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Biomedical subjects

M Rossi

Publications and source records attributed to M Rossi.

At least 541 records · Page 30Linked to original sources

A digital computer model for optimal programming of hemodialytic treatment.

A mathematical model of hydroelectrolyte exchanges and arterial pressure regulation in the human body during dialysis has been set up. It is conceived as a tool for a new dialysis unit which will be able to "interpret" the signals supplied by suitable instruments connected to the patient and modify the machine set-points in real time in order to obtain clinical results defined by the physician. The main aim is the prevention of hypotensive episodes during treatment. An experimental protocol has been developed for parameter estimation of each patient during a single dialysis. Clinical tests illustrated the model's ability to fit the patient's state during dialysis. This is the first step in the more general task of validation of the model, necessary for the achievement of a closed-loop dialysis unit.

Computer Simulation↗

A novel archaebacterial NAD+-dependent alcohol dehydrogenase. Purification and properties.

An NAD+-dependent alcohol dehydrogenase (alcohol: NAD+ oxidoreductase, EC 1.1.1.1) was detected in cellular extracts of the extreme thermophilic archaebacterium Sulfolobus solfataricus. The enzyme was purified to homogeneity and shown to be a dimer with a native molecular mass of 71 kDa by sucrose gradient centrifugation and SDS electrophoresis. The enzyme has a broad substrate specificity that includes linear and branched primary alcohols, linear and cyclic secondary alcohols, linear and cyclic ketones and anisaldehyde. The enzyme has an extraordinary thermophilicity and a remarkable thermostability, and appears to have some properties and a structure different from those previously described for thermophilic alcohol dehydrogenases.

Alcohol Dehydrogenase↗

Malic enzyme from archaebacterium Sulfolobus solfataricus. Purification, structure, and kinetic properties.

An NADP-preferring malic enzyme ((S)-malate:NADP oxidoreductase (oxalacetate-decarboxylating) EC 1.1.1.40) with a specific activity of 36.6 units per mg of protein at 60 degrees C and an isoelectric point of 5.1 was purified to homogeneity from the thermoacidophilic archaebacterium Sulfolobus solfataricus, strain MT-4. The purification procedure employed ion exchange chromatography, ammonium sulfate fractionation, affinity chromatography, and gel filtration. Molecular weight determinations demonstrated that the enzyme was a dimer of Mr 105,000 +/- 2,000 with apparently identical Mr 49,000 +/- 1,500 subunits. Amino acid composition of S. solfataricus enzyme was determined and found to be significantly higher in tryptophan content than the malic enzyme from Escherichia coli. In addition to the NAD(P)-dependent oxidative decarboxylation of L-malate, S. solfataricus malic enzyme was able to catalyze the decarboxylation of oxalacetate. The enzyme absolutely required divalent metal cations and it displayed maximal activity at 85 degrees C and pH 8.0 with a turnover number of 376 s-1. The enzyme showed classical saturation kinetics and no sigmoidicity was detected at different pH values and temperatures. At 60 degrees C and in the presence of 0.1 mM MnCl2, the Michaelis constants for malate, NADP, and NAD were 18, 3, and 250 microM, respectively. The S. solfataricus malic enzyme was shown to be very thermostable.

Amino Acids↗

Alteration of methotrexate metabolism in rats by administration of an elemental liquid diet. I. Changes in drug enterohepatic circulation.

Severe enteritis and death consistently occur within 150 hours of a single intraperitoneal dose of 25 mg/kg methotrexate given to rats fed an elemental diet. Rats fed a regular chow diet show no clinical evidence of gastrointestinal morbidity or mortality at this dose. The etiology of this enhanced toxicity is not clear, however. It this study rats were randomized to receive an elemental diet (n = 45) or a regular chow diet (n = 45) for 7 days. They were then given a bolus dose of 3H methotrexate (25 mg/kg) intraperitoneally. At 20 and 40 minutes and at 1, 2, 12, 24, 48, 72, and 96 hours after injection, five animals from each group were anesthetized, and mean methotrexate levels in bile and serum, and tissue methotrexate concentrations in proximal, mid, and distal small intestine and in liver were obtained. Mean methotrexate levels in bile were significantly elevated in rats fed an elemental, chemically defined diet at 12, 24, 48, and 72 hours compared with regular diet fed rats. Mean serum methotrexate levels were elevated in both the inferior vena cava (IVC) and portal vein (PV) at 12 (IVC), 24 (PV), and 48 hours (IVC) in elemental, liquid diet fed rats. There were no statistical differences between methotrexate levels in rats fed an elemental diet or a regular chow diet in proximal or mid small intestine at any of the time points measured. In the distal small intestine, methotrexate levels were significantly elevated at 24 hours in rats fed an elemental, chemically defined liquid diet (P less than 0.03) compared with regular diet fed rats. Methotrexate levels in liver of rats fed an elemental, chemically defined liquid diet were significantly elevated at 24 and 48 (P less than 0.05) hours. Administration of an elemental, chemically defined liquid diet prolongs the enterohepatic circulation of methotrexate in rats and delays clearance of the drug from the systemic circulation. Thus, prolonged exposure of methotrexate to the cells of the intestinal mucosa explains the increased gastrointestinal side effects of the drug in rats fed an elemental, chemically defined liquid diet. If these results are applicable to man, elemental, chemically defined liquid diets are contraindicated as the sole nutritional source in patients receiving methotrexate. Such qualitative alteration of dietary intake may be a factor in the unpredictability of gastrointestinal side effects associated with high dose methotrexate administration.

Animals↗

Defining the active site of cytochrome P-450: the crystal and molecular structure of an inhibitor, SKF-525A.

The crystal and molecular structure of the cytochrome P-450 inhibitor, SKF-525A [2-(diethylamino)ethyl 2,2-diphenylpentenoate; proadifen hydrochloride] is described. Proadifen hydrochloride crystallized from an ethyl acetate and acetic acid mixture in the space group P2(1)/c with one molecule in the asymmetric unit. Cell constants are a = 18.716(4), b = 8.906(1), c = 14.201(3), beta = 109.41(1) degrees. The structure was solved using direct methods and was refined to an R value of 0.047; weighted R of 0.061 using 3757 reflections. From the crystal and molecular structure, it is seen that SKF-525A has two principal modes of complementary interactions with the enzyme available: polar and non-polar. Polar interactions that principally involve the chloride anion, the quaternary nitrogen atom and the carbonyl oxygen atom. In particular, there are two strong hydrogen bonds, one between Cl ... H-N, 3.090(1) A, the other between O2 ... H-C111 (one of the ethyl hydrogen atoms) at 3.411(2) A. The other is through non-polar interactions involving the phenyl and alkyl groups. Comparisons between proadifen hydrochloride and other inhibitors whose atomic coordinates are available reveal common features which correlate with their function. These include groups to provide necessary intermolecular contacts and bulk, such as a phenyl group and a hydrogen bond acceptor, as well as a tetrahedral atom, which allows for substrate flexibility.

Crystallization↗

Subaortic fibrous ridge and ventricular septal defect: role of septal malalignment.

The purpose of this study was to test the hypothesis that the presence of a subaortic ridge associated with a ventricular septal defect (VSD) is related to a malaligned ventricular septum caused by anterior or posterior deviation of the infundibular septum with or without obstructive lesions of the aortic arch. Thirty-two of 295 patients in whom a diagnosis of VSD was made by two-dimensional echocardiography and who were studied from June 1983 to April 1985 presented with a subaortic shelf. Every patient (p less than .00001) had a malalignment type of defect; the defect was produced by anterior deviation of the outlet septum (without compromise of the right ventricular outflow tract) in 28 and by posterior deviation of the infundibular septum in four. The prevalence of a subaortic shelf in the malalignment VSD group was 82% (32/39). Among the 28 patients with a subaortic ridge and anterior deviation of the outlet septum only three had aortic coarctation, but all four patients with subaortic stenosis and posterior infundibular malalignment had obstructive lesions of the aortic arch--coarctation in three and interruption of the aortic arch in one (p less than .001). We conclude that a malalignment type of VSD may be a consistent feature in patients with VSD and associated discrete subaortic stenosis. We also noted a high prevalence of subaortic ridge in the presence of a malalignment VSD and therefore speculate that there may be a common morphogenesis for malalignment VSD, subaortic shelf, and obstructive lesions of the aortic arch.

Adolescent↗

Adenocarcinoma of the cardia: the choice of surgical treatment.

The ideal surgical treatment for adenocarcinoma of the cardia is still controversial. Out of 168 consecutive patients resected in a 10-year period, 98 underwent esophagogastric resection (EGR) and 70 total gastrectomy with esophageal resection (TGER). Early and long-term results were compared in order to define specific indications for both surgical procedures. Abdominal nodes were metastatic in 62% of the cases; mediastinal nodes were metastatic in 20.3% of 138 thoracotomized patients. Neoplastic permeation of the section margin occurred in 4.7% of the patients. No positive section margins were found in the cases with 10 cm or more of uninvolved esophagus resected. The superiority of the thoracoabdominal approach was therefore evident in terms of oncologic radicality. Anastomotic leakages occurred in 13.3% of EGR and in 7.1% of TGER patients. No correlation between the stage of the tumor or the neoplastic permeation of the section margin and the incidence of leak was found. Operative mortality was 7.1% after EGR and 10% after TGER, which may suggest that EGR is the procedure of choice in poor-risk and elderly patients. Loco-regional or systemic neoplastic recurrence was responsible for long-term mortality in 70% of the cases. Anastomotic recurrence was found in 12.2% of EGR patients and in 1.4% of TGER patients. Overall five-year survival was 19.1%. Mean survival was 29.5 months, 30 after EGR and 27 after TGER (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

[Determination of lymphocyte subpopulations in multiple myeloma and monoclonal gammopathies of undetermined significance].

By means of monoclonal antibodies, the lymphocyte subpopulation in 12 patients affected by multiple myeloma, 3 by Waldenström's macroglobulinemia, 7 by M.G.U.S. and 8 patients affected by accompanying monoclonal gammopathy have been determined. The group of patients affected by multiple myeloma or Waldenström's macroglobulinemia presented, against control, a significant reduction in the OK T3+ and OK T4+ cell percentage, with a remarkable reduction of the OK T4+/OK T8+ ratio. The OK T8+ cell average, if considered as an absolute value, was not modified in comparison to normal value, while the absolute number of OK T4+ cells was substantially reduced. No significant modifications have been ascertained in the percentage of SIg+ cells. The patients affected by M.G.U.S. did not present significant difference against controls, with regard to the lymphocyte number and the percentage of OK T3+ and OK T4+ cells. On the contrary, a significant increase of the percentage and absolute number of OK T8+ cells was observed. Also in these cases, a significant reduction of the OK T4+/OK T8+ ratio was observed. Finally, the patients affected by accompanying monoclonal gammopathy presented a significant reduction of OK T3+ and OK T8+ cells, with an increase of the percentage of OK T4+ cells and of the OK T4+/OK T8+ ratio.

Aged↗