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Biomedical subjects

M Giralt

Publications and source records attributed to M Giralt.

At least 127 records · Page 7Linked to original sources

[Monoclonal gammopathies of undetermined significance. Clinical course and biological aspects of 397 cases].

The diagnostic criteria, incidence, clinical characteristics and outcome of 397 patients with monoclonal gammopathies of undetermined significance, all of them diagnosed and followed-up at the Haematology Service of the Miguel Servet Hospital, in Zaragoza, between January 1970 and December 1988, were revised. The patients' mean age was 64.7 years (range: 2-89). The M/F ratio was 236/161. The mean concentration of the M component (MC) was 1.17 g/dL (range: 0.20-3.50), this being under 0.50 in 65 cases. IgG was the most frequent MC (71.26%), followed by IgA (14.34%) and IgM (10.82%). Multiple MC was present in 14 cases (3.58). Light chains were passed in urine by 33 patients (8.31%). No associated pathology was found in 213 patients (53.65%) upon MC discovery, while 65 other (16.31%) were carriers of different blood disorders, chronic lymphoproliferative diseases being the commonest (11.57%). In 30 patients (7.30%) the MC was associated to nonhaematological malignancies, and 29 others had an underlying chronic infection. Chronic liver disease was present in 25 cases, and autoimmune disease in 14. Transient monoclonal gammopathy was seen in a small group of patients (6.54%), most of them suffering from acute infectious illness. With regard to the group of patients without any associated pathology, their median follow-up was 37.8 months (range: 18-228). Of them, the MC kept unchanged in 134 cases (62.91%); 47(22.06%) died from any unrelated cause, and 10 others evolved into malignant monoclonal gammopathy. The median clinical course of these last expanded to 60 months (range: 11-124), with an accumulated actuarial risk of 4.5% at 5 years, 15% at 10 years and 26% at 15 years.

Actuarial Analysis↗

Effect of morphine administration on rat liver metallothionein and zinc metabolism.

The putative involvement of opioid receptors in rat liver metallothionein (MT) regulation has been studied by means of morphine administration. Rat liver MT levels were significantly increased by morphine (10 mg kg-1). This increase was blocked by the opiate antagonist naloxone (4 mg kg-1), suggesting that the effect of morphine on liver MT could involve opioid receptors. The effect of morphine appears to be mediated, at least in part, by glucocorticoids and catecholamines, inasmuch as the administration of specific receptor blockers, RU 486 (100 mg kg-1) for glucocorticoids and labetalol (5 mg kg-1) for catecholamines, diminished liver MT increase induced by morphine. These results identify a potential mediation mechanism for regulating liver MT levels. The putative role of endogenous opioids on liver MT response to stress was also studied by means of opioid receptor blockers. The effect of stress on liver MT levels was not altered by blockade of opioid receptors with either naloxone (4 mg kg-1) or naltrexone (4 mg kg-1) or diprenorphine (4 and 20 mg kg-1), suggesting that endogenous opioids are not involved in MT response to stress. Zn metabolism was also altered by morphine, as morphine administration increased liver cytosolic Zn and decreased serum Zn levels. In contrast to those found in liver MT, these changes were not naloxone-sensitive. The results obtained with RU 486 and labetalol suggest that the effect of morphine on Zn metabolism was mediated in part by glucocorticoids and catecholamines.

Animals↗

Ontogeny and perinatal modulation of gene expression in rat brown adipose tissue. Unaltered iodothyronine 5'-deiodinase activity is necessary for the response to environmental temperature at birth.

We have performed a sequential study on the abundance of the mRNA for uncoupling protein (UCP), subunit II of cytochrome-c oxidase (COII) and lipoprotein lipase in brown adipose tissue during the fetal and postnatal periods. Moreover, we have determined whether these parameters can be modulated by ambient temperature in the early hours after birth, and at which point in development this sensitivity first appears. UCP gene expression in the fetal and neonatal period has particular features when compared with overall mitochondriogenesis (COII mRNA expression) or with the expression of lipoprotein lipase mRNA. There is a specific induction of UCP gene expression between days 18 and 19 of pregnancy followed by a specific increase of UCP gene expression in utero and a further increase after birth. The acquisition of the physiological apparatus capable of the response to UCP and lipoprotein lipase gene expression to the environmental temperature is not achieved until the last day of fetal development. This result suggests that mechanisms of beta-adrenergic modulation of gene expression in brown fat are already established at birth. From an experiment on iopanoic acid treatment of pregnant mothers, it was concluded that iodothyronine 5'-deiodinase activity is not necessary for the expression of the mRNAs for UCP, COII and lipoprotein lipase in the fetus whereas it is necessary for the acquisition of temperature sensitivity to these parameters at birth.

Adipose Tissue, Brown↗

Glutathione-S-transferase activity in human superficial transitional cell carcinoma of the bladder. Comparison with healthy controls.

Glutathione-S-transferase (GST) activity and glutathione (GSH) content have been studied in human urinary bladder (UB) specimens obtained from healthy controls (HC) (n = 8) and from patients with superficial transitional cell carcinoma (TCC) (n = 9), either in TCC and in adjacent normal (ANE) tissues of the same patient. The GST activity was significantly higher in TCC in comparison with ANE (ten fold) and with HC (five fold). This activity was also significantly higher in HC than in ANE (two fold). The Km values obtained in the whole population (1.26 +/- 0.3 X 10(-3) mol/l) suggest that a unique form of isoenzyme is present in the UB epithelium and that it is the same acidic form "rho" described in erythrocytes. The GSH content was significantly higher in TCC than in ANE (2.5 fold) and also that in HC (three fold). A good correlation between GST activity and GSH content was observed in HC but not in TCC or ANE. These results demonstrate the relation between the activity of the GST system and the development of the TCC as well as its role in the cellular resistance to chemotherapy. A possible decrease of the GST activity before the development of the tumor is also discussed.

Aged↗

Lipoprotein lipase mRNA expression in brown adipose tissue: translational and/or posttranslational events are involved in the modulation of enzyme activity.

Lipoprotein lipase mRNA abundance in rat brown adipose tissue increases during the first 24 h of cold exposure. Lipoprotein lipase mRNA levels do not change in brown fat throughout pregnancy and lactation, whereas enzyme activity is significantly lowered. After 5 h of acute cold or noradrenaline administration there is a 2-fold increase in lipoprotein lipase mRNA abundance, whereas lipoprotein lipase activity is stimulated to more than 6-fold the basal values. It is concluded that translational and/or posttranslational mechanisms are involved in the noradrenergic modulation of lipoprotein lipase activity in brown fat.

Acclimatization↗

Adaptative decrease in expression of the mRNA for uncoupling protein and subunit II of cytochrome c oxidase in rat brown adipose tissue during pregnancy and lactation.

Uncoupling-protein (UCP) mRNA expression is decreased to 15% of virgin control levels between days 10 and 15 of pregnancy, and remains at these low values during late pregnancy and lactation. Abrupt weaning of mid-lactating rats causes a slight but significant increase in UCP mRNA. Expression of mRNA for subunit II of cytochrome c oxidase (COII) decreased to half that of virgin control in late pregnancy and during lactation. Whereas COII mRNA expression is in step with the known modifications of brown-fat mitochondria content during the breeding cycle of the rat, UCP mRNA expression appears to be diminished much earlier than the mitochondrial proton-conductance-pathway activity. On the other hand, the reactivity of brown fat to increase expression of UCP and COII mRNAs in response to acute cold or noradrenaline treatment is not impaired during lactation.

Adipose Tissue, Brown↗

Iodothyronine 5'-deiodinase activity as an early event of prenatal brown-fat differentiation in bovine development.

Iodothyronine 5'-deiodinase activity appears to be a type I enzyme in bovine brown adipose tissue, on the basis of its high Km for 3,3',5'-tri-iodothyronine ('reverse T3') (in the micromolar range) and sensitivity to propylthiouracil inhibition. This enzyme activity is already detectable in perirenal adipose tissue of bovine fetuses in the second month of gestation, reaches peak values around the seventh month of fetal life, declines before birth, becomes lower after parturition and finally undetectable in the adult cow. Iodothyronine 5'-deiodinase activity is present in the pericardic, peritoneal and intermuscular adipose depots of the neonatal calf, but it is always undetectable in the subcutaneous adipose tissue. It is concluded that iodothyronine 5'-deiodinase is a specific feature of brown fat in the bovine species that is not shared by white adipose tissue. white adipose tissue. Peak values of 5'-deiodinating activity appear as an early event in the prenatal differentiation programme of bovine brown-fat cells as they occur when uncoupling-protein-gene expression first starts.

Adipose Tissue, Brown↗

Individual housing does not influence the adaptation of the pituitary-adrenal axis and other physiological variables to chronic stress in adult male rats.

Although the influence of housing conditions on the physiological response to stress has been extensively studied for several years, no attempts have been made to investigate the effect of this variable on the capacity for adaptation to chronic stress. To this end, adult male rats were housed either individually or in groups of four per cage and subjected to 2 hr of daily immobilization stress for 14 days. Housing did not influence any of the physiological variables measured either in unstressed or in stressed rats except the corticosterone response to stress which was higher in individually housed rats. Of the behavioral measures, individual housing significantly decreased defecation rate in the novel environment. Other behavioral measures were not influenced by housing. Chronic stress significantly reduced ambulation but no significant interaction between housing and chronic stress was observed. Taken together, these data indicate that a short period of individual housing did not affect the physiological and behavioral consequences of repeated exposure to chronic stress.

Adaptation, Physiological↗

[Incidence of monoclonal components in lymphoproliferative syndromes. Apropos of 234 cases ].

A series of 234 sera from 104 patients with non-Hodgkin's lymphoma (NHL), 77 with Hodgkin's disease (HD) and 53 with chronic lymphocytic leukaemia (CLL) was studied by cellulose acetate gel electrophoresis, agarose gel electrophoresis, immunoelectrophoresis and electroimmunodiffusion, in order to assess the incidence and type of monoclonal components (MC) in these diseases. Monoclonal component was found by cellulose acetate gel electrophoresis in 22 of the 234 cases studied (9.8%); agarose gel electrophoresis disclosed MC in 22 other cases (18.8%), all of them showing rates lower than 5.0 g/L. MC was present in 29 of the 104 NHL cases (27.9%), it being characterised as IgM in 16 patients and IgG in 13 others. The MC was observed in 13 of the 21 cases of lymphoplasmacytoid forms, but it was less conspicuous in the remaining histological forms. With regard to HD, MC was present in 5 cases (6.5%), of IgG, type in all instances, and in 10 of the 53 CLL patients (18.9%), IgG in 8 and IgM in two other cases. The methods used in the present study made it possible to detect and characterise MC in about 20% of the lymphoproliferative syndromes studied. It can be inferred that the use of more sensitive techniques would disclose the presence of MC in the majority of B-cell lymphoproliferative syndromes.

Adult↗

Iodothyronine 5'-deiodinase activity and thyroid hormone content in brown adipose tissue during the breeding cycle of the rat.

Brown adipose tissue iodothyronine 5'-deiodinase activity is significantly lower in 17-day pregnant rats compared with virgin controls and remains low during late pregnancy and lactation. It fully recovers with abrupt weaning, but only partially with spontaneous weaning. Even though this profile of changes is remarkably in step with the known pattern of modifications in brown fat thermogenesis during the breeding cycle, the lowered iodothyronine 5'-deiodinase activity appearing between days 15 and 17 of pregnancy occurs earlier than the reduction in brown adipose tissue thermogenesis. Brown fat 3,3',5-tri-iodothyronine content is also reduced in late pregnant, early and mid-lactating rats, most probably as a consequence of the lowered 5'-deiodination of thyroxine in situ. Acute insulin treatment increases brown fat iodothyronine 5'-deiodinase activity in virgin animals as well as in late-pregnant and lactating rats, despite the lowered basal enzyme activity levels in the latter groups. Thus an impaired response to insulin in brown fat does not appear to be a factor leading to the lowered iodothyronine 5'-deiodinase activity during late pregnancy and lactation.

Adipose Tissue, Brown↗

Evidence for a differential physiological modulation of brown fat iodothyronine 5'-deiodinase activity in the perinatal period.

Brown adipose tissue iodothyronine 5'-deiodinase increases progressively in fetuses from the day 17 of pregnancy on, it reaches peak values on the 20th day of gestation and declines in the last days of fetal life as well as during the first day of life. Birth of premature fetuses causes a sudden drop in the enzyme activity. Postmaturity is associated to a decrease in brown fat 5'-deiodinase similar to that found after birth in fetuses born at term. In the first hours of life brown fat iodothyronine 5'-deiodinase is essentially insensitive to the cold-stimulus. Present data indicates that, differently from adult rats, brown fat iodothyronine 5'-deiodinase activity during the perinatal period is dissociated from the thermogenic activity of the tissue. It is suggested that factors different from the action of the sympathetic nervous system may play a main role in brown fat iodothyronine 5'-deiodinase activity modulation in the fetal and neonatal life.

Adipose Tissue, Brown↗

Previous chronic chlorimipramine treatment did not modify some physiological responses to acute and chronic stress in rats.

The effects of previous chronic administration of the tricyclic antidepressant drug chlorimipramine (CMI) on some physiological responses of adult male rats to stress has been studied. CMI significantly reduced food intake and body weight gain, but did not alter either adrenal weight or basal serum corticosterone levels. Corticosterone response to 1 h of immobilization stress was the same in saline and CMI-treated rats. When the rats previously treated with CMI were subjected to chronic immobilization stress, it was found that the drug did not alter the anorexic effects of the stressor, but reduced the rate of adaptation of adrenocorticotropin response to stress. These data indicate that previous chronic CMI administration does not prevent changes in the secretory activity of the pituitary-adrenal system or the reduction of food intake and body weight caused by strong stressors.

Adrenal Glands↗

Physiological role of glucocorticoids on rat serum and liver metallothionein in basal and stress conditions.

Serious contradictions exist at present in our understanding of the physiological role of glucocorticoids on the synthesis of the metal-binding protein, metallothionein (MT). In addressing this problem, we have examined in vivo the role of glucocorticoids on liver and serum MT levels in the rat under a spectrum of experimental conditions. The experiments confirm that stress has a major positive effect on hepatic MT levels. It was found that adrenocorticotropic hormone (ACTH) administration has an inhibitory effect on hepatic MT levels in response to restraint stress and that adrenalectomy (ADX) leads to an increase in basal MT levels and in MT levels in response to acute and chronic immobilization stress. Similar results followed treatment with the glucocorticoid receptor blocker, RU 486. The effect of ADX was abolished by corticosterone replacement. The relations found among hepatic MT, serum MT, and glucocorticoid concentrations indicate that in some circumstances glucocorticoids have a permissive role in mobilizing MT from tissues to serum and that in physiological conditions corticosterone has an inhibitory role in the maintenance of hepatic MT levels.

Adrenalectomy↗

Evidence that the pituitary-adrenal axis does not cross-adapt to stressors: comparison to other physiological variables.

The effects of previous chronic immobilization stress on the physiological responses of male rats to a novel chronic stressor (shock) were studied. Previous chronic exposure to immobilization reduced adrenocorticotropin (ACTH) and lactate responses to acute immobilization stress without altering the response to a novel acute stressor (tail shock). When subjected to chronic tail shock, body weight inhibition caused by chronic shock was greater in the rats not previously exposed to chronic immobilization, which suggests that there is cross-adaptation between different stressors. However, adrenocorticotropin adaptation to chronic shock was impaired by previous chronic immobilization. These data indicate that the existence of cross-adaptation to stressors might depend on the variable measured, the central nervous system pathways controlling the pituitary-adrenal axis being, apparently, resistant to cross-adaptation. This lack of cross-adaptation at certain levels can assure the maintenance of an adequate response to unknown environmental stimuli.

Adaptation, Physiological↗