Biomedical subjects

J J Corrales

Publications and source records attributed to J J Corrales.

At least 19 recordsLinked to original sources

PubMed2006

Androgen-replacement therapy depresses the ex vivo production of inflammatory cytokines by circulating antigen-presenting cells in aging type-2 diabetic men with partial androgen deficiency.

Androgens are considered to have immunomodulatory effects but their cellular mechanisms of action remain largely unknown. In the present study we prospectively analyzed the serial effects of androgen-replacement therapy on both the distribution of peripheral blood lymphocytes, monocytes and dendritic cells as well as on the production of interleukin (IL)-1beta, IL-6 and tumor necrosis factor alpha (TNFalpha) inflammatory cytokines by circulating monocytes and CD33 myeloid, CD16 and plasmacytoid dendritic cell subsets, the most potent antigen-presenting cells (APCs) in type-2 diabetic men with partial androgen deficiency. Analyses were performed before therapy and at 1, 3, 6 and 12 months after treatment with 150 mg testosterone enanthate every 2 weeks in a group of 13 type-2 diabetic men. Our results show for the first time that testosterone-replacement therapy is associated with a reduction or complete abrogation of spontaneous ex vivo production of IL-1beta, IL-6 and TNFalpha by APCs. Meanwhile, the in vitro production of inflammatory cytokines by these cells after stimulation with lipopolysaccharide plus recombinant human interferon-gamma remained unchanged, suggesting that APCs preserve their constitutive machinery to produce inflammatory cytokines under androgen treatment. These results confirm and extend previous observations about the anti-inflammatory effects of androgen therapy on APCs in a new, previously unexplored model of androgen deficiency; namely, aging type-2 diabetic men. A decreased production of inflammatory cytokines by APCs might have important consequences for sex differences in susceptibility to autoimmune diseases, inflammatory response to injury and atheromatosis.

Aged↗

PubMed2004

Testosterone replacement therapy: current trends and future directions.

Male hypogonadism is characterized by abnormally low serum testosterone levels associated with typical symptoms, including mood disturbance, sexual dysfunction, decreased muscle mass and strength, and decreased bone mineral density. By restoring serum testosterone levels to the normal range using testosterone replacement therapy, many of these symptoms can be relieved. For many years, injectable testosterone esters or surgically implanted testosterone pellets have been the preferred treatment for male hypogonadism. Recently, newer treatment modalities have been introduced, including transdermal patches and gels. The development of a mucoadhesive sustained-release buccal tablet is the latest innovation, which will provide patients with an additional option. The availability of new treatment modalities has helped to renew interest in the management of male hypogonadism, highlighting the need to address a number of important but previously neglected questions in testosterone replacement therapy. These include the risks and benefits of treatment in different patient populations (e.g. the elderly) and the need for evidence-based diagnosis and treatment monitoring guidelines. While some recommendations have been developed in individual countries, up-to-date, internationally accepted evidence-based guidelines that take into account national differences in clinical practice and healthcare delivery would optimize patient care universally.

Androgens↗

PubMed2004

Partial androgen deficiency in aging type 2 diabetic men and its relationship to glycemic control.

Aging in the male is associated with both a higher incidence of type 2 diabetes and hypogonadism. However, little information is available about the complex of symptoms and hormonal changes related to partial androgen deficiency in aging (called andropause) in type 2 diabetic men. Here, for the first time, we used a combination of clinical and hormonal criteria to define andropause and to analyze the relationships between the androgen environment and glucose metabolism in 55 type 2 diabetic men (63.6 +/- 7.9 years, mean +/- SD). Low plasma levels of total testosterone (< or =3.4 ng/mL) and free testosterone (< or =11 pg/mL) were found in 20% and 54.5%, respectively, of the diabetic men. The fraction of diabetic men with subnormal levels of total testosterone increased with aging: 14.2% (50 to 59 years), 17.4% (60 to 69 years) and 36% (> 70 years). The corresponding figures for subnormal values of free testosterone were 38%, 69.6%, and 54.5%, respectively. In the whole group of type 2 diabetic men, no significant linear correlations between total or free testosterone with fasting plasma glucose, insulin, C-peptide, or fructosamine values could be established. Total testosterone was positively correlated with glycosylated haemoglobin (HbA(1c)) levels (r =.322, P =.01). Although fasting plasma glucose was marginally higher in aging type 2 diabetic patients with andropause than in those without andropause (162 +/- 6.9 v 139 +/- 8.9, mean +/- SEM, P =.05), there were no differences between both subgroups for plasma fasting insulin, C-peptide, fructosamine, or HbA(1c) levels. Replacement therapy (150 mg intramuscular [IM] of enanthate of testosterone every 14 days for 6 months) was applied in 10 type 2 diabetic men with clinical features of andropause associated with subnormal concentrations of serum testosterone. The treatment induced significant increases in total plasma testosterone (baseline: 3.9 +/- 0.3; at 6 months: 7.1 +/- 0.9 ng/mL, mean +/- SEM, P =.003) and free testosterone (baseline: 9.3 +/- 0.6; at 6 months 17.6 +/- 2.4 pg/mL, P =.003), but had a neutral effect on overall glycemic control. These data show a high prevalence of andropause in aging type 2 diabetic men and suggest that the endogenous androgen environment, as well as correction of the partial androgen deficiency, do not have a meaningful effect on glycemic control.

Adult↗

PubMed2002

Abnormal expression of acid glycosidases in seminal plasma and spermatozoa from infertile men with varicocele.

The activities of acid beta-glucuronidase, alpha-mannosidase, alpha-glucosidase, alpha-galactosidase, beta-galactosidase and beta-N-acetylglucosaminidase were analysed in seminal plasma and spermatozoa from 26 infertile men with varicocele and from 36 men of normal fertility. Semen samples from ten men with non-obstructive azoospermia were used as control specimens that contained the other components of semen. Spermatozoa were solubilized by both physical (homogenization) and chemical (Triton-X100) methods to obtain the soluble and non-soluble fractions. The activities of several glycosidases measured both in seminal plasma and spermatozoa were directly correlated with the numbers of spermatozoa and sperm motility, confirming previous studies. As some infertile patients with varicocele have normal semen parameters, whereas others have low numbers of spermatozoa and low sperm motility, the varicocele patients were prospectively divided into two groups: one (n = 15) with normal spermiograms and the other (n = 11) with abnormal spermiograms. The activities (expressed in mU ml(-1)) of alpha-mannosidase, beta-galactosidase and beta-N-acetylglucosaminidase in seminal plasma of normozoospermic infertile patients with varicocele were significantly higher than those of fertile controls, but not when expressed in U per 10(8) spermatozoa. The activities of beta-glucuronidase, alpha-mannosidase, beta-galactosidase and beta-N-acetylglucosaminidase in seminal plasma when expressed in U per 10(8) spermatozoa in varicocele patients with abnormal spermiograms were significantly higher than in those of men of normal fertility. The activity of alpha-mannosidase in the soluble fraction of sperm homogenates, expressed as U per 10(8) spermatozoa, was significantly higher in infertile patients with varicocele and abnormal spermiograms than in controls. In the non-soluble fraction of spermatozoa from infertile patients with varicocele, there was an increase in the expression of beta-galactosidase and beta-N-acetylglucosaminidase activities compared with the fraction of spermatozoa from fertile subjects. In summary, infertile patients with varicocele displayed an overexpression of acid alpha-mannosidase, beta-galactosidase and beta-N-acetylglucosaminidase activities in seminal plasma and spermatozoa that may be associated with functional defects in spermatozoa as these glycosidases play an important role in mammalian fertilization.

Acetylglucosaminidase↗

PubMed2001

Monoallelic deletion in the 5' region of the thyroglobulin gene as a cause of sporadic nonendemic simple goiter.

The cause of sporadic simple goiter is unknown in most cases. Family studies have suggested that this disorder may have a genetic component in some patients. We have previously demonstrated that some cases of endemic and nonendemic simple goiter are associated with a mutation within exon 10 of the thyroglobulin gene. Here we report a study of 50 cases diagnosed as having nonendemic simple goiter, and found 1 case with a large heterozygous deletion within the thyroglobulin gene. The deletion involves the promoter region and the 11 first exons of this gene and is associated with a euthyroid state. We hypothesize that the absence of thyroglobulin synthesis from the deleted allele may be responsible for a decreased level of thyroglobulin mRNA. Euthyroidism would be achieved by thyrotropin (TSH) stimulation but at the expense of goiter development.

Aged↗

PubMed2000

Abnormalities in sperm acid glycosidases from infertile men with idiopathic oligoasthenoteratozoospermia.

OBJECTIVE: To analyze and compare acid beta-glucuronidase, alpha-mannosidase, alpha-glycosidase, alpha-galactosidase, beta-galactosidase, and beta-N-acetylglucosaminidase activities in fertile and infertile patients. DESIGN: An observational, controlled, clinical study. SETTING: A university tertiary hospital. PATIENT(S): Thirty-six fertile controls, 24 infertile oligoasthenoteratozoospermic (OAT) patients, and 10 azoospermic patients, who served as negative controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Analysis of the six glycosidase activities in seminal plasma and in solubilized spermatozoa. RESULT(S): alpha-galactosidase and beta-galactosidase activities in spermatozoa were significantly correlated with the serum levels of gonadotropins both in fertile controls and in OAT patients. The relative contribution of alpha-galactosidase and beta-galactosidase from the soluble fraction of spermatozoa to the total activity measured in the ejaculate of OAT patients was significantly lower than in fertile controls. The activities of beta-galactosidase and beta-N-acetylglucosaminidase in the soluble fraction of spermatozoa from OAT patients were significantly lower than in fertile controls. In seminal plasma, the activity of alpha-mannosidase from OAT patients was significantly higher than in fertile controls. The activity of beta-N-acetylglucosaminidase in the nonsoluble fraction of spermatozoa from OAT patients was three times higher than in fertile controls. CONCLUSION(S): The abnormalities in the distributions and contents of alpha-galactosidase, beta-galactosidase, and beta-N-acetylglucosaminidase in sperm suggest possible functional defects in spermatozoa from OAT infertile patients.

Acetylglucosaminidase↗

PubMed1997

Analysis of IL-2 and IL-6 binding to peripheral blood lymphocytes in Graves disease: relationship with disease activity.

Growing evidence points to the involvement of cytokines in the pathogenesis of some autoimmune diseases. To investigate the possible role of interleukin 2 (IL-2) and interleukin 6 (IL-6) on the pathogenesis of Graves disease (GD), the binding of both exogenous IL-2 and IL-6 and the expression of the IL-2 receptor subunit p55 (CD25) were evaluated by flow cytometry in peripheral blood T and B cells from 70 GD patients, in different states of the disease, and from 19 age- and sex-matched healthy volunteers. Serum levels of total T3 and T4, of free T4, and of anti-TSH receptor antibodies were also simultaneously determined. All GD patients displayed significantly increased numbers of B cells bound to IL-2. Hyperthyroid untreated GD patients had significantly higher numbers of T and B cells expressing the IL-2 receptor subunit p55 as compared to euthyroid patients in long-term remission. In addition, serum anti-TSH receptor antibody levels were directly correlated with the absolute numbers of T cells bound to IL-2 (r = 0.565, P < 0.05) and to IL-6 (r = 0.653), P = 0.02) in the hyperthyroid untreated patients, but not in long-term remission euthyroid GD patients or in patients treated with methimazole. The serum levels of total T3 and free T4 were significantly correlated with the absolute numbers of circulating T cells binding IL-2 (r = 0.720, P < 0.01 and r = 0.783, P < 0.002, respectively) as well as with the absolute numbers of circulating T cells binding IL-6 (r = 0.671, P < 0.02 and r = 0.626, P < 0.02, respectively). The serum levels of total T3 were also correlated with both the absolute numbers of B cells binding to IL-2 (r = 0.586, P < 0.05) and to IL-6 (r = 0.757, P < 0.001). These findings suggest that IL-2 and IL-6 may play a role in the pathogenesis of GD.

Adult↗

PubMed1997

Methimazole therapy in Graves' disease influences the abnormal expression of CD69 (early activation antigen) on T cells.

At present, the in vivo response of T, B and natural killer (NK) cells to antithyroid drug therapy remains largely unknown. In the present study, we have prospectively analyzed the in vivo effects of methimazole treatment on a large number of circulating T and NK cell subsets, some of them expressing cell surface activation antigens involved in the very early phase of the immune response, in a group of 17 hyperthyroid, untreated patients with Graves' disease (GD). As one of the first events during T cell activation is the expression of interleukin (IL) receptors, we also studied the binding of IL-2 and IL-6 to T cells. Patients with Graves' disease were sequentially studied at diagnosis/before treatment (day 0) and 7, 14, 30, 90 and 180 days after methimazole therapy. The results were compared with both a group of 19 age- and sex-matched control volunteers and a group of 20 untreated/euthyroid patients with Graves' disease in long-term remission. The combination of flow cytometry and three-color immunofluorescence revealed a clear (P < 0.01) decrease in the percentage of NK cells before and during the whole course of therapy with respect to both controls and patients with Graves' disease who were in long-term remission. Before therapy, a marked increase (P < 0.001) in the ratio of B to NK cells was also observed; thereafter, a slight decrease in this ratio was observed, although normal values were detected only in patients in long-term remission. Expression of the CD69 early activation antigen in the hyperthyroid untreated patients with Graves' disease was clearly increased (P < 0.01) with respect to both controls and patients with Graves' disease who were in long-term remission. This abnormal CD69 expression was found to be significantly reduced (P < 0.001) by methimazole therapy, and this represents a new effect of the drug. Expression of the low-affinity receptor for IL-2 (CD25)--another early T cell activation marker--was not altered in Graves' disease, but the binding of IL-2 and IL-6 to T cells exhibited a progressive and parallel increase during the first 30 days of therapy, decreasing thereafter. Our results show that methimazole therapy downregulates the abnormally high expression of the CD69 early activation antigen on T cells, being less effective on inducing changes in other T cell activation markers and in NK cells.

Adult↗

PubMed1996

CD5+ B cells in Graves' disease: correlation with disease activity.

In the present paper the distribution of peripheral blood CD5+/CD19+ (CD5+B) and CD5-/CD19+ (CD5-B) B-lymphocytes in Graves' disease (GD) patients is analyzed in order to correlate them with disease activity, interleukin-2 (IL-2) and IL-6 binding to T and B cells as well as with anti-thyrotropin (TSH) receptor antibodies and the thyroid hormone serum levels. The combination of flow cytometry and 3-color immunofluorescence revealed a remarkable increase in the absolute numbers of CD5+ B cells in hyperthyroid-untreated GD patients (218 +/- 137 x 10(6)/l vs. 66 +/- 69 x 10(6)/l in healthy subjects, p < 0.01) that gradually fell to normal values once hyperthyroidism had been controlled by methimazole. However, relative numbers of CD5+ B cells persisted at a relatively stable but increased level in GD patients in long term remission of an average of 3.1 years. This was also confirmed in a follow-up study of a group of 12 newly diagnosed patients during the first 90 days of anti-thyroid drug therapy with methimazole. No correlation was observed between either CD5+ B cells or CD5- B cells and the serum levels of pathogenic anti-TSH receptor antibodies. Increased numbers of CD5+ B cells were related to the increased free thyroxine and total triiodothyronine serum levels. In addition, a strong correlation between both the absolute levels of B cells binding to exogenous IL-2 and IL-6 and the absolute number of CD5+ B cells in hyperthyroid GD patients (LR = 0.798, p < 0.001; LR = 0.569, p < 0.01, respectively) was observed. These results suggest that CD5+ B cells in GD are partly regulated by thyroid hormone serum levels as well as by IL-2 and IL-6 binding to B cells. Nevertheless, they are not involved, at least directly, in the production of anti-TSH receptor antibodies.

Adult↗

PubMed1996

Thyroglobulin exon 10 gene point mutation in a patient with endemic goiter.

Iodine deficiency is the most relevant etiologic factor in endemic goiter. However, the fact that not all residents in the same area eventually develop goiter suggests that individual factors might also be involved in the etiology of endemic goiter. We have previously reported a point mutation in thyroglobulin exon 10 associated with nonendemic simple goiter. In an attempt to determine whether the mutation in thyroglobulin exon 10 might be linked to endemic goiter, we studied the genomic organization of thyroglobulin exon 10 in 36 patients diagnosed with endemic goiter by Southern blot, PCR, and sequencing analysis. We also analyzed by Southern blot the organization of the genomic region that contains thyroglobulin exons 1 to 11. In one case, we observed a point mutation in thyroglobulin exon 10. Sequencing analysis revealed a mutation at position 2610 of the cDNA, which implies a G to T substitution. This single base change results in a glutamine to histidine substitution and is the same as that previously reported by our group in patients with nonendemic goiter. To our knowledge, this is the first time that a mutation in the thyroglobulin gene has been described in a patient with endemic simple goiter and further confirms the association between the exon 10 mutation and development of goiter.

Adult↗

PubMed1996

Serial analysis of the effects of methimazole therapy on circulating B cell subsets in Graves' disease.

The immunosuppressive effects of antithyroid drug therapy are well recognized; however, the cellular mechanisms underlying their action remain largely unknown. In the present paper we have prospectively analyzed the in vivo effects of methimazole treatment on a large number of circulating B cell subsets, involved in the effector phase of the immune response, in a group of 18 hyperthyroid patients with Graves' disease (GD). The patients were sequentially studied before (day 0) and 7, 14, 30, 90 and 180 days after methimazole therapy. The results were compared with both a group of 19 age- and sex-matched healthy controls and a group of 20 untreated/euthyroid GD patients in long-term remission. The combination of flow cytometry and three colour immunofluorescence revealed a clear increase (P < 0.001) in the numbers of circulating total B cells (CD19+) due to a significant increase (P < 0.001) in the CD5+, FMC7+, CD5+/ FMC7+ and CD23+ B cell subsets in hyperthyroid GD patients with respect to both healthy individuals and to GD patients in long-term remission. The absolute numbers of all these B cell subsets analyzed before treatment, although abnormal, were not statistically different from those observed during the whole period of therapy. When comparing the percentages of these B cell subsets during treatment, significant changes (P < 0.001) were only observed in the proportion of CD5+, CD5+/FMC7+ and CD5- B cells at the end of the follow-up period with respect to those found both before and during the first month of therapy. Whereas CD5+ and CD5+/FMC7+ B cells decreased (P < 0.001) after 3 months of therapy, CD5- B cells showed a significant increase (P < 0.001) at the end of therapy. It is remarkable that the percentage of CD5+, CD5+/FMC7+, CD5- and CD23+ B cell subsets were abnormal during the whole period of treatment and that they never reached normal values. These results show that, in vivo, GD patients treated with methimazole exhibited an abnormal but rather stable pattern of B cell distribution, similar to that present in hyperthyroid untreated GD patients, except for the CD5+ and CD5- B cell populations. Our findings suggest that in vivo methimazole therapy would not directly have an important influence on circulating B cell subsets.

Adult↗

PubMed1994

The relationship between hyperthyroidism and the distribution of peripheral blood T, NK and B-lymphocytes in multinodular goiter.

Peripheral blood T, NK and B-cell subsets were analyzed in 18 patients with nontoxic multinodular goiter (NMG) and 11 patients with toxic multinodular goiter (TMG) in order to evaluate whether hyperthyroidism modifies the distribution of these cell populations. As a control group, 26 age and sex-matched healthy individuals were included in the study. Lymphoid subsets were analyzed with flow cytometry by double staining immunofluorescence techniques using a large panel of monoclonal antibodies. No differences were found in the absolute or relative numbers in any of the cell populations analyzed in both groups--NMG and TMG--, with the exception of a significant decrease in CD19+ cells in TMG. However, patients with multinodular goiter showed important abnormalities in the distribution of T, NK and B lymphocytes with respect to the control subjects. The pattern of abnormalities detected was characterized by a marked increase in the absolute and relative counts of activated T-lymphocytes (CD3+/HLA-DR+), cytotoxic T-cells (CD57+/CD8+) and of cells expressing NK-related antigens. None of these alterations were related to the serum levels of T3, T4 or TSH. Our results point to the existence of important abnormalities in the distribution of several lymphoid subsets in multinodular goiter, regardless of whether the subjects are euthyroid or hyperthyroid.

Adult↗

PubMed1993

Immunological features of sporadic multinodular goiter.

The origin of sporadic multinodular goiter is still uncertain. To obtain information on a number of unexplored immunological features, the distribution and characterization of T, B, and natural killer lymphocyte subsets were studied in the peripheral blood of 15 patients with multinodular goiter; 8 patients with Graves' disease (for reference purposes with a well-characterized autoimmune disease) and 29 age- and sex-matched healthy controls, combining double-staining immunofluorescence technique with monoclonal antibodies and flow cytometry. Although in both thyroid diseases increased CD3+ HLA-DR+ activated T cells (P < 0.01) were detected, in Graves' disease this was associated with decreased numbers of CD8 cells (P < 0.05) and an increased CD4/CD8 ratio (P < 0.01). These abnormalities were absent in multinodular goiter, which displayed increased CD8+ CD57+ cytotoxic/suppressor cells (P < 0.01). There was an increase in the percentage of natural killer cells expressing CD16 and CD57 antigens in multinodular goiter but not in Graves' disease. The B-cell associated antigens CD19 and CD19+ CD5+ were significantly increased in Graves' disease (P < 0.01), while the multinodular goiter patients exhibited only an increased number of B cells coexpressing the CD5 antigen (CD19+ CD5+), which was unrelated to the titers of anti-microsomal and antithyroglobulin autoantibodies. Our results point to the presence of several abnormalities of peripheral T, B, and natural killer lymphocytes in sporadic multinodular goiter, with a distribution pattern quite different from that observed in Graves' disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Increased serum N-acetyl-beta-D-glucosaminidase and alpha-D-mannosidase activities in obese subjects.

We have studied N-acetyl-beta-D-glucosaminidase and alpha-D-mannosidase activities in human sera from 35 control subjects, 47 normo- and hyperinsulinemic obese persons, and 12 diabetic patients after a fasting period of 12 h and at 30, 60, 90, and 120 min after an oral glucose overload. The results show a significantly higher activity of these 2 enzymes in obese subjects and diabetic patients, of similar magnitude, especially in those obese persons with a higher grade of obesity. Moreover, the activity of these glycosidases decreases in a similar way in all these 3 groups after the oral glucose overload.

Acetylglucosaminidase↗

PubMed1992

Enzymatic glycosidase activities in experimental obesity.

Glycosidases are lysosomal enzymes that participate in the catabolism of glycoproteins and other glycoconjugates, and in some way may modify their activity in situations in which carbohydrate metabolism could be altered, such as the case of obesity. Using a fluorometric assay, a study was made of four glycosidase activities: N-acetyl-beta-D-hexosaminidase (NAG), alpha-mannosidase and alpha- and beta-glucosidase in the serum, pancreas, liver and kidney of 22 Zucker fa/fa genetically obese rats and of 23 fa/? controls, both with ages ranging between 13 and 15 weeks. After 12-14 hours fast and prior anaesthesia with sodium pentobarbital intraperitoneally, blood and the afore-mentioned organs were removed for enzymatic study of the serum and the organs after homogenization and centrifugation. In the serum a statistically significant increase in alpha-mannosidase (p < 0.0001) and alpha-glucosidase (p < 0.02) activities was found in the fa/fa obese rats as compared with the controls. No statistically significant differences were found in serum hexosaminidase activity between the two groups, and no serum beta-glucosidase enzymatic activity was detected. In liver, a decrease was observed in hexosaminidase (p < 0.002) and alpha-glucosidase (p < 0.01) activities in the obese rats as compared with the controls. In whole pancreas an increase was found in alpha-glucosidase activity in the obese rats with respect to the controls (p < 0.001), with no statistically significant differences in the hexosaminidase, alpha-mannosidase and beta-glucosidase activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Effects of subclinical hyperthyroidism on renal handling of water and electrolytes in patients with nodular goiter.

Evidence is beginning to accumulate that minor degrees of hyperthyroidism lead to adverse effects in various tissues, even though clinically the patients are euthyroid. To determine whether these anomalies in thyroid function have deleterious effects on renal function and electrolyte metabolism, the plasma concentrations of electrolytes, urea, and creatinine, the renal handling of water and sodium, and the urinary excretion of these substances were measured in patients with nodular goiter who were displaying stable subclinical hyperthyroidism. The studies were carried out before and after correcting the thyroid dysfunction. Restoration of euthyroidism did not modify any of the renal function parameters studied and did not cause changes in blood analyte levels. The data show that treatment of minor degrees of hyperthyroidism does not have any effects on renal function and electrolyte metabolism, and confirm the well-known capacity of the kidney to adjust its functions to changes induced by an abnormal secretion of thyroid hormones.

Adult↗

PubMed1991

A study of thyroglobulin and peroxidase activity in the thyroid tissue of patients with non-endemic non-toxic nodular goitre.

1. A study was made of the activity of the enzyme thyroid peroxidase and of the concentration, carbohydrate composition and the degree of iodination of thyroglobulin in the thyroid glands of 60 patients with non-endemic non-toxic goitre in the nodular phase and in those of 25 control subjects. 2. Thyroid peroxidase activity was determined by the guaiacol assay and was significantly higher in patients with non-endemic non-toxic goitre than in control subjects (3.60 +/- 2.51 and 2.07 +/- 1.08 mumol of guaiacol oxidized min-1 g-1 of tissue, respectively; ranges 0.16-10.57 and 0.52-4.85 mumol of guaiacol oxidized min-1 g-1 of tissue, respectively; P less than 0.05). 3. Thyroglobulin was purified by precipitation with ammonium sulphate and Sephadex G-200 gel filtration. Two protein peaks were obtained which were identified as thyroglobulin and measured by radioimmunoassay. The concentration of thyroglobulin in the first peak was 98.94 (SD 84.87, range 0.60-455.54) mg/g of tissue for the patients with non-endemic, non-toxic goitre and 51.41 (SD 28.34, range 14.99-106.39) mg/g of tissue for the control subjects (P less than 0.01). The second peak showed 1.26 (SD 1.27, range 0.09-6.50) mg of thyroglobulin/mg of tissue for the group with non-endemic non-toxic goitre and 0.51 (SD 0.25, range 0.15-0.98 mg of thyroglobulin/mg of tissue) for the control subjects (P less than 0.01). 4. The carbohydrate composition of thyroglobulin was determined by acid hydrolysis and colorimetry, evaluating the levels of hexoses, hexosamines and sialic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Cytoplasmic enzyme activities in human hypernephroma compared with normal renal cortical tissue.

Cytoplasmic lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzymatic activities were measured in normal renal cortical tissue and in hypernephroma. Significantly lower activities were always found in tumoral tissue than in normal renal tissue. Their respective values (mean +/- SD) were: LDH, 4,333 +/- 747 (normal tissue) vs. 997 +/- 748 U/l (tumor); HBDH, 2,554 +/- 466 vs. 387 +/- 290 U/l; AST, 529 +/- 109 vs. 65 +/- 37 U/l, and ALT, 205 +/- 45 vs. 9.9 +/- 5.4 U/l. The LDH/HBDH ratio was significantly greater in tumoral (2.69 +/- 0.69) than in normal tissue (1.70 +/- 0.11). These results indicate that hypernephroma exhibits a low metabolic rate when compared to normal tissue. Their enzymatic activities suggest a decreased energy metabolism, predominantly of the anaerobic type, and a reduced synthesis of nonessential amino acids in the tumor. These findings could explain in part the slow growth rate of hypernephroma.

Alanine Transaminase↗