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1.  Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians 
Diabetologia  2011;55(4):981-995.
Aims/hypothesis
FTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians.
Methods
All studies published on the association between FTO-rs9939609 (or proxy [r2 > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes.
Results
The FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10−19), overweight by 1.13-fold/allele (p = 1.0 × 10−11) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10−8). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10−5). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m2 per allele (p = 2.8 × 10−17), WHR by 0.003/allele (p = 1.2 × 10−6), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12–20%) than South Asians (30–33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations.
Conclusions/interpretation
FTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI.
Electronic supplementary material
The online version of this article (doi:10.1007/s00125-011-2370-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
doi:10.1007/s00125-011-2370-7
PMCID: PMC3296006  PMID: 22109280
Asians; FTO; Meta-analysis; Obesity; Type 2 diabetes
2.  A phase II study of cisplatin, vindesine and continuously infused 5-fluorouracil in the treatment of advanced non-small-cell lung cancer. Osaka Lung Cancer Chemotherapy Study Group. 
British Journal of Cancer  1996;73(9):1096-1100.
Fifty-two previously untreated patients with advanced non-small-cell lung cancer (NSCLC) were treated on a 14 day cycle with cisplatin (60 mg m-2 i.v.) and vindesine (3 mg m-2 i.v.) on day 1, followed by a 3 day continuous infusion of 5-fluorouracil (800 mg m-2 day-1) starting on day 8. An overall response rate of 40.4% was observed in 47 evaluable patients, which included one complete response and 18 partial responses. Responses were achieved in 61.1% of stage 3 patients and 27.6% of stage 4 patients. The median progression-free interval was 19.3 weeks, and median survival time was 41.6 weeks (47.1 weeks for patients with stage 3 disease and 38.7 weeks for those with stage 4 disease). Toxicity was well tolerated. Gastrointestinal and renal toxicities did not exceed WHO grade 2. Grade 3 or 4 leucopenia and anaemia occurred in nine (19%) and four (9%) patients respectively, but only grade 2 thrombocytopenia was observed. Phlebitis at the infusion site was observed in 24 patients (53%). This treatment programme achieved a response rate similar to other active combination regimens for the treatment of advanced NSCLC, and was less toxic.
PMCID: PMC2074391  PMID: 8624270
3.  Identification of a new susceptibility locus for insulin-dependent diabetes mellitus by ancestral haplotype congenic mapping. 
Journal of Clinical Investigation  1995;96(4):1936-1942.
The number and exact locations of the major histocompatibility complex (MHC)-linked diabetogenic genes (Idd-1) are unknown because of strong linkage disequilibrium within the MHC. By using a congenic NOD mouse strain that possesses a recombinant MHC from a diabetes-resistant sister strain, we have now shown that Idd-1 consists of at least two components, one in and one outside the class II A and E regions. A new susceptibility gene (Idd-16) was mapped to the < 11-centiMorgan segment of chromosome 17 adjacent to, but distinct from, previously known Idd-1 candidates, class II A, E, and Tap genes. The coding sequences and splicing donor and acceptor sequences of the Tnfa gene, a candidate gene for Idd-16, were identical in the NOD, CTS, and BALB/c alleles, ruling out amino acid changes in the TNF molecule as a determinant of insulin-dependent diabetes mellitus susceptibility. Our results not only map a new MHC-linked diabetogenic gene(s) but also suggest a new way to fine map disease susceptibility genes within a region where strong linkage disequilibrium exists.
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PMCID: PMC185830  PMID: 7560085
4.  In vivo binding of circulating immune complexes by C3b receptors (CR1) of transfused erythrocytes. 
Annals of the Rheumatic Diseases  1989;48(4):287-294.
The effects of packed erythrocyte transfusion with high CR1 activity on circulating immune complex concentrations were studied in 14 transfusion experiments involving 12 patients with immune complex related diseases. Before erythrocyte transfusion circulating immune complex concentrations ranged from 8 to 128 micrograms/ml. After transfusion (2-3 units) immune complex concentrations decreased depending on the levels of CH50 titres in the recipients. In 11 experiments, in which the patients' CH50 titres ranged from 21 to 44, immune complex concentrations decreased by 75-100% within five days. The CH50 titres were also decreased after erythrocyte transfusion but subsequently increased to initial ranges within 6-35 days. In three patients with low CH50 titres (1.0-10.0) decreases in immune complexes were not observed. Direct Coombs' tests for IgG and C3 were performed before and after erythrocyte transfusion to determine potential in vivo binding of circulating immune complexes. Thus in eight of 14 experiments, in which erythrocytes carried no IgG before packed erythrocyte transfusion, seven became Coombs' positive for IgG after the transfusion. In seven of 14 experiments, in which erythrocytes were negative for complement before transfusion, five became positive afterwards. Moreover, in 12 instances slight increases of CR1 activity of patients' erythrocytes were observed within eight days, which improved further within 35 days after erythrocyte transfusion. These studies suggest that transfusion of erythrocytes with high CR1 activity results in the removal of circulating immune complexes and that this process is dependent on complement consumption. These experiments support the hypothesis that erythrocyte-CR1 has a functional role in the removal of circulating immune complexes and may thereby inhibit the deposition of immune complexes within body tissue constituents.
PMCID: PMC1003743  PMID: 2523692
5.  Major histocompatibility complex-linked diabetogenic gene of the nonobese diabetic mouse. Analysis of genomic DNA amplified by the polymerase chain reaction. 
Inheritance of insulin-dependent diabetes mellitus (IDDM) is polygenic, and at least one of the genes conferring susceptibility to diabetes is tightly linked to the MHC. Recent studies have suggested that DQB1 of humans and I-A beta of mice are closely associated with susceptibility and resistance to IDDM. For further characterization and localization of the MHC-linked diabetogenic gene, we studied the genomic sequence of the A beta gene of the nonobese diabetic (NOD) mouse, an animal model of IDDM, in comparison with those of its sister strains, nonobese nondiabetic and cataract Shionogi (CTS) mice, and the original strain, outbred Imperial Cancer Research (ICR) mice. Genomic DNAs from these strains were amplified in vitro by the polymerase chain reaction with thermostable Taq polymerase. The amplified sequences were analyzed by restriction endonuclease digestion, hybridization with allele-specific oligonucleotide probes, and direct sequencing. The unique I-A beta sequence of NOD mice was observed in the sister strain, CTS mice, and in one mouse of the original strain, outbred ICR mice. These data together with the results of MAb typing of MHC molecules and restriction mapping of the I-A region suggest that the unique class II MHC of NOD mice is not the result of a recent mutation, but is derived from the original strain. Since class I MHC of CTS mice is different from the MHC of NOD mice at both the K and D loci, CTS mice are a naturally occurring recombinant strain with NOD type class II MHC and non-NOD type class I MHC. Thus, breeding studies in crosses of NOD with CTS mice should provide biological information on whether the unique class II MHC of NOD mice is diabetogenic.
Images
PMCID: PMC296381  PMID: 2295694
6.  Bronchial brushing and bronchial biopsy: comparison of diagnostic accuracy and cell typing reliability in lung cancer. 
Thorax  1986;41(6):475-478.
A total of 443 patients with lung cancer underwent brush and forceps biopsy through a fibreoptic bronchoscope. The biopsy was taken from the area of suspected malignancy which had been brushed. Of 443 patients, 400 (90.3%) showed positive results on brushing and 287 (64.8%) on biopsy. A combination of both techniques yielded the highest percentage of positive diagnosis (93.7%). Histologically, there was a high incidence of positive diagnosis for squamous and small cell carcinoma. One hundred and three (83.7%) of 123 specimens obtained by brushing and 75 (81.5%) of 92 specimens obtained by biopsy agreed with the cell type found in the surgical or necropsy specimen. Cell typing accuracy was higher in squamous and in small cell carcinoma in both techniques. As the cell typing accuracy of the two methods is similar, the results obtained by both techniques should be taken into consideration in the management of individual cases of lung cancer.
PMCID: PMC460368  PMID: 3024348
7.  Immunoglobulin E-suppressing and immunoglobulin G-enhancing tetanus toxoid prepared by conjugation with pullulan. 
Infection and Immunity  1982;36(3):971-976.
Immunoglobulin E (IgE) antibody response was found to be suppressed selectively and antigen specifically in mice given an antigen conjugated with pullulan, a linear copolymer of maltotriose, whereas IgM and IgG antibody responses were enhanced. On the basis of this finding, tetanus toxin was conjugated with pullulan by cyanuric chloride in the hope that the toxin would be detoxified by the conjugation procedure and could be used as an IgE-suppressing and IgG-enhancing toxoid without the aid of an aluminum adjuvant. This procedure of tetanus toxoid-pullulan conjugation apparently detoxified the toxin. Administration of the resulting tetanus toxoid, tetanus toxin-pullulan conjugate, to mice induced strong suppression of IgE antibody response with fairly good IgG response, whereas the alum-precipitated toxoid or plain toxoid, customarily used for vaccination, elicited high IgE antibody formation. The IgE antibody response was minimal, but the IgG antibody response was maximal in the conjugate-primed mice even after a booster injection with an IgE antibody-inducing dose of the alum-precipitated toxoid.
Images
PMCID: PMC551426  PMID: 7095857

Results 1-8 (8)