PAC) was conducted on 24 test cases with two controls per case, matching age, tumor grade, tumor size and axillary lymph nodes status. During seven years of this study, 6% of all patients with breast cancer had PAC. In this study, 67% of the test cases showed positive axillary lymph nodes compared to 49% in our series of 315 cases of non-pregnancy/non-lactating women with breast carcinoma (p < 0.05). The expression of nine prognostic markers, i.e. ER, PR, p53, C-erbB-2, EGFR, Cathepsin-D, PCNA, DNA ploidy and S-phase fraction, were studied by immunohistochemistry and flow cytometry. Hormone receptor status showed a statistically significant difference between the two groups, i.e. 29% immunoreactivity in test cases compared to 58% in controls with a p value of 0.007. Among p53, C-erbB-2, EGFR and Cathepsin-D in the test group, only EGFR showed a significant correlation, i.e. 33% immunoreactivity in test cases and 19% immunoreactivity in controls (p < 0.05). Higher PCNA positivity was seen in the test group compared to controls, i.e. 35% in test patients and 28% in controls (p < 0.05). Metastasis to bone and liver was a common feature of test patients as compared to controls (p < 0.05). After a median follow-up of 72 months, there was no significant difference in the overall survival (OS) of test cases and controls as 54% deaths were recorded in test patients and 44% in controls at the end of this study (p > 0.05). In summary, in spite of some significant differences in the expression of few prognostic markers, i.e. ER/PR, EGFR, PCNA and metastatic potential, there was no significant difference in the OS of PAC vs. control group if compared stage for stage.

• Squamous cell carcinoma of true vocal cords (T1) lesion metastasis to lung--a case report.

  J A Mallick, S A Ali, A Aziz

  JPMA. The Journal of the Pakistan Medical Association. 07/2002; 52(6):258-63.
• 1.32

  Impact points

  Increased uptake of 99Tcm-ethyl cysteinate dimer in patients with brain tumours.

  Y Ogawa, R Hashmi, A Aziz, M Ochi, K Hayashi

  Nuclear medicine communications. 06/2001; 22(5):479-83.

  We performed 229 99Tcm-ethyl cysteinate dimer (ECD) single photon emission tomography (SPET) studies in 185 patients with brain tumour. Increased uptake of the tracer was observed in 11 cases. In six of these 11 patients, focal intense activity was seen in the area surrounding the tumour. Five of th... [more] We performed 229 99Tcm-ethyl cysteinate dimer (ECD) single photon emission tomography (SPET) studies in 185 patients with brain tumour. Increased uptake of the tracer was observed in 11 cases. In six of these 11 patients, focal intense activity was seen in the area surrounding the tumour. Five of these six patients had episodes of seizure, and ictal SPET showed further increased uptake in the area of hyperperfusion in one patient. Hyperperfusion surrounding the tumour might be related to seizure. In the remaining five patients, increased accumulation was seen in the tumour. Three of these five patients had a discrepancy between 99Tcm-ECD SPET and 201Tl SPET imaging. There could be some difference in the mechanism of accumulation in the tumour between 99Tcm-ECD and 201Tl.
• 3.92

  Impact points

  Central scar in hepatic focal nodular hyperplasia revealed by scintigraphy.

  Y Ogawa, I Sakamoto, T Fukuda, A Aziz, R Hashmi, K Hayashi, S Okudaira

  Clinical nuclear medicine. 11/2000; 25(10):831-2.
• 1.44

  Impact points

  Tc-99m-MIBI scintimammography; SPECT versus planar imaging.

  A Aziz, R Hashmi, Y Ogawa, K Hayashi

  Cancer biotherapy & radiopharmaceuticals. 12/1999; 14(6):495-500.

  This study compares single photon emission tomography (SPECT) with planar scintimammography. 16 normal, 54 benign and 80 malignant lesions were studied (total 150). 700 MBq of Tc99m-sestamibi (MIBI) was injected intravenously. Anterior supine, right and left lateral planar images were acquired in pr... [more] This study compares single photon emission tomography (SPECT) with planar scintimammography. 16 normal, 54 benign and 80 malignant lesions were studied (total 150). 700 MBq of Tc99m-sestamibi (MIBI) was injected intravenously. Anterior supine, right and left lateral planar images were acquired in prone position at 2 hours post injection. After this a SPECT study (64 projections, 64 x 64 matrix, 30 sec/frame, anterior 180 degrees arc) was acquired in supine position. Attenuation coefficient of 0.12 and Butterworth order 5 Nyquist 0.9 filter was applied for reconstruction. A scoring system for visualization of lesions was devised with scores of 0 or 1 as negative and 2 or 3 as positive for MIBI uptake. Scores for each group of patients were added together and then compared between planar and SPECT studies. RESULTS: Planar imaging missed 10 malignant lesions while SPECT missed only 4. Ten benign lesions showed uptake of MIBI on planar imaging while 11 showed uptake on SPECT. Cumulative scores for normal and benign groups did not show any significant difference between planar and SPECT imaging. The malignant group showed significant increase in score for SPECT. Specificity, false negative fraction and positive predictive value for planar imaging were 85.7%, 14.3% and 87.5%. These values did not show any significant difference for SPECT (84.5%, 15.5% and 87.4% respectively). Sensitivity, false negative fraction and negative predictive value for planar imaging (87.5%, 12.5% and 85.7%) was significantly different (p < 0.005) than SPECT (95%, 5% and 93.7% respectively). MIBI SPECT scintimammography improves the sensitivity, false negative fraction and negative predictive value of the planar imaging. In the absence of MIBI uptake on SPECT imaging, malignancy can be ruled out with great confidence, while only uptake should be further evaluated.

• Pneumothorax: a review of 146 adult cases admitted at a university teaching hospital in Pakistan.

  S F Hussain, A Aziz, H Fatima

  JPMA. The Journal of the Pakistan Medical Association. 11/1999; 49(10):243-6.

  OBJECTIVE: There is a lack of data on the etiology and outcome of pneumothorax among the Pakistani population. Our aim was to review the etiology, clinical course, management and outcome of patients presenting with pneumothorax. PATIENTS AND METHODS: All adult cases with pneumothorax admitted to a U... [more] OBJECTIVE: There is a lack of data on the etiology and outcome of pneumothorax among the Pakistani population. Our aim was to review the etiology, clinical course, management and outcome of patients presenting with pneumothorax. PATIENTS AND METHODS: All adult cases with pneumothorax admitted to a University Teaching Hospital in Karachi, between January 1992 and June 1996, were reviewed and analyzed. RESULTS: A total of 146 patients were reviewed. Their mean age was 46.3 years (SD +/- 17.8 years) with a male to female ratio of 3.7:1. Secondary pneumothorax was the commonest type seen (45%), followed by traumatic (21%), iatrogenic (18%) and primary (16%). Tuberculosis (47%) and COPD (45%) were most common lung diseases associated with secondary pneumothorax. Pneumothorax secondary to TB presented at an earlier age than that with COPD (49.6 vs. 60.1 years). Similarly, patients with primary pneumothorax were significantly younger than patients with secondary pneumothorax (42.3 vs. 51.7 years). Rib fracture was the most common cause of traumatic pneumothorax. Coronary artery bypass grafting, transthoracic fine needle aspiration and neck vein cannulations were the leading iatrogenic causes. The commonest symptoms of pneumothorax were dyspnea (68%) and chest pain (40%). Most cases (81%) were successfully managed by intercostal tube drainage. CONCLUSION: In our study population, secondary pneumothorax was the commonest variety seen. TB was the commonest cause of secondary pneumothorax, closely followed by COPD. Nearly 40% of pneumothorax were either traumatic or iatrogenic. Intercostal tube drainage remains the treatment of choice for pneumothorax.
• 1.32

  Impact points

  Clinical significance of a solitary hot spot in the skull.

  R Hashmi, M Uetani, Y Ogawa, A Aziz

  Nuclear medicine communications. 09/1999; 20(8):703-10.

  Retrospective evaluation of bone scintigrams over the last 10 years was performed to determine the incidence of a solitary hot spot in the skull, examine its significance in patients with and without extra-skeletal malignancy, and determine if location along the suture lines is clinically significan... [more] Retrospective evaluation of bone scintigrams over the last 10 years was performed to determine the incidence of a solitary hot spot in the skull, examine its significance in patients with and without extra-skeletal malignancy, and determine if location along the suture lines is clinically significant or not. Review of the reports of bone scintigrams in 9968 patients yielded 37 (0.37%) patients with a solitary hot spot in the skull. In the group of 27 patients with extra-skeletal malignancy, the hot spot was secondary to metastasis in four patients and of a non-metastatic origin in 15. In the remaining eight patients, the cause was indeterminate. Two of the four metastatic foci were located along the suture lines. In another group of 10 patients without extra-skeletal malignancy, the cause was non-metastatic in eight patients and indeterminate in two. No significant differences between the scintigraphic features (intensity of uptake, location and relationship with sutures) of metastatic and non-metastatic foci were noted. We conclude that a solitary hot spot in the skull is rare and is predominantly benign in nature. However, in patients with known extra-skeletal malignancy, approximately 21% are secondary to a solitary bone metastasis of the skull. Location of a hot spot along the suture lines may not always be a normal variation and can represent a solitary bone metastasis.

• Persistent müllerian duct syndrome: report of two boys with associated transverse testicular ectopia.

  P Mandhan, I Hussain, R Naqvi, J Ahmed, M A Ali, A Aziz

  JPMA. The Journal of the Pakistan Medical Association. 04/1999; 49(3):74-6.

• View box--case 3.Pulmonary lymphangioleiomyomatosis.

  R Hashmi, M Uetani, A Aziz, K Hayashi

  JPMA. The Journal of the Pakistan Medical Association. 04/1999; 49(3):76-8.

• HLA-DR2 haplotypic diversity in populations of South-East Asia, northern China, Melanesia and Australian aborigines using PCR-RFLP for DRB1, DRB5, DQA1 and DQB1. A novel DRB1 allele: DRB1*16022.

  J Trejaut, K Bhatia, W D Greville, K R Hu, G Duraisamy, C Nuchprayoon, J Donald, A Aziz, H Dunckley

  European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics. 01/1997; 23(6):437-49.

  The polymorphism of the human leucocyte antigen HLA-DR2 and the heterogeneity of HLA-DR2 class II-related haplotypes (HLA-DRB1-DRB5-DQA1-DQB1) were investigated in four populations of east and south-east Asia (SEA) and five Melanesian populations using TaqI restriction fragment length polymorphism (... [more] The polymorphism of the human leucocyte antigen HLA-DR2 and the heterogeneity of HLA-DR2 class II-related haplotypes (HLA-DRB1-DRB5-DQA1-DQB1) were investigated in four populations of east and south-east Asia (SEA) and five Melanesian populations using TaqI restriction fragment length polymorphism (RFLP) analysis, and the polymerase chain reaction (PCR) amplification-based techniques PCR-RFLP and sequence-specific oligonucleotide (SSO) typing. The haplotype DRB1*1502-DRB5*0101-DQA1*0102-DQB1*0601 was common in Malaysians, Javanese, Thursday Islanders, Madang, Goroka and the Australian Aborigines, while DRB1*16021-DRB5*0101-DQA1*0102-DQB1*0502 was common in the Thai and Thursday Islanders. DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602 was present at a high frequency in Northern Chinese, Goroka, Watut and Australian Aborigines. The study describes four rare or unusual haplotypes: HLA-DRB1*1501-DRB5*0101-DQA1*0101-DQB1*0601, DRB1*1502-DRB5*0101-DQA1*0101-DQB1*0502, DRB1*1502-DRB5*0102-DQA1* 0102-DQB1*0502 and DRB1*1501-DRB5*0101-DQA1*0101/2-DQB1*0503; the latter two were confirmed by segregation in two Javanese families. A new DR2 allele, initially detected by PCR-RFLP and confirmed by DNA sequencing as DRB1*16022 (previously designated DRB1*16Madang), was seen in a Madang individual. A new HLA-DR2 TaqI RFLP subtype, locally designated as DR15U, is also described. This RFLP subtype segregated in a Javanese family and correlated with a typically SEA haplotype, DRB1*1502-DRB5*0102-DQA1*0101-DQB1*0501. The allele HLA-DR16Thai, determined by TaqI DRB RFLP, was found by PCR-RFLP and SSO typing to correlate with a unique SEA haplotype, HLA-DRB1*16021-DRB5*0101-DQA1*0102-DQB1*0502, and was observed in the Thai, Malaysian, Thursday Islander, Javanese and Northern Chinese populations.
• 2.59

  Impact points

  Identification of a new plasma alpha(1,3)fucosyltransferase (FUT6) allele requires an extended genotyping strategy.

  G Larson, C Börjeson, A Elmgren, A Kernholt, S Henry, A Fletcher, A Aziz, R Mollicone, R Oriol

  Vox sanguinis. 02/1996; 71(4):233-41.

  Screening the FUT6 gene of 40 Swedish individuals, originally selected for genotyping of FUT3, revealed an unexpected high frequency of mutations. Four were originally typed as homozygous for the enzyme lethal mutation G739A by Taq alpha I restriction pattern, but only one lacked plasma alpha(1,3)fu... [more] Screening the FUT6 gene of 40 Swedish individuals, originally selected for genotyping of FUT3, revealed an unexpected high frequency of mutations. Four were originally typed as homozygous for the enzyme lethal mutation G739A by Taq alpha I restriction pattern, but only one lacked plasma alpha(1,3)fucosyltransferase activity. Cloning and sequencing of FUT6 from 2 of them revealed a new allele, without the G739A mutation, but with two new point mutations C738T and G977A. Segregation of this allele was confirmed in Swedish and Indonesian families. Since G739A and C738T mutations are only one nucleotide apart and induce the same modification of Taq alpha I cleavage, a new screening strategy for FUT6 was adopted. The homozygous inactivating G739A mutation was for the first time identified in Caucasian and Polynesian individuals, both lacking plasma enzyme activity. The mutation C370T was present in 25 of the 40 Swedish individuals and the inactivating mutation C945A was not found at all. These findings stress the dangers of transferring restriction enzyme genotype strategies from one population to another and of inferring phenotypes from genotypes without phenotyping and/or performing confirmatory cloning and sequencing.
• 5.33

  Impact points

  Molecular basis for Lewis alpha(1,3/1,4)-fucosyltransferase gene deficiency (FUT3) found in Lewis-negative Indonesian pedigrees.

  R Mollicone, I Reguigne, R J Kelly, A Fletcher, J Watt, S Chatfield, A Aziz, H S Cameron, B W Weston, J B Lowe

  The Journal of biological chemistry. 09/1994; 269(33):20987-94.

  The Le(a) and Le(b) human blood group antigens are synthesized in tissues producing exocrine secretions; they also circulate in plasma, where they are adsorbed by erythrocytes. They are synthesized by two fucosyltransferases, encoded by Lewis (FUT3) and secretor (FUT2) loci. This genetic model has b... [more] The Le(a) and Le(b) human blood group antigens are synthesized in tissues producing exocrine secretions; they also circulate in plasma, where they are adsorbed by erythrocytes. They are synthesized by two fucosyltransferases, encoded by Lewis (FUT3) and secretor (FUT2) loci. This genetic model has been challenged because some erythrocyte Lewis-negative individuals express Lewis antigens in saliva. To define the molecular basis of this apparent discrepancy, we sequenced FUT3 in Lewis-negative individuals. We identified two single base pair changes. One, termed L1, yields a Leu-20-->Arg substitution in the enzyme's transmembrane domain. When expressed in COS-7 cells, enzyme substrate affinities are essentially identical to those of wild type. However, the mutant enzyme is found at substantially reduced levels in transfected cells. This suggests that the L1 mutation may alter the Golgi membrane anchoring of the enzyme. It was found alone in double dose in 10 of 30 erythrocyte Lewis-negative individuals, nine of whom express Lewis antigens in saliva. Therefore, L1 can account for erythrocyte/saliva-discrepant Lewis typing results. The L2 mutation creates an Ile-356-->Lys change in the enzyme's catalytic domain and inactivates the enzyme. It was found in double dose in 18 of 19 individuals bearing the double erythrocyte and salivary Lewis deficiency and can account for this phenotype.
• 5.33

  Impact points

  Molecular basis for plasma alpha(1,3)-fucosyltransferase gene deficiency (FUT6).

  R Mollicone, I Reguigne, A Fletcher, A Aziz, M Rustam, B W Weston, R J Kelly, J B Lowe, R Oriol

  The Journal of biological chemistry. 05/1994; 269(17):12662-71.

  While most humans express an alpha(1,3)-fucosyltransferase in plasma, 9% of individuals on the isle of Java (Indonesia) do not express this enzyme. Ninety-five percent of these plasma alpha(1,3)-fucosyltransferase-deficient individuals have Lewis negative phenotype on red cells, suggesting strong li... [more] While most humans express an alpha(1,3)-fucosyltransferase in plasma, 9% of individuals on the isle of Java (Indonesia) do not express this enzyme. Ninety-five percent of these plasma alpha(1,3)-fucosyltransferase-deficient individuals have Lewis negative phenotype on red cells, suggesting strong linkage disequilibrium between these two traits. To define the molecular basis for this plasma deficiency and to determine which of two candidate human alpha(1,3)-fucosyltransferase genes encode this enzyme (FUT5 and FUT6), we cloned and analyzed alleles at these two loci from an Indonesian individual deficient in plasma alpha(1,3)-fucosyltransferase activity. Single base pair changes were identified in the coding region of each gene, relative to previously published wild type alleles. These changes in turn yield three codon changes in FUT5 and three in FUT6. The codon changes in the FUT5 gene do not yield detectable diminutions in alpha(1,3)-fucosyltransferase activity when tested by expression in transfected COS-1 cells, and none of the FUT5 alleles co-segregate with plasma alpha(1,3)-fucosyltransferase deficiency in Indonesian pedigrees. By contrast, two of the codon changes in the FUT6 alleles inactivate this gene when tested by expression in transfected COS-1 cells. One of these inactivating changes is a missense mutation (Glu-247-->Lys) within the enzyme's catalytic domain. The other inactivating mutation represents a nonsense mutation (Tyr-315-->stop) that truncates the COOH terminus of the enzyme by 45 amino acids. The Glu-247-->Lys missense mutation is present in double dose in the nine plasma alpha(1,3)-fucosyltransferase-deficient individuals tested, whereas the nonsense mutation at tyrosine 315 is present in double dose in just one of these persons. These results demonstrate that the alpha(1,3)-fucosyltransferase activity in human plasma is encoded by the FUT6 gene and that the missense mutation within codon 247 of this gene is responsible for deficiency of this activity in these Indonesian families.