RESUMEN
Binding proteins (BP) for growth hormone (GH) have recently been discovered in human plasma. The main BP is related to the GH receptor and probably corresponds to the extracellular portion of the receptor. The BP influence several aspects of GH homeostasis and action. Their level and activity in blood, therefore, become important variables in overall GH physiology. However, to date little is known about the regulation of GH-BP in health and disease. To gain initial information about this point, GH-BP activity was examined in the plasma of 124 subjects with various physiologic and pathologic conditions. The conditions were selected to provide basic physiologic data (men, women, children, age, pregnancy and to investigate key disease states attended by abnormal GH physiology (liver cirrhosis, uremia, infection, acromegaly). A standardized GH binding assay was used to measure BP activity as an index of BP levels. Both the principal, high affinity BP (peak II) and the minor, low affinity BP (peak I) showed considerable individual variation in all groups. Neonates had the lowest levels of both BPs, but by the age of 1 year the levels had increased and remained fairly stable through the seventh decade. In males but not females between the ages of 1 and 20 years, the main (peak II) BP showed a slight upward trend, whereas the minor (peak I) BP declined moderately. Patients with cirrhosis showed the most variation in both BP, and uremic patients demonstrated decreased peak II, but not peak I, binding. Neither BP was affected in acromegaly. We conclude that BP activity in plasma is well conserved in most conditions, but substantial individual variability exists. BP activity increases dramatically during the first year of life.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Proteínas Portadoras/sangre , Enfermedad/sangre , Hormona del Crecimiento/sangre , Adulto , Niño , Femenino , Sangre Fetal/análisis , Humanos , Recién Nacido , Cinética , Masculino , Embarazo , Unión Proteica , Valores de ReferenciaRESUMEN
The serum complement profile of patients with systemic or discoid lupus erythematosus, synovitis, vasculitides, certain recurrent or chronic skin rashes, recurrent or fulminant infections, particularly with Neisseria, may reveal homozygous deficiencies of complement components causally related to the illness. The nephritis of systemic lupus erythematosus (SLE) is often accompanied by a distinctive complement profile which indicates classical pathway activation and which can be used as an index of the success of treatment. In membranoproliferative glomerulonephritis (MPGN), the hypocomplementemia may reflect classical pathway activation in type I, the nephritic factor of the amplification loop in type II, or a nephritic factor activating terminal components in type III. In acute poststreptococcal glomerulonephritis, the cause of the hypocomplementemia is not known but the profile usually differs from that of MPGN or SLE. In these acquired hypocomplementemias, the profile supplements the renal biopsy in providing diagnostic information.
Asunto(s)
Biomarcadores/sangre , Proteínas del Sistema Complemento/análisis , Enfermedad/sangre , Proteínas del Sistema Complemento/deficiencia , Proteínas del Sistema Complemento/genética , Humanos , Valores de ReferenciaRESUMEN
Considerable controversy exists concerning the assessment of thyroidal state in critically ill patients with decreased serum T4 and T3 concentrations, in part because serum free T4 values are often low in such patients no matter what method of measurement is used. We developed an ultrafiltration method to measure free T4 and free T3 in undiluted serum and compared the results with those obtained using a standard equilibrium dialysis method to measure free T4 and T3. In 30 consecutive intensive care unit (ICU) patients, serum free T4 values were similar to or higher than those in 12 normal subjects by both methods in most patients and were clearly distinguishable from those in hypothyroid patients. The serum total T4 concentrations in these patients ranged from 12.9-131.3 nmol/L (mean, 68.2; normal mean, 115.8). Free T4 by equilibrium dialysis was highly correlated with free T4 by ultrafiltration in the ICU group (r = 0.91; P less than 0.001). Serum free T3 levels, however, whether measured by equilibrium dialysis or ultrafiltration, were decreased in the ICU patients, confirming other reports of lowered free T3 in critically ill clinically euthyroid patients. Our findings suggest that the use of equilibrium dialysis of undiluted serum or ultrafiltration to measure serum free T4 concentrations will distinguish euthyroid hypothyroxinemic ICU patients from those with hypothyroidism.
Asunto(s)
Enfermedad/sangre , Tiroxina/sangre , Adulto , Anciano , Anciano de 80 o más Años , Cromatografía en Papel , Diálisis , Femenino , Humanos , Hipertiroidismo/sangre , Hipotiroidismo/sangre , Masculino , Persona de Mediana Edad , Triyodotironina/sangre , UltracentrifugaciónRESUMEN
The liver manufactures albumin at a massive rate and decreases production in times of environmental, nutritional, toxic and trauma stress. Osmotic pressure is a basic evolutionary regulatory factor, and hormonal control over albumin production has been demonstrated. Where and why new or old albumin is degraded are questions which have not been clarified, although the vascular endothelium may well be the degradative site. Albumin is important as a transport protein, as a measure of evolution and as a model to study secretion following synthesis without the intervening steps of glycosylation. Investigations as to how this protein enters the endoplasmic membrane may well answer some of the questions concerning signal peptide insertion (288). The role of the urea cycle intermediate ornithine and its participation in polyamine synthesis, which has a positive effect on albumin synthesis, is under study. Likewise, the inverse relation between acute-phase protein synthesis and albumin synthesis regulated by interleukin 1 and other cytokines will merit further study. These are a few of the concepts which will be tested in the future.
Asunto(s)
Albúmina Sérica , Envejecimiento/sangre , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Fenómenos Químicos , Química , Enfermedad/sangre , Etanol/farmacología , Variación Genética , Hormonas/fisiología , Humanos , Membranas Intracelulares/metabolismo , Cirrosis Hepática Experimental/metabolismo , Albúmina Sérica/metabolismo , Albúmina Sérica/fisiología , Albúmina Sérica/uso terapéutico , Estrés Fisiológico/sangre , TemperaturaRESUMEN
Serum and red cell ferritin were determined in a heterogeneous group of 59 patients with chronic disease undergoing a bone marrow biopsy. There was very little correlation between serum and red cell ferritin (r = 0.53). Although serum ferritin increased in relation to increased bone marrow iron stores, only 1 out of 8 patients with absent marrow iron stores and none of 8 patients with reduced marrow iron stores had a decreased serum ferritin. In contrast, 6 of 8 patients with absent iron stores had a reduced red cell ferritin concentration. There was no significant difference between the mean red cell ferritin of the patients with reduced, normal and mild-moderately increased marrow iron stores (30, 26 and 34 ag/cell). Red cell ferritin was decreased in 78% of a group of 32 patients with a low mean cell volume. In the patients studied, red cell ferritin was a better indicator of absent iron stores than serum ferritin. However, red cell ferritin did not detect a reduction in the iron status until the marrow iron stores were completely depleted. Apparently, during normal erythropoiesis the primitive erythroblasts continue to take up iron irrespective of the amount of iron available in the stores.
Asunto(s)
Médula Ósea/metabolismo , Enfermedad/sangre , Eritrocitos/metabolismo , Ferritinas/sangre , Hierro/metabolismo , Adolescente , Adulto , Anciano , Enfermedad Crónica , Enfermedad/metabolismo , Eritrocitos/patología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Development of a simple and reliable method to determine the lipid peroxide level in human serum or plasma has made it possible to survey the levels in human diseases. Since in some human diseases lipid peroxides are increased in various organs or tissues and leak into the bloodstream, the increased lipid peroxide level in the blood aids the diagnosis of such diseases. Furthermore, determination of the level provides useful information as to their prognosis, since the increased lipid peroxides in the blood primarily attack the endothelial cells of vessels and then intact organs or tissues as well. The present paper describes a method to determine the lipid peroxide level in human serum or plasma and its profile of change in several human diseases. Intervention of lipid peroxides in the pathogenesis of certain diseases is also mentioned.
Asunto(s)
Enfermedad/metabolismo , Peróxidos Lipídicos/sangre , Enfermedad/sangre , Humanos , Valores de ReferenciaRESUMEN
The simple spectroscopic measurement of diene conjugation has long been an established but somewhat problematic marker of free-radical activity in biological systems. The main diene-conjugated compounds in human tissues and tissue fluids have now been identified as esters of octadeca-9,11-dienoic acid (18:2(9,11)), a non-peroxide isomer of linoleic acid (18:2(9,12)); and a range of high-performance liquid chromatographic methods has been developed for their detection and measurement. Significant abnormalities of phospholipid-esterified 18:2(9,11) have been found in the serum of chronic alcoholics and in paraquat poisoning and of non-esterified 18:2(9,11) in lipolytic states. The phospholipid-esterified 18:2(9,11) is increased in the bile of patients with pancreatic disease. In exfoliated cells from the cervix uteri an abnormal molar ratio between phospholipid-esterified 18:2(9,11) and 18:2(9,12) may prove to be the most sensitive biochemical marker of precancerous change.
Asunto(s)
Enfermedad/sangre , Ácidos Linoleicos/sangre , Peróxidos Lipídicos/sangre , Radicales Libres , Humanos , Ácido LinoleicoRESUMEN
It has been established that the pyrogallol autoxidation method for the estimation of the activity of superoxide dismutase (SOD) (EC 1.15.1.1) is superior in precision and sensitivity to a superoxide-generating method (NADH/phenazine methosulfate linked to nitroblue tetrazolium reduction). Reference intervals were established in an urban population in the Far East for SOD activity in erythrocytes using the pyrogallol method, and for glutathione peroxidase (GSH-Px) (EC 1.11.1.9) activity in erythrocytes using a standard glutathione reductase-linked method. On this basis, erythrocyte SOD activities were significantly (P less than 0.05) depressed in cases of visceral cancer, acute myocardial infarct, congestive heart failure, respiratory failure, chronic renal failure, and diabetes mellitus, but within the reference interval in cases of lung cancer and asthma. Erythrocyte GSH-Px activity was significantly (P less than 0.05) depressed in cases of diabetes mellitus and chronic renal failure but elevated in respiratory failure and asthma. GSH-Px and SOD activities were well correlated in patients but not in the reference population.
Asunto(s)
Enfermedad/sangre , Eritrocitos/enzimología , Glutatión Peroxidasa/sangre , Oxígeno/sangre , Superóxido Dismutasa/sangre , Humanos , Presión Parcial , Valores de ReferenciaRESUMEN
Depressed thyroid hormone levels are commonly found in sick patients. Low serum testosterone concentrations have also been described in men suffering from a number of illnesses. To investigate whether this might be a non-specific marker of illness, various endocrine parameters were measured in 30 male patients in a general medical ward. Patients were suffering from a wide spectrum of medical disorders and were not receiving drugs known to affect endocrine function. Results were compared with a healthy age-matched control group. Serum testosterone concentrations (mean +/- SE) were low in the patient group (8.9 +/- 1.1 vs. 18.2 +/- 1.4 nmol/l, p less than 0.001), correlated significantly with serum T3 levels but were not related to prognosis. Half the patients had testosterone levels below the normal control range. Changes in testosterone concentrations could not be explained on the basis of binding protein changes, hyperprolactinaemia or depressed pituitary secretion of gonadotrophins. Depression of serum testosterone concentrations is a non-specific marker of illness.
Asunto(s)
Enfermedad/sangre , Testosterona/sangre , Adolescente , Adulto , Anciano , Humanos , Hormona Luteinizante/sangre , Masculino , Persona de Mediana Edad , Triyodotironina/sangreRESUMEN
Using a two-site immunoradiometric assay, we measured concentrations of thyrotropin (TSH) in serum of 134 clinically euthyroid subjects, 93 patients with nonthyroidal illness, and 80 patients who were being treated with various drugs. Abnormal concentrations of TSH, free thyroxin, and free triiodothyronine, respectively, were recorded in serum of three (3.2%), 19 (20.4%), and 37 (39.8%) of the patients with nonthyroidal illness and in three (3.8%), five (6.3%), and 10 (12.5%) of the patients taking drugs. TSH could be detected in all patients' serum samples. We conclude that, for most patients without thyroid disease, a basal (i.e., unstimulated) measurement of their TSH concentration in serum will indicate their thyroid status more reliably than will assay of free thyroxin or free triiodothyronine.
Asunto(s)
Enfermedad/sangre , Tirotropina/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pruebas Diagnósticas de Rutina , Quimioterapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radioinmunoensayo/métodos , Pruebas de Función de la Tiroides , Tiroxina/sangre , Triyodotironina/sangreRESUMEN
A syndrome of elevated PRA accompanied by inappropriately low plasma aldosterone (ALDO) levels has been identified in some critically ill patients. To determine whether this phenomenon is due to a disturbance in factors that stimulate ALDO, we measured PRA, angiotensin II (AII), potassium (K+), and ACTH levels in 83 patients admitted to an intensive care unit. In 59 patients, PRA was greater than 2.0 ng/ml X h. Of these, 24 had an ALDO to PRA ratio (ALDO/PRA) below 2 (group I), and 35 had an ALDO/PRA ratio of 2 or more (group II). An ALDO/PRA ratio below 2 was deemed inappropriately low. Despite markedly elevated PRA [34 +/- 12 (+/- SE) ng/ml X h], the group I patients had inappropriately low ALDO levels (19 +/- 5 ng/dL). Patients in group II had significantly higher ALDO levels (48 +/- 6 ng/dL) despite lower PRA (9 +/- 1 ng/ml X h). AII levels were appropriately elevated in group I (39 +/- 26 pg/mL) and significantly greater (P less than 0.5) than those in group II. PRA correlated well with AII in both groups. There were no differences in plasma ACTH or K+ in these 2 groups, and plasma cortisol levels were similarly elevated in both groups of patients. Of 66 consecutively studied patients, 14 (21%) had inappropriate ALDO (group I). Mortality was significantly greater in group I (75%) than in group II (46%; P less than 0.001). In summary, a significant subset (21%) of seriously ill patients have inappropriately low ALDO levels despite elevated PRA. This dissociation is not due to an impairment of AII production or changes in plasma ACTH or K+. This phenomenon is associated with a higher mortality during critical illness. In light of evidence of decreased adrenal androgen secretion during severe illness, this dissociation of renin and aldosterone may represent an additional adrenal adaptation designed to promote cortisol production in critically ill patients.