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Biomedical subjects

F Keller

Publications and source records attributed to F Keller.

At least 55 records · Page 3Linked to original sources
PubMed2000

New High-Resolution Analysis of the 3nu(3) and 2nu(1) + nu(3) Bands of Nitrogen Dioxide (NO(2)) by Fourier Transform Spectroscopy.

Using new high-resolution Fourier transform spectra recorded at the University of Denver in the 2-µm region, a new and more extended analysis of the 2nu(1) + nu(3) and 3nu(3) bands of nitrogen dioxide, located at 4179.9374 and 4754.2039 cm(-1), respectively, has been performed. The spin-rotation energy levels were satisfactorily reproduced using a theoretical model that takes into account both the Coriolis interactions between the spin-rotation energy levels of the (201) vibrational "bright" state with those of the (220) "dark" state. The interactions between the (003) bright state with the (022) dark state were similarly treated. The spin-rotation resonances within each of the NO(2) vibrational states were also taken into account. The precise vibrational energies and the rotational, spin-rotational, and coupling constants were obtained for the two dyads {(220), (201)} and {(022), (003)} of the (14)N(16)O(2) interacting states. From the experimental line intensities of the 2nu(1) + nu(3) and 3nu(3) bands, a determination of their vibrational transition moment constants was performed. A comprehensive list of line positions and line intensities of the {2nu(1) + 2nu(2), 2nu(1) + nu(3)} and the {2nu(2) + 2nu(3), 3nu(3)} interacting bands of (14)N(16)O(2) was generated. In addition, assuming the harmonic approximation and using the Hamiltonian constants derived in this work and in previous studies (A. Perrin, J.-M. Flaud, A. Goldman, C. Camy-Peyret, W. J. Lafferty, Ph. Arcas, and C. P. Rinsland, J. Quant. Spectrosc. Radiat. Transfer 60, 839-850 (1998)), we have generated synthetic spectra for the {(022), (003)}-{(040), (021), (002)} hot bands at 6.3 µm and for the {(220), (201)}-{(100), (020), (001)} hot bands at 3.5 µm, which are in good agreement with the observed spectra. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Differential regulation of adenosine A(1) and A(2A) receptors in serotonin transporter and monoamine oxidase A-deficient mice.

The serotonin (5HT) transporter (5HTT) removes 5HT from the synaptic cleft and is thus critical to the control of serotonergic neurotransmission. Mice with a targeted inactivation of the 5HTT represent a novel and unique tool to study serotonergic system functioning. Because the release of 5HT is regulated by adenosine, we investigated 5HTT-deficient mice for possible adaptive changes of adenosine A(1) and A(2A) receptors. A(1) and A(2A) receptors were studied by means of quantitative autoradiography using the radioligands [3H]8-cyclopentyl-1,3-dipropylxanthine and [3H]CGS 21680, respectively. A comparison of 5HTT knockout versus control mice revealed upregulation of A(1) receptors in the dorsal raphe nucleus (DRN, +21%), but not in any of the serotonergic projection areas, and downregulation of A(2A) receptors in basal ganglia. The adaptive changes of A(1) and A(2A) receptors in 5HTT-deficient mice are likely to represent a compensatory neuroprotective effect mediated by the adenosinergic modulatory system. For comparison, these receptors were also studied in monoamine oxidase A (MAOA) knockout mice and in 5HTT/MAOA double knockout mice. 5HTT/MAOA double knockout mice showed adaptive changes of adenosine A(1) and A(2A) receptors similar to 5HTT knockout mice, while investigation of MAOA-deficient mice revealed an upregulation of A(2A) receptors, which may relate to a role of both MAOA and adenosine A(2A) receptors in anxiety.

Animals↗
PubMed2000

Allocation of raffinose family oligosaccharides to transport and storage pools in Ajuga reptans: the roles of two distinct galactinol synthases.

Raffinose family oligosaccharides (RFOs) are important phloem transport and storage carbohydrates for many plants. Ajuga reptans, a frost-hardy evergreen labiate, ideally combines these two physiological roles and served as our model plant to study the regulation and importance of RFO metabolism. Galactinol is the galactosyl donor for the synthesis of raffinose (RFO-trisaccharide) and stachyose (RFO-tetrasaccharide), and its synthesis by galactinol synthase (GolS) is the first committed step of the RFO biosynthetic pathway. Two cDNAs encoding two distinct GolS were isolated from A. reptans source and sink leaves, designated GolS-1 and GolS-2, respectively. Warm- and cold-grown sink and source leaves were compared, revealing both isoforms to be cold-inducible and GolS-1 to be source leaf-specific; GolS-1 expression correlated positively with GolS activity. Conversely, GolS-2 expression was comparatively much lower and its contribution to the total extractable GolS activity is most probably only minor. These observations, together with results from phloem exudation and leaf shading experiments suggest that GolS-1 is mainly involved in the synthesis of storage RFOs and GolS-2 in the synthesis of transport RFOs. Furthermore, in situ hybridization studies showed GolS-1 to be primarily expressed in the mesophyll, the site of RFO storage, and GolS-2 in the phloem-associated intermediary cells known for their role in RFO phloem loading. A model depicting the spatial compartmentation of the two GolS isoforms is proposed.

Amino Acid Sequence↗
PubMed2000

Deafferentation-induced apoptosis of neurons in thalamic somatosensory nuclei of the newborn rat: critical period and rescue from cell death by peripherally applied neurotrophins.

This study shows that unilateral transection of the infraorbital nerve (ION) in newborn (P0) rats induces apoptosis in the contralateral ventrobasal thalamic (VB) complex, as evidenced by terminal transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) and electron miscroscopy. Double-labelling experiments using retrograde transport of labelled microspheres injected into the barrel cortex, followed by TUNEL staining, show that TUNEL-positive cells are thalamocortical neurons. The number of TUNEL-positive cells had begun to increase by 24 h postlesion, increased further 48 h after nerve section, and decreased to control levels after 120 h. Lesion-induced apoptosis in the VB complex is less pronounced if ION section is performed at P4, and disappears if the lesion is performed at P7. This time course closely matches the critical period of lesion-induced plasticity in the barrel cortex. Nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF), applied on the ION stump alone or in combination, are able to partially rescue thalamic neurons from apoptosis. Total cell counts in the VB complex of P7 animals that underwent ION section at P0 confirm the rescuing effect of BDNF and NGF. Blockade of axonal transport in the ION mimics the effect of ION section. These data suggest that survival-promoting signals from the periphery, maybe neurotrophins, are required for the survival of higher-order neurons in the somatosensory system during the period of fine-tuning of neuronal connections. We also propose that anterograde transneuronal degeneration in the neonatal rat trigeminal system may represent a new animal model for studying the pathways of programmed cell death in vivo.

Animals↗
PubMed2000

Insulin-like growth factor system components in hyperparathyroidism and renal osteodystrophy.

BACKGROUND: The insulin-like growth factor (IGF) system plays a key role in regulation of bone formation. In patients with renal osteodystrophy, an elevation of some IGF binding proteins (IGFBPs) has been described, but there is no study measuring serum levels of both IGF-I and IGF-II as well as IGFBP-1 to -6 in different forms of renal osteodystrophy and hyperparathyroidism. METHODS: In a cross-sectional study, we investigated 319 patients with mild (N = 29), moderate (N = 48), preuremic (N = 37), and end-stage renal failure (ESRF; N = 205). The ESRF group was treated by hemodialysis (HD; N = 148), peritoneal dialysis (PD; N = 27), or renal transplantation (RTX; N = 30). As controls without renal failure, we recruited age-matched healthy subjects (N = 87) and patients with primary hyperparathyroidism (pHPT; N = 25). Serum levels of total and free IGF-I, IGF-II, IGFBP-1 to -6, and biochemical bone markers including intact parathyroid hormone (PTH), bone alkaline phosphatase (B-ALP), and osteocalcin (OSC) were measured by specific immunometric assays. IGF system components and bone markers were correlated with clinical and bone histologic findings. Mean values +/- SEM are given. RESULTS: With declining renal function a significant increase was measured for IGFBP-1 (range 7- to 14-fold), IGFBP-2 (3- to 8-fold), IGFBP-3 (1.5- to 3-fold), IGFBP-4 (3- to 19-fold), and IGFBP-6 (8- to 25-fold), whereas IGFBP-5 levels tended to decrease (1.3- to 1. 6-fold). In contrast, serum levels of IGF-I, free IGF-I, and IGF-II remained constant in most patients. Compared with renal failure patients, pHPT patients showed a similar decline in IGFBP-5 levels and less elevated levels of IGFBP-1 (3.5-fold), IGFBP-2 (2-fold), IGFBP-3 (1.2-fold), and IGFBP-6 (4-fold) but no elevation of IGFBP-4 levels. In all subjects, free and total IGF-I levels showed significant negative correlations with IGFBP-1, IGFBP-2, and IGFBP-4 (that is, inhibitory IGF system components) and significant positive correlations with IGFBP-3 and IGFBP-5 (that is, stimulatory IGF system components). A positive correlation was observed between IGF-II and IGFBP-6. ESRF patients with mixed uremic bone disease and histologic evidence for osteopenia revealed significantly (P < 0.05) higher levels of IGFBP-2 and IGFBP-4 but lower IGFBP-5 levels. Histologic parameters of bone formation showed significant positive correlations with serum levels of IGF-I, IGF-II, and IGFBP-5. In contrast, IGFBP-2 and IGFBP-4 correlated positively with indices of bone loss. Moreover, dialysis patients with low bone turnover (N = 24) showed significantly (P < 0.05) lower levels of IGFBP-5, PTH, B-ALP, and OSC than patients with high bone turnover. CONCLUSION: Patients with primary and secondary hyperparathyroidism showed lower levels of the putative stimulatory IGFBP-5 but higher levels of IGFBP-1, -2, -3, and -6, whereas total IGF-I and IGF-II levels were not or only moderately increased. The marked increase in serum levels of IGFBP-4 appeared to be characteristic for chronic renal failure. IGFBP-5 correlated with biochemical markers and histologic indices of bone formation in renal osteodystrophy patients and was not influenced by renal function. Therefore, IGFBP-5 may gain significance as a serological marker for osteopenia and low bone turnover in long-term dialysis patients.

Adult↗
PubMed2000

Serotonin depletion and barrel cortex development: impact of growth impairment vs. serotonin effects on thalamocortical endings.

Converging evidence supports a role of serotonin (5-hydroxytryptamine; 5-HT) in barrel cortex development. Systemic administration of 5-HT-depleting drugs reduces cross-sectional whisker barrel areas in the somatosensory cortex (SSC) of neonatal rats. Here we assess the relative impact on barrel pattern formation of (i) 5-HT depletion and (ii) decreased brain growth, which is often associated with pharmacological 5-HT depletion, by comparing the effects of 5-HT-depleting drugs with those of reduced protein intake. Left hemisphere 5-HT levels in the SSC and right hemisphere whisker barrel areas were assessed at postnatal day 6 (P6) in the same animal following injection of p-chloroamphetamine (PCA) or p-chlorophenylalanine (PCPA) at P0. Both drugs significantly reduced cortical 5-HT content and mean barrel areas at P6, but also body and brain growth. Differences in brain weight accounted for 84.4% of the variance in barrel size, with negligible contributions by cortical 5-HT content. PCPA-treated animals sacrificed at P14 yielded similar trends, albeit less pronounced. Finally, reduced protein intake resulted in lower body weight and cortical 5-HT levels at P6, but yielded no change in brain weight or mean barrel area. Barrel formation therefore appears markedly less sensitive to 5-HT depletion per se than to drug-induced growth impairment.

Aging↗
PubMed2000

Assessment of viral loads in patients with chronic hepatitis C with AMPLICOR HCV MONITOR version 1.0, COBAS HCV MONITOR version 2.0, and QUANTIPLEX HCV RNA version 2.0 assays.

The correlation between response to antiviral therapy and pretreatment viral load in patients with chronic hepatitis C has prompted the development of quantitative assays to measure viral load. The aim of our study was to assess the clinical relevance of the newly developed semiautomated PCR system COBAS HCV MONITOR version 2.0 in comparison with (i) the AMPLICOR HCV MONITOR version 1.0 assay, which underestimates RNA concentration of hepatitis C virus (HCV) genotypes 2 to 6, and (ii) the QUANTIPLEX HCV RNA version 2.0 assay, which achieves equivalent quantification for each HCV genotype, with samples from 174 patients diagnosed with chronic hepatitis C before therapy. The level and range of quantification measured with AMPLICOR HCV MONITOR version 1.0 were 1 log lower than when measured with the COBAS HCV MONITOR version 2.0, at 0.261 x 10(6) RNA copies/ml (range, 0.001 x 10(6) to 2.50 x 10(6) RNA copies/ml) and 4.032 x 10(6) RNA copies/ml (range, 0.026 x 10(6) to 72.6 x 10(6) RNA copies/ml), respectively. The two assays showed a poor correlation (r(2) = 0.175). The level and range of quantification were similar when measured with the COBAS HCV MONITOR version 2.0 and QUANTIPLEX HCV RNA version 2.0 assays, at 3.03 x 10(6) RNA copies/ml (range, 0.023 x 10(6) to 72.6 x 10(6) RNA copies/ml) and 4.91 Meq/ml (range, 0.200 to 49.5 Meq/ml), respectively. The two assays showed a strong correlation (r(2) = 0. 686) for each HCV genotype. The duration of treatment (6 or 12 months) is modulated according to HCV genotype and viral load. Our results indicate that COBAS HCV MONITOR version 2.0 and QUANTIPLEX HCV RNA version 2.0 assays showing an equal dynamic range for each HCV genotype are suitable tools to assess patients before therapy.

Evaluation Studies as Topic↗
PubMed2000

Evaluation of IGF system component levels and mitogenic activity of uremic serum on normal human osteoblasts.

To test the hypothesis that impairment in bone formation in renal osteodystrophy in adults with chronic renal failure (CRF) might be mediated in part by alterations in circulating levels of the insulin-like growth factor (IGF) system components, we compared serum levels of IGF-I, IGF-II, IGF-binding protein (IGFBP)-3, IGFBP-4 and IGFBP-5 in adults with CRF (CRF patients with parathyroid hormone (PTH) < 100 pg/ml, PTH > 300 pg/ml and end-stage renal failure (ESRF) patients) versus age-matched controls. To evaluate the biological significance of alterations in circulating level of IGF system components, we compared the mitogenic activity of the sera on proliferation of normal human osteoblasts in vitro by using [(3)H]thymidine incorporation. We found severalfold increased serum levels of IGFBP-3 (2-fold), IGFBP-4 (5-fold) and slightly increased IGF-II levels in ESRF patients as well as a 2.6-fold increase in free IGF-I in CRF patients with PTH < 100 pg/ml. The mitogenic activity was found to be increased in serum of kidney failure patients compared to controls. This was most pronounced in CRF patients with PTH < 100 pg/ml showing also a significant increase in free IGF-I and the lowest levels of the IGF-inhibitory IGFBP-4. Our data support the hypothesis that alterations in serum levels of stimulating (i.e. free IGF-I) and inhibitory IGF system components (i.e. IGFBP-4) may influence osteoblastic cell proliferation in renal osteodystrophy.

Alkaline Phosphatase↗
PubMed2000

A concept for pharmacokinetic-pharmacodynamic dosage adjustment in renal impairment: the case of aminoglycosides.

BACKGROUND: For patients with impaired renal function, dosage adjustment is necessary for many drugs. Adjustment with respect only to pharmacokinetic parameters may be insufficient. OBJECTIVE: To apply the theory of pharmacokinetics and pharmacodynamics to derive a mathematical model that links the concentration-time course and the clinical response by means of the pharmacokinetic-pharmacodynamic parameter 'area under the effect-time curve' (AUETC), and to use this analysis and clinical data for aminoglycosides to calculate dosage adjustments in renal impairment. METHODS: Model parameters were estimated for the antimicrobial and nephrotoxic effects of aminoglycosides on the basis of data from the literature. Effect parameters were calculated for various degrees of impaired renal function. RESULTS: Use of the model parameters gave a high correlation between the predicted and the observed (literature) values for antimicrobial efficacy and nephrotoxicity. When calculating dosage adjustments in renal impairment, it was possible to hold only one effect (antimicrobial or nephrotoxic) constant by dosage adjustment, whereas the other changed unfavourably. This was explained by differences between the pharmacodynamic parameters for each effect. For high antimicrobial efficacy, a target peak concentration of 9 mg/L (for gentamicin) should be obtained every 48 hours in advanced renal impairment. For low nephrotoxicity, the peak concentration should not exceed 3 mg/L. CONCLUSIONS: The parameter AUETC could be a useful pharmacokinetic-pharmacodynamic surrogate marker for dosage adjustment in renal impairment. Using the AUETC method, the beneficial effect can be balanced against the adverse effect.

Algorithms↗
PubMed2000

Reply to Satomura.

Explore the source record for details and available documents.

Glomerulonephritis, IGA↗
PubMed2000

The outcome of acute interstitial nephritis: risk factors for the transition from acute to chronic interstitial nephritis.

BACKGROUND: Acute interstitial nephritis has been known as a complication of mainly streptococcal infection for nearly a century. With the advent of infection control, it became a complication caused by antibiotics and later by other drugs, which might have changed the outcome. To determine risk factors for the development of chronic renal insufficiency, and thus, the transition from acute to chronic interstitial nephritis, we performed a retrospective study of all cases of acute interstitial nephritis found by reviewing 1,068 renal biopsies from 1968 to 1997. METHODS: Patients with permanent and reversible renal insufficiency after acute interstitial nephritis were compared with respect to the causative event, the symptoms, and the clinical and histological findings. Differences between the groups were calculated by applying bi- and multivariate analysis. RESULTS: Acute interstitial nephritis was found in 6.5% of all biopsies (64 patients with 68 episodes of acute interstitial nephritis); it was infection-induced in 10%, idiopathic in 4%, and drug-induced in 85% of the cases (antibiotics in 13 cases, analgesics in 17, non-steroidal anti-inflammatory drugs (NSAIDs) in 16, diuretics in 5, and various other drugs in 7). Renal insufficiency was reversible in 69% and permanent in 31% (12% partially reversible, 19% irreversible). The infection-induced and idiopathic types of acute interstitial nephritis were always reversible. Drug-related acute interstitial nephritis caused permanent renal insufficiency in 36% with a maximum of 56% in NSAID-induced cases. In drug-induced cases, intake of the suspected drug for more than a month prior to diagnosis caused permanent renal insufficiency in 88% and interstitial granuloma in 31%. Multivariate analysis disclosed the following significant features separating the permanent from the reversible renal insufficiency group: patients in the first group had more tubular atrophy in their histology, more chronic use of mixed analgesics and/or NSAIDs, less oliguria or anuria as an acute symptom, fewer antibiotics as causative agents, more interstitial granuloma, more pronounced interstitial cell infiltration in their histology, and more imaging of renal shrinkage. Renal histology had the highest predictive value. CONCLUSION: Today, acute interstitial nephritis is mainly drug-induced. NSAIDs are the most frequent cause of permanent renal insufficiency after acute interstitial nephritis. Clinically, subacute symptoms, a prolonged intake of the suspect drug, and chronic analgesic or NSAID use are related to a more chronic course of interstitial nephritis. In histology, tubular atrophy, interstitial granuloma, and pronounced interstitial cell infiltration indicate chronicity.

Acute Disease↗
PubMed1999

Drug interactions with diosmectite: a study using the artificial stomach-duodenum model.

Drug interactions with diosmectite, a gastric-protective drug, were studied in vitro using an artificial stomach-duodenum model. The behavior of neutral and ionisable drugs with pKa values ranging between 2 and 8 was monitored to determine the physicochemical characteristics of the interactions. The main neutral (digoxin) and acid (valproic acid) drug substances were moderately fixed by clay (<27%), in a pH-independent manner. Basic compounds with a pKa<7 (dapsone, metronidazole, cimetidine) were strongly fixed in acid medium (?62%), and fully released under neutral conditions. Amphoteric (fluoroquinolones) and basic compounds with a pKa>/=7 (ranitidine, pyrimethamine) were adsorbed by more than 81% by diosmectite in gastric and duodenal compartments. In the part of the model representing the distal duodenum, the potential site for drug absorption, only the active substances which remained positively charged (amphoteric and basic compounds) showed a large reduction (>/=80%) in their available free fraction. Ionisation of drug substances administered per os concomitantly with diosmectite plays a crucial role in these interactions.

Adsorption↗
PubMed1999

Cerium-doped diosmectite for topical application studies of the cerium-clay interaction.

Cerium is used for its antiseptic and immunomodulatory properties in burn injury. We have developed a cerium-doped clay to replace existing ointments. Adsorption and release of cerium (Ce3+) by diosmectite were studied at 22+/-2 degrees C, in the presence of various other cationic species. Simple spectrofluorimetric determination of cerium was used (lambdaexc=240 nm/lambdaem=360 nm). Cerium binding reached a plateau within 2 min and was a function of the electrolyte content of the solution in contact with the clay. Langmuir isotherm treatment led to a maximal binding capacity of 66 mg of Ce3+ per gram of clay. Partial release occurred within 2 min (19% in the presence of isotonic NaCl solution). The ionic strength of the solution, and the ionic radius and charge of the electrolytes present in the bathing solution significantly influenced cerium release, in contrast to pH and temperature changes. These results strongly point to a cationic exchange mechanism between diosmectite and cerium solution.

Administration, Topical↗
PubMed1999

[Advantages of insulin Lispro (short-acting) in terminal kidney failure].

Diabetic management of dialysis patients with end-stage renal failure is often problematic. Renal failure interferes with the metabolism of glucose and insulin. Many of these diabetics have wide fluctuations in their daily blood glucose profile. The kinetics of regular insulin may be appreciably prolonged in consequence of the failure of renal insulin degradation, making the dose-effect profile of the insulin difficult to control, and hypoglycemia more likely. Intensified conventional insulin treatment (ICT) using the short-acting insulin, Lispro, facilitates the calculation of insulin requirements and helps to avoid large fluctuations in blood glucose levels. The present case report illustrates these difficulties in a patient on dialysis, and shows how ICT with Lispro can improve the quality of life of diabetics with renal failure.

Blood Glucose↗