Dihydropyridines,phenylalkylamines and benzothiazepines block N-, P/Q- and R-type calcium currents

We compared the effects of representative members of three major classes of cardiac L-type channel antagonists, i.e. dihydropyridines (DHPs), phenylalkylamines (PAAs) and benzothiazepines (BTZs) on high-voltage-activated (HVA) Ca²⁺ channel currents recorded from a holding potential of –100 mV in rat ventricular cells, mouse sensory neurons and rat motoneurons. Nimodipine (DHP), verapamil (PAA) and diltiazem (BTZ) block the cardiac L-type Ca²⁺ channel current (EC₅₀: 1 M, 4 M and 40 M, respectively). At these concentrations, the drugs could also inhibit HVA Ca²⁺ channel currents in both sensory and motor neurons. Large blocking effects (> 50%) could be observed at 2–10 times these concentrations. The -conotoxin-GVIA-sensitive (-CTx-GVIA, N-type), -agatoxin-IVA-sensitive (-Aga-IVA, P- and Q-types) and non-L-type -CTx-GVIA-, -Aga-IVA-insensitive (R-types) currents accounted for more than 90% of the global current. Furthermore, our data showed that CTx-GVIA and -Aga-IVA spare L-type currents and have only additive blocking effects on neuronal HVA currents. We conclude that DHPs, PAAs and BTZs have substantial inhibitory effects on neuronal non-L-type Ca²⁺ channels. Inhibitions occur at concentrations that are not maximally active on cardiac L-type Ca²⁺ channels.     

Characterization of the small subgenomic RNA of <Emphasis Type="Italic">Soybean dwarf virus</Emphasis>

Summary. We have characterized a small subgenomic RNA of Japanese strains of Soybean dwarf virus (SbDV). Northern blot analyses of SbDV-infected plants showed that the small RNA contained the 3 terminal sequence of the genome and was detected in four typical Japanese SbDV strains, YS, YP, DS and DP. In the case of SbDV-DS, the RNA was 220 nucleotides in length and was transcribed from the 3 terminal region of the genome. This RNA appeared at a similar time to genomic RNA and a large sgRNA, and thereafter persisted in the infected plant. Since no conserved open reading frame (ORF) among the strains was postulated in the 3 terminal region, the small subgenomic RNA may have some regulatory roles in SbDV infections.Received December 12, 2002; accepted April 16, 2003 Published online July 2, 2003     

Characterization and localization of α-connectin (titin 1): An elastic protein isolated from rabbit skeletal muscle

Summary A simplified procedure to isolate-connectin (titin 1, TI), a gigantic elastic protein, from rabbit skeletal muscle is described. A rapid column chromatography step to concentrate-connectin is introduced. Separation of-connectin from-connectin is introduced. Separation of-connectin from-connectin (titin 2, TII) in the presence of 4 M urea at pH 7.0 did not cause any change in the secondary structure of-connectin as judged by circular dichroic spectra. Ultraviolet absorption spectra and the amino acid composition of-connectin (MW, approximately 3×10⁶) were similar to those of its proteolytic product,-connectin (MW, approximately 2×10⁶). Circular dichroic spectra suggested that both- and-connectin consist of 60%-sheet and 30%-turn. It thus appears that the whole elastic filament of connectin has a folded-strand structure. Proteolysis of-connectin by calpain resulted in formation of-connectin and smaller peptides. The-connectin interacted with both myosin and actin filaments similarly to-connectin. Polyclonal antibodies raised against 1200 kDa peptides obtained from aged rabbit skeletal myofibrils reacted with-connectin (titin 1, TI) but only weakly with-connectin (titin 2, TII) in rabbit skeletal muscle. Immunoelectron microscopy and indirect immunofluorescence microscopy revealed that the antibodies bound at the Z-line and at the epitope regions in the I-band near the binding site of a monoclonal antibody SMI whose position depends on sarcomere length. It thus appears that-connectin extends from the edge of M-line to the above epitope region in the I-band.     

Phosphaturic response of hydrocortisone in the presence and the absence of parathyroid hormone

The effect of hydrocortisone (HC) on the renal Pi transport in the presence and in the absence of parathyroid hormone (PTH) in the rat was examined using clearance techniques. During constant infusion of PTH in parathyroidectomized (PTX) rats, HC decreased the reabsorption of Pi from 2.84 to 2.33 mol/min (P<0.001), the Tm_Pi from 4.55 to 3.83 mol/min (P<0.001), the reabs. Pi/GFR values from 0.93 to 0.74 (P<0.001) and the Tm_Pi/GFR from 1.73 to 1.42 mol/ml (P<0.001). In the absence of PTH, HC diminished the Tm_Pi from 8.36 to 6.58 mol/min (P<0.005) and the Tm_Pi/GFR from 3.36 to 2.51 mol/ml (P<0.001). It is concluded that the phosphaturic response of hydrocortisone may be important in the homeostasis of inorganic phosphate in the body.This work was supported by a grant from the Deutsche Forschungsgemeinschaft (Fr 239/8)     

Partitioning of Cortical and Deep Cytoskeleton Responses from Transient Magnetic Bead Twisting

We attempted to estimate in living adherent epithelial alveolar cells, the degree of structural and mechanical heterogeneity by considering two individualized cytoskeleton components, i.e., a submembranous cortical cytoskeleton and a deep cytoskeleton (CSK). F-actin structure characterizing each CSK component was visualized from spatial reconstructions at low and high density, respectively, especially in a 10-m-cubic neighborhood including the bead. Specific mechanical properties (Young elastic and viscous modulus E and ) were revealed after partitioning the magnetic twisting cytometry response using a double viscoelastic solid model with asymmetric plastic relaxation. Results show that the cortical CSK response is a faster ( ₁ 0.7s), softer (E₁: 63-109 Pa), moderately viscous (₁: 7-18 Pa s), slightly tensed, and easily damaged structure compared to the deep CSK structure which appears slower (₂ min), stiffer (E₂: 95-204 Pa), highly viscous (₂: 760-1967 Pa s), more tensed, and fully elastic, while exhibiting a larger stress hardening behavior. Adding drug depolymerizing actin filaments decreased predominantly the deep CSK stiffness. By contrast, an agent altering cell–matrix interactions affected essentially the cortical CSK stiffness. We concluded that partitioning the CSK within cortical and deep structures is largely consistent with their respective functional activities. © 2003 Biomedical Engineering Society. PAC2003: 8716Ka, 8716Ac, 8380Lz     

Molecular characterization of h − mutants of Schizosaccharomyces pombe

Summary Meade and Gutz (1976) have described mat2:2 mutants of Schizosaccharomyces pombe having various defects in the Plus (P) function; four different classes were distinguished. Of special interest are the class II mutants in which none of the P mating-type functions is expressed. We made Southern analyses of 23 class II strains. In most of these, the P cassette and the K region are deleted as in h ^–s strains, however, some distinct differences were found as to the intensity of the bands in the blots (classes Ila, Ilb 1, and IIb2). The class Ilb mutants have strong bands characteristic of lethal deletions (h ^–L) and mat2:1 ⁰ plasmids. Two class II mutants turned out to have a typical h⁹⁰ mating-type region with an intact P cassette, but they seem to have a completely defective switching signal at matl:1 (new class V). Mutants of classes I, III, and IV yielded band patterns identical to those of an h ⁹⁰ strain; they obviously have point mutations in the P cassette.     

The role ofγδ T cells in the normal and disordered immune system

Summary A small population of T cells does not express the conventional T cell receptor characterized by the and polypeptide chains (TCR) but instead, two polypeptides termed and (TCR). This alternative receptor is able to recognize antigen. It appears early in T cell ontogeny, but its role in the thymus prior to the availability of TCR remains unclear. In selected sites such as skin or gut TCR predominates in mice which might suggest a role of T cells in the first line of defense against infection, T cells secrete lymphokines and display cytotoxic activity. However, their activation requirements may differ from what is known for T cells since MHC-nonrestricted and also CD4 and CD8 negative T cells have been described. Preferential activation by mycobacterial antigens possibly indicates a special repertoire of the T cells. In various diseases slightly increased numbers of T cells were found, but these preliminary studies have not yet provided evidence for a major pathogenetic role of T cells.List of abbreviations C constant region (immunoglobulin or TCR gene segment) - CD4 cluster of differentiation 4 (mainly on helper cells) - CD8 cluster of differentiation 8 (mainly on cytotoxic cells) - D diversity region (immunoglobulin or TCR gene segment) - DNA desoxyribonucleic acid - IL2 interleukin 2 - J joining region (immunoglobulin or TCR gene segment) - kD kiloDalton - MHC major histocompatibility complex - NK natural killer (cells) - RA rheumatoid arthritis - TCR T cell receptor - V variable region (immunoglobulin or TCR gene segment)     

ω-Grammotoxin blocks action-potential-induced Ca2+ influx and whole-cell Ca2+ current in rat dorsal-root ganglion neurons

Field-potential stimulation of rat dorsal-root ganglion (DRG) neurons evoked action-potential-mediated transient increases in intracellular free calcium concentration ([Ca²⁺]_i) as measured by indo-1-based microfluorimetry. Field-potential-evoked [Ca²⁺]_i transients were abolished by tetrodotoxin, and their dependence on stimulus intensity exhibited an abrupt threshold. -Conotoxin GVIA (-CgTx, 100 nM) inhibited action-potential-mediated Ca²⁺ influx by 79%, while nitrendipine (1 M) had little effect. -Grammotoxin SIA (-GsTx, 267 nM), a peptide toxin purified from the venom of the tarantula spider, Grammostola spatulata, blocked action-potential-mediated Ca²⁺ influx as effectively as did -CgTx, suggesting that -GsTx blocks N-type Ca²⁺ channels. In contrast to block by -CgTx, the block produced by -GsTx reversed upon washout of the peptide. -GsTx (270 nM) blocked 80%, and -CgTx (1 M) blocked 64%, of whole-cell Ca²⁺ current (I _Ca) elicited by step depolarization to 0 mV from a holding potential of –80 mV. -GsTx completely occluded inhibition of I _Ca by -CgTx. However, when applied after -CgTx, -GsTx produced an additional inhibition of 27%, indicating that -GsTx also blocked a non-N-type Ca²⁺ channel. BayK8644 (1 M) elicited an increase in I _Ca in the presence of maximally effective concentrations of -GsTx, suggesting that -GsTx does not block L-type channels. Thus, -GsTx displays a selectivity for Ca²⁺ channel subtypes which should prove useful for studying Ca²⁺ channels and Ca²⁺-channel-mediated processes.     

Recombinant HuIFN-gamma prevents herpes simplex keratitis in African green monkeys: Demonstration of synergism with recombinant HulFN-alpha 2

Human interferon gamma (HuIFN-) was found to prevent herpes-simplex virus (HSV 1) induced keratitis in monkey eyes, when administered topically at concentrations of 3×10⁵ reference units/ml. Protective efficacy demonstrated with lower concentrations of HuIFN- in combination with low titers of HuIFN- provided evidence of synergistic interferon activity in vivo. Tolerance problems observed in eyes affected by virus inoculation seem to be attributable to the experimental conditions including species heterology.     

Genetic characterization of an α-specific gene responsible for sexual agglutinability in Saccharomyces cerevisiae: mapping and gene dose effect

Summary A recessive ag1 mutation leads to specific defect in sexual agglutinability specifically in cells of the yeast Saccharomyces cerevisiae. The cryptopleurine resistance gene cry^R 1, closely linked to the mating type locus, was used to select / strains which emerged from / strains by mitotic nonreciprocal recombination, to genetically analyse ag1, since ag1 is expressed only in mating type. The ag1 gene was found to be linked to the centromere tightly, to met3 at 4.4 cM, and to ilv3 at 12 cM on chromosome X. Sexual agglutinability of cells was shown to be dependent on the dose of the AG1 gene, using / isogenic strains carrying AG1/AG1, AG1/ag1 or ag1/ag1. The sst2-1 mutation did not suppress the ag1 mutation. Based on these results, function of the AG1 gene is discussed.Abbreviations cM centimorgan - FDS first division segregation - NPD nonparental ditype - PD parental ditype - SDS second division segregation - TT tetratype     

Untersuchungen zur Frage der Entfernung von Pyrogenen aus Flüssigkeiten durch Filtration

Zusammenfassung In Ergänzung früherer Versuche^{3, 4} im Zusammenhange mit der Frage der Entfernung pyrogener Stoffe aus Flüssigkeiten, z. B. aus Arzneimittellösungen in Apotheken, wurde festgestellt, daß es gelingt, die von uns verwendeten Pyrogene (50, 100 bzw. 250 E Pyrifer) durch Filtration mittels bestimmter Membranfilter der Firma Membranfiltergesellschaft Sartorius-Werke AG. & Co., Göttingen, zurückzuhalten. Von den von uns neuerdings geprüften Filtern eignen sich hierzu die Filter 25–30 sec (maximaler Porendurchmesser 300 m) und 40–60 sec (maximaler Porendurchmesser 250 m), während bei der Verwendung der Filter 80 bis 100 see (maximaler Porendurchmesser 200 m) gelegentlich Versager beobachtet wurden. Gleichzeitig wurden unsere früheren Ergebnisse bestätigt, nach denen die Seitz-Filter EKS zum gleichen Zwecke brauchbar sind.     

<Emphasis Type="Italic">Apolipoprotein E</Emphasis> polymorphism is associated with age of onset in schizophrenia

The aims of the study were to investigate the relationship between Apolipoprotein E (APOE) polymorphism, risk of schizophrenia, treatment response to conventional anti-psychotics, and age of onset in schizophrenia. The sample comprised 94 Finnish patients with a DSM-IV diagnosis of schizophrenia. Forty-three of the patients were good responders to conventional anti-psychotics and 51 were classified as non-responders. The control group consisted of 98 healthy blood donors. The APOE allele frequencies (2, 3, and 4) were 4.8, 72.3, and 22.9% in patients and 7.1, 75.0, and 17.9 in controls. None of the differences between groups were statistically significant. No association between treatment response and APOE genotype was found. Patients with APOE 4/4 genotype had a markedly lower age of onset compared with rest of the sample (p=0.0015), which remained significant when controlling for gender (p=0.02). There was an increasing linear trend between the number of 3 alleles (0, 1, or 2) and age of onset in schizophrenia (p=0.08). An inverse trend was found between the number of 4 alleles and age of onset (p=0.07). No relationship between APOE polymorphism and risk for schizophrenia was found. APOE 4/4 genotype may be associated with early onset schizophrenia. APOE 3 allele may function protectively in later onset in this disease.     

An α-mating-type-specific mutation causing specific defect in sexual agglutinability in the yeast Saccharomyces cerevisiae

We have identified a recessive -mating-type-specific gene agl causing agglutinability defect without significant effects on other sexual activities. a cells carrying agl showed sexual agglutination with cells but cells carrying agl showed sexual agglutination with neither cells nor a cells. cells carrying agl produced pheromone and responded to a pheromone just like wild cells. cells carrying agl showed a little decreased but significant mating ability when tested on solid media or membrane filter. The agl mutant is different from any -specific ste mutants found so far in many sexual activities. The agl gene is recessive, and unlinked to the mating type locus. Biological significance of the mating type agglutinability is discussed based on the results obtained with the mutant.     

On the regulation of the expressed L-type calcium channel by cAMP-dependent phosphorylation

The Ca²⁺ channel subunits _1C-a and _1C-b were stably expressed in Chinese hamster ovary (CHO) and human embryonic kidney (HEK) 293 cells. The peak Ba²⁺ current (I _Ba) of these cells was not affected significantly by internal dialysis with 0.1 mM cAMP-dependent protein kinase inhibitor peptide (mPKI), 25 M cAMP-dependent protein kinase catalytic subunit (PKA), or a combination of 25 M PKA and 1 M okadaic acid. The activity of the _1C-b channel subunit expressed stably in HEK 293 cells was depressed by 1 M H 89 and was not increased by superfusion with 5 M forskolin plus 20 M isobutylmethylxanthine (IBMX). The _1C-a·₂·₂/ complex was transiently expressed in HEK 293 cells; it was inhibited by internal dialysis of the cells with 1 M H 89, but was not affected by internal dialysis with mPKI, PKA or microcystin. Internal dialysis of cells expressing the _1C-a·₂·₂/ channel with 10 M PKA did not induce facilitation after a 150-ms prepulse to +50 mV. The Ca²⁺ current (I _Ca) of cardiac myocytes increased threefold during internal dialysis with 5 M PKA or 25 M microcystin and during external superfusion with 0.1 M isoproterenol or 5 M forskolin plus 50 M IBMX. These results indicate that the L-type Ca²⁺ channel expressed is not modulated by cAMP-dependent phosphorylation to the same extent as in native cardiac myocytes.     

Evidence that arachidonic acid derived from neutrophils and prostaglandin E<Subscript>2</Subscript> are associated with the induction of acute lung inflammation by lipopolysaccharide of <Emphasis Type="Italic">Escherichia coli</Emphasis>

Objective: The involvement of arachidonic acid (AA) and PGE₂ during the E. coli lipopolysaccharide (LPS)-induced acute lung injury was investigated.Material: Adult male Wistar rats were used. For in vitro studies, rat neutrophils, bronchoalveolar lavage (BAL) fluid, and lug vascular endothelium were used, as described below.Treatment: Rats were given an intratracheal injection of LPS (750 g).Methods: Total and differential cell counts in BAL fluid; enzyme-linked immunoassay (ELISA) analyses of TNF-, IL-1, LTB₄ and PGE₂ in BAL, and immunohistochemical detection of ICAM-1 on lung vascular endothelium were performed six h after LPS challenge. Fatty acid composition of blood neutrophils and plasma was analyzed by HPLC.Results: Rats instilled with LPS presented a sixty three-fold increase in the number of neutrophils in BAL (from 0.5 × 10⁶ to 31.5 × 10⁶ cells), accompanied by increased levels of TNF- and IL-1 (p < 0.001), and a three-fold increase in ICAM-1 expression on vascular endothelium. The content of AA in blood neutrophils was reduced by 50%, whereas the level of PGE₂ in BAL was increased by 3.5 fold, without changes in the levels of LTB₄.Conclusions: These findings suggest that AA and PGE₂ are associated with LPS challenge.Received 19 October 2003; returned for revision 30 November 2003; accepted by N. Boughton-Smith 15 July 2004     

Acute and chronic inflammatory responses to local administration of recombinant IL-1α, IL-β, TNFα, IL-2 and Ifnγ in mice

The contention that cytokines are important mediators of inflammation prompted the present studies which were designed to compare acute and chronic pathological effects of locally-administered recombinant (r) IL-1, IL-1, TNF, IL-2 and Ifn. Acute (6 hr), resolving (48 hr) inflammation was induced by the following, in order of potency: rIL-1>rIL-1>rTNF>rIfn=BSA (control) following a single sc. injection. However, only rIL-1 and rIL-2 initiated and maintained chronic granulomatous reactions when delivered locally from a sc. ethylene vinyl acetate (EVA) slow-release polymer. The predominance of macrophages in EVA-rIL-1 lesions contrasted with the proliferative lymphoid granulomata induced by EVA-rIL-2 implants. These in vivo observations reinforce, the roles of both IL-1 and IL-2 as potent mediators of chronic immunoinflammatory disease.     

Effects of aerobic endurance training status and specificity on oxygen uptake kinetics during maximal exercise

The main purpose of this study was to analyze the effects of exercise mode, training status and specificity on the oxygen uptake (O₂) kinetics during maximal exercise performed in treadmill running and cycle ergometry. Seven runners (R), nine cyclists (C), nine triathletes (T) and eleven untrained subjects (U), performed the following tests on different days on a motorized treadmill and on a cycle ergometer: (1) incremental tests in order to determine the maximal oxygen uptake (O_2max) and the intensity associated with the achievement of O_2max (IO_2max); and (2) constant work-rate running and cycling exercises to exhaustion at IO_2max to determine the effective time constant of the O₂ response (O₂). Values for O_2max obtained on the treadmill and cycle ergometer [R=68.8 (6.3) and 62.0 (5.0); C=60.5 (8.0) and 67.6 (7.6); T=64.5 (4.8) and 61.0 (4.1); U=43.5 (7.0) and 36.7 (5.6); respectively] were higher for the group with specific training in the modality. The U group showed the lowest values for O_2max, regardless of exercise mode. Differences in O₂ (seconds) were found only for the U group in relation to the trained groups [R=31.6 (10.5) and 40.9 (13.6); C=28.5 (5.8) and 32.7 (5.7); T=32.5 (5.6) and 40.7 (7.5); U=52.7 (8.5) and 62.2 (15.3); for the treadmill and cycle ergometer, respectively]; no effects of exercise mode were found in any of the groups. It is concluded that O₂ during the exercise performed at IO_2max is dependent on the training status, but not dependent on the exercise mode and specificity of training. Moreover, the transfer of the training effects on O₂ between both exercise modes may be higher compared with O_2max.     

Tierexperimentelle Untersuchungen über die Netznekrose in der Leber

Zusammenfassung Bei 8 Kaninchen wurden 100 mg unkonjugiertes Bilirubin in die Pfortader injiziert. Danach entstanden bei einem Teil der Tiere in der Leber Netznekrosen, deren Entstehung und Schicksal durch Keilexcisionen 5 min, 3, 24, 48 und 58 Std nach der Injektion verfolgt wurde.Erste Veränderungen der Leberzellen können in Form einer Auflockerung und verminderten Anfärbbarkeit des Cytoplasma bereits 5 min nach der Injektion auftreten. Nach 3 Std sind voll ausgebildete sog. Netznekrosen vorhanden. In der Mehrzahl der Herde kommt es dann ohne wesentliche entzündliche Begleitreaktion zu einer vom Zentrum zur Peripherie fortschreitenden Auflösung und Resorption der Leberzellen, die eine vorübergehende Entlastungshyperämie und gelegentlich einen Gerüstkollaps zur Folge hat. Daneben sind Übergänge in Coagulationsnekrosen und eine sekundäre gallige Imbibition zu beobachten. Die primär aufgelösten und die sekundär in Form einer Coagulationsnekrose zugrunde gehenden Zellen werden durch eine Vermehrung der benachbarten, erhaltenen Leberzellen ersetzt, so daß in der Regel eine Wiederherstellung der ursprünglichen Acinusstruktur erfolgt. Schließlich ist eine Rückbildung der regressiven Veränderungen in der geschädigten Zelle möglich. Die Netznekrose stellt also nicht von vornherein eine irreversible, zwangsläufig zum Zelluntergang führende, regressive Veränderung dar.Netznekrosen sind nicht Folge einer bestimmten Leberparenchymschädigung. Sie treten vielmehr nach sehr verschiedenen Schädigungen auf, unter denen eine Cholestase, eine atypische Zusammensetzung der Galle und intrahepatische Zirkulationsstörungen im Vordergrund stehen. Die Netznekrosen werden als eine besondere Form der hydropischen Degeneration aufgefaßt, die von der blasigen Entartung zu trennen ist.

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Experimental studies in animals of net-necroses (reticular necroses) in the liver

Summary Unconjugated bilirubin (100 mg) was injected into the portal vein of each of eight rabbits. The development and fate of the resulting small net-necroses was followed by resecting wedges of liver at five minutes and at three, twenty-four, forty-eight, and fifty-eight hours after the injection.Within five minutes the first change appearing in the liver cells was a clearing of the cytoplasm with a decrease in its stainability. After three hours complete net-necroses had developed. In a majority of the foci the liver cells underwent dissolution and absorption, progressing from the centers to the periphery, with little inflammatory reaction. A transient hyperemia developed and occasionally the supporting recticulum network collapsed.Transitions to coagulation necroses also developed and occasionally a secondary imbibition of bile become evident.Both the initially destroyed cells and those that underwent a secondary coagulation necrosis were replaced by proliferation of neighboring liver cells, with ultimate restoration of the original acinar structure. The degenerative changes in the damaged liver in part were able to resolve. The net-necroses represented no irreversible, degenerative change necessitating only cell death. Net-necroses are not the result of a specific injury to liver parenchyma. They appear rather after very different injuries; for example, particularly after cholestasis, after abnormal composition of bile, and after intrahepatic circulatory disturbances.The net-necrosis represent a special form of hydropic degeneration which is to be distinguished from vacuolar degeneration.

     

Volume flow,hydraulic conductivity and electrical properties across bovine tracheal epithelium in vitro: Effect of histamine

Volume flow (J _v), potential difference (), shortcircuit current (i ₀) and electrical resistance (R) were measured simultaneously across bovine tracheal epithelium in vitro. Under basal conditions, with no applied hydrostatic or osmotic pressure gradient (P=0, =0), no spontaneousJ _v was observed. was 31±2 mV (lumen negative),i ₀ 161±8 A cm^–2 andR 202±9 cm²,n=50. When a was applied, by adding 20–80 mM sucrose into the medium bathing either the luminal or the serosal side of the tissue, a linear relationship was found between andJ _v toward the lumen or toward the serosa. The apparent hydraulic conductivity (apparentL _p) was 4.6–4.910^–6 cm s^–1 atm^–1. Histamine 10^–4 M did not induce any spontaneousJ _v under basal conditions and had no effect oni ₀ nor onR. However, histamine caused a 100% increase inJ _v elicited by sucrose gradients. It was concluded that histamine exerts a selective action on the hydraulic conductivity of bovine tracheal epithelium. Experiments using H₁-receptors antagonists (diphenhydramine, dimetindene, chloropyramine) and H₂-antagonists (cimetidine, metiamide) or a H₂-agonist (impromidine) showed that the increase ofL _p induced by histamine was mediated via H₂-receptors.Supported by the Swiss National Foundation (SNF), grant no. 3.5880.79     

Lichtmikroskopische Untersuchungen über die Entwicklung vonTheileria annulata (Dschunkowsky und Luhs, 1904) inHyalomma anatolicum excavatum (Koch, 1844)

Summary Fully differentiated kinetes, average length 17.6m, appeared in the haemolymph of engorged nymphs usually 17 to 20 days after repletion. Kinetes were observed at first in the salivary glands on day 18 after repletion. The kinetes then transformed into fission bodies of about 10m in diameter, mainly in type III alveoli and less frequently in type II alveoli. The fission bodies grew up to a size of about 20m after several divisions of their nucleus. At this time the ticks moulted and no further development occurred until activation. Shortly before infestation the salivary glands began to proliferate, and rapid growth of the fission bodies was observed, especially in young ticks where development of infective particles (sporozoites) was concluded within two days. Development in feeding adult ticks apparently occurred in four major steps: (1) Division of primary fission bodies (sporonts) into numerous secondary fission bodies (primary sporoblasts), (2) division of secondary fission bodies into tertiary fission bodies (secondary sporoblasts), (3) production of particles (sporozoites) by tertiary fission bodies and release of particles into the saliva, and (4) degeneration of fission bodies and their host cell but further release of particles.The host cell was stimulated to giant growth, thus its diameter increased, on average, from 15 to 110 m. Heavy infections resulting from parasitaemias of >40% caused disease and mortality in the tick population. Development was much retarded by aging. In ticks starved for six months sporozoites did not develop before day five to seven of infestation. Sporozoites may not develop at all in six to nine month old female ticks during the infestation period. The significance of the described developmental stages ofT. annulata was discussed and a sexual generation postulated. The hypothetic development ofT. annulata in its tick vector was illustrated.

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Gefördert von der Deutschen Forschungsgemeinschaft (DFG)