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Biomedical subjects

W Berger

Publications and source records attributed to W Berger.

At least 91 records · Page 5Linked to original sources
PubMed1997

Opitz G/BBB syndrome, a defect of midline development, is due to mutations in a new RING finger gene on Xp22.

Opitz syndrome (OS) is an inherited disorder characterized by midline defects including hypertelorism, hypospadias, lip-palate-laryngotracheal clefts and imperforate anus. We have identified a new gene on Xp22, MID1 (Midline 1), which is disrupted in an OS patient carrying an X-chromosome inversion and is also mutated in several OS families. MID1 encodes a member of the B-box family of proteins, which contain protein-protein interaction domains, including a RING finger, and are implicated in fundamental processes such as body axis patterning and control of cell proliferation. The association of MID1 with OS suggests an important role for this gene in midline development.

Abnormalities, Multiple↗
PubMed1997

Diagnostic heterogeneity of diabetes in lean young adults: classification based on immunological and genetic parameters.

The aim of our study was to investigate the relative prevalence of the different forms of diabetes in young adults and their respective clinical characteristics. Included were 51 nonobese patients (BMI < 27 kg/m2) with diabetes diagnosed before age 40, excluding typical IDDM. Each patient was subjected to screening for glucokinase gene (MODY2) and mitochondrial DNA (at nucleotide 3243) mutations, to HLA class II genotyping, and screening for the presence of islet cell antibodies (ICAs) and anti-GAD antibodies. Informative families were analyzed for linkage of diabetes to chromosome 12q (MODY3). Based on clinical criteria, patients were subdivided into MODY (n = 19) and non-MODY (n = 32). In the MODY group, we identified three patients with MODY2, one with the 3243 mitochondrial mutation, and another with autoimmune diabetes. One of the five MODY families available for linkage study was shown to have MODY3. In the non-MODY group, we found five patients with autoimmune diabetes and one with MODY2. No clinical parameter was helpful to classify patients in one of these subclasses of diabetes; however, the glucagon-stimulated C-peptide was useful to discriminate between MODY2 patients and the others. In conclusion, young and lean non-insulin-dependent diabetic patients constitute a very heterogeneous group, although they present similar clinical characteristics. The clinical distinction of MODY and non-MODY patients allows correct classification in, at most, 75% of the patients and thus is not sufficient to predict clinical course. However, immunological and genetic parameters allowed us to classify only 25% of the patients in specific diagnostic classes.

Adult↗
PubMed1997

Retinoschisislike alterations in the mouse eye caused by gene targeting of the Norrie disease gene.

PURPOSE: To investigate the retinal function and morphology of mice carrying a replacement mutation in exon 2 of the Norrie disease gene. METHODS: Recently, Norrie disease mutant mice have been generated using gene targeting technology. The mutation removes the 56 N-terminal amino acids of the Norrie gene product. Ganzfeld electroretinograms (ERGs) were obtained in five animals hemizygous or homozygous for the mutant gene and in three female animals heterozygous for the mutant gene. As controls, three males carrying the wild-type gene were examined. Electroretinogram testing included rod a- and b-wave V-log I functions, oscillatory potentials, and cone responses. The fundus morphology has been visualized by scanning laser ophthalmoscopy. RESULTS: Rod and cone ERG responses and fundus morphology were not significantly different among female heterozygotes and wild-type mice. In contrast, the hemizygous mice displayed a severe loss of ERG b-wave, leading to a negatively shaped scotopic ERG and a marked reduction of oscillatory potentials. The a-wave was normal at low intensities, and only with brighter flashes was there a moderate amplitude loss. Cone amplitudes were barely recordable in the gene-targeted males. Ophthalmoscopy revealed snowflakelike vitreal changes, retinoschisis, and pigment epithelium irregularities in hemizygotes and homozygotes, but no changes in female heterozygotes. CONCLUSIONS: The negatively shaped scotopic ERG in male mice with a Norrie disease gene mutation probably was caused by retinoschisis. Pigment epithelial changes and degenerations of the outer retina are relatively mild. These findings may be a clue to the embryonal retinoschisislike pathogenesis of Norrie disease in humans or it may indicate a different expression of the Norrie disease gene defect in mice compared to that in humans.

Animals↗
PubMed1996

Biceps femoris tendon jerk reflexes are enhanced at the end of the swing phase in humans.

The phase-dependent modulation of the biceps femoris (BF) tendon jerk reflexes was investigated in a reduced form of walking. All subjects (12) investigated showed tendon reflexes throughout the whole step cycle but the amplitude was largest in the middle and late swing phase of the ipsilateral leg. It is concluded that the normally occurring BF burst at end swing could be due to stretch-induced activity.

Electromyography↗
PubMed1996

Medial gastrocnemius is more activated than lateral gastrocnemius in sural nerve induced reflexes during human gait.

In humans the sural nerve was stimulated at one of 16 phases of the step cycle. In MG (medial gastrocnemius) the amplitude of the P2 responses (latency 80-93 ms) was on average 1.3 times larger than the corresponding background activity while this was 0.9 for LG (lateral gastrocnemius; predominantly suppressive responses). It is speculated that such differences contribute to an exorotation moment during gait.

Adult↗
PubMed1996

Specific genetic deficiencies of the A and B isoenzymes of monoamine oxidase are characterized by distinct neurochemical and clinical phenotypes.

Monoamine oxidase (MAO) exists as two isoenzymes and plays a central role in the metabolism of monoamine neurotransmitters. In this study we compared the neurochemical phenotypes of previously described subjects with genetically determined selective lack of MAO-A or a lack of both MAO-A and MAO-B with those of two subjects with a previously described X chromosome microdeletion in whom we now demonstrate selective MAO-B deficiency. Mapping of the distal deletion breakpoint demonstrates its location in intron 5 of the MAO-B gene, with the deletion extending proximally into the Norrie disease gene. In contrast to the borderline mental retardation and abnormal behavioral phenotype in subjects with selective MAO-A deficiency and the severe mental retardation in patients with combined MAO-A/MAO-B deficiency and Norrie disease, the MAO-B-deficient subjects exhibit neither abnormal behavior nor mental retardation. Distinct neurochemical profiles characterize the three groups of MAO-deficient patients. In MAO-A-deficient subjects, there is a marked decrease in deaminated catecholamine metabolites and a concomitant marked elevation of O-methylated amine metabolites. These neurochemical changes are only slightly exaggerated in patients with combined lack of MAO-A and MAO-B. In contrast, the only biochemical abnormalities detected in subjects with the MAO-B gene deletion are a complete absence of platelet MAO-B activity and an increased urinary excretion of phenylethylamine. The differences in neurochemical profiles indicate that, under normal conditions, MAO-A is considerably more important than MAO-B in the metabolism of biogenic amines, a factor likely to contribute to the different clinical phenotypes.

Adult↗
PubMed1996

Dissection of the vertebral artery with cervical nerve root lesions.

Vertebral artery dissection may cause upper limb peripheral motor deficit. We report three young patients presenting with nuchal pain followed by a nearly painless proximal paresis of the arm several days later. The cause, as detected by colour-coded Duplex sonography and MRI, was an extracranial dissection of the vertebral artery. The proximity of the intervertebral segment to the vertebral artery and the nerve roots indicated that compression by an intramural haematoma was the likely cause of the disorder. Subsequent examinations during anticoagulation treatment showed almost complete disappearance of the intramural haematoma and of the neurological deficits within a few weeks. We believe that the occurrence of an upper limb peripheral motor deficit should be added to the spectrum of potentially misleading signs of vertebral artery dissection.

Adult↗
PubMed1996

A comparative study of unsedated transnasal esophagogastroduodenoscopy and conventional EGD.

BACKGROUND: A significant portion of the cost and complications associated with conventional esophagogastroduodenoscopy (EGD) is attributed to conscious intravenous sedation, which usually results in loss of work on the day of the endoscopy. Earlier studies have described the feasibility and safety of unsedated transnasal EGD in normal volunteers. METHODS: We compared the diagnostic yield and patient acceptability of this new technique performed first, with conventional EGD performed second in 24 outpatients. RESULTS: The sensitivity of transnasal EGD was 89% and its specificity was 97%. Transnasal EGD was more acceptable and less stressful to the patients than conventional EGD (p < 0.05). Oxygen saturation and blood pressure did not change during transnasal EGD. CONCLUSION: Transnasal EGD is feasible, safe, and well tolerated by patients. Specificity of transnasal EGD is similar to, but its sensitivity is lower than, conventional EGD. By eliminating the need for sedation-related work loss and postprocedural monitoring, transnasal EGD potentially is more cost-effective than conventional EGD.

Adult↗
PubMed1996

An animal model for Norrie disease (ND): gene targeting of the mouse ND gene.

In order to elucidate the cellular and molecular processes which are involved in Norrie disease (ND), we have used gene targeting technology to generate ND mutant mice. The murine homologue of the ND gene was cloned and shown to encode a polypeptide that shares 94% of the amino acid sequence with its human counterpart. RNA in situ hybridization revealed expression in retina, brain and the olfactory bulb and epithelium of 2 week old mice. Hemizygous mice carrying a replacement mutation in exon 2 of the ND gene developed retrolental structures in the vitreous body and showed an overall disorganization of the retinal ganglion cell layer. The outer plexiform layer disappears occasionally, resulting in a juxtaposed inner and outer nuclear layer. At the same regions, the outer segments of the photoreceptor cell layer are no longer present. These ocular findings are consistent with observations in ND patients and the generated mouse line provides a faithful model for study of early pathogenic events in this severe X-linked recessive neurological disorder.

Amino Acid Sequence↗
PubMed1996

Identification of a gene disrupted by a microdeletion in a patient with X-linked retinitis pigmentosa (XLRP).

The gene for the most frequent from of X-linked retinitis pigmentosa (XLRP), RP3, has been assigned by genetic and physical mapping to a segment of less than 1000 kbp, which is flanked by the marker DXS1110 and the ornithine transcarbamylase (OTC) gene. In search of microdeletions, we have screened the DNA of 30 unrelated patients with XLRP by employing a representative set of YAC-derived DNA fragments that were generated by restriction enzyme digestion and PCR amplification. In one of these patients, a 6.4 kbp microdeletion was detected which was not present in the DNA of 444 male controls. A cosmid contig spanning the deletion was constructed and used to isolate cDNAs from retina-specific libraries. Exons corresponding to these expressed sequences as well as other putative exons were identified by sequencing more than 30 kbp of the critical region. So far, no point mutations in these putative exon sequences have been identified.

Cell Line↗
PubMed1996

Positional cloning of the gene for X-linked retinitis pigmentosa 3: homology with the guanine-nucleotide-exchange factor RCC1.

The gene for retinitis pigmentosa 3 (RP3), the most frequent form of X-linked RP (XLRP), has been mapped previously to a chromosome interval of less than 1000 kbp between the DXS1110 marker and the OTC locus at Xp21.1-p11.4. Employing a novel technique, YAC Representation Hybridization (YRH)', we have recently identified a small XLRP associated microdeletion in this interval, as well as several putative exons including the 3' end of a gene that was truncated by the deletion. cDNA library screening and sequencing of a cosmid centromeric to the deletion has now enabled us to identify numerous additional exons and to detect several point mutations in patients with XLRP. The predicted gene product shows homology to RCC1, the guanine-nucleotide-exchange factor (GEF) of the Ras-like GTPase Ran. Our findings suggest that we have cloned the long-sought RP3 gene, and that it may encode the GEF of a retina-specific GTP-binding protein.

Amino Acid Sequence↗
PubMed1996

[Experimental studies of the biomechanics of scaphoid screws].

The purpose of this study was to determine the anchoring forces of four commonly used scaphoid screws in synthetic polyurethane foam. A linear relation was found between the length of the probe and the anchoring forces. The leading thread of the Herbert screw showed a anchoring force of 54 N/mm, the trailing thread 80 N/mm, and the Ulrich screw 75 N/mm. This linear relation of the shaft screws was only relevant upto a border probe length no longer that of the thread. Furthermore, it is valid for screws with continuous threads up to a probe length of 12 mm respectively. The cortical screw developed an anchoring force of 59 N/mm and the cancellous screw, 63 N/mm. With short probes of 4 and 6 mm, the trailing threads of the Herbert and Ulrich screws have the best anchoring forces, with values of 319 N/399 N and 307 N/435 N, respectively. The forces necessary for extraction of the tested scapoid bone screws placed in 8 mm polyurethane cubes were between 404 N and 527 N and were narrowly distributed. An additional conclusion of this study was that the application of screws with flat ends (Herbert and Ulrich screws) which were placed perpendicular to the dense material layer, significantly increased the anchoring forces.

Bone Screws↗
PubMed1996

A mathematical model of temperature distribution in frozen tissue.

A computer simulation for a frozen region expansion around a cryoprobe in liver tissue is presented and compared with experimental measurements in liver tissue. Both the analytical solution under simplifying assumptions and the numerical solution of the heat equation were tested. No analytical solution is possible when studying the freezing process in the time scope of minutes. The problem is that the solution needs spherical coordinate transformation, which is singular in the origin. For the frozen region, the analytical solution is not constrained, and conclusions are unrealistic. Neither does it account for the cryoprobe diameter. The numeric solution to the same problem is much more informative. It adopts the natural boundary conditions that are the constant temperatures of both the cooling medium and the bath. Comparisons between the numerical solution and experimental measurements show good approximation of the problem by the model of temperature distribution in a homogeneous medium which freezes around a cryoprobe. Differences were smaller than the apparent measurement errors. Our approach allows relevant results to be obtained within the time period available during the surgery.

Animals↗
PubMed1996

[Insulin therapy of Type I diabetes].

Since the controlled long-term study DCCT has clearly demonstrated that the progression of diabetic late complication is highly dependant on metabolic control an adaptation of insulin therapy became mandatory. In the eighties first successful attempts were made with the so-called Basis-Bolus-Principle (regular insulin before meals and depot-insulin at bedtime), the dosis being adapted depending on blood sugar tests. Near normoglycemia could only be achieved by a very strict time-schedule concerning meal-times and quantity of meals and still was accompanied by an increase of severe hypoglycemia. Only with the so-called functional insulin therapy it was possible to reach the goal of normoglycemia and maintaining the flexibility of patients as well as to reduce the risk of hypoglycemia. This type of therapy is based on the optimized adaptation of the daily insulin substitution to the physiological need of insulin. The pre-requisite is a separate substitution of basal and prandial insulin requirement. The basal substitution is divided in two to three injections of depot-insulin. Prandial insulin is injected according to the amount of desired carbohydrate content of the meal. Furthermore, high blood glucose values are immediately corrected by regular insulin given s. c. or i. m. To learn the basic knowledge of functional insulin therapy, special training is required in which the individualized rules have to be determined by self-experiments. This training is based on evening ambulatory sessions of 1 1/2 hours weekly during four weeks and then two further follow me seminars. The whole course takes three months. More than six years of experience with diabetic outpatient clinic at the university hospital of Basel have revealed that about 60% of type I diabetics were able to learn this therapy and preferred it to the conventional intensive insulin treatment. The secret of success of the functional insulin therapy is due to the self-determination of the therapy promoting a creative handling with the different kind of insulin treatment. The excellent experiences of this therapy oblige to offer this treatment to all type I diabetics. Being the achilles-heel of each insulin treatment, special efforts must be undertaken to reduce the risk of hypoglycemia. An increased risk of hypoglycemia exists with a duration of diabetes for more than ten years, or with a severe hypoglycemic attack in the past, furthermore with impaired renal function, loss or reduction of hypoglycemia awareness and with near-normo-glycemic blood glucose regulation. In this situation, a special training of strategies preventing hypoglycemia is indicated. As by avoiding low blood glucose values the awareness of hypoglycemia could be improved, it is mandatory to make special efforts to reduce or avoid low blood glucose values [< 3 mmol]. It is important that in determining the target of blood sugar regulation the risk of hypoglycemia has to be considered. In case of increased risk of hypoglycemia the target of blood sugar must be elevated. The goal of a good metabolic control while minimizing the risk of hypoglycemia and of increased flexibility in daily life can only be reached by special efforts of the teamwork between physician, diabetes nurse and dieticians with the diabetic patient. Different sorts of problems and recommendations of insulin treatment are discussed in a supplement.

Adult↗
PubMed1995

Benzothiazepine binding domain of purified L-type calcium channels: direct labeling using a novel fluorescent diltiazem analogue.

We have synthesized a series of N-propylamino-substituted benzazepinones (NPSBs) as specific probes for the benzothiazepinone (BTZ) binding domain of muscle L-type calcium channels (LTCCs). NPSBs were identified which possess high affinity for the channel after purification. We synthesized a fluorescent NPSB, DMBODIPY-BAZ, as the first benz(othi)azepinone derivative known to reversibly label partially purified LTCCs. DMBODIPY-BAZ binds to the partially purified channel with high affinity (Kd = 25 nM, Bmax = 580 pmol/mg of protein). Fluorescence resonance energy transfer (FRET) occurred between tryptophan residues of the channel protein and the DMBODIPY fluorophore upon specific drug binding. FRET was exploited to allow highly time-resolved detection of specific drug binding kinetics. We found that the dissociation half-life (t1/2) of DMBODIPY-BAZ decreased with the concentration of an unlabeled competitor, which indicates ligand-induced accelerated dissociation. In contrast, t1/2 was concentration-dependently increased by the dihydropyridine (DHP) (+)-isradipine. These kinetic properties of DMBODIPY-BAZ indicate that a high-affinity BTZ binding domain also exists on purified LTCCs. NPSBs represent novel tools to provide further insight into the molecular pharmacology of the BTZ binding domain on LTCCs.

Animals↗
PubMed1995

Linkage analysis in a Dutch family with X-linked recessive congenital stationary night blindness (XL-CSNB).

Linkage analysis has been performed in a large Dutch pedigree with X-linked recessive congenital stationary night blindness (CSNB) by utilizing 16 DNA markers from the proximal short arm of the human X chromosome (Xp21.1-11.2). Thirteen polymorphic markers are at least partially informative and have enabled pairwise and multipoint linkage analysis. For three loci, i.e. DXS228, the monoamine oxidase B gene and the Norrie disease gene (NDG), multipoint linkage studies have yielded maximum lod scores of > 3.0 at a recombination fraction of zero. Analysis of recombination events has enabled us to rule out the possibility that the underlying defect in this family is allelic to RP3; the gene defect could also be excluded from the proximal part of the region known to carry RP2. Linkage data are consistent with a possible involvement of the NDG but mutations in the open reading frame of this gene have not been found.

Chromosome Mapping↗