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Biomedical subjects

I Bogdan

Publications and source records attributed to I Bogdan.

At least 19 recordsLinked to original sources

Spitz nevi display allelic deletions.

BACKGROUND: Spitz nevi are acquired benign melanocytic lesions that occur in childhood and adolescence. Histologically, they resemble malignant melanoma and were first termed benign juvenile melanoma. Several studies have attempted the difficult task of establishing diagnostic criteria to differentiate between Spitz nevi and malignant melanoma. OBJECTIVE: To elucidate sets of diagnostic criteria for differentiation between the 2 lesions. DESIGN: We aimed to search for allelic deletions in Spitz nevi and to evaluate whether loss of heterozygosity (LOH) or microsatellite instability (MSI) would be a valuable diagnostic tool to differentiate between Spitz nevi and malignant melanoma. SETTING: Two areas within each of 5 lesions were microdissected, and LOH and MSI were evaluated at chromosomes 6q (using polymorphic DNA marker D6S305), 9p21 (D9S171, IFNA, D9S265, and D9S270), 10q (D10S185), and 14q (D14S53). PATIENTS: Five Swiss patients with Spitz nevi. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Allelic deletions may serve as a diagnostic tool to distinguish Spitz nevi from melanoma. RESULTS: All lesions were informative, displaying LOH or MSI with at least one marker. No LOHs were found at 14q. At 6q, MSI was found in 2 dissected areas from the same lesion; the remaining lesions were noninformative. Loss of heterozygosity was found in 2 of 6 areas at D9S171, 2 of 6 at IFNA, 3 of 6 at D9S270, 3 of 4 at D9S265, and 1 of 4 at D10S185. Microsatellite instability was found in 1 of 4 areas at D9S265. CONCLUSIONS: With the markers used in our study, Spitz nevi display LOH and MSI similar to those in melanoma. Analysis of LOH or MSI is therefore not a suitable diagnostic tool in distinguishing Spitz nevi from melanoma.

Adolescent↗

Heterogeneity of allelic deletions within melanoma metastases.

During the initiation and progression of malignant melanoma, a series of different genetic events accumulate on several different chromosomes. The biological heterogeneity of tumour cells presents a major problem, preventing effective treatment of melanoma. To examine the degree of genetic heterogeneity, we searched for allelic losses (loss of heterozygosity; LOH) on chromosomes 9p, 9q, 1p and 17p, examining different areas within human melanoma metastases. All of the examined metastases were informative within at least one dissected area for at least one marker. Out of 29 areas in 11 melanoma metastases, 58% showed LOH with at least one marker. On chromosome 9p21-22, eight out of 26 informative loci (31%) showed LOH at D9S171 (three not informative), two out of 18 (11%) at IFNA (11 not informative) and seven out of 24 (29%) at D9S169 (five not informative). LOH on chromosome 9q22.3 was examined by the microsatellite marker D9S12; three out of 24 areas (12.5%) showed LOH, and five were not informative. Deletions on chromosome 1p were assessed using D1S450. Four out of 25 (16%) showed LOH; four were not informative. Deletions on chromosome 17p13 were examined with TP53; two out of 21 cases (9%) showed LOH, and eight were not informative. Our data demonstrate an impressive heterogeneity of allelic losses in the investigated chromosomal areas within the same metastatic lesion. This suggests that there is not one specific genetic alteration that accounts for melanoma progression to metastases. Rather there seem to be multiple genetic alterations accumulating even on the same chromosome, and progression from melanoma to metastases is paralleled by the accumulation of clones harbouring multiple genetic abnormalities.

Adult↗

[Cytogenetic aspects of malignant melanoma].

In analogy to colon carcinoma, where a stepwise accumulation of genetic changes have been described during tumor progression, a sequence of genetic events may be responsible for the transformation of melanocytes to dysplastic nevi and melanoma with horizontal and vertical growth phases and finally the formation of distant metastases. The current literature supporting this concept as well as own contributions are presented.

Cell Transformation, Neoplastic↗

Tumor necrosis factor-alpha contributes to apoptosis in hippocampal neurons during experimental group B streptococcal meningitis.

To evaluate the role of tumor necrosis factor-alpha (TNF-alpha) in neuronal injury in experimental group B streptococcal meningitis, infected neonatal rats were treated with a monoclonal antibody against TNF-alpha (20 mg/kg intraperitoneally) or saline given at the time of infection. Histopathology after 24 h showed necrosis in the cortex and apoptosis in the hippocampal dentate gyrus. Treated animals had significantly less hippocampal injury than did controls (P < .001) but had similar cortical injury and cerebrospinal fluid (CSF) inflammation. The antibody was then administered directly intracisternally (170 microg) to test whether higher CSF concentrations reduced inflammation or cortical injury. Again, hippocampal apoptosis was significantly reduced (P < .01), while cortical injury and inflammation were not. Thus, TNF-alpha played a critical role in neuronal apoptosis in the hippocampus, while it was not essential for the development of inflammation and cortical injury in this model.

Animals↗

[Relation between helper and suppressive/cytotoxic T lymphocytes in the peripheral blood in patients with dilated cardiomyopathy].

In 32 patients with dilated cardiomyopathy the percentages of helper (CD4+) and suppressor (CD8+) T lymphocytes, as well as their ratio, have been analyzed. The percentage of CD8+ lymphocytes in the group with dilated cardiomyopathy was 20.62 +/- 8.27% (X +/- SD), vs. 26.38 +/- 6.19% in control group; the difference was not statistically significant. The percentages of CD4+ lymphocytes were similar in both groups, 39.55 +/- 12.86% vs. 40.52 +/- 6.59%. The CD4+/CD8+ ratio was markedly higher in the group with dilated cardiomyopathy, 2.49 +/- 2.10 vs. 1.65 +/- 0.49, but the difference was not statistically significant, probably because of great variability in the group. In the subgroup of 12 patients with possible alcoholic etiology of dilated cardiomyopathy, the values were almost identical to those of the remaining 20 patients. No correlation between echocardiographic fractional shortening of the left ventricle and any of the aforementioned values of T lymphocytes in the group of patients with dilated cardiomyopathy was found. The tendency toward decline in number of suppressor T lymphocytes is in accordance with the hypothesis that the "overreacting" inflammatory response to (viral) myocarditis might be the cause of dilated cardiomyopathy. However, the specificity of the decline of suppressor activity in respect to the other causes of heart failure is questionable and the analysis of its significance is complex. This is due to dynamic character of immune disorders, and a considerable number of other theories considering the etiology and pathogenesis of the disease also exist. The need to perform complex studies is anticipated, including continual observation of clinical, immunologic and bioptic parameters of the disease.

Adult↗

[Echocardiographic analysis of changes in the heart in patients with systemic lupus erythematosus].

Fifty-six patients, 49 females and 7 males, with the confirmed diagnosis of systemic lupus erythematosus were examined by M-mode, 2--D and Doppler echocardiography. Pericardial effusion was found in 15 patients (27%), while pericardial thickening was suspected in 6 additional patients (37.5% altogether). Two patients had the signs of a pericardial tamponade, but both of them were uraemic. Libman-Sacks endocarditis was suspected in 4 patients (7.5%) because of verrucous changes in the aortic or mitral valve and regurgitant jet. Slight to moderate left ventricular hypocontractility was present in 3 patients (5%), while 3 additional patients had borderline values of the left ventricular contractility parameters. Left ventricular hypertrophy, usually mild, was found in 21 patients (37.5%). Echocardiographic signs of pulmonary hypertension were present in 2 patients (3.6%). It has been concluded that pericardial affection is frequent during the course of systemic lupus erystematosus, while a diffuse myocardial involvement is rare, except the consequences of arterial hypertension and accelerated coronary atherosclerosis. Libman-Sacks endocarditis still represents a diagnostic problem. For a more precise definition of cardiac involvement in systemic lupus erythematosus, a comparative analysis of the disease activity and immunosuppressive therapy is needed.

Adolescent↗

[From Rumanian folk medicine: Non-specific stimulus therapy using transcutaneous implantation of hellebore (Helleborus purpurascens, Fam. Ranunculaceae) in agriculturally useful animals].

In the Rumanian traditional medicine a transcutaneous implantation of the root of Helleborus purpurascens is used to provoke leucocytosis and neutrophils with the aim to activate chronic diseases for better healing. The skin is perforated with a thick needle (in cattle and horses in the area of the thorax, in sheep and pigs in the ear flap), the transplant is introduced and after 24 hours removed. Though the method is more than 100 years old, it is not reported in the literature. The way of action is unknown. The investigation are performed to show the efficacy of this method of Helleborus-implants in comparison with the effect of an placebo. It could be shown that Helleborus-implant increased leucocytes in horses, sheep and pigs and increased neutrophils in all animal species. In the same way the phagocytosis was increased. Only in horses an abscess was observed. As a loss of performance may occur and fever and inappetence is followed by the implantation the authors dissuade from the use of Helleborus-implants in cattle and horses. Pigs and sheep tolerate this procedure without any problems, so that the methods may be used in modern treatment.

Animals↗

[Quantification of mitral regurgitation using Doppler echocardiography].

Examining 18 patients without regurgitation (control group) and 20 patients with mitral regurgitation the method of Doppler echokardiography, the pulsating and continual wave, was applied. Both groups consisted of patients with heart diseases in whom a heart catheterization was indicated for the evaluation of the actual state. Thus, the competence of the mitral orifice was also evaluated. The aim of the investigation was to quantify or more accurately estimate the degree of mitral regurgitation. The accuracy of the Doppler method was tested by means of the measured cardiac stroke volumes of the right heart side in both groups with the probability higher than 80% but lower than 90% (0.80 less than p 0.23 less than 0.90), and by testing the cardiac stroke volumes of the right heart and the diastolic volumes of the left heart (control group: mitral and pulmonal orifice) with the probability higher than 70% and lower than 80% with the error of 6% of the measured volume. The regurgitation mitral fraction (RF) was presented as the difference between the total forwards volume (TFV) in the mitral orifice and the net forwards volume (NFV) in the pulmonal orifice and calculated in cm3, and as the regurgitation fraction index (RFI) in percentages (RFI = 1--NFV/TFV). It was also expressed as the regurgitation volume index (RVI) whose values were divided into degrees, according to the literature data. Numerical values of the regurgitation fraction and the regurgitation fraction index were classified in the mitral insufficiency degrees from 1 to 4. A fast regurgitation screening was possible due to the regurgitation fraction index, which is lower than the 45% of the diastolic volume in the cases of mild mitral insufficiency, while the values over 45% denote severe mitral insufficiency. The obtained values of the regurgitation fraction and index divided into degrees showed a close correlation with the angioventriculographic degrees obtained by heart catheterization. Cardiac output measured by the Doppler and Fick methods in the group with regurgitation showed a high correlation coefficient (r = 0.85) (0.60 less than p 0.47 less than 0.70).

Echocardiography, Doppler↗

[Evaluation of the effectiveness of streptokinase in acute myocardial infarct with respect to the pump function of the heart].

During 2 years and 3 months 230 patients suffering from acute myocardial infarction were treated at an Intensive Care Unit and a Department of Cardiology. Streptokinase was given intravenously to 54 of them. Out of 54 patients, in 52% the localisation of the myocardial infarction was in the anterior and in 48% in the posterior wall. The patients were divided in the three categories according to the onset of symptoms: up to 2 hours, 2-4 hours and 4-6 hours. The dose of streptokinase was 1,500,000 i.u. during 1.5 hours. The CPK and MBCPK level reached the maximum values up to 12 hours and was to lowest in the first group. In 74% of the patients the serum enzyme level showed successful reperfusion of a coronary artery. Electrocardiographic findings of a successful myocardial reperfusion amounted to 36% in the first, 40% in the second, and 17% in the third group. Malignant ventricular arrhythmias appeared in the first group in 3.6%, in the second in 12.5% and in the third group in 14.2%. The criteria for successful myocardial reperfusion by echocardiography (analysed regional wall motion) were present in 52% in the first, in 50% in the second, and in 17% in the third group. Coronarography and ventriculography were performed in 17 patients after 21 days of treatment, with successful results in 88% (15 out of 17 patients). In a group of 176 patients unable to be treated with streptokinase because of the onset of symptoms of myocardial infarction (more than 6 hours) or because of contraindications for that treatment, the lethality rate reached 17.6%. The lethality rate in the group of 54 patients treated with streptokinase was 5.5%. Local complication (hemorrhage) during the treatment was observed in one patient (2%).

Heart↗

Endothelial cells express a spectrin-like cytoskeletal protein.

Vascular endothelium was investigated by indirect immunofluorescence and immunoautoradiography for the possible presence of spectrin-like molecules. Antibodies were raised against electrophoretically purified rat, rabbit, and bovine red blood cell spectrin and against rabbit brain fodrin. Antibody specificity was assessed by immunoblotting and double-diffusion technique. Homogenates of endothelial cells freshly isolated from heart microvasculature or aorta, as well as cultured aortic endothelial cells, were analyzed by gel electrophoresis. Immunoautoradiograms of gels incubated with spectrin specific antibody, followed by radio-labeled protein A, revealed two bands of electrophoretic mobility similar to that of the alpha- and beta-subunits of spectrin. Indirect immunofluorescence of endothelial cells, both in situ and in vitro, showed the existence of a protein which cross-reacted with the antibodies against spectrin and fodrin. Controls, in which endothelial cells were exposed to spectrin antibody absorbed with pure spectrin or preimmune serum, were negative. These findings indicate that endothelial cells express a protein antigenically related to the spectrin family; both spectrin- and fodrin-like molecules, in various proportions, may coexist. In the endothelial cell, these proteins may play an important role in modulation of the cytoskeleton in response to various stimuli, and in maintaining the biochemically differentiated microdomains of plasmalemma.

Animals↗

[Antiphlogistic and antipyretic effect of sodium salicylate in rats and rabbits].

Inflammatory processes were provoked in 35 rats by subcutaneous implantation of sterile cotton-wool pads and treated five days by means of various antiphlogistic substances. The action of sodium salicylate (administered alone or in conjunction with gamma-globulin or with glucose) proved similar to that of prednisolone which was given as control substance. Human gamma-globulin exhibited neither anti-inflammatory nor pro-inflammatory effects. Experiments with twelve rabbits revealed that the pyretogenic potential of sodium nucleinate, one per cent (0.01 g/kg body weight) was stronger than that of animal charcoal or peptone. Yet, the two latter substances may be used, as well. The antipyretic effect of sodium salicylate was not as intensive but just as reliable as that of aminophenazone, when both preparations were applied to rabbits with induced fever. Concomitant administration of glucose is recommended to prevent development of undesired side-effects, such as giddiness or ataxia.

Aminopyrine↗