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Biomedical subjects

M Paoletti

Publications and source records attributed to M Paoletti.

At least 19 recordsLinked to original sources

Reproduction in Aspergillus fumigatus: sexuality in a supposedly asexual species?

Aspergillus fumigatus has long been considered to reproduce only by asexual means. However, accumulating evidence suggest that a sexual stage for A. fumigatus may yet be identified. We describe results from published and ongoing studies involving population genetic analyses, genome analysis, studies of mating-type gene presence and distribution, expression of sex-related genes, and taxonomic work which support the assertion that A. fumigatus has the potential to reproduce by sexual means. The consequences of sexual reproduction for the population biology and disease management of the species are discussed. The possible mechanisms of evolution of asexuality are then considered. It is proposed that asexual species may arise in one step by mutation or loss of a key gene(s), and/or there may be a 'slow decline' in sexual fertility within the species as a whole. Thus, it is argued that species should not be considered simply as sexual or asexual, but rather as individual isolates being present on a continuum of sexual fertility, with the implications for understanding sexuality/asexuality in A. fumigatus discussed.

Aspergillus fumigatus↗

Identification and characterization of a gene encoding a subtilisin-like serine protease induced during the vegetative incompatibility reaction in Podospora anserina.

In the filamentous fungi, cell fusion between unlike individuals generally triggers a cell-death reaction known as vegetative incompatibility. In Podospora anserina, it was shown that, during this cell-death reaction, there is a strong increase in proteolytic activity. Here, we report the purification of a 36-kDa protease that is induced during the incompatibility reaction. An internal peptide of this protein displayed a strong similarity with the PEPC subtilisin-like serine protease from Aspergillus niger. This led us to use the pepC gene as a probe to clone the homologous gene from P. anserina, which we called pspA. The expression of pspA is upregulated at the transcript level during the progress of the incompatibility reaction. This induction is diminished in strains bearing suppressors of the vegetative incompatibility reaction. The fact that pspA is homologous to PrB, a vacuolar protease involved in autophagy in yeast, suggests that the incompatibility cell-death reaction and autophagy might be related processes.

Amino Acid Sequence↗

Nerve growth factor and neuropeptides circulating levels in systemic sclerosis (scleroderma).

OBJECTIVE: To determine the circulating levels of nerve growth factor (NGF), neuropeptide Y (NPY), and vasoactive intestinal peptide (VIP) in systemic sclerosis (SSc), and to correlate these levels with clinical and laboratory features. METHODS: Forty four patients with SSc were evaluated for circulating NGF (immunoenzymatic assay), NPY and VIP (radioimmunoassay), anticentromere and antitopoisomerase I autoantibodies, lung disease (pulmonary function tests with carbon monoxide transfer factor (TLCO), ventilation scintiscan with 99mTc DTPA radioaerosol, high resolution computed tomography (HRCT), pulmonary pressure (echo colour Doppler)), heart disease (standard and 24 ECG, echocardiography), cutaneous involvement (skin score), joint involvement (evidence of tender or swollen joints, or both), peripheral nervous system (PNS) involvement (electromyography), rheumatoid factor, angiotensin converting enzyme (fluorimetric method), von Willebrand factor (ELISA), and erythrocyte sedimentation rate (ESR) (Westergren). RESULTS: Circulating NGF levels in SSc were significantly increased compared with controls (p<0.00001) and significantly higher in the diffuse than in the limited subset of patients (p<0.01). Patients with articular disease had significantly higher levels of NGF. A significant indirect correlation between NGF levels and TLCO was detected (p<0.01), but no correlation was found between NGF and HRCT, DTPA, skin score, PNS involvement and angiotensin converting enzyme and von Willebrand factor levels, antitopoisomerase or anticentromere antibodies, and ESR. NGF levels increased progressively as the disease worsened. Similarly, VIP circulating levels were significantly increased in patients with SSc (p<0.001), whereas the increase of NPY levels did not reach statistical significance. However, both neuropeptides, following the same trend as NGF, increased as the disease worsened (skin score and lung disease). CONCLUSIONS: The increase of NGF and VIP in patients with SSc, the former in the diffuse subset of the disease, and in patients with prominent articular disease, may suggest a link between neurotransmitters and the disease pathogenesis. Neuropeptide circulating levels seem to increase only in patients with the most severe disease.

Biomarkers↗

[Association between breast and colorectal cancer and polyps. Screening and epidemiological study].

BACKGROUND: Studies regarding the associations between different types of cancer in the same patient are very few and not always come to the same conclusions. Several hypothesis are suggested and particularly genetic and socioeconomical ones seem to offer an interpretation of this issue. Early detection of a second neoplasm allows to improve prognosis and survival. The knowledge of correlations between tumors help to select a population, with a high risk to develop a second cancer, to be included in a screening program. Nowadays thanks to early detection of breast cancer, ten years survival is more than 75%. Women who had breast cancer now live longer and so could have a higher risk to develop a second cancer. METHODS: From September 1998 to September 1999 in our Department 71 patients operated for breast cancer, underwent screening colonscopy. No patients refused to be included in the study. Mean age was 61 years (range 36-87). Each patient had a clinician interview in order to explain the goals of the study. RESULTS: Results show that among all patients 3 (4.2%) presented a history of colon cancer, 18.3% (13 cases) presented large bowel polyps. In 84.60% patients (11 cases) polyps were found not over 40 cm. This study shows that 93% of patients (66 cases) had a relative with cancer history. CONCLUSIONS: Our results compared with those of other authors seem to show an increased risk for breast cancer patients in developing polyps or colon cancer, so we suggest to insert sigmoidoscopy in standard follow-up of breast cancer patients.

Adult↗

Duodenal ulcer relapse is not always associated with recurrence of H. pylori infection: a prospective three-year follow-up study.

BACKGROUND: Long-term data concerning the reappearance of Helicobacter pylori infection and duodenal ulcer (DU) recurrence after successful eradication are still few and conflicting. Inadequate histological assessment or use of indirect tests for the determination of H. pylori and bias in the selection of patients to be controlled can influence reported results. The aim of this study was to determine the rate of recurrence of H. pylori infection and ulcer relapse in a population of cured DU patients followed up for 3 years irrespective of their symptomatology. METHODS: Between 1992 and 1994, 126 patients with DU disease were treated with double or triple therapy. Patients using nonsteroidal antiinflammatory drugs or aspirin or receiving maintenance antisecretory therapy were excluded. H. pylori infection was assessed by three bioptic tests from both the antrum and the body (culture, urease, histopathological examination). After 2 months from cessation of treatment, DU had healed and H. pylori infection was cured in 102 of 126 patients (81%). These patients were endoscopically followed up after 1 and 3 years, respectively, and were advised to contact us at symptom recurrence. At 1 and 3 years, we studied 95 (93.2%) and 79 (77.4%) patients, respectively, of the 102 who were cured. The other patients were untraceable or refused endoscopy because they were asymptomatic. RESULTS: After 1 year, no patient had H. pylori recurrence, whereas three patients had a relapse of DU without evidence of infection. After 3 years, recurrence of H. pylori occurred in six patients (annual rate, 2.5%), DU relapsed in five H. pylori-positive patients (6.3%) and in two H. pylori-negative patients (annual rate, 1.9%). Fasting gastrin and acid secretion values studied in all relapsed patients were within the normal range except for one H. pylori-positive patient. CONCLUSIONS: Recurrence of H. pylori infection is very low where treatment is effective, but a DU relapse, not related to acid hypersecretion, can occur in a small percentage of cured patients.

Adolescent↗

Characterization of a gene from the filamentous fungus Podospora anserina encoding an aspartyl protease induced upon carbon starvation.

In an attempt to characterize proteases associated with vegetative incompatibility, a Podospora anserina gene (papA) encoding an aspartyl protease (podosporapepsin) was cloned using a heterologous probe. The deduced papA coding region was 1278 nucleotides long, interrupted by a single 71bp intron. The corresponding amino acid sequence presented a high degree of similarity to other aspartyl proteases. Sequence analysis and proteolytic activity measurement suggested that the podosporapepsin could be intracellular rather than secreted. The papA gene was expressed under carbon starvation, but not under nitrogen starvation conditions. Its disruption led to a slight decrease in the growth rate of the mutant strain when bovine serum albumin was the sole carbon source in the medium. Disruption or overexpression of papA gene had no obvious consequence on vegetative incompatibility. Transcription of papA induced by carbon starvation was strongly reduced in the presence of a suppressor of vegetative incompatibility. This result suggests a relationship between adaptation for starvation and vegetative incompatibility.

Amino Acid Sequence↗

Does pretreatment with omeprazole decrease the chance of eradication of Helicobacter pylori in peptic ulcer patients?

OBJECTIVE: It has been reported that pretreatment with omeprazole could decrease the efficacy of Helicobacter pylori eradication. Our aim was to compare the efficacy, safety, and tolerability of the eradicating regimen, omeprazole/amoxicillin/metronidazole. The two antibiotics were scheduled either during the first or during the last 2 wk of omeprazole administration. METHODS: In this prospective controlled study conducted in a single center, 78 symptomatic peptic ulcer patients were treated for 4 wk with omeprazole 40 mg o.m.; the patients were randomly assigned to receive amoxicillin 1 g t.i.d. postprandially and metronidazole 250 mg t.i.d. postprandially, either during the first 2 wk (group A, n = 40) or the last 2 wk of therapy with omeprazole (group B, n = 38). H. pylori status was assessed by culture, histology, urease test, and IgG antibodies. Each patient's course was followed for 1 yr. RESULTS: H. pylori infection was cured in 97.4% of group A (95% CI: 0.84-0.99) and in 89% of group B (95% CI: 0.73-0.96, p = 0.28). Healing was achieved in 80% of the patients in group A (95% CI: 0.63-0.90) and in 75.7% of patients in group B (95% CI: 0.60-0.90, p = 0.60) At 12-month follow-up, 72 patients were evaluated: 37/38 (97%) of patients in group A and 33/33 (100%) in group B were confirmed as cured of the infection (NS). Peptic ulcer healing rate reached 100% in the two groups. Furthermore, between the two groups, there were no significant differences in symptom relief or improvement. Both regimens were well tolerated, and no patient had to be withdrawn from therapy because of an adverse event. Minor side-effects appeared to be similar in the two groups (40% vs. 38%). CONCLUSIONS: This randomized study clearly indicates that omeprazole pretreatment does not significantly reduce the efficacy of eradicating therapy for H. pylori in peptic ulcer patients.

Adult↗

[Cystic polyps of the stomach: review of our case series].

The Authors report their experience with gastric polyps based upon 3,384 endoscopies performed from October 1992 to August 1995. The incidence of cystic polyps with respect to the examinations performed and to the number of gastric polyps found was 0.45% and 21.3% respectively. The cases were taken into account with respect to sex, age, number of lesions, location, size and association to Gardner's syndrome. A comparison between the observed cases and a comprehensive review of the relevant Literature was performed.

Female↗

[Changes in myocardial Tc-99m-sestamibi uptake in asynergic territories during low-dose echo-dobutamine test].

BACKGROUND: Recent data suggest that contractile reserve in dysfunctional but viable myocardium during low-dose dobutamine infusion might be elicited not only by a direct inotropic stimulation but also by an increase in coronary blood flow. Aim of the study was to evaluate the effects of low-dose dobutamine on myocardial perfusion and function in asynergic but viable myocardium. METHODS: Nineteen patients with coronary artery disease and severe regional dysfunction were studied. Both regional ventricular function and myocardial perfusion were assessed at rest (PRE), during low-dose dobutamine (DOB) and, in twelve patients, after revascularization (POST). Regional ventricular function was evaluated with two-dimensional echocardiography using a score index ranging from 1 to 4. Myocardial perfusion was studied using Tc-99m-sestamibi Single Photon Emission Tomography (SPET); uptake defects were graded from 0 (normal) to 4 (absent uptake). For both evaluations the left ventricle was divided in 16 segments and two vascular territories were considered. RESULTS: Low-dose dobutamine elicited contractile reserve in 12 of 24 asynergic vascular territories (DOB+). Compared with PRE scintigraphy, DOB SPET showed perfusion improvement in 10/12 DOB+ and in 3/12 DOB- asynergic territories (p = 0.006). Mean uptake score decrease significantly in DOB+ (from PRE SPET 21.0 +/- 7.2 to DOB SPET 17.6 +/- 7.1; p = 0.0005) but not in DOB- (from SPET PRE 19.0 +/- 5.3 to SPET DOB 19.5 +/- 6.8, p = NS) abnormal territories. Fourteen asynergic territories underwent revascularization. Among them, 9 showed functional recovery after intervention (viable myocardium) and 5 showed no changes (fibrotic myocardium). A functional improvement under dobutamine was observed in 7 viable and in 1 fibrotic territories. Conversely, perfusion improved under dobutamine in 8 viable and in one fibrotic territory. After revascularization the perfusion defect score decreased significantly in viable territories (from PRE SPET 22.1 +/- 7.9 to POST SPET 13.3 +/- 6.6; p = 0.00001) but not in fibrotic regions (from PRE SPET 17.8 +/- 6.0 to POST SPET 15.6 +/- 4.9). CONCLUSIONS: In asynergic myocardium contractile reserve elicited by low-dose dobutamine is associated in most cases with an improvement in Tc-99m-sestamibi uptake. This suggests a possible link between increased blood flow and functional improvement during dobutamine in viable myocardium.

Aged↗

[Large cystic polyps of the stomach].

The Authors report the case of a 83 year old woman with large cystic polyps of the stomach. Gastric cystic polyps are polypoid lesions which may develop following functional disorders such as increased mucosal stimulation by gastrin, or excessive retention of gastric secretions. The incidence of these polyps is variable, depending on their being underestimated since they are not always macroscopically visible. The case here reported is very interesting not only for the number of lesions (over 50), but also for their size (5-25 mm in diameter).

Aged↗

[Staplers and pulmonary surgery].

The Authors report their experience with staplers (model T.A. 30) in lung surgery: 152 stapled sutures were, in fact, performed in the IV Surgical Department of the University "La Sapienza" of Rome, during the period 1980/90. The use of staplers assures a perfect closure and prevents granulomas due to suture materials in typical as well as atypical lung resections.

Adenocarcinoma↗

Age-related changes in the pharmacodynamics of intravenous glyceryl trinitrate.

Comparable hemodynamic effects were obtained administering a much lower intravenous dose of glyceryl trinitrate (GTN) in elderly than in younger patients. The pharmacodynamics and kinetics of GTN were thus assessed in 2 groups of patients with acute myocardial infarction (group A: less than or equal to 65 years, 6 patients; group B: greater than or equal to 75 years, 6 patients). The arterial and venous dose-concentration relationship and the associated hemodynamic changes at end-point (EP: 10% reduction in mean systemic arterial pressure) were similar in the 2 groups. However, in older subjects EP was reached at a lower GTN infusion rate (0.11 +/- 0.04 vs 0.33 +/- 0.11 micrograms.kg-1.min-1, mean +/- S.D.; p less than 0.001), and with lower arterial and venous drug concentrations (arterial [GTN]: 1.2 +/- 0.1 vs 4.6 +/- 1.2 ng.ml-1; p less than 0.01; venous [GTN]; 0.09 +/- 0.05 vs 0.35 +/- 0.15 ng.ml-1; p less than 0.05), whereas overall GTN kinetics appeared to be substantially independent of age. Thus, the enhanced efficacy of GTN in advanced age seems to stem mainly from pharmacodynamic changes, which may be the consequence of dampened baroreceptor reflexes, as suggested by a lower heart rate increase per unitary fall in systolic arterial pressure observed in group B (0.12 +/- 0.07 vs 0.41 +/- 0.29 b.min-1.mmHg-1; p less than 0.05).

Aged↗

Age-related hemodynamic effects of intravenous nitroglycerin for acute myocardial infarction and left ventricular failure.

Acute hemodynamic effects of intravenous nitroglycerin (NTG) were assessed in 24 patients with acute myocardial infarction and left ventricular failure, and results were compared between 2 groups of different age (group A--65 years or less, n = 12; group B--75 years or more, n = 12). Overall, hemodynamic effects of NTG consisted of an increase in stroke volume index and left ventricular stroke work index (+21 and +23%), coupled with a 16% reduction in systemic vascular resistance, and of a marked decrease in right atrial and pulmonary artery (PA) pressures. The hemodynamic end-point (5 to 10% reduction in mean systemic arterial pressure) used for NTG titration was achieved with a significantly lower dose in group B, in which a greater percent reduction in mean PA and mean PA wedge pressures was also observed. However, because effects of NTG on systemic vascular resistance were similar in groups A and B, it was concluded that the vasodilating action of NTG is maintained in advanced age, as opposed to what has been demonstrated for beta-adrenergic agents.

Aged↗

Improved exercise tolerance by i.v. fructose-1,6-diphosphate in chronic, stable angina pectoris.

The effect of IV fructose-1,6-diphosphate (FDP) on transient, reproducible myocardial ischemia was evaluated in ten patients, aged 50 to 66 years, with chronic, stable exertional angina. FDP or placebo (glucose) were administered between basal and posttreatment ergometric stress testing; an identical procedure was repeated in each patient with the second treatment on the following day according to a single-blind, cross-over design. FDP improved exercise tolerance and total work capacity, significantly delaying the onset of ST-segment depression and angina. Nevertheless, the critical level of the rate x pressure (R X P) product, causing appearance of myocardial ischemia, was not remarkably changed. However, the R X P product at same workload was significantly lower after FDP. These results suggest that improved exercise tolerance might have resulted from peripheral (increased oxygen delivery to skeletal muscle) rather than from central (cardiac) effects of FDP.

Aged↗

Hairy-cell leukemia. Morphologic, cytochemical, and immunologic features.

Hairy-cell leukemia is a unique lymphoproliferative disorder that has fascinated clinicians and researchers for nearly 3 decades. It can, in most cases, be diagnosed correctly on the basis of a bone marrow biopsy specimen, and the diagnosis is supported by the demonstration of tartrate-resistant acid phosphatase activity in the leukemic cells. Nevertheless, as outlined, rare "variant" cases may pose diagnostic problems, and other lymphoproliferative disorders may have features that closely mimic those of HCL. In virtually all cases of HCL, the hairy cells are of B-cell lineage, representing a relatively mature B cell that is closely related to plasma cells. Treatment of HCL with splenectomy, IFN-alpha, or 2' deoxycorformycin has led to excellent responses in most cases. Much of the progress in our understanding of the nature of this rare leukemia has been made possible through the cooperation of community physicians with referral institutions, or groups of institutions, that are interested in studying HCL. Despite the remarkable advances in the treatment of this disorder over the last 5 years, and the ready availability of IFN-alpha, much remains to be learned regarding the biology of hairy cells, and further advances in therapy still must be made. The needed information can be obtained only through continued referral of patients to centers with expertise and an interest in HCL.

Antibodies, Monoclonal↗

A stromal Leydig cell tumor of the ovary occurring in a pregnant 15-year-old girl. Ultrastructural findings.

The first case of stromal Leydig cell tumor of the ovary occurring during pregnancy is reported. A 15-year-old girl presented in labor at 36.5 weeks of gestation. The tumor mass was obstructing labor and the patient had to be delivered by cesarean section. Unique features of this case included the young age of the patient, the large size of the tumor, and the associated pregnancy. The tumor was encapsulated and showed the typical histologic and ultrastructural features of ovarian stromal Leydig cell tumor. The literature is reviewed, and the differential diagnosis is discussed.

Adolescent↗

Prediction of left ventricular function in acute anterior myocardial infarction by serum creatine kinase activity and precordial ECG mapping.

Right cardiac catheterization, serial determination of creatine phosphokinase (CPK) and of CPK-MB activities, and precordial 35-lead ECG mapping were performed in 17 consecutive patients with a first anterior acute myocardial infarction (AMI) within 6 hours of the onset of symptoms. Left ventricular function as determined by the stroke index (SI, ml/m2) to mean pulmonary capillary wedge pressure (PCWP, mmHg) ratio inversely correlated either with the total CPK and CPK-MB released and with peak enzymatic activity, or with the entity of early (6th hour ECG) ST-segment elevation. Conversely, a direct correlation was found between the SI/PCWP ratio and the ratio of R to Q+S waves from late (48th hour) ECG. Residual left ventricular function after a first anterior AMI can therefore be estimated noninvasively in the individual patient by early precordial ECG mapping and by peak enzymatic activity.

Adult↗