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Biomedical subjects

M Lab

Publications and source records attributed to M Lab.

At least 37 records · Page 2Linked to original sources
PubMed1994

Oncogene activation: an informative marker for the human papillomavirus-lesions severity.

The aim of this study was the detection of c-Ha-ras and c-myc activation and p21ras and p62myc expression in anogenital HPV-associated lesions. Thirty-two women with cervical and vaginal lesions and forty men with anal or penile warts were enrolled for the study. Biopsies were subjected to histological assessment, in situ hybridization with biotinylated probes, and immunohistochemistry. In both women and men, most of the biopsies showing no major histological abnormalities were negative for HPV detection. The low-grade squamous intraepithel-)ial lesions (SIL) harbored HPV in more than 50% of cases. The high-grade SIL contained mostly oncogenic HPV. C-Ha-ras and c-myc activation was detected in 31/41 HPV-positive lesions, especially in lesions harboring HPV 31/35/51 or multiple HPV. Simultaneous activated oncogenes were found in 7 out of 9 high-grade SIL and in 21 out of 45 low-grade SIL. In most of the lesions, we demonstrated concurrent detection of p21ras and p62myc proteins and oncogene activation. Our study shows that c-Ha-ras and c-myc activation is correlated with oncoprotein expression and associated with the presence of oncogenic HPV. Such activation might play a role in the development of high-grade anogenital dysplasia.

Anus Diseases↗
PubMed1993

[Anogenital papillomavirus lesions in humans with or without HIV infection. Comparison of colposcopic, histopathological and virological results].

Anal and genital lesions caused by human papilloma virus (HPV) may be associated with severe dysplasia and cancer, chiefly in cases of "high risk" HPV types 16, 18, 31, 35, 51. The frequency of HPV infections and the severity of genital cancers seem to be increased in patients with human immunodeficiency virus (HIV) infection. PATIENTS AND METHOD. The distribution of different HPV types was compared with the anatomical and clinical features of the lesions in two populations, one HIV+ (n = 40) and the other HIV- (n = 48), who had anal and genital lesions. The HPV DNA was determined by molecular hybridization in situ, using biotinylated probes which recognized HPV types 6/11, 16/8 and 31/35/51 on 99 lesions. RESULTS. HIV+ subjects differed from HIV- subjects in that a higher proportion of them had anal lesions (50 p. 100 vs 10 p. 100) and condyloma latum (80 p. 100 vs 50 p. 100). Koilocytosis without dysplasia was more often found in HIV- subjects (12.5 p. 100 vs 55 p. 100). Conversely, dysplasia was more frequent among the lesions of HIV+ subjects: grade I 39.5 p. 100 vs 17.5 p. 100; grade II 25 p. 100 vs 4 p. 100; grade III 12.5 p. 100 vs 0 p. 100. Koilocytosis was preferentially associated with condyloma acuminatum. In HIV+ subjects the DNA of HPV, detected in 73 p. 100 of the lesions, was "high risk" HPV DNA in 86 p. 100 of the cases, whereas in HIV- subjects 51 p. 100 of the samples were positive in hybridization, and 61.5 p. 100 had "low risk" HPV DNA. In subjects of all groups "high risk" HPV was found in dysplastic lesions. CONCLUSION. HIV seropositive subjects show an imbalanced distribution of HPV with predominance of "high risk" HPV. This suggests that immunodepression encourages infection by this oncogenic virus, thereby contributing to the frequency of cancer in HIV+ subjects.

AIDS-Related Opportunistic Infections↗
PubMed1992

Viral co-infections in human papillomavirus-associated anogenital lesions according to the serostatus for the human immunodeficiency virus.

In HIV-infected men, human papillomavirus (HPV) infection is strongly linked with the development of anogenital lesions but is not a sufficient factor to explain the neoplastic transformation of such lesions. We investigated the association between HPV and herpesvirus infections in penile and anal lesions from 54 HIV-seronegative and 54 HIV-seropositive men by means of colposcopy, histopathology and in situ hybridization. Our patients showed condyloma acuminata (39%), papular warts (35%) and macular warts (26%). High-grade lesions were predominant in the HIV+ men, whereas low-grade lesions were more frequent in the HIV- men. In the HIV+ group, potential oncogenic HPV were the most frequently detected (83.4%) whereas the "low-risk" HPV were found chiefly in HIV- men (62.1%). The CD4 number was lower in patients showing "high-risk" HPV than in men showing lesions without HPV or with non-oncogenic HPV. HPV types 6/11 were found mainly associated with koilocytosis or with AIN(PIN)I. Oncogenic HPV were more often detected in AIN(PIN)II-III. The herpesviruses DNA detection revealed a higher prevalence of HSVI and -2 than CMV and EBV in the studied biopsies. The frequency of HSV and CMV detection was higher in the HIV+ than in the HIV- men. A link was found between the "high-risk" HPV and the CMV detection whatever the population considered. The detection in HPV lesions of other sexually transmitted viral agents could therefore represent an important means of preventing progression of the anogenital disease, especially in immunosuppressed patients.

Anus Diseases↗
PubMed1992

Monophasic action potential recordings during acute changes in ventricular loading induced by the Valsalva manoeuvre.

OBJECTIVE: The strong association between ventricular arrhythmia and ventricular dysfunction is unexplained. This study was designed to investigate a mechanism by which a change in ventricular loading could alter the time course of repolarisation and hence refractoriness. A possible mechanism may be a direct effect of an altered pattern of contraction on ventricular repolarisation and hence refractoriness. This relation has been termed contraction-excitation feedback or mechano-electric feedback. METHODS: Monophasic action potentials were recorded from the left ventricular endocardium as a measure of the time course of local repolarisation. The Valsalva manoeuvre was used to change ventricular loading by increasing the intrathoracic pressure and impeding venous return, and hence reducing ventricular pressure and volume (ventricular unloading). PATIENTS: 23 patients undergoing routine cardiac catheterisation procedures: seven with no angiographic evidence of abnormal wall motion or history of myocardial infarction (normal), five with a history of myocardial infarction but with normal wall motion, and 10 with angiographic evidence of abnormal wall motion--with or without previous infarction. One patient was a transplant recipient and was analysed separately. SETTING: Tertiary referral centre for cardiology. RESULTS: In patients with normal ventricles during the unloading phase of the Valsalva manoeuvre (mean (SD)) monophasic action potential duration shortened from 311 (47) ms to 295 (47) ms (p less than 0.001). After release of the forced expiration as venous return was restored the monophasic action potential duration lengthened from 285 (44) ms to 304 (44) ms (p less than 0.0001). In the group with evidence of abnormal wall motion the direction of change of action potential duration during the strain phase was normal in 7/21 observations, abnormal in 6/21, and showed no clear change in 8/21. During the release phase 11/20 observations were normal, five abnormal, and four showed no clear change. In those with myocardial infarction four out of five patients had changes that resembled those with normal ventricles but the changes were less pronounced. There were no differences in any of the three groups between the changes in monophasic action potential duration in patients taking beta blockers and those who were not. The changes in monophasic action potential duration in the transplanted heart resembled those in the group with normal ventricles. Inflections on the repolarisation phase of the monophasic action potential consistent with early afterdepolarisations were seen in three of the patients with abnormal wall motion and in none of those with normal wall motion. CONCLUSIONS: These results are further evidence that changes in ventricular loading influence repolarisation. When wall motion was abnormal the effects on regional endocardial repolarisation were often opposite in direction to those when it was normal. Thus regional differences in wall motion could generate local electrophysiological inhomogeneity which may be relevant to the association of arrhythmia with impaired left ventricular function.

Action Potentials↗
PubMed1992

Effect of abrupt changes in ventricular loading on repolarization induced by transient aortic occlusion in humans.

We have investigated the influence of ventricular loading on repolarization from beat to beat in the human heart. Sixteen patients undergoing routine coronary artery surgery were studied. Left ventricular epicardial monophasic action potentials and local electrograms were recorded during acute changes in ventricular loading induced by transient aortic occlusion. Monophasic action potential duration shortened (P less than 0.0001) and returned to control values within one or two beats after release (P less than 0.0001). Values at 90% repolarization were 325 +/- 31 ms preocclusion, 311 +/- 29 ms during occlusion, 326 +/- 32 ms postocclusion. The Q-T interval of the local epicardial electrogram shortened during occlusion (P less than 0.001) and returned to control values after release (P greater than 0.0001): 396 +/- 44 ms preocclusion, 379 +/- 41 ms during occlusion, and, 399 +/- 42 ms postocclusion. A significant correlation was obtained between changes in peak systolic pressure and changes in monophasic action potential duration (R = 0.96; P less than 0.0001 at 90% repolarization). A significant correlation was also observed between changes in peak systolic pressure and the Q-T interval of the local electrogram (R = 0.91; P less than 0.0001). This study shows that abrupt changes in ventricular loading from one beat to the next induce significant changes in the timing of ventricular repolarization. These results may well be relevant to the initiation of arrhythmia by a single ventricular ectopic beat, particularly under pathological conditions.

Action Potentials↗
PubMed1992

[Study by in situ hybridization of the prevalence of herpes virus as cofactors of the tumoral development of papillomatous lesions of the anogenital region in seropositive and seronegative men against HIV].

Infection with specific types of HPV has emerged as necessary but not sufficient factor in the neoplastic transformation of anogenital condylomas. Some viruses (HIV, Herpes viridae: HSV, CMV, EBV) might act as cofactors in the neoplastic changes and cancer. To study the prevalence of these viral pathogens in anogenital lesions, biopsies were obtained from HIV seropositive or seronegative men and tested using in situ hybridization technique. Infection by "high risk" HPV, HSV and CMV are facilitated in patients immunocompromised by HIV. Presence of CMV is more frequent in high risk HPV-induced lesions than in low risk HPV lesions.

Anus Neoplasms↗
PubMed1991

Detection of human papillomavirus and human cytomegalovirus in cervical lesions by in situ hybridization using biotinylated probes.

Infections with specific types of human papillomavirus (HPV) have emerged as necessary but not sufficient factors in the development of the majority of cervical cancers. The infection by human cytomegalovirus (HCMV) has also been implicated in both cervical intraepithelial neoplasia (CIN) and cancer. In order to test prevalence of these viral pathogens in genital lesions with suspect cytopathic changes after observation of smears, cervical biopsies from 131 patients were obtained under colposcopic guidance. The biopsies were tested for the presence of HPV and HCMV by the in situ hybridization technique using biotinylated DNA probes on paraffin-embedded sections. Presence of HCMV is twice more frequent in women with HPV-induced cervical lesions (40%) than in women with any detectable HPV (20%). It may be concluded that HCMV might contribute as one synergistic factor in the development of cervical dysplasia.

Cervix Uteri↗
PubMed1991

Alternans of epicardial repolarization as a localized phenomenon in man.

Electrophysiological alternans (beat-to-beat alternation of the configuration of the action potential and/or electrocardiogram) may be important in the causation of ventricular arrhythmias. We recorded monophasic action potentials from the left ventricular epicardium in patients undergoing routine cardiac surgery. We set out to determine: (a) whether a small increase in atrial pacing rate could elicit electrophysiological alternans; (b) whether different phases of the operation influence the incidence and; (c) whether electrical alternans was a localized phenomenon. Thirty-six patients were studied, and alternans of action potential duration was observed in 14 (39%). The difference between alternate long and short action potential durations ranged from 4 to 112 ms. The mean differences during each stage of the protocol were: pacing before bypass 33.3 +/- 22.7 ms (three of 17 patients); pacing after bypass 46.7 +/- 37.8 ms (nine of 36 patients); pacing during transient graft occlusion 28.0 +/- 23.1 ms (five of 17 patients); pacing following release of the grafts 29.6 +/- 30.0 ms (five of 17 patients). None of the patients showed any evidence of alternans in the electrocardiogram or mechanical alternans in radial artery pressure. In seven of the 14 patients showing alternans, recordings were made in closely adjacent (approximately 1 cm) areas showing that alternans could be a localized phenomenon. The findings indicate that electrical alternans was a frequent occurrence in this study (39% of patients) and may be a localized phenomenon.

Action Potentials↗
PubMed1991

Optimization of in situ hybridization for detection of viral genomes in cultured cells on 96-microwell plates: a cytomegalovirus model.

In situ hybridization (ISH) for identification of infectious replicative cytomegalovirus (CMV) in cell culture microplates (96 microwells) infected by clinical specimens was tested by using a biotin-labeled DNA probe and an avidin-alkaline phosphatase conjugate. A total of 395 specimens were examined by using ISH and a monoclonal antibody (MAb) specific for an early antigen of CMV. Of 47 specimens that gave a positive signal for CMV by ISH, 33 were confirmed virus positive by MAb staining. Of 141 blood samples tested, 4.96% were positive by ISH, and 0.7% were positive by the MAb technique. ISH shows 40% more sensitivity than MAb staining. This technique should be widely applicable for the specific identification of viral isolates (e.g., herpesvirus, myxovirus, paramyxovirus, and enterovirus) in cell culture 96-microwell microplates, thereby making it feasible to screen a larger number of samples than is possible with classical methods using conventional culture tubes, shell vials, or 24-well plates.

Antibodies, Monoclonal↗
PubMed1990

[The other types of viral hepatitis].

Hepatitis due to viruses other than A, B, C, D, E are numerous but uncommon in adults. Among the group of Herpesviridae (HSV, CMV, EBV, VZV), clinical hepatitis is usually suggestive of disseminated viral infection. Fulminant hepatitis occasionally observed in immunocompromised hosts are due to HSV, and VZV, but exceptionally to EBV. Many new techniques using specific monoclonal antibodies permit an accurate and fast diagnosis. Three drugs (vidarabine, acyclovir, ribavirine) have been shown to be efficient in the treatment of severe forms of the disease. Hepatitis due to exotic viruses (Amaril, Ebola, Lassa) are exceptional in France, but require specific prophylactic measures.

Chickenpox↗
PubMed1990

Interplay between adrenaline and interbeat interval on ventricular repolarisation in intact heart in vivo.

STUDY OBJECTIVE: The aim was to examine the hypothesis that an interaction between adrenaline and change in heart rate may alter the normal time sequence of ventricular repolarisation (and hence refractoriness) in a manner that (1) may favour arrhythmia formation, (2) may partly explain conflicting reports of the effect of adrenaline, ie, there are two opposing effects on action potential duration, and (3) be relevant to T wave abnormalities that sometimes occur in normal people. DESIGN: As a measure of the time course of repolarisation, monophasic action potentials were recorded simultaneously from three epicardial sites in the porcine heart (left ventricular apex, left ventricular base, and mid right ventricle). During steady state pacing, test pulse intervals were interposed at progressively shorter intervals in order to construct restitution curves. MEASUREMENTS AND MAIN RESULTS: Adrenaline infusion (0.4-1.5 micrograms.kg-1.min-1) resulted in earlier repolarisation in the beats after shorter interbeat intervals, and delayed repolarisation after longer interbeat intervals, tending to turn the restitution curve anticlockwise (ie, there were two opposing effects on action potential duration). The effects were not homogeneous between regions. To show this inhomogeneity, pairs of monophasic action potentials from different regions were subtracted using a differential input amplifier to produce an ECG like waveform at the amplifier output. The resulting T wave was thereby a measure of the time difference in repolarisation between the monophasic action potentials from which it was derived. The inhomogeneity of repolarisation induced by adrenaline and rate change was reflected in the morphology of this derived T wave, particularly at early (premature) beats. These T wave changes correlated closely with the true T wave changes in bipolar electrograms recorded between the same recording sites (R = 0.89; p less than 0.0001). CONCLUSIONS: These results show that adrenaline altered the normal relationship between interbeat interval and the timing of repolarisation. The effect was not homogeneous and when regional differences were observed they were reflected in changes in T wave morphology. These were marked at short intervals. It is possible that in addition to increased excitability observed with adrenaline, a combination of raised sympathetic activity and early beats predisposes to arrhythmias by exaggerating dispersion of repolarisation.

Action Potentials↗
PubMed1990

[Prevalence of and changes in hepatitis C virus antibodies in 64 patients with liver transplant].

The aim of this retrospective study was to assess the prevalence of hepatitis C virus antibodies and their follow-up in a series of 64 orthotopic liver transplantation patients. Indications for transplantation were cirrhosis in 28 cases, primary biliary cirrhosis in 6 cases, liver cancer in 11 cases, fulminant hepatitis in 2 cases, and alveolar echinococcosis in 17 cases. The prevalence of serum antibodies to hepatitis C virus was assessed by an ELISA test (Ortho-Diagnostic-Systems). Sera were tested before liver transplantation and every two months after. Twenty-nine patients seronegative before transplantation remained negative. Four patients seropositive before liver transplantation remained seropositive. Twenty-eight patients seropositive before transplantation, became seronegative after, and 3 patients seronegative before transplantation became seropositive after. The prevalence of seroconversion was 9.3 percent. The prevalence of seropositive patients after transplantation was 11 percent. The high number of seropositive patients before transplantation (50 percent) could be explained by false positive results. Seropositivity before transplantation appeared to be related to hypergammaglobulinemia (p less than 0.001). This hypothesis was confirmed a posteriori by a concomitant disappearance of both seropositivity and hypergammaglobulinemia after transplantation in 62 percent of patients.

Adolescent↗
PubMed1989

Pyoderma gangrenosum in an allogeneic bone marrow transplant recipient.

We present the case of a 15-year-old boy who developed facial pyoderma gangrenosum following an allogeneic bone marrow transplantation for the treatment of a 'blast' crisis developing in the course of chronic myelogenous leukaemia. The lesion appeared 7 months before any evidence of relapse. The discussion is focused on both the presentation of pyoderma gangrenosum associated with myelo-proliferative disorders and its pathogenesis via the underlying immunosuppression.

Adolescent↗
PubMed1988

Monophasic action potentials at discontinuation of cardiopulmonary bypass: evidence for contraction-excitation feedback in man.

Mechanical dysfunction is the strongest predictor of sudden cardiac death due to arrhythmia. Contraction-excitation feedback whereby changes in myocardial length/tension influence the time course of repolarization and excitability would provide a possible mechanism. Such a relationship has been shown in animals but has yet to be demonstrated in man. A useful model for studying this relationship is provided by the process of weaning off cardiopulmonary bypass after routine coronary artery surgery. During this weaning period of approximately 1 min, the heart is converted from being partially empty and flaccid (i.e., a "nonworking" state) to being filled and stretched to support the circulation (i.e., a "working" state). Monophasic action potentials (MAPs) were recorded from the left ventricular epicardium as a measure of repolarization time in 16 patients at discontinuation of cardiopulmonary bypass. Systolic pressure was recorded from the radial artery line. Measurements were made at three stages that related to different dynamic states of the heart: (1) starting to come off bypass ("minimally working"), defined as the time of first appearance of an inflection on the arterial pressure trace indicating the start of left ventricular ejection and valve opening, when arterial pressures represent left ventricular pressure, (2) half off bypass ("partially working"), and (3) off bypass ("wholly working"). During the process of discontinuing bypass MAP duration shortened, while systolic pressure increased. MAP duration at 90% and 60% repolarization (MAP D90, MAP D60) decreased from 288.0 +/- 29.5 msec (mean +/- SEM) and 235.0 +/- 27.9 msec in the minimally working heart to 274.5 +/- 30.2 msec and 224.2 +/- 27.3 msec in the partially working heart (p less than .001), with a subsequent decrease to 261.0 +/- 28.8 and 214.0 +/- 28.7 when the heart was wholly working (p less than .001). Systolic pressure increased from 54.1 +/- 9.3 mm Hg in the minimally working heart to 65.9 +/- 13.8 mm Hg in the partially working heart (p less than .001) and subsequently increased to 75.5 +/- 13.3 mm Hg when the heart was wholly working (p less than .001). Mean heart rates did not change significantly. A strong correlation was obtained between absolute MAP duration and systolic pressure. Regression analysis revealed: MAP D90 vs systolic pressure (p less than .001) and MAP D60 vs systolic pressure (p less than .01).(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗