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Biomedical subjects

P Russo

Publications and source records attributed to P Russo.

At least 235 records · Page 13Linked to original sources
PubMed1993

Ischemia in collateral-dependent myocardium: effects of nifedipine and diltiazem in man.

It has recently been shown that ischemia in collateral-dependent myocardium may develop at a very variable threshold in anginal patients; accordingly, the aim of this study was to assess whether nifedipine and diltiazem can increase blood flow to collateralized myocardium in man. Nine patients with complete coronary occlusion filled by collaterals, with no other coronary stenosis, normal left ventricular function, and reproducibly positive exercise tests were studied. They underwent exercise tests off therapy and after acute randomized administration of nifedipine (10 mg sublingually), diltiazem (120 mg orally), and nitroglycerin (0.5 mg sublingually), the latter a drug known to increase blood flow to collateralized myocardium. Following nifedipine, time to 1 mm ST segment depression increased significantly (from 430 +/- 176 to 576 +/- 205 seconds, p < 0.01), while heart rate and rate-pressure product remained unchanged (115 +/- 16 vs 121 +/- 17 beats/min and 199 +/- 29 vs 204 +/- 44 beats/min.mm Hg.10(2), respectively, p = NS for both). Similarly, diltiazem significantly increased time to ischemic threshold from baseline to 638 +/- 125 seconds (p < 0.01), but did not change heart rate and rate-pressure product at 1 mm ST segment depression. Submaximal rate-pressure products were significantly lowered by both nifedipine and diltiazem. Nitroglycerin not only significantly improved time to ischemic threshold (from baseline to 666 +/- 76 seconds, p < 0.01), but also increased heart rate (from baseline to 137 +/- 16 beats/min, p < 0.01) and rate-pressure product (from baseline to 242 +/- 48 beats/min.mm Hg.10(2), p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Intracardiac teratoma 15 years after treatment of a nonseminomatous germ cell tumor.

A patient presented to our center with a 15-year history of medical, surgical and radiation treatment for a nonseminomatous germ cell tumor and contralateral seminoma. He experienced a cerebral infarction, which led to the diagnosis of an intracardiac tumor. The tumor was resected and found to be a mature teratoma. We discuss the diagnosis and management of this unusual metastatic nonseminomatous germ cell cancer.

Adult↗
PubMed1993

Potentiation of tumour necrosis factor-mediated cell killing by VP16 on human ovarian cancer cell lines. In vitro results and clinical implications.

Synergism between recombinant human tumour necrosis factor (rHuTNF) and DNA topoisomerase II inhibitor VP16 during the killing of cells has been studied in six human ovarian cancer cell lines (A2774, A2780, SW626, IGROV-1, SKOV3, Pa1) and a cervical carcinoma cell line (Me180). Studies were performed using an assay of colony formation inhibition (drug treatment for 1 h) and a growth inhibition assay (continuous exposure for 20 h). Concomitant treatment of cells with VP16+rHuTNF enhanced cell killing in all the cell lines tested--an effect observed in both short- and long-term cytotoxicity assays. This study suggests that the activity of VP16 in ovarian cancer cell lines might be enhanced by rHuTNF in in vitro models.

Cell Survival↗
PubMed1993

Surgical and metabolic aspects of liver transplantation for tyrosinemia.

Tyrosinemia is the diagnosis of a very small percentage of patients undergoing liver transplantation worldwide. Tyrosinemia is endemic within our referral area however, and fully one-third of the liver transplantations at our institution are done for this disease. Since 1986, 15 patients with tyrosinemia (TYR) and 31 patients with various other indications (non-TYR) have undergone a total of 51 liver transplantations. The 36-month actuarial survival for TYR patients is 87%, compared with 74% for non-TYR patients. Liver transplantation for hereditary tyrosinemia and other metabolic disorders without portal hypertension or previous portohepatic operations is notably easier to perform. Intraoperative blood loss was less, length of hospital stay was shorter, and incidence of infections was lower in TYR than in non-TYR patients. Less than 10% of TYR patients had foci of hepatocellular carcinoma at the time of transplantation. For this reason, and while most patients with tyrosinemia will eventually require liver transplantation, our results do not support systematic early transplantation before the age of two years.

Adolescent↗
PubMed1993

Signals that produce 3' termini in CYC1 mRNA of the yeast Saccharomyces cerevisiae.

The cyc1-512 mutant was previously shown to contain a 38-bp deletion, 8 nucleotides upstream from the major wild-type poly(A) site, in the CYC1 gene, which encodes iso-1-cytochrome c of the yeast Saccharomyces cerevisiae. This 38-bp deletion caused a 90% reduction in the CYC1 transcripts, which were heterogeneous in size, aberrantly long, and presumably labile (K. S. Zaret and F. Sherman, Cell 28:563-573, 1982). Site-directed mutagenesis in and adjacent to the 38-bp region was used to identify signals involved in the formation and positioning of CYC1 mRNA 3' ends. In addition, combinations of various putative 3' end-forming signals were introduced by in vitro mutagenesis into the 3' region of the cyc1-512 mutant. The combined results from both studies suggest that 3' end formation in yeast cells involves signals having the following three distinct but integrated elements acting in concert: (i) the upstream element, including sequences TATATA, TAG ... TATGTA, and TTTTTATA, which function by enhancing the efficiency of downstream elements; (ii) downstream elements, such as TTAAGAAC and AAGAA, which position the poly(A) site; and (iii) the actual site of polyadenylation, which often occurs after cytidine residues that are 3' to the so-called downstream element. While the upstream element is required for efficient 3' end formation, alterations of the downstream element and poly(A) sites generally do not affect the efficiency of 3' end formation but appear to alter the positions of poly(A) sites. In addition, we have better defined the upstream elements by examining various derivatives of TATATA and TAG ... TATGTA, and we have examined the spatial requirements of the three elements by systematically introducing or deleting upstream and downstream elements and cytidine poly(A) sites.

Alleles↗
PubMed1993

Management of airway obstruction in patients with congenital heart defects.

Airway obstruction may complicate the course of infants undergoing repair of congenital heart disease. Airway obstruction was encountered in seven patients following surgery for complex congenital heart defects (two with interrupted aortic arch, one with pulmonary atresia and a ventricular septal defect, one with tetralogy of Fallot and an abnormal left anterior descending coronary artery, one with truncus arteriosus, and two with complex univentricular heart). In four patients, a conduit was implanted at the time of surgery. In all cases, bronchoscopy accurately demonstrated the cause of the airway obstruction. Two infants had hypoplasia of the left bronchus, and five had tracheobronchomalacia associated with extrinsic compression of the airway by a great vessel or conduit. All were treated conservatively with therapeutic bronchoscopy, tracheotomy, and/or stenting with prolonged mechanical ventilation. Follow-up ranged from 2 to 40 months. Four infants have been weaned from mechanical ventilation and decannulated; two are awaiting decannulation; and one was decannulated and died awaiting surgical repair. To reduce morbidity in infants undergoing surgery for congenital heart disease, the presence of preoperative airway anomalies should be sought and surgery planned to avoid airway compression. Conservative management using diagnostic and therapeutic bronchoscopy, tracheotomy, and stenting together with prolonged ventilator care is rewarding.

Bronchial Diseases↗
PubMed1993

An intact and functional soluble form of the insulin receptor is secreted by cultured cells.

We have recently reported that the insulin receptor (IR), a tetrameric transmembrane protein located on the surface of target cells, is present as a soluble form in human plasma. In the present study we investigated whether human cells in culture release an intact and functional form of the IR. We found that IRs are secreted into the incubation medium by four cell lines (IM-9 human lymphoblasts, MCF-7 human breast cancer cells, HepG2 human hepatoma cells, and 3T3 mouse fibroblasts transfected with human IRs). IR secretion was further characterized in IM-9 cells. IR release was time, temperature, and energy dependent, and enhanced by incubation with insulin. The dilution slope of secreted IRs in a specific IR RIA was parallel to that produced by highly purified human placenta IRs. Ligand binding studies revealed that secreted receptors bound insulin with high affinity, and the Scatchard analysis revealed two orders of binding sites (the high affinity site had a dissociation constant of 0.32 +/- 0.08 nM). Analysis of secreted receptors by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated a molecular size of 135 kilodaltons for the alpha-subunit and 95 kilodaltons for the beta-subunit. Other experiments indicated that the beta-subunit tyrosine kinase activity of the secreted receptor was stimulated by insulin. These studies indicate, therefore, that a soluble, intact, and functional IR is secreted by cultured cells, and that this soluble protein could be involved in certain insulin-mediated functions, such as receptor down-regulation.

3T3 Cells↗
PubMed1993

Insulin-resistant MDA-MB231 human breast cancer cells contain a tyrosine kinase inhibiting activity.

In most human breast cancer cell lines, insulin, via its own receptor, stimulates cell growth. However, in MDA-MB231 breast cancer cells, insulin at concentration as high as 100 nM has no effect on cell growth, although insulin receptors (IRs) are overexpressed in these cells (29.1 ng IR/10(6) cells), and IR binding characteristics are similar to other breast cancer cell lines. IR tyrosine kinase activity is markedly reduced both in intact MDA-MB231 cells and in isolated IRs purified on a wheat germ agglutinin affinity column. MDA-MB231 cells contain a factor that inhibits both basal and insulin-stimulated IR tyrosine kinase activity in a concentration-dependent manner. This inhibitory activity copurifies with the IR on insulin-Sepharose affinity chromatography and is also effective against the tyrosine kinase activity of the IR-related insulin-like growth factor-I receptor and the oncoprotein v-abl but is ineffective against c-src tyrosine kinase activity. It is possible, therefore, that this tyrosine kinase inhibitor plays a role in regulating the mitogenic potential of the IR in some human breast cancers.

Breast Neoplasms↗
PubMed1993

Reversal of "atypical"-multidrug resistance by recombinant human tumor necrosis factor in the human ovarian cancer cell line A2780-DX3.

A2780 human ovarian cancer cell line and its multidrug resistant counterpart A2780-DX3 were utilized for this in vitro study. A2780-DX3 is resistant in various degrees to several topoisomerase II inhibitors but sensitive to vinca alkaloids. Simultaneous treatment of the A2780-DX3 line with 1000 U/mL rHuTNF largely reverses resistance to most topoisomerase II inhibitors. By itself, 1000 U/mL rHuTNF is not toxic to the resistant line. Uptake and retention of [3H]-Mitoxantrone are not modified by rHuTNF, whereas rHuTNF is very active in potentiating the effects of Mitoxantrone. After treatment with topoisomerase II inhibitors, Doxorubicin, Mitoxantrone, or VP16, rHuTNF restores DNA-SSB and DNA-protein cross-links in the resistant line to the level of the wild type. The cleavage activity of topoisomerase II in the resistant line is about 40% of the level present in the parental line. Five minutes after the addition of 1000 U/mL of rHuTNF, the cleavage activity in the resistant line is about 85% of the level present in the parental line. The catalytic activity of topoisomerase II is only 15% lower in the resistant line, but it is increased by about 50% 5 min after the addition of rHuTNF to the resistant line. These effects are transient and cannot be observed after 30 min. These transient direct effects of rHuTNF on topoisomerase II could be associated with its ability to restore sensitivity to inhibitors of topoisomerase II in the A2780-DX3 line.

Antineoplastic Agents↗
PubMed1993

Ultrastructural localization of DNA in immune deposits of human lupus nephritis.

DNA molecules were revealed in the glomerular wall of lupus nephritis patients by applying two specific colloidal gold cytochemical approaches at the electron microscope level: immunocytochemistry using a monoclonal anti-DNA antibody in conjunction with protein A-gold and enzyme-gold cytochemistry using DNAse-gold complexes. Application of both techniques has demonstrated that DNA molecules are preferentially located over the electron-dense deposits found in the glomerular basement membrane and mesangial matrix of SLE patients, as well as over the nuclei. Their distribution within the glomerular wall was correlated with electron-dense immune deposits revealed by anti-light chain antibodies. In normal control kidney, DNA labeling was restricted to the cell nuclei. Several control experiments have demonstrated the high specificity of the results. These data thus suggest a possible role for DNA as an antigenic component in the formation of immune complexes.

Adolescent↗
PubMed1993

Focal segmental glomerulosclerosis (FSG) 20 years later. From toddler to grown up.

In 1981, we reported the outcome of 25 children with FSG after a follow-up of 10 years. In 1991, all the living patients were reevaluated. Ten patients are now in sustained remission. Four patients still present heavy proteinuria with a normal glomerular filtration rate, four required dialysis and seven patients have died. The renal survival curve has stabilized at 56%. These data show an overall outcome slightly more favourable than we had initially reported in 1981. The difference probably stems from our referral system which enables us to see the patients at an earlier stage of their disease. The percentage of deaths is important. Among the various clinical or histological factors of predictive prognostic value only the degree of interstitial damage has reached statistical significance (p < 0.02).

Actuarial Analysis↗
PubMed1993

Poly-L-lysine-gold probe for the detection of anionic sites in normal glomeruli and in idiopathic and experimentally-induced nephrosis. A comparative ultrastructural study.

Anionic sites play a key role in the charge selectivity of glomerular filtration as well as in the maintenance of the structural integrity of the visceral epithelium and podocytes. Alterations in these sites are believed to be a major factor underlying human idiopathic nephrosis and puromycin-nephrosis in the rat. The poly-L-lysine-gold complex was used for the ultrastructural detection of anionic sites in renal glomeruli of patients with idiopathic nephrosis as well as of rats with puromycin-induced nephrosis, allowing for study of the changes occurring in the anionic sites during nephrosis and for the comparison between human disease and this experimental model. In both normal human and rat controls, the probe was detected on epithelial and endothelial cell surfaces and on the glomerular basement membrane, mainly in both laminae rarae. In proteinuric rats, a decrease in labeling intensity was noted on podocyte membranes and in the lamina rara externa, with a corresponding increase in the more central areas of the glomerular basement membrane. These changes were not as evident in proteinuric humans. Furthermore, a reduction in labeling density was noted in the glomerular basement membrane of proteinuric animals, although this could not be substantiated in human tissues. Poly-L-lysine-gold is a useful probe for anionic sites in fixed tissues, and allows for comparison between human disease and its experimental counterpart.

Adolescent↗
PubMed1992

Chiral separation of leucovorin with bovine serum albumin using affinity capillary electrophoresis.

A method for the determination of the (6R)- and (6S)-stereoisomers of leucovorin using electrokinetic chromatography (EKC) in the affinity mode has been developed. Bovine serum albumin (BSA) is used as a run buffer additive to incorporate enantiomeric selectivity into the system. Protein-wall interactions are minimized by using a poly(ethylene glycol) (PEG) coated capillary. Chiral resolution is obtained in 12.5 min with efficiencies greater than 200,000 theoretical plates using BSA as an additive, while no resolution is obtained in the absence of BSA. A general equation is derived to calculate the free energy of interaction between the leucovorin isomers and the BSA molecule. This method represents a new means of obtaining thermodynamic data for substrate binding interactions and for the general study of drug cross-reactions and interactions of drugs with serum and other proteins.

Electrolytes↗