Showing papers by "University of Cologne published in 1992"

A cellular automaton model for freeway traffic

Abstract: We introduce a stochastic discrete automaton model to simulate freeway traffic. Monte-Carlo simulations of the model show a transition from laminar traffic flow to start-stop- waves with increasing vehicle density, as is observed in real freeway traffic. For special cases analytical results can be obtained.

Structure, expression, and functional analysis of a Na(+)-dependent glutamate/aspartate transporter from rat brain.

Abstract: Transport systems specific for L-glutamate and L-aspartate play an important role in the termination of neurotransmitter signals at excitatory synapses. We describe here the structure and function of a 66-kDa glycoprotein that was purified from rat brain and identified as an L-glutamate/L-aspartate transporter (GLAST). A GLAST-specific cDNA clone was isolated from a rat brain cDNA library. The cDNA insert encodes a polypeptide with 543 amino acid residues (59,697 Da). The amino acid sequence of GLAST suggests a distinctive structure and membrane topology, with some conserved motifs also present in prokaryotic glutamate transporters. The transporter function has been verified by amino acid uptake studies in the Xenopus laevis oocyte system. GLAST is specific for L-glutamate and L-aspartate, shows strict dependence on Na+ ions, and is inhibited by DL-threo-3-hydroxy-aspartate. In situ hybridization reveals a strikingly high density of GLAST mRNA in the Purkinje cell layer of cerebellum, presumably in the Bergmann glia cells, and a less dense distribution throughout the cerebrum. These data suggest that GLAST may be involved in the regulation of neurotransmitter concentration in central nervous system.

breathless, a Drosophila FGF receptor homolog, is essential for migration of tracheal and specific midline glial cells.

Abstract: A Drosophila homolog of the fibroblast growth factor (FGF) receptor was isolated and structurally characterized. After EMS mutagenesis or imprecise excisions of marked P elements inserted upstream to the gene, a phenotypic series of mutations in the locus was isolated. The mutants exhibit defects in the two embryonic tissues in which the receptor is expressed: the tracheal system and the midline. The tracheal cells fail to migrate in severe mutants and remain within the tracheal pits. Hypomorphic alleles exhibit partial migration of all tracheal branches; thus, the locus was termed breathless (btl). In the midline of the mutant embryos, the posterior pair of midline glial cells begins to migrate anteriorly, but fails to reach the posterior commissure. Abnormalities in cell migration appear to be a common denominator for the btl defects in these two disparate tissues. In hypomorphic mutants the cells exhibit partial migration but follow the normal tracts, suggesting that the presence of this receptor is essential for the ability of the migrating cells to recognize external guiding cues.

Targeted disruption of µ chain membrane exon causes loss of heavy-chain allelic exclusion

Abstract: BURNET'S clonal selection theory1 suggests that each B lymphocyte is committed to a single antibody specificity. This is achieved by a programme of somatic rearrangements of the gene segments encoding antibody variable (V) regions, in the course of B-cell development2,3. Evidence from immunoglobulin-transgenic mice and immunoglobulin-gene-transfected transformed pre-B cells suggests that the membrane form of the immunoglobulin heavy (H) chain of class µ (µm), expressed from a rearranged H-chain (IgH) locus, may signal allelic exclusion of the homologous IgH locus in the cell4–6 and initiation of light (L)-chain gene rearrangement in the Ig/c loci6. We report here that targeted disruption of the membrane exon of the µ chain indeed results in the loss of H-chain allelic exclusion. But, some K chain gene rearrangement is still observed in the absence of µm expression.

Preclinical Cushing's syndrome in adrenal "incidentalomas": comparison with adrenal Cushing's syndrome.

Abstract: Adrenal tumors are usually diagnosed by clinical symptoms of hormone excess. The increasing use of ultrasound and computed tomography results in the detection of a substantial number of incidentally discovered adrenal tumors. Most of these tumors are nonfunctional adrenocortical adenomas, but a few cases of subclinical cortisol production in “incidentalomas” have been reported. We investigated prospectively the prevalence of autonomous cortisol production in 68 patients (44 females and 24 males, aged 25-90 yr) with adrenal incidentalomas at our institution. As a screening procedure all patients with incidentalomas underwent an overnight dexamethasone suppression test (1 mg). Patients who failed to suppress serum cortisol below 140 nmol/L (5 pg/dL) underwent more comprehensive studies (prolonged dexamethasone suppression test, determination of the diurnal rhythm of cortisol secretion in saliva, and CRH stimulation test). Eight patients (12% of all patients with incidentalomas; 5 females and 3 males, aged 25-71 yr) were finally identified as having cortisol-producing tumors, and the findings in these patients were compared with those of overt Cushina’s syndrome in 8 uatients (8 females. awd 26-50 yr) suffering from coriisoi-producing adrenal adenomas. The tumor size of patients with cortisol-producing incidentalomas ranged from 2-5 cm. No specific signs and symptoms of hypercortisolism were present, but arterial hypertension (seven of eight subjects), diffuse obesity (four of eight subjects), and noninsulin-dependent diabetes mellitus (NIDDM; two of eight subjects) were frequently observed. Baseline cortisol levels were in the normal to upper normal range, whereas baseline ACTH levels were suppressed in five of the eight patients. In none of the patients was serum cortisol suppressible by low dose or high dose dexamethasone. The ACTH and cortisol responses to CRH were normal in two, blunted in one, and suppressed in four patients. Unilateral adrenalectomy was performed in seven patients and resulted in temporary adrenal insufficiency in four of them. After surgery, improvement of arterial hypertension, a permanent weight loss in obese subjects, and a better metabolic control of NIDDM were noted in the majority of patients. The following conclusions were reached. Incidentally diagnosed adrenal tumors with pathological cortisol secretion in otherwise clinically asymptomatic patients are more frequently observed than previously assumed. Adrenocortical insufficiency is a major risk in these patients after adrenalectomy. After surgery, hypertension, obesity, and NIDDM may improve. Patients with asymptomatic adrenal incidentalomas, therefore, should be screened for cortisol production by means of an overnight dexamethasone suppression test. (J Clin Endocrinol Metab 75: 826-832, 1992)

The dentate gyrus as a regulated gate for the propagation of epileptiform activity.

Abstract: Properties of the interaction between the entorhinal cortex (EC) and the dentate gyrus were studied in a combined EC hippocampal slice preparation in which most of the fiber connectivity within this structure is intact. Epileptiform activity was induced by lowering extracellular Mg2+ concentration. This caused short recurrent discharges in the hippocampus while seizure-like events (SLE) slowly spread from the site of initiation to neighboring areas. At the end of a SLE, the EC, the subiculum and the neocortical area Te2 discharged in synchrony. This activity could develop into a state of recurrent tonic discharges highly synchronized between the different areas. These discharges were insensitive to treatment with currently available antiepileptic drugs. Although the SLE increased neuronal firing and extracellular potassium concentration in the dentate gyrus, this activity had only moderate effects on the activity generated in areas CA3 and CA1. Removing GABAergic inhibition with baclofen and bicuculline caused the spread of SLE from the EC to the dentate gyrus. Slow inhibitory postsynaptic potentials and intrinsic properties of dentate gyrus granule cells appear to underlie the filtering function of the dentate gyrus.

Human brain tumors: spectral patterns detected with localized H-1 MR spectroscopy.

Abstract: Image-guided localized proton magnetic resonance (MR) spectroscopy of intracranial tumors was performed to correlate spectral patterns and histologic findings. Thirty-six patients were examined prior to any specific treatment. Evaluation based on signal intensity ratios showed that all tumor spectra differed from spectra of healthy brain tissue. Ratios of creatine to choline-containing compounds (Cr/Cho) and nitrogen acetyl-aspartate to Cho (NAA/Cho) were reduced significantly in all tumor spectra compared with spectra of normal tissue in contralateral brain hemispheres (P less than .005). Noncerebral tumors typically showed a vanishing or missing NAA signal, strongly reduced Cr signal, and additional signals, assigned to alanine in meningiomas and lipids in metastases. In contrast, 11 gliomas of grades 2 and 3 exhibited NAA/Cho ratios and Cr/Cho ratios that were less than normal but that were significantly larger (P less than .01) than corresponding values in eight meningiomas. Ten glioblastomas displaye...

Paramagnetic Meissner effect in Bi high-temperature superconductors.

Abstract: For certain ceramic samples of the Bi-based high-temperture superconductors, the dc-field-cooling signal becomes paramagnetic in fields below a few 100 mOe This effect correlates with an anomaly in the low-field microwave absorption The data are consistent with orbital paramagnetic moments due to the appearance of spontaneous supercurrents in fields smaller than the lower critical field ${\mathit{H}}_{\mathit{c}1\mathit{a}}$ parallel to the CuO planes

Proteolipid protein (PLP) of CNS myelin: positions of free, disulfide-bonded, and fatty acid thioester-linked cysteine residues and implications for the membrane topology of PLP

Abstract: Proteolipid protein (PLP), the major integral membrane protein of central nervous system myelin, contains 14 cysteine residues within its 276-residue polypeptide chain. We determined the state of all cysteine residues and localized four of them as free thiols at positions 24, 32, 34, and 168. Four cysteines are connected by disulfide bonds: Cys200-Cys219 and Cys183-Cys227. The remaining six cysteine residues at positions 5,6,9, 108, 138, and 140 are modified by long-chain fatty acids, mainly palmitic acid, in thioester linkage. The extreme hydrophobicity of PLP can therefore be explained by two structural features: a composition of approximately 50% apolar amino acid residues and a high degree of fatty acid acylation. A differential fluorescent-labeling technique was developed for the structural studies: the cysteine residues belonging to one of the three states were derivatized by N-(iodoacetylaminoethy1)-5-naphthylamine- 1 -sulfonic acid (I-AEDANS) either directly (a), after thioester cleavage with hydroxylamine (b), or after disulfide cleavage with dithiothreitol (c). The protein was then proteolytically digested with thermolysin, and the labeled peptides were isolated by reversed-phase HPLC followed by sequence analysis. The results were further confirmed by determination of the fatty acid to protein stoichiometry. The structural data not only demand the revision of our concept of the membrane topology of PLP but will also promote more sophisticated studies on the mechanism of myelination and new functions of PLP.

Dynamics of Interface Depinning in a Disordered Medium

Abstract: The motion of an interface in a disordered medium driven by a constant force is one of the paradigms of condensed matter physics. Well known examples are domain walls in random magnets1 and interfaces between two immiscible fluids pushed through a porous medium2. Closely related problems include impurity pinning in type-II superconductors3 and in charge-density waves (CDWs)4. Despite the importance of these problems, significant progress has been made only recently by Nattermann et al. for interface motion5 (see also6) and by Narayan and Fisher for CDWs7.

Seven genes of the Enhancer of split complex of Drosophila melanogaster encode helix-loop-helix proteins.

Abstract: Enhancer of split [E(spl)] is one of the neurogenic loci of Drosophila and, as such, is required for normal segregation of neural and epidermal cell progenitors. Genetic observations indicate that the E(spl) locus is in fact a gene complex comprising a cluster of related genes and that other genes of the region are also required for normal early neurogenesis. Three of the genes of the complex were known to encode helix-loop-helix (HLH) proteins and to be transcribed in nearly identical patterns. Here, we show that four other genes in the vicinity also encode HLH proteins and, during neuroblast segregation, three of them are expressed in the same pattern. We show by germ-line transformation that these three genes are also necessary to allow epidermal development of the neuroectodermal cells.

On superluminal barrier traversal

Abstract: We report on microwave measurements of barrier traversal time of electromagnetic wave packets in an undersized waveguide. This time was significantly shorter than the ratio L/c, with L the barrier length and c the velocity of light in vacuum. Consequently the transport velocity for the wave packet inside the barrier has to be superluminal, i.e. larger than c.

Interaction of BiP with newly synthesized immunoglobulin light chain molecules: cycles of sequential binding and release.

Abstract: Here we show that not only transport defective but all immunoglobulin light chains interact with BiP. Association of BiP with its ligand takes place during or shortly after translation of the light chains. The biological half life of the BiP-light chain complex depends on the fate of the light chains. Light chains which are secreted interact with BiP for only a very short time. In contrast, the complex is biologically more stable in cells which do not secrete their L chains. In these cells, dissociation from BiP correlates with the biological half life of the L chains arguing for a degradation pathway in the endoplasmic reticulum. Instead of being degraded in association with its ligand, BiP is released from the complex and binds to newly synthesized polypeptides. These results support the notion that both H and L chains require the chaperoning function of BiP before or during the process of antibody assembly.

Groundstate properties of a generalized VBS-model

Abstract: We study a generalized “q-deformed” VBS-model. This is a spin-1 quantum antiferromagnet with nearest neighbour interaction on a linear chain. The exact grounstate is determined in the form of a matrix-product of individual site-contributions. All relevant groundstate properties are calculated. The groundstate is unique, it has a finite gap to the excitations, and correlations decay exponentially. Thus the model has all the properties described by Haldane to be generic for certain quantum antiferromagnets with integral spin.

Carpholite, sudoite, and chloritoid in low-grade high-pressure metapelites from Crete and the Peloponnese, Greece

Abstract: In the high-pressure metamorphic Phyllite-Quartzite Unit of Crete and the Peloponnese, aluminous metasediments contain assemblages with Fe-Mg-carpholite, sudoite, chloritoid, pyrophyllite, chlorite, garnet, white mica and quartz. Variations of parageneses and mineral reactions in response to varying pressure, temperature and activity of H 2 O have been studied in detail. In Eastern Crete (≃300 ° C, 8 kbar), metapelites with high Mg/Fe 2+ are characterized by sudoite-bearing assemblages with chlorite or pyrophyllite. In rocks with low Mg/Fe 2+ , chlorite+pyrophyllite occur instead, suggesting the (continuous) reaction sudoite+quartz=chlorite+pyrophyllite+H 2 O. Additional carpholite rarely occurs in chlorite-pyrophyllite schists, probably through the hydration reaction chlorite+pyrophyllite+H 2 O=carpholite+quartz. Progress of this reaction requires relatively high a H2O , otherwise chlorite+pyrophyllite persist. In Central Crete (≃350 ° C, 9 kbar), the paragenesis chlorite+pyrophylite is no longer stable and chloritoid appears as a widespread rock-forming mineral, occasionally associated with carpholite, through the reactions carpholite=chloritoid+quartz+H 2 O, chlorite+pyrophyllite+I2O=chloritoid+carpholite+quartz. As in Eastern Crete, reactions involving carpholite proceed only in the case of relatively high a H2O ; the estimated values range between 1.0 and 0.7. This variability of H2O is reflected in AFM diagrams by the compositional shift of the three-phase assemblages carpholite-chloritoid-pyrophyllite and carpholite-chloritoid-chlorite. At lower a H2O , probably the normal case inCrete, no carpholite appears and chloritoid directly forms after chlorite+pyrophyllite=chloritoid+quartz+H 2 O. In this case, no minerals or parageneses diagnostic for high-P/low-T metamorphism appear. The same parageneses as in Central Crete have been observed in Western Crete (400 ° C, 10 kbar) and in the Peloponnese (≃450 ° C, 17 kbar), but with carpholites richer in Mg. For these rocks, AFM three-phase parageneses show fixed mineral compositions, suggesting equilibrium with a hydrous fluid phase of constant composition. The highest grade of metamorphic evolution of metapelites from the Phyllite-Quartzite Unit is reflected by the appearance of almandine-rich garnet in the Peloponnese

Free energy and correlation lengths of quantum chains related to restricted solid-on-solid lattice models†

Abstract: An approach is presented for calculating the free energy as well as the correlation lengths of integrable quantum chains at arbitrary finite temperatures. The method is applied to critical Hamiltonians related to restricted solid-on-olid models comprising the hierarchy by Andrews, Baxter and Forrester, and generalizations hereof by the fusion procedure. The derived non-linear integral equations can be studied analytically in the low-temperature and high-temperature limits. The central charges and all primary conformal weights are obtained for the generalized minimal unitary series of conformal field theory and the Z N parafermion theories. Thus an extension of the thermodynamic Bethe Ansatz is realized which recently has been speculated on in the literature

Adverse Effects of Systemic Opioid Analgesics

Abstract: Adverse effects of opioids are multiple. They are most often receptor-mediated and inseparable from their desired effects. The most severe mishaps with opioids are related to their respiratory depressant effect, which is widely influenced by factors such as pain, previous opioid experience and awareness. Other relevant central nervous system effects of opioids include cough suppression, nausea and vomiting, rigidity, pruritus and miosis. The cardiovascular adverse effects of opioids are mainly related to histamine release and differ widely between agonists and agonist-antagonists. Gastrointestinal effects such as constipation, reflux and spasms of the bile duct are well described. Adverse effects on endocrine, immunological and haematological functions are possible, while allergic reactions are extremely rare. The adverse effects of long term use are overestimated. Systemic toxicity is negligible and development of tolerance is minimal while treating pain. In the clinical setting of pain control, addiction and withdrawal do not pose significant problems. Nevertheless, the possible effects of opioids on the unborn child should always be considered. Overall, opioids show a good record of safety. Their use should not be unduly limited by unfounded fears of adverse effects, but these effects should be avoided by anticipation and prevention.

Laser surgery for the treatment of larynx carcinomas: indications, techniques, and preliminary results.

Abstract: The authors have developed four different types of endolaryngeal laser resections for the treatment of larynx carcinomas. These new techniques are based on traditional concepts employed in partial larynx resections. From 1986 onward, 110 patients with laryngeal cancers were treated by endoscopic laser surgery. One hundred six patients were operated on for cure and 4 for palliation. In 9 cases of T3 tumor, complete removal of the tumor was not possible, requiring total laryngectomy. In all T2 cancers of the glottis and subglottis (n = 36), a total resection was possible. Additional staged neck dissection was performed in 16 cases, and postoperative radiotherapy in 10 cases. Follow-up investigations of the patients treated for cure (n = 106) cover a period of 3 to 42 months (mean, 22 months). These revealed 6 recurrences in the larynx, which were treated by laryngectomy. Recurrences in the cervical nodes were seen in 2 patients following resection of a supraglottic tumor and a subglottic tumor, respectively. Seven patients could not be followed up, 4 patients died of intercurrent disease, and 87 patients are alive and free of tumor. At present the number of recurrences and the rate of survival show no significant difference from those previously reported after conventional surgery. The phonatory function is not always predictable and still remains to be investigated. The authors believe that laser surgery may obviate the need for total laryngectomies in selected cases of laryngeal cancer, especially in T2 tumors. However, T3 tumors should not be treated by endolaryngeal laser surgery.

Slow and fast transient potassium currents in cultured rat hippocampal cells.

Abstract: 1. Potassium currents have been recorded from rat hippocampal neurons in dissociated cultures prepared at E17-E19. Currents were studied with the whole-cell version of the patch clamp method. The kinetics and pharmacological properties of two transient outward currents have been characterized. 2. Most of the recordings have been done in cells which had been in culture 10-18 days. Both a fast and a slow transient current could be elicited. A subtraction procedure was used to isolate the fast transient current. The fast transient current decayed monoexponentially with a time constant of about 10 ms. The slow transient current decayed with two time constants in the order of 500 ms and of 3.4 s. The reversal potential of the slow current shifted by 54 mV for a tenfold change in extracellular potassium concentration. 3. Studies on the removal of inactivation for the two currents revealed time constants of 29 and 107 ms for the fast and slow transient current, respectively. 4. The steady-state inactivation properties of the fast transient current were determined by studying the current with a fixed depolarizing command of -10 mV and varying pre-pulse amplitudes from a holding potential of -50 mV. The inactivation curve could be fitted with a Boltzmann equation. Half-maximal inactivation occurred at -81 mV. The steady-state activation properties of the fast transient current were determined by varying the depolarizing voltage commands following a fixed pre-pulse to -110 mV. The threshold for activation was between -70 and -60 mV. Half-maximal activation was reached at -19 mV. 5. The steady-state inactivation properties of the slow transient current were determined by studying the current elicited by varying the hyperpolarizing voltage steps from a holding potential of 0 mV. The inactivation curve could be fitted with a Boltzmann equation. Half-maximal inactivation was obtained at -61 mV. The steady-state activation properties were determined in a manner similar to the fast current. The threshold for activation was between -40 and -30 mV. 6. The slow transient current was not inactivated immediately when the conditioning pre-pulse was stopped. The rate of current decay increased with stimulus frequency. 7. Both transient currents were sensitive to 4-aminopyridine (4-AP). The fast transient current was blocked completely by 5 mM provided a pre-pulse of 1 s to -110 mV was employed. The slow transient current was already depressed by 4-AP applied in the 100 microM range but could never be blocked completely.(ABSTRACT TRUNCATED AT 400 WORDS)

Hypoxia-induced functional alterations in adult rat neocortex.

Abstract: 1. Brief periods of hypoxia (2-7 min) were induced in rat neocortical slices maintained in an interface-type recording chamber at 34-35 degrees C by changing the aerating gas from 95% O2-5% CO2 to 95% N2-5% CO2. Field potential (FP) and intracellular recordings were obtained in layers II/III of primary somatosensory cortex. Intracellular injection of biocytin revealed the characteristic morphology of supragranular spiny pyramidal neurons. 2. Excitatory synaptic transmission reversibly decreased by 45% as estimated from FP responses to orthodromic stimulation of the underlying white matter/layer VI. Excitatory postsynaptic potentials (EPSPs) were suppressed by 36% in amplitude and recovered within 2-3 min after reoxygenation. During the recovery period, EPSPs showed a reversible increase in duration by 72%. 3. Inhibitory synaptic transmission was completely blocked as determined in FP responses with a paired-pulse inhibition protocol. The fast inhibitory postsynaptic potential (IPSP) declined by 58% during hypoxia. The long-lasting IPSP was suppressed by 75% and showed incomplete recovery. During hypoxia, the amplitude of both IPSPs was significantly more strongly suppressed than the EPSP. 4. In 40% of the cells, hypoxia induced an early anoxic hyperpolarization with a reversal potential of E = -80.8 mV, followed by a postanoxic hyperpolarization (E = -89.4 mV). In a second group of cells (37%), a gradual anoxic depolarization with E = -57.5 mV was observed instead of an early hyperpolarization. In both groups of cells, the anoxic response was associated with a marked decrease in input resistance, by 42 and 31%, respectively. 5. The spike discharge frequency was reversibly suppressed by 71% during hypoxia. A transient hyperexcitability accompanied with a rise in input resistance and discharge rate was observed in 38% of the cells on reoxygenation. 6. The reversal potential of the anoxic hyperpolarization was unaffected by tetrodotoxin (TTX) but was significantly altered by application of the ATP-sensitive K+ channel (KATP) blocker gliquidone. Application of gliquidone additionally resulted in a significantly smaller hypoxia-induced decline in paired-pulse inhibition. 7. Increases in tissue high-energy phosphates induced by preincubating the slices in 25 mM creatine for greater than 2 h had a pronounced protective effect on excitatory and inhibitory synaptic transmission. 8. These data suggest a selective vulnerability of the neocortical inhibitory system during hypoxia. Our results further indicate that hypoxia activates a pre- and postsynaptic KATP conductance because of the decline in intracellular ATP.

The Enhancer of split complex and adjacent genes in the 96F region of Drosophila melanogaster are required for segregation of neural and epidermal progenitor cells.

Abstract: The Enhancer of split complex [E(spl)-C] of Drosophila melanogaster is located in the 96F region of the third chromosome and comprises at least seven structurally related genes, HLH-m delta, HLH-m gamma, HLH-m beta, HLH-m3, HLH-m5, HLH-m7 and E(spl). The functions of these genes are required during early neurogenesis to give neuroectodermal cells access to the epidermal pathway of development. Another gene in the 96F region, namely groucho, is also required for this process. However, groucho is not structurally related to, and appears to act independently of, the genes of the E(spl)-C; the possibility is discussed that groucho acts upstream to the E(spl)-C genes. Indirect evidence suggests that a neighboring transcription unit (m4) may also take part in the process. Of all these genes, only gro is essential; m4 is a dispensable gene, the deletion of which does not produce detectable morphogenetic abnormalities, and the genes of the E(spl)-C are to some extent redundant and can partially substitute for each other. This redundancy is probably due to the fact that the seven genes of the E(spl)-C encode highly conserved putative DNA-binding proteins of the bHLH family. The genes of the complex are interspersed among other genes which appear to be unrelated to the neuroepidermal lineage dichotomy.

In vivo imaging of glucose consumption and lactate concentration in human gliomas

Abstract: Twenty patients with histologically confirmed gliomas were studied with positron emission tomography (PET) and proton magnetic resonance spectroscopy (1H-MRS). PET with 18F-2-fluoro-2-deoxy-D-glucose (FDG) provided tomograms of the metabolic rate of glucose. MRS images were obtained by combining volume-selective excitation with phase-encoded acquisition. With 32 x 32 gradient phase-encoding steps, an in-plane resolution of 7 x 7 mm was achieved. From this set of spectra, lactate maps were created and compared with PET maps of glucose metabolism. Maximum glucose metabolic rates within tumors (relative to metabolic rates of glucose in contralateral regions of the brain) were correlated significantly with maximum lactate concentrations (relative to N-acetyl aspartate peaks in the contralateral part of the brain). In 8 tumors, no lactate was detected, and in 7 of these the maximum glucose metabolic rate was below the median value. The tumor with the highest lactate concentration also had the highest glucose metabolic rate. The topographic relation between glucose metabolic rate and lactate concentration could be analyzed in 9 patients by three-dimensional alignment of the PET and MRS images. In that analysis, maximum lactate concentrations were often not found in the same location as maximum glucose metabolism, but lactate tended to accumulate in tumor cysts, necrotic areas, and the vicinity of the lateral ventricles. The combination of FDG PET and 1H-MRS imaging demonstrates details of the spatial relation between the two poles of nonoxidative glycolysis, glucose uptake and lactate deposition.(ABSTRACT TRUNCATED AT 250 WORDS)

Contribution of Ca(2+)-induced Ca2+ release to the [Ca2+]i transients in myocytes from guinea-pig urinary bladder.

Abstract: 1. Smooth muscle cells from guinea-pig urinary bladder were studied at an extracellular Ca2+ concentration ([Ca2+]o) of 3.6 mM and 36 degrees C. Fluorescence of Indo-1 was used to monitor the cytosolic calcium concentration ([Ca2+]i) and its changes ([Ca2+]i transients) induced by step membrane depolarizations. 2. During a 6 s depolarization step from -60 to 0 mV [Ca2+]i increased from a resting 118 +/- 22 nM to 1150 +/- 336 nM and decayed to a sustained level of 295 +/- 62 nM. The experiments were designed to evaluate the contribution of the release of intracellularly stored Ca2+ to components of the depolarization-induced [Ca2+]i transient, i.e. 'phasic', which decayed during a maintained depolarization step, and 'tonic' which constituted the sustained elevation of [Ca2+]i above resting level. 3. A short (1 s) application of 10 mM caffeine mimicked the phasic component. After wash-out of caffeine, the subsequent depolarization induced a [Ca2+]i transient with reduced peak, the degree of suppression depending on the interval between wash-out of caffeine and depolarization. The phasic component of the depolarization and the caffeine-induced [Ca2+]i transients were not additive but saturative. 4. The phasic component was largely abolished in the continuous presence of 10 mM caffeine. It was also abolished by a 10 min cell dialysis of 10 microM ryanodine from the pipette solution and was strongly reduced by dialysis of 5 microM thapsigargin. Changes of the tonic component of the depolarization-induced [Ca2+]i transient were much less pronounced with all three interventions. 5. The tonic component of the depolarization-induced [Ca2+]i transient was increased when [Ca2+]o was elevated briefly before a depolarization close to 0 mV, whereas the phasic component was not significantly changed. Similarly, brief application of 1 microM Bay K 8644 increased the tonic component several-fold without modifying significantly the phasic component. 6. It is concluded that depolarization-induced influx of Ca2+ through L-type Ca2+ channels induces the release of Ca2+ from intracellular caffeine-sensitive stores which constitutes the major part of the phasic component. Ca2+ release superimposes on the effects of Ca2+ influx through L-type Ca2+ channels, the non-inactivating part of which constitutes the tonic component of the [Ca2+]i transient. Since the two processes interact, a dissection by simple subtraction is not possible.

Enhancer of splitD, a dominant mutation of Drosophila, and its use in the study of functional domains of a helix-loop-helix protein.

Abstract: Helix-loop-helix proteins play important roles in developmental processes, such as myogenesis, neurogenesis, and sex determination. The gene Enhancer of split [E(spl)] of Drosophila, a member of a gene complex that is involved in early neurogenesis, encodes a protein with a basic domain and a helix-loop-helix motif. We took advantage of a dominant mutation of this gene, E(spl)D, to define in vivo structural features of this protein for proper function. The mutation renders the otherwise recessive eye phenotype of spl dominant. By germ-line transformation of different in vitro mutagenized versions of the E(spl) gene, we could demonstrate that the basic domain of this helix-loop-helix protein is functional and necessary for expression of the dominant phenotype. These results are supported by in vitro DNA-binding assays, which showed that the basic domain is in fact necessary for DNA binding, despite the presence of a proline residue. Furthermore, we could show that the dominant enhancement of spl is caused by truncation of the E(SPL)D protein in combination with deletion of a putative regulatory element.

Invertebrate immunity: another viewpoint.

Abstract: All vertebrates and invertebrates manifest self/non-self recognition. Any attempt to answer the question of adaptive significance of recognition must take into account the universality of receptor-mediated responses. These may take two forms: (1) rearranging, clonally distributed antigen-specific receptors that distinguish in the broadest sense between self and non-self, and non-self A from non-self B, latecomers on the evolutionary scene; (2) pattern recognition receptors, the earliest to evolve and still around, necessitating the requirement for induced second signals in T- and B-cell activation. Either strategy need not force upon invertebrates the organization, structure and adaptive functions of vertebrate immune systems. Thus, we can freely delve into the unique aspects of the primitive immune mechanisms of invertebrates. In contrast, using the opposite strategy which is still problematic, i.e. linking invertebrate and vertebrate defence, seems to give us an approach to universality that might eventually reveal homologous kinship.