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R Bonfanti

Publications and source records attributed to R Bonfanti.

36 records · Page 2Linked to original sources
PubMed1994

Disseminated intravascular coagulation and severe peripheral neuropathy complicating ketoacidosis in a newly diagnosed diabetic child.

Disseminated intravascular coagulation is a very rare complication of diabetic ketoacidosis. Central nervous system palsy but not peripheral neuropathy has been reported in these patients. On the other hand, signs of peripheral neuropathy may also be present at the onset of diabetes, but they are usually reversible within a few days after correction of the metabolic derangement. We describe an unusual case of mononeuritis multiplex syndrome still present after 2 months of follow-up in a child with diabetic ketoacidosis complicated by disseminated intravascular coagulation at the onset of insulin-dependent diabetes. These neurological impairments may be consistent with functional neural lesions due to vasa nervorum thrombosis and prolonged ischaemia.

Blood Pressure↗
PubMed1994

Combined analysis of autoantibodies improves prediction of IDDM in islet cell antibody-positive relatives.

Prediction of insulin-dependent diabetes mellitus (IDDM) is still largely based on islet cell antibodies (ICAs), but it may be improved by combined analysis with other humoral markers. We examined autoantibodies to insulin (IAAs), glutamic acid decarboxylase (GAD), and M(r) 37,000 and M(r) 40,000 fragments of islet antigens (37 and 40 kDa) together with ICA subtypes in 101 family members with ICAs > or = 10 Juvenile Diabetes Foundation units (JDF U) followed for up to 14 years, of whom 18 have developed IDDM. Life-table analysis showed a 43% risk of IDDM within 10 years for those with ICAs > or = 10 JDF U, rising to 53% for those with ICAs > or = 20 JDF U. The risk for ICAs > or = 10 JDF U was 62% in the family members in the youngest age quartile (< 13.2 years) and fell with increasing age to 4% in those > 40.7 years of age (P = 0.03). ICAs > or = 10 JDF U combined with IAAs gave a risk of 84% (P = 0.03 compared with IAA-), and ICAs > or = 10 JDF U combined with GAD antibodies gave a risk of 61% (P = 0.018). The risk for ICAs > or = 10 JDF U with antibodies to 37-kDa antigen was 76% (P < 0.0001). Risk increased with the number of autoantibodies, from 8% for ICAs alone to 88% with > or = 3 autoantibodies (14 cases detected) (P < 0.0001). The increased risk associated with multiple antibodies was observed independent of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Nicotinamide and insulin secretion in normal subjects.

Nicotinamide has been given both before and after clinical onset of Type 1 (insulin-dependent) diabetes mellitus in an attempt to prolong beta-cell survival. Nicotinic acid, structurally similar to nicotinamide, induces insulin resistance and increases insulin secretion in healthy individuals. It is not known if nicotinamide has similar effects. Since insulin secretion, as measured by the acute insulin response to intravenous glucose, is used to predict diabetes and to monitor therapy, the effects of nicotinamide must be established before trials in individuals at high risk of progression to Type 1 diabetes can be interpreted. Intravenous tolerance tests were performed according to the ICARUS standard protocol in 10 healthy, adult subjects (age 32 +/- 5.7 years) before and after 14 days of treatment with nicotinamide 25 mg.kg-1.day-1. The acute insulin response after nicotinamide did not differ from the control study, whether measured as the incremental 0-10 min insulin area (278 +/- 142 vs 298 +/- 130 mU.l-1.10 min-1) or as the 1 +/- 3 min insulin level (78 +/- 39 vs 81 +/- 44 mU/l). The late insulin response was equally unaffected, as were basal insulin (5.2 +/- 1.6 vs 5.6 +/- 2.1 mU/l) and glucose (5.0 +/- 0.4 vs 4.9 +/- 0.2 mmol/l) levels and glucose disposal rates (1.98 +/- 0.88 vs 2.04 +/- 0.68%/min). Nicotinamide does not affect insulin secretion and glucose kinetics in normal subjects, confirming its suitability for trials designed to delay or prevent the onset of Type 1 diabetes.

Adult↗
PubMed1993

Decrease of glomerular hyperfiltration in short-term diabetic adolescents without microalbuminuria.

OBJECTIVE: This study has been designed to follow prospectively the GFR and UAE of young patients with short-term IDDM and normal UAE. RESEARCH DESIGN AND METHODS: The study population consisted of 19 patients with glomerular hyperfiltration and 19 patients with normal GFR, matched for duration of diabetes and age. GFR has been assessed by radioisotopic tracer and UAE by RIA at the beginning of the study and after 30.5 +/- 10.4 mo of follow-up. RESULTS: GFR decreased in the two groups btt delta GFR of patients with glomerular hyperfiltration was greater than delta GFR of patients with normal GFR (0.83 +/- 0.55 vs. 0.28 +/- 0.63 ml.min-1.mo-1; P < 0.01). UAE, BP, and prevalence of microalbuminuria were comparable between the two groups at follow-up. Rate of fall of GFR was positively correlated with initial GFR (r = 0.59, P < 0.001) but not with initial UAE, BP, or changes in HbA1C, UAE, BP, or pubertal development during follow-up. CONCLUSIONS: Investigation of kidney function in children and adolescents with IDDM over a 3-yr follow-up period shows that glomerular hyperfiltration is characterized by a greater decline in GFR without an increased rate of appearance of microalbuminuria, than in patients with normal GFR.

Adolescent↗
PubMed1991

Induction of specific storage organelles by von Willebrand factor propolypeptide.

Endothelial cells store the multimeric adhesive glycoprotein von Willebrand factor (vWf), which promotes the formation of a platelet plug at the site of vessel injury. To investigate the packaging of vWf into the granules called Weibel-Palade bodies, we expressed pro-vWf cDNA and cDNA lacking the prosequence in a variety of cell lines. Storage granules formed only in cells that contain a regulated pathway of secretion. Furthermore, packaging required the prosequence. Pro-vWf, lacking the C-terminal region involved in interchain disulfide bonding, formed granules. We conclude that the signal for storage is universal in that an adhesive glycoprotein can be stored by a hormone-secreting cell; the storage of vWf is independent of its covalent multimeric structure; the unusual rod shape of Weibel-Palade bodies is due to vWf; and the vWf propolypeptide is necessary for the formation of vWf storage granules.

Animals↗
PubMed1991

von Willebrand factor and the endothelium.

Endothelial cells are the principal source of plasma and basement membrane von Willebrand factor (vWF). To arrive at its biologically active multimeric form, vWF undergoes a series of intracellular processing steps. The protein is synthesized as a large precursor pro-vWF, which dimerizes in the endoplasmic reticulum through disulfide bonds located in the carboxyl-terminal portion of the subunit. Only dimers are transported to the Golgi apparatus. Expression of truncated pro-vWF subunits, which lack the last 20 kd, abolishes the requirement for dimerization and thereby allows the monomeric protein to be secreted. Another requirement for intracellular transport from the endoplasmic reticulum is N-linked glycosylation. Inhibition of N-linked glycosylation prevents exit of both the wild-type and the truncated vWF from the endoplasmic reticulum. In the acidic environment of the trans-Golgi and post-Golgi compartments, pro-vWF dimers multimerize by a second set of interchain disulfide bonds. The presence of the vWF propolypeptide and acidic pH conditions are necessary for the multimerization process. The largest vWF multimers are stored in endothelial cell-specific organelles called Weibel-Palade bodies. At the site of vascular injury and inflammation, physiologic secretagogues such as thrombin, fibrin, and histamine may cause release of these large, biologically potent vWF multimers from the Weibel-Palade bodies into the surrounding blood and subendothelium.

Endoplasmic Reticulum↗
PubMed1991

Simultaneous determination of retinol, tocopherols, carotenes and lycopene in plasma by means of high-performance liquid chromatography on reversed phase.

The determination of the vitamins A and E as well as of carotenes and lycopene is important for studies of cardiovascular diseases and cancer. A method for laboratory routine is reported to separate simultaneously retinol, tocopherols, alpha- and beta-carotene, lycopene and beta-cryptoxanthin in human plasma or serum by HPLC on reversed phase starting from one extract. Two detectors with programmable wavelength are used sequentially, a spectrophotometer for the detection of the carotenoids in the visible region and a fluorometer for the assay of retinol and the tocopherols.

Carotenoids↗
PubMed1989

PADGEM protein: a receptor that mediates the interaction of activated platelets with neutrophils and monocytes.

PADGEM (platelet activation dependent granule-external membrane protein) is an integral membrane protein of the alpha granules of platelets and Weibel-Palade bodies of endothelial cells that is expressed on the plasma membrane upon cell activation and granule secretion. Activated platelets, but not resting platelets, bind to neutrophils, monocytes, HL60 cells, and U937 cells. This interaction is inhibited by anti-PADGEM antibodies, PADGEM, and EDTA; anti-GPIIb-IIIa, anti-thrombospondin, anti-GPIV, and thrombospondin produce no effect. Neutrophils and U937 cells, in contrast to Jurkatt cells, contain PADGEM recognition sites, as shown by binding of PADGEM contained in phospholipid vesicles. These results indicate that PADGEM mediates adhesion of activated platelets to monocytes and neutrophils. Therefore, PADGEM shares not only structural but also functional homology with ELAM-1 and MEL-14, members of a new family of vascular cell adhesion molecules.

Antibodies, Monoclonal↗
PubMed1989

PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells.

PADGEM protein (PADGEM), also known as GMP140, is a platelet alpha-granule membrane protein that is translocated to the external membrane after platelet activation. Although the biosynthesis of this protein was originally thought to be confined to megakaryocytes, the synthesis of PADGEM in endothelial cells was recently demonstrated (McEver et al: Blood 70:1974a, 1987). We now describe the subcellular localization of this protein in endothelial cells. Immunofluorescence staining of permeabilized human umbilical vein endothelial cells with KC4, a well characterized monoclonal antibody to PADGEM, showed positively stained elongated structures similar in distribution and shape to Weibel-Palade bodies. Their identity as Weibel-Palade bodies was confirmed by double label immunofluorescence using KC4 and a polyclonal antiserum to von Willebrand factor (vWf), a protein known to be specifically stored in these organelles. All Weibel-Palade bodies were found to contain PADGEM. In contrast to strong perinuclear staining produced with anti-vWf antibodies, no significant perinuclear staining was obtained with KC4, indicating that relatively little PADGEM is present in the endoplasmic reticulum and in the Golgi apparatus. In endothelial cells treated with secretagogues that stimulate vWf release the elongated structures positive for PADGEM disappeared, further identifying these structures as Weibel-Palade bodies. This observation extends the parallels between Weibel-Palade bodies and alpha-granules and suggests a possible functional association between vWf and PADGEM.

Calcimycin↗
PubMedDate not supplied

Prevalence and correlations of early microvascular complications in young type I diabetic patients: role of puberty.

The prevalence and correlates of the early signs of renal, retinal and neurological microvascular complications were evaluated in 317 young patients with type I diabetes mellitus. Microalbuminuria was detected in 11% of patients and appeared to be strongly and positively related to HbA1c (p < 0.01) and less significantly to duration of diabetes (p < 0.02). Retinopathy was detected in 22.7% of patients and it was associated with duration of diabetes (p < 0.001). Peripheral neuropathy was detected in 18.5% of patients and there was a strong association with HbA1c (p < 0.01) and a weaker one with duration of diabetes (p < 0.05). Microalbuminuria was not detected in prepubertal patients while a similar frequency of retinopathy and neuropathy was observed in prepubertal and postpubertal patients. These results suggest that: 1) In short-term type I diabetic patients neuropathy is the most frequent microvascular complication, but after 10 years of diabetes, retinopathy exceeds the other complications; 2) Short-term metabolic control may influence the frequency of neuropathy and microalbuminuria but not retinopathy; 3) Puberty is involved in the appearance of microalbuminuria.

Adolescent↗