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Biomedical subjects

R Frank

Publications and source records attributed to R Frank.

At least 145 records · Page 8Linked to original sources
PubMed1996

Increased urinary nitrite excretion in children with minimal change nephrotic syndrome.

OBJECTIVE: We tested the hypothesis that nitric oxide synthesis by the kidney is increased in children with primary nephrotic syndrome. METHODS: We examined the urinary excretion of nitrite, a stable metabolite of nitric oxide, using the Griess reaction, in children with nephrotic syndrome. RESULTS: In comparison with healthy children, patients with minimal change nephrotic syndrome had increased urinary nitrite excretion regardless of whether the disease was in relapse or remission (p < 0.025). In contrast, urinary nitrite excretion was similar in control subjects and patients with focal segmental glomerulosclerosis or IgA nephropathy. CONCLUSION: These findings indicate that measurement of urinary nitrite excretion may be a useful test to help discriminate between minimal change nephrotic syndrome and focal segmental glomerulosclerosis in children with idiopathic nephrotic syndrome.

Adolescent↗
PubMed1996

CD26 mediates the action of HIV-1 Tat protein on DNA synthesis and cytokine production in U937 cells.

The human immunodeficiency virus 1 (HIV-1) Tat protein is known to be capable of suppressing antigen- and CD3-induced activation of human T cells. Previously, it was shown that Tat can bind to the dipeptidyl peptidase IV (DP IV, CD26) and inhibit the degradation of the chromogenic substrate Gly-Pro-p-nitroanilide. Using the method of free zone capillary electrophoresis, here we have shown that the DP IV-catalyzed hydrolysis of the NH2-X-Pro-containing cytokine peptides IL-2(1-12), IL-1 beta(1-6), and IL-6(1-12) was also significantly inhibited by the Tat protein. Moreover, HIV-1 Tat at a concentration of 10 micrograms/ml was found to have a strong suppressive effect on DNA synthesis and IL-1 beta production, but stimulates secretion of IL-1 receptor antagonist (IL-1RA) and TNF-alpha of CD26-expressing U937-H cells. It did not impair neither DNA synthesis nor cytokine production of low CD26-expressing U937-L cells. Similar results have been found with synthetic DP IV/CD26 inhibitors (Immunobiol., 1994, vol. 192, pp. 121-136). These data strongly suggest that Tat protein is a potent "natural" inhibitor of DP IV/CD26, and they support the hypothesis that DPIV plays a role in Tat's immunosuppressive activity.

Cytokines↗
PubMed1996

Evaluation of spectral correction techniques for fluorescence measurements on pigmented lesions in vivo.

Recently, the use of optical spectroscopy for non-invasive diagnosis of malignant melanoma has been suggested. The reliability of such optical measurements can be seriously compromised by spatial variations in the optical properties of the tissue that are not related to malignancy. In the present paper we report a novel approach to fluorescence spectroscopy which allows for elimination of spatial variations in the optical properties of the tissue investigated. To test this concept we performed fluorescence and color measurements on moles and unpigmented control skin in human volunteers before and after topical application of delta-aminolevulinic acid (ALA). Two types of fluorescence data analysis were investigated; a single ratio technique based on the ratio of the red to the yellow fluorescence (660-750 nm to 550-600 nm) at 405 nm excitation and a double-ratio technique, the red-to-yellow ratio at 405 nm excitation divided by the red-to-yellow ratio at 435 nm excitation. The two excitation wavelengths were selected to be located close to the maximum and at some distance from the Soret excitation band of the porphyrins. The single ratio showed a significant correlation between fluorescence and color. The double ratio was independent of the color of the lesion. These findings indicate that the double-ratio technique is suitable for in-vivo detection of local differences in concentration of fluorescent tumor-localizing drugs in pigmented lesions. This enables in-vivo studies of the pharmacokinetics of tumor-localizing agents in pigmented lesions and may significantly contribute to the development of a non-invasive diagnostic tool for malignant melanoma.

Adult↗
PubMed1996

Tenascin-C contains distinct adhesive, anti-adhesive, and neurite outgrowth promoting sites for neurons.

The glia-derived extracellular matrix glycoprotein tenascin-C (TN-C) is transiently expressed in the developing CNS and may mediate neuron-glia interactions. Perturbation experiments with specific monoclonal antibodies suggested that TN-C functions for neural cells are encoded by distinct sites of the glycoprotein (Faissner, A., A. Scholze, and B. Götz. 1994. Tenascin glycoproteins in developing neural tissues--only decoration? Persp. Dev. Neurobiol. 2:53-66). To characterize these further, bacterially expressed recombinant domains were generated and used for functional studies. Several short-term-binding sites for mouse CNS neurons could be assigned to the fibronectin type III (FNIII) domains. Of these, the alternatively spliced insert TNfnA1,2,4,B,D supported initial attachment for both embryonic day 18 (E18) rat and postnatal day 6 (P6) mouse neurons. Only TNfn1-3 supported binding and growth of P6 mouse cerebellar neurons after 24 h, whereas attachment to the other domains proved reversible and resulted in cell detachment or aggregation. In choice assays on patterned substrates, repulsive properties could be attributed to the EGF-type repeats TNegf, and to TNfnA1,2,4. Finally, neurite outgrowth promoting properties for E18 rat hippocampal neurons and P0 mouse DRG explants could be assigned to TNfnB,D, TNfnD,6, and TNfn6. The epitope of mAb J1/tn2 which abolishes the neurite outgrowth inducing effect of intact TN-C could be allocated to TNfnD. These observations suggest that TN-C harbors distinct cell-binding, repulsive, and neurite outgrowth promoting sites for neurons. Furthermore, the properties of isoform-specific TN-C domains suggest functional significance of the alternative splicing of TN-C glycoproteins.

Amino Acid Sequence↗
PubMed1996

Transforming growth factor-beta controls cell-matrix interaction of microvascular dermal endothelial cells by downregulation of integrin expression.

Transforming growth factor-beta (TGF-beta) is a pleiotropic regulatory factor of tissue remodeling. Angiogenesis, a prerequisite of tissue repair and tissue expansion, is induced by TGF-beta in vivo, while proliferation and migration of cultured endothelial cells are inhibited by TGF-beta. Indirect mechanisms stimulating angiogenesis and modification of TGF-beta effects by cell-matrix interaction have been postulated to account for this paradigm. Because cellular behavior in tissue remodeling is decisively determined by cell-matrix interactions, which in turn is mediated via integrins, we investigated the effect of TGF-beta on matrix-dependent endothelial cell functions. Integrin expression of human dermal microvascular endothelial cells (HDMEC) was measured by Northern blot and fluorescence-activated cell sorter analysis after TGF-beta treatment and correlated to cell-matrix interactions, which were studied in a colorimetric cell attachment assay as well as the Boyden chamber chemotaxis assay. We found a cell-specific downregulation of integrin expression in HDMEC on the level of mRNA as well as on the cell surface. This effect correlated well with the reduction of integrin-dependent cell adhesion to several matrix proteins, in particular to fibronectin. Moreover, TGF-beta decreased fibronectin-induced chemotaxis of HDMEC. Thus, TGF-beta controls cell-matrix interaction of HDMEC by down-regulation of integrin expression. This effect of TGF-beta reflects direct and cell-specific control mechanisms on microvascular cells that may be critical for the coordinated process of angiogenesis requiring a balance of stimulatory and inhibitory factors.

Cell Adhesion↗
PubMed1996

Diagnostic clues from the surface ECG to identify idiopathic (fascicular) ventricular tachycardia: correlation with electrophysiologic findings.

INTRODUCTION: An RS interval > 100 msec in precordial leads has been recently described for the diagnosis of ventricular tachycardia (VT). The aim of this study was to assess the value of this criterion when applied to patients with right bundle branch block pattern, left-axis deviation (fascicular) VT sensitive to verapamil. METHODS AND RESULTS: Eleven patients (mean age 31 +/- 11 years; range 16 to 51) had a mean heart rate of 164 +/- 37 beats/min (range 107 to 230) during VT. The QRS complex axis was -92 degrees +/- -15 degrees (range -80 to -115). The mean QRS duration was 121 +/- 9 msec (range 105 to 140). The mean RS interval was 67 +/- 9 msec (range 60 to 80). Fusion beats were present in 2 patients (18%), and AV dissociation confirmed by electrophysiologic study was found on ECG in 8 (73%) of 11. During tachycardia, the QRS-H' interval was 19 +/- 10 msec (range 10 to 30) in 6 of 11 patients. In seven patients, a fast, unique (or double) presystolic potential lasting 32 msec (range 12 to 40) occurring before the onset of the QRS complex was found at the site of origin of VT, localized in the inferior apical left ventricular septum. In all cases, VT was successfully treated by catheter ablation. CONCLUSION: A wide QRS complex tachycardia with right bundle branch block and left-axis deviation sensitive to verapamil observed in a young patient without structural heart disease should not be confused with supraventricular tachycardia with aberrancy but rather suggests the presence of fascicular VT. As opposed to VT associated with structural heart disease, the RS interval is < 80 msec in all precordial leads in all cases. Independent of this parameter, AV dissociation detectable on surface ECG has a sensitivity of 73%, which increases to 82% in the presence of fusion beats.

Adolescent↗
PubMed1996

Resistance of chimpanzee T cells to human immunodeficiency virus type 1 Tat-enhanced oxidative stress and apoptosis.

CD4+ T-cell depletion in AIDS patients involves induction of apoptosis in human immunodeficiency virus (HIV)-infected and noninfected T cells. The HIV type 1 (HIV-1)-transactivating protein Tat enhances apoptosis and activation-induced cell death (AICD) of human T cells. This effect is mediated by the CD95 (APO-1/Fas) receptor-CD95 ligand (CD95L) system and may be linked to the induction of oxidative stress by Tat. Here we show that HIV-1 Tat-induced oxidative stress is necessary for sensitized AICD in T cells caused by CD95L expression. Tat-enhanced apoptosis and CD95L expression in T cells are inhibited by neutralizing anti-Tat antibodies, antioxidants, and the Tat inhibitor Ro24-7429. Chimpanzees infected with HIV-1 show viral replication resembling early infection in humans but do not show T-cell depletion or progression towards AIDS. The cause for this discrepancy is unknown. Here we show that unlike Tat-treated T cells in humans, Tat-treated chimpanzee T cells do not show downregulation of manganese superoxide dismutase or signs of oxidative stress. Chimpanzee T cells are also resistant to Tat-enhanced apoptosis, AICD, and CD95L upregulation.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Local application of antimycotics in mucormycosis cerebri: a case report.

A 65 year old man was found to have mucormycosis cerebri during immunosuppression after treatment of hairy cell leukaemia with 2-chlorodeoxyadenosine. Although mucormycosis cerebri has a poor prognosis, the patient survived after systemic administration of high dose amphotericin B, extensive excision of the abscess, and additional local application of amphotericin B with the help of an absorbable gelatin sponge.

Administration, Topical↗
PubMed1996

Effects of sequential neuropsychological testing of an elderly community-based sample.

The magnitude and importance of changes in scores of neuropsychological tests on retest in the elderly, especially over long time periods, is not well established. Three neuropsychological tests and one mental status test were initially administered to screen for potential dementia and were readministered to 380 of the surviving individuals 2.4 years later who either failed the screening examination or were an age matched control. Of the 380 women and men aged 65 and older, 56 were diagnosed as having Alzheimer disease (AD), 82 as at risk for developing AD, and 242 as having normal cognition. The present report focuses on changes in test scores between the two visits. In the normal and at risk groups, significant improvements were seen on retest of the Visual Reproduction Test (VRT), the Trails B test, and the Mini-Mental Status examination; verbal fluency decreased, and savings score of the VRT showed small variations. On most tests, scores of the AD group decreased. Practice effects, biases, and other variables may have played a role in the improvements seen in those labeled normal and at risk. If these results are confirmed, savings score of the VRT (which remained stable over time in normals and individuals at risk and decreased in patients with dementia) and verbal fluency (which decreased in all groups) may be better measures of true cognitive performance than the other tests that we evaluated.

Aged↗
PubMed1996

Flexural rigidity of microtubules measured with the use of optical tweezers.

The flexural rigidity of single microtubules is measured using optical tweezers. Two new methods are presented. In both the optical forces of the laser trap are used to directly manipulate microtubules grown off the ends of Chlamydomonas axonemes. The shapes of the microtubules are observed by video microscopy as the hydrodynamic forces of viscous flow counteract the elastic restoring forces when the microtubules are moved actively relative to the surrounding buffer medium. To determine the flexural rigidity, the bending of a microtubule is analyzed under a given velocity distribution along its length. Microtubules incubated with taxol after polymerization are measured to be more flexible than those without taxol added. On the other hand, MAPs are shown to increase microtubule stiffness.

Animals↗
PubMed1996

Selective binding of soluble Abeta1-40 and Abeta1-42 to a subset of senile plaques.

Alzheimer's disease is characterized by the progressive accumulation of amyloid-beta protein (Abeta) in senile plaques and cerebral amyloid angiopathy. It is not known whether the plaque growth is a continuous and homogeneous process or whether some plaques have a more rapid evolution. As plaques grow by the deposition of Abeta, we used an in situ binding technique to analyze the deposition of fluorescein-conjugated and biotinylated Abeta1 40 and Abeta1-42 in cryosections of brains from Alzheimer's disease patients. Only a subset of senile plaques but all cerebrovascular Abeta deposits were labeled by both Abeta1-40 and Abeta1-42. Striking differences in binding were observed among adjacent plaques. Quantitative analysis showed that on average 60% of all plaques were labeled with Abeta1-42 and 31% of all plaques were labeled with Abeta1-40 (n=7; P<0.001). Confocal laser scanning microscopy of double-labeled sections revealed that the newly deposited Abeta was only partially co-localized to pre-existing Abeta and apolipoprotein E and was not co-localized to heparan sulfate proteoglycan. Abeta binding was preserved after glycolytic pretreatment with periodic acid. Our results suggest that at a given time point only a subset of active senile plaques accumulate A(beta) and that plaque growth may be conditioned by the presence of other distinct plaque components different from Abeta, apolipoprotein E or heparan sulfate proteoglycan.

Aged↗
PubMed1996

[Role of power and temperature monitoring in radiofrequency ablation].

Variations of temperature, impedance and power and the relationship between these three factors were studied in 20 patients during 351 applications of radiofrequency energy delivered by a generator with a regulated output power. The applications were divided into 3 groups according to the maximal temperature attained: group I (< 50 degrees C; n = 112), group II (50-60 degrees C; n = 100), and group III (60-70 degrees C; n = 139). Analysis of the total duration of time of applications (average +/- standard deviation) showed: the duration (seconds) was 23.9 +/- 11.9 seconds for group I, 36.1 +/- 18.7 seconds for group II and 45 +/- 23.6 seconds for group III. The time to attain maximal temperature was 6.8 +/- 9.6 seconds in group I, 11.7 +/- 12.7 in group II and 10 +/- 10.4 seconds in group III. The impedance remained under 200 omega in all applications, the target temperature being set at 70 degrees C. Analysis of the first three seconds of application: correlations coefficients between temperature and impedance were -0.08 (p < 0.001) in group I and -0.23 (p < 0.0001) in groups II and III. These coefficients were recalculated with respect to the average power delivered during the applications: < 40 watts (n = 79), r = -0.33; < 30 watts (n = 55), r = -0.41; < 20 watts (n = 33), r = 0.49 and < 10 watts (n = 15), r = -0.7 (p < 0.0001). The authors conclude that radiofrequency generators with thermal regulation allow early interruption of ineffective applications of radiofrequency and avoid increases in impedance. The poor correlations observed between increase in temperature (measured at the tip of the catheter) and the fall in impedance (related to tissue heating) for the first 3 groups, show that temperature alone is not a good indicator of contact. The improvement of the correlations for decreasing output power applications indicates better thermal transfer between the electrode and endocardium. Therefore a low power delivered in the first seconds at > 50 degrees C is to be interpreted as a marker of the quality of contact and a predictive factor of efficacy.

Adolescent↗
PubMed1996

[Radiofrequency catheter ablation of ventricular tachycardia].

Radiofrequency energy was used for the ablation of chronic recurrent ventricular tachycardia (VT) in 58 patients who were divided into two groups: 44 cases with structural myocardial disease (36 men and 8 women: mean age 55 years; range: 14 to 85 years) with an average left ventricular ejection fraction of 38% (range: 15 to 80%): these patients had myocardial infarction (28 cases), arrhythmogenic right ventricular dysplasia (11 cases), idiopathic dilated cardiomyopathy (2 cases), operated congenital heart disease (2 cases) and operated valvular heart disease (1 case). The clinical success rate after the first session of radiofrequency ablation was 34%. When (according to our modified protocol of fulguration) 160 joule cathodal shocks were delivered to the same catheter previously used for RF ablation during the same session or secondarily (13 cases), the success rate increased to 76%. The average follow-up period of the 37 survivors was 16.7 months. The second group consists of 14 cases without structural myocardial disease (10 men and 4 women, mean age 41 years, range 14 to 69 years) with an average left ventricular ejection fraction of 61%. These patients had idiopathic ventricular tachycardia (10 cases) and verapamil-sensitive ventricular tachycardia (4 cases). The primary success of radiofrequency ablation alone was 43%. When combined with fulguration during the same of radiofrequency ablation alone was 43%. When combined fulguration during the same of at a later session, the success rate increased to 71.3%. The average follow-up period of the 13 survivors was 19 months (range 0.3 to 39 months). No significant difference was observed between the groups with or without structural myocardial disease after radiofrequency or fulguration ablation, not only with respect to global results but also after analysis of subgroups with, for example, post-infarction ventricular tachycardia or arrhythmogenic right ventricular dysplasia. However, clinical success was obtained after a single session of radiofrequency ablation alone in 8 of the 9 cases of incessant ventricular tachycardia in patients with structural myocardial disease.

Adolescent↗
PubMed1996

[Combination of celiprolol and amiodarone in the treatment of recurrent ventricular tachycardia].

The combination of beta-blockers and amiodarone has been shown to be affective in the treatment of refractory chronic ventricular tachycardia. However, the possible induction of excessive sinus bradycardia can constitute a limitation to the use of this treatment. Celiprolol is a cardioselective beta-blocker with a partial beta-2 agonist activity and an alpha-2 blocking activity, with a minimal depressant effect on heart rate. It therefore seemed useful to evaluate this drug in combination with amiodarone in patients with chronic ventricular tachycardia refractory to amiodarone alone. Twelve men with age of 57 +/- 16 years (9 with a history of myocardial infarction) received 200 mg of celiprolol per day associated with an average of 2 grams of amiodarone per week. Failure of oral amiodarone alone was confirmed by "reloading" (1,200 mg per day for 4 days) in 11 patients. The mean left ventricular ejection fraction was 36 +/- 19%, and was < or = 30% in 5 patients. Three patients were classified as stage 3-4 of the NYHA functional classification. Episodes of tachycardia were paroxysmal in 10 patients and diurnal in 10 cases. The effects of treatment were evaluated by clinical examination, continuous electrocardiographic monitoring, stress test and endocavitary electrophysiological investigation. No patient developed cardiac decompensation or collapse during beta-blocker treatment. In one case, the dose of celiprolol had to be decreased to 100 mg per day because of hypotension. No proarrhythmic effect was observed. The sinus rate remained unchanged after addition of celiprolol to amiodarone (57 +/- 3 bpm before versus 56 +/- 4 bpm after). On the stress test, the exercise capacity was maintained and no tachyarrhythmia was induced. Right ventricular refractory periods were not modified by celiprolol (mean effective period 289 +/- 20 ms before versus 294 +/- 20 ms after). Following a hospital stay of 17 +/- 7 days, the beta-blocker was discontinued in 5 patients because of persistence of permanent tachycardia in 1 case, and because of inducibility of a tachycardia with the same frequency as before treatment in the other 4 cases. No sudden death or haemodynamically unstable recurrence of ventricular tachycardia were observed during follow-up over a period of 38 +/- 24 months (range: 2-55) of the 7 patients in whom treatment was considered to be effective. Only one patient presented a temporary and reversible deterioration of heart failure. The absence of excessive bradycardia was also observed during follow-up. In one patient, celiprolol was replaced by another antiarrhythmic due to the recrudescence of inducibility to programmed stimulation. Three patients developed a spontaneous recurrence of sustained monomorphie ventricular tachycardia, which was well tolerated. In conclusion, these results suggest that celiprolol in combination with amiodarone in the treatment of refractory chronic ventricular tachycardia is a valuable therapeutic option because of its good inotropic and particularly chronotropic safety. However, the efficacy of treatment must be evaluated by a stress test and by endocavitary electrophysiological investigation including programmed ventricular stimulation in every case.

Adrenergic beta-Antagonists↗
PubMed1996

[Right precordial leads and sudden death. Relation with arrhythmogenic right ventricular dysplasia].

Non-coronary ST-segment elevation during right sided chest pain has been described in subjects with episodes of ventricular fibrillation at rest. This syndrome has been attributed to functional phenomena or to structural myocardial changes. A personal case has features belonging to two categories: ST-segment elevation observed before, during and after episodes of arrhythmia was compared to 11 previously recorded ECG recordings. Right ventricular dysplasia was shown by electrocardiography, electrophysiology and echocardiography. In addition, ST-segment elevation is classified in 3 categories: triangular and dome-shaped are the most commonly observed forms during the arrhythmias: the third form with "saddle"-shaped appearances has not been previously described and would seem to be a minor equivalent observed during intercritical periods. This form is found in 30% of clinically documented cases of arrhythmogenic right ventricular dysplasia.

Arrhythmias, Cardiac↗