Search PubMed⌕ Search

Biomedical subjects

C Klein

Publications and source records attributed to C Klein.

At least 181 records · Page 10Linked to original sources
PubMed1999

Assessment of a carcinogenic risk for treatment of Graves' ophthalmopathy in dependence on age and irradiation geometry.

In view of the probable carcinogenic risk due to the irradiation of Graves' ophthalmopathy in young patients the effective dose was assessed for two geometries. Adjusting the field to the conical outline of the orbit resulted in appreciable reduction in dose to uninvolved areas such as brain and bone marrow. In Leiden and in Essen the initial target dose was 20 Gy in 10 fractions of 2 Gy. Since 1996 the target dose in Essen was lowered to 10 fractions of 1.6 Gy with equal positive results. The combined effect of field optimization and 20% reduction in target dose has lowered the effective dose from 65 to 34 mSv. The attributable lifetime risk for fatal malignancies of 0.3% as a population average will be considerably reduced when the exposure occurs at older age.

Adult↗
PubMed1999

Search for the PARK3 founder haplotype in a large cohort of patients with Parkinson's disease from northern Germany.

A founder haplotype on chromosome 2p for autosomal dominant Parkinson's disease (PD) has been postulated for two families of Northern European descent, and a new mutation in the alpha-synuclein gene (Ala30Pro) has been found in a German PD family. We evaluated 85 German PD patients and 85 ethnically matched controls for shared markers on chromosome 2p and for the new alpha-synuclein mutation. We found no evidence for linkage disequilibrium, suggesting that the putative founder mutation on chromosome 2p is not a common cause of PD in the local population. Furthermore, no patient carried the Ala30Pro change, supporting earlier findings that mutations in the alpha-synuclein gene are extremely rare.

Aged↗
PubMed1999

Genetics of primary dystonia.

Currently, at least 12 types of dystonia can be distinguished on a genetic basis. Advances in the molecular genetics of dystonia have led to the recent identification of a 3-bp deletion in the DYT1 gene, causing early-onset generalized torsion dystonia (TD), and to the detection of mutations in the GTP cyclohydrolase I and the tyrosine hydroxylase genes causing dopa-responsive dystonia (DYT5). A missense change in the D2 dopamine receptor has been shown to be associated with myoclonus-dystonia in one family. In addition, six other dystonia gene loci have been mapped to chromosomal regions, including a locus for a mixed dystonia phenotype (DYT6), one form of focal dystonia (DYT7), two types of paroxysmal dystonia (DYT8, DYT9), X-linked dystonia-parkinsonism (DYT3), and rapid-onset dystonia parkinsonism (DYT12). No positive linkage studies have as yet been reported for autosomal recessive TD (DYT2) and in several other large families with various types of dominantly inherited TD (DYT4). It may be anticipated that the traditional clinical and etiological classifications of dystonia will increasingly be replaced by a genetic one and that the identification of more dystonia genes may lead to a better understanding of these largely nondegenerative disorders.

Carrier Proteins↗
PubMed1999

Genetic testing for early-onset torsion dystonia (DYT1): introduction of a simple screening method, experiences from testing of a large patient cohort, and ethical aspects.

Early-onset, generalized primary torsion dystonia (PTD) is an autosomal dominantly inherited disorder, characterized by involuntary movements and abnormal postures. The majority of cases are caused by a 3-bp deletion in the DYT1 gene on chromosome 9q34 that allows for specific genetic testing. We developed a simple, reliable, and cost-effective, PCR-based screening method for this mutation. Testing results from a cohort of 550 cases, including patients with different forms of dystonia and unclassified movement disorders, revealed that 72.2% of the patients with typical early-onset generalized PTD carried the GAG deletion in the DYT1 gene. Among 300 cases with late-onset focal/segmental dystonia, only 3 patients tested positive for the GAG deletion whereas 12.8% of the patients with an unclassified movement disorder were GAG positive. Our results confirm a genotype/phenotype correlation in early-onset PTD and show that application of strict clinical criteria leads to accurate prediction of carrier status in more than two-thirds of patients with this type of dystonia. Currently, we suggest that testing be recommended in individuals with age of onset of dystonia below 30 years and/or a positive family history of early-onset PTD. Testing is not recommended in patients with onset of symptoms after 30 years or in asymptomatic individuals under the age of 18.

Adult↗
PubMed1999

Recombinant growth differentiation factor-9 (GDF-9) enhances growth and differentiation of cultured early ovarian follicles.

Transgenic mice with deletion of the GDF-9 (growth differentiation factor-9) gene are characterized by the arrest of ovarian follicle development at the primary stage. Based on the hypothesis that GDF-9 is important for early follicle development, we isolated rat GDF-9 complementary DNA (cDNA) and generated recombinant GDF-9 protein to study its physiological role. Using bacteria-derived GDF-9-glutathione S-transferase (GST) fusion protein, specific antibodies to the mature form of GDF-9 was generated. Immunohistochemical staining of ovarian sections indicated the localization of GDF-9 protein in the oocyte of primary, secondary and preantral follicles, whereas immunoblotting demonstrated the secretion of GDF-9 by mammalian cells transfected with GDF-9 cDNAs. Recombinant GDF-9 was shown to be an N-glycosylated protein capable of stimulating early follicle development. Growth of preantral follicles isolated from immature rats was enhanced by treatment with either GDF-9 or FSH whereas the combined treatment showed an additive effect. In addition, treatment with GDF-9, like forskolin, also stimulated inhibin-alpha content in explants of neonatal ovaries. In contrast, the stimulatory effects of GDF-9 were not mimicked by amino-terminal tagged GDF-9 that was apparently not bioactive. Thus, the present study demonstrates the important role of GDF-9 in early follicle growth and differentiation. The availability of recombinant bioactive GDF-9 allows future studies on the physiological role of GDF-9 in ovarian development in vivo.

Amino Acid Sequence↗
PubMed1999

The biological action of choriogonadotropin is not dependent on the complete native quaternary interactions between the subunits.

Human CG (hCG) is a member of the glycoprotein hormone family characterized by a heterodimeric structure consisting of a common alpha-subunit noncovalently bound to a hormone-specific beta-subunit. The two subunits are highly intertwined and only the heterodimer is functional, implying that the quaternary structure is critical for biological activity. To assess the dependence of the bioactivity of hCG on the heterodimeric interactions, alpha- and beta-subunits bearing mutations that prevent assembly were covalently linked to form a single chain hCG. Receptor binding and signal transduction of these analogs were tested and their structural integrity analyzed using a panel of monoclonal antibodies (mAbs). These included dimer-specific mAbs, which react with at least four different epitope sites on the hormone, and some that react only with the free beta-subunit. We showed that there was significant loss of quaternary and tertiary structure in several regions of the molecule. This was most pronounced in single chains that had one of the disulfide bonds of the cystine knot disrupted in either the alpha- or beta-subunit. Despite these structural changes, the in vitro receptor binding and signal transduction of the single chain analogs were comparable to those of the nonmutated single chain, demonstrating that not all of the quaternary configuration of the hormone is necessary for biological activity.

Animals↗
PubMed1999

Genetic analysis of three patients with an 18p- syndrome and dystonia.

Some patients with an 18p- syndrome show dystonia, and a focal dystonia gene has been mapped to chromosome 18p. The authors evaluated the extent of the deletion in three patients with an 18p- syndrome and dystonia using 14 DNA markers on 18p. A common deleted area, covering the DYT7 locus, places the putative dystonia gene between the telomere of 18p and D18S1104 (49.6 cM). Dystonia in these patients may be caused by haploinsufficiency of the DYT7 gene, a new dystonia gene on 18p, or may result from developmental brain anomalies.

Adult↗
PubMed1998

cMeso-1, a novel bHLH transcription factor, is involved in somite formation in chicken embryos.

The segmentation of somites from the paraxial mesoderm is a crucial event in vertebrate embryonic development; however, the mechanisms underlying this process are not well understood. In a yeast two-hybrid screen we have identified the novel basic-helix-loop-helix (bHLH) protein cMeso-1 which is expressed in the presomitic mesoderm of early chicken embryos. Initially the gene is activated in the epiblast and transcripts concentrate later in and around the primitive streak. When the segmental plate is laid down the cMeso-1 expression domain successively retracts toward the caudal end but a second domain appears in bilateral stripes in the anterior paraxial mesoderm. This highly dynamic domain of cMeso-1 transcripts demarcates the area immediately posterior to the next prospective pair of somites in cyclic waves which apparently correspond to the formation of new somites. Loss of cMeso-1 function by antisense RNA or oligonucleotides results in severe attenuation of somitogenesis suggesting that it plays an important role in setting up the segmentation process. The dynamic and periodically reiterated expression of cMeso-1 along the anteroposterior axis is not dependent on anterior structures or the propagation of a signal along the anteroposterior axis but seems to follow an intrinsic patterning program which is already set up in the segmental plate.

Amino Acid Sequence↗
PubMed1998

The function of the periplasmic Sud protein in polysulfide respiration of Wolinella succinogenes.

The periplasmic Sud protein was previously isolated as a sulfide dehydrogenase from Wolinella succinogenes. Sud modified by a C-terminal His-tag (Sud-His6) was produced in Escherichia coli by expression of the sud gene. Sud-His6 catalyzed thiocyanate formation from cyanide and polysulfide. The Vmax of this activity was more than one order of magnitude higher than that of sulfide oxidation by dimethyl-naphthoquinone and that of polysulfide reduction by BH4-. The apparent Km was less than 20 microM polysulfide. Polysulfide and not elemental sulfur was found to be the product of sulfide oxidation by dimethyl-naphthoquinone, in contrast to the earlier view [Kreis-Kleinschmidt, V., Fahrenholz, F., Kojro, E. & Kröger. A. (1995) Arch. Microbiol. 165, 65-68]. Sud-His6 did not contain metal ions or other prosthetic groups. Replacement by site-directed mutagenesis of the single cysteine residue of the Sud monomer caused complete loss of activity, while the exchange of the single histidine residue or of the lysine residue situated next to cysteine did not affect activity. In equilibrium dialysis, the Sud-His6 monomer bound up to ten polysulfide sulfur atoms with a dissociation constant of 0.2 mM. Sud-His6 loaded with polysulfide sulfur showed an absorption spectrum in the range of 350-400 nm; this spectrum differed from that of free polysulfide. Electron transport from H2 to polysulfide catalyzed by the membrane fraction of W. succinogenes was stimulated by the presence of small amounts of Sud-His6. The apparent Km for polysulfide decreased sevenfold in the presence of saturating amounts of Sud-His6 (1 microM Sud-His6 dimer). Similar results were obtained with intact W. succinogenes cells containing low and high amounts of Sud. Sud appears to function as a polysulfide binding protein and probably binds polysulfide sulfur to its cysteine residue and transfers it to the substrate site of the membraneous polysulfide reductase.

Amino Acid Sequence↗
PubMed1998

Clinical and genetic evaluation of a family with a mixed dystonia phenotype from South Tyrol.

The gene causing early-onset torsion dystonia (DYT1) has recently been identified, and two new dystonia genes, one for adult-onset focal dystonia (DYT7) and one for a mixed dystonia phenotype (DYT6), have been mapped. We evaluated clinically a family from South Tyrol (Northern Italy) with 6 definitely affected individuals who display an unusually large phenotypic range of dystonic symptoms. We excluded the GAG deletion in the DYT1 gene and linkage to any of the above-mentioned dystonia loci, thus suggesting an as yet undefined dystonia gene in our family.

Adolescent↗
PubMed1998

Voluntary palatal tremor in two siblings.

We report two siblings with palatal tremor (PT) and ear clicks who can voluntarily elicit or suppress both PT and ear clicks by just "thinking" about starting or stopping the sounds. The patients were also able to voluntarily modulate the frequency of their ear clicks and PT. They did not have any signs of cerebellar, brain stem, or other neurologic disease. These familial palatal movements may represent a variant of palatal tremor but can not satisfactorily be classified as either symptomatic or essential PT.

Adult↗
PubMed1998

Neurosurgical intervention for cervical disk disease in dystonic cerebral palsy.

We report five young patients with athetoid-spastic cerebral palsy who had deteriorated neurologically. Magnetic resonance imaging (MRI) was used to investigate suspected compressive cervical spine lesion. Cervical spondylosis with disk protrusions was found in all patients. Four patients underwent surgery by an anterior approach with insertion of a bone graft resulting in substantial clinical improvement. The other patient, diagnosed 8 years after onset of symptoms, was treated conservatively. The availability of MRI makes early recognition of cervical cord compression possible, allowing effective surgical intervention in this special group of patients.

Adult↗
PubMed1998

High-level secretion of a wheat lipid transfer protein in Pichia pastoris.

Plant nonspecific lipid transfer proteins are small basic proteins with eight cysteine residues, all engaged in disulfide bonds. The sequence encoding the wheat 9-kDa LTP was cloned into the secretion vector pYAM7SP8 giving rise to pYTdltp4.90. Production in shake-flasks and a fermentor led to the synthesis of two major species of LTP: a larger than expected species of 14 kDa and a species of 10 kDa, close to the expected size of wheat LTP. When production was carried out in a fermentor with regulation of pH, oxygen level, and feed rate of carbon source, the 10-kDa species was the main protein at the end-point of culture. The recombinant wheat LTP (rLTP), secreted at a level of 720 mg/liter into the culture medium, is soluble. The rLTP was purified to homogeneity by ammonium sulfate precipitation, gel filtration, and anion-exchange chromatography, with a recovery yield of 36%. However, the molecular mass of rLTP, determined by mass spectrometry, is 9996 Da, while its naturally occurring counterpart has a molecular mass of 9607 Da. This discrepancy in size corresponds to a protein carrying three extra amino acids (DKR) at its N-terminal end, and this was confirmed by sequencing. In vitro lipid transfer activity showed that rLTP behaves in a similar way to the naturally occurring protein. These data indicate that Pichia pastoris is an efficient system for production of large quantities of soluble and biologically active rLTP for structure/function analysis.

Amino Acid Sequence↗
PubMed1998

[Midfacial callus distraction in a patient with Crouzon syndrome].

The treatment of syndromic hypoplasias of the midfacial complex, for example in Crouzon patients, is necessary at an early stage for functional and aesthetic reasons. If midfacial advancement is done by the traditional technique using bone grafts, it has often been seen that the normal occlusion originally achieved changes in an Angle class III, because the mandible grows regularly but not the midface. This problem could probably be solved if midfacial advancement is done by the gradual callus-distraction procedure. The local osteogenesis involves the possibility that there is normal growth of the midfacial complex even if the operation is performed in young children. Based on experience in mandibular bone lengthening, this new method was used in a 10-year-old Crouzon patient. As successful lengthening of the midface needs a stable device and a reliable base, a new midfacial distractor was designed using the principle of the halo-frame. With an advancement of about 22 mm the midfacial position was normalized and a regular overbite was achieved. In a case report the new technique is shown and the results are demonstrated and discussed. Despite this encouraging early result a long-term follow-up is not yet possible.

Cephalometry↗
PubMed1998

[Non-epileptic paroxysmal movement disorders].

Non-epileptic paroxysmal dyskinesias present with different forms of extrapyramidal hyperkinesias (dystonia, chorea, athetosis, ballism) in variable combinations and with cerebellar signs, respectively. They may be classified as: 1. paroxysmal dystonias/choreoathetoses (paroxysmal dystonic choreoathetosis = PDC), paroxysmal kinesigenic choreoathetosis = PKC, intermediate form) and 2. paroxysmal ataxias (PA) (PA with myokymia and neuromyotonia, azetazolamide-responsive PA). Nocturnal paroxysmal dystonia is now regarded as one form of nocturnal frontal lobe epilepsy. Research in molecular genetics has substantially contributed to the etiologic understanding of paroxysmal dyskinesias: In different families linkage has been successfully completed for PDC (chromosome 2q) and PA (chromosomes 12p, 19p). PA are now identified as channelopathies with mutations in the potassium channel (PA with myokymia and neuromyotonia) and the calcium channel gene (azetazolamide-responsive PA).

Athetosis↗