Determination of the puncture force of microneedles by means of a digital recording complex

Scientific-Industrial Association Medinstrument, Kazan. Translated from Meditsinskaya Tekhnika, No. 2, pp. 13–17, March–April, 1988.     

Two types of potassium channel regulated by ATP in pancreatic B cells isolated from a type-2 diabetic human

Two types of K channel regulated by ATP were observed in pancreatic cells from a type-2 diabetic man. One type had a conductance of 67 pS at-70 mV in symmetrical 140 mM KCl and was inhibited by intracellular ATP with a half-maximal concentration of 40 M. ATP inhibition was antagonised by ADP. Tolbutamide inhibited the whole-cell K currents half-maximally at 25 M. This channel has properties similar to those found for the ATP-sensitive K channel in rodent and normal human cells. The second channel type observed was an ATP-activated K channel. It had a conductance of 37 pS at -70 mV in symmetrical 140 mM KCl and was activated half-maximally by 9 M intracellular ATP. This channel was unaffected by 1 mM tolbutamide. In cell-attached patches, one cell out of four tested responded to 20 mM glucose with depolarization. The role of the ATP-activated K channel with respect to the (patho)physiology of the cell is uncertain.     

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.     

Role of potassium channels in the regulation of cytokine release from THP-1 cells

The role of K⁺ channels in the regulation of cytokine release was investigated. Quinine, a non-selective K⁺ channel blocking agent inhibited both TNF and IL-1 release but had non-specific effects on cell function. Glipizide and glibenclamide, inhibitors of ATP-sensitive K⁺ channels, reduced IL-1 release but not TNF, whereas apamin, a selective inhibitor of low-conductance Ca²⁺-sensitive channels, inhibited TNF release, potentiated IL-1 but had no effect on IL-6 or IL-8 release. These results suggest that K⁺ channels may differentially regulate cytokine production by THP-1 cells.     

Die Empfindlichkeit einiger sporenfreier Anaerobier gegen Spiramycin in vitro

Zusammenfassung Es wurden 18 Stämme gramnegativer sporenfreier Anaerobier der GattungenFusobacterium, Treponema undBorrelia auf ihre Empfindlichkeit gegen Spiramycin geprÜft.Alle (10) Fusobakterienstämme erwiesen sich als völlig resistent gegen dieses Antibioticum.Die minimalen Hemmungskonzentrationen fÜrTreponema microdentium (6 Stämme) lagen zwischen 0,1 und 0,5/ml, fÜrTreponema sp. Reiter bei 0,25/ml.Das Wachstum vonBorrelia vincentii (1 Stamm) wurde ebenfalls durch 0,25 Spiramycin je Milliliter Nährboden gehemmt.Das Verhalten von oralen Fusobakterien und Treponemen gegenÜber den vier Antibiotica der Erythromycingruppe wird vergleichend besprochen.Die vorliegenden Untersuchungen wurden mit UnterstÜtzung der Deutschen Forschungsgemeinschaft durchgefÜhrt.FÜr die Überlassung des Selectomycin bin ich Herrn Dr. Dr. Dipl.-chem. H. W.v. Schrader-Beielstein in Fa. Chemie GrÜnenthal, Stolberg (Rhld.), zu Dank verpflichtet.     

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)     

Effects of pyridinyl imidazole compounds on murine TNF-α production

The effects of SK&F 86002 and other pyridinyl imidazole compounds on murine cytokine production were investigated.In vitro, SK&F 86002 inhibited LPS stimulated TNF- production by the RAW 264.7 cell line and by oil elicited peritoneal macrophages with an IC₅₀ of 5M. In general, the activity was reflective of previous results obtained with human monocytes as SK&F 86002 and its analogs demonstrated identical rank order potency for TNF- inhibition in both species. These compounds also inhibited TNF-in vivo in a murine model of endotoxin shock. Following oral administration, SK&F 86002 and its analogs reduced serum TNF- levels by >80% and afforded 100% protection from lethality. In contrast, tenidap, a novel anti-inflammatory drug, had minimal to no effect on murine TNF- production in the same assays. These data further extend the pharmacological profile of the pyridinyl imidazoles by demonstrating that these compounds potently inhibit murine TNF- production bothin vitro andin vivo.     

Application of the polymerase chain reaction to study the M protein(-like) gene family in beta-hemolytic streptococci

Evaluation of homologous regions of published M protein (emm) gene sequences from group A streptococci (GAS; Streptococcus pyogenes) was used to design three primer pairs for polymerase chain reaction (PCR) and three oligonucleotide probe sequences internal to the amplified products. One set of primers and corresponding probe should detect and lead to amplification of emm(-like) genes of virtually every type (all M), another (SOR^-M) should only amplify emm(-like) genes from GAS negative for serum opacity reaction (SOR) and the third (SOR⁺M) should expand only emm(-like) genes from SOR⁺ GAS. Using the all M primer pair for PCR on the genomic DNA from GAS of 29 different M types as well as from a group C and a group G streptococcal isolate, DNA fragments within the expected size range were amplified in every assay. All PCR products reacted with the all M probe. Related sequences were not detected in genomic DNA of an S. agalactiae and an Enterococcus faecalis isolate. Applying the SOR^-M and SOR⁺M primers to identical assays led to mutually exclusive amplification products. The SOR⁺M and SOR⁺M probes hybridized only to their corresponding products. Exceptions to this exclusivity were the SOR⁺ GAS of M types 3, 8, 27, 34, 42, 67, and 69, which consistently reacted only with the SOR⁺M primer/probe set. Analysis of sequence data from the amplified emm(-like) 2, 3, 18, and 19 genes revealed interesting specific features such as conserved gaps in the C-terminal sequence regions from SOR⁺ and the exceptional SOR^- GAS strains. These data indicate the existence of a subgroup of strains among SOR^- GAS and may advance our understanding of phylogenetic relationship between different serotypes of GAS.     

Evidence for a direct relationship between mitochondrial genome organization and regeneration ability in hexaploid wheat somatic tissue cultures

Summary Embryogenic and non-embryogenic long-term callus cultures of hexaploid wheat exhibit differences in the organization of their mitochondrial genome. Embryogenic and non-embryogenic fractions of callus cultures initiated from immature embryos of the wheat cultivar Chinese Spring have been isolated and subsequently subcultured. DNA-DNA hybridization experiments using labelled cloned wheat mitochondrial DNA fragments have shown that the mitochondrial DNA organization of embryogenic subcultures derived from embryogenic parts of Chinese Spring calli is closely related to that of the initial Chinese Spring calli, while non-embryogenic subcultures derived from non-embryogenic fragments of Chinese Spring calli exhibit a mitochondrial DNA organization similar to that found in non-embryogenic calli derived from cultivar Aquila. In addition, somatic tissue cultures initiated from three other non-embryogenic wheat cultivars (Talent, Thésée and Capitole) display mitochondrial DNA arrangements similar to those found in cultivar Aquila. These results strongly suggest that, in wheat callus cultures, a particular mitochondrial genome organization is correlated with the ability of cultured cells to regenerate whole plants.Abbreviations mtDNA mitochondrial DNA - ctDNA chloroplast DNA - rRNA ribosomal RNA - kb kilobase pair - cv cultivar - 2,4-D 2,4-dichlorophenoxyacetic acid     

Pharmacological profile of β-adrenoceptor blockers with vasodilating properties, especially carvedilol — rationale for clinical use

The rationale for the combined use of -adrenoceptor antagonists and vasodilators is to improve the efficacy of the antihypertensive therapy and to reduce the incidence of side effects. If suitable coagents are selected and used at appropriate doses, the disadvantages of each separate component (compromised blood flow to individual organs, increase in total peripheral resistance, unfavorable lipid profile for -blockers; stimulation of counter-regulatory mechanisms, retention of water and electrolytes for vasodilators) can be balanced. In addition, the favorable effects of each (reduction in cardiovascular morbidity and mortality for -blockers, and favorable hemodynamic profile for vasodilators) may be used to advantage. Such a treatment rationale can be accomplished by a free combination or by using a dual-acting drug. From the practical point of view, the latter may be preferable. The basic requirement for such a drug is that the two effects are evoked in the same dose range. Carvedilol is a dual-acting drug designed to produce -blockade and vasodilatation in the same dose range. The vasodilatation is mediated predominantly by specific ₁-adrenoceptor blockade; at markedly higher concentrations additional vasodilating actions can be observed. These effects resemble those of Ca²⁺ -antagonistic properties. However, they do not contribute to the acute blood-pressure-lowering activity, but may be responsible for the increased blood flow to some organs. At -blocking doses, carvedilol reduces the total peripheral resistance, and blood flow to the kidneys is preserved. Cardioprotection has been demonstrated in a variety of experimental investigations     

Foraging strategies ofDrosophila melanogaster: A chromosomal analysis

Two larval foraging strategies inDrosophila melanogaster were identified, rover and sitter. Rovers traverse a large area while feeding whereas sitters cover a small area. The difference between rovers and sitters was analyzed genetically by chromosomal substitutions between isogenic stocks. Differences in larval locomotor behavior (crawling behavior) can be attributed to the second chromosome, the rover strategy being dominant over the sitter strategy. Differences in feeding rate (shoveling behavior) are affected additively by both the second and third chromosomes. Natural populations ofDrosophila larvae were sampled three times over a 2-month period; rovers and sitters were at constant frequencies in these populations. The two foraging strategies are discussed in the light of resource utilization in environments where food is distributed continuously or discontinuously.