Biomedical subjects
H Reyes
Publications and source records attributed to H Reyes.
Multireactive pattern of serum autoantibodies in asymptomatic individuals with immunoglobulin A deficiency.
Selective immunoglobulin A (IgA) deficiency (sIgAD) is associated with certain autoimmune states. Increased production of autoantibodies and eventual development of overt autoimmune disease are related in part to genetic and environmental factors as well as to the immune deficiency. We surveyed serum specimens from 60 healthy subjects with sIgAD for the presence of 21 different autoantibodies by enzyme-linked immunosorbent assays. The frequencies of 16 autoantibodies were higher in sIgAD patients than in normal healthy controls. Autoantibodies to Jo-1 (28%), cardiolipin (21%), phosphatidylserine (20%), Sm (15%), asialo-GM1 (21%), sulfatide (32%), sulfoglucuronyl paragloboside (11%), and collagen type I (10%) were detected at high frequencies in comparison to those of normal healthy controls. Many of the serum samples were multireactive (i.e., exhibited binding to more than two autoantigens). Forty percent (24 of 60) of sIgAD serum samples reacted against six or more autoantigens; 10% (6 of 60) of sIgAD serum samples were not reactive with any of the 21 autoantigens. Three percent (7 of 209) of consecutive serum samples submitted for autoimmune antibody analysis that were positive for autoantibodies were from patients with IgA deficiency. Our finding of an increased frequency of autoantibodies in sIgAD patients supports the notion of polyclonal stimulation by repeated environmental stimuli as an etiologic mechanism. Alternatively, the increased frequency may be caused by a dysregulation of the immune response in such individuals. The mere detection of autoantibodies cannot predict whether a subject with sIgAD will develop an autoimmune disease or determine which specific disease will emerge.
[Can a selenium deficiency affect the pathogenesis of cholestasis in pregnancy?].
UNLABELLED: In search of an environmental factor which modulates the expressivity of cholestasis of pregnancy and explains the seasonal and annual variations observed in Finland and Chile, the authors measured selenium (Se) concentration in the plasma and erythrocytes by atomic absorption spectrophotometry and the activity of the glutation peroxidase enzyme dependent on Se (GSH-Px) by a spectrophotometric method in 10 patients with cholestasis of pregnancy, 22 normal pregnant women, 43 non pregnant women and in 15 men, all of whom had normal weight/height, and similar ages, ethnic and geographic origin. Blood samples were obtained weekly from the pregnant women during the third trimester and 24-72 hours postpartum. RESULTS: In non pregnant women and in men plasma Se was 0.83 +/- 0.02 mumol/l (range 0.6-1.2) and the GSH-Px activity was 306 +/- 5 U/L (range 203-459). Both parameters were correlated and were similar to those of other populations whose ingestion of Se is low (Finland, New Zealand, and certain regions of China). In normal pregnant women studied between weeks 20 and 32, the plasma Se and GSH-Px activity were lower than in non pregnant women (0.71 +/- 0.02 mumol/l and 260 +/- 5 U/l, respectively) with both progressively decreasing at the end of pregnancy and rapidly recovering post partum. The erythrocytic GSH-Px activity was similar in normal pregnant women than in non pregnant women (27.7 +/- 0.8 versus 28.1 +/- 0.6 U/g Hb). In patients with cholestasis of pregnancy, plasma and erythrocytic Se and GSH-Px activity were lower than in normal pregnant women (p < 0.05 in similar stages of pregnancy).(ABSTRACT TRUNCATED AT 250 WORDS)
Is dietary erucic acid hepatotoxic in pregnancy? An experimental study in rats and hamsters.
The hypothesis that dietary erucic acid may contribute to the pathogenesis of intrahepatic cholestasis of pregnancy has been examined in pregnant rats and hamsters after prolonged feeding of diets containing 25% rapeseed oil rich in erucic acid (40% of fatty acids) or corn oil, without erucic acid. Both dietary oils were well tolerated, although weight gain was 17% to 20% less in animals receiving rapeseed oil. Rats and hamsters were studied on the last day of pregnancy and compared with age- and diet-matched nonpregnant animals. Histological examination showed no major morphologic abnormalities in liver, heart, kidneys, and adrenals. Similar microscopic deposits of fat were found in the livers and hearts of pregnant hamsters of both dietary groups. Chromatographic analysis of fatty acids in liver, heart, and kidney homogenates of hamsters and in isolated rat liver cells reflected the fatty acid composition of the dietary oils: oleic (18:1) and linoleic (18:2) acids were among the predominant fatty acids. Erucic acid was found in a higher proportion in the heart (14% by weight of total fatty acids) than in the liver (3%) and kidneys (3%) of animals fed rapeseed oil. Bile flow and biliary lipid composition was similar in rats and hamsters fed rapeseed or corn oil. Bile flow tended to be less in pregnant than in nonpregnant animals. Pregnant hamsters fed rapeseed oil tended to have the lowest bile flow. The lithogenic index of bile was slightly decreased in pregnant rats and increased in pregnant hamsters, although these proportional changes were similar for both diets. In all circumstances the lithogenic index remained below a value of 1.(ABSTRACT TRUNCATED AT 250 WORDS)
Laboratory diagnosis of antiphospholipid syndromes.
The search for clinical outcomes associated with antiphospholipid antibodies (aPL) has been ongoing for a decade. This article focuses on the clinical use of tests for the detection of aPL. A review of the current thinking regarding the pathophysiology of antiphospholipid syndromes is relevant to the discussion of different aPL assays and methodologies. The value of aPL testing in specified patient populations is analyzed.
Frequency of biochemical hypothyroidism in sera referred for autoantibody testing.
We examined sera submitted for autoantibody testing for thyroid microsome antibodies (TMA), elevated thyroid-stimulating hormone (TSH), and free thyroxine concentrations. The frequency of TMA in antinuclear antibody-positive sera was higher (19%) than that in antinuclear antibody-negative sera (12%). Elevated TSH concentrations in serum and subnormal thyroxine concentrations in serum were associated with the presence of TMA; TMA titer and the frequency of elevated TSH concentrations were also associated with the presence of TMA.
[Phylogenetic vision of bile acids].
Bile acids are the most important solutes of bile: they are essential in cholesterol degradation, solubilization and excretion; they are determinants of bile flow and secretion; and their role is crucial in the intestinal absorption of lipids and lipid soluble vitamins. In amphibia and in cartilaginous fish, the 27C cholestane molecule is hydroxylated to alcohols. In birds, the terminal 27C-OH group is oxydated to cholestanoic acids. In vertebrates of a more recent evolutionary origin, the lateral chain is shortened to 24C and oxydated to cholestanoic acids. Further transformations include chemical changes in the cholestane skeleton and in the lateral chain (hydroxylations, dehydroxylations, epimerization, etc). In the intestinal lumen, the saprophytic flora provides enzymes catalysing new changes that originate "secondary" bile acids. During entero-hepatic circulation, another variety of bile acids appear, commonly termed "tertiary" bile acids. A recent study of Lee R Hagey characterized bile acid composition of over 600 species of vertebrates, showing that bile acid composition of bile has been the subject of an interesting evolutionary phenomenon and that it is a chemical marker of biodiversity in vertebrates.
Management of intrahepatic cholestasis in pregnancy.
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Identification of the Ah receptor nuclear translocator protein (Arnt) as a component of the DNA binding form of the Ah receptor.
The Ah (dioxin) receptor binds a number of widely disseminated environmental pollutants, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polycyclic aromatic hydrocarbons, and mediates their carcinogenic effects. The ligand-bound receptor activates Cyp 1a1 gene transcription through interaction with specific DNA sequences, termed xenobiotic responsive elements (XREs). The Ah receptor nuclear translocator protein (Arnt) is required for Ah receptor function. Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. Furthermore, Arnt and the ligand-binding subunit of the receptor were extracted as a complex from the nuclei of cells treated with ligand. Arnt contains a basic helix-loop-helix motif, which may be responsible for interacting with both the XRE and the ligand-binding subunit.
Effects of ursodeoxycholic acid in patients with intrahepatic cholestasis of pregnancy.
The efficacy and safety of ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy was investigated in an open pilot study. Five patients received 1 gm/day of ursodeoxycholic acid during 20 days and another three patients received two identical periods of treatment separated by a 14-day interval free of the drug. Pruritus and serum levels of total bile salts and glutamic-pyruvic transaminase improved significantly during treatment with ursodeoxycholic acid. In the three patients who received two periods of treatment with ursodeoxycholic acid, pruritus and the laboratory alterations relapsed in the second week after the drug was discontinued, but they improved again when ursodeoxycholic acid was readministered. No adverse reactions were detected in the mothers or in their babies. All newborns were thriving normally during a follow-up period that lasted 5 mo after delivery. It is concluded that UDCA appears to be safe when administered in late pregnancy; its promising efficacy in the treatment of intrahepatic cholestasis of pregnancy should now be confirmed in controlled clinical trials.
High-dose vitamin C therapy for extensive deep dermal burns.
We studied the haemodynamic effects of antioxidant therapy with high-dose vitamin C administration (170 mg/kg/24 h) in guinea-pigs with 70 per cent body surface area deep dermal burns. The animals were divided into three groups of six animals each. Group 1 was resuscitated with Ringer's lactate solution according to the Parkland formula; group 2 with 25 per cent of the Parkland formula with vitamin C; and group 3 with 25 per cent of the Parkland formula without vitamin C. There were no significant differences in heart rates or in blood pressures between the groups throughout the 24-h study period. Group 3 showed significantly higher haematocrit values at 3 h postburn and thereafter as compared with those of group 2. The cardiac output values of group 2 were significantly higher than those of group 3, but equivalent to those of group 1. The water content of the burned skin in group 2 was significantly lower than that in the other groups, indicating that increased postburn capillary permeability was minimized by the administration of vitamin C. With adjuvant high-dose vitamin C administration, we were able to reduce the 24-h resuscitation fluid volume from 4 ml/kg/per cent burn to 1 ml/kg/per cent burn, while maintaining adequate cardiac output.
Epomediol ameliorates pruritus in patients with intrahepatic cholestasis of pregnancy.
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An MspI RFLP in the human ARNT gene, encoding a subunit of the nuclear form of the Ah (dioxin) receptor.
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[Symptomatic effect of epomediol in patients with cholestasis of pregnancy].
Epomediol is a terpenoid that prevents and reverses cholestasis induced by ethinylestradiol in the rat, apparently by improving liver cell membrane fluidity. Assuming that the pathogenesis of intrahepatic cholestasis of pregnancy (ICP) is related with increased estrogen levels, we studied the effects of epomediol in this disease. Patients hospitalized due to ICP received epomediol 900 mg/day (n = 7), or 1,200 mg/day (n = 4) orally, during 15 days. Biochemical parameters of liver dysfunction (serum bilirubin, bile salts, aminotransferase, alkaline phosphatases) were not modified during nor after epomediol administration. The severity of pruritus was significantly reduced in comparison to pretreatment status, with both doses of epomediol. A greater amelioration of pruritus was observed in patients treated with epomediol 1,200 mg/day than in patients who received 900 mg/day (to 20.7 +/- 6.2, as percent of pre-treatment severity score, versus 48.8 +/- 7.5 respectively; p < 0.05). After epomediol administration was stopped, pruritus relapsed in 6 patients; 3 of them had received the higher drug dose. After delivery, pruritus vanished and liver function tests returned to normal, in all patients. No adverse effects attributable to the drug were observed in the mothers or in their babies. The beneficial effect of epomediol on pruritus in patients with ICP appeared greater in this study than that observed recently in similar patients who received a placebo.
[Can we improve primary adult medical care?].
In Chile, primary medical care of adult patients is delivered mostly by young physicians, who work with little or insufficient interaction with their referral centers and with the main teaching hospitals. These physicians have no defined expectancies of a professional career in the field of primary care and they generally recent the lack of a programmed post-graduate education. After 3 to 5 years as general practitioners, some of them may have access to a formal teaching program to become specialists in internal medicine but, as in many other countries, it usually becomes a transit stage leading them to a subspecialty. This position paper adopted most of the proposals raised in a recent meeting, with the participation of universities, scientific and medical organizations, and the Ministry of Health, and modifies some of them. Because financial limitations may hinder the possibility of residency training programs in primary care internal medicine (as established in the USA), primary care of adults is proposed to be organized as a basic medical specialty, with formal teaching activities designed, delivered or supervised by the universities and medical scientific societies, and given as "credits" to be taken along 3 to 5 years. Simultaneously, outpatient care facilities should be improved, in the hospitals and in community units, allowing them to be used in under-graduate and post-graduate teaching programs. General practitioners, focused in adult patients, would receive a new professional status with the stimulus of a specific program of continuing medical education.
The spectrum of liver and gastrointestinal disease seen in cholestasis of pregnancy.
A mild form of intrahepatic cholestasis is an infrequent complication of pregnancy, with a spontaneous cure almost immediately after delivery and that often recurs in future pregnancies. Pruritus alters maternal well-being, and a subclinical steatorrhea may impair the patient's nutritional status; otherwise, it is a mild disease in the mother, and no maternal mortality has been attributed to it. In contrast, cholestasis of pregnancy is often identified as a risk of increased perinatal morbidity and mortality. The cause of cholestasis of pregnancy is unknown. A hereditary predisposition seems to induce in the maternal liver an abnormal reaction to female sex hormones, but some still unidentified environmental (possibly dietary) factor could also be involved in the pathogenesis of the disease. Pruritus, but not the biochemical alterations, can be alleviated by the use of cholestyramine, silymarin, or epomediol. Ursodeoxycholic acid has been beneficial in pruritus and in liver function tests; an improvement in fetal prognosis should be evaluated in future controlled studies.
Cloning of a factor required for activity of the Ah (dioxin) receptor.
The aryl hydrocarbon (Ah) receptor binds various environmental pollutants, such as polycyclic aromatic hydrocarbons, heterocyclic amines, and polychlorinated aromatic compounds (dioxins, dibenzofurans, and biphenyls), and mediates the carcinogenic effects of these agents. The complementary DNA and part of the gene for an 87-kilodalton human protein that is necessary for Ah receptor function have been cloned. The protein is not the ligand-binding subunit of the receptor but is a factor that is required for the ligand-binding subunit to translocate from the cytosol to the nucleus after binding ligand. The requirement for this factor distinguishes the Ah receptor from the glucocorticoid receptor, to which the Ah receptor has been presumed to be similar. Two portions of the 87-kilodalton protein share sequence similarities with two Drosophila proteins, Per and Sim. Another segment of the protein shows conformity to the consensus sequence for the basic helix-loop-helix motif found in proteins that bind DNA as homodimers or heterodimers.
Genetic and molecular analysis of the Ah receptor and of Cyp1a1 gene expression.
The Ah receptor is a soluble protein complex that mediates carcinogenesis by a wide range of environmental pollutants, including polycyclic aromatic hydrocarbons, heterocyclic amines, and polychlorinated aromatic compounds. The best understood activity of the receptor concerns its role in the induction of cytochrome P450IA1. We undertook a somatic cell genetic analysis of P450IA1 induction using the mouse hepatoma cell line, Hepa-1. Clones of Hepa-1 were isolated that are defective in induction of P450IA1. Evidence was obtained that the clones are mutational in origin. Cell fusion experiments demonstrated that a few of the mutants are dominant, while the majority are recessive. The dominant mutants were shown to synthesize a repressor of P450IA1 transcription. The recessive mutants were assigned to 4 complementation groups (probably corresponding to 4 different genes). Complementation group A corresponds to the P450IA1 structural gene. Mutations in the B, C and D genes all affect functioning of the Ah receptor. A 'reverse selection procedure', whereby cells that express P450IA1 inducibility can be selected from a majority population of cells lacking inducibility, was developed. The reverse selection procedure was used to isolate transfectants of representative recessive mutants in which the mutational defects are complemented by exogenously applied genomic DNA. A human DNA-derived transfectant of a C- mutant was used to clone the human C gene. The C gene is not the ligand-binding subunit of the Ah receptor but is a protein that is required for translocation of Ah receptor-ligand complexes from cytoplasm to nucleus. In analogous experiments the dominant gene from one of the dominant mutants was transfected into wild-type Hepa-1 cells. Success in transfecting the dominant gene should provide the means for cloning it.