Correlation between intracellular interferon-gamma (IFN-gamma) production by CD4+ and CD8+ lymphocytes and IFN-gamma gene polymorphism in patients with type 2 diabetes mellitus and latent autoimmune diabetes of adults (LADA)

IFN-gamma is considered to be involved in the pathogenesis of diabetes mellitus. In this study, the presence of T/A mutation at position -874 in IFN-gamma gene was assessed in patients with latent autoimmune diabetes of adults (LADA), in patients with type 2 diabetes and in healthy individuals. Subsequently, an attempt was made to correlate the presence of this mutation with the ability of CD4+ or CD8+ lymphocytes from these individuals to release IFN-gamma following mitogenic stimulation. There were no significant differences in the distribution of genotypes and haplotypes in the three study groups. However, the frequency of the low IFN-gamma production allele (IFN-gamma 874( *)A) was significantly higher in type 2 diabetics compared to controls. CD4+ and CD8+ cells obtained from type 2 diabetics released significantly lower amounts of IFN-gamma in the intracellular space, compared to those released by cells obtained from LADA patients and healthy volunteers. Furthermore, even CD4+ and CD8+ from type 2 diabetics bearing the TT genotype (high producers) released significantly lower amounts of IFN-gamma than LADA patients carrying the same genotype, probably due to the activity of molecules directly or indirectly inhibiting IFN-gamma production. The results of this study indicate that IFN-gamma may contribute to the development of type 2 diabetes, based on a combination of molecular and immunological observations.     

Newly diagnosed latent autoimmune diabetes in adults (LADA) is associated with low level glutamate decarboxylase (GAD65) and IA-2 autoantibodies. Diabetes Incidence Study in Sweden (DISS).

A quantitative assay with microSepharose was used to determine GAD65Ab and IA-2Ab levels in 771 population-based patients diagnosed with diabetes mellitus at 15 to 34 years of age, and in 828 matched controls. Among the patients, 587 (76%) were classified with type I, 108 (14%) with type II, and 76 (10%) with unclassifiable diabetes. The levels above normal demonstrated a prevalence of GAD65Ab in 66% of type I diabetes, 50% of type II diabetes and 54% of unclassifiable patients and for IA-2Ab in 40%, 17% and 21%, respectively. Among the autoantibody-positive sera, the LADA patients had a lower GAD65Ab index (median 0.19, p < 0.0001) and IA-2Ab index (median 0.28, p < 0.0001) than the type I patients (median 0.37 and 0.66). Patients with unclassifiable diabetes had a GAD65Ab (median 0.43) or IA-2Ab (median 0.63) index which was not different from the type I diabetes patients. Our data demonstrate that young adult new-onset LADA patients have low level GAD65Ab and IA-2Ab. The low-level autoantibodies may signify a less aggressive beta-cell autoimmunity, which may explain why these patients are often classified with type II or non-insulin-dependent diabetes.     

LADA--latent autoimmune diabetes in adults

Latent Autoimmune Diabetes In Adults (LADA) is a form of autoimmune-mediated diabetes in adults. The progression of beta-cell failure is slower than in childhood type 1 diabetes. Patients with LADA present with more preserved beta-cell function than those with classic type 1 diabetes. The diagnosis of LADA according to Immunology of Diabetes Society is based on three features: age over 35 years, the presence at least one of four circulating autoantibodies to pancreatic islet cell antigens and lack of requirement for insulin at least 6 month after diagnosis. The level of C-peptide secretion after stimulation with intravenous glucagon helped to diagnosis. There are different opinions in relation to treatment of LADA. Some studies suggest, that insulin treatment is indicated at the time of diagnosis LADA, some of them--when patients upon failure of oral hypoglycemic treatment.     

Family incidence of latent autoimmune diabetes in adults--case report

We describe a 37 year-old woman case of latent autoimmune diabetes in adults (LADA). She was presented with unfounded weight loss. The diagnosis of diabetes mellitus was established on twice plasma glucose measurements above 200 mg/dl. In other routine biochemical examinations we did not observe dehydratation, electrolyte depletion, acidosis. However plasma level of C peptide basal and after stimulation with glucagon was reduced. Initially, the patient responded well to sulphonylurea treatment. To test immunological pathogenesis we examine autoimmune markers of diabetes type 1. Autoimmune antibodies (GAD, IAA) were found in patients and her parents, which were until now diabetic type 2. We report this case because incidence of latent autoimmune diabetes in adults is underestimate and rarely diagnosed in clinical practice.     

BF types and the mode of inheritance of insulin-dependent diabetes mellitus (IDDM)

Insulin-dependent diabetes mellitus (IDDM) has been found to be highly associated with a rare allele of the complement protein, properdin factor B (BF). Assuming that there is a susceptibility gene for IDDM tightly linked to the genetic locus forBF and the major histocompatibility complex (MHC), the distribution of BF types in more than 1100 North American IDDM patients strongly argues for the rejection of dominant, epistatic, and overdominant modes of inheritance. Other evidence suggesting complex modes of inheritance for IDDM is reviewed and it is concluded that our observations and published data are consistent with the idea of susceptibility to IDDM being inherited as a simple autosomal recessive trait. — C4 and C2 types, also linked toBF and theMHC, were investigated too. C4 Fs⁰ was found to be increased in association with BF F1, while C4 f⁰S and C2 B were each found to occur twice as frequently as in a control population and will be of value in defining haplotypes associated with susceptibility to IDDM.     

The study of HLA class II and autoimmune diabetes

Many autoimmune diseases have genetic associations with the Major Histocompatibility Complex (MHC) class II loci. Susceptibility to Type 1 diabetes mellitus (TIDM) is particularly associated with Human Leucocyte Antigen (HLA) DR3, 4 and associated DQ2, 8 alleles and this is well documented in genetic association studies. These molecules play an important role in presentation of peptide antigens after intracellular processing to CD4 T lymphocytes. During the last decade, a number of approaches have been used to elucidate the molecular basis for the association of particular alleles with susceptibility to or protection from TIDM. These studies have focused on investigating the structure of the antigen presenting molecules, together with their peptides. Through binding studies, peptide elution, molecular modelling and crystallization of the peptide MHC complex, it has been possible to define the peptide binding regions and examine the stability of binding of peptides from putative autoantigens. This knowledge has also facilitated the development of reagents such as multimeric MHC-peptide complexes that will help to track the low frequency, potentially pathogenic antigen specific cells. Recently, HLA transgenic mice have been generated and used to study T cell epitopes. In addition, although it is clear that the presence of HLA molecules alone does not by itself cause disease, these transgenic mice will develop diabetes when there is an islet "insult", even if the islet "insult" is, itself, not sufficient to precipitate disease in the absence of the HLA class II transgene. These mice will allow further study of the role of these HLA molecules in vivo. We now have a much greater general understanding of the possible reasons why particular molecules may encode susceptibility to or protection from disease. All these studies will provide information to ultimately define a rational basis for the development of targeted immunotherapy.     

An autoimmune diabetes locus (Idd21) on mouse Chromosome 18

Twenty-four named Idd loci that contribute to the development of autoimmune diabetes in the nonobese diabetic (NOD) mouse have been mapped by linkage and congenic analysis. Previously, meta-analysis of genome-wide linkage scans supported the existence of a locus for susceptibility to autoimmune phenotypes on rodent Chromosome (Chr) 18, in a position orthologous to the human type 1 diabetes susceptibility locus IDDM6 (human Chr 18q12-q23). However, an autoimmune diabetes susceptibility locus has not previously been reported on mouse Chr 18. In this study, we demonstrate linkage of the majority of mouse Chr 18 to diabetes in a (ABH × NOD)F₁ × NOD backcross. Congenic analysis, introgressing at least 92% of Biozzi ABH Chr 18 onto the NOD background, confirmed the presence of a diabetes locus. The chromosome substitution strain (NOD.ABH-Chr18) had reduced diabetes incidence compared with NOD mice (P < 0.0001). We have named the Chr 18 diabetes locus Idd21.     

Unusual features in the inheritance of ataxia telangiectasia

Summary A prevalence study of ataxia telangiectasia was conducted in the West Midlands, with a population of over 5 million. The prevalence in those aged 50 or less was found to be 1 in 514 000 and the birth frequency to be about 1 in 300 000. A genetic study of 47 families ascertained throughout the United Kingdom was carried out concurrently. A low parental consanguinity rate was found, no parents being first cousins or more closely related, whereas 10% had been expected. The incidence of ataxia telangiectasia in the 79 sibs of index cases was 1 in 7. These two features demonstrate that ataxia telangiectasia may not always be an autosomal recessive condition. Other possible explanations are that some cases are double heterozygotes or new dominant mutations.     

Morphological features and inheritance of Foliaceous Stipules of primary leaves in cowpea (Vigna unguiculata)

BACKGROUND AND AIMS: The presence of connate foliaceous stipules of primary leaves and their inheritance in cowpea (Vigna unguiculata) genotype EC394736 is reported for the first time. METHODS: The development of foliaceous stipules (FS) and their persistence were examined throughout the growth and developmental stages of the plants of the genotype EC394736. The shape, size, colour, texture and other parameters were examined in the field during the period 15-50 d after sowing. The area of FS was measured using image analysis software. The inheritance of FS was studied by making a cross between the genotype EC394763 with rudimentary stipules (RS) and the genotype EC394736, which has connate foliaceous stipules of primary leaves. The presence or absence of FS in plants of the F1, F2 and F3 generations was recorded. KEY RESULTS: The stipules developed along with the primary leaves in the genotype EC394736. One stipule of each primary leaf fused with the adjacent stipule of the other primary leaf forming a foliaceous structure. These stipules persisted on the plants for >50 d, even after the primary leaves had withered off. The F1 plants showed an absence of FS indicating the rudimentary stipules to be dominant over foliaceous stipules. The F2 segregation into 15 (RS) : 1 (FS) indicated that duplicate recessive genes controlled the presence of the FS. This was confirmed from the segregation pattern in the F3 generation. CONCLUSIONS: The presence of FS is a unique feature in cowpea genotype EC394736 and duplicate recessive genes govern it. The FS can be used as a morphological marker for identification of cowpea varieties.     

A study on the inheritance of the transverse cephalic curvature index

The transverse cephalic curvature index defined by Dash Sharma (Proc. Indian Sci. Cong. 54:496, 1967) was studied in 38 families of both the Adivasi population of Orissa and the Andhras of Visakhapatnam (Andhra Pradesh). Correlation coefficients estimated for the different familial combinations gave a negative result, suggesting the non-hereditary nature of the index.     

Expression of the db (diabetes) gene in mice with hereditary load by generalized autoimmune pathology]

A model of genetically determinate diabetes mellitus in hybrid db/db mice with hereditary load by generalized autoimmune pathology has been described. The data on the character of hormonal-metabolic disturbances permit a conclusion on more serious course of diabetes mellitus in mice (C57Bl/Ks x NZB)F2 db/db as against (C57BL/Ks x NZW)F2 db/db, that is correlated with expression of autoimmune pathology in parent lines of New Zealand mice NZB and NZW. It is stated that diabetic syndrome in males proceeds in more serious form than in females.     

Characterization and inheritance of the Anthocyanin fruit (Aft) tomato

Tomato (Lycopersicon esculentum) accession LA1996 with the Anthocyanin fruit (Aft) gene has dark green foliage, elevated anthocyanin expression in the hypocotyls of seedlings, and anthocyanin in the skin and outer pericarp tissues of the fruit. Interest in the health benefits and antioxidant capacity of anthocyanins led to this study of the genetic potential for increased levels of this important class of phytonutrients in tomato fruit. In order to conform to tomato gene nomenclature rules, we propose changing the symbol Af for Anthocyanin fruit to Aft. Segregation ratios of anthocyanin expression in F(2) and BC(1) populations of a cross between the processing tomato UC82B and LA1996 were consistent with a single dominant gene hypothesis. Anthocyanin expression was reduced in backcross populations compared to F(2 )populations. Anthocyanin concentration, as measured by the pH differential method, of pigment-rich pericarp and skin tissues from LA1996 was estimated to be 20.6 mg/100 g and 66.5 mg/100 g, respectively. Anthocyanidin composition was characterized by high-performance liquid chromatography (HPLC). Fruit of accession LA1996 contained predominantly petunidin, followed by malvidin and delphinidinin. Lycopene, beta-carotene, phytoene, and phytofluene levels were similar to those of normal tomatoes and lower than those found in high pigment tomatoes.     

Paternal inheritance of mitochondrial DNA in the sheep (Ovine aries)

Paternal inheritance of mitochondria DNA in sheep was discovered by examination of 152 sheep from 38 hybrid families for mtDNA D-loop polymorphisms using PCR-RFLP, amplification of repeated sequence somain, and PCR-SSCP of the D-loop 5' end region of a 253 bp fragment. Our findings have provided the first evidence of paternal inheritance of mtDNA in sheep and possible mechanisms of paternal inheritance were discussed.     

苹果蠹蛾成虫产卵特性

苹果蠹蛾Cydia pomonella(L.)是全球温带地区果园主要害虫之一,是中国的重要检疫性有害生物,对我国苹果、梨等水果的安全生产造成极大危害及威胁。为详细了解苹果蠹蛾的产卵特性,从而为进行有效的监测与防控提供基础信息,作者于2006年在甘肃省山丹县梨果园中对树冠不同高度与朝向的蛀果率进行了调查,并于2010在内蒙古阿拉善左旗对梨树果枝上不同部位的产卵量进行了详细调查。主要研究结果如下:1)树冠2.5m以上的蛀果率显著高于2.5m以下的蛀果率,树冠东面的蛀果率最高,南面的蛀果率最低;2)在整个果园中,靠近北侧的果树上果实受害程度要高于南侧果树上的果实受害程度,整个果园中蛀果率由北向南逐渐降低;3)叶片上的卵数最多,占总卵数的73.1%,果实上的卵数次之,占总卵数的14.6%,枝条上的卵数最少,占总卵数的12.2%;4)在产卵的叶片上,卵主要产在叶背面,叶片背面卵量是叶正面的6.65倍。鉴于以上研究结果,在开展化学防治或颗粒体病毒防治时,应注意充分喷施果树上层树冠,且在对果实进行处理的同时,叶片和枝条也需要充分喷药。