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Biomedical subjects

M Pagano

Publications and source records attributed to M Pagano.

At least 199 records · Page 11Linked to original sources
PubMed1988

Prevalence of late-onset 11 beta-hydroxylase deficiency in hirsute patients.

Serum levels of 11-deoxycortisol were determined in 182 hirsute women. Three patients presented high basal 11-deoxycortisol levels and an exaggerated response of this steroid to ACTH stimulation. A fourth patient had normal basal 11-deoxycortisol but was hyperresponsive to ACTH stimulation. Therefore diagnosis of late-onset 11 beta-hydroxylase deficiency was made in 4 out of 182 hirsute women with a prevalence of 2.2% in the group studied. In these patients, clinical findings and other hormonal patterns were not different from those of other women suffering from hirsutism.

Adolescent↗
PubMed1988

Maternal toxemia and neonatal germinal matrix hemorrhage in intubated infants less than 1751 g.

Two hundred seventy-two intubated infants who weighed less than 1751 g were enrolled in a clinical trial of phenobarbital prophylaxis of postnatal germinal matrix hemorrhage. The incidence of germinal matrix hemorrhage was 3.1% (one of 32) among infants born to women with toxemia, and 23% (55 of 240) among those born to women without toxemia. The apparent protective effect of toxemia could not be explained by intrauterine growth retardation, mode of delivery, or maternal receipt of any medication. Infants born to toxemic women were less likely than their peers to develop pneumothorax, become acidotic, and to require extensive respiratory assistance. This apparently protective effect of maternal toxemia was not seen in infants born to nontoxemic, hypertensive women. Thus, maternal toxemia, but not hypertension, might reduce the risk of germinal matrix hemorrhage by reducing the occurrence and/or severity of pulmonary and related problems that place infants at high risk of germinal matrix hemorrhage.

Cerebral Hemorrhage↗
PubMed1988

Hemorrhage, phenobarbital, and fluctuating cerebral blood flow velocity in the neonate.

Fifty-one sequential intubated babies with birth weights of less than 1,751 were evaluated by serial Doppler ultrasound during the first three days of life. These babies were part of a phenobarbital prophylaxis trial cohort study. Subependymal-intraventricular hemorrhage developed in 17 of the babies. Infants with subependymal-intraventricular hemorrhage, whether or not they received pancuronium or phenobarbital, had coefficients of variation comparable to those of babies without hemorrhage. Coefficient of variation values of the right were comparable to values obtained from the left anterior cerebral artery complex and did not appear to be consistently altered by the presence of subependymal-intraventricular hemorrhage. Coefficient of variation values appeared to be consistently greatest on day 1 and lowest on day 2. In addition, the values overall increased as the number of waves used to determine the coefficient of variation enlarged from five to 20. This phenomena, however, was not seen among pancuronium recipients and suggests that movement artifact may be a determinant of coefficient of variation values. We conclude that, when the best 20 waves are chosen to evaluate the coefficient of variation, no association exists between coefficient of variation values and development of subependymal-intraventricular hemorrhage or administration of phenobarbital.

Blood Flow Velocity↗
PubMed1988

Purification and characterization of two different precursor forms of the cathepsin B-like proteinase from human malignant ascitic fluid.

We have purified two different precursors of a cathepsin B-like proteinase (PCBT) from malignant ascitic fluid. The molecular mass of these proteins were 45-47 kDa and 36 kDa, respectively. This report is the first which shows cathepsin-B precursors as purified proteins. By using sheep immunoglobulins directed against denatured lysosomal cathepsin B, we have found that both precursors, together with the 33-kDa pepsin generated cathepsin B-like proteinase, reacted in immunoblotting: the three components are thus cathepsin B-related. These antibodies allow us the show that during pepsin activation the 45-47 kDa precursor is converted to the 33-kDa cathepsin B-like proteinase together with the 36-kDa PCBT. We have also prepared sheep immunoglobulins directed against the 36-kDa precursor. The generation of the cathepsin B-like proteinase by pepsin digestion of purified precursors followed a time and dose dependent process. This latter result argues for activation through peptide bond cleavages.

Ascitic Fluid↗
PubMed1988

Arterial blood gas derangements associated with death and intracranial hemorrhage in premature babies.

We evaluated to what extent acidosis and alkalosis and their respiratory and metabolic components during the first 12 hours of life occurred prior to early neonatal death and postnatal intracranial hemorrhage among 206 low birth weight, intubated premature babies participating in a clinical trial of phenobarbital prophylaxis for intracranial hemorrhage. Time-weighted indices included the time each baby spent with abnormal values of pH, PaCO2 and HCO3-. Babies whose birth weight was less than 1 kg suffered adversities associated with prolonged pH less than 7.35. Heavier birth weight babies were at increased risk of adversity if their pH fell below 7.2. Babies who were not severely acidotic initially, but became so within hours, were at prominently increased risk of death and hemorrhage. Babies who had a mild increase of PaCO2 between 45 and 60 mmHg were less likely to develop germinal matrix hemorrhage than their peers who had more severe hypercapnia. A time-weighted measure of metabolic deficit correlated with death, but not with hemorrhage. Prolonged exposure to pH greater than 7.55 was associated with reduced risk of subependymal/intraventricular hemorrhage and death, especially in babies below 1 kg birth weight. We conclude that acidosis is an antecedent of intracranial hemorrhage in low birth weight premature babies, that duration of exposure might convey important risk information, and that birth weight is a correlate of vulnerability to some pH disturbances.

Acidosis↗
PubMed1988

Bilirubin, intraventricular hemorrhage, and phenobarbital in very low birth weight babies.

The relationships among serum bilirubin concentration on days 5 and 7, birth weight, the presence of intraventricular hemorrhage, and the receipt of phenobarbital were examined in a group of 232 newborns weighing less than 1,751 g who were intubated, mechanically ventilated by 12 hours after birth, and whose parents had given permission for a randomized trial of phenobarbital prophylaxis of intraventricular hemorrhage. The ratio of serum bilirubin concentration to birth weight (the bilirubin divided by birth weight index [BBI]) was used to examine the impact of 25 variables on a clinical guideline for therapy of hyperbilirubinemia in newborn infants. A linear regression model was used; the most powerful covariate was a birth weight less than 1.0 kg. The only other variable that reduced the BBI was phenobarbital receipt. The presence of intraventricular hemorrhage and ecchymoses had a significant influence increasing the BBI.

Bilirubin↗
PubMed1987

Phosphorylation on tyrosine of oestradiol-17 beta receptor in uterus and interaction of oestradiol-17 beta and glucocorticoid receptors with antiphosphotyrosine antibodies.

In whole rat uterus incubated in the presence of [32P]orthophosphate the oestradiol receptor is [32P]phosphorylated on tyrosine. This finding follows our previous observation that in vitro this receptor can be phosphorylated on tyrosine by a uterus kinase that endows the receptor with oestradiol-binding activity. The calf uterus oestradiol receptor interacts with high affinity with 2G8 and 1G2 antiphosphotyrosine antibodies coupled to Sepharose (Kd values of 0.28 and 1.1 nM, respectively). The interaction with 2G8 antibody has been exploited to purify the oestradiol receptor. This interaction disappears after inactivation of the oestradiol receptor by the nuclear phosphatase that hydrolyses phosphotyrosine of the receptor. This fact substantiates the evidence that the oestradiol receptor in uterus is phosphorylated on tyrosine and that this phosphorylation is required for hormone binding to the receptor. The rat liver glucocorticoid receptor also interacts with high affinity with 2G8 antiphosphotyrosine antibody coupled to Sepharose (Kd value of 0.21 nM). This receptor has been purified by using in sequence heparin-Sepharose and antiphosphotyrosine antibody-Sepharose.

Animals↗
PubMed1986

Activation-inactivation of hormone binding sites of the oestradiol-17 beta receptor is a multiregulated process.

The calf uterus oestradiol-17 beta receptor exists in a hormone binding form, which is phosphorylated on tyrosine, and in a non-hormone binding form, which is dephosphorylated. Two enzymes regulate the number of hormone binding sites of the receptor: a kinase which has been purified from cytosol and a phosphatase purified from nuclei. Recent and new findings on the regulation of this activation-inactivation process are reported. In vitro only a fraction (30-60%) of the receptor binding sites are inactivated by the phosphatase. Evidence is given suggesting that this is due to the production during the inactivation process of a powerful inhibitor of the phosphatase. Ca2+-calmodulin stimulates the kinase activity with a parallel increase of phosphorylation on tyrosine and hormone binding sites of the receptor. Nanomolar concentrations of oestradiol-17 beta also stimulate the kinase to activate hormone binding sites. These results suggest that in intact cells inactivation-activation of the oestradiol receptor is a multiregulated process.

Animals↗
PubMed1986

Inhibition of the cathepsin B like proteinase by a low molecular weight cysteine-proteinase inhibitor from ascitic fluid and plasma alpha 2 macroglobulin.

The cathepsin B like proteinase present in ascitic fluid of a patient with neoplasia has been purified and characterized after pepsin activation. From this fluid we have prepared the low molecular weight (LMW) cysteine-proteinase inhibitors. Three major inhibitor forms were found with isoelectric points of 7.4, 5.4, and 5.1, respectively. The interaction of the enzyme with the former inhibitor was studied because this inhibitor was the most abundant. The Ki value was found to be 4.3 X 10(-8) M. Two molecules of this proteinase were bound by one molecule of plasma alpha 2 macroglobulin (alpha 2M). The LMW inhibitor was able to bind to the enzyme entrapped in alpha 2M and reduced its endopeptidase activity on benzyloxycarbonyl-L-phenylalanyl-L-arginine-4-methyl-7-coumarylamide. These results may have a physiological significance in the regulation of the enzyme which, among other extracellular hydrolases, probably plays an important role in tumor invasion.

Ascites↗
PubMed1985

A randomized comparison of cyclophosphamide, Adriamycin, and 5-fluorouracil with triethylenethiophosphoramide and methotrexate, both as sequential and as fixed rotational treatment in patients with advanced ovarian cancer.

The combinations of triethylenethiophosphoramide and methotrexate (TM) and cyclophosphamide, Adriamycin (doxorubicin), and 5-fluorouracil (CAF) were compared, both as sequential and fixed rotational treatments for advanced ovarian cancer, with L-phenylalanine mustard (L-PAM). Treatment with CAF produced a higher response rate (25% complete responses plus 31% partial responses) than treatment with L-PAM (15% complete responses plus 18% partial responses). A fixed rotation of TM and CAF resulted in longer survival (median of 15 months and 75th percentile of 27 months) than sequential treatment with TM initially, followed by CAF upon failure (median of 12 months and 75th percentile of 22 months). The fixed rotation of TM and CAF also increased progression-free survival (median of 12 months and 75th percentile of 24 months) over that achieved by initial treatment with TM (median of 6 months and 75th percentile of 15 months) or L-PAM (median of 9 months and 75th percentile of 21 months). Most patients (96%) on the fixed rotation were treated with both TM and CAF. Fewer patients (62%) on the sequential schedule with TM actually received both combination regimens, and even fewer patients (37%) beginning on CAF ever crossed over to TM. Patient age of 50 years or younger was a favorable prognostic factor for response, survival, and time to first treatment failure (progression-free survival). Disease Stage IIIA or IIIB, surgery including a bilateral salpingo-oophorectomy plus hysterectomy, and treatment within 6 months of initial diagnosis were favorable predictors for both survival and time to first treatment failure. Ambulatory performance status and well-differentiated disease were favorable prognostic factors for survival. Patients with unevaluable disease failed later than those with evaluable disease who, in turn, failed later than patients with measurable disease.

Adenocarcinoma↗
PubMed1985

Prophylactic versus no brain irradiation in regional small cell lung carcinoma.

Among 104 complete responders entered in a randomized prospective trial of treatments for regional small cell undifferentiated carcinoma of the lung, 52 received prophylactic irradiation of the brain, 3,000 rad in 10 fractions, and 52 did not. The median survivals were 53 and 52 weeks respectively, and the incidences of brain metastases were 5% and 20%. Prophylactic brain irradiation was not associated with significant long-term toxicity.

Brain Neoplasms↗
PubMed1985

[Regulation of neoplasm-specific cathepsin B by cysteine-protease inhibitors present in cancerous exudates].

The Cathepsin B-like proteinase, a secretory form of lysosomal cathepsin B, is present in some cancerous exudates (i.e. pleural and ascitic fluids). It has been suggested that this enzyme may be involved in the invasive process, one of the most important aspects of cancer pathology. In the same fluids, two kinds of cysteine-proteinase inhibitors (C.P.I.'s) are found- HMr-CPI (90,000 daltons) and LMr-CPI's (11,000-13,000 daltons). The Cathepsin B-like enzyme is more strongly inhibited by the LMr-CPI's than by the HMr-CPI, the Ki values are 4.0 X 10(-9) M and 1.2 X 10(-7) M respectively. Theses results underline the similarity between this enzyme and the lysosomal Cathepsin B. On the other hand, the inhibitors could play a protective role against tumor invasion.

Ascitic Fluid↗
PubMed1984

Inhibition of human liver cathepsin L by alpha 2 cysteine-proteinase inhibitor and the low-Mr cysteine proteinase inhibitor from human serum.

The inhibition of human liver cathepsin L by two specific proteinase inhibitors present in human serum, namely alpha 2 cysteine-proteinase inhibitor and the low-Mr cysteine-proteinase inhibitor, was studied. Kinetic parameters, including inhibition constants (Ki) and rate constants for association and dissociation (k+1 and K-1), were determined. The values found are consistent with a possible physiological function of these inhibitors to control cathepsin L activity. Furthermore, a transfer of active proteinase from the complex with either cysteine-proteinase inhibitor species to alpha 2-macroglobulin was demonstrated in vitro. Given the rate of dissociation of both cathepsin-L-cysteine-proteinase inhibitor complexes, a function of transitory inhibitor can therefore be hypothesized for these proteins and might then provide an explanation of the clearance of lysosomal proteinases.

Binding Sites↗
PubMed1984

Alpha 2 high molecular mass cysteine proteinase inhibitor: HMr alpha 2-CPI. An inhibitor of human liver cathepsin H as probed by kinetic study.

HMr alpha 2CPI was found to be an inhibitor of human liver cathepsin H by the measurement of the dissociation constant (Ki), the association rate constant (k1) and the dissociation rate constant (k-1) between the enzyme and the inhibitor. These data suggest that this protein-proteinase inhibitor can play a physiological role in the regulation of free cathepsin H.

Cathepsins↗
PubMed1984

Phase II study of methyl-glyoxal bis-guanylhydrazone (NSC 3296) in advanced ovarian cancer.

Thirty-nine patients received 600 mg/m2 OF MGBG intravenously every week for the treatment of advanced refractory ovarian cancer. Twenty-seven of these received adequate trials, and only two had partial remissions lasting 3 1/2 and 4 months each. Toxicity was substantial, with severe hematologic toxicity in 26%, diarrhea in 22% (severe in 7%), skin rash in 26% (severe in 7%), and vomiting in 70% (severe in 11%). Fatigue, facial paresthesias, and flushing during drug administration were frequent. It appears that MGBG in this dose and schedule has little activity against advanced ovarian cancer.

Blood↗