Biomedical subjects
Publications and source records attributed to P Vitale.
The phase transition of the Gross-Neveu model with N fermions is investigated by means of a nonperturbative evolution equation for the scale dependence of the effective average action. The critical exponents and scaling amplitudes are calculated for various values of N in d = 3. It is also explicitly verified that the Neveu-Yukawa model belongs to the same universality class as the Gross-Neveu model.
A transgenic mouse line expressing the lacZ reporter under the control of a regulatory region of the col6a1 gene has been used to investigate differentiation of Schwann cells. The data suggest that: (1) activation of col6a1 gene transcription in the peripheral nervous system is part of the differentiation program of Schwann cells from neural crest cells stimulated by neuregulins; (2) once the Schwann cell precursors have acquired the competence of transcribing the col6a1 gene, transcriptional regulation becomes independent from neuregulins and is modulated by different mechanisms, including cell cycle; (3) activation of transgene expression after birth in sciatic nerves corresponds to the time of withdrawal of immature Schwann cells from the cell cycle and the beginning of their differentiation into myelinating Schwann cells.
The region extending from -5.4 to -3.9 kilobase pairs from the transcription start site of the Col6a1 gene has been previously shown to contain sequences activating tissue-specific transcription in articular cartilage, intervertebral disks, subepidermal, and vibrissae mesenchyme and peripheral nervous system (Braghetta, P., Fabbro, C., Piccolo, S., Marvulli, D., Bonaldo, P., Volpin, D., and Bressan, G. M. (1996) J. Cell Biol. 135, 1163-1177). Analysis of expression of deletions of this region in transgenic mice has identified the 383-base pair fragment E-L as the most active sequence of the region. Linker-scanning mutagenesis analysis of segment E-J, which spans the 5' 245 base pairs of E-L and is sufficient for high frequency expression in articular cartilage, showed that all the mutations reduced transcription considerably, suggesting that the integrity of the entire cluster of elements is necessary for enhancer activity. Electrophoretic mobility shift assays with nuclear extracts derived from various sources showed that fragment E-J binds numerous transcription factors (at least 22). These factors are present in most cells, expressing and nonexpressing alpha1(VI) collagen mRNA, but in different relative proportions, and none of them appears to be cell type-specific. Several lines of evidence indicate that sequence elements of the enhancer may have different functional roles in various cells. The data configure the -5.4/-3.9 region of the Col6a1 gene as a new type of tissue-specific enhancer, characterized by a variety of tissues supporting its activation and by the dependence of its function only on ubiquitous transcription factors. This type of enhancer is postulated to be particularly important for genes such as those of the extracellular matrix, which are often expressed with broad tissue specificity.
Cis-acting regions regulating transcription of the alpha1(VI) collagen chain have been investigated in vitro by transfection of promoter-CAT (where CAT is chloramphenicol acetyltransferase) constructs in different types of cultured cells and in vivo in transgenic mice carrying the same CAT constructs or minigenes derived from the fusion of genomic and cDNA sequences in which small deletions of the collagenous domain had been engineered. 215 bp of 5'-flanking sequence showed promoter activity in vitro, yet were not expressed in any tissue of six transgenic lines, indicating that this fragment contains the basal promoter, but not activator sequences. Constructs with 0.6 and 1.4 kb of the 5'-flanking region produced significantly higher CAT activity in transfected cells and were expressed in tissues of about 30% of transgenic lines. Although CAT activity was totally unrelated to the pattern of expression of the alpha1(VI) mRNA, these results suggest the presence of an activator(s) between -0.2 and -0.6 kb from the transcription start site. When the promoter size was increased to 5.4 or 6.5 kb, CAT activity was stimulated severalfold relative to the construct p1.4CAT and p4.0CAT in NIH3T3 fibroblasts and chick embryo chondroblasts. This stimulation was, however, not observed in C2C12 myoblasts. Transgenic mice generated with 6.5CAT construct or minigenes, containing 6.2 kb of promoter, exhibited very high levels of expression, which was similar to the relative amount alpha1(VI) mRNA in the majority of tissues, with the exception of lung, adrenal gland and uterus. CAT activity in tissues was 100-1000-fold higher than that measured in transgenic mice with shorter promoter (0.6 or 1.4 kb). Since expression of minigenes was determined by RNase protection assay, the levels of mRNA per transgene copy were compared to those of the chromosomal gene and found to be always less than one quarter. These data suggest that the region -4.0/-5.4 contains an important activator(s) sequence which induces transcription in several, but not all, type VI collagen-producing tissues. Finally, analysis with the longest promoter fragment (7.5 kb) revealed a complex effect of the region -6.5/-7.5 on alpha1(VI) chain transcription. The sequence was inhibitory in NIH3T3 cells, indifferent in myoblasts and activating in chondroblasts in vitro, whereas transgenic animals generated with 7.5CAT construct produced a pattern of expression comparable to that of 6.5CAT and minigenes. During postnatal development transcription from both the endogenous gene and the transgenes decreased. However, the ratio of transgene/chromosomal gene expression was not constant, but varied in a way dependent on the tissue. This observation suggests that the fragment studied contains key sequences for the age-dependent regulation of the alpha1(VI) gene. No phenotypic alterations were induced by the presence of mutations in the minigenes.
Explore the source record for details and available documents.
During differentiation of ClC12 myoblasts in vitro, expression of alpha 1(VI) collagen mRNA was transiently stimulated severalfold. Promoter assays on cells transfected with chloramphenicol acetyltransferase (CAT) chimeric constructs have identified a region of the alpha 1(VI) a collagen promoter that increases CAT activity about 8-fold during differentiation. The region, which overlaps with transcription initiation sites, was shown to contain three protected segments (A, B, and C) in DNase I footprinting assays. The contact points between nuclear factors and the protected segments were determined by methylation interference assay and included the sequence GGGAGGG (GA box) in all segments. Experiments in which CAT constructs were cotransfected with double-stranded oligonucleotides containing the GA box suggested that this motif was necessary for induction. Transfections with deletion constructs of the natural promoter and with minipromoters made of three copies of A, B, or C showed that the elements have inducing activity and that elements C and, to a lower extent, B are stimulatory for basal transcription, whereas the contribution of A in this process is limited. Electrophoretic mobility shift assays with nuclear extracts from C2C12 cells indicated that the three GA box-containing elements bound several transcription factors, including Sp1. Comparison of the properties of the bands shifted under different experimental conditions (presence of 10 mM EDTA, heating of the nuclear extracts, addition of different concentrations of competitor oligonucleotides) established that A, B, and C probes form nine, eight and five main retarded complexes, respectively, and indicated that nuclear factors binding to C and B are subsets of proteins binding to A. UV cross-linking assays identified several peptides (seven with probe A, six with B, And five with C) in the range of 150-32 kDa. Comparison of the gel retardation pattern obtained with nuclear extracts from proliferating and differentiating cells revealed a particular increased intensity of two retarded bands. The data establish that multiple GA boxes mediate induction of the alpha 1(VI) collagen promoter during myoblast differentiation and suggest the attractive hypothesis that the effect may be related to variations of expression of transcription factors binding to these motifs.
A 50 year old woman with no evidence of structural heart disease was referred for ectopic incessant repetitive atrial tachycardia uncontrolled by medical therapy. Intracavitary and transesophageal simultaneous recordings revealed the earliest atrial electrical activity to be located in the left atrium. Intraoperative electrophysiologic mapping demonstrated that the site of earliest atrial activation was in a small diverticulum of the left atrial appendage. Excision of the appendage and isolation of left atrium was carried out with restoration of sinus rhythm. The patient was arrhythmia-free till 24 months later. Surgical treatment appears to be an effective therapeutic option for drug-resistant ectopic atrial tachycardia.
A method of rapid screening for appropriateness of certain drug doses is described. The program extracts patient information from a hospital mainframe computer system, performs an estimation of creatinine clearance (CrCl), and prints a report of patients, drugs, doses, and CrCl for patients within a specified CrCl range.
In a patient with atrioventricular nodal reentrant tachycardia, during programmed stimulation, an atrial extrastimulus induced a double ventricular response due to a single atrial depolarization, with simultaneous and delayed anterograde conduction through fast and slow pathways, and induced the tachycardia. Pacing-induced type I block involving both pathways put these pathways out of phase, so that the distal conduction system and the ventricle responded to both the fast and slow pathways anterograde impulses.
Paraneoplastic pemphigus is a recently described disease in which patients have polymorphous skin lesions suggestive of both erythema multiforme major and pemphigus vulgaris in association with internal neoplasms, especially non-Hodgkin's lymphoma. These patients have characteristic autoantibodies that bind specific epidermal proteins. A Nikolsky-negative bullous pemphigoid-like eruption developed within the radiation therapy field in a 72-year-old man receiving palliative treatment for recurrent large cell lymphoma. The eruption rapidly progressed to a Nikolsky-positive bullous process more typical of pemphigus vulgaris with extensive involvement of respiratory epithelia. Despite aggressive treatment with high-dose corticosteroids and antibiotics, the patient rapidly succumbed. Results of immunofluorescence studies and autopsy findings confirmed the diagnosis of paraneoplastic pemphigus.
Two cases of phase 3 intraventricular block and linking phenomenon of type 1 and type 2 (or bigeminal rhythm linking) are presented. In the first case, complexes that follow the extrasystolic blocked beat are wide, although they are associated with relative long R-R cycle:type 1 linking. In the second case, bundle branch block and normal conduction alternate in bigeminal extrasystolic beats:type 2 linking. The linking phenomenon is due to concealed retrograde penetration of the bundle branch that is blocked in anterograde direction. It delays the cycle and the refractory period of the bundle branch. Therefore, in type 1 linking, the subsequent stimulus, although occurring with a long R-R cycle, is again blocked in the same bundle branch. In type 2 linking, the R-R cycle and refractory period, occurring after bundle branch block, are shorted because comprised between retrograde activation by extrastimulus and anterograde activation by subsequent sinus stimulus. The subsequent ectopic impulse, although premature, is normally conducted.
Electrophysiologic studies in a patient with intermittent ventricular pre-excitation revealed several types of paroxysmal narrow-QRS tachycardia (PSVT). One type of PSVT was characterized by normal retrograde atrial sequences with P waves occurring simultaneously with QRS. This type of PSVT reflected AV nodal reentry with anterograde slow pathway and retrograde fast pathway conduction. A second PSVT reflected alternation of anterograde fast and slow AV nodal pathway conduction and retrograde anomalous pathway conduction. A third PSVT reflected anterograde slow AV nodal pathway and retrograde anomalous pathway conduction. Moreover, discontinuous AV nodal conduction curves (A1A2/H1H2), characteristic of dual AV nodal pathway conduction, were obtained with programmed atrial extra stimulation. These observations suggest that dual AV nodal pathway conduction can coexist with abnormal bypass tract and can be the cause of PSVT in patients with Wolff-Parkinson-White syndrome.
Intermittent left bundle branch blocks are present in the ECGs of 1 patient with mitral valve disease. By occurring either after short or long cycles they represent respectively phase 3 and phase 4 blocks. Such mechanisms emphasize the relationship between automatism and conduction. The occurrence of block and of normal conduction during cycles of the same length, its correlation with the conduction of the previous cycle, demonstrate the presence of a functional linking between successive impulses. This linking may occur every time a potential or active macroreentry circuit exist. In our case the circuit is formed by the 2 bundle branches which join distally in the ventricular septum.
Thermal maps of the lumbo-sacral and gluteal regions and of the lower limbs were obtained with telethermography in 30 subjects suffering from painful lumbo-sciatic syndromes in order to assess whether there were differences of thermal index between painful and opposite side, and to evaluate the telethermographic patterns of the irritative and deficitary forms. Among 25 patients with lumbo-sciatalgia in the irritative or early stage, 16 showed hypothermia of the affected side; in three of the five patients in the deficitary stage, hyperthermia of the affected side was observed while two did not show changes of the thermal gradient. The authors stress the importance of telethermography and suggest that this method, which is not costly, non-invasive and easily reproducible, should be used to complete diagnosis of and to monitor lumbo-sciatalgic syndromes.
A case of permanent atrial standstill suspected upon electrocardiogram is reported, and confirmed by electrophysiological investigation. The originality of this case resides in the fact that the atrial standstill marks the developmental outcome of a bradycardia-tachycardia syndrome. This developmental sequence is the subject on discussion. It is concluded that a combination of auricular muscle lesion and sinus node tissue remains the most plausible anatomical and pathophysiological substratum of the bradycardia-tachycardia syndrome which developed into atrial standstill.
The ECGs of four patients with implanted dual chamber VDD and DDD PMKs are shown to demonstrate the difficulty of their interpretation and show some arrhythmias related to dual chamber pacing. In the first patient the DDD PMK caused a high ventricular frequency synchronizing on the atrial fibrillation "f" waves which occurred suddenly some time after PMK implantation; this problem was solved by programming the PMK in VVI. The second and third case, with implanted DDD and VDD PMK respectively, exemplify atrial sensing dysfunction due to atrial catheter displacement. In the fourth patient, with implanted VDD PMK, VDD stimulation periods and VVI ones alternated due to non-adjusted programming. Therefore, the paper re-emphasizes the need for accurate and periodic controls of patients with implanted PMK to correct dysfunction or undesirable patterns of stimulation.
In order to determine the relationship among ventricular arrhythmias, left ventricular dysfunction and sudden cardiac death (SCD), 75 consecutive patients with myocardial infarction, 38 of whom resuscitated from SCD, were studied retrospectively by 48 hour Holter electrocardiographic monitoring (ECGD), cardiac catheterization and radionuclide angiography (ACRD). The patients were divided in 3 groups, related to SCD occurrence and to the interval between acute myocardial infarction (AMI) and SCD: Group I (37 patients-control group) no cardiac arrest occurred; Group II (26 patients) resuscitated less than or equal to 48 hours after AMI; Group III (12 patients) resuscitated 6-12 weeks after AMI. ECGDs were recorded with an average of 2 (ECGD 1), 16 (ECGD 2) and 36 months (ECGD 3) after AMI. In ECGD 1, there were no differences in the frequency and complexity of ventricular arrhythmias among the 3 groups, whereas in ECGD 2 and 3 the incidence of complex ventricular arrhythmias was significantly higher in Group III than in the other 2 groups (p less than 0.05). In Group III, the complexity and frequency of ventricular arrhythmias increased both in ECGD 2 and 3 compared to ECGD 1 (p less than 0.05). Furthermore, between patients of Group II and III higher grade arrhythmias and more frequent ventricular premature beats (VPB) were noted in sudden death patients than in survivors. There was no statistical difference in mean cardiac index, left ventricular end-diastolic pressure and ejection fraction among the groups. In the ACRD 1 performed an average of 8 months after AMI, a slight decrease of ejection fraction in Group III compared to the other groups was noted (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
In a patient without a demonstrable heart disease a congestive heart failure developed during an atrioventricular tachycardia which persisted for 20 days at the rate of 180/b/m'. After conversion to sinus rhythm, by means of transesophageal pacing, a quick regression of the failure symptoms followed. The heart rate increase and the persistence of tachycardia may have determined the depletion of myocardial stores and therefore, the myocardial dysfunction responsible for the cardiac failure. In order to prevent myocardial dysfunctions, it is necessary to interrupt supraventricular tachycardias as early as possible, even when they are observed in patients without any heart disease.