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Background: Insulin resistance is defined as an inappropriate high level of plasma insulin required to maintain metabolic homeostasis. It is associated with type 2 diabetes and cardiovascular diseases. The glucose clamp technique is the standard method for the measurement of insulin resistance. However, this method is laborious, expensive and impractical to perform in epidemiological investigations. The homeostasis model assessment (HOMA) has been proposed to assess insulin resistance and secretion, using fasting glucose and insulin concentrations., Aim: To measure insulin resistance using HOMA (HOMAIR) in a population sample from the Metropolitan Region in Chile., Material and Methods: One hundred twenty subjects (59 female) with a normal body mass index and fasting blood glucose were studied. Fasting plasma glucose was measured by a glucose oxidase method and serum insulin was measured by radio immunoassay., Results: Fasting blood glucose was 81.6 +/- 9.4 mg/dl and serum insulin was 9.7 +/- 2.4 microU/ml. Mean HOMA insulin resistance was 1.96 +/- 0.57 (range 0.5 and 3.0)., Conclusions: These HOMA values can be used as reference for Chilean non obese individuals.

Objective: Anti-Sa antibodies have been described to be a highly specific marker for rheumatoid arthritis (RA). We demonstrate the existence of 2 different subsets of anti-Sa antibodies, only one of which is specific for RA. Our objective was to purify the Sa antigen, and to achieve partial characterization of these proteins., Methods: Saline extract and mitochondrial extract from human placenta were used as antigenic sources. Antigens were purified by immunoaffinity chromatography and studied by ELISA and immunoblotting., Results: Three antigenically active bands of 68, 50, and 46 kDa were purified from the saline extract by immunoaffinity chromatography. Two other bands of 29 and 10 kDa that do not react with anti-Sa antibodies were obtained as well. The 68 kDa band was purified from a mitochondrial extract. These bands are not the same as other known mitochondrial autoantigens such as M2, M4, or M9. The amino terminal sequence of the 68 kDa Sa band is DEPKXEVP. The sequence of the 68 kDa Sa band is not compiled in the databases we searched, as either aminoterminal or internal sequence. Antibodies to 50/46 kDa anti-Sa bands detected by immunoblotting were highly specific for RA, while the 68 kDa antigen reacted in ELISA with sera from patients with RA and systemic lupus erythematosus, the latter showing a marked increase in features of RA. Antibodies directed against the 68 and 50/46 kDa Sa bands fluctuated with time, the 50/46 kDa anti-Sa antibodies present during the active period of the disease, and the 68 kDa anti-Sa antibodies during the remission period., Conclusion: At least 2 subsets of autoantibodies are present in anti-Sa sera, one directed against a 68 kDa Sa protein and another to the typical 50/46 bands of the Sa system.

Twin and family studies have demonstrated that a large part of a population's variance in bone mineral density (BMD) is attributable to genetic factors. A polymorphism in the collagen type I alpha1 (COLIA1) gene has recently been associated with low bone mass and fracture incidence. We analyzed the relationship between COLIA1 gene polymorphism, lumbar spine and hip BMD, and fracture prevalence in a population of 319 postmenopausal women classified by WHO standards, including 98 nonosteoporotic women (NOPW) and 221 osteoporotic postmenopausal women (OPW), divided into 139 osteoporotic women without fracture (OPWnF) and 82 osteoporotic women with fracture (OPWwF). The COLIA1 genotype was assessed by polymerase chain reaction and BalI endonuclease digestion. Genotype frequencies for the total group were 49.2% GG homozygotes, 39.5% GT heterozygotes, and 11.3% TT homozygotes. We found significant differences in the percentage of homozygous TT between NOPW and OPW (6.1% and 13.6%, respectively). Significantly, the occurrence of genotype TT in OPWnF was 6.2%, and 28% in OPWwF. We observed no associations between the COLIA1 genotype and lumbar spine and hip BMD. The prevalence of fractures varied significantly by genotype: GG, 26.1%; GT, 15.9%; and TT, 58.3%. Logistic regression analysis of fracture prevalence showed that, for prevalent fractures, the women with the TT genotype had a 5.9-fold increased risk when compared with the other genotypes (GG + GT). When prevalence was adjusted for age, body mass index, and BMD, the fracture risk was 4.8 for the TT group vs. the genotype GG, whereas it was 0.6 for the GT genotype. In conclusion, we found the COLIA1 Sp1 TT genotype to be associated with an increased fracture risk in postmenopausal women. Interestingly, this genotype-dependent risk could not be explained completely by BMD differences.

The role of the switch II region in the conformational transition of activation of Ha-ras-p21 has been investigated by mutating residues predicted to act as hinges for the conformational transition of this loop (Ala59, Gly60, and Gly75) (Díaz JF, Wroblowski B, Schlitter J, Engelborghs Y, 1997, Proteins 28:434-451), as well as mutating the catalytic residue Gln61. The proposed mutations of the hinge residues decrease the rate of the conformational transition of activation as measured by the binding of BeF3- to the GDP-p21 complex. Also, the thermodynamic parameters of the binding reaction are altered by a factor between three and five, depending on the temperature. (Due to changes in activation and reaction enthalpies, partially compensated by entropy changes.) The control mutation Q61H in which only the catalytic residue is changed has only a limited effect on the kinetic rate constants of the conformational transition and on the thermodynamic parameters of the reaction. The fact that mutations of the hinge residues of the switch II region affect both the binding of the phosphate analog and the conformational transition of activation indicates that the switch II is implicated both in the early and the late states of the transition.

Background: The early detection of peripheral neuropathy in diabetics is important since it is the main risk factor for lower limb trophic lesions in diabetics., Aim: To assess the relationship between feet thermal sensation threshold and metabolic control in ambulatory non-insulin-dependent diabetics., Patients and Methods: A random sample of 34 non-insulin-dependent diabetics followed for more than five years in a special clinic, out of 368 patients, was selected. Warmth sensation thresholds were measured in the dorsum of both feet using a MSTP-III thermostimulator. The average value of all glycosylated hemoglobins obtained during the 9.7 +/- 5.3 years of follow up for each patient was calculated. A multiple stepwise regression analysis was performed between thermal sensation as the dependent variable and glycosylated hemoglobin, fasting blood glucose, age and diabetes duration., Results: The regression model disclosed glycosylated hemoglobin as the only independent predictor of warmth sensation threshold (partial r = 0.385; p = 0.043). Fifteen diabetic patients with good metabolic control, defined as those with a mean glycosylated hemoglobin of less than 9.5%, had a warmth sensation threshold of 35.6 +/- 3.7 degrees C, whereas 19 diabetics with a had control (glycosylated hemoglobin > or = 9.5%) had a threshold of 39 +/- 3.8 degrees C (p = 0.017)., Conclusions: In this group of diabetics, there is a relationship between the severity of distal polyneuropathy and the metabolic control, assessed with glycosylated hemoglobin levels.

The so called mixed connective tissue disease (MCTD), continues to be a controversial entity, while some authors considered it a good characterized disease, others think that is an undifferentiated connective tissue disease. OBJECTIVE. To analyse the clinical and serological evolution of a group of patients diagnosed of MCTD, with particular consideration to the meaning of anti-nRNP and anti-Sm antibodies. METHOD. We have studied 20 patients diagnosed of MCTD and 112 with systemic lupus erythematosus (SLE). Anti-nRNP and anti-Sm antibodies were detected through counter immunoelectrophoresis, immunoblotting and ELISA. RESULTS. After an average time of evolution of 10 years, 70% (14/20) of the patients diagnosed of MCTD fulfill criteria for SLE (6 cases), scleroderma (6 cases) or polymyositis (2 cases). Anti-nRNP response is persistent, directed mainly against the 70 Kd and A-nRNP polypeptides and qualitatively higher in MCTD in SLE (absorbencies 2.64 vs 1.25. The immunoblotting test detected anti-Sm antibodies in 5 patients (25%) and ELISA test in 14 (70%). CONCLUSIONS. Clinical and serological evolution suggest that MCTD is an undifferentiated connective tissue disease. Anti-nRNP antibodies are characteristic, although anti-Sm antibodies can be detected with ELISA regardless whether on not patients fulfill SLE criteria.

Objective: The immune response to the Ro(SSA) antigen is heterogeneous. Anti-Ro(SSA) positive sera may contain antibodies recognizing either a 60 or a 52 kDa polypeptide component of the Ro(SSA) particle. Thus we sought to determine the profile of anti-Ro(SSA) antibodies defined by immunoblotting in patients with rheumatic diseases., Methods: Immunoblotting against human placenta extract and ELISA against recombinant Ro(SSA) antigen as confirmatory tests were done to detect anti-Ro(SSA) antibodies in 563 sera from patients with systemic lupus erythematosus (SLE). Sjögren's syndrome (SS), rheumatoid arthritis (RA) and other connective tissue diseases., Results: Anti-52 kDa antibodies were more common in primary patients with SS (9/22; 40.9%) than in patients with SLE (29/135; 21.4%) or patients with RA (7/315; 2.2%). Anti-60 kDa antibodies were more frequent in patients with SLE (26/135; 19.2%) than in patients with primary SS (2/22; 9%) or RA (17/315; 5.3%). None of the 22 patients with primary SS had only antibodies to the 60 kDa polypeptide. Among the 153 patients whose sera were positive by ELISA, 73 (47.7%) were negative by immunoblotting. The most frequent diagnoses in these sera were RA and SLE. The anti-52 kDa sera had higher optical density values compared to anti-60 kDa sera., Conclusions: Our observations indicate the existence of qualitatively and quantitatively different anti-Ro(SSA) responses in the rheumatic diseases. The major responses are anti-52 kDa antibodies in primary SS, both anti-52 and anti-60 kDa antibodies in SLE, and anti-60 kDa antibodies in RA and other connective tissue diseases.

Energy expenditure was measured in 55 patients with acute pancreatitis, during variable periods ranging from 1 to 5 weeks and it was compared with estimated energy expenditure according to Harris Benedict equations. Patients with severe pancreatitis had similar measured and measured/estimated energy expenditure rations, compared to those with mild pancreatitis (1678 +/- 349.6 kcal/day and 1.1 +/- 0.19 vs 1632 +/- 383 kcal/day and 1.06 +/- 0.19). There was a high dispersion of measured/estimated rations (0.67 - 1.7) that precluded the calculation of a reliable energy expenditure correction factor for this disease. It is concluded that energy expenditure must be measured and not estimated, when planning an adequate nutritional support in patients with acute pancreatitis.

With the aim to analyze the prognostic value of anti-RNP/Sm and anti-Ro/La antibodies (Ab) in lupus nephropathy, we have studied through Contraimmunoelectrophoresis (CIE) and Immunoblotting (IB) the serum of 63 patients diagnosed of systemic lupus erythematosus. Mean age was 36.5 years (15-71) and 90% were females. We have classified the patients into three subgroups: I, 25 patients without nephropathy; II, 26 patients with evidence of nephropathy (persistent proteinuria and/or microhematuria) and normal renal function; and III, 12 patients with renal failure (servu creatinine > 1.5 mg/dl). 21 patients had kidney biopsy. IB allows to identify a higher number of positive serum, specially in the case of anti-RNP (7.9% CIE vs 28.5% IB) and anti-Sm antibodies (6.3% vs 30.1%). Prevalence of anti-RNP Ab is lower in subgroup III (32% I vs 34% II vs 8% III) (p > 0.05). Anti-Sm Ab are more frequent in group II and are not associated with renal failure (16% vs 54% vs 8%) (p > 0.05). Anti-Ro Ab are related with the absence of nephropathy (52% vs 15% vs 0%) (p < 0.05). We conclude that IB is more sensitive than CIE in the detection of these Ab and its use in Systemic Lupus Erythematosus permits to identify patient subgroups with lesser risk to develop renal failure. Even though our data are preliminary, we suggest that the detection of anti-RNP/Sm and/or anti-Ro/La antibodies are a good prognostic factor in lupus nephropathy.