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PubMed1991

[Neoplasms of the major and minor salivary glands. The diagnostic and therapeutic approaches and case presentations].

Between January 1982 and December 1988, 37 patients with neoplasm of salivary glands have been treated in our Division of Surgical Oncology. The sites of tumors were: parotid 26, submandibular gland 4, minor salivary gland 7. The preoperative diagnostic procedures were: sialogram, ultrasonogram, fine needle aspiration. Malignant tumors were 16:5 adenoca., 4 metastases, 3 adenoid cystic, 2 mucoepidermoid, 1 acinic cells, 1 lymphoma. Twenty-one patients affected by neoplasms and 5 by malignant tumors were treated with surgery only. Nine patients affected by malignant tumors were treated with surgery and RT. Two patients were treated with RT only. The first therapeutic step is surgery; in order to control local evolution of tumor, postoperative irradiation is recommended. Possible indications of preoperative diagnostic procedures and the therapeutic choices are discussed.

Adult↗

PubMed2002

The evolving genome of Salmonella enterica serovar Pullorum.

Salmonella enterica serovar Pullorum is a fowl-adapted bacterial pathogen that causes dysentery (pullorum disease). Host adaptation and special pathogenesis make S. enterica serovar Pullorum an exceptionally good system for studies of bacterial evolution and speciation, especially regarding pathogen-host interactions and the acquisition of pathogenicity. We constructed a genome map of S. enterica serovar Pullorum RKS5078, using I-CeuI, XbaI, AvrII, and SpeI and Tn10 insertions. Pulsed-field gel electrophoresis was employed to separate the large DNA fragments generated by the endonucleases. The genome is 4,930 kb, which is similar to most salmonellas. However, the genome of S. enterica serovar Pullorum RKS5078 is organized very differently from the majority of salmonellas, with three major inversions and one translocation. This extraordinary genome structure was seen in most S. enterica serovar Pullorum strains examined, with different structures in a minority of S. enterica serovar Pullorum strains. We describe the coexistence of different genome structures among the same bacteria as genomic plasticity. Through comparisons with S. enterica serovar Typhimurium, we resolved seven putative insertions and eight deletions ranging in size from 12 to 157 kb. The genomic plasticity seen among S. enterica serovar Pullorum strains supported our hypothesis about its association with bacterial evolution: a large genomic insertion (157 kb in this case) disrupted the genomic balance, and rebalancing by independent recombination events in individual lineages resulted in diverse genome structures. As far as the structural plasticity exists, the S. enterica serovar Pullorum genome will continue evolving to reach a further streamlined and balanced structure.

Chromosome Mapping↗

PubMed2005

Immunology of scorpion toxins and perspectives for generation of anti-venom vaccines.

Scorpions and other venomous animals contain concentrates of biologically active substances developed to block vital physiological and biochemical functions of the victims. These have contrasting human health concerns, provide important pharmacological raw material and pose a serious threat to human life and health in tropical and subtropical regions. Because only occasional and minor quantities of venom are introduced into the human organism with a scorpion sting and their mortal effect is an acute phenomenon these substances are unknown to the immune defense system and thus no immunity has appeared against them during evolution. Antidotes prepared from animal anti-sera are effective against some species of scorpions but depend on the manufacturer and the availability of product to the medical community. Although significant progress has been made in immunological studies of certain groups of toxins, few centers are dedicated to this research. Information is still insufficient to generate a comprehensive picture of the subject and to propose vaccines against venoms. A novel approach based on mimotopes selected from phage-displayed random peptide libraries show potential to impel further progress of toxin immunological studies and to provide putative vaccine resources. In this report we revise the "state of the art" in the field.

Animals↗

PubMed1983

A pair of regulatory isozymes for 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase is conserved within group I pseudomonads.

Two closely related subgroups of group I pseudomonads, which differ from one another in the overall enzymatic makeup of aromatic amino acid biosynthesis, possess in common the recently characterized major (tyrosine-sensitive) and minor (tryptophan-sensitive) isozymes of 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase of Pseudomonas aeruginosa (17). Since these characterizations were made for strains whose phylogenetic positions have been determined by oligonucleotide cataloging, an initial perception of the evolution of aromatic pathway construction and regulation is emerging.

3-Deoxy-7-Phosphoheptulonate Synthase↗

PubMed1970

A clinical and histochemical study of cholestasis.

A histochemical study of conjugated and total bilirubin was made on liver biopsies of 150 patients. Three types of cholestasis were defined: type I, characterized by the presence of intracellular pigment granules in the hepatocytes; type II, showing intracellular granules and extracellular thrombi (this group may be subdivided according to the eventual presence of coarse pigment deposits in the parenchymal cells); and type III, showing intracellular granules, extracellular thrombi, and also bile pigment in the Kupffer cells. The fine liver cell granules correspond mainly to conjugated bilirubin, whereas the coarse deposits usually contain unconjugated pigment. The extracellular thrombi mostly contain conjugated bilirubin; the Kupffer cell pigment is predominantly of the unconjugated type. In cholestasis types II and III a diffuse directly reacting pigment is also observed. The finding of unconjugated pigment in different locations and the eventual deconjugation by beta-glucuronidase is discussed. A correlation was found between the different types of cholestasis, the level of bilirubinaemia, and its dynamic evolution. This suggests that the proposed types of cholestasis may represent successive stages of increasing cholestasis. The type of cholestasis and the nature of the pigment are largely independent of the aetiology. It is shown that a large percentage of minor degrees of cholestasis is missed when only conventional histological methods are used. The mechanisms by which morphological cholestasis is brought about are discussed in the light of the present findings.

Bilirubin↗

PubMed2003

Congenital dyserythropoietic anemia type II: epidemiology, clinical appearance, and prognosis based on long-term observation.

Congenital dyserythropoietic anemia type II (CDA II) is the most frequent type of congenital dyserythropoietic anemia. More than 200 cases have been described, but with the exception of a report by the International CDA II Registry, these reports include only small numbers of cases and no data on the lifetime evolution of the disease. Since 1967, we were able to follow 48 cases of CDA II from 43 families for up to 35 years. All patients exhibit chronic anemia of variable severity requiring regular red cell transfusions only in a minority of children; 60% developed gallstones before the age of 30 years, and 16 patients had cholecystectomy between 8 and 34 years of age. Iron overload was a frequent complication. In 16 cases, iron depletion started between 7 and 36 years. Three patients died from secondary hemochromatosis. Splenectomy, performed in 22 cases, led to moderate increases in hemoglobin values and eliminated the need for transfusions but did not prevent further iron loading. The current recommendation is to consider splenectomy if the anemia compromises patients' performance, and to manage iron overload according to the guidelines derived from patients with thalassemia.

Adolescent↗

PubMed2003

The evolutionary demography of duplicate genes.

Although gene duplication has generally been viewed as a necessary source of material for the origin of evolutionary novelties, the rates of origin, loss, and preservation of gene duplicates are not well understood. Applying steady-state demographic techniques to the age distributions of duplicate genes censused in seven completely sequenced genomes, we estimate the average rate of duplication of a eukaryotic gene to be on the order of 0.01/ gene/million years, which is of the same order of magnitude as the mutation rate per nucleotide site. However, the average half-life of duplicate genes is relatively small, on the order of 4.0 million years. Significant interspecific variation in these rates appears to be responsible for differences in species-specific genome sizes that arise as a consequence of a quasi-equilibrium birth-death process. Most duplicated genes experience a brief period of relaxed selection early in their history and a minority exhibit the signature of directional selection, but those that survive more than a few million years eventually experience strong purifying selection. Thus, although most theoretical work on the gene-duplication process has focused on issues related to adaptive evolution, the origin of a new function appears to be a very rare fate for a duplicate gene. A more significant role of the duplication process may be the generation of microchromosomal rearrangements through reciprocal silencing of alternative copies, which can lead to the passive origin of post-zygotic reproductive barriers in descendant lineages of incipient species.

Animals↗

PubMed1984

[Evolution of the treatment of tuberculosis].

An evolution analysis of tuberculosis management includes four essential times. The first time coincides with the streptomycin therapeutic employment; the second develops with isoniazid disposing; the third time takes in the period of identification of several drugs a long time called "minor", but very important to formulate some "ad personam" therapeutic patterns. At last, the fourth time is characterized by formulation of short-course chemotherapy. Now the suggested protocol is a regimen of short-course chemotherapy with daily administration of INH and RIF for six-nine months with an initial supplement of ethambutol, or streptomycin or pyrazinamide for the first two months.

Ambulatory Care↗

PubMed1994

[Upper digestive hemorrhage in the operated stomach (Billroth I and II): clinical course and prognosis].

AIM: To determine course and prognosis of upper gastrointestinal bleeding in gastrectomized patients. MATERIALS AND METHODS: We have conducted a retrospective study on 34 patients (one female, mean age 38.2 +/- 12.14 years) admitted with upper gastrointestinal bleeding between November 1989 and August 1991. All patients had been previously gastrectomized because of benign gastric pathology. Eight had a Billroth I type gastrectomy, and 26 a Billroth II. RESULTS: The causes of gastrointestinal bleeding were recurrent ulcer in 20 patients and alkaline reflux gastritis in 13 patients, both located at the surgical anastomosis; in one case it was not possible to determine the lesion responsible of the bleeding. Initial symptoms were maelena in 16 patients (47%), hematemesis in 12 patients (35.2%) and hematemesis and maelena in 6 (17.6%). Only one patient developed hemodynamic changes (systolic arterial tension < 10 mm Hg and pulse > 100 pm). After admission 3 patients rebled (8.8%) and the mortality reached 8.8%. Although rebleeding and mortality rates were higher than the rates for peptic ulcer in non gastrectomized patients, mortality and rebleeding occurred in patients with severe diseases (chronic hepatopathy), whose evolution conditioned in 2 of 3 patients the course of the upper gastrointestinal bleeding. CONCLUSIONS: The evolution of bleeding was not influenced by the causal lesion or the gastric resective procedure. We conclude that the course and prognosis of upper gastrointestinal bleeding in gastrectomized patients is not severe; hemostatic surgical procedures are indicated in only a minority of patients.

Adult↗

PubMed1993

[The neurosurgeon's role in the treatment of cerebral arteriovenous malformations. A study of a series of 100 cases and review of the literature].

The Neurosurgeons's place in the management of cerebral A.V.M.'s is discussed in the light of a personal experience and of the review of the neurosurgical literature. A personal series of 100 treated patients is presented. Patients were admitted between 1985 and April 1992. Two groups are considered: the first group including 52 patients treated before the availability of radiosurgery (1985-1988), and the second group including 48 patients treated afterwards (1989-1992). A.V.M.'s were classified in five grades according to the Spetlzer's Grading System. Three techniques of treatment were used: Surgical Resection, Intravascular Embolization (cyanoacrylate) and Radiosurgery (linear accelerator). These three techniques were used either alone or in association, giving four types of management: surgical resection alone, embolization and resection, embolization alone, and radiosurgery (alone, or after embolization or after surgical resection). From 1989 on, the availability of radiosurgery was responsible for the diminution of the "embolization and resection" group, which until then was predominantly used, for the low-grade A.V.M.'s (I.II.III) and for the high grade A.V.M.'s (IV.V) as well. Overall, for the low grade A.V.M.'s, the treatment of choice was the surgical resection (79% of cases), with a preoperative embolization in one half of these cases; the other A.V.M.'s were irradiated, with various combinations. For the high-grade A.V.M.'s, the treatment of choice was the intravascular embolization (95% of cases), either alone, or followed by exeresis (45%) or radiosurgery (9%). Results were evaluated in terms of deterioration due to treatment, in five groups: no deterioration (59%), minor deterioration (20%), long-lasting deficit (10%), major deterioration (5%) and death (6%). Overall, results improved after 1989: favourable outcome (no deterioration and minor deterioration) increased from 67% to 90%. Results were not related to the patient's age. More favourable results were obtained for low grade A.V.M.'s (93%) than for high grade A.V.M.'s (60%). For the low grade A.V.M.S. the evolution form 1989 on (favourable outcome increasing from 89% to 96%) occurred with the suppression of death cases. For the high grade A.V.M.'s, the evolution from 1989 on (favourable outcome increasing from 46% to 78%), occurred with the decreasing of the deficit cases. The angiographic eradication was strongly related to the management: 95% of complete eradication after surgical resection and 5% only after embolization alone. Concerning the results in irradiated cases, the follow-up is not long enough. The review of the neurosurgical literature since 1972 demonstrates progressive modifications in the therapeutic attitude as regards A.V.M.'s. The surgical management which was predominantly used at the beginning gave progressively way to a combined management, with a combination of embolization, surgery, and lately radiosurgery.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed2005

Intraspecific competition and the evolution of virulence in a parasitic trematode.

Intrahost competition between parasite genotypes has been predicted to be an important force shaping parasite ecology and evolution and has been extensively cited as a mechanism for the evolution of increased parasite virulence. However, empirical evidence demonstrating the existence and nature of intraspecific competition is lacking for many parasites. Here, we compared within-host competitiveness between genetic strains of Schistosoma mansoni with high (HIGH-V) or low (LOW-V) virulence to their intermediate snail host, Biomphalaria glabrata. Groups of snails were exposed to either one or the other of two parasite strains, or a mixed infection of both strains, and the resulting progeny were identified using a molecular marker. In two separate experiments investigating simultaneous and sequential infections, we demonstrated that the lifetime reproductive success of parasite strain HIGH-V was reduced in the presence of a faster replicating parasite genotype, LOW-V, regardless of whether it was in a majority or minority in the initial inoculum of the simultaneous exposure or of its relative position in the sequential exposure experiment. Thus, we demonstrate competition between parasite genotypes and asymmetry in competitive success between parasite strains. Moreover, since the less virulent strain investigated here had a competitive advantage, we suggest that a high frequency of multiple infections could favor the evolution of less, rather than more, virulent parasites in this system.

Animals↗

PubMed2004

Hepatitis C virus quasispecies variability modulates nonstructural protein 5A transcriptional activation, pointing to cellular compartmentalization of virus-host interactions.

Hepatitis C virus (HCV) behaves in infected patients as a complex mixture of genetically distinct but closely related variants referred to as a "quasispecies." By using quasispecies analysis strategies, we showed that HCV nonstructural protein 5A (NS5A) has a quasispecies distribution in infected humans and that NS5A quasispecies undergo significant genetic evolution over time, as a result of random accumulation of nucleotide mutations during replication. Genetic evolution of the NS5A quasispecies results in sporadic amino acid changes in the protein sequence. By using the functional in vitro model of HCV NS5A transcriptional activation in Saccharomyces cerevisiae, we showed that natural NS5A quasispecies variants induce different levels of transcriptional activation, according to the charge of the residues (and possibly minor conformational changes) in the quasispecies variant sequence. These findings show that the accumulation of mutations on HCV genomes during replication randomly generates variant proteins with quantitatively different functional properties. The fact that each new variant protein is initially produced in a single infected hepatocyte and may or may not subsequently spread throughout the liver (depending on the replication capacities of the variant virus) points to cellular compartmentalization of virus-host interactions during chronic infection. This feature of quasispecies-distributed viruses could play an important role in various aspects of the viral life cycle and related disease.

Amino Acid Sequence↗

PubMed1996

Evolution of pregnancies and initial follow-up of newborns delivered after intracytoplasmic sperm injection.

OBJECTIVE: To analyze the in vivo development of embryos conceived after intracytoplasmic sperm injection (ICSI), as well as obstetric outcome, occurrence of chromosomal abnormalities, and rate of congenital malformations in neonates born as a result of this treatment. DESIGN: Retrospective study. SETTING: University-based in vitro fertilization (IVF) clinic. PATIENTS: A total of 751 couples in whom the male partners were presumed to be the cause of repeated failed IVF attempts or whose semen parameters were unacceptable for conventional IVF treatment. INTERVENTIONS: Analysis of pregnancies resulting from 987 ICSI cycles; pregnancy outcome data were obtained from the records of obstetrician-gynecologists and/or pediatricians. MAIN OUTCOME MEASURES: Pregnancy rates, obstetric outcome, and frequency of chromosomal abnormalities and congenital malformations. RESULTS: The overall clinical pregnancy (fetal heartbeat) rate was 44.3%, with a resultant delivery rate per ICSI cycle of 38.7% (n=382). In 8 of 11 miscarriages for which cytogenetic data were available, an autosomal trisomy was found, and 7 additional pregnancies were terminated because of a chromosomal abnormality after prenatal diagnosis. There was an equal distribution of vaginal vs cesarean deliveries (n=192 and n=190, respectively). Of the 578 neonates resulting from treatment by ICSI, 15 (2.6%) presented with congenital abnormalities (9 major and 6 minor abnormalities). However, this frequency of malformations is lower than that observed in offspring born after standard IVF at our institution. Furthermore, when pregnancy outcome of ICSI vs IVF was analyzed in terms of semen origin, no differences were found in the frequency of miscarriages or in the rate of congenital malformations. CONCLUSIONS: The evolution of pregnancies and occurrence of congenital malformations following treatment by ICSI were within the range observed with standard in vitro fertilization.

Adult↗

PubMed1985

Glucagon- and PP-related peptides of intestinal L cells and pancreatic/gastric A or PP cells. Possible interrelationships of peptides and cells during evolution, fetal development and tumor growth.

The immunohistochemical detection of six distinct sequences of proglucagon and its derivatives (GRPP, glicentin, glucagon-37, glucagon-29, GLP1, GLP2 and MPGF) in both intestinal L cells and pancreatic or gastric A cells of some mammals (dog, man, guinea pig) confirms that the two cell types produce the same proglucagon molecule, although the final step of its post-translational processing differs in the two cells. Immunohistochemical and ultrastructural patterns of glucagon/glicentin cells in the pancreas of lower vertebrates and early human fetuses, as well as tumor cell studies, suggest an evolution of gastropancreatic A cells from L cells. On the contrary, the PP-related peptide PYY of intestinal L cells, and PP with its C-terminal icosapeptide extension of pancreatic PP cells, likely originate from different prohormones. Although intermediate patterns of peptide expression can be observed, including some F-type PP cells of the dog pancreas (uncinate process) and pyloric mucosa showing PYY immunoreactivity or rare PYY and/or HPP immunoreactive cells of the human rectum lacking glicentin reactivity, no obvious relationship can be established between L cells and pancreatic (F-type) PP cells. However, some evolutionary, embryogenetic and oncogenetic link may exist between L cells and human D1-type PP cells, a minor population of PP cells scattered in the pancreatic tissue of dorsal pouch origin and a major fraction of tumor PP cells.

Animals↗

PubMed2000

Divergence with gene flow in the rock-dwelling cichlids of Lake Malawi.

Within the past two million years, more than 450 species of haplochromine cichlids have diverged from a single common ancestor in Lake Malawi. Several factors have been implicated in the diversification of this monophyletic clade, including changes in lake level and low levels of gene flow across limited geographic scales. The objectives of this study were to determine the effect of recent lake-level fluctuations on patterns of allelic diversity in the genus Metriaclima, to describe the patterns of population structure within this genus, and to identify barriers to migration. This was accomplished through an analysis of allele frequencies at four microsatellite loci. Twelve populations spanning four species within Metriaclima were surveyed. The effect of lake-level fluctuations can be seen in the reduced genetic diversity of the most recently colonized sites; however, genetic diversity is not depressed at the species level. Low levels of population structure exist among populations, yet some gene flow persists across long stretches of inhospitable habitat. No general barrier to migration was identified. The results of this study are interpreted with respect to several speciation models. Divergence via population bottlenecks is unlikely due to the large allelic diversity observed within each species. Genetic drift and microallopatric divergence are also rejected because some gene flow does occur between adjacent populations. However, the reduced levels of gene flow between populations does suggest that minor changes in the selective environment could cause the divergence of populations.

Alleles↗

PubMed1987

Primary and quaternary structure of the catabolic ornithine carbamoyltransferase from Pseudomonas aeruginosa. Extensive sequence homology with the anabolic ornithine carbamoyltransferases of Escherichia coli.

We have determined the complete nucleotide sequence of the arcB gene from Pseudomonas aeruginosa strain PAO and we have purified the arcB product, the catabolic ornithine carbamoyltransferase (EC 2.1.3.3), to apparent homogeneity from the same strain. The N-terminal amino acid sequence, the total amino acid composition and the subunit size of the purified enzyme were in agreement with nucleotide sequencing results, which predict a polypeptide of 336 amino acids (Mr 38,108). Crosslinking experiments suggest that the native enzyme (apparent Mr approx. 420,000) basically consists of a trimer aggregating to form nonamers or dodecamers. The arcB gene of P. aeruginosa had strong homology with the argF and argI genes which code for the anabolic ornithine carbamoyltransferase isoenzymes in Escherichia coli; 63% of the nucleotides and 57% of the amino acids were absolutely conserved in arcB and argF. This indicates a close evolutionary relationship between these genes although their products have different physiological functions in the cell. Under conditions of induction (energy depletion) the catabolic ornithine carbamoyltransferase represented greater than or equal to 10% of the total cellular protein. Like other highly expressed Pseudomonas genes, the arcB gene was found not to use seven codons which correspond to minor or weakly interacting tRNA species in E. coli.

Amino Acid Sequence↗

PubMed1999

Identification of both shared and distinct proteins in the major and minor spliceosomes.

In metazoans, two distinct spliceosomes catalyzing pre-messenger RNA splicing have been identified. Here, the human U11/U12 small nuclear ribonucleoprotein (snRNP), a subunit of the minor (U12-dependent) spliceosome, was isolated. Twenty U11/U12 proteins were identified, including subsets unique to the minor spliceosome or common to both spliceosomes. Common proteins include four U2 snRNP polypeptides that constitute the essential splicing factor SF3b. A 35-kilodalton U11-associated protein homologous to the U1 snRNP 70K protein was also identified. These data provide fundamental information about proteins of the minor spliceosome and shed light on its evolutionary relationship to the major spliceosome.

Amino Acid Sequence↗

PubMed2006

Evolution of BK virus based on complete genome data.

The human polyomavirus BK virus (BKV) is ubiquitous in humans, infecting children asymptomatically. BKV is the only primate polyomavirus that has subtypes (I-IV) distinguishable by immunological reactivity. Nucleotide (nt) variations in a major capsid protein (VP1) gene region (designated the epitope region), probably responsible for antigenic diversity, have been used to classify BKV isolates into subtypes. Here, with all the protein-encoding gene sequences, we attempted to elucidate the evolutionary relationships among 28 BKV isolates belonging to subtypes I, III, and IV (no isolate belonging to subtype II, a minor one, was included). First, using the GTR + Gamma + I model, maximum likelihood trees were reconstructed for individual viral genes as well as for concatenated viral genes. On the resultant trees, the 28 BKV isolates were consistently divided into three clades corresponding to subtypes I, III, and IV, although bootstrap probabilities are not always high. Then we used more sophisticated likelihood models, one of which takes account of codon structure, to elucidate the phylogenetic relationships among BKV subtypes, but the phylogeny of the deep branchings remained ambiguous. Furthermore, the possibility of positive selection in the evolution of BKV was examined using the nonsynonymous/synonymous rate ratio as a measure of selection. An analysis based on entire genes could not detect any strong evidence for positive selection, but that based on the epitope region identified a few sites potentially under positive selection (these sites were among those showing subtype linked polymorphisms).

Adaptation, Physiological↗