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Biomedical subjects

C Kopp

Publications and source records attributed to C Kopp.

At least 37 records · Page 2Linked to original sources

[From vestibular nystagmus to the transfer function of the vestibulo-ocular reflex].

A new method for the separation of the two phases of the vestibular nystagmus (slow eye velocity and fast eye velocity) is presented. The aim is to calculate the transfer coefficients of the human vestibulo-ocular reflex (VOR). With a combination of thresholds on the eye velocity and the eye acceleration signals, the different phases of fast eye velocity in the vestibular nystagmus can be located with a good accuracy. So this phases which are not of vestibular origin can be eliminated. The dependence of the transfer function and of the coherence function from the values of the thresholds is studied. This study shows that our method is very robust and that the consequence of the systematic errors occurring with the preceding methods, we have used, is a bad estimation of the gain of the VOR. The values of the coherence function we obtained show that the VOR has a linear behaviour within the range of frequencies we studied (0.01-0.5 Hz).

Electronystagmography↗

Effects of a daylight cycle reversal on locomotor activity in several inbred strains of mice.

There is some evidence of melatonin implication in the nycthemeral regulation of running activity rhythm in rodents. Because some inbred strains of mice such as C57BL/6 and BALB/c have been generally found to present no nocturnal melatonin peak, in contrast to others such as C3H/He and CBA mice, the aim of this study was to examine the adaptation of daily locomotor activity to a light/dark cycle phase shift in these four strains. An apparatus consisting of two boxes connected by a tunnel was used to record spontaneous locomotor activity, defined as the number of transitions between the two boxes. Locomotor activity was monitored continuously during 3 days before and 14 days after a 12-h phase delay of the light/dark cycle. Results essentially showed that the adaptation of the locomotor activity rhythm to the phase shift was faster in C57BL/6 and BALB/c mice than in C3H/He and CBA mice. This could be related, at least in part, to the differences in melatonin synthesis between the former strains and the latter ones. Although melatonin nocturnal peak is not necessary to a daylight regulation of circadian functions in rodents, it could be considered as an endocrine message that takes part in the anticipation of the following light/dark cycle.

Animals↗

Detection of mi transcription factor (MITF) mRNA in a case of myelodysplastic syndrome and bone marrow mastocytosis.

Myelodysplastic syndromes (MDS) may be accompanied by systemic mastocytosis. The mechanisms which play a role in the evolution of mastocytosis, however, are not well understood. We report on a case of refractory and anemia with ringed sideroblasts (RARS), and co-existing bone marrow mastocytosis. Compact mast cell (MC) infiltrates were detected in bone marrow sections by immunohistochemistry using an antibody to tryptase. In addition, the MC were found to express c-kit, the tyrosine kinase receptor for MGF (mast cell growth factor = stem cell factor, SCF). Activating point mutations in the kinase domain of c-kit (often found in mastocytosis) were not detectable. However, the mononuclear cells (MNC) of the bone marrow expressed mRNA specific for MITF, a transcription factor that regulates expression of c-kit and differentiation of MC. Surprisingly, the c-kit ligand SCF was found to augment expression of MITF mRNA in bone marrow MNC. Whether this augmentation represents a general response (preventing loss of growth factor receptor expression during cell maturation) common to all types of hemopoietic progenitors, or is confined to (some forms of) mastocytosis, remains unknown.

Aged↗

A 6-month comparison between formoterol and salmeterol in patients with reversible obstructive airways disease.

The aim of this randomized, open, parallel group study was to compare the clinical efficacy of formoterol dry powder capsule 12 micrograms b.i.d. and salmeterol dry powder 50 micrograms b.i.d. in the treatment of patients with reversible obstructive airways disease. The 6-month treatment was preceded by a 2 week run-in period. Morning pre-dose peak expiratory flow (PEF) during the last 7 days of treatment was the primary variable. Throughout the study, patients recorded morning and evening pre-dose PEF, use of rescue medication, respiratory symptoms and adverse events. Clinic visits were scheduled at monthly intervals. Of the 482 patients randomized (equal numbers in the two treatment groups), 428 completed the study. Four hundred and twenty-five patients were included in the efficacy analysis for the primary variable. For mean morning pre-dose PEF during the last 7 days of treatment, the 95% confidence interval (CI) for the treatment contrast formoterol minus salmeterol was included entirely in the pre-defined range of equivalence (CI limits = -8.69, +9.841 min-1). This was also the case for the morning PEF during the last week before each clinic visit. For mean evening pre-dose PEF, the estimated treatment contrasts showed a trend towards superiority of formoterol over salmeterol, which became statistically significant at 2, 3 and 4 months (P < 0.05; estimated contrasts 7.27, 10.45 and 10.511 min-1, respectively). No treatment group differences were found in use of rescue medication and respiratory symptom scores. The incidence of adverse events was similar in the two groups. These findings demonstrate that formoterol 12 micrograms b.i.d. and salmeterol 50 micrograms b.i.d., both formulated as dry powders, have similar long-term efficacy and safety profiles in patients with reversible obstructive airways disease.

Administration, Inhalation↗

Differential effects of systemic metronidazole and amoxicillin on Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in intraoral habitats.

48 adult patients with untreated periodontitis harboring subgingival Actinobacillus actinomycetemcomitans and/or Porphyromonas gingivalis were randomly assigned to receive full mouth scaling alone (control) or scaling with systemic metronidazole plus amoxicillin and supragingivai irrigation with chlorhexidine digluconate (test). Subgingival plaque and swab samples from tongue, tonsils, and buccal mucosa were taken at baseline, 10 days and 3, 6, 9, and 12 months. A. actinomycetemcomitans was detected in the oral cavity, i.e., subgingival plaque and/or mucous membranes, less frequently in test patients compared to controls at 9 and 12 months (p<0.01), whereas, the intraoral detection frequency of P. gingivalis was significantly reduced only 10 days following therapy (p<0.001). At any time after therapy, A. actinomycetemcomitans was not detected intraorally in 5 of 10 (50%) test and 1 of 13 (8%) control patients harboring this pathogen at baseline; P. gingivalis was not detected in only 1 of 18 (6%) test and none of the 17 control patients harboring this pathogen at baseline. Although the data indicated that the assessed antimicrobial therapy may suppress A. actinomycetemcomitans from the entire oral cavity below detectable levels over a minimum of 12 months, P. gingivalis persisted or reoccurred.

Administration, Oral↗

Pseudorandom rotational stimuli of the vestibulo-ocular reflex in humans: normal values of the transfer function.

Pseudorandom binary rotatory stimulation is used to study the vestibulo-ocular reflex (VeOR) frequency response (from 0.01 to 0.64 Hz). Fifty-two normal subjects volunteered for this test. The transfer function's gain and phase, and the corresponding coherence function between slow phase eye velocity and head velocity were computed. According to the linearity hypothesis, the results match the sinusoidal stimulation studies. In both cases, the variability of the gain was higher than that of the phase shift. Identification of some parameters of the VeOR's mathematical model were performed, using the experimental results.

Adult↗

Analysis of 21 Stargardt's disease families confirms a major locus on chromosome 1p with evidence for non-allelic heterogeneity in a minority of cases.

BACKGROUND: Autosomal recessive Stargardt's disease is a macular degeneration characterised by a juvenile onset and a rapidly progressive course resulting in an atrophic macular area typically surrounded by yellowish retinal flecks. METHOD: The disease locus has previously been assigned to markers from chromosome 1p21-p13 by genetic linkage analysis in eight multiplex Stargardt's disease families. RESULTS: In an extended analysis, the assignment to chromosome 1p was confirmed in the majority of the 21 families with Stargardt's disease who were studied. In addition, a series of recombinant chromosomes further narrowed the Stargardt's disease region to an approximately 3 cM interval between markers at D1S424 and D1S497. CONCLUSION: Multipoint linkage analysis most probably excludes this locus in three of these families suggesting non-allelic heterogeneity with at least one additional minor Stargardt's disease locus.

Chromosomes, Human, Pair 1↗

Inhibition of degranulation of polymorphonuclear leukocytes by angiogenin and its tryptic fragment.

A degranulation inhibiting protein was purified to apparent homogeneity from plasma ultrafiltrates of patients with uremia using gel-permeation chromatography, ion-exchange chromatography, affinity chromatography on blue Sepharose, and ion-exchange chromatography on a Mono S HR 5/5 fast protein liquid chromatography column. The identity of the isolated degranulation inhibiting protein with angiogenin was demonstrated by amino acid sequence determination, immunoblotting, and identical inhibitory activity effects on leukocyte degranulation. At concentrations in the nanomolar range, the protein inhibited spontaneous degranulation of polymorphonuclear leukocytes (PMNL) to 40%. The protein discharge of cells, which were preincubated with nanomolar concentrations of angiogenin and then stimulated with the chemotactic peptide formyl-norleucyl-leucyl-phenylalanyl-norleucyl-tyrosyl-leucine (FNLPNTL), was inhibited by 70%. Cellular functions such as chemotaxis, phagocytosis, and the oxidative respiratory burst were not obviously affected by angiogenin. A polyclonal antibody to human recombinant angiogenin abolished the inhibitory effect of the isolated protein upon PMNL. The same but reduced effect was induced by the disulfide C39-C92 containing tryptic angiogenin fragment L-H-G-G-S-P-W-P-P-C92-Q-Y-R-G-L-T-S-P-C39-K, indicating a new, so far unknown biologically active site of angiogenin which is different from the sites responsible for angiogenic or ribonucleolytic activity. Two synthetic peptides containing residues 83-95, one with S92 instead of C92, revealed the same inhibitory effect on the protein degranulation of PMNL as the entire tryptic fragment.

Amino Acid Sequence↗

Treatment of non-healing skin ulcers with autologous activated mononuclear cells.

The aim of this study was to investigate whether cultured autologous mononuclear cells (MNC) effectively initiate, accelerate and improve granulation and epithelialisation of skin ulcers. Thirty-three patients with chronic arterial occlusive disease (CAOD; n = 21) or venous post-thrombotic syndrome (PTS; n = 12) were treated with autologous MNC and compared with a control group of 30 patients who received tissue culture medium alone. Previous treatments had been unsuccessful for a mean of 9.23 (3-19) months. MNC were harvested from the peripheral blood of each patient by standard techniques, cultured for three days and applied to the ulcer twice a week. After 4.6 +/- 1.9 weeks, 29/33 ulcers were closed in the MNC group. Patients in the control group took 8.1 +/- 1.2 weeks for 17/30 ulcers. Thus ulcer healing was significantly speedier with MNC seeding; 48% of all ulcers were closed after 30 days of MNC treatment and 92% after 60 days. Patients with PTS responded significantly faster than patients with CAOD. In 90% of patients with painful ulcers MNC treatment resulted in pain relief, whereas in the control group only 50% of patients became pain-free.

Aged↗

Effects of interleukin-1, -2, -4, -6, interferon-gamma and granulocyte/macrophage colony stimulating factor on human vascular endothelial cells.

Human vascular endothelial cells (HUVEC) exhibit various immunological functions, i.e. expression of HLA class-II antigens after incubation with IFN-gamma or antigen presenting function. It has also been reported that HUVEC are able to produce IL-1, IL-6, GM-CSF and immunologically active cleavage products of arachidonic acid. In our study we investigated whether various cytokines, namely IL-1, IL-2, IL-6, GM-CSF and IFN-gamma, do alter the proliferative capacity of HUVEC, the production of van Willebrandt factor (vWF) and the expression of MHC class-II antigens. HUVEC were prepared by the collagenase digestion of human umbilical veins. Monolayers of cells were incubated with cytokines in different concentrations for 24 and 48 h. IFN-gamma inhibits the HUVEC [3H]thymidine uptake in a dose-dependent manner. Suppression of proliferation (40.1%) could be observed after 24 h incubation with 100 U IFN-gamma/ml. IL-1 was a more effective inhibitor of HUVEC proliferation (54% at 10 U/ml and 24 h incubation and 48.4% after 48 h) than IFN-gamma. IL-6 and GM-CSF showed an increasing effect on proliferation with 226% and 151% of the control group, respectively. IFN-gamma after an incubation period of 12 h and IL-1 after 24 h reduced the vWF content by about 30%. Bright MHC class-II expression was induced only by IFN-gamma. In conclusion, some of the immunoregulative cytokines might play an important role in the control of HUVEC proliferation.

Cell Division↗

Effects of neurogenic bladder dysfunction in utero seen in neonates with myelodysplasia.

Twenty neonates with myelodysplasia were prospectively evaluated during the first month of life with urodynamic studies, contrast voiding cystourethrograms (VCUG) and renal ultrasound scans. Ten of 20 infants had abnormal VCUGs--6 with vesicoureteric reflux (VUR) and 4 with bladder trabeculation alone. Only 2/20 neonates had abnormal ultrasounds--both with hydroureteronephrosis secondary to VUR. Elevated leak point pressure (LPP) and/or detrusor sphincter dyssynergia (DSD) were present in 10/20 infants--6 with elevated LPP and DSD, 3 with elevated LPP alone and 1 with DSD alone. Eight of 10 neonates with DSD or elevated LPP had abnormal VCUGs--4 with VUR and 4 with bladder trabeculation alone. Conversely, 8/10 neonates without DSD or elevated LPP had normal VCUGs. Contrast VCUG performed shortly after birth, therefore, is essential for the discovery of bladder trabeculation and reflux. There is a strong correlation between an abnormal VCUG and the presence of DSD and elevated LPP, suggesting that neurogenic bladder dysfunction in utero can lead to these structural abnormalities.

Abnormalities, Multiple↗

A highly sensitive immunoenzymometric assay for the determination of angiogenin.

A polyclonal antibody to human recombinant angiogenin was prepared in rabbits using a Pam3CysSerGly conjugate. The antibody was then used to develop the first highly sensitive enzyme-labelled immunometric assay for this vascularisation inducing and tumour associated protein. The assay was suitable for quantification of angiogenin in body fluids between 2.5 and 0.05 micrograms/l. The mean intra-assay imprecision was 6.0% and the inter-assay imprecision 7.9%. Angiogenin in human plasma was found to lie in the range of 0.38 to 0.11 mg/l with a mean of 0.25 +/- 0.07 mg/l.

Angiogenesis Inducing Agents↗

[Pediatric liver transplantation and related live donor. Technical and ethical considerations].

With improved results of liver transplantation, the number of candidates is increasing. However the scarcity of suitable grafts from cadaveric donors remains a limitation. In spite of the use of full size or reduced size grafts or partial grafts from split livers, some children still die while waiting for liver transplantation. We describe a successful orthotopic liver transplantation in a 10 months old female using the left lateral lobe (segments II and III) from her 27 years old father. The child suffered from biliary atresia, her condition was deteriorating with intractable ascites and increasing jaundice. The father asked us to give a part of his own liver to his daughter. The concept of this innovative therapy had already been submitted to a research-ethics consultation which gave us favorable conclusions. After careful donor evaluation, the left lateral lobe was harvested on July 22, 1992, including the left hepatic artery, left portal vein and left hepatic vein; hepatic artery for segment IV, which arose from the right structures, was preserved, The graft was immediately transplanted orthotopically after recipient total hepatectomy with inferior vena cava preservation. Cold ischemia time was 1 hour and 45 minutes, revascularization of the graft was homogeneous from the very beginning and its early function was excellent. Thirteen days after the operation, the donor was discharged in good condition. The child was reoperated at day 9 for a small biliary leak originating from the cut surface of the liver. After resolution of an episode of rejection and an intra-abdominal abscess, the child was discharged in good health with normal liver function 1 month post-transplant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[A new approach to the mechanism of vestibular response to caloric stimulation].

Barany's classical hydrodynamic theory has been called into question by the zero-gravity Spacelab experiments, and several new hypotheses are put forth to explain the vestibular response to caloric stimulation. We have developed a mathematic model based on the analysis of an experimental model of the semicircular canal, incorporating observations done with zero-gravity and with gravity. Two purely mechanical phenomena are involved: one one hand, the modification of the hydrostatic pressure on both sides of the cupula due to a temperature variation if the semicircular canal is not in the horizontal plane in normal gravity conditions; on the other hand, local changes in endolymph pressure and volume due to the mechanical and osmotic properties of the canal, which are independent from gravity and from the position of the canal. These mechanical processes, though not exclusive, are predominant and therefore sufficient to explain the caloric response of the vestibulum in all cases.

Caloric Tests↗