Zur Bedeutung des cyclischen Adenosin-3′:5′-monophosphat als „second messenger“ bei der Säuresekretion des Magens

Zusammenfassung Ob bei einer bestimmten Hormonwirkung cyclisches Adenosin-3:5-monophosphat (cAMP) als intracellulärer Vermittler fungiert, läßt sich nach den von Sutherland entwickelten Kriterien beurteilen; dabei sind die qualitativen, quantitativen und zeitlichen Beziehungen zwischen dem Hormoneffekt auf den intracellulären cAMP-Spiegel und die jeweilige physiologische Antwort zu prüfen. Im Falle der Histamin- bzw. Pentagastrin-stimulierten gastralen Säuresekretion des Frosches (Necturus maculosus) und der Ratte erfüllt das cAMP die Bedingungen eines second messenger. Dagegen ließ sich beim Hund und Menschen eine derartige Funktion des cAMP bisher nicht verifizieren; ob bei diesen Species cyclisches Guanosin-3:5-monophosphat anstelle des cAMP die intracelluläre Vermittlerrolle übernimmt, werden erst noch systematische Untersuchungen erweisen müssen.Die in diesem Zusammenhang zitierten eigenen Arbeiten wurden von der Deutschen Forschungsgemeinschaft, Bad Godesberg, unterstützt.     

Cyclische Nucleotide als intracelluläre Überträgerstoffe bei Hormonwirkungen

Zusammenfassung Hormone dienen als extracelluläre Informationsüberträger zwischen ihrem Bildungsort, einer endokrinen Drüse, und den Zellen, deren Funktion sie regulieren. Durch die Reaktion des Hormons mit den an der Zellmembran gelegenen Receptoren wird die Aktivität der mit diesen eng verknüpften Adenyl-Cyclase beeinflußt. Die meisten Hormone erhöhen in ihrem Zielorgan die Aktivität dieses Enzyms und führen hierdurch zu einem raschen Anstieg der intracellulären Konzentration von Adenosin-3:5-monophosphat (Ado-3:5-P). Dieses cyclische Nucleotid wird durch eine spezifische Phosphodiesterase zu Adenosin-5-monophosphat abgebaut. Auch die Aktivität dieses Enzyms bestimmt die intracelluläre Ado-3:5-P-Konzentration, die im Vergleich zu der anderer Nucleotide sehr gering ist.Ado-3:5-P beeinflußt als zweiter, intracellulärer Überträgerstoff die Aktivität zahlreicher Schlüsselenzyme. Die Ado-3:5-P-Konzentration bestimmt hierdurch das Gleichgewicht verschiedener Stoffwechselwege zueinander und damit die Reaktion einer Zelle auf eine hormonale Stimulierung. An einer Reihe von Enzymen wird die durch Ado-3:5-P bedingte Aktivitäts-Änderung durch einen gleichartigen Mechanismus bewirkt. Das cyclische Nucleotid stimuliert Proteinkinasen, die eine Phosphatgruppe des ATP auf verschiedene Proteine übertragen und hierdurch deren Eigenschaften verändern können. So steigt bei Phosphorylierung durch eine Ado-3:5-P-stimulierbare Proteinkinase die Aktivität der Triglyceridlipase und der Glykogen-Phosphorylase-b-kinase an, dagegen nimmt die Aktivität der Glykogen-Synthetase ab; durch Phosphorylierung von Histonen kann deren Repressorcigenschaft vermindert und die Synthese von Enzymen gesteigert werden.In manchen tierischen Geweben wurde auch eine spezifisch durch Guanosin-3:5-monophosphat (Guo-3:5-P) stimulierbare Proteinkinase nachgewiesen. Dieses cyclische Nucleotid kommt wie Ado-3:5-P in allen Säugerorganen vor. Die Bildung von Guo-3:5-P aus GTP wird durch die Guanyl-Cyclase katalysiert, ein Ferment, das im Gegensatz zur Adenyl-Cyclase zum großen Teil nicht an die Zellmembranen gebunden ist. Die Konzentration von Guo-3:5-P in verschiedenen Geweben, im Blutplasma und im Urin wird durch Hormone beeinflußt. Es ist noch nicht bekannt, welche hormonalen Regulationen durch Guo-3:5-P vermittelt werden; dagegen ist bei vielen, rasch einsetzenden Hormonwirkungen die Beteiligung von Ado-3:5-P nachgewiesen worden.

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Abkürzungen Ado-3:5-P Adenosin-3:5-monophosphat - dAdo-3:5-P Desoxy-adenosin-3:5-monophosphat - Guo-3:5-P Guanosin-3 : 5-monophosphate - Nuc-3:5-P Nucleosid-3:5-monophosphat - NTP Nucleosidtriphosphat - NMP Nuclcosid-5-monophosphat - dATP Desoxyadenosintriphosphat - P_i anorganisches Phosphat - PP_i anorganisches Pyrophosphat - DNS Desoxyribonucleinsäure - RNS Ribonucleinsäure - r-RNS ribosomale RNS - m-RNS Boten-RNS - Glykogen-Synthetase UDP-Glucose--1,4-glucan--4-glucosyltransferase - ICSH interstitial-cell-stimulating hormone     

Sequence determination of the extreme 5′ end of equine arteritis virus leader region

The extreme 5 end of the leader sequence of four equine arteritis virus (EAV) strains was obtained by using rapid amplification of cDNA end method (5 RACE), and sequenced. Seventeen more nucleotides were added upstream of the 5 end of the EAV published genomic sequence. A common feature among the analyzed EAV isolates was the presence of an AUG start codon within the added sequence and the appearance of an intraleader open reading frame (ORF) of 111 nucleotides which was predicted to encode a peptide of 37 amino acids. The role of this putative intraleader ORF has yet to be determined.     

Messenger RNA 3′-end formation of a DNA fragment from the human c-myc 3′-end region in Saccharomyces cerevisiae

We have tested the functioning of the human c-myc polyadenylation signal in Saccharomyces cerevisiae. A DNA fragment containing the two AATAAA polyadenylation signals of the c-myc gene was inserted into a plasmid designed for the in-vivo testing of polyadenylation signals in yeast. The c-myc fragment had a partial capacity for directing mRNA 3-end formation in yeast. The 3-endpoints were 50–100 bp distant from the mRNA 3-ends mapped in humans. This human DNA fragment is therefore unspecifically functional in yeast, indicating that other sequence elements than the human polyadenylation signal, AATAAA, are necessary for 3-end formation.     

Genetic Analysis of Pestiviruses at the 3′ End of the Genome

Specific PCR primers were selected for each pestivirus genotype which flanked the 3-part of the NS5B gene and more than three quarters of the 3-UTR. PCR products were sequenced in both directions using an automatic sequencing device and analyzed by computer package program DNASTAR. A comparative analysis of the 3 untranslated region (3-UTR) of 82 viruses, representing the four genotypes of the Pestivirus genus, provided a similar phylogenetic grouping as other genomic regions. Intertypic recombination was not observed, but Border disease virus (BDV) and Bovine viral diarrhoea virus type 1 (BVDV I) showed great intragenotypic variability. In most pestiviruses the stop codon is TGA, but BDV isolates were found to have either a TAG or a TAA stop codon. Various deletions and insertions were observed in the 3-UTR region. Viruses of the BVDV Ib group contained a characteristic deletion of 41 nucleotides. Compared to the 5-UTR, the 3-UTR was less conserved. The first 50–60 nucleotides were particularly variable, whilst the most conserved part was found at the 3 end of the studied region. All 82 viruses contained AT-rich stretches, the positions and sizes of which differed between the genotypes.     

Characterization of the hog cholera virus 5′ terminus

Hog cholera virus (HoCV) 5 terminus of the ALD and GPE(–) strains were analyzed by using rapid amplification of cDNA end method (5RACE). An additional nine nucleotides were found at the 5 termini of genomic RNA in the ALD and GPE(–) strains of HoCV. These nine nucleotides were also conserved in BVDV and were suggested to form a hairpin structure at the 5 terminus by computer-assisted analysis. It seems possible that the secondary structure and/or the 5 terminus sequence has a significant role in the HoCV virus genome.     

The 5′ untranslated region of PVY RNA,even located in an internal position,enables initiation of translation

Potato virus Y (PVY) is the type member of the potyvirus group. Potyviruses, like picorna-, como-, and nepoviruses, belong to the picornavirus-like supergroup. All these viral RNAs have a VPg at their 5 end, and for four picornaviruses and one comovirus internal initiation of translation has been reported. To know if such a translational mechanism holds true for potyviral RNAs, the 5 nontranslated region (NTR) of PVY RNA was placed in an internal position, either by adding 91 bases upstream of the PVY 5NTR or by inserting the PVY 5NTR into an intercistronic region. The addition of extra bases stimulates translation in a rabbit reticulocyte lysate, and the presence of the PVY 5NTR in the intercistronic region allows the synthesis of the second cistron. These findings strongly suggest that PVY RNA initiates translation by an internal ribosome-binding mechanism. Furthermore, the use of antisense oligodeoxynucleotides indicates that the entire 5NTR seems to be involved in such a mechanism.     

The nonselective cation channel in the basolateral membrane of rat exocrine pancreas

Nonselective Ca²⁺-sensitive cation channels in the basolateral membrane of isolated cells of the rat exocrine pancreas were investigated with the patch clamp technique. With 1.3 mmol/l Ca²⁺ on the cytosolic side, the mean openstate probabilityP _o of one channel was about 0.5. In insideout oriented cell-excised membrane patches the substances diphenylamine-2-carboxylic acid (DPC), 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) and 3,5-dichlorodiphenylamine-2-carboxylic acid (DCDPC) were applied to the cytosolic side. These compounds inhibited the nonselective cation channels by increasing the mean channel closed time (slow block). 100 mol/l of NPPB or DPC decreasedP _o from 0.5 (control conditions) to 0.2 and 0.04, respectively, whereas 100 mol/l of DCDPC blocked the channel completely. All effects were reversible. 1 mmol/l quinine also reducedP _o, but in contrast to the abov mentioned substances, it induced fast flickering. Ba²⁺ (70 mmol/l) and tetraethylammonium (TEA⁺; 20 mmol/l) had no effects. We investigated also the stilbene disulfonates 4-acetamido-4-isothiocyanatostilbene-2,2-disulfonic acid (SITS), 4,4-diisothiocyanatostilbene-2,2-disulfonic acid (DIDS) and 4,4-dinitro-2,2-stilbenedisulfonate (DNDS). 10 mol/l SITS applied to the cytosolic side increasedP _o from 0.5 to 0.7 and with 100 mol/l SITS the channels remained nearly permanently in its open state (P _o1). A similar activation of the channels was also observed with DIDS and DNDS. These effects were poorly reversible. The stilbene disulfonates acted by increasing the channel mean open time. When the channel was inactivated by decreasing bath Ca²⁺ concentration to 0.1 mol/l, addition of 100 mol/l of SITS had no effect. Similarly, reducing bath Ca²⁺ concentration from 1.3 mmol/l in presence of 100 mol/l SITS (channels are maximally activated) to 0.1 mol/l, inactivated the channels completely. These results demonstrate, that SITS can only activate the channels in the presence of Ca²⁺. SITS had no effects, when applied to the extracellular side in outside out patches. In summary, the substances DPC, NPPB and DCDPC inhibit nonselective cation channels, where DCDPC has the most potent and NPPB the smallest effect; whereas SITS, DIDS and DNDS activate the channel when applied from the cytosolic side in the presence of Ca²⁺ ions.     

Aspects of the oxidative metabolism of nicotine

Conclusions The balance of the excreted sum of nicotine and its known metabolites from confirmed results reflects great progress in recent years and today accounts for about 40–60% of the estimated or known intake of the alkaloid, calculating on the basis of parts of well-defined and reliably determined species. The main part of this balance is accounted for by products of the -oxidation of nicotine in the 5-position. A further 40% has recently been attributed to those parts of metabolites which are additionally found after the treatment of urine samples with enzymes generally known to act on phase II metabolites. Conjugates of nicotine, cotinine, and trans-3-hydroxycotinine are held responsible for this. Recently, some of these products have been definitely characterized and determined by direct measurements.Quantitative data are missing on the 1,2-iminium ion, the very recently identified tautomer of 2-hydroxynicotine in urine, and the nature of its prevailing tautomeric form which both are biologically high importance, have there been reports so far on the mechanism for their metabolic formation. Further, the metabolic fate of nornicotine, the first metabolite of the intermediary methylene iminium species, is still awaiting elucidation. Nornicotine is excreted in only a very small ratio. This may be caused by demythylation or by oxidation. Further conclusions require knowledge of the actual structures of the nicotine metabolites under different analytical pH values or in organic solvents. The respective proportions of the tautomeric structures in the biological media in general and especially at the active sites of enzymes determine the metabolic pathways of nicotine and its subsequent metabolites and should be the aim of intense investigations.     

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     

Intracellular pH in renal tubules in situ: single-cell measurements by confocal laserscan microscopy

Confocal laserscan microscopy with a dual-excitation device was used to record intracellular pH (pH_i) regulation in rat proximal convoluted tubules microperfused in vivo. Cells were loaded with the pH-sensitive, fluorescent dye 2,7-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF). Single cells could be distinguished within the tubules and separate measurements were possible. Application of an NH₄Cl pulse by peritubular perfusion caused an immediate increase in intracellular pH. Intraluminal injection of NH₄Cl led to a slower increase in intracellular pH. In both cases, cessation of perfusion led to an immediate acidification. Peritubular perfusion with 300 M 4,4-diisothiocanatodihydrostilbene-2, 2-disulphonic acid (H₂DIDS) caused an intracellular alkalinisation. Microperfusion, pH-sensitive dyes and confocal laserscan microscopy provide a new non-invasive method to measure intracellular pH effectively in individual cells of near-surface structures of the intact kidney.     

Effect of o,p-dichlorodiphenyldichloroethane and perthane in vitro on glutathione reductase activity in the adrenals of dogs and guinea pigs

o,p-Dichlorodiphenyldichloroethane (o,p-DDD) and Perthane, when added in a concentration of 312 M to homogenate and cytoplasmic fraction of dog adrenals, activate glutathione reductase. In a concentration of 156 M, o,p-DDD and Perthane do not affect glutathione reductase activity of the dog adrenals. When given in vitro, o,p-DDD and Perthane activate glutathione reductase of the guinea pig adrenals. o,p-DDD has no effect on glutathione reductase activity of the cytoplasmic fraction of dog liver and kidney, thus confirming the high specificity of its effect on the adrenal cortex.Laboratory of Pathophysiology, Institute of Endocrinology and Metabolism, Kiev. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 2, pp. 159–161, February, 1978.     

Inverse Correlation Between IgG-Antihinge Region and Antierythrocyte Autoantibody in Chronic Benign and Malignant Cold Agglutination

Previous reports provided evidence of an immunosuppressive role of natural anti-F(ab)₂ antibodies. If suppressive anti-F(ab)₂ antibodies also regulated the autoantibody production in cold agglutination, one would expect high titers of anti-F(ab)₂ to be associated with low titers of cold agglutinins. Indeed, our previous studies revealed an inverse correlation between IgG-anti-F(ab)₂ and cold agglutinins. Many previous experiments focused on anti-F(ab)₂ of an antiidiotypic nature. Recent epitope mapping showed that anti-F(ab)₂ of healthy persons is not an antiidiotype but recognizes a hinge region sequence. We attempted to answer the question whether this IgG-antihinge antibody is responsible for the previously described association between anti-F(ab)₂ and cold agglutinins. IgG-antihinge and IgG-anti-F(ab)₂ antibody was determined and statistically analyzed in the serum of 334 patients with cold agglutination. Our experiments revealed a strong correlation between the concentrations of antihinge and the previously described anti-F(ab)₂ antibody. The anti-F(ab)₂ activity was competitively inhibited by a synthetic hinge peptide. Moreover, patients with high antihinge titers had low cold agglutinin titers, and vice versa. A stratification according to cold agglutinin specificity and disease etiology showed that the inverse correlation is present only in anti-I and anti-i patients suffering from monoclonal B-lymphocyte proliferation. In conclusion, our results confirm the correlation previously described for anti-F(ab)₂ antibody and antierythrocyte autoantibody and define for the first time an association between an idiotype-independent anti-IgG autoantibody and cold agglutinin.     

DNA fingerprinting involving fluorescence-labeled termini of any enzymatically generated fragments of DNA

Summary We have developed a new fluorescence-based method for DNA fingerprinting that does not require a fluorescent linker or a synthetic oligonucleotide primer, both of which are normally used for labeling of DNA. Cosmid DNAs are digested with appropriate restriction enzymes and the 3 termini of DNA fragments are labeled with the corresponding, fluorescent dye-conjugated dideoxynucleotide triphosphate terminator (dye-ddNTP) by the Klenow fragment of DNA polymerase I fromEscherichia coli, which has 35 exonuclease and replacement activities as well as its main 53 polymerase activity. Samples are separated on a DNA-sequencing gel and data are analyzed by application of both the Version 0.3.8a mapper program (Applied Biosystem Inc., Foster City, CA) and our Overlap I program that facilitate rapid analysis of the frequency of overlapping of cosmid DNAs. Using this method we have determined the overlap frequency of DNA fragments of each cosmid clone from the mouse MHC class I gene cluster.     

Negative inotropic effect of cyclic GMP in cardiac fiber fragments

Summary The force of spontaneously beating cardiac cellular fragments obtained from mice heart by homogenization was recorded in presence of cyclic guanosine –3.5-monophosphate (cGMP) and cyclic 8-bromguanosine –3.5-monophosphate in concentrations of 3×10^–6 M –33×10^–6 M. The nucleotide decreased the force and reduced the rate of spontaneity. Eventually the preparation became quiescent. It is thought that this nucleotide either reduces the capacity to sequester calcium or affects its release from the sarcotubular system.     

High Level of Sequence Variation in the 3′ Noncoding Region of Japanese Encephalitis Viruses Isolated in Korea

The 3 noncoding region (NCR) of Japanese encephalitis (JE) viruses isolated in Korea and Nakayama-NIH strain have been sequenced and compared with the 3 NCR sequences of other JE isolates reported previously. Sequence alignment of about 60 nucleotides (based on consensus sequence number) immediately downstream of the open reading frame (ORF) stop codon in the 3 NCR of the Korean isolates showed high degree of sequence variation and deletion; thus, this region was termed as the variable region. However, in the predicted RNA secondary structures, a similar type loop exists at the 5-terminus of the 3 NCR of JE viruses, despite low level of sequence homology (22%) and deletion in the variable region. The phylogenetic tree based on the 3 NCR sequences of JE viruses including the variable region showed a similar pattern to that based on envelope genes; in that, there are two genetically different types of JE viruses in Korea. Therefore, the variable region would be a useful genetic marker for JE viruses.     

A point mutation in the 5′-untranslated leader that affects translational activation of the mitochondrial COX 3 mRNA

The 613-base 5-untranslated leader (5-UTL) of the Saccharomyces cerevisiae mitochondrial COX 3 mRNA contains the target of an mRNA-specific translational activator complex composed of at least three nuclearly encoded proteins. We have genetically mapped a collection of cox 3 point mutations, using a set of defined COX 3 deletions, and found one to be located in the region coding the 5-UTL. The strain carrying this allele was specifically defective in translation of the COX 3 mRNA. Nucleotide-sequence analysis showed that the allele was in fact a double mutation comprised of a single-base insertion in the 5-UTL (T inserted between bases-428 and-427 with respect to the start of translation) and a G to A substitution at+3 that changed the ATG initiation codon to ATA. Both mutations were required to block translation completely. The effects of the ATG to ATA mutation alone (cox 3-1) had previously been analyzed in this laboratory: it reduces, but does not eliminate, translation, causing a slow respiratory growth phenotype. The T insertion in the 5-UTL had no detectable respiratory growth phenotype as a single mutation. However, the 5-UTL insertion mutation enhanced the respiratory defective phenotype of missense mutations in pet 54, one of the COX 3-specific translational-activator genes. This phenotypic enhancement suggests that the-400 region of the 5-UTL, where the mutation is located, is important for Pet54p-COX 3 mRNA interaction.     

Isomerisierung und biologische Verfügbarkeit von β- und α-Acetyldigoxin

Zusammenfassung An gesunden Versuchspersonen wurde die biologische Verfügbarkeit der Acetylester des Digoxins nach einmaliger wie nach mehrfacher Applikation bestimmt. Die relative Verfügbarkeit von -Acetyldigoxin (Dioxanin®) ist um 30% geringer als die von -Acetyldigoxin (Novodigal®). Auch eine Inkorporation von -Acetyldigoxin in eine Aerosilmatrix als Trägersubstanz bewirkt keine signifikante Veränderung der biologischen Verfügbarkeit gegenüber dem -Acetyldigoxin. In alkalischem Medium wird die Acetylgruppe aus der -Position in die -Position verlagert. Diese Isomerisierung führt zu einer Abnahme der biologischen Verfügbarkeit bei solchen Kombinationspräparaten, die -Acetyldigoxin und hygroskopische Salze des Kalium-Magnesium-Aspartats (z.B. Gladixol®) enthalten. Nach Abisolierung des -Acetyldigoxinanteils vom Kalium-Magnesium-Aspartat in der Tablette wird eine dem Monopräparat (Novodigal®) vergleichbare biologische Verfügbarkeit erreicht und damit auch eine gleiche therapeutische Äquivalenz. Die Untersuchungen zeigen, daß die biologische Verfügbarkeit entscheidend von den physiko-chemischen Eigenschaften des Wirkstoffes und seiner galenischen Zubereitung beeinflußt werden kann.Mit Unterstützung des Ministeriums für Jugend, Familie und Gesundheit     

Distribution of anti-F(ab′)2 antibodies and the 16/6 idiotype in systemic lupus erythematosus (SLE) probands and kindreds

Levels of serum anti-F(ab)₂ antibodies and expression of the 16/6 anti-DNA idiotype were studied in 103 sera from first-degree relatives of 17 systemic lupus erythematosus (SLE) kindreds. Among healthy SLE relatives, 35.9% showed anti-F(ab)₂ elevations and 24%, Id 16/6 expression. Forty-three and two-tenths percent of healthy SLE relatives with elevated anti-F(ab)₂ also showed expression of 16/6; when Id 16/6 was positive, 16 of 25 relatives (64%) showed parallel elevations of anti-F(ab)₂. However, within individual families, distribution patterns of elevated anti-F(ab)₂ and Id 16/6 often did not coincide. Affinity-isolated anti-F(ab)₂ from four members of a single SLE kindred showed relative enrichment for Id 16/6 in only two of the four individuals studied. Moreover, none of the isolated anti-F(ab)₂ antibodies within this kindred or another kindred showing 16/6 Id expression reacted directly with 16/6 Id. Our studies suggest that whereas both anti-F(ab)₂ and Id 16/6 are increased within SLE kindreds, expression of the two does not always coincide. Furthermore, anti-F(ab)₂ antibodies do not show direct reactivity with Id 16/6. A number of anti-DNA idiotypic markers may play a role in idiotypic networks among such SLE kindreds.     

Increase in TCRγδ T lymphocytes in synovia from rheumatoid arthritis patients with active synovitis

To determine the relative presence of TCR+ and TCR+ T cells in synovial tissue from patients with various types of inflammatory synovitis and in tissues from patients with a number of chronic T cell-mediated conditions, we stained frozen tissue sections with monoclonal antibodies in indirect immunofluorescence assays. In tissues obtained from patients with chronic T cell-mediated granulomatous conditions (Wegener's granulomatosis, lymphomatoid granulomatosis, granuloma annulare, Langerhan's cells granulomatosis, pigmented villonodular synovitis, Takayasu's arteritis, and talc granulomatosis), the T cells present were predominantly TCR+, without an increased presence of TCR+ cells. In contrast, 6 of 14 (43%) synovia from patients with rheumatoid arthritis (RA) showed increased TCR+ T cells (3–10 cells/hpf). The RA synovia with increased TCR+ cells present had an increased tissue inflammation score compared to RA synovia with few TCR+ cells [18.6±5.8 versus 11.6±4.2 (mean±SE),P<0.05]. In contrast, synovia from patients with osteoarthritis, systemic lupus erythematosus, and trauma did not show an increased presence of TCR+ T cells. Thus, in cellular inflammatory infiltrates the presence of increased TCR cells is not a component of noninfectious granulomatous inflammation but is found in approximately 40% of RA synovia with high levels of inflammation.