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Biomedical subjects

Peter Weber

Publications and source records attributed to Peter Weber.

At least 19 recordsLinked to original sources

Development of a species-specific RNA polymerase I-based shRNA expression vector.

RNA interference (RNAi) can be induced in vitro either by application of synthetic short interfering RNAs (siRNAs), or by intracellular expression of siRNAs or short hairpin RNAs (shRNAs) from transfected vectors. The most widely used promoters for siRNA/shRNA expression are based on polymerase III (Pol III)-dependent transcription. We developed an alternative vector for siRNA/shRNA expression, using a mouse RNA polymerase I (Pol I) promoter. Pol I-dependent transcription serves in cells for production of ribosomal RNA (rRNA), and as such, is ubiquitously and stably active in different cell types. As Pol I-dependent transcription is highly species-specific, Pol I-based system provides an important biosafety advantage with respect to silencing of genes with unknown functions.

Animals↗

Fast improvement of verbal memory function after left temporal tumour resection.

CASE REPORT: A 7-y-old, right-handed girl presented at our clinic with complex partial seizures, behavioural problems and word-finding difficulties. Clinical examination was normal, but electroencephalogram revealed bilateral epileptic discharges in the temporal and paracentral leads. Magnetic resonance imaging showed an intracerebral mass in the left mesial temporal lobe in the areas of the gyrus temporooccipitalis medialis and gyrus parahippocampalis. Neuropsychological testing brought to light an above-average general intelligence, but the girl performed below average in verbal memory tests and average in figural memory tests. RESULTS: The tumour was completely removed by surgery. Neuropsychological testing 3 and 11 wk after tumour resection demonstrated above-average verbal learning and memory abilities and improved visual memory. The emotional disturbances, seizures and electroencephalogram abnormalities disappeared completely during the postoperative follow-up. CONCLUSION: After resection of a left temporal brain tumour, the patient was free of seizures, and neuropsychological functions recovered completely within weeks.

Brain Neoplasms↗

Epigallocatechin gallate supplementation alleviates diabetes in rodents.

As the prevalence of type 2 diabetes mellitus is increasing at an alarming rate, effective nutritional and exercise strategies for the prevention of this disease are required. Specific dietary components with antidiabetic efficacy could be one aspect of these strategies. This study investigated the antidiabetic effects of the most abundant green tea catechin, epigallocatechin gallate (EGCG, TEAVIGO), in rodent models of type 2 diabetes mellitus and H4IIE rat hepatoma cells. We assessed glucose and insulin tolerance in db/db mice and ZDF rats after they ingested EGCG. Using gene microarray and real-time quantitative RT-PCR we investigated the effect of EGCG on gene expression in H4IIE rat hepatoma cells as well as in liver and adipose tissue of db/db mice. EGCG improved oral glucose tolerance and blood glucose in food-deprived rats in a dose-dependent manner. Plasma concentrations of triacylglycerol were reduced and glucose-stimulated insulin secretion was enhanced. In H4IIE cells, EGCG downregulated genes involved in gluconeogenesis and the synthesis of fatty acids, triacylgycerol, and cholesterol. EGCG decreased the mRNA expression of phosphoenolpyruvate carboxykinase in H4IIE cells as well as in liver and adipose tissue of db/db mice. Glucokinase mRNA expression was upregulated in the liver of db/db mice in a dose-dependent manner. This study shows that EGCG beneficially modifies glucose and lipid metabolism in H4IIE cells and markedly enhances glucose tolerance in diabetic rodents. Dietary supplementation with EGCG could potentially contribute to nutritional strategies for the prevention and treatment of type 2 diabetes mellitus.

Acyl-CoA Oxidase↗

Early fatal pontocerebellar hypoplasia with simplified cerebral gyration and pseudolissencephaly. A neuroradiological pitfall.

We report the observation of a child born at 38 5/7 weeks' gestation, who presented with marked microcephaly and suffered from persistent intractable epilepsy up to his death at the age of 5 days. Magnetic resonance imaging suggested lissencephaly. But interestingly no submicroscopical deletion in LIS-1 gene could be detected and true lissencephaly could not be confirmed histologically. Instead, primary degenerative process was considered the most probable cause of congenital pontocerebellar hypoplasia II in this case, which may be associated with a maturation delay of the cerebral hemispheres. The present case points to possible pitfalls in neuroradiological interpretation of simplified cerebral gyration and to the necessity to take into account cerebral pathologies leading to slowing or arrest of intrauterine cerebral development and delay of cerebral gyration.

Brain↗

Development of bioactive substances for functional foods--scientific and other aspects.

The discovery and development of bioactive substances and their use in the manufacture of food products has the potential to contribute to the optimal health of populations and in reducing the risk of chronic disease. In assessing the efficacy of these substances in man, the concept of biomarkers could play a key role. However, it is the validation of such biomarkers which is crucial to the eventual availability of foods containing bioactive substances. Determining the safety and efficacy of these substances, and in particular in establishing claims, requires close cooperation between industry, regulatory authorities and the scientific community.

Biomarkers↗

Acceptance and timeliness of standard vaccination in children with chronic neurological deficits in north-western Switzerland.

UNLABELLED: There are no special recommendations for basic vaccinations in patients with chronic neurological deficits distinct from the nationwide advocated schedule in Switzerland. Reports describing adverse neurological events possibly related to vaccinations have attracted public attention. It is unclear if patients with chronic neurological deficits are more reluctantly vaccinated compared to healthy children. We therefore investigated the acceptance of vaccinations in such patients and healthy controls in a retrospective case-control study. At the University Children's Hospital, Basel, Switzerland we investigated 100 patients with chronic neurological deficits and 200 age-matched healthy controls regarding the issue of vaccination rates and ages. The total number of administered vaccinations against diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b (Hib), mumps, measles, rubella and hepatitis B were significantly lower in patients compared to healthy controls ( P < 0.01 for each of the respective vaccines). Patients had an increased risk to receive the third pertussis, diphtheria, and tetanus vaccinations (relative risks (RR) for late vaccination 1.53, 1.53, and 1.54 respectively, P < 0.01 for all comparisons), the second (RR = 1.60, P < 0.05) and third Hib vaccinations (RR = 1.52, P < 0.05), and the third polio vaccination (RR = 1.43, P < 0.05) later than controls. CONCLUSION: Children with chronic neurological deficits received fewer vaccinations than healthy controls. In addition, patients received vaccinations later than healthy children. Hence, it may be assumed that children with chronic neurological deficits are at an increased risk to acquire preventable infections. Therefore, vaccination should be promoted as part of the consultation during a routine appointment with the specialist.

Adolescent↗

TEAVIGO (epigallocatechin gallate) supplementation prevents obesity in rodents by reducing adipose tissue mass.

BACKGROUND: This study investigated the antiobesity effects of TEAVIGO, a product providing the most abundant green tea catechin, epigallocatechin gallate (EGCG), in a pure form. Two models of diet-induced obesity and an in vitro adipocyte differentiation assay were employed. METHODS: Prevention and regression of diet-induced obesity by dietary supplementation with EGCG was studied in C57BL/6J mice and Sprague-Dawley rats, respectively. Expression of genes regulating lipid metabolism was assessed in adipose tissue. The effects of EGCG on adipocyte differentiation were investigated in vitro. RESULTS: In C57BL/6J mice, EGCG supplementation prevented diet-induced increases in body weight and in fed state plasma levels of glucose, triglycerides, and leptin. EGCG decreased subcutaneous and epididymal adipose tissue weights. Supplementation of EGCG reversed the established obesity in Sprague-Dawley rats. Fatty acid synthase and acetyl-CoA carboxylase-1 mRNA levels were markedly decreased in adipose tissue of EGCG-supplemented mice. EGCG dose dependently inhibited adipocyte differentiation in vitro. CONCLUSION: This study shows for the first time that supplementation with the most abundant green tea polyphenol, EGCG, abolishes diet-induced obesity. This effect is at least partly mediated via a direct influence on adipose tissue. Thus, dietary supplementation with EGCG should be considered as a valuable natural treatment option for obesity.

Adipose Tissue↗

An astronomical 2175 angstrom feature in interplanetary dust particles.

The 2175 angstrom extinction feature is the strongest (visible-ultraviolet) spectral signature of dust in the interstellar medium. Forty years after its discovery, the origin of the feature and the nature of the carrier(s) remain controversial. Using a transmission electron microscope, we detected a 5.7-electron volt (2175 angstrom) feature in interstellar grains embedded within interplanetary dust particles (IDPs). The carriers are organic carbon and amorphous silicates that are abundant in IDPs and in the interstellar medium. These multiple carriers may explain the enigmatic invariant central wavelength and variable bandwidth of the astronomical 2175 angstrom feature.

Carbon↗

Cerebral hemodynamic changes in response to an executive function task in children with attention-deficit hyperactivity disorder measured by near-infrared spectroscopy.

The aim of the present study was to evaluate the hemodynamic changes in both prefrontal regions induced by a cognitive task in children with a developmental attention-deficit disorder in comparison to normal controls using near-infrared spectroscopy (NIRS). A total of 11 boys with a mean age of 10.4 (+/-1.2) years that met the DSM-IV criteria for attention-deficit hyperactivity disorder (ADHD) participated in the study and were compared with 9 healthy age- and sex-matched controls. Using a trail-making test designed for the task of connecting numbers from 1-90 in four sets, changes in oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin, tissue oxygenation index (TOI), and cerebral blood volume (CBV) were measured by near-infrared spectroscopy. During the first test set, designed as a short-attention task, the children with ADHD showed significant increases in O2Hb and CBV, whereas the controls showed no significant changes. During the 4 task cycles in which extended attention was demanded, both groups showed increases in O2Hb and CBV, but only the controls showed an additional increase in HHb in the left prefrontal region. In the ADHD group only, TOI showed an increase mainly on the left side. NIRS is a sensitive tool for measuring differences in hemodynamic changes between boys with ADHD and normal controls. Overall, the normal controls showed lateralized oxygen consumption in the left prefrontal cortex during an extended-attention task, whereas the boys with ADHD showed an imbalance between oxygenated and deoxygenated hemoglobin during the short- and extended-attention tasks.

Age Factors↗

Combined ultrasound and optoacoustic system for real-time high-contrast vascular imaging in vivo.

In optoacoustic imaging, short laser pulses irradiate highly scattering human tissue and adiabatically heat embedded absorbing structures, such as blood vessels, to generate ultrasound transients by means of the thermoelastic effect. We present an optoacoustic vascular imaging system that records these transients on the skin surface with an ultrasound transducer array and displays the images online. With a single laser pulse a complete optoacoustic B-mode image can be acquired. The optoacoustic system exploits the high intrinsic optical contrast of blood and provides high-contrast images without the need for contrast agents. The high spatial resolution of the system is determined by the acoustic propagation and is limited to the submillimeter range by our 7.5-MHz linear array transducer. A Q-switched alexandrite laser emitting short near-infrared laser pulses at a wavelength of 760 nm allows an imaging depth of a few centimeters. The system provides real-time images at frame-rates of 7.5 Hz and optionally displays the classically generated ultrasound image alongside the optoacoustic image. The functionality of the system was demonstrated in vivo on human finger, arm and leg. The proposed system combines the merits and most compelling features of optics and ultrasound in a single high-contrast vascular imaging device.

Acoustics↗

Sudden unexplained death in children with epilepsy: a cohort study with an eighteen-year follow-up.

AIM: Sudden unexplained death is a significant cause of mortality in adults with epilepsy. Only a few data exist about this risk in childhood. METHODS: Cases of sudden unexplained death in epilepsy (SUDEP) up to the age of 18 y occurring at our hospital between 1984 and 2001 were identified. The incidence rate was calculated on the basis of diagnosed epileptics registered with a statutory disability insurance scheme. RESULTS: Four cases of SUDEP were identified during the 18-y period. The incidence of SUDEP was 4.3 per 10,000 patient-years. All children showed polytherapy-refractory epilepsy, developmental retardation and early-onset epilepsy. Two witnessed cases had shown no previous signs of seizure. CONCLUSION: SUDEP is rare in childhood. Children with uncomplicated epilepsy seem not to be at risk.

Anticonvulsants↗

Incidence and diagnosis of unilateral arterial cerebral infarction in newborn infants.

AIMS: Magnetic resonance imaging (MRI) is accepted as the gold standard for the diagnosis of arterial cerebral infarction (ACI), but few studies have reported the incidence of neonatal ACI based on MRI findings. We provide new population-based epidemiologic and diagnostic data on all infants diagnosed between 1997 and 2002 in our center with an MRI-confirmed diagnosis of unilateral neonatal ACI. RESULTS: Nine patients were identified, giving an incidence of 1:2300 unilateral ACIs in our inborn population. In all patients the middle cerebral artery was affected. Seven patients showed epileptic seizures, usually starting within the first 3 days of life. EEG was pathologic in all patients. Only three infarctions were diagnosed by ultrasound. Initial MRI established diagnosis of ACI in eight out of nine patients and subsequent MRI described the exact location of infarctions in all patients. Six out of nine patients developed hemiparesis and five had deficits in language development. There is a substantial need for special care facilities and long-term therapeutic interventions. CONCLUSIONS: The incidence of neonatal ACI is higher than previously reported. The sensitivity of early cerebral ultrasound for diagnosis of ACI is low. Seizures in the first 3 days of life combined with pathologic EEG findings should lead to MRI, regardless of normal cerebral ultrasound.

Cerebral Infarction↗

Unilateral or asymmetric localization of lambda waves is not a pathologic finding.

This article reports on three children who underwent an electroencephalographic examination. All three showed the feature of asymmetric lambda waves, which is usually interpreted as a pathologic focal phenomenon. The report documents that asymmetric lambda waves and photic driving might be normal variants, not requiring further investigation.

Brain↗

Beyond deficiency: potential benefits of increased intakes of vitamin K for bone and vascular health.

Vitamin K is well known for its role in the synthesis of a number of blood coagulation factors. During recent years vitamin K-dependent proteins were discovered to be of vital importance for bone and vascular health. Recommendations for dietary vitamin K intake have been made on the basis of the hepatic requirements for the synthesis of blood coagulation factors. Accumulating evidence suggests that the requirements for other functions than blood coagulation may be higher. This paper is the result of a closed workshop (Paris, November 2002) in which a number of European vitamin K experts reviewed the available data and formulated their standpoint with respect to recommended dietary vitamin K intake and the use of vitamin K-containing supplements.

Antifibrinolytic Agents↗

Efficient separation and analysis of peroxisomal membrane proteins using free-flow isoelectric focusing.

We have elaborated a protocol for the fractionation of both hydrophilic and hydrophobic proteins using as a model the matrix and membrane compartments of highly purified rat liver peroxisomes because of their distinct proteomes and characteristic composition with a high quota of basic proteins. To keep highly hydrophobic proteins in solution, an urea/thiourea/detergent mixture, as used in traditional gel-based isoelectric focusing (IEF), was added to the electrophoresis buffer. Electrophoresis was conducted in the ProTeam free-flow electrophoresis (FFE) apparatus of TECAN separating proteins into 96 fractions on a pH 3-12 gradient. Consecutive sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis demonstrated that both matrix and the integral membrane proteins of peroxisomes could be successfully fractionated and then identified by mass spectrometry. This is documented by the detection of PMP22, which is the most hydrophobic and basic protein of the peroxisomal membrane with a pI > 10. The identification of 96 prominent spots corresponding to polypeptides with different physical and chemical properties, e.g., the most abundant integral membrane polypeptides of peroxisomes and specific ones of the mitochondrial and microsomal membrane, reflects the fractionation potential of free-flow (FF)-IEF, accentuating its value in proteomic research as an alternative perhaps superior to gel-based IEF.

Animals↗

Ototoxicity of ototopical antibiotic drops in humans.

OBJECTIVE: We sought to determine the incidence of injury to the cochlea or vestibular system from the use of ototopic antibiotic ear drops. STUDY DESIGN: We conducted a MEDLINE search of the published literature from 1966 to the present using the search items of "ototopic antibiotics," "ototopic drops," "antibiotic resistance," and others to identify pertinent articles. These articles were reviewed and graded according to evidence quality. Forty-four articles were found; 27 articles were considered appropriate for review and 14 of these articles were thought to warrant further extensive review. The latter 14 articles dealt directly with the evaluation of either hearing loss or changes in vestibular function after the use of ototopic ear drops. We eliminated studies that did not consider hearing or vestibular function. We considered only articles in the English language, eliminating articles that not address the ototoxicity of ototopical ear drops. RESULTS: Most of these articles were in the level 3 to 3b category. Two of the articles were in the 1b category, evaluating evidence-based studies. An article that reviewed case reports of ototopical ototoxicity and a survey article are included in this study, as case reports of ototopical ototoxicity and survey articles. CONCLUSION: We found a total of 54 cases of gentamicin vestibular toxicity and, in 24 of these patients, cochlear toxicity was also documented. Our review also found 11 cases of cochlear and 2 cases of vestibular toxicity in neomycin-based ear drops.

Administration, Topical↗