Although protein kinase C (PKC) has been shown to participate in skeletal myogenic differentiation, the functions of individual isoforms of PKC in myogenesis have not been completely elucidated. These studies focused on the role of nPKC straight theta, an isoform of the PKC family whose expression has been shown to be regulated by commitment to the myogenic lineage, myogenic differentiation and innervation. We used the myogenic cell line C(2)C(12) as a tissue culture model system to explore the role of nPKC straight theta in the formation of multinucleated myotubes. We examined endogenous levels of nPKC straight theta in C(2)C(12) cells and showed that it is expressed at low levels in myoblasts compared to mouse skeletal muscle and that expression is maintained in myotubes. We overexpressed nPKC straight theta in C(2)C(12) myoblasts and examined the ability of overexpressing cells to differentiate into myotubes. Using an nPKC straight theta - green fluorescent protein (GFP) chimera to detect transfected myoblasts, we showed that overexpressed nPKC straight theta-GFP translocates to the plasma membrane in response to phorbol ester treatment of myoblast cultures in situ. nPKC straight theta-GFP was found to be completely extracted into the detergent-soluble fraction of cell lysates and was stably expressed throughout the extent of differentiation into myotubes. No difference was seen in the ability of myoblasts either overexpressing nPKC straight theta - GFP or GFP alone to form myotubes. These studies demonstrate that overexpression of nPKC straight theta does not interfere with fusion of myoblasts into myotubes suggesting that nPKC straight theta activity is not inhibitory for myogenesis. These studies also demonstrate a method for transfecting myoblasts and identifying differentiated cells that overexpress nPKC straight theta-GFP for investigating the function of nPKC straight theta in living myotubes.

Animals↗

PubMed2000

Purification and biochemical characterization of a basic superantigen (SPEX/SMEZ3) from Streptococcus pyogenes.

A potent basic superantigen (designated streptococcal pyrogenic exotoxin X, SPEX/SMEZ3) was purified to homogeneity from culture supernatants of a Streptococcus pyogenes scarlatina strain of type 12 (genotype speA(-), speC(-)) and characterized. Sequence alignments revealed SPEX to be an allele of the streptococcal mitogens type Z (SMEZ). The N-terminal amino acid sequence of SPEX was found with LEVDNNSLLR to be identical to the recently described acidic superantigen SMEZ. Although SPEX/SMEZ genes were present in all of the streptococcal strains tested, a toxin production could only be detected in a small number of strains. The produced toxin concentration in the culture supernatants of positive strains differed between 0 and 20 ng ml(-1). The purified SPEX stimulated human T-lymphocytes with Vbeta8 specificity at extremely low concentrations (lower than 100 pg ml(-1)).

Amino Acid Sequence↗

PubMed2000

Probing pauli blocking factors in quantum pumps with broken time-reversal symmetry

A recently demonstrated quantum electron pump is discussed within the framework of photon-assisted tunneling. Because of lack of time-reversal symmetry, different results are obtained for the pump current depending on whether or not final-state Pauli blocking factors are used when describing the tunneling process. While in both cases the current depends quadratically on the driving amplitude for moderate pumping, a marked difference is predicted for the temperature dependence. With blocking factors the pump current decreases roughly linearly with temperature until k(B)T approximately Planck's over 2piomega is reached, whereas without them it is unaffected by temperature, indicating that the entire Fermi sea participates in the transport.

Journal Article↗

PubMed2000

The amyloid beta peptide abeta (25-35) induces apoptosis independent of p53.

Apoptosis of neuronal cells apparently plays a role in Alzheimer's disease (AD). The amyloid beta (Abeta) peptide derived from beta-amyloid precursor protein is found in AD brain in vivo and can induce apoptosis in vitro. While p53 accumulates in cells of AD brain, it is not known if p53 plays an active role in Abeta-induced apoptosis. We show here that inactivation of p53 in two experimental cell lines, either by expression of the papillomavirus E6 protein or by a shift to restrictive temperature, does not affect apoptosis induction by Abeta (25-35), indicating that Abeta induces apoptosis in a p53-independent manner.

Amyloid beta-Peptides↗

PubMed2000

Redetermination of [Ni(NH(3))(6)]Cl(2) at 173 K.

The structure of hexaamminenickel(II) dichloride determined previously by Essmann et al. [Essmann, Kreiner, Niemann, Rechenbach, Schmieding, Sichla, Zachwieja & Jacobs (1996). Z. Anorg. Allg. Chem. 622, 1161-1166] was redetermined at 173 K. There are no significant differences between these two structures.

Journal Article↗

PubMed2000

The p44S10 locus, encoding a subunit of the proteasome regulatory particle, is amplified during progression of cutaneous malignant melanoma.

Gene amplification is frequently present in human tumors, although specific target genes relevant to many amplified loci remain unidentified. An expression cloning assay enabled identification of a candidate oncogene derived from human chromosome 3p14.1. The cDNA retrieved from morphologically transformed cells contained the full-length protein coding region and detected an abundant transcript in the same cells. Sequence analysis revealed identity with the wild-type sequence of p44S10, a highly conserved subunit of the 26S proteasome that exhibits similarity to the Arabidopsis fus6/cop11 family of signaling molecules. p44S10 gene copy number and mRNA expression were increased in association with segmental 1.8 - 11-fold chromosomal gains in cutaneous malignant melanoma cell lines (5/13; 40%) and tumors (2/40; 5%), and in breast cancer MCF-7 cells. Likewise, malignant progression of human radial growth phase WM35 melanoma cells was associated with amplification and increased expression of endogenous p44S10, and increased expression of p44S10 was sufficient to induce proliferation of WM35 cells in vivo. The results demonstrate segmental copy number gains within chromosome 3p in cutaneous malignant melanoma and suggest that deregulation of a proteasome regulatory particle subunit may contribute to the malignant phenotype.

Adenosine Triphosphatases↗

PubMed2000

Role of MT-MMPs and MMP-2 in pancreatic cancer progression.

Activation of matrix metalloproteinase-2 (MMP-2) by the membrane-type matrix metalloproteinases (MT-MMPs) has been associated with tumor progression. In the present study, we examined the role of MMP-2 and its activators MT1-MMP, MT2-MMP and MT3-MMP in pancreatic tumor cell invasion and the development of the desmoplastic reaction characteristic of pancreatic cancer tissues. Northern blot analyses revealed that transcript levels of MT1-MMP and MT2-MMP, but not MT3-MMP, were enhanced in pancreatic cancer tissues (n = 18) compared with both chronic pancreatitis (n = 9) and healthy pancreas (n = 9). A good correlation was found between MT1-MMP and both MMP-2 expression (p < 0.01) and activity in pancreatic cancer tissues. In addition, expression and activation of MMP-2 were strongly associated with the extent of the desmoplastic reaction in pancreatic cancer tissues. Invasion assays showed a good correlation between MMP-2 expression and activity and the invasive potential of pancreatic cancer cell lines. In cell lines with high levels of MMP-2 expression and activity, the MMP inhibitor Batimastat led to significant reduction of the number of invading cells. Our results suggest that MT1-MMP is involved in the progression of pancreatic cancer via activation of MMP-2. MMP-2 itself plays an important role in tumor cell invasion and appears to be associated with the development of the characteristic desmoplastic reaction in pancreatic cancer.

Adenocarcinoma↗

PubMed2000

Limitations of magnetic resonance imaging in the evaluation of perineural tumor spread causing facial nerve paralysis.

OBJECTIVE: To present and discuss the clinical presentation and treatment in patients with long-duration unilateral facial paralysis and normal magnetic resonance imaging (MRI) findings. DESIGN: Case series. SETTING: Ear, nose, and throat department of the University of Cologne, Cologne, Germany. PATIENTS: A total of 486 patients with unilateral facial paralysis who were treated from 1986 to 1998. Besides the usual diagnostic workup, a complete electrophysiological evaluation, including investigations such as needle electromyography and neuromyography (also known as electroneurography), of the facial nerve was performed at repeated intervals. In 19 patients, a malignant tumor was delineated with ultrasonography or MRI. In 8 of these patients, the initially performed MRI did not detect any parotid gland lesion causing the paralysis, whereas long duration of the paralysis and electroneurography indicated malignancy. RESULTS: Exploration surgery was performed as total parotidectomy in these 8 patients and malignant parotid gland tumors were proved in all 8 patients. CONCLUSIONS: Individuals with facial nerve paralysis without any signs of regeneration 6 months after the onset of paralysis and/or persistent electrophysiological evidence of ongoing neuronal degeneration should undergo surgical exploration of the parotid gland and facial nerve, even if MRI studies show no tumoral lesion.

Adenocarcinoma↗

PubMed2000

Relapsing nasal glioma in a three-week-old infant.

Explore the source record for details and available documents.

Choristoma↗

PubMed2000

Visualization of pressure distribution within loaded joint cartilage by application of angle-sensitive NMR microscopy.

High-resolution MRI measurements on knee joints show a multilaminar appearance of the cartilage. This intracartilaginar structure, visualized as hypointense zones in T(2)-weighted MR images is based on the dipolar interaction of water molecules within regions of anisotropic arrangement of collagen network. Using the different angle dependence of the MR signal, zones of radially and tangentially oriented network structures can be distinguished. Information equivalent to that from polarization light microscopy can be derived noninvasively. This is demonstrated by polarization light microscopic reference investigations. It is shown that this multilaminar MRI appearance is sensitively influenced by mechanical stress. A model explaining the contrary behavior of loaded tangential and radial network structures is given. Based on this pressure dependence, a noninvasive determination of mechanical properties is possible. Using the variation of size and intensity of the hypointense zones under pressure, dynamic high resolution MRI yields noninvasive information about the intracartilaginar pressure distribution similar to photoelastic measurements. Magn Reson Med 43:884-891, 2000.

Animals↗

PubMed2000

Differential sustained attention/vigilance changes over time in schizophrenics and controls during a degraded stimulus Continuous Performance Test.

The Continuous Performance Test (CPT) is a widely used procedure for sustained attention/vigilance measurement. However, though the key index of vigilance impairment is the decrement of sensitivity over time during the test period, only few studies have examined whether schizophrenics show a larger drop in CPT performance than do healthy controls. 48 schizophrenic inpatients and 48 controls were investigated with the Munich CPT (480 visual stimuli, 25% target stimuli, one stimulus per second). Stimuli were degraded by randomly inverting 40%, 41%, 42%, or 43% of the pixels. Results were calculated separately for three consecutive trial sections. Additionally, PANSS ratings, medication, and other clinical data were documented. Schizophrenics show a vigilance decrement over time, controls show a vigilance increase. Differential vigilance changes were not related to the level of stimulus degradation. Schizophrenics performed worse than controls only at the lowest degradation level. While overall sensitivity correlated negatively with the dose of atypical neuroleptics and benzodiazepines, vigilance shifts over time correlated negatively with the dose of typical neuroleptics. Furthermore, sensitivity was related to the cognitive PANSS syndrome, number of admissions/duration of illness. Differential sensitivity decrements of schizophrenics and controls can be shown if suited CPT procedures are used. The need for basic research on experimental conditions of the CPT as well as examination of the relationship between sustained attention/vigilance decrements and clinical features of schizophrenia is suggested.

Adult↗

PubMed2000

Cone prosthesis for the hip joint.

The shape of the proximal segment of the femur must be taken into account when implanting femoral endoprostheses, especially those intended for cementless anchorage. Numerous femoral prostheses are available for the proximally broadly extending, "trumpet-shaped" morphology. However, the femur often has a narrow, more cylindrical configuration, as is frequently seen with dysplastic hip joints, but variants of the anatomical constitution or ethnic variants are also found. Conventional femoral prostheses with a proximal transverse oval or rectangular cross-section are often incorrectly positioned in those cases because they can fracture the narrow bones. In many instances, even a pathological anteversion attachment cannot be adequately corrected. The cone prosthesis is ideal for this morphology when pre-operative planning indicates good contact between the bone cortex and the middle third of the prosthetic stem. The tapered anchorage of the cone stem in the medullary cavity reamed to a cone shape promotes primary stability, which is a fundamental prerequisite for the osseointegration of a coarse blasted titanium implant. The sharp longitudinal ridges on the prosthetic stem, which tend to cut into the bone, ensure extensive rotational stability, which explains why thigh pain is not associated with the cone prosthesis. The cone prosthesis has proved its worth in 635 implants performed over 9 years, with highly satisfactory clinical and X-ray results. The surgical technique is relatively straightforward, and complications are rare. The patients' subjective satisfaction is particularly remarkable. The success of the operation lies in correct preoperative planning, which ensures that the morphology of the selected femur guarantees contact between the bone cortex and the middle third of the prosthetic stem.

Adolescent↗

PubMed2000

Serial extraction or premolar extraction in the permanent dentition? Comparison of duration and outcome of orthodontic treatment.

Treatment outcome and duration of 2 different treatment approaches in 2 groups of comparable extraction cases were analyzed: Group I: serial extraction performed in the early mixed dentition followed by orthodontic treatment in the permanent dentition; group II: extractions as well as orthodontic treatment in the permanent dentition. The following conclusions were reached: 1. The treatment period with fixed appliances was highly significantly shorter in group I; however, the number of appointments was significantly higher and the total duration of treatment/observation time significantly longer. 2. In both groups the reduction in PAR score was either improved or greatly improved in all cases.

Adolescent↗

PubMed2000

The effects of non-identifiability on testing for detailed balance in aggregated Markov models for ion-channel gating.

Aggregated Markov models are a widely used tool to model patch clamp data measured from single ion channels. These channels must obey the principle of detailed balance in thermodynamic equilibrium; otherwise, the channel is driven by an external source of energy. We investigate the power of a likelihood ratio test for detailed balance for a number of data points which is in the order of magnitude of patch clamp experiments. We show that for certain models with nearly equal dwell times, a test for detailed balance suffers from a loss of power to detect violations of detailed balance which is due to the non-identifiability of the transition rates for models with equal dwell times.

Computer Simulation↗