Short, natural, and extended photoperiod response in BC2F4 lines of bread wheat with different photoperiod-1 (Ppd-1) alleles.

Flowering is a critical period in the life cycle of flowering plant species, resulting in an irreversible commitment of significant resources. Wheat is photoperiod sensitive, flowering only when daylength surpasses a critical length; however, photoperiod insensitivity (PI) has been selected by plant breeders for >40 years to enhance yield in certain environments. Control of flowering time has been greatly facilitated by the development of molecular markers for the Photoperiod-1 (Ppd-1) homeoloci, on the group 2 chromosomes. In the current study, an allelic series of BC2F4 lines in the winter wheat cultivars 'Robigus' and 'Alchemy' was developed to elucidate the influence on flowering of eight gene variants from the B- and D-genomes of bread wheat and the A-genome of durum wheat. Allele effects were tested in short, natural, and extended photoperiods in the field and controlled environments. Across genetic background and treatment, the D-genome PI allele, Ppd-D1a, had a more potent effect on reducing flowering time than Ppd-B1a. However, there was significant donor allele effect for both Ppd-D1a and Ppd-B1a, suggesting the presence of linked modifier genes and/or additional sources of latent sensitivity. Development of Ppd-A1a BC2F4 lines derived from synthetic hexaploid wheat provided an opportunity to compare directly the flowering time effect of the A-genome allele from durum with the B- and D-genome variants from bread wheat for the first time. Analyses indicated that the reducing effect of Ppd-A1a is comparable with that of Ppd-D1a, confirming it as a useful alternative source of PI.

Epitope-specific anti-nuclear antibodies are expressed in a mouse model of primary biliary cirrhosis and are cytokine-dependent.

Although the hallmark of primary biliary cirrhosis (PBC) is the presence of anti-mitochondrial antibodies (AMA), a significant number of patients have anti-nuclear antibodies (ANA) directed primarily against two nuclear proteins, gp210 and sp100. In PBC, there are considerable data on the specificity of these anti-nuclear antibodies as well as suggestive evidence that antibodies to gp210 predict a poor outcome. However, a further understanding of the significance of these autoantibodies has been hampered by limitations in accessing human subjects in a preclinical or early asymptomatic stage. To overcome this limitation, we have taken advantage of transgenic mice with abrogated transforming growth factor-ß signalling in T cells (dnTGF-ßRII) that develop histological features of PBC as well as the same AMA specificity. We studied these mice for serum ANA, including specific autoantibodies against gp210 and sp100. We further examined sera from dnTGF-ßRII mice with concurrent deletions of the genes encoding interleukin (IL)-12p35, IL-12p40, IL-23p19, IL-17, IL-6, interferon (IFN)-γ or tumour necrosis factor (TNF)-α. Sera from all the dnTGF-ßRII mouse lines contained antibodies against gp210 and sp100. Of significance, mice with germline deletions of the genes encoding IL-12p40, IL-23p19, IL-17, IL-6 and TNF-α had significantly lower titres of anti-gp210 antibodies. These results provide a platform to dissect the mechanisms of gp210 and sp100 autoantibody production in dnTGF-ßRII mice as well as to study the possible role of ANA in the pathophysiology of PBC.

Reanalyses of the historical series of UK variety trials to quantify the contributions of genetic and environmental factors to trends and variability in yield over time.

Historical datasets have much to offer. We analyse data from winter wheat, spring and winter barley, oil seed rape, sugar beet and forage maize from the UK National List and Recommended List trials over the period 1948-2007. We find that since 1982, for the cereal crops and oil seed rape, at least 88% of the improvement in yield is attributable to genetic improvement, with little evidence that changes in agronomy have improved yields. In contrast, in the same time period, plant breeding and changes in agronomy have contributed almost equally to increased yields of forage maize and sugar beet. For the cereals prior to 1982, contributions from plant breeding were 42, 60 and 86% for winter barley, winter wheat and spring barley, respectively. These results demonstrate the overwhelming importance of plant breeding in increasing crop productivity in the UK. Winter wheat data are analysed in more detail to exemplify the use of historical data series to study and detect disease resistance breakdown, sensitivity of varieties to climatic factors, and also to test methods of genomic selection. We show that breakdown of disease resistance can cause biased estimates of variety and year effects, but that comparison of results between fungicide treated and untreated trials over years may be a means to screen for durable resistance. We find the greatest sensitivities of the winter wheat germplasm to seasonal differences in rainfall and temperature are to summer rainfall and winter temperature. Finally, for genomic selection, correlations between observed and predicted yield ranged from 0.17 to 0.83. The high correlation resulted from markers predicting kinship amongst lines rather than tagging multiple QTL. We believe the full value of these data will come from exploiting links with other experiments and experimental populations. However, not to exploit such valuable historical datasets is wasteful.

Induction of autoimmune cholangitis in non-obese diabetic (NOD).1101 mice following a chemical xenobiotic immunization.

Our laboratory has suggested that loss of tolerance to pyruvate dehydrogenase (PDC-E2) leads to an anti-mitochondrial antibody response and autoimmune cholangitis, similar to human primary biliary cirrhosis (PBC). We have suggested that this loss of tolerance can be induced either via chemical xenobiotic immunization or exposure to select bacteria. Our work has also highlighted the importance of genetic susceptibility. Using the non-obese diabetic (NOD) congenic strain 1101 (hereafter referred to as NOD.1101 mice), which has chromosome 3 regions from B6 introgressed onto a NOD background, we exposed animals to 2-octynoic acid (2OA) coupled to bovine serum albumin (BSA). 2OA has been demonstrated previously by a quantitative structural activity relationship to react as well as or better than lipoic acid to anti-mitochondrial antibodies. We demonstrate herein that NOD.1101 mice immunized with 2OA-BSA, but not with BSA alone, develop high titre anti-mitochondrial antibodies and histological features, including portal infiltrates enriched in CD8(+) cells and liver granulomas, similar to human PBC. We believe this model will allow the rigorous dissection of early immunogenetic cause of biliary damage.

An actin-myosin functional assay for analysis of smooth muscle (anti-microfilament) autoantibodies in human plasma.

The detection of serum autoantibodies to smooth muscle (SMA) on rodent gastric mucosa by indirect immunofluorescence (IIF) has long been an immunodiagnostic marker for autoimmune hepatitis type 1 (AIH-1). The reactive antigenic moieties are cytoskeletal proteins which include polymeric F-actin as judged by the staining of microfilaments of tissue by IIF. However, their specificity for actin in AIH-1 can be and usually is uncertain. Using an in vitro functional assay, we compared the effects of Fab fragments of immunoglobulin (IgG) prepared from SMA-positive plasma from two patients with the effects of Fabs from 10 healthy subjects. Fabs are incorporated into an assay where actin (the putative antigen) activates skeletal muscle heavy meromyosin (HMM) ATPase activity. The data from these functional assays provide new insights into the significance of anti-microfilament assays in the diagnosis, and perhaps also pathogenesis, of AIH-1.

Chronic complications and mortality in community-based patients with latent autoimmune diabetes in adults: the Fremantle Diabetes Study.

AIMS: To compare (i) the prevalence and incidence of chronic complications and (ii) cardiac and all-cause mortality in community-based patients with latent autoimmune diabetes in adults (LADA) with those in Type 2 diabetic patients without antibodies to glutamic acid decarboxylase (GAD). METHODS: Of the 1294 patients with clinically-defined Type 2 diabetes recruited to the longitudinal, observational Fremantle Diabetes Study between 1993 and 1996, 1255 (97%) had GAD antibodies measured at baseline. Complications were ascertained using standard criteria in patients returning for annual assessments until November 2001. Data on hospital admissions and mortality were available to the end of June 2006. Cox proportional hazards modelling was used to determine independent predictors of first occurrence of complications and cardiac and all-cause mortality. RESULTS: Forty-five (3.6%) subjects had LADA. Compared with the GAD antibody-negative patients, they had a similar prevalence and incidence of coronary heart (P = 0.48 and 0.80, respectively) and cerebrovascular (P = 0.64 and 0.29) disease and cardiac and all-cause mortality (P = 0.62 and 0.81, respectively). There was also a similar prevalence and incidence of retinopathy (P = 0.22 and 0.64, respectively) and neuropathy (P = 0.25 and 0.95), but microalbuminuria was less frequent both at baseline and during follow-up in the LADA subgroup in unadjusted models (P = 0.046) and after adjustment for other risk factors (P = 0.014 and 0.013). CONCLUSIONS: Except for a lower prevalence and incidence of nephropathy, LADA patients have a similar risk of complications and death to patients with clinically-diagnosed Type 2 diabetes without GAD antibodies. Cardiovascular risk factor management in LADA should, therefore, be as intensive as that for GAD antibody-negative patients.

Characterisation of a newly identified human rhinovirus, HRV-QPM, discovered in infants with bronchiolitis.

BACKGROUND: Human rhinoviruses (HRVs) are some of the earliest identified and most commonly detected viruses associated with acute respiratory tract infections (ARTIs) and yet the molecular epidemiology and genomic variation of individual serotypes remains undefined. OBJECTIVES: To molecularly characterise a novel HRV and determine its prevalence and clinical impact on a predominantly paediatric population. STUDY DESIGN: Nucleotide sequencing was employed to determine the complete HRV-QPM coding sequence. Two novel real-time RT-PCR diagnostic assays were designed and employed to retrospectively screen a well-defined population of 1244 specimen extracts to identify the prevalence of HRV-QPM during 2003. RESULTS: Phylogenetic studies of complete coding sequences defined HRV-QPM as a novel member the genus Rhinovirus residing within the previously described HRV-A2 sub-lineage. Investigation of the relatively short VP1 sequence suggest that the virus is resistant to Pleconaril, setting it apart from the HRV A species. Sixteen additional HRV-QPM strains were detected (1.4% of specimens) often as the sole micro-organism present among infants with suspected bronchiolitis. HRV-QPM was also detected in Europe during 2006, and a closely related virus circulated in the United States during 2004. CONCLUSIONS: We present the molecular characterisation and preliminary clinical impact of a newly identified HRV along with sequences representing additional new HRVs.

Assessment of burn depth: a prospective, blinded comparison of laser Doppler imaging and videomicroscopy.

INTRODUCTION AND AIMS: There is a need, both in clinical and research settings, for an affordable, objective method of assessing burn depth. This study compares burn depth assessment by videomicroscopy with laser Doppler imaging (LDI) in patients with dermal burns. The videomicroscope is inexpensive compared to LDI, and can visualise the dermal capillary structure, therefore potentially allowing objective assessment of dermal burn injuries. METHODS: Patients admitted <72 h post-injury were included in the trial. Blinded LDI and videomicroscopy assessments were carried out. The patients were then followed up to one of three end-points: primary healing without surgery; early surgery; delayed healing and subsequent split skin grafting. The incidence of infection was also noted. RESULTS: Twenty-seven burn wounds were examined. In superficial partial thickness injuries, the videomicroscope reliably demonstrated an intact or nearly intact dermal vascular structure, progressing through to large amounts of capillary destruction and haemoglobin deposition in deep partial thickness injuries and complete destruction in full thickness injuries. The videomicroscope findings correlated strongly with both those of the LDI (p<0.001) and with clinical outcome (p<0.001). DISCUSSION: The videomicroscope is capable of accurately and objectively assessing burn depth. The results correlated well with both the clinical outcome and the laser Doppler findings. In addition, videomicroscopy is significantly cheaper than LDI and avoids several of the disadvantages of LDI.

A genome-wide screen in 1119 relative pairs with autoimmune thyroid disease.

CONTEXT: Autoimmune thyroid diseases (AITD), comprising Graves' disease and autoimmune hypothyroidism, are characterized by loss of immunological self-tolerance to thyroid antigens. These are complex diseases arising from a combination of genetic and environmental factors. An understanding of the genetic susceptibility factors for AITD could help to target treatments more effectively and identify people at risk for these conditions. OBJECTIVE: The objective of this study was to identify regions of genetic linkage to AITD that could potentially harbor genetic susceptibility factors for these conditions. DESIGN: The study design was a genome-wide screen performed on affected relative pairs with AITD. SETTING: Patients were recruited through hospital endocrinology clinics. PARTICIPANTS: Some 1119 Caucasian relative pairs affected with AITD (Graves' disease or autoimmune hypothyroidism) were recruited into the study. INTERVENTION: Blood samples were obtained from each participant for DNA analysis, and clinical questionnaires were completed. MAIN OUTCOME MEASURE: The study aimed to identify regions of genetic linkage to AITD. RESULTS: Three regions of suggestive linkage were obtained on chromosomes 18p11 (maximum LOD score, 2.5), 2q36 (maximum LOD score, 2.2), and 11p15 (maximum LOD score, 2.0). No linkage to human leukocyte antigen was found. CONCLUSIONS: The absence of significant evidence of linkage at any one locus in such a large dataset argues that genetic susceptibility to AITD reflects a number of loci, each with a modest effect. Linkage analysis may be limited in defining such loci, and large-scale association studies may prove to be more useful in identifying genetic susceptibility factors for AITD.

History of immunology in Australia: events and identities.

Immunology originated in Europe during the latter 1900s, and applications can be discerned in colonial Australia. The actual beginnings of immunology in Australia followed Burnet's enunciation of two fundamental principles: natural immune tolerance as an acquired characteristic in 1948 and clonal selection theory in 1957. Laboratory and clinical immunology flourished at various centres from the 1950s. The Australian Society of Immunology was founded in 1971. The merger of clinical immunology with allergy in 1991 created the Australian Society of Clinical Immunology and Allergy, exemplary for the reamalgamation of these related specialties. Australian immunology over the past 50 years has become recognized nationally and abroad as a highly visible component of the academic, research and biomedical scene and is still on a rising trajectory.

New murine model for hepatocellular carcinoma: transgenic mice expressing metallothionein-ovine growth hormone fusion gene.

Hepatocellular carcinomas developed at a high frequency in the livers of transgenic (C57BL/6 X SJL/J)F1 mice under the influence of growth hormone. Three lines of giant transgenic mice expressing a mouse metallothionein-ovine growth hormone fusion gene were generated. The giant mice weighed twice as much as control littermates. The three lines of giant mice expressing very high levels of growth hormone were bred over several generations. Mice from all three lines developed hepatocellular tumors, including adenoma and carcinoma. The occurrence of tumors was age-dependent, and their incidence increased to 70% of the mice studied after 43 weeks of age. Pathologic changes in the livers resembled those observed in rats in which hepatocellular carcinomas are induced chemically. Transgenic mice carrying the metallothionein-ovine growth hormone fusion gene represent a new model for hepatocellular carcinogenesis. This model exemplifies the oncogenic potential for a sustained proliferative growth stimulus within an organ.

Antiproliferative potencies of interferons on melanoma cell lines and xenografts: higher efficacy of interferon beta.

BACKGROUND: Human melanomas have shown only limited responsiveness to clinical therapy with interferon (IFN). PURPOSE: Our aim was to determine the most effective class of IFN for inhibiting growth of melanoma cells and to establish whether variation exists in response of various cell lines to different IFNs. METHODS: We compared the direct antiproliferative effects of the type I IFN alpha-2b, IFN alpha-4a, and IFN-beta and the type II IFN-gamma on eight melanoma cell lines grown in vitro. We did this comparison by determining the concentration of each IFN that resulted in 50% growth inhibition, using the MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium tetrazolium bromide] dye uptake method. We also tested IFN alpha-2a and IFN-beta for their ability to inhibit the growth of xenografts of the LiBr melanoma cell line in vivo in nude mice. Receptor binding was determined using [35S]methionine-labeled IFN alpha-4a, in competition with unlabeled IFN alpha-2b, IFN alpha-4a, and IFN-beta. RESULTS: The melanoma cell lines differed markedly in their sensitivity to the IFNs tested: Five were sensitive to low concentrations (less than 30 pM) of IFN-beta, only one was sensitive to similar concentrations of IFN alpha-2b, and none were sensitive to IFN alpha-4a at concentrations up to 920 pM. For all cell lines, the antiproliferative potency of the type I IFNs was IFN-beta greater than IFN alpha-2b greater than IFN alpha-4a. IFN-gamma was less active than IFN-beta on all except one of the cell lines. Similarly, IFN-beta was more potent than IFN alpha-2a in inhibiting the growth of the LiBr xenograft in nude mice. Labeled IFN alpha-4a bound with high specificity in all four melanoma lines tested, and competitive binding experiments showed that the order of binding affinity (IFN-beta greater than IFN alpha-2b greater than IFN alpha-4a) correlated with the order of antiproliferative potency. CONCLUSION: The finding that melanoma cell lines differ intrinsically in their sensitivity to IFNs may explain differences in clinical response. Our results suggest that IFN-beta may be the most effective IFN in the treatment of melanoma, although confirmation will require clinical trials involving large numbers of patients.

Pharmacokinetics, tissue distribution, and cell localization of [35S]methionine-labeled recombinant human and murine alpha interferons in mice.

The pharmacokinetics, tissue distribution, cell localization, and penetration into tumor xenografts of recombinant [35S]methionine-labeled human alpha interferon (HuIFN-alpha) and murine alpha interferon (MuIFN-alpha) were examined in mice. Both interferons (IFNs) were removed from the blood in a rapid biphasic manner; HuIFN-alpha was cleared faster than MuIFN-alpha. Tissues were analyzed for radioactivity and over 90% of the IFNs was accounted for. The IFNs were detected predominantly in liver, kidney, gastrointestinal tract, pancreas, spleen, and lung. The levels of MuIFN-alpha compared with HuIFN-alpha were greater in the liver, spleen, and lung and less in the kidney, pancreas, and gastrointestinal tract. Heart, brain, testes, thymus, lymph nodes, fat, skin, and skeletal muscle contained much lower but measurable levels of both IFNs. There was penetration of HuIFN-alpha into tumor xenografts. The pharmacokinetics of IFN-alpha were independent of the strain of mouse, BALB/c or CBA, immune deprivation, or the presence of a tumor xenograft. Autoradiography of tissue sections from mice given injections of HuIFN-alpha or MuIFN-alpha indicated focal radioactivity in proximal convoluted tubules in the kidney and diffuse radioactivity in the liver, gastrointestinal tract, and pancrease. MuIFN-alpha, but not HuIFN-alpha, showed intense localization in cells in hepatic sinusoids, marginal zones in the spleen, and pulmonary alveolar walls, suggesting uptake by cells of the monocyte/macrophage lineage in these sites. The study shows the utility of biosynthetic labeling for pharmacokinetic studies of cytokines, clear differences in tissue distribution of IFN-alpha according to its species of origin, and targeting of homologous IFN-alpha to cells of the monocytic lineage.

Fluctuations in the expression of a glycolipid antigen associated with differentiation of melanoma cells monitored by a monoclonal antibody, Leo Mel 3.

A monoclonal antibody, Leo Mel 3, raised against a melanoma cell line (LiBr), binds to a carbohydrate determinant of cell surface gangliosides, the simplest of which is GD3. This monoclonal antibody was screened for by its capacity to block the recognition and lysis of the melanoma cells by cytotoxic T-lymphocytes with anomalous killer cell function, illustrating a novel approach for identifying monoclonal antibody to biologically relevant tumor-associated antigens. Leo Mel 3 reacted selectively with melanoma cells by indirect immunofluorescent and immunoperoxidase staining; it reacted with tissue from all primary and metastatic melanoma tested, and it bound to cells from all but one of six cultured melanoma cell lines. Leo Mel 3 did not react with a variety of carcinomas, lymphomas, leukemias, and other neuroectodermal tumors, nor with adult or fetal tissues, except fetal liver. Very weak staining of cutaneous basal melanocytes was noted in a minority of skin sections, and 50 to 80% of melanocytes in four of seven benign nevi showed weak to moderate reactivity. The antibody was relatively specific for human adherent melanoma cells, since it did not bind to the adherent murine B16 melanoma line nor to a nonadherent human melanoma cell line (PMC-22). Expression of the Leo Mel 3-defined antigen was unrelated to changes in cell cycle. When cells from an adherent melanoma cell line were detached and maintained briefly in suspension culture, the cells became markedly less reactive with Leo Mel 3 and, after readherence to plastic, they rapidly reexpressed higher levels of the ganglioside antigen; since Leo Mel 3 prevented attachment and growth of melanoma cells in vitro, a functional role for the ganglioside is suggested in cell adhesion and metastasis. Differentiation of melanoma cells with dimethyl sulfoxide, retinoic acid, and theophylline resulted in a marked and selective increase in the amount of Leo Mel 3-defined antigen, together with an increase in the target cell binding ability of these cells, assessed by cold target competition assays using anomalous killer cells.

The human pyruvate dehydrogenase complex: a polymorphic region of the lipoate acetyl transferase (E2) subunit gene.

A major issue in the study of the pathogenesis of primary biliary cirrhosis is whether the E2 subunit of the pyruvate dehydrogenase complex (PDH-E2), the major autoantigen in the disease, exists as a tissue-specific isoform. cDNA clones spanning a segment of the 3'-catalytic region of PDH-E2 (nt 1158-1361) have been isolated from human kidney, placenta and bile epithelium cells. Nucleotide sequence analysis of the clones showed differences consistent with the presence of normal variants of PDH-E2 in the human population. However, the existence of tissue-specific isoforms of PDH-E2 cannot yet be discounted.

Antibodies to glutamic acid decarboxylase reveal latent autoimmune diabetes mellitus in adults with a non-insulin-dependent onset of disease.

The classification of adults with diabetes mellitus can be invalidated by patients who initially present as NIDDM but who later become frankly insulin dependent. In some of these, the pathogenesis could be similar to that in IDDM, namely autoimmune destruction of the pancreatic beta-cells. We studied 102 patients > 35 yr of age at diabetes onset who had initially been nonketotic and non-insulin-dependent for > or = 6 mo. They were classified according to glucagon-stimulated C-peptide levels into an insulin-deficient group (n = 33) and a non-insulin-deficient group (n = 69). We measured antibodies to GAD, islet cell cytoplasm, thyroid antigens, and gastric parietal cells in both groups. Anti-GAD was significantly higher in the insulin deficient group, 76% (25 of 33), than in the non-insulin deficient group, 12% (8 of 69), and this difference was substantially greater than that shown for ICAs. Thus, in a proportion of adults who present with NIDDM, a slowly evolving autoimmune insulitis can be revealed by testing for anti-GAD. This could have important connotations not only for early intervention, but also for the correct classification of diabetes.

Antibodies to glutamic acid decarboxylase discriminate major types of diabetes mellitus.

Insulin-dependent diabetes mellitus (IDDM) is marked by circulating antibodies to a 64,000-M(r) islet cell antigen identified as glutamic acid decarboxylase (GAD). We describe a radioimmunoprecipitation assay with GAD isolated from pig brain. The sera tested were from 80 patients with IDDM including 26 with disease of recent onset and 54 with disease of longer duration (3-42 yr), 20 with non-insulin-dependent diabetes mellitus (NIDDM), and 55 nondiabetic subjects. Conventional assays for islet cell cytoplasmic antibodies were performed concurrently. The level of antibody in serum was expressed in units based on percentage reactivity of a standard reference serum. The frequency of antibody to GAD in IDDM was 69% in short-duration cases and 59% in long-duration cases. The latter was substantially higher than the frequency of islet cell cytoplasmic antibody. Antibodies to GAD were elevated (means +/- 3 SD) in 5% NIDDM cases and in none of the nondiabetic subjects. A simple laboratory test with a defined autoantigen has substantial implications for population screening and early diagnosis of IDDM and for better understanding of its pathogenesis.

GAD antibody negative NIDDM in adult black subjects with diabetic ketoacidosis and increased frequency of human leukocyte antigen DR3 and DR4. Flatbush diabetes.

The objective of this study is to understand the metabolic and immunologic basis of diabetes in adult blacks with diabetic ketoacidosis (DKA). Twenty-one black adults presenting with DKA ([mean +/- SD] blood pH = 7.18 +/- 0.09, plasma glucose = 693 +/- 208 mg/dl, and positive serum ketones) had a subsequent clinical course of non-insulin-dependent diabetes mellitus (NIDDM). Human leukocyte antigens (HLAs) DR and DQ and antibodies to glutamic acid decarboxylase (GAD) and islet cell cytoplasmic proteins (ICP) were measured to assess autoimmunity. Insulin action was evaluated by the euglycemic insulin clamp, and insulin secretion was measured by C-peptide responses to oral glucose. Ketoacidosis was treated with insulin. Two subjects had a precipitating illness; four had a history of NIDDM. At the time of study, subjects' glycemic control was good (HbA1c = 5.7 +/- 1.6%). Nine subjects were treated with insulin, and 12 were on either sulfonylurea treatment or diet alone. Men (n = 12) were younger than women (n = 9) (40.8 +/- 9.8 and 51.1 +/- 6.3 years of age, respectively, P < 0.05) but similar in body mass index (27.8 +/- 2.7 and 29.98 +/- 4.1 kg/m2, respectively). Antibodies to GAD and ICP were absent. All but one subject was insulin resistant compared with normal subjects (glucose disposal 3.56 +/- 0.04 vs. 6.86 +/- 0.02 mg.kg-1.min-1), and insulin secretion was lower. HLA DR3 and DR4 frequency was higher than in nondiabetic black control subjects (65 vs. 30%, P < 0.012).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative epitope mapping of antibodies to collagen in women with silicone breast implants, systemic lupus erythematosus and rheumatoid arthritis.

Previous work has shown that women with silicone gel breast implants have an increased frequency of autoantibodies to collagen types I and II. 70 women without a specific autoimmune disease, using criteria of the American College of Rheumatology, but who had silicone breast implants were studied for the presence of serum antibodies to native and denatured human types I and II collagen by ELISA. 82 women with systemic lupus erythematosus (SLE), 94 women with rheumatoid arthritis (RA), and 133 healthy controls were also studied. There was a high frequency of autoantibodies to collagen in each of the groups when compared to the healthy controls. The specificities of these antibodies were found to differ markedly when examined by immunoblotting using peptides derived by cyanogen bromide digestion of the collagens. Sera from women with silicone implants reacted with multiple peptides of type I collagen in an individual-specific manner, but sera from women with SLE or RA reacted weakly with a restricted range of peptides. Against type II collagen, sera from women with RA reacted strongly with multiple peptides, while sera from women with silicone implants or SLE reacted only weakly or not at all. The patterns of reactivity against collagens by sera from women with silicone implants suggest that silicone can act as an adjuvant to enhance the immunogenicity of type I collagen.

A multilingual self-administered symptom history.

A multilingual computer-derived symptom history was developed from a two-stage yes-no symptom questionaire, based on a library of 4,000 numbered questions. The English primary and secondary questionaires were translated into German, Italian, French, Spanish, Greek and Yugoslav. "Yes" answers to the numbered primary questions presented in these languages were processed by a computer that generated individualized secondary questions in the same language. "Yes" answers to these numbered questions were processed by a second computer program that printed out the narrative history in English. As well as other benefits of automated symptom histories, there is now a facility for the computer to acquire a patient's history in one language and print it out in any other.