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Biomedical subjects

P Bernasconi

Publications and source records attributed to P Bernasconi.

At least 19 recordsLinked to original sources
PubMed1992

Evolution of structure and function of V-ATPases.

Proton pumping ATPases/ATPsynthases are found in all groups of present-day organisms. The structure of V- and F-type ATPases/ATP synthases is very conserved throughout evolution. Sequence analysis shows that the V- and F-type ATPases evolved from the same enzyme already present in the last common ancestor of all known extant life forms. The catalytic and noncatalytic subunits found in the dissociable head groups of the V/F-type ATPases are paralogous subunits, i.e., these two types of subunits evolved from a common ancestral gene. The gene duplication giving rise to these two genes (i.e., encoding the catalytic and noncatalytic subunits) predates the time of the last common ancestor. Mapping of gene duplication events that occurred in the evolution of the proteolipid, the noncatalytic and the catalytic subunits, onto the tree of life leads to a prediction for the likely subunit structure of the encoded ATPases. A correlation between structure and function of V/F-ATPases has been established for present-day organisms. Implications resulting from this correlation for the bioenergetics operative in proto-eukaryotes and in the last common ancestor are presented. The similarities of the V/F-ATPase subunits to an ATPase-like protein that was implicated to play a role in flagellar assembly are evaluated. Different V-ATPase isoforms have been detected in some higher eukaryotes. These data are analyzed with respect to the possible function of the different isoforms (tissue specific, organelle specific) and with respect to the point in their evolution when these gene duplications giving rise to the isoforms had occurred, i.e., how far these isoforms are distributed.

Amino Acid Sequence↗
PubMed1991

Localization of DNA probes tightly linked to the Friedreich's ataxia locus by in situ hybridization in a case of pericentric inversion of chromosome 9.

The gene for Friedreich's ataxia (FA), an autosomal recessive neurodegenerative disorder, has been recently assigned to the long arm of chromosome 9. Linkage disequilibrium between FA and two diverse chromosome 9 markers, D9S5 and D9S15, has been detected in French, French-Canadian and Italian populations. Here, we report the physical localization of these loci by in situ hybridization of probes 26P and MCT112S identifying the D9S5 and D9S15 loci, respectively. Experiments performed on lymphocytes carrying a chromosome 9 pericentric inversion have allowed us to assign both the loci to band 9q21. Furthermore, in situ hybridization data and partial sequencing of the probe MCT112S indicate the presence of alphoid satellite DNA within this region. This suggests that MCT112S is more proximal to the centromere than 26P.

Base Sequence↗
PubMed1991

Acute noise stress in rats increases the levels of diazepam binding inhibitor (DBI) in hippocampus and adrenal gland.

We investigated the effect of acute noise-induced stress on the concentrations of diazepam binding inhibitor (DBI) and its processing products in brain regions and adrenal glands of rats. DBI levels in hippocampus began to increase at 15 and 30 min and became significantly higher (+100%) at 90 and 120 min after stress; they returned to normal values at 360 min. While basal DBI levels were similar in the left and right hippocampus, the stress-induced increase of DBI levels was significantly higher in the left compared to the right side. A significant increase was also detected in the adrenals; here, the time course of DBI increase paralleled that of previously reported plasma corticosterone in stressed rats, being significantly higher 30 min after stress, and recovering to normal values at 60 and 90 min. After acute noise-induced stress, no significant change of DBI levels was detectable in cerebral cortex, striatum, hypothalamus and cerebellum. The present study reports for the first time the occurrence of a modification of DBI and its processing products (ODN-like immunoreactivity) in an experimental model of stress, and suggests a role for these neuropeptides in emotional responses.

Adrenal Glands↗
PubMed1991

Evolving modalities of treatment with interferon alfa-2b for Ph1-positive chronic myelogenous leukaemia.

We have administered interferon alfa-2b, alone or in combination with chemotherapy, to 126 Ph1-positive chronic myelogenous leukaemia patients. Of 71 early chronic phase (CP) patients (less than 12 months from diagnosis), 41 (58%) obtained a complete haematological response (CHR). Daily interferon was more effective than intermittent administration. In previously untreated patients, the response was significantly influenced by risk status at diagnosis. Thirty-four out of 71 (48%) patients improved cytogenetically, the median of Ph1+ mitoses declining from 100% to 66% with complete Ph1-suppression in one case. Of 46 late CP patients (greater than 12 months from diagnosis), 32 (70%) achieved CHR with interferon alone or combined with chemotherapy. All 10 patients with disease well controlled by chemotherapy obtained stable CHR with interferon alone. Of 36 partial responders to conventional chemotherapy, 22 (61%) obtained CHR on interferon plus low-dose hydroxyurea. Ph1 mosaicism was reached by 16 (35%) late CP patients (median Ph1+ cells 75%). Of nine accelerated phase patients on interferon plus chemotherapy, one attained CHR, and two responded partially. At a median follow up of 36 months, of 41 CHR patients in early CP, 15 are controlled on interferon, 12 have had autologous bone marrow transplantation (BMT), and two allogeneic BMT. Blastic transformation (BT) has occurred in eight of 41 CHR patients (19%) versus 17 of 30 (57%) non-responders and partial responders to interferon. At a median follow up of 22 months, of 32 late CP patients obtaining CHR, 26 remain on interferon, one had allogeneic BMT, one had autologous BMT, and one developed BT (versus five out of 14 with less than CHR). These studies confirm the haematological and cytogenetic efficacy of interferon in CML and indicate that the disease status at the start of treatment is critical in determining the success of therapy.

Combined Modality Therapy↗
PubMed1991

[Imaging of the breast treated with quadrantectomy and radiotherapy. Interpretative difficulties in diagnosing asymptomatic recurrences].

This study was aimed at evaluating the incidence of breast carcinoma recurrences in a group of female patients treated with QU.A.RT. July 1989 to December 1990, 111 asymptomatic patients underwent physical examination, mammography (in both cranio-caudal and 45 degrees oblique projections), and US with 7.5 and 10 MHz probes. The study population was made of patients operated between 1984 and 1989 and subsequently treated with radiotherapy. Twenty-seven cases with suspect mammographic and US findings were selected and submitted to cytology with needle biopsy under US or stereotaxic guidance. Ten of them exhibited recurrences (9%) at cytology. Of the extant 17 cases, 5 had inflammatory lesions, 1 had liponecrosis, and 11 patients presented with no pathologic cells. The interpretative difficulties of mammographic and US findings were also examined. Problems were found to be related to both correct execution of the technique due to the treatment the breast is submitted to (volumetric reduction and structural distortion) and to correct image interpretation. Therefore we conclude that the two diagnostic methods be combined for they are complementary in the early detection of breast carcinoma recurrence.

Breast Neoplasms↗
PubMed1991

[Response of the IRD intestinal epithelial cell line to Clostridium difficile toxins A and B in rats. Effect of Saccharomyces boulardii].

In vivo, Clostridium difficile acts by releasing 2 toxins: toxin A, an enterotoxin, and toxin B, a cytotoxin. This study was performed to determine: a) whether the rat epithelial intestinal cell line IRD 98 responds to Clostridium difficile toxin A and B; b) whether the yeast Saccharomyces boulardii has an effect on this model. Evaluation of 3H-thymidine incorporation into IRD 98 cells exposed to toxin B revealed that DNA synthesis was inhibited for low concentrations (10 ng/ml). For higher concentrations, DNA synthesis was not modified. Evaluation of 14C-leucine incorporation into IRD 98 cells exposed to toxin B revealed that this toxin affected protein synthesis. Whereas cholera toxin stimulates adenylate cyclase in IRD 98 cells, cAMP levels in cells exposed to various quantities of toxin A was similar to that in control cells. As opposed to cholera toxin, which does not affect the cytoskeletal structure of IRD 98 cells, 7 micrograms/ml of toxin A and even smaller amounts of toxin B (1 ng/ml) were found to cause structural alterations by immunofluorescence studies. Prior exposition of cells to Saccharomyces boulardii reduced or prevented the rounding of cells in the presence of these toxins. IRD 98 cells can thus be considered a good model for in vitro investigation of the effects of Clostridium difficile toxins A and B, and findings suggest that Saccharomyces boulardii has a protective effect against the action of these toxins.

Animals↗
PubMed1991

Burkitt's lymphoma/leukemia: a clinicopathologic study on 24 adult patients.

We have retrospectively analyzed the characteristics of 24 adult patients affected with non-endemic Burkitt's lymphoma (BL) and Burkitt cell acute leukemia (L3 ALL). The median age of the entire group was 29 years with a male preponderance (75%). Median LDH value was 580 mU/mL. Test for HIV-antibodies was carried-out in 16 patients; 5 of them (21%) showed HIV positive. CNS was involved in 25% of patients at diagnosis. In all cases studied for karyotype, the t(8;14) translocation was evident. As to therapy, 5 patients were not evaluable for early death, 12 were given an intensive ALL program, 5 a cyclic chemotherapy and 2 a new protocol alternating high-dose cyclophosphamide, high-dose cytarabine with mitoxantrone and the CHOP regimen. The overall complete remission rate was 42%; among 7 remitters, 4 have relapsed so far within a median time of 6 months. Three of 13 (23%) patients with lymphoma presentation are long remitters and may be cured; all cases had stage II disease and low LDH at diagnosis (less than 250 mU/mL). No patients with Burkitt's leukemia survive. CNS disease (8 cases) and septic shock (6 cases) were the most frequent terminal events. In our experience, the prognosis of advanced stage BL and L3 ALL in adults does remain dismal; the high prevalence of CNS disease and HIV-positivity may have contributed to the poor outcome.

Adult↗
PubMed1991

[Myocardial infarction caused by closed thoracic injury: pathogenic and angiocoronarographic aspects. Apropos of 4 cases and review of the literature].

The 4 cases of transmural myocardial infarction by closed chest trauma reported by the authors bring the number of angiographically documented and published cases to 52. This group serves as a basis for a detailed review of coronary and myocardial anatomical lesions and their pathophysiological mechanism is suggested. Long controversial, direct traumatic coronary damage has been confirmed by coronary angiography and is the essential mechanism of transmural infarctions. Myocardial contusion, much commoner, is responsible for non transmural lesions which remain difficult to diagnose. The authors stress the twin value of coronary arteriography: pathophysiological with its medicolegal consequences, and also therapeutic since a revascularisation procedure may be particularly beneficial in situations where thrombolysis is generally contraindicated.

Adolescent↗
PubMed1990

[Treatment of cardiac insufficiency by beta-blockaders. A review of the literature and discussion].

The use of beta-blockers in the treatment of heart failure at first seems paradoxical because of their negative inotropic effect. Nonetheless, clinical studies performed over the last ten or so years in patients with dilated cardiomyopathy or ischemic heart failure indicate functional improvement and a tendency to reduced mortality. These preliminary studies were carried out with a limited number of patients and were sometimes by nature methodologically imperfect. They have since been succeeded by large, randomized, prospective studies also based on solid experimental arguments concerning the supposed mechanisms of action of beta-blockers. The themes of these studies include: protection against the cardiotoxicity of catecholamines, up-regulation, reduction in myocardial energy requirements and in heart rate, improved diastolic function and compliance, inhibition of vasoconstriction induced by catecholamines, and antiarrhythmic action.

Adrenergic beta-Antagonists↗
PubMed1990

[Thrombolysis and intravenous beta-blockaders in the acute phase of myocardial infarction].

Since proof exists of the individual efficacy of thrombolytics and intravenous beta-blockers in the acute phase of myocardial infarction (MI), it seemed to us logical and interesting to combine them. The aim of this retrospective study was to evaluate the safety and potential benefit of this drug combination for left ventricular function. We compared 40 patients (group I) of mean age 53.9 +/- 8.5 years admitted for MI in the six hours following the onset of symptoms treated by thrombolysis and intravenous beta-blockers (metoprolol or atenolol), with 27 patients (group II) of mean age 57.1 +/- 9.4 years treated within the same time lapse by thrombolysis alone. All patients underwent coronary arteriography and only two in group I were not examined by ventriculography. The two groups were comparable in terms of age, coronary history, localization of MI, clinical status at the outset, and time lapse before administration of the thrombolytic. Only heart rate differed at the outset (lower in group II; p = 0.05). A significant reduction in heart rate of 18% was seen in group I. When administration of the two drugs was simultaneous (less than or equal to 30-min lapse between each drug) this reduction was greater (22%) than when they were given separately (13%). In group II, the drop in heart rate was not significant (63%). In contrast, the decrease in systolic pressure in both groups was significant and comparable (group I: 16.6%; group II: 14.5%) even in the case of simultaneous administration (22%). There was no between-group difference in left ventricular ejection fraction (LVEF).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1979

[Severe pulmonary embolism and recurrent thrombophlebitis caused by hereditary antithrombin III deficiency].

Severe pulmonary embolism with thrombosis of the inferior vena cava was observed in a 16 year old girl with no risk factors and treated successfully by fibrinolytic therapy. Secondarily, despite heparino-therapy, upper limb venous thrombosis occurred. Investigation of the clotting factors in the patient and her family revealed a hereditary deficit of antithrombin III. The features of the haemotological diagnosis of this rare condition and the therapeutic implications are discussed.

Adolescent↗
PubMed1979

[Artefacts during continuous electrocardiography by the Holter method].

Continuous ECG by the Holter method provides valuable information on the electrical activity of the heart but the interpretation of the playback may be made difficult by the presence of artefacts. The principal artefacts which may mimic arrhythmias or blocks, disturb QRS detection or deform the ventricular depolarisation are described. The majority are caused by incomplete preparation of the patient or the electrodes, but others may arise from a mechanical or electrical fault. Artefacts interfere with the automatic analysis of the tape, which is one reason for knowing the limitations of these systems of automatic analysis, and therefore control visual reinterpretation is necessary in cases where there is the slightest doubt. The presence of these artefacts is a limitation of the Holter method, the practice of which demands a certain amount of experience to avoid incorrect diagnoses which could lead to inappropriate or injustified therapy.

Diagnosis, Differential↗
PubMed1978

[Hyperventilation test in coronary disease: a comparison with a bicycle ergometer exercise test. Report of 100 cases].

A hundred cases have been studied and divided into three categories:--60 normal subjects;--30 coronary subjects with a positive exercise test;--10 subjects with defective nervous control of the circulation; using the exercise test, we studied the effects of hyperventilation on repolarisation of the ventricle. In the normal subjects there was no ischaemic depression of the ST segment, but there were minor changes in repolarisation which affected the T wave in 73% of subjects and were essentially posterior in distribution. In the coronary subjects, we found three with ischaemic depression of the ST segment and one with ST elevation of 2.5 mm (6.7% of the coronary subjects). This last finding is evidence against the commonly held hypothesis that reproduction of ST depression by hyperventilation during the exercise test indicates a false positive test. In the patients with defective nervous control of the circulation, 9 had an ischaemic type of ST depression, either as a new feature or as a more severe one compared with that found at rest. The mechanism by which these depressions are produced has not been totally explained:--in the cases with defective nervous control of the circulation, it appears that latent increased sympathetic activity is increased by the hyperventilation;--in the coronary subjects, it may be caused by true ischaemia or by an associated defect in nervous control of the circulation.

Adult↗
PubMed1978

[Comparison of echocardiography and phonomecanography in adult aortic valve stenosis. 55 cases].

The results of echocardiography and phonomecanography were compared in 55 cases of adult valvular aortic stenosis. Although the most reliable echocardiographic sign of the severity of stenosis is the systolic separation of the aortic valve echos, it should be amphasised that: -- this cannot be measured in 25 % cases; --in 10 % cases the values obtained vary with the angle of the transducer. In these cases, the finding of a left ventricular posterior wall thickness greater than or equal to 15 mm is specific for severe aortic stenosis. On the other hand, the left atrial, left ventricular and aortic internal dimensions and the morphology of the mitral leaflets do not help in the estimation of the severity of adult aortic stenosis. The best correlations between echo and phonocardiography are the values of aortic valve opening and : --hemi-ascension time (r = 0.67); --left ventricular ejectiontime (r = 0.93) when patients in cardiac failure are excluded. The complementary nature of these two investigations is notable, and should, in pure aortic stenosis without angina, spare patients who are often elderly and fragile from heamodynamic investigation.

Aged↗