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Biomedical subjects

C Klein

Publications and source records attributed to C Klein.

At least 235 records · Page 13Linked to original sources

Contingent negative variation (CNV) and determinants of the post-imperative negative variation (PINV) in schizophrenic patients and healthy controls.

A slowly rising cortical potential shift with negative polarity following the imperative stimulus of a forewarned reaction time task, the 'post-imperative negative variation' (PINV), is regularly observed in schizophrenic patients but not in controls. The topography of the PINV suggests that it may originate in frontal cortical regions. We used a task designed to test two putative prefrontal cortical functions: working memory and processing of ambiguity. Nineteen patients with a chronic schizophrenic disorder and 19 control subjects matched for age, sex, and education participated in two experimental sessions. The EEG was recorded from frontal, central, temporal, and parietal leads over both hemispheres using a DC amplifier. PINV amplitudes were generally larger in patients than in controls. If the result of comparing physical features of the two successively presented stimuli (warning and imperative stimulus) was ambiguous rather than clear, an augmentation of the PINV amplitudes was seen in both groups. If this comparison required high rather than low involvement of working memory functions, PINV amplitudes were augmented in schizophrenic patients only. Scalp distribution of the PINV indicated a left-hemisphere fronto-central PINV maximum in patients, and a right-hemisphere predominance in controls, which was larger following ambiguous stimulus comparisons. These results suggest that ambiguity during the comparison of physical features of successively presented stimuli may be a general factor of the PINV in schizophrenic patients and healthy controls. Augmented involvement of working memory functions, presumably subserved by the prefrontal cortex, specifically affected the fronto-centrally predominant PINV in schizophrenic patients. This result is compatible with the hypothesis of prefrontal cortical dysfunctions in schizophrenia.

Adult↗

An uncleaved glycosylphosphatidylinositol signal mediates Ca(2+)-sensitive protein degradation.

Inv-gp80 is a chimeric protein which contains a signal for the attachment of a glycosylphosphatidylinositol (GPI) anchor. When expressed in Dictyostelium discoideum, this protein fails to become GPI anchored and is retained within the cell as an integral membrane protein. We have compared the subcellular localization and degradation of Inv-gp80 with that of its intracellular but soluble counterpart, Inv-gp80sc. Inv-gp80sc lacks the hydrophobic C-terminal 22 amino acids of Inv-gp80. The N-linked oligosaccharides of both Inv-gp80 and Inv-gp80sc remained sensitive to endoglycosidase H, and both proteins co-fractionated with endoplasmic reticulum marker enzymes on Percoll gradients. Under normal conditions, Inv-gp80 displayed a half-life (t 1/2) of 90 min, while Inv-gp80sc displayed a t 1/2 of 120 min. The degradation of both proteins required ATP, was inhibited by tosyl phenylalanylchloromethane (Tos-Phe-CH2Cl) and was insensitive to inhibitors of lysosomal function. While depletion of Ca2+ from the endoplasmic reticulum had no effect on the degradation of Inv-gp80sc, it stimulated the degradation of Inv-gp80. When the GPI anchor signal sequence of Inv-gp80 was replaced with the transmembrane domain of the interleukin-2 receptor, the degradation of the protein was no longer influenced by Ca2+ fluxes. The data suggest that while the GPI anchor sequence of Inv-gp80 does not contain determinants regulating the degradation of the protein under basal conditions, it targets Inv-gp80 for rapid degradation under conditions where Ca2+ is depleted from the endoplasmic reticulum.

Animals↗

Development of a surface acoustic wave immunosensor.

In this paper the first application of horizontal polarized surface acoustic waves (HP-SAW) in LiTaO3 for an immunosensor is presented. A SAW device with two paths, a sensitive path and a reference path operating in liquid at 345 MHz, is used as the sensor. Antigens and antibodies were both immunoglobulins. The antibodies were immobilized via protein A on the sensitive path with a mass density of 0.4 ng/mm2, as shown by ELISA measurements. A theoretical detection limit of approximately 33 pg and a high sensitivity of 110 kHz/(ng/mm2) could be derived from the experiments. High signal enhancement factors of 4.5 and 12 are achievable by gold colloid labeled antigens with colloid diameters of 5 and 10 nm, respectively. Specificity of the antibody was demonstrated by a preabsorption experiment. As a further antibody/antigen system the binding of the anti-human serum albumin (HSA) to HSA was examined.

Antibodies↗

Dual-energy X-ray absorptiometry for histologic bone sections.

In fundamental osteoporosis research precise and accurate assessment of the mineral quantity in histological bone sections is of particular importance when studying the local effects of implants releasing bone modulating agents. A potentially useful technique to estimate the bone mineral density (BMD) is dual-energy X-ray absorptiometry (DXA). A highly collimated (0.13 mm) Hologic 2000 with a line spacing and point resolution of 0.13 mm was used. The mineral content was measured in regions of 3.1 mm(2). A ceramic hydroxyapatite (CHA) phantom was developed as a reference standard. The phantom was made of a single-phase hydroxyapatite starting powder by compressing and sintering at 1000 degrees Celsius. The true density was 3.14 + or - 0.001 g/cm(3). The calcium/phosphorus ratio was close to the theoretical one of 1.67. The mean precision error expressed as the coefficient of variation (CV) of the mineral density (MD) measurements of the phantoms with thicknesses of 1, 2, and 3 mm was 0.2%. Embedded undecalcified alveolar bone sections of dogs (0.0015-1 mm in thickness) were scanned simultaneously with a phantom 1 mm in thickness. The precision error (CV) of the BMD measurements calculated by DXA for sections > or = 0.1 mm and with a BMD > or = 0.14 g/cm(2) was 0.81%. There was a linear relationship between the BMD calculated by DXA and the estimated BMD in the histological bone sections by means of the true density of the phantom. It is concluded that DXA using a standard CHA phantom is a precise and accurate method to measure MD changes as small as 1% in histological bone areas of 3.1 mm(2) provided that the loss or gain in BMD is > or = 0.14 g/cm(2).

Absorptiometry, Photon↗

Ataxia without telangiectasia masquerading as benign hereditary chorea.

We report a nonconsanguineous family in whom two (of three) sons developed isolated chorea in early childhood, suggesting a diagnosis of benign hereditary chorea (BHC). However, cerebellar ataxia and oculomotor apraxia, without telangiectasia, subsequently developed. Chromosome analysis showed increased radiosensitivity in both brothers and translocations in the younger one. We conclude that ataxia with chromosomal instability may masquerade as BHC in some patients.

Adolescent↗

Mandibular distraction osteogenesis as first step in the early treatment of severe dysgnathia in childhood.

The sole orthodontic treatment of severe dysgnathias in childhood often leads to unsatisfactory results. On the other hand, standard surgical procedures are very difficult and due to their high risks not practicable in early childhood. The distraction osteogenesis enables us to correct hypoplastic mandibles, so that secondary malformations of the midfacial complex can be avoided. During the operation the hypoplastic site of the mandible is osteotomized behind the last visible tooth bud and a bidirectional distractor is inserted. Following the principles of Ilizarov the new callus is lengthened gradually until the required length of the mandible has been achieved. Out of a total sample of 27 patients 3 case reports of young children are presented. The new surgical concept describes new treatment perspectives.

Adolescent↗

Nitric oxide inhibits the initiation of cAMP pulsing in D. discoideum without altering receptor-activated adenylate cyclase.

We have previously demonstrated that nitric oxide (NO)-releasing compounds inhibit the differentiation and aggregation of D. discoideum cells (Tao et al., FEBS Lett. 314:49, 1992). In the present study, we demonstrate that treatment of intact cells with NO-releasing compounds inhibits their production of cAMP. This occurred even though the developmental expression of the known components necessary for proper cAMP signalling was unaffected. The inhibitory effects of NO-releasing compounds on cell aggregation were reversed by stimulating cells with pulses of cAMP. In response to an applied cAMP pulse, NO-treated cells displayed a normal signal relay response, indicating that receptor-activated adenylate cyclase activity was not inhibited by NO. This also argues that the processes of desensitization/resensitization occur normally in NO-treated cells. The data indicate that the developmental expression of the components of the chemotactic signalling occurs independently of cAMP production and that the activity of the adenylate cyclase may be regulated by cAMP/ cAMP-receptor independent pathway. These findings indicate both a new mechanism for the regulation of adenylate cyclase in D. discoideum and a novel means by which NO can function to alter cellular processes.

Adenylyl Cyclases↗

Effect of ciprofloxacin on the pharmacokinetics and pharmacodynamics of warfarin.

To determine if ciprofloxacin therapy alters the response to warfarin treatment, 36 adult patients attending three university-affiliated outpatient anticoagulation clinics randomly received a 12-day course of ciprofloxacin (750 mg twice daily) and a 12-day course of placebo; each course was separated by a 2-week washout period. Prothrombin times (PTs), concentrations of S-warfarin and R-warfarin (the isomers of warfarin), and concentrations of clotting factors II and VII were determined three times weekly for 9 weeks. By day 12 of ciprofloxacin therapy, concentrations of S-warfarin remained unchanged compared with those after placebo therapy, but R-warfarin concentrations increased significantly (1.15 times those after placebo therapy; P = .001); concentrations of clotting factors II and VII decreased (0.903 and 0.872 times those after placebo therapy, respectively, P < or = .020). The mean PT ratio after 12 days of ciprofloxacin therapy increased slightly (1.032 times that after placebo therapy; P = .057), but no patient had bleeding or a change in PT that required alteration in warfarin or ciprofloxacin therapy. We conclude that warfarin therapy is not a contraindication to the use of ciprofloxacin.

Adult↗

Correction of mandibular hypoplasia by means of bidirectional callus distraction.

The method of gradual callus distraction proved to be very useful in augmenting hypoplastic mandibles. When performing our first series using a unidirectional distractor, we faced some problems in determining the direction of lengthening. Moreover, postoperative adjustments were not possible. On the basis of this experience, we developed a bidirectional lengthening device consisting of two limbs and a variable angulation piece. This allows distinct control of the vertical and horizontal components of the distraction. The method proved effective and reliable in 18 patients with various degrees of mandibular hypoplasia. The median follow-up period was 10 months (range, 1-19 months).

Adolescent↗

The impact of performance uncertainty on the postimperative negative variation.

In a delayed matching-to-sample task, the impact of clear or ambiguous go versus clear no-go signals on the post-imperative negative variation (PINV) was examined in 11 patients with a chronic schizophrenic disorder (DSM-III-R) and in a control group of 13 healthy subjects matched to the patient sample by age, sex, and education. Size and spatial position of a visual S2 had to be matched to one of two visual patterns in the S1 presented 4 s earlier. In 96 trials, the S2 was identical in size with one of the two patterns of S1 (clear matching). These trials varied pseudorandomly, with 60 trials in which the S2 was of intermediate size. On a randomly interspersed additional 48 trials, an S2 differing in color and shape signaled no-go. The electroencephalogram was recorded from Fz, Cz, Pz, F3, F4, C3, C4, P3, and P4. Although groups did not differ in contingent negative variation amplitude, the PINV was generally more pronounced in patients than in controls. In both groups, ambiguity of the to-be-matched S2 produced larger PINV amplitudes; the no-go signal elicited only a small PINV. Differential effects of ambiguity and no-go on PINV amplitude and its scalp distribution suggest that "performance" and "action" uncertainty contribute to PINV generation and that thresholds for both effects are reduced in schizophrenics.

Acoustic Stimulation↗

Dual X-ray absorptiometry for alveolar bone: precision of peri-implant mineral measurements ex vivo.

The precision of measurements of minor mineral changes in alveolar bone mineral content (ABMC) and alveolar bone mineral density (ABMD) on implant surfaces was determined in small regions (0.03 +/- 0.005 cm2) using dual X-ray absorptiometry (DXA). Dog hemimandibles with alveolar processes containing 17 implants were studied ex vivo. The precision was expressed as the coefficient of variation in percent (c.v. %). The ultra-high resolution protocol was applied to the mesial, distal and apical subregions of each implant. The line spacing was 0.0254 cm and the point resolution was 0.0127 cm. The mean c.v. (%) +/- s.d. for the ABMC in the mesial, distal and apical regions were 0.42 +/- 17, 0.47 +/- 0.21 and 0.48 +/- 0.18, respectively. For the ABMD these values were 0.42 +/- 0.16, 0.47 +/- 0.19 and 0.48 +/- 0.16. For each region approximately 68% of the 17 c.v. values were distributed within 1 s.d. from the mean c.v. These results indicate that measurements are highly reproducible (better than 0.48%) and that there are no differences in precision between several peri-implant regions. Changes as small as 0.85% in ABMC and ABMD in small areas adjacent to implant surfaces are measurable with a confidence level of 95%. Therefore the DXA technique will be expedient for our research evaluating the efficacy of the ceramic hydroxyapatite implant releasing agents affecting or inducing alveolar bone- and root cementum-like materials on its surface.

Absorptiometry, Photon↗

Novel mechanisms of Escherichia coli succinyl-coenzyme A synthetase regulation.

Low concentrations of ADP are shown to increase the rate of phosphoenzyme formation of E. coli succinyl-coenzyme A (CoA) synthetase (SCS) without altering the fraction of phosphorylated enzyme. This is true when either ATP or succinyl-CoA and Pi are used to phosphorylate the enzyme. The stimulatory effect of ADP is not altered by sample dilution, is retained upon partial purification of the enzyme, and reflects the binding of ADP to a site other than the catalytic site. GDP also alters the phosphorylation of the E. coli SCS but does so primarily by enhancing the level of the phosphoenzyme and only when ATP is used as the phosphate donor. GDP appears to function by neutralizing the action of a specific inhibitory protein. This inhibitor of SCS allows for interconversion of succinate and succinyl-CoA in a manner dissociated from changes in ATP-ADP metabolism. These previously unidentified and varied mechanisms by which SCS is regulated focus attention on this enzyme as an important control point in determining the cell's potential to meet its metabolic demands.

Adenosine Diphosphate↗

Yeast alpha mating factor structure-activity relationship derived from genetically selected peptide agonists and antagonists of Ste2p.

alpha-Factor, a 13-amino-acid pheromone secreted by haploid alpha cells of Saccharomyces cerevisiae, binds to Ste2p, a seven-transmembrane, G-protein-coupled receptor present on haploid alpha cells, to activate a signal transduction pathway required for conjugation and mating. To determine the structural requirements for alpha-factor activity, we developed a genetic screen to identify from random and semirandom libraries novel peptides that function as agonists or antagonists of Ste2p. The selection scheme was based on autocrine strains constructed to secrete random peptides and respond by growth to those that were either agonists or antagonists of Ste2p. Analysis of a number of peptides obtained by this selection procedure indicates that Trp1, Trp3, Pro8, and Gly9 are important for agonist activity specifically. His2, Leu4, Leu6, Pro10, a hydrophobic residue 12, and an aromatic residue 13 are important for both agonist and antagonist activity. Our results also show that activation of Ste2p can be achieved with novel, unanticipated combinations of amino acids. Finally, the results suggest the utility of this selection scheme for identifying novel ligands for mammalian G-protein-coupled receptors heterologously expressed in S. cerevisiae.

Amino Acid Sequence↗

Progressive deterioration of brainstem auditory evoked potentials in Creutzfeldt-Jakob disease: clinical and electroencephalographic correlation.

Brainstem auditory evoked potentials (BAEP) were recorded and correlated with the clinical and electroencephalographic (EEG) findings in three verified cases of Creutzfeldt-Jakob disease (CJD). In contrast to previous reports, there was progressive deterioration of the BAEPs, through initial asymmetry of wave latencies to abnormal wave morphology, and increased interpeak latencies. Consequently, in two of the patients, disorganization of the wave pattern and generalized conduction-time slowing appeared by the time there was a fully developed clinical picture of CJD with periodic EEG waves. In the third, clinically mild CJD, asymmetry of wave latencies in the BAEP emerged, correlating with the appearance of periodicity on EEG. Our findings are consistent with the late, progressive involvement of the brainstem by the pathological process in CJD.

Brain Death↗

Posterior fossa lesions associated with neuropsychiatric symptomatology.

We reviewed 7 cases with posterior fossa structural abnormalities (3 tumors, 2 megacisterna magna and 2 Dandy-Walker syndrome) presenting with neuropsychiatric symptomatology. Derangement in the balance of dopamine, serotonin and noradrenergic networks has been implicated in the pathogenesis of schizophrenia, affective and even personality disorders. Disruption of the cerebellar output to mesial dopaminergic areas, locus coeruleus and raphe nuclei, or deafferentation of the thalamolimbic circuits by a cerebellar lesion may lead to behavioral changes. Seven patients (pts) (comprising 4 men and 3 women with mean age 22 years) were diagnosed as suffering from psychosis (2 pts), major depression (1 pt), personality disorders (2 pts) and somatoform disorders (2 pts) (DSM-IV criteria). Brain CT scan (7 pts) and MRI (4 pts) revealed tumors of the posterior fossa (2 pts), megacisterna magna (2 pts) and Dandy-Walker variant (2 pts). In one patient a IVth ventricle tumor was removed in childhood.

Adult↗