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Biomedical subjects

F Confalonieri

Publications and source records attributed to F Confalonieri.

At least 19 recordsLinked to original sources
PubMed1995

Cloning and sequencing of the gene coding for topoisomerase I from the extremely thermophilic eubacterium, Thermotoga maritima.

A 2767 bp fragment containing a gene coding for a topoisomerase I from the extremely thermophilic eubacterium Thermotoga maritima (Tm TopA) has been cloned and sequenced. The protein is composed of 633 amino acids with a calculated molecular mass of 72,695 Da. It shares significant similarity with the topoisomerases I of mesophilic eubacteria. The highest score is obtained with Bacillus subtilis (44% identity); in particular, T. maritima and B. subtilis possess an insertion of 7-8 amino acids in the vicinity of the active site, that is absent in topoisomerases of other organisms. A specific feature of T. maritima topoisomerase I is its low cysteine content compared to its mesophilic homologs. It contains 5 cysteine residues, of which 4 could constitute a zinc finger motif. Finally, analysis of the regions flanking the gene reveals that Tm TopA is surrounded by two other ORFs, suggesting the occurrence of a polycistronic transcriptional unit.

Amino Acid Sequence↗
PubMed1995

A 200-amino acid ATPase module in search of a basic function.

A fast growing family of ATPases has recently been highlighted. It was named the AAA family, for ATPases Associated to a variety of cellular Activities. The key feature of the family is a highly conserved module of 230 amino acids present in one or two copies in each protein. Despite extensive sequence conservation, the members of the family fulfil a large diversity of cellular functions: cell cycle regulation, gene expression in yeast and HIV, vesicle-mediated transport, peroxisome assembly, 26S protease function etc. In addition, several members of this family can be found in the same organism (up to 17 in S. cerevisiae). The contrast between functional diversity and structural conservation of the module, from archaebacteria to mammals, suggests that it plays an essential, but as yet unknown, role at key points of the cellular machinery. Two (non-exclusive) such possibilities are: (1) ATP-dependent proteasome function and (2) ATP-dependent anchorage of proteins. Finally, the basic biochemical activity of the AAA module is still a matter of speculation, and we propose that it acts as an ATP-dependent protein clamp.

Adenosine Triphosphatases↗
PubMed1995

Autonomic neuropathy and prolongation of QT interval in human immunodeficiency virus infection.

Autonomic neuropathy has been reported in human immunodeficiency virus positive (HIV+) patients. Since alterations in cardiac innervation may determine QT interval prolongation, this interval was studied in a group of HIV+ subjects to evaluate if it is prolonged and to compare this measurement with other diagnostic tests for autonomic neuropathy. Fifty-seven HIV+ and 23 human immunodeficiency virus negative (HIV-) subjects were studied. Autonomic function was tested by noninvasive cardiovascular reflex tests, and the QT interval on the electrocardiogram was measured at rest, at maximum tachycardia during Valsalva manoeuvre, and afterwards at maximum bradycardia. QT intervals were corrected for heart rate according to Bazzett's formula (QTc). Autonomic neuropathy was found in 37 HIV+ subjects: 25 had moderate autonomic neuropathy (HIV+/mAN) and twelve had severe autonomic neuropathy (HIV+/sAN). The 23 HIV- and 20 HIV+ (HIV+/AN-) patients did not have autonomic neuropathy. QTc intervals were significantly longer in HIV+/sAN and HIV+/mAN than in HIV- at rest; in HIV+/sAN than in HIV- at maximum tachycardia; in HIV+/sAN and HIV+/mAN than in HIV+, in HIV+/sAN and HIV+/mAN than in HIV+/AN- and in HIV+/sAN than in HIV+/mAN at maximum bradycardia. QTc was > or = 440 ms in 24 out of 37 (64.8%) patients with autonomic neuropathy and in five out of 20 (25%) HIV+/AN- patients (sensitivity 65%, specificity 75%). A significant correlation was observed between scores of autonomic involvement and QTc interval prolongation. This study confirms that the QTc measurement is a reliable parameter indicating the presence of autonomic neuropathy. Since QT prolongation may determine ventricular arrhythmias, such patients must be followed because they may be at increased risk of sudden death.

Adult↗
PubMed1995

[Cholecystolithotomy with cholecystojejunostomy as surgical solution for cholelithiasis in portal hypertension caused by hepatic cirrhosis].

Cholecystolithotomy and cholecystojejunostomy has been carried out on 11 patients with severe hypertension from cirrhosis. The indications were frequently recurring attacks of biliary cholic or acute cholecystitis at onset. There was 1 postoperative death from cardiac infarction and only minor in-hospital morbidity. None of the remaining patients has to date developed post-cholecystojejunostomy sequelae. Except the case of extensive inflammation on gangrena, this procedure appears to be a safe and definitive operation, alternative to subtotal cholecystectomy.

Adult↗
PubMed1994

SAV, an archaebacterial gene with extensive homology to a family of highly conserved eukaryotic ATPases.

Nucleotide sequencing of a region of the hyperthermophilic archaebacterium Sulfolobus acidocaldarius allowed us to identify an open reading frame of 780 amino acids strikingly similar to a family of eukaryotic ATPases, involved in a variety of biological functions. Sequence analysis of the predicted polypeptide revealed 63 to 66% similarity with S. cerevisiae CDC 48p and its related genes in amphibians (p97ATPase) and mammals (Valosin Containing Protein, VCP), all possibly involved in the regulation of the cell cycle. The finding of an archaebacterial equivalent of these proteins with a high degree of similarity suggests that it represents the same gene in these various species. The new archaebacterial ORF, called SAV (S. acidocaldarius VCP-like) exhibited the usual signature of all members of the family, a highly conserved domain of about 200 amino acids, which is duplicated. Thus, apart from the VCP-like proteins, SAV also appeared similar, although less clearly, to other ATPases, members of the family, involved in vesicle-mediated transport (NSF, Sec18p), peroxysome assembly (PAS1p), and gene expression in yeast (SUG1p) and in human immunodeficiency virus (TBP-1). Finally, the discovery of the archaebacterial gene could enlighten not only the evolutionary relationships between the members of this complex ATPase family, but also the cellular function of these proteins, that is presently obscure.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1993

Reverse gyrase: a helicase-like domain and a type I topoisomerase in the same polypeptide.

Reverse gyrase is a type I DNA topoisomerase able to positively supercoil DNA and is found in thermophilic archaebacteria and eubacteria. The gene coding for this protein was cloned from Sulfolobus acidocaldarius DSM 639. Analysis of the 1247-amino acid sequence and comparison of it with available sequence data suggest that reverse gyrase is constituted of two distinct domains: (i) a C-terminal domain of approximately 630 amino acids clearly related to eubacterial topoisomerase I (Escherichia coli topA and topB gene products) and to Saccharomyces cerevisiae top3; (ii) an N-terminal domain without any similarity to other known topoisomerases but containing several helicase motifs, including an ATP-binding site. These results are consistent with those from our previous mechanistic studies of reverse gyrase and suggest a model in which positive supercoiling is driven by the concerted action of helicase and topoisomerase in the same polypeptide: this constitutes an example of a composite gene formed by a helicase domain and a topoisomerase domain.

Amino Acid Sequence↗
PubMed1992

Central diabetes insipidus due to acute monocytic leukemia: case report and review of the literature.

We describe a 69-year-old man who presented with a four-month history of polyuria and polydipsia. Plasma vasopressin levels were undetectable, and a dehydration test was abnormal. Based on these findings, a diagnosis of central diabetes insipidus has been established. Hematologic studies showed acute monocytic leukemia. A relationship between the hematologic and endocrine disturbance has been hypothesized, and histological examination at autopsy showed leukemic infiltration of the pituitary stalk. This patient represents the third case in the world literature of central diabetes insipidus associated with acute monocytic leukemia.

Diabetes Insipidus↗
PubMed1992

The nature of the last universal ancestor and the root of the tree of life, still open questions.

The nature of the last universal ancestor to all extent cellular organisms and the rooting of the universal tree of life are fundamental questions which can now be addressed by molecular evolutionists. Several scenarios have been proposed during the last years, based on the phylogenies of ribosomal RNA and of duplicated proteins, which suggest that the last universal ancestor was either an RNA progenote or an hyperthermophilic prokaryote. We discuss these hypotheses in the light of new data on the evolution of DNA metabolizing enzymes and of contradictions between different protein phylogenies. We conclude that the last universal ancestor was a member of the DNA world already containing several DNA polymerases and DNA topoisomerases. Furthermore, we criticize current data which suggest that the rooting of the universal tree of life is located in the eubacterial branch and we conclude that both rooting the universal tree and the nature of the last universal ancestor are still open questions.

Archaea↗
PubMed1992

Autonomic nervous system dysfunction associated with HIV infection in intravenous heroin users.

OBJECTIVE: To evaluate the presence of autonomic nervous system (ANS) involvement in HIV-positive drug users. DESIGN: We investigated 37 HIV-positive (and 18 HIV-negative controls) intravenous heroin users who were without symptoms and signs of autonomic or peripheral neuropathy. METHODS: The patients were clinically and immunologically assessed and subjected to a battery of five cardiovascular reflex function tests. RESULTS: The tests revealed ANS involvement in 22 HIV-positive subjects but only in one HIV-negative subject. Immunoglobulin (Ig) G and C1q immune complex levels were significantly higher in HIV-positive subjects with severe cardiovascular reflex function tests alteration compared to those with normal tests. In a follow-up of 17 HIV-positive subjects, nine presented deteriorated reflexes in the tests and higher IgG immune complex levels. CONCLUSIONS: The results confirm that, by using sufficiently sensitive tests, signs of preclinical autonomic neuropathy can frequently be found in HIV-positive intravenous heroin users, as previously observed in homosexual patients, and suggest the existence of an HIV-related autoimmune pathogenesis. Early diagnosis of ANS involvement could be important, since the presence of autonomic dysfunction could increase the risk of cardiorespiratory arrest during invasive procedures.

Adult↗
PubMed1991

Terlipressin-induced metabolic acidosis.

Vasopressin and its analogue terlipressin are potent vasoconstrictors which reduce mesenteric blood flow and have been used in the therapy of variceal hemorrhage. This vasoconstrictor effect applies on vascular beds throughout the body. Since in literature vasopressin is rarely described to determine lactic acidosis, we report of a patient in whom a severe metabolic (probably lactic) acidosis appeared, associated with terlipressin administration for bleeding esophageal varices. By exclusion, the temporal sequence with terlipressin therapy, the contemporary increase of arterial blood pressure and autoptic data in the case presented make likely a diagnosis of terlipressin-induced lactic acidosis. Because of the seriousness of metabolic acidosis observed in our patient we suggest a careful monitoring of acid-base parameters in patients under treatment with vasopressin analogues.

Acidosis↗
PubMed1989

[Transitory efficacy of potassium perchlorate in hypothyroidism caused by amiodarone].

We report a case of a patient with hypothyroidism due to amiodarone. The short-term administration (1 g/die for 10 days) of potassium perchlorate (KClO4) led to normalization of serum thyroid hormone concentrations and marked reduction of thyrotropic hormone. The reduction of KClO4 (400 mg/die) and its following withdrawal led to reappearance of hypothyroidism signs. No side-effects or toxic reactions occurred during KClO4 therapy. This anion competitively inhibits thyroid iodide transport, reducing intrathyroidal iodide content and removing thyroid hormone synthesis inhibition. We suggest KClO4 therapy when amiodarone-associated hypothyroidism impairs a pre-existent cardiac disease and when a quick restoration of euthyroidism is necessary. Nevertheless, we emphasize that its effect can be transitory in cases of short-term treatment or low doses.

Aged↗