The role of complement in the progression of renal fibrosis: a clinical study.
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Animals↗
Biomedical subjects
K Nishikawa
Publications and source records attributed to K Nishikawa.
A comparison of hemodynamic changes after endotracheal intubation by using the lightwand device and the laryngoscope in normotensive and hypertensive patients.
We compared the effects of the lightwand technique on hemodynamic responses, time-to-intubation, number of attempts, and complications during tracheal intubation with those of direct-vision laryngoscopy in normotensive (LN and TN group; n = 20, respectively) and hypertensive (LH and TH group; n = 20, respectively) patients. Lightwand or laryngoscopic oral endotracheal intubation was performed after the induction of anesthesia with fentanyl and propofol and muscle relaxation with vecuronium. Systolic blood pressure, diastolic blood pressure, and heart rate were recorded, and the change from "before intubation" to "immediately after intubation" (DeltaP) in each variable was calculated. In normotensive patients, significantly larger DeltaP in systolic blood pressure was observed in the LN group than in the TN group (P < 0. 05). In hypertensive patients, there were no significant differences between the LH group and the TH group in DeltaP after intubation. The time-to-intubation and number of attempts in the lightwand groups were significantly longer and more frequent than those in the laryngoscope groups (P < 0.05). The number of patients who complained of hoarseness was larger in the lightwand groups than in the laryngoscope groups (P < 0.05). We conclude that the lightwand technique significantly attenuates hemodynamic changes after intubation in comparison with the laryngoscopic technique in normotensive patients. However, in hypertensive patients, there is no difference in hemodynamic changes between the two techniques.
Anesthesia↗
Fentanyl improves analgesia but prolongs the onset of axillary brachial plexus block by peripheral mechanism.
UNLABELLED: We evaluated the effects of fentanyl added to lidocaine for axillary brachial plexus block in 66 adult patients scheduled for elective hand and forearm surgery. In this double-blinded study, all patients received 40 mL of 1.5% lidocaine with 1:200,000 epinephrine, injected into the brachial plexus sheath using the axillary perivascular technique, and they were randomized into three groups. Group 1 was given lidocaine containing 2 mL of normal saline plus 2 mL of normal saline IV. Patients in Group 2 received lidocaine containing 100 microg fentanyl plus 2 mL of normal saline IV. Group 3 patients received lidocaine containing 2 mL of normal saline plus 100 microg fentanyl IV. Sensory and motor blockade were evaluated by using a pinprick technique and by measuring the gripping force, respectively. The success rate of sensory blockade for radial and musculocutaneous nerves and the duration of the sensory blockade significantly increased in Group 2 (323 +/- 96 min) as compared with Group 1 (250 +/- 79 min). However, onset time of analgesia was prolonged in every nerve distribution by adding fentanyl to brachial plexus block. IV fentanyl had no effect on the success rate, onset, or duration of blockade. We conclude that the addition of fentanyl to lidocaine causes an improved success rate of sensory blockade but a delayed onset of analgesia, although this may be accounted for by the decreased pH caused by the fentanyl. IMPLICATIONS: It is still unclear whether the addition of a peripheral opioid is useful for nerve blockade in humans. Peripheral application of fentanyl to lidocaine for axillary brachial plexus blockade in this study provided an improved success rate of sensory blockade and prolonged duration.
Analgesics, Opioid↗
Excitatory synaptic transmission mediated by NMDA receptors is more sensitive to isoflurane than are non-NMDA receptor-mediated responses.
BACKGROUND: Effects of volatile anesthetic agents on N-methyl-D-aspartate (NMDA) receptor-mediated excitatory synaptic transmission have not been well characterized. The authors compared effects produced by halothane and isoflurane on electrophysiologic properties of NMDA and non-NMDA receptor-mediated synaptic responses in slices from the rat hippocampus. METHODS: Field excitatory postsynaptic potentials (fEPSPs) in the CA1 area were recorded with extracellular electrodes after electrical stimulation of Schaffer-collateral-commissural fiber inputs. NMDA or non-NMDA receptor-mediated fEPSPs were pharmacologically isolated using selective antagonists. Clinically relevant concentrations of halothane or isoflurane were applied to slices in an artificial cerebrospinal fluid perfusate. Paired pulse facilitation was used as a measure of presynaptic effects of the anesthetic agents. RESULTS: Clinically relevant concentrations of halothane (1.2 vol% approximately 0.35 mM) depressed fEPSP amplitudes mediated by NMDA receptors and non-NMDA receptors to a similar degree (mean +/- SD: 63.3 +/- 14.0% of control, n = 5; 60.2 +/- 7.3% of control, n = 7, respectively). In contrast, isoflurane (1.4 vol% approximately 0.50 mM) preferentially depressed fEPSP amplitudes mediated by NMDA receptors (44.0 +/- 7.4% of control, n = 6, P < 0.001) compared with those for non-NMDA receptors (68.7 +/- 5.4% of control n = 6), indicating a selective, additional postsynaptic effect. Paired pulse facilitation of fEPSPs was increased significantly by both anesthetic agents from 1.37 +/- 0.13 to 1.91 +/- 0.25 (n = 5, P < 0.05 for halothane) and from 1.44 +/- 0.04 to 1.64 +/- 0.08 (n = 5, P < 0.01 for isoflurane), suggesting that presynaptic mechanisms are also involved in fEPSP depression produced by the anesthetic agents. Neither rise times nor decay times of fEPSPs were changed in the presence of the anesthetic agents. CONCLUSIONS: These results indicate that fEPSPs mediated by postsynaptic NMDA receptors are more sensitive to clinically relevant concentrations of isoflurane than are non-NMDA receptor-mediated responses, but this selective effect was not observed for halothane. Both agents also appeared to depress release of glutamate from nerve terminals via presynaptic actions.
Anesthetics, Inhalation↗
Non-Helicobacter pylori and non-NSAID peptic ulcer disease in the Japanese population.
BACKGROUND: Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs) are recognized as the major causes of peptic ulcer disease. The status of H. pylori infection in the background population may influence the incidence of H. pylori-negative peptic ulcer disease. OBJECTIVE: To examine the incidence of H. pylori-negative peptic ulcer disease without intake of NSAIDs in Japan. PATIENTS: A total of 398 patients who had no eradication therapy for H. pylori prior to this study, including 246 patients with gastric ulcer (GU) and 152 patients with duodenal ulcer (DU), were enrolled. METHODS: H. pylori status was assessed by rapid urease tests, histological examinations (haematoxylin & eosin stain, Giemsa stain and/or immunostaining) and serum IgG antibody. Two biopsy specimens were taken from the antrum within 3 cm of the pyloric and two from the middle corpus of the stomach, along the greater curvature. Patients were asked a series of questions regarding risk factors, including the use of NSAIDs. The presence of gastritis, gastric atrophy and intestinal metaplasia was examined according to the updated Sydney system. RESULTS: Of the 246 patients with GU, 12 patients (4.9%) were considered to be H. pylori-negative. Of the 152 patients with DU, two patients (1.3%) were considered to be H. pylori-negative. Hence, a total of 14 patients were found to be H. pylori-negative. Nine of them were taking NSAIDs. Consequently, the frequency of H. pylori-negative ulcer without intake of NSAIDs was 1.3%. There was no significant difference in the frequencies of H. pylori-negative patients between the GU and DU groups. CONCLUSION: The incidence of H. pylori-negative peptic ulcer disease without intake of NSAIDs was very low in the Japanese population.
Adult↗
Identification of a two-component signal transduction system involved in fimbriation of Porphyromonas gingivalis.
Porphyromonas gingivalis, a periodontopathogen, is an oral anaerobic gram-negative bacterium with numerous fimbriae on the cell surface. Fimbriae have been considered to be an important virulence factor in this organism. We analyzed the genomic DNA of transposon-induced, fimbria-deficient mutants derived from ATCC 33277 and found that seven independent mutants had transposon insertions within the same restriction fragment. Cloning and sequencing of the disrupted region from one of the mutants revealed two adjacent open reading frames (ORFs) which seemed to encode a two-component signal transduction system. We also found that six of the mutants had insertions in a gene, fimS, a homologue of the genes encoding sensor kinase, and that the insertion in the remaining one disrupted the gene immediately downstream, fimR, a homologue of the response regulator genes in other bacteria. These findings suggest that this two-component regulatory system is involved in fimbriation of P. gingivalis.
Amino Acid Sequence↗
[Angiotensin II receptor antagonists: candesartan cilexetil].
Blockade of the action of angiotensin II (AII) has long been a target for the development of novel antihypertensive agents. We recently discovered a novel class of potent nonpeptide AII receptor antagonists, benzimidazole-7-carboxylic acids including candesartan. Candesartan is a highly potent and insurmountable AII type-1 receptor (AT1)-selective antagonist. Structure-activity relationship (SAR) studies revealed that the adjacent arrangement of a lipophilic substituent, a tetrazolylbiphenylmethyl moiety and a carboxyl group was the important structural requirement for potent AII antagonistic activity. Especially, the presence of a carboxyl group at the 7-position was found to be essential for insurmountable antagonism. To improve bioavailability of candesartan, chemical modification was examined to yield candesartan cilexetil, a prodrug of candesartan. Candesartan cilexetil is a potent and long-acting blocker that, when given once a day to patients, provides effective 24 hr blood pressure control.
Angiotensin Receptor Antagonists↗
[Pulsatile flow detection for evaluation of tumor vessels of hepatocellular carcinoma].
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Aged↗
[Myocardial involvement in rheumatic diseases].
The rheumatic diseases share many features. Clinically, they are often systemic diseases affecting multiple organs. Pathologically, these diseases share in common a diffuse vasculitis with an inflammatory process. Involvement of myocardium is also pathologically a common finding in rheumatic diseases, especially systemic sclerosis and dermatopolymyositis. Although clinical symptoms are often silent, potentially life-threatening manifestations are well known. Non invasive techniques such as nuclear imaging and echocardiography are useful to detect occult cardiac lesions. Clinically overt cardiac involvement portends an unfavorable prognosis. Early detection of subclinical involvement of myocardium is essential to improve prognosis.
Cardiomyopathies↗
Basis of variable sensitivities of GABA(A) receptors to ethanol.
BACKGROUND: The GABA(A) system is believed to be one of the crucial target sites for ethanol. However, in the literature, data using various preparations yielded controversial conclusions regarding the ethanol potency to modulate the activity of GABA(A) receptors. We have previously shown that the potency of n-alcohols to potentiate GABA-induced currents is correlated with their carbon chain length. This correlation was further compared among four cell types in an attempt to explain the variable potencies of ethanol to potentiate GABA responses. METHODS: Whole-cell patch clamp experiments were performed to determine and compare the potencies of n-alcohols in potentiating GABA-induced currents in rat dorsal root ganglion (DRG) neurons, human embryonic kidney cells expressing the rat alpha1beta2gamma2S or alpha1beta2gamma2L subunits, and rat cortical neurons. RESULTS: The GABA(A) receptors of the four cell types tested were all sensitive to n-alcohols, albeit with different potencies and efficacies. The effective concentration to increase GABA-induced currents to 125% of control (EC125) was correlated with the carbon chain length of n-alcohols, but slopes for this relationship are different among DRG neurons, the alpha1beta2gamma2S, and alpha1beta2gamma2L subunits. Thus, the potencies of lower alcohols such as ethanol differed among these cell types although higher alcohols such as n-octanol were almost equally potent. In cortical neurons, however, the relationship was shifted in the direction of longer carbon chains, indicating that their sensitivity was lower than those of the other three cell types. The ethanol EC125 values as obtained by experiments or those by extrapolation (in parenthesis) from the EC125-carbon chain length relationship were: 169 (103) mM for DRG neurons, 501 (333) mM for the alpha1beta2gamma2L subunits, 781 (674) mM for the alpha1beta2gamma2S subunits, and (1897) mM for cortical neurons. CONCLUSIONS: It was concluded that the GABA(A) receptors of these four cell types were basically sensitive to n-alcohols including ethanol but the sensitivity curve was shifted to the lower side in the order of decreasing sensitivity of DRG neurons > alpha1beta2gamma2L > alpha1/beta2gamma2S > cortical neurons.
Action Potentials↗
[Treatment of common bile duct stones--from the viewpoint of physicians].
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Adult↗
Antigen-driven expansion and contraction of CD8+-activated T cells in primary EBV infection.
The origin of the increased numbers of CD8+ atypical lymphocytes, expressing activated markers such as HLA-DR or CD45RO, in the peripheral blood of patients with infectious mononucleosis (IM) has been debated. Using a recently developed assay to detect intracellular accumulation of IFN-gamma in EBV-reactive T cells by FACS, we have demonstrated that 34-54% of HLA-DR+/CD8+ and 34-60% of CD45RO+/CD8+ T cells in the PBMCs of febrile patients suffering from IM are EBV-specific. The EBV-specific CD8+ T cell counts in the PBMCs of four febrile patients suffering from IM ranged between 2,260 and 8,200/microl, decreasing to 5.1% and 7.9% of the counts in the first samples over 10 days in two donors. The decline of CD8+ T cell subpopulations, namely HLA-DR+, CD45RO+, and EBV-specific T cells, was in parallel with the drop in the EBV genome load. These data indicate that the Ag-driven expansion of CD8+ T cells and subsequent contraction with the Ag decline in vivo in humans is effective for clearing virus-infected cells with minimal disturbance of the homeostasis of the immune system.
Antigens, Viral↗
Direct Observation by Electrospray Ionization Mass Spectrometry of
The use of methanol as solvent is essential for the formation of the double-bookshelf-type oxide cluster [(Cp*Rh)(2)Mo(6)O(20)(OMe)(2)](2-) from [{Cp*Rh(µ-Cl)Cl}(2)] and four equivalents of [Mo(2)O(7)](2-). The reaction proceeds via [Cp*RhMo(3)O(8)(OMe)(5)](-). The proposed structure for this key intermediate (shown schematically) is supported by electrospray ionization mass spectrometry and labeling experiments with CD(3)OD as solvent. Cp*=eta(5)-C(5)Me(5).
Journal Article↗
Strong hydrophobic nature of cysteine residues in proteins.
The differences between disulfide-bonding cystine (Cys_SS) and free cysteine (Cys_SH) residues were examined by analyzing the statistical distribution of both types of residue in proteins of known structure. Surprisingly, Cys_SH residues display stronger hydrophobicity than Cys_SS residues. A detailed survey of atoms which come into contact with the sulfhydryl group (sulfur atom) of Cys_SH revealed those atoms are essentially the same in number and variety as those of the methyl group of isoleucine, but are quite different to those of the hydroxyl group of serine. Moreover, the relationships among amino acids were also determined using the 3D-profile table of known protein structures. Cys_SH was located in the hydrophobic cluster, along with residues such as Met, Trp and Tyr, and was clearly separated from Ser and Thr in the polar cluster. These results imply that free cysteines behave as strongly hydrophobic, and not hydrophilic, residues in proteins.
Algorithms↗
Octopamine inhibits synaptic transmission at the larval neuromuscular junction in Drosophila melanogaster.
The effect of octopamine, a biogenic amine, on synaptic transmission at the neuromuscular junction (NMJ) in first instar larvae of Drosophila melanogaster was examined using the patch clamp technique. Muscle cells were voltage-clamped at -60 mV in the whole-cell configuration, and nerve-evoked excitatory junctional currents (EJCs) and miniature excitatory junctional currents (MEJCs) were recorded. Octopamine significantly decreased the mean amplitude of nerve-evoked EJCs in a dose-dependent manner and increased the failure rate. However, the mean amplitude and amplitude distribution of MEJCs were not affected by octopamine. These results suggest that octopamine is acting presynaptically. This effect was abolished by pretreatment with the octopamine receptor blocker, yohimbine. On the other hand, octopamine significantly decreased the decay time constant of MEJCs from 6.0+/-0.3 ms (mean+/-S.E., n=16) to 4.2+/-0.3 ms (n=14) (p<0.001), which might be the effect on the kinetic properties of junctional glutamate receptor channels. However, the mean open time of extrajunctional glutamate receptor channels was not changed by octopamine. Taken together, these results suggest that octopamine inhibits synaptic transmission by affecting both pre- and postsynaptic mechanisms.
Animals↗
Design and synthesis of a globin fold.
We propose a simple method to find an amino acid sequence that is foldable into a globular protein with a desired structure based on a knowledge-based 3D-1D compatibility function. An asymmetric alpha-helical single-domain structure of sperm whale myoglobin consisting of 153 amino acid residues was chosen for the design target. The optimal sequence to fit the main-chain framework has been searched by recursive generation of the protein 3D profile. The heme-binding site was designed by fixing His64 and His93 at the distal and proximal positions, respectively, and by penalizing residues that protrude into the space with a repulsive function. The apparent bumps among side chains in the computer model of the converged, self-consistent sequence were removed by replacing some of the bumping residues with smaller ones according to the final 3D profile. The finally obtained sequence shares 26% of sequence with the natural myoglobin. The designed globin-1 (DG1) with the artificial sequence was obtained by expression of the synthetic gene in Escherichia coli. Analyses using size-exclusion chromatography, circular dichroism spectroscopy, and solution X-ray scattering showed that DG1 folds into a monomeric, compact, highly helical, and globular form with an overall molecular shape similar to the target structure in an aqueous solution. Furthermore, it binds a single heme per protein molecule, which exhibited well-defined spectroscopic properties. The radius of gyration of DG1 was determined to be 20.6 A, slightly larger than that of natural apoMb, and decreased to 19.5 A upon heme binding based on X-ray scattering analysis. However, the heme-bound DG1 did not stably bind molecular oxygen as natural globins do, possibly due to high conformational diversity of side-chain structures observed in the NMR and denaturation experiments. These results give insight into the relationship between the sequence selection and the structural uniqueness of natural proteins to achieve biological functions.
Amino Acid Sequence↗
Inhibition of a membrane complement regulatory protein by a monoclonal antibody induces acute lethal shock in rats primed with lipopolysaccharide.
Rats pretreated with traces of LPS developed acute fatal shock syndrome after i.v. administration of a mAb that inhibits the function of a membrane complement regulatory molecule. Such a shock was not observed after the administration of large amounts of LPS instead of the mAb following LPS pretreatment. The lethal response did not occur in rats depleted of either leukocytes or complement, and a C5a receptor antagonist was found to inhibit the reaction. Furthermore, LPS-treated rats did not suffer fatal shock following the injection of cobra venom factor, which activates complement in the fluid phase so extensively as to exhaust complement capacity. Therefore, complement activation on cell membranes is a requirement for this type of acute reaction.
Acute Disease↗
Domain dislocation: a change of core structure in periplasmic binding proteins in their evolutionary history.
Periplasmic binding proteins (PBPs) serve as receptors for various water-soluble ligands in ATP-binding cassette (ABC) transport systems, and form one of the largest protein families in eubacterial and archaebacterial genomes. They are considered to be derived from a common ancestor, judging from their similarities of three-dimensional structure, their mechanism of ligand binding and the operon structure of their genes. Nevertheless, there are two types of topological arrangements of the central beta-sheets in their core structures. It follows that there must have been differentiation in the core structure, which we call "domain dislocation", in the course of evolution of the PBP family. To find a clue as to when the domain dislocation occurred, we constructed phylogenetic trees for PBPs based on their amino acid sequences and three-dimensional structures, respectively. The trees show that the proteins of each type clearly cluster together, strongly indicating that the change in the core structure occurred only once in the evolution of PBPs. We also constructed a phylogenetic tree for the ABC proteins that are encoded by the same operon of their partner PBP, and obtained the same result. Based on the phylogenetic relationship and comparison of the topological arrangements of PBPs, we obtained a reasonable genealogical chart of structural changes in the PBP family. The present analysis shows that the unidirectional change of protein evolution is clearly deduced at the level of protein three-dimensional structure rather than the level of amino acid sequence.
ATP-Binding Cassette Transporters↗