Association of acromegaly and two malignancies: colorectal cancer and non-Hodgkin's lymphoma.
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Biomedical subjects
Publications and source records attributed to A Goday.
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The maize abscisic acid (ABA)-responsive rab17 mRNA and Rab17 protein distribution in maize embryo tissues was investigated by in situ hybridization and immunocytochemistry. rab17 mRNA and Rab17 protein were found in all cells of embryo tissues. Synthesis of rab17 mRNA occurred initially in the embryo axis. As maturation progressed, rab17 mRNA was detectable in the scutellum and accumulated in axis cells and provascular tissues. However, the response to exogenous ABA differed in various embryo cell types. The Rab17 protein was located in the nucleus and in the cytoplasm, and qualitative differences in the phosphorylation states of the protein were found between the two subcellular compartments. Based on the similar domain arrangements of Rab17 and a nuclear localization signal (NLS) binding phosphoprotein, Nopp140, interaction of Rab17 with NLS peptides was studied. We found specific binding of Rab17 to the wild-type NLS of the SV40 T antigen but not to an import incompetent mutant peptide. Moreover, binding of the NLS peptide to Rab17 was found to be dependent upon phosphorylation. These results suggest that Rab17 may play a role in nuclear protein transport.
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BACKGROUND: The aim of the present study was to evaluate the geographic distribution of the incidence of diabetes mellitus type I (DMI) in Catalonia from 1987-1990. METHODS: The base of the study is the Catalonian registry of incidence of DMI in the period from 1987-1990. The definition criteria were: diagnostic criteria of diabetes (WHO norms 1985), age of diagnosis under 30 years, residence in Catalonia in the period of diagnosis and exclusion of other types of diabetes. The population at risk was estimated according to the general census of the population of 1986. The total incidence of Catalonia was calculated by provinces and counties according to the Poisson distribution. RESULTS: The incidence of DMI observed in Catalonia was of 11.5/100,000 inhabitants per year (CI 95%, 10.6-12.4) in the age group from 0-14 years and 10.7/100,000 inhabitants per year (CI 95% 10.1-11.3) in the age group from 0-29 years. The exhaustivity in the detection of the cases was of 90.3%. No differences were found in interprovincial incidence in the 0-14 age group: Barcelona 11.6 (10.6-12.7), Girona 10.2 (7.2-13.4), Lleida 11.7 (7.7-15.8), Tarragona 10.5 (7.6-13.5). In the 15-29 age group a lower incidence was observed in Tarragona. The incidence by counties varied between 2.9 and 15.0/100,000 inhabitants per year with those of greatest incidence being observed in the Vallés Oriental (15.0/100,000 inhabitants/years), Alt Penedés (14.5/100,000 inhabitants/year), Segrià (15.0/100,000 inhabitants/year) and the Priorat (13.7/100,000 inhabitants/year). CONCLUSIONS: No differences were found in the incidence of diabetes mellitus type I in the four Catalonian provinces. Distribution by counties was more heterogeneous without defining zones with a much higher incidence to that observed in the whole of Catalonia.
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The effect of corticosteroids on beta cell function and humoral immune response in type 1 diabetes was tested in a 2-month trial conducted on 32 newly diagnosed patients (age 22.8 +/- 1.4 years, mean +/- S.E.M.). Prednisone was administered at immunosuppressive dosage (1 mg.kg-1.day-1) during the initial 10 days and at a maintenance dosage (0.3 mg.kg-1.day-1) for 50 days. Patients (n = 32) were enrolled within 6 weeks after diagnosis and matched in pairs for age, sex, presence of islet cell antibodies (ICA) and glucagon stimulated C-peptide levels. Insulin discontinuation was not contemplated. All the patients who received prednisone became ICA during treatment but in some (4 out of 10) this effect was only transient. Insulin antibodies (IA) were significantly lower in the prednisone group at second and third month (P < 0.05). No patient experienced complete remission but in 10 prednisone and 4 control patients the insulin requirements were below 0.3 IU/kg (P < 0.05). With similar glycemia the fasting C-peptide levels were higher in the treated patients. The profile of the insulin requirements during the follow-up was different in the two groups and at 9 months the prednisone group needed less insulin than the control (P < 0.05). Interestingly, within the prednisone-treated group and after 6 months, the levels of stimulated C-peptide improved significantly among the ICA+ patients while they were steady or declined in ICA- (P < 0.01). The analysis of variance covariance confirmed a positive interaction between ICA and the administration of prednisone on the outcome of beta cell function.(ABSTRACT TRUNCATED AT 250 WORDS)
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The incidence of Type 1 (insulin-dependent) diabetes mellitus was prospectively evaluated in Catalonia, Spain in patients up to 30 years of age during the period 1987-1990. The population at risk (0-29 years) consisted of 2,690,394 inhabitants (total population of Catalonia 5,978,638). All the cases were independently identified from four sources: endocrinologists, sales of blood glucose monitors and insulin pen injectors, diabetes societies and diabetic summer camps. The degree of ascertainment was 90.1%. The overall observed incidence rate was 10.7 per 100,000 per year, being 11.5 per 100,000 per year in the 0-14 age group. The incidence in males (12.0 per 100,000 per year) was higher than in females (9.3 per 100,000 per year), with a male/female ratio of 1.36/l. The sex differences were only present in cases over 14 years of age. Age specific incidence rates per 100,000 per year were 4.4 (confidence interval 95%: 3.2-5.7) in the age group 0-4, 9.9 (8.5-11.4) in 5-9, 17.5 (15.7-19.4) in 10-14, 11.4 (9.9-13.0) in 15-19, 11.3 (9.7-13.0) in 20-24 and 8.5 (7.2-9.9) in 25-29. There was a seasonal onset pattern, with the highest incidence in winter (December-February). We conclude that the incidence of Type 1 diabetes observed in Catalonia during the period 1987-1990 is higher than that recently reported in other Mediterranean countries. This study offers the first standardized data on Type 1 diabetes incidence in Catalonia, including cases up to 30 years, and contributes to the knowledge of the epidemiology of diabetes in South Europe.
In recent years there has been great concern that human insulin (HI) may induce fewer hypoglycaemic warning symptoms than porcine insulin (PI). We addressed this issue in eight patients aged 25.6 +/- 3.3 (SEM) years with Type I (insulin-dependent) diabetes mellitus of 15.1 +/- 3.7 years duration who complained that hypoglycaemia unawareness had appeared after transferring from PI to HI. Acute induction of hypoglycaemia was induced on two occasions with semisynthetic HI and purified PI under double-blind conditions. Blood glucose was first clamped for 2 h at 4.4-6.7 mmol l-1 with an intravenous infusion of HI or PI at 50 mU kg-1 h-1 and 20% glucose at a variable rate. Thereafter, insulin infusion alone was maintained for 100 minutes. Heart rate, arterial pressure, reflex times, autonomic and neuroglycopenic signs and symptoms were assessed every 10 min. Arterialized venous blood samples were taken to measure blood glucose every 10 min and catecholamines, insulin, glucagon, growth hormone, and cortisol every 20 min. Autonomic symptoms first appeared at a plasma glucose level of 2.92 +/- 0.21 mmol l-1 with HI vs 2.92 +/- 0.48 mmol l-1 with PI (NS). There were no significant differences between the two studies concerning any of the above mentioned clinical parameters or the counterregulatory hormone responses. A differential effect of insulin species on the ability to perceive hypoglycaemia in patients who ascribed diminished perception of hypoglycaemia to the use of HI was thus not observed.
The maize gene RAB-17, which is responsive to abscisic acid, encodes a basic glycine-rich protein containing, in the middle part of its sequence, a cluster of 8 serine residues followed by a putative casein kinase 2-type substrate consensus sequence. This protein was found to be highly phosphorylated in vivo. Here, we show that RAB-17 protein is a real substrate for casein kinase 2. RAB-17 protein is phosphorylated in vitro by casein kinase 2 isolated from rat liver cytosol and from maize embryos. A maximum of 4 mol of phosphate were incorporated per mol of RAB-17 protein following incubation with casein kinase 2. Phosphopeptide mapping experiments show that the peptide phosphorylated by casein kinase 2 in vitro is identical to that derived from the protein phosphorylated in vivo. Purification by high performance liquid chromatography and partial sequencing of the phosphopeptide indicate that it corresponds to the region of the protein (residues 56-89) containing the cluster of serine residues. Our results indicate that RAB-17 is phosphorylated by casein kinase 2 or a kinase with a similar specificity and that phosphorylation takes place in the serine cluster region of the protein both in vitro and in vivo.
We have isolated a new maize gene, rab28, that responds to abscisic acid (ABA) treatment. This gene has been characterized by determining the sequence of the cDNA and corresponding genomic copy, and by mapping the start site of its transcript. The rab 28 gene encodes a protein of predicted molecular weight 27713 Da which shows strong homology with the Lea D-34 protein identified in cotton. The proximal promoter region contains the conserved ABA-response element, CACGTGG, reported in other plant genes to be responsible for ABA induction. rab 28 mRNA has been identified as ABA-inducible in embryos and young leaves. It is also induced by water-stress in leaves of wild-type plants. Regulation of the rab 28 gene was studied in maize viviparous mutants. The results obtained with the ABA-insensitive vp1 mutant show that rab 28 transcripts do not accumulate to a significant level during embryogenesis. Surprisingly, induction of rab 28 mRNA can be achieved in young embryos by exogenous ABA treatment. Moreover, water-stressed or ABA-treated seedlings of vp1 contain significant levels of rab 28 mRNA which is not detectable in well-watered seedlings. Regulation of the rab 28 gene in excised young embryos of ABA-deficient vp2 mutants, in which influences of the maternal environment are absent, closely resembles that found in non-mutant excised young embryos. The significance of these results is discussed.
The natural history of islet cell antibodies (ICA), using standardized Juvenile Diabetes Foundation (JDF) units, was studied for two years in 64 type 1 (insulin dependent) diabetic patients, aged 7-45 years prospectively from clinical onset. While ICA were present among 44/64 (68.8%) of the newly diagnosed patients, only 9.3% remained positive at 24 months. The only factor which showed significant predictive value for ICA survival was high initial JDF ICA titres: Maximal persistence of ICA was observed in patients with 80 JDF units at diagnosis (100% at 12 and 24 month). This persistence was lower in patients with 40 JDF units at diagnosis (77% at 12 month, 40% at 24 month) and the lowest for patients with 5 JDF at diagnosis (14% at 12 month, 0% at 15 month). 14/20 (70%) of patients negative for the ICA test at diagnosis became positive during follow-up, but always with a low titre (5-10 JDF units) and for a short period (3-6 months). It is concluded that initial titre is the most important variable in predicting the maintenance of ICA during the first two years of clinical type 1 diabetes.
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The ABA-induced MA12 cDNA from maize, which encodes a set of highly phosphorylated embryo proteins, was used to isolate the corresponding genomic clone. This gene, called RAB-17 (responsive to ABA), encodes a basic, glycine-rich protein (mol. wt. 17,164) containing a cluster of 8 serine residues, seven of them contiguous. It is a homologue of the rice RAB-21 gene (Mundy J, Chua NH, EMBO J 7; 2279-2286, 1988). Phosphoamino acid analysis of the isolated protein indicates that only the serine residues are phosphorylated and a putative casein-type kinase phosphorylatable sequence was identified in the protein. The pattern of expression and in vivo phosphorylation of the RAB-17 protein was studied during maize embryo germination and in calli of both meristematic or embryonic origin. ABA treatment induced the synthesis of RAB-17 mRNA and protein in calli, however, the RAB-17 proteins were found to be highly phosphorylated only in embryos.
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Previous studies have identified a set of highly phosphorylated proteins of 23-25 kDa accumulated during normal embryogenesis of Zea mays L. and which disappear in early germination. They can be induced precociously in embryos by abscisic acid (ABA) treatment. Here the synthesis and accumulation of this group of proteins and their corresponding mRNAs were examined in ABA-deficient viviparous embryos at different developmental stages whether treated or not with ABA, and in water-stressed leaves of both wild-type and viviparous mutants. During embryogenesis and precocious germination of viviparous embryos the pattern of expression of the 23-25 kDa proteins and mRNAs closely resembles that found in non-mutant embryo development. They are also induced in young viviparous embryos by ABA treatment. In contrast, leaves of ABA-deficient mutants fail to accumulate mRNA in water stress, yet do respond to applied ABA. In water-stressed leaves of wild type plants the mRNAs are induced and translated into 4 proteins with a molecular weight and isoelectric point identical to those found in embryos. These results indicate that the 23-25 kDa protein set is a new member of the recently described class of proteins involved in generalized plant ABA responses. The different pattern of expression for the ABA-regulated 23-25 kDa proteins and mRNAs found in embryo and in vegetative tissues of viviparous mutants is discussed.