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Biomedical subjects

K Schultz

Publications and source records attributed to K Schultz.

At least 37 records · Page 2Linked to original sources
PubMed1996

Ca(2+)-dependency of spinule plasticity at dendrites of retinal horizontal cells and its possible implication for the functional role of spinules.

Calcium is involved in many aspects of synaptic plasticity and we have analyzed its involvement in spinule dynamics at retinal horizontal cell dendrites. We show here that in particular the retraction of spinules is a Ca(2+)-dependent process. Inhibiting calmodulin or CaMKII, blocked the retraction that was also impaired in low calcium Ringer. Changes of the cytosolic Ca(2+)-concentration through depletion of internal Ca(2+)-stores were without effect. This suggested that Ca(2+)-influx during dark adaption and subsequent activation of CaMKII is an important step for spinule retraction. Voltage dependent Ca(2+)-channels were not responsible for the Ca(2+)-influx, rather Ca2+ leaking through alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate-gated channels. This suggested a close local link between AMPA/kainate receptors and CaMKII indicating a possible postsynaptic function of spinules. The distribution of bound, omega-shaped vesicles within the cone pedicles and its dependence on artificial depolarization further supported the idea of a postsynaptic function of spinules.

Adaptation, Ocular↗
PubMed1996

Perceptual responses to linear acceleration after spaceflight: human neurovestibular studies on SLS-2.

Perceptual responses of four astronauts were measured before and after a 14-day Spacelab Life Sciences-2 mission during interaural (y-axis) and rostrocaudal (z-axis) linear acceleration to measure adaptive changes in perceptual responses to inertial cues. In one test, subjects used a joystick to null a pseudorandom velocity disturbance. Postflight, two of three subjects showed a significantly enhanced ability to null linear self-motion in the y-axis and z-axis orientations. In another test, the subjects used a joystick to indicate their direction of motion during a series of low-acceleration steps. The postflight responses of three of the four subjects showed a significant increase in the response latency for both y-axis and z-axis orientations. In a third test, subjects were asked to track a stationary but unseen target with their eyes while they translated linearly in the dark. No significant changes were observed in the postflight responses. The observed changes, when present, may be due to a reinterpretation of inertial cues that are functionally adaptive for the microgravity environment but are not optimal for responses on Earth.

Acceleration↗
PubMed1996

Plasma and cerebrospinal fluid hyperinsulinism in asphyxiated piglets.

Insulin (I) plays a crucial role in the maturation of the perinatal brain, and it may also be involved in the pathogenesis of neonatal brain injuries. The aim of the present study was to reveal the effect of neonatal asphyxia on the regulation of I and glucose (G) metabolism in plasma and cerebrospinal fluid (CSF) in newborn piglets. The I concentrations were measured by radioimmunoassay, while the G levels were analyzed by the G oxidase method during three phases (basal, critical, recovery) of bilateral pneumothorax in newborn piglets. We observed a significant hyperinsulinism (p < 0.001) both in plasma and CSF and a mild hypoglycemia (p < 0.05) during the recovery period. Postasphyxial G infusion (1.1 M, 10 ml.kg-1) amplified the hyperinsulinism. The ICSF/plasma ratio (mean +/- SEM; n = 16) was decreasing during cardiovascular failure (0.09 +/- 0.02; NS) as compared with the initial value (0.12 +/- 0.04), then it returned to basal values by 60 min (0.14 +/- 0.04; NS), and increased significantly 180 min (0.40 +/- 0.14; p < 0.05) after resuscitation of the piglets. There was a similar increase in GCSF/plasma ratio in asphyxiated animals at the end of experiments (0.99 +/- 0.15 vs. initial 0.76 +/- 0.05; p < 0.05). In conclusion, neonatal asphyxia resulted in plasma and CSF hyperinsulinism which may alter hypoxic-ischemic cerebral damages.

Acid-Base Equilibrium↗
PubMed1995

Different composite regulatory elements direct expression of the human alpha subunit gene to pituitary and placenta.

To identify elements of the human alpha subunit gene necessary for cell-specific expression, we generated an array of block mutations spanning approximately 400 base pairs (bp) of promoter proximal region and examined them using transient transfection analysis in pituitary (alpha T3) and placental (BeWo) cell lines. Comparison of promoter activity in the two cell types revealed both common and unique elements required for transcription in pituitary and placenta. Two strong elements, the cyclic AMP response element (CRE) and the upstream regulatory element (URE), regulate expression of the alpha subunit gene in BeWo cells. In contrast, promoter activity in alpha T3 cells requires an array of weaker elements. These include the CREs, the URE, as well as two previously described elements, pituitary glycoprotein hormone basal element (PGBE) and gonadotrope-specific element (GSE), and two new elements we designated as the alpha basal elements 1 and 2 (alpha BE1 and alpha BE2). These new elements reside between -316 and -302 bp (alpha BE1) and -296 and -285 bp (alpha BE2) of the human alpha subunit promoter and bind distinct proteins designated alpha BP1 and alpha BP2, respectively. Southwestern blot analysis revealed that alpha BE1 specifically binds 54- and 56-kDa proteins. Additional studies disclosed several potential interactions between proteins that bind the CRE and proteins that occupy PGBE, alpha BE1, and alpha BE2, suggesting that gonadotrope-specific expression occurs through a unique composite regulatory element that includes components of the placenta-specific enhancer.

Animals↗
PubMed1995

Retraction of spinule-type neurites from carp retinal horizontal cell dendrites during dark adaptation involves the activation of Ca2+/calmodulin-dependent protein kinase II.

The formation of spinules at the terminal dendrites of retinal horizontal cells with the onset of light and their subsequent retraction during darkness is a remarkable example of synaptic plasticity where sensory experience modifies reversibly, and on a time scale of minutes the ultrastructure of synaptic connectivity. The signals and the subsequent intracellular cascades underlying the prominent morphological alterations are only partially understood. We show here that lowering the external calcium concentration did prevent dark- and AMPA-induced retraction of spinules in a eyecup preparation. Furthermore, spinule retraction was prevented in vivo by the injection of calmidazolium, an inhibitor of calmodulin, into the eyeball, and also by the injection of KN-62, an inhibitor of Ca2+/calmodulin-dependent protein kinase (CaMkII). We conclude that local Ca2+ influx through AMPA-gated channels followed by activation of CaMkII is an important step for spinule retraction during dark adaptation. The phosphorylation patterns of phosphoproteins derived from purified horizontal cells was affected by the inhibitors of calmodulin and CaMkII respectively. Some of the affected phosphoproteins appeared to be cytoskeleton-associated proteins, including GAP-43. Based on these observations, a putative scenario for the retraction of spinules is proposed.

Animals↗
PubMed1995

Activation of adenylate cyclase and phosphodiesterase inhibition enhance neutral endopeptidase activity in human endothelial cells.

Endothelial neutral endopeptidase (EC 3.4.24.11, NEP) contributes to the inactivation of vasoactive and inflammatory peptides such as f-Met-Leu-Phe, substance P, atrial natriuretic peptide, and bradykinin. The aim of the present study was to investigate the cellular regulation of NEP expression in human endothelial cells, focusing on the role of cyclic nucleotides and cellular phosphodiesterases (PDE). Activation of adenylate cyclase by forskolin or prostaglandin E1 (PGE1) induced an increase of NEP activity and NEP protein after 24 h of incubation. This effect was mimicked by two activators of protein kinase A, dibutyryl-cAMP and 8-bromo-cAMP. The nonspecific PDE inhibitor, 3-isobutyl-1-methylxanthine (200 microM), increased NEP activity up to 192%. The activator of guanylate cyclase, sodium nitroprusside (SNP), did not affect NEP activity but completely inhibited the 3-isobutyl-1-methylxanthine-mediated increase of NEP activity. The PDE-III inhibitors motapizone (100 microM) and enoximone (100 microM) enhanced NEP activity up to 188% and 213%, the PDE-IV inhibitor rolipram (3 microM) up to 162%, and the combined PDE-III/IV inhibitor zardaverine (1 microM) up to 176% of control values. The present data provide evidence for a cAMP-mediated increase of NEP activity in human endothelial cells.

Adenylyl Cyclases↗
PubMed1993

Ionotropic non-N-methyl-D-aspartate agonists induce retraction of dendritic spinules from retinal horizontal cells.

Horizontal cells invaginate the photoreceptors in the retina and form reciprocal synaptic connections in the cone pedicles. In fish retina the pattern of synaptic connections is plastic and modulated by the ambient light conditions. Numerous dendritic spinules protrude from the terminal horizontal-cell dendrites into the cone pedicle when the retina is light-adapted and are retracted during dark adaptation. The retraction of spinules can be induced during maintained illumination by an injection of the putative cone transmitter L-glutamate or its analogue kainic acid into the vitreous humor. The formation and the retraction of spinules have a time course of minutes. Activation of protein kinase C through phorbol esters initiates the formation of spinules, but the retraction has not yet been linked to a specific second messenger. Herein we report that physiological concentrations of the glutamate analogs quisqualic acid and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid induce retraction of spinules during maintained illumination. (+/-)-trans-1-Amino-1,3-cyclopentanedicarboxylic acid, an agonist for the metabotropic quisqualic acid receptor, was without effect on spinule retraction. N-Methyl-D-aspartate and L-2-amino-4-phosphonobutyric acid, agonists at other types of glutamate receptors, were also without any effect. The effects of the active agonists persisted when synaptic transmission was blocked. In the presence of the ionotropic quisqualate receptor antagonist 6-cyclo-7-nitro-quinoxaline-2,3-dione the effects of all active agonists were blocked. These results demonstrate that activation of ionotropic quisqualate receptors on the horizontal-cell membrane can induce dendritic spinule retraction, a process associated with dark adaptation.

Aminobutyrates↗
PubMed1993

Spectral and topographic analysis of EEG in schizophrenic patients.

The authors performed spectral analysis of electroencephalograms (EEG), recorded awake, with eyes closed, in 13 patients with schizophrenia and 9 age-matched individuals without psychiatric diagnosis. We tested several possible parameterizations of the data, and two data-reduction strategies; these yielded similar results. Comparison of the two groups revealed a relative increase in alpha frequency activity in the frontal regions in the patient group. The authors believe that this finding is consistent with data from neuropsychologic tests, metabolic imaging studies, and evoked potential studies that suggest impaired activation of frontal brain areas in patients with schizophrenia.

Adult↗
PubMed1993

Serum inhibitors precede the development of SAIDS.

Rhesus macaque monkeys infected with the simian immunodeficiency virus develop a syndrome mimicking AIDS in humans. We have demonstrated previously that sera from individuals infected with human immunodeficiency virus type 1 inhibit the proliferation of lymphocytes from healthy noninfected subjects and that this phenomenon is associated with the development of clinical AIDS. We have also shown that sera from monkeys infected with SIV also have such inhibitors. In this body of work, we attempted to document the onset of these inhibitors in relation to the time of SIV infection. Twenty rhesus macaques were injected with one of two tissue strains of SIV or media. Blood was drawn on a set schedule and the serum samples frozen at -70 degrees C. The animals were monitored and observed for up to 42 weeks. All test animals were autopsied. Sera from all the draws were assayed against the same populations of human peripheral blood mononuclear cells in the same experiment using suboptimal amounts of phytohemagglutinin (PHA). Sera from those animals that subsequently developed SAIDS were more likely to demonstrate serum inhibition. This inhibition could be seen as early as 8-10 weeks after infection. By week 14, the assay could differentiate animals into SAIDS or healthy groups with a sensitivity of 67% and a specificity of 89%.

Analysis of Variance↗
PubMed1992

[Double liver-kidney transplantation in the presence of a positive T cross-match].

Kidney transplantation, when performed across a positive T lymphocyte cross-match, is always followed by the occurrence of a hyperacute rejection. On the other hand, successful hepatic allografts have been reported under these same conditions. Furthermore, clinically and experimentally hepatic allograft has been reported to induce tolerance of other organs from the same donor. Thus, combined liver-kidney transplantation constitutes an ideal application of these immunological events. We report here the case of a sequential liver-kidney transplantation in which liver transplantation performed prior to kidney transplantation with an organ from the same donor induced kidney tolerance despite an initial positive T lymphocyte cross-match.

Adult↗
PubMed1992

Sera from simian immunodeficiency virus-infected rhesus macaques inhibit lymphocyte proliferation.

Rhesus macaque monkeys infected with the simian immunodeficiency virus (SIV) develop a syndrome mimicking acquired immunodeficiency syndrome (AIDS) in humans. We had demonstrated previously that sera from individuals infected with human immunodeficiency virus (HIV) inhibit the proliferation of lymphocytes from healthy noninfected subjects and that this phenomenon was associated with the development of clinical AIDS. Thus, we sought to determine whether sera from SIV-infected monkeys would also inhibit lymphocytes from healthy humans and SIV-negative rhesus monkeys. Sera from SIV-infected monkeys were compared with sera from uninfected animals and cultured with cells from healthy human volunteers or SIV-negative monkeys in the presence or absence of phytohemagglutinin (PHA). Cell proliferation was determined by measuring the incorporation of radiolabeled thymidine into cellular DNA. Sera from SIV-infected monkeys suppressed the proliferation of human and non-human primate lymphocytes. This activity appears to be similar to that described for sera from HIV-1-infected humans. Therefore, rhesus macaques infected with SIV provide a model for the study of serum inhibitory factors previously reported in AIDS patients.

Animals↗
PubMed1992

Neoplastic expression in murine cells induced by halogenated hydrocarbons.

The neoplastic expression in mouse embryo fibroblasts exposed to 1,2-dibromoethane and its chloroanalogue, 1,2-dichloroethane in vitro, was examined. Both substances are widely used as fumigants for carpet and upholstery, as gasoline additives, and as organic solvents. Both are known to be highly toxic, mutagenic, and carcinogenic agents. C3H10T1/2 cells treated with these haloalkanes exhibited altered morphology and were selected further by cloning in soft agar. Soft agar clones were found to induce a 100% multitumor occurrence in the nude mouse model. These results suggest that this pair of mutagens have altered the normal phenotype of mouse embryo cells, and these cells have become neoplastic. These neoplastic cell lines will be useful as an in vitro model to study the role of genetic changes in the transformation processes induced by halogenated hydrocarbons.

Animals↗
PubMed1992

Rapid detection of respiratory viruses by shell vial culture and direct staining by using pooled and individual monoclonal antibodies.

The Bartels respiratory virus panel detection kit is an indirect fluorescent-antibody (IFA) method that uses pooled and individual antisera for tissue culture confirmation of seven respiratory viruses. We evaluated these reagents for detecting viral antigen in shell vial cultures and by direct staining of cells from respiratory specimens. The isolation from 254 specimens of respiratory viruses in shell vial cultures compared with standard tube cultures was highly sensitive (94%) and specific (97.3%). The numbers of viral isolates detected in three consecutive years of testing with shell vial cultures were 68 of 254 (26.8%), 101 of 381 (26.5%), and 122 of 430 (28.4%). IFA direct staining of all 1,065 specimens resulted in 183 (17.2) being uninterpretable because of inadequate numbers of cells or interfering fluorescence. The sensitivity and specificity of the interpretable IFA direct stains in comparison with shell vial cultures were 85.9 and 87.1%, respectively. For detection of 881 adequate specimens, Bartels respiratory syncytial virus IFA direct staining compared with an Ortho Diagnostics Systems direct fluorescent-antibody test for respiratory syncytial virus RSV was highly sensitive (95.5%) and specific (97%). Shell vial cultures combined with Bartels IFA reagents are a rapid alternative to standard tube cultures. Bartels IFA direct staining with individual antisera provides useful same-day screening of respiratory specimens, but the antiserum pool was not effective in screening for positive specimens because of excessive amounts of nonspecific fluorescence.

Antibodies, Monoclonal↗
PubMed1991

Transient hyperinsulinism in asphyxiated newborn infants.

Hypoglycemia in birth asphyxiated infants is attributed to glycogen depletion. We observed three term AGA (Appropriate for Gestational Age) infants with birth asphyxia, who developed hyperinsulinemic hypoglycemia postnatally. All had inappropriately high serum insulin concentrations for their blood glucose levels, and needed glucose infusion rates of greater than 8 mg/kg/min for several days to maintain normoglycemia. All infants recovered spontaneously.

Asphyxia Neonatorum↗
PubMed1991

[Pain perception during simulated static work].

The purpose of this study was to determine the effect of current design recommendations (additional rest allowances) for static work on the development of temporary musculo-skeletal pains. The subjects were healthy, relatively fit young adults (16 men). Static work at 25% MVC was performed both in a commonly-used working posture and in a nontypical posture (overhead work). The ratios of work-to-rest corresponded to the ergonomical recommendations. Estimates of pain-perceptions concerning the neck, shoulders and back/trunk were recorded during the muscular exercise. The results show that under certain conditions (commonly-used working posture) the additional rest allowances render possible an exercise without musculoskeletal pains. During overhead work the development of temporary pain-perceptions is not inhibited by additional rest allowances. A revision of the current design recommendations for overhead work is suggested.

Adult↗
PubMed1991

[Perceived exertion during simulated static work].

The purpose of this study was to determine the effect of static work on the rating of perceived exertion (RPE). The subject were healthy, relatively fit young adults (16 men). Exercise was performed at 25% MVC both in a commonly-used work posture and in a non-typical working posture (overhead-work). Estimates of effort were recorded using the CR-20-Scale by Borg. A nonparametric analysis was carried out to examine the relationship between the level of static load and RPE. The results show that the level of static load is reflected in the RPE systematically. It is concluded that RPE measurements render possible comparative evaluation of strain by muscular static work demands.

Adult↗
PubMed1990

Kluyveromyces as a host for heterologous gene expression: expression and secretion of prochymosin.

We have developed the yeast Kluyveromyces lactis as a host organism for the production of the milk-clotting enzyme chymosin. In contrast to Saccharomyces cerevisiae, we found that this yeast is capable of the synthesis and secretion of fully active prochymosin. Various signal sequences could be used to efficiently direct the secretion of prochymosin in Kluyveromyces, but not in S. cerevisiae. We conclude that the efficient synthetic and secretory capacity of this heterologous protein is a property of the yeast Kluyveromyces. These results have led to the development of a large scale production process for chymosin.

Amino Acid Sequence↗