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Biomedical subjects

G Murano

Publications and source records attributed to G Murano.

At least 37 records · Page 2Linked to original sources

Tumor cell autocrine motility factor.

A cell motility-stimulating factor has been isolated, purified, and partially characterized from the serum-free conditioned medium of human A2058 melanoma cells. We term this activity "autocrine motility factor" (AMF). AMF has the properties of a protein with an estimated size of 55 kDa. At concentrations of 10 nM or less, AMF stimulated the random or directed motility of the producer cells. However, AMF is not an attractant for neutrophils. Amino acid analysis of the purified AMF protein revealed a high content of serine, glycine, glutamic acid, and aspartic acid residues. The activity of AMF was not replaced or blocked by known growth factors such as epidermal growth factor or type beta transforming growth factor. Mechanistic studies showed that AMF stimulated the incorporation of [3H]methyl into cell membrane phospholipids after incubation with [methyl-3H]methionine with a sustained increase in the methylation of phosphatidyldimethylethanolamine to phosphatidylcholine. In contrast, AMF did not affect the incorporation of [1,2-14C]choline into phosphatidylcholine. AMF was produced in large amounts by three different clones of ras oncogene-transfected metastatic NIH 3T3 cells but not by the nontransformed parental cells. AMF may play a major role in the local invasive behavior of tumor cells and may also facilitate the concerted invasion by groups of tumor cells.

Animals↗

[Disorders of renin secretion in arterial hypertension].

The present work is devoted to investigate the meaning of disorders in renin secretion in primary and secondary hypertension and report the results of bayesan analysis applied to a group of 125 hypertensives who underwent selective renal angiography and polydistrictual renal vein samplings for the determination of plasma renin activity for diagnostic and therapeutic purposes. Data obtained from statistical analysis allow specifications on the prevalence of disorders, rates of false positives and false negatives, predictive value, diagnostic value, sensitivity and specificity. The weighted data are useful to validate the reliability of the renin renal vein measurements which are used in clinical practice for identifying the potentially surgically curable forms of arterial hypertension.

Adolescent↗

May a lymphocytic infiltration have a pathogenic role in an aldosterone-producing adrenal tumor?

A 38-year-old woman is described to have a primary hyperaldosteronism due to an aldosteronoma with foci of lymphocytic infiltration. The finding suggests: a concomitant lymphoid adrenalitis; or, an immunological attack to neoplastic cells. The hypothesis is that there may be a relationship in the association. The lymphocytic infiltrates could have a pathogenic role in the development of the aldosterone-producing adrenocortical neoplasm by interrupting some inhibitory mechanism(s) of the cells that secrete aldosterone.

Adrenal Cortex Neoplasms↗

Temporal correlation of some endocrine circadian rhythms in elderly subjects.

The aim of this chronobiological study was to investigate temporal correlations in the circadian patterns of 6 hormones, namely somatotrophic hormone (STH), prolactin (PRL), cortisol (F), aldosterone (ALD), insulin (IRI) and C-peptide (CP), assayed in systemic blood serum drawn at 07:00, 10:00, 13:00, 16:00, 19:00 and 22:00 h from an antecubital vein in 19 young subjects (aged 20-29 yr, comprising 10 males and 9 females; and 20 elderly subjects (aged 70-81 yr, comprising 10 males and 10 females). All subjects were sampled on a normal dietary sodium intake (120-140 mEq/24h) while following a social routine of diurnal activity (07:00-23:00) and nocturnal rest (23:00-07:00). Time-qualified data were analyzed by lead-lag correlation and by cosinor analysis. According to the lead-lag correlation findings, it would appear that the correlation which exists between several time-qualified series in young subjects is no longer present in elderly subjects. The circadian rhythms which were found to have lost their temporal correlations with advancing age were those between STH and IRI, STH and ALD, PRL and IRI, PRL and CP, and ALD and CP. It should be noted that the correlation between hormonal rhythms breaks down mainly on account of a peculiar age-related change in the magnitude of the circadian fluctuation. This chronological decline in amplitude led to the conclusion that the senescence of endocrine rhythmic functions is a biological phenomenon characterized by altered circadian variability.

Adult↗

Human antithrombin concentrates and experimental disseminated intravascular coagulation.

The effect of human antithrombin III concentrates was studied in a dog model in which DIC was produced by the infusion of 0.66 M lactic acid. In 35 animals infused with lactic acid only, platelet counts, fibrinogen levels, alpha 2-antiplasmin levels, and antithrombin levels decreased significantly over a 4-hour observation period. At the same time, the levels of fibrin(ogen) split products increased. At the end of the experimental period, the glomeruli of the dogs' kidneys contained significant quantities of fibrin. Hemodynamically, the dogs experienced a significant decrease in cardiac output, whereas the mean arterial blood pressures remained unchanged. Urine output seemed to decline during the time of study. Appreciable quantities of heparin could be measured in the dogs' plasmas. In 13 dogs that were treated in the same manner as the just described 35 animals, 1 U of human antithrombin concentrate per ml of calculated dog plasma was infused over a 90-minute time span, beginning after 1 hour of acidosis. Although no differences were noted in the decrease in platelet counts between the two groups, fibrinogen levels and alpha 2-antiplasmin levels declined less drastically in the antithrombin-treated group. Also the levels of fibrin(ogen) split products increased less in the treated group. The antithrombin activity levels increased markedly and remained at their high levels even after the infusion of antithrombin had ceased. The amount of human antithrombin circulating was followed by immunologic assays using a human antibody to antithrombin. Also, with this technique, the levels of infused antithrombin did not decrease. The amount of fibrin found in the glomeruli of this group of animals was significantly lower than in the nontreated group (p less than 0.001). Even cardiac output was higher in the treated group and urine production seemed to increase. Also, these dogs had appreciable quantities of heparin in their plasmas. In a control group of six animals who were infused with saline instead of lactic acid, no major changes were observed in the coagulation and cardiovascular parameters. These data seem to suggest that antithrombin concentrates exert a certain protective effect in this particular DIC animal model.

Acidosis↗

Circadian rhythms of plasma renin activity and aldosterone: changes related to age, sex, recumbency and sodium restriction. Chronobiologic specification for reference values.

Plasma renin activity (PRA) and aldosterone (PA) levels are characterized by a circadian rhythmicity (CR). The present study revealed that this rhythmicity is influenced by several factors including posture, sodium intake and age. Time-qualified PRA and PA reference intervals can reduce the incidence of false positives and false negatives in a diagnostic work-up. The circadian rhythmicity of PRA and PA have been quantified in relation to posture, sodium intake and age. The cosinor procedure has been applied to quantify the properties of the circadian rhythmicity under these conditions. Chronograms and circadian parameters can be used to optimize the use of PRA and PA measurements in clinical practice. The chronobiological specification of reference values for PRA and PA is of valuable importance since the assessment of PRA and PA circadian rhythmicity has a diagnostic interest for a certain type of clinical disorder. It should be noted that several studies have described circannual variations for renin and aldosterone. The next step in the optimation of laboratory time-qualified reference values is the assessment of changes induced by the deterministic factors on a circannual domain.

Adult↗

Lysis of intracranial hematomas with urokinase in a rabbit model.

Urokinase (UK), a potent thrombolytic agent, was tested in a rabbit model for safety and efficacy in lysing intracranial hematomas. Intracerebral-intraventricular (IC-IV) hematomas were created by stereotaxically injecting 0.2 ml of clotted human blood into the frontal lobe and lateral ventricle of a total of 57 anesthetized adult New Zealand White rabbits (weighing 1.6 to 2.5 kg). Control animals received 0.2 ml of normal saline injected into the clot, and the experimental group received an equal volume of UK solution (50,000 units/ml) immediately after the clot injection. Some animals were sacrificed at 3 hours and others at 24 hours postinjection. At 3 hours, clot lysis had been achieved in nine (90%) of 10 UK-treated animals as compared to one (14%) of seven controls. By 24 hours, clots had been lysed in 10 (83%) of 12 UK-treated animals and in two (33%) of six controls. Overall, clot lysis was demonstrated in 19 (86%) of the 22 UK-treated animals and in only three (23%) of the 13 controls (p less than 0.001). There was no significant difference in results between these animals and a further set of 22 rabbits that were treated with UK or saline 24 hours after clot injection. There was no histological evidence of damage or inflammation noted on careful light microscopic examination of three to five sections from each brain, although findings consistent with encephalitozoonosis, an incidental protozoan infestation, were encountered in four animals. These studies suggest that UK may be safely and effectively employed for the lysis of intracranial hematomas in this animal model, and that a delay in therapy of up to 24 hours does not significantly compromise its efficacy.

Animals↗

Study of the diurnal variation of human lymphocyte subsets.

The diurnal variation of peripheral white cells and in particular of different lymphocyte subsets has been investigated in 11 normal subjects. Monoclonal antibodies (Mab) phenotyping total T lymphocytes (UCHT1), cytotoxic/suppressor (UCHT4), helper T cells (Leu 3a), B lymphocytes (231) and K/NK cells (H25) have been used. In addition to the traditional parametric statistics, the chronobiological approach of cosinor was adopted in order to inferentially obtain the waveform covering the 24-hr period. Cosinor analysis validated the existence of a significant rhythm for leucocytes (p = 0.04, lymphocytes (p = 0.03), and Leu 3a positive cells (p = 0.04). The best fitting period was equal to 28 hr. No circadian rhythm was documented for lymphocyte subsets positive for Mab UCHT4, 231, H25, by testing the variability with a frequency ranging from 1 cycle every 12hr to 1 cycle every 28 hr. By the non-inferential analysis of temporal curves, a significant peak of Leu 3a positive cells at 20.00 hr (p less than 0.001) was observed. The acrophase has been recorded by cosinor analysis at 20.36 hr. We conclude that the circadian variability of Leu 3a positive cell profile must be taken into account when the helper/suppressor ratio is calculated. The time-dependence of this lymphocyte subpopulation suggests that when therapy with corticosteroids is considered in autoimmunity, it should be planned by keeping the peak of Leu 3a positive cells as a marker time.

Adult↗

[Clinical significance of anomalies of renin secretion in arterial hypertension].

Aim of the present investigation is to define the clinical meaning of disorders in renin secretion in the field of vascular hypertensive diseases. In view of this scope, we report the results of a retrospective study on the levels of plasma renin activity assayed in renal veins, aorta and peripheral vein of 124 hypertensive, angiographically studied for a diagnostic work-up. The behavior of renal vein renin has been related to epidemiologic, clinical and etiopathogenetic factors. Results indicate that disorders in renin secretion occur in every type of arterial hypertension. However, some disorders are prevalent in a determined type of hypertensive disease. The incidence of disorders in renin secretion is different in relation to sex, age and duration of hypertension. Hypersecretion is prevalent in men and young hypertensives, while hyposecretion of renin is more frequent in the oldest hypertensive patients. Vascular damage is prevalent in men and young hypertensives, while hyposecretion of renin is more frequent in the oldest hypertensive patients. Vascular damage is prevalent in renin hyposecretive hypertensives. Hypersecretion and lateralization in renin release can be mainly encountered in the renovascular type of hypertension and, less frequently, in unilateral nephroparenchymal hypertension. However, totally lateralized hypersecretion can be detected even in essential hypertensive patients suggesting the possibility of false positives for the diagnosis of renovascular hypertension.

Adult↗

Toward a chronophysiology of circulating aldosterone.

The physiology of aldosterone secretion has been prominently investigated by homeostatic studies on the levels of the steroid in plasma and/or urine. Aldosterone secretion is, however, arranged in a rhythmic fashion along the 24-hr cycle. The dynamics of aldosterone should thus be reanalyzed chronobiologically in order to gain further insight into the physiology of the hormone. Such a revisitation has been performed in the present study on four groups of clinically healthy volunteers categorized according to sex and age. Aldosterone has been assayed in the plasma of systemic venous blood six times a day (0600, 0800, 1200, 1800, 2000, 0000) in different conditions of physical activity and sodium intake. Time-qualified data have been analyzed by the single-cosinor method and then summarized by the population-mean cosinor procedure to quantify the circadian rhythms in their properties (mesor, amplitude, acrophase). Differences in rhythmometric parameters have been tested by a multivariate analysis for vectorial units. (Hotelling's T2 test). Cosinor analysis indicates that the dynamics of circulating aldosterone substantially changes in relation to posture. The habit of having a routine of diurnal activity leads the circadian rhythm of aldosterone to delay its acrophase from morning to afternoon. The postural shift of acrophase is essentially accompanied by an elevation in the 24-hr mean level. The restriction of salt intake is associated with an increase in mesor; the temporal localization of the circadian crest shows, however, a very high stability. Sex is not characterized by significant differences in the 24-hr patterns of aldosterone in the sense that young males and females show substantially identical time-qualified curves and circadian parameters. Increasing age until the seventh decade in life is responsible for changes mainly in 24-hr mean levels with a slight modification in amplitude. Such a chronophysiology for circulating aldosterone related to the motor-rest schedule, sodium intake, sex, and age, is of interest not only to heuristic but also to practical approaches in clinical medicine.

Adolescent↗

[Parametric methods applied to the standardization of gestational reference intervals for blood renin activity, aldosterone and cortisol using the transversal and longitudinal approach].

This investigation is devoted to define monthly-qualified gestational reference intervals for plasma renin, aldosterone and cortisol as derived by transverse or longitudinal approaches. Reference intervals refer to 95% confidence interval, 90% tolerance interval, the 95% predictive interval, in addition to the mean plus or minus the standard error and standard deviation. By applying both methodological approaches it has been found that plasma renin and aldosterone exhibit a progressive gestational increase. By contrast, cortisol shows an initial increase and thereafter stays on the same values. Statistical analysis revealed the transversally--and longitudinally--derived reference intervals to be not statistically different. Because of such a similarity, laboratory medicine can interchangeably use both kinds of reference intervals for estimating the normality of plasma renin, aldosterone and cortisol values in a single case of pregnancy. This interchangeability of values leads to simplify the methodology for measuring plasma renin and aldosterone in pregnancy since it is not necessary to standardize the gestational nomograms for renin-sodium and/or aldosterone-sodium relationship. This is a real way to reduce the costs and to optimize the compliance in the monitoring of pregnancy.

Adolescent↗