Regulatory T cell networks in the secretory immune system.
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Administration, Oral↗
Biomedical subjects
K Kitamura
Publications and source records attributed to K Kitamura.
Mapping of the ras1 gene of Schizosaccharomyces pombe.
The ras1 gene, an oncogene homologue, is known to be essential for recognition of the mating pheromone and hence for conjugation but not for vegetative growth in Schizosaccharomyces pombe. To facilitate further characterization and genetic manipulation of this gene, we have mapped it by using S. pombe strains which carry the Saccharomyces cerevisiae LEU2 gene inserted next to ras1 on the chromosome. Crosses with tester strains revealed that ras1 is tightly linked to pro2 on chromosome I. Furthermore, we have shown that ras1 is allelic with ste5, one of the sterility genes described by O. Girgsdies. The map position previously reported for ste5 eventually turned out to be false.
Alleles↗
Blocking actions of Ca2+ antagonists on the Ca2+ channels in the smooth muscle cell membrane of rabbit small intestine.
Actions of Ca2+ antagonists, verapamil, nicardipine and diltiazem, were investigated on the Ca2+ inward current in the fragmented smooth muscle cell membrane (smooth muscle ball; SMB) obtained from the longitudinal muscle layer of the rabbit ileum, by enzymatic dispersion. All Ca2+ antagonists inhibited the inward current, in a dose-dependent manner. The ID50 value on the maximum amplitude of the inward current of nicardipine was 24 nM, and this value was roughly 50 times lower than values obtained with verapamil and diltiazem, when the inward current was provoked by 0 mV command pulse from the holding potential of -60 mV. Lowering the holding potential to -80 mV shifted the dose-response curve to the right. When depolarizing pulses (100 ms, stepped up to 0 mV from -60 mV or -80 mV) were applied every 20 s, the peak amplitude of the inward current remained unchanged, but nicardipine immediately, and diltiazem and verapamil slowly reduced the peak amplitude. These slow inhibitions by the latter two drugs depended on the frequency or number of stimulations. Nicardipine but not diltiazem and verapamil shifted the voltage-dependent inactivation curve to the left (3 s duration of the conditioning pulse). However, with a longer conditioning pulse (10 s) verapamil and diltiazem shifted the voltage-dependent inactivation curves to the left. Therefore, the inhibitory actions of these Ca2+ antagonists differ. Namely, diltiazem and verapamil inhibit the Ca2+ channels, mainly in a frequency- or use-dependent manner while nicardipine does so in a voltage-dependent manner.
Animals↗
Different inhibitions of the voltage-dependent K+ current by Ca2+ antagonists in the smooth muscle cell membrane of rabbit small intestine.
Actions of Ca2+ antagonists (verapamil, nicardipine and diltiazem) on the voltage-dependent K+ current, obtained from the fragmented smooth muscle cell membrane (smooth muscle ball; SMB) of the rabbit small intestine, were investigated using voltage clamp techniques. To eliminate the influence of the Ca2+-dependent K+ current, the voltage-dependent K+ current was recorded in 2.5 mM Mn2+ (Ca2+ omitted) solution. These three Ca2+ antagonists inhibited the peak amplitude of the K+ current, in a dose-dependent manner. During application of a long command pulse (duration, 3 s), the amplitude of the voltage-dependent K+ current decreased slowly with time. Diltiazem inhibited the K+ current with a slight prolongation of the 20% decay time, while TEA (tetraethyl-ammonium), a K+ channel blocker, inhibited the current, without affecting the decay. By contrast, verapamil and nicardipine accelerated inactivation. In the control, the voltage-dependent inactivation was also seen in the K+ current. This inactivation curve below 0 mV was not modified by 10 microM diltiazem, 5 microM verapamil nor 3 microM nicardipine. These results indicate that inhibition of the voltage-dependent K+ current by verapamil or nicardipine differed from that by diltiazem.
Animals↗
Effects of neurotensin on electrical and mechanical properties of smooth muscles in longitudinal and circular layers of the guinea-pig ileum.
Effects of neurotensin (NT) on the electrical and mechanical activities of longitudinal and circular muscles of the guinea-pig ileum were investigated using the microelectrode and isometric tension recording methods. In longitudinal muscles, the resting membrane potential was not affected by NT (0.1-30 nmol/l), but NT did provoke the contraction when applied in concentrations over 1 nmol/l. TTX (0.1 mumol/l) neither modified the resting membrane potential nor the contraction evoked by NT, under condition of pretreatment with alpha- and beta-adrenoceptor blockers. In circular muscles, NT (over 0.1 nmol/l) consistently hyperpolarized the membrane and increased the ionic conductance. The hyperpolarization appeared with a transient hyperpolarization, which gradually declined with a long time course. Using apamin and various concentrations of Ca, the NT-induced hyperpolarization was classified into two subtypes; fast and slow. The former was composed of maximum hyperpolarization due to activations of the Ca independent K channel, and the latter was composed of late hyperpolarization, due to activations of the Ca dependent K channel. During the NT-induced hyperpolarization in circular muscles, the amplitude of non-adrenergic, non-cholinergic inhibitory junction potential (i.j.p.) evoked by field stimulation was reduced. This reduction induced by 0.5 nmol/l NT was mainly due to hyperpolarization of the membrane, and that observed in a high concentration of NT (3 nmol/l) was directly involved in ionic mechanisms contributing to the generation of i.j.p. In circular muscles, NT (over 3 nmol/l) did relax the tissue pre-contracted with 17.8 mmol/l K, but NT (below 30 nmol/l) did not relax the tissue pre-contracted by 39.6 mmol/l K.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
D600 blocks the Ca2+ channel from the outer surface of smooth muscle cell membrane of the rabbit intestine and portal vein.
The voltage dependent Ca2+ inward current in single smooth muscle cells dispersed from the longitudinal muscle layer of the rabbit ileum and rabbit portal vein was recorded using the whole-cell voltage clamp technique. D600 added to the bathing solution inhibited the Ca2+ current, while the intracellular perfusion of this agent did not reduce the amplitude of this current. Thus, D600 probably acts from the outer surface of the membrane. The nature of the Ca2+ channel in smooth muscle cells seems to differ from that in cardiac muscle cells.
Animals↗
Acetylcholine activates single sodium channels in smooth muscle cells.
Using the whole-cell clamp technique with a patch electrode, single channel activities were recorded in dispersed single smooth muscle cells of the guinea-pig ileum in response to application of greater than 1 microM acetylcholine (ACh) or carbachol (CCh). Under physiological conditions (bath:Krebs, pipette:High K), these channels have a single channel conductance of 20-25 pS at the membrane potentials ranging between -100 and -40 mV and are activated in the membrane potential dependent manner. The amplitude of the channel current showed a strong dependence on the extracellular Na concentration but the reversal potential obtained by the extrapolation of the I-V relationship was not consistent with the equilibrium potential of Na ion. An approximate estimation of permeability ratio based on the independent principle described by Hodgkin et al. gave a value of Na:K = 1.0:0.3-0.4 to this channel. From features of the macroscopic and single channel currents, it is concluded that these muscarinic ACh(CCh)-activated channels mainly pass Na ion and play a major part in the membrane depolarization produced by ACh or CCh in mammalian intestinal smooth muscles.
Acetylcholine↗
Features of 4-aminopyridine sensitive outward current observed in single smooth muscle cells from the rabbit pulmonary artery.
The 4-aminopyridine (4AP) sensitive outward current of enzymatically dispersed single smooth muscle cells of the rabbit main pulmonary artery were investigated using the voltage clamp method. When the cell was exposed to physiological salt solution (PSS) in the bath and high K+ in the pipette no inward current was generated by depolarization of the membrane, but when 4AP was present in the bath or when Cs+ with tetraethylammonium+ (Cs+-TEA+) in the pipette, an inward current was generated. This current was enhanced by Ba2+ or high Ca2+ and was blocked by inorganic or organic Ca2+ channel blockers. The outward current was partly inhibited by the Ca2+ channel blockers, Ca2+-free or Mn2+ containing solution. The residual outward current was blocked by external application of 10 mM 4AP, whereas it was inhibited by half with 100 mM TEA+. To investigate further natures of 4AP sensitive outward current, the following experiments were done in the bath solution containing 2.5 mM Mn2+. The reversal potential of this outward current, estimated from the tail current, remained the same in Na+-deficient solution, but shifted to near the K+-equilibrium potential in Cl- deficient solution. Thus, the main current carrier for the outward current seems to be K+, but Cl- may participate to some extent. The amplitude of the outward current decreased slowly. However, the reversal potential was not changed, suggesting the reduction in amplitude of the outward current was not due to the accumulation of K+ on the outer surface of the membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
4-Aminopyridine↗
Modulation of ionic currents in smooth muscle balls of the rabbit intestine by intracellularly perfused ATP and cyclic AMP.
The effects of intracellularly perfused ATP and cyclic-AMP (c-AMP) on ionic currents recorded from fragmented smooth muscle cells (smooth muscle ball; SMB) were investigated, using the single electrode whole cell voltage clamp method. The Ca2+ current was distinguished from K+ currents, using pipette solution containing Cs+, TEA+ and 4 mM EGTA. ATP enhanced the Ca2+ current dose-dependently between 0.3 and 10 mM, and slightly slowed the slow component of the decay of the Ca2+ current, while the steady-state inactivation curve remained unaffected. Intracellular application of 5'-adenylyl-imidodiphosphate (AMP-PNP; 1 mM) inhibited the Ca2+ current by competition with ATP, but c-AMP (up to 300 microM) had no effect. With a high-K+ solution containing 0.3 mM EGTA and ATP in the pipette and physiological salt solution in the bath, a net inward current with transient (Ca2+ dependent) and delayed (Ca2+ independent) K+ outwart currents were evoked. Increased concentrations of ATP (above 1 mM) but not c-AMP (up to 100 microM) in the pipette enhanced the transient K+ outward current. Neither agent had any effect on the delayed outward current. When repetitive stimulations of intervals shorter than 5 s were applied, the amplitude of the transient outward current was markedly reduced, and 100 microM c-AMP partially prevented this attenuation. ATP may act on the Ca2+ channel either by phosphorylating the channel protein or by other ATP requiring mechanisms, independently from those induced by the action of c-AMP.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine Triphosphate↗
Cell kinetics of the malignant evolution of meningothelial meningioma.
A meningotheliomatous meningioma occurred in the right parietal parasagittal region of a 43-year-old woman. A total excision was carried out. Three years and 9 months later, one parasagittal and two falx tumors in close proximity recurred and were excised. The falx tumors showed the features of an anaplastic transitional meningioma with increased mitoses. The falx meningioma recurred locally and repeatedly, despite radiation therapy and chemoimmunotherapy. She died 7 years and 8 months after the onset. At autopsy, the tumor was found to have metastasized via the cerebrospinal fluid to the spinal cord and pituitary stalk. Extracranial metastases were not evident. At the fourth craniotomy, bromodeoxyuridine (BrdU) was administered intravenously to label tumor cells in the S phase of the cell cycle. The BrdU-labeled cells accounted for 9.0%; they are usually less than 1% in benign meningiomas. Meningothelial meningiomas with a high labeling index recur rapidly, even after Simpson's grade 2 removal, and treatment for a malignant meningioma should be instituted.
Antibodies, Monoclonal↗
Monoclonal antibodies against human scirrhous carcinoma of the stomach.
We established three monoclonal antibodies (MoAbs) S43, S74 and S202 which reacted strongly with scirrhous carcinomas of the stomach. MoAb S43 reacted with culture supernatants of the scirrhous gastric cancer cell line MK-01, and thus may be useful for in vivo detection of markers for this tumor. MoAb S74 reacted with the majority of gastric cancer tissues, but showed no reaction with normal tissues. It may be useful as a drug carrier in targeting chemotherapy against scirrhous gastric cancer, because of its tumor specificity. MoAb S202 reacted strongly with 100% of scirrhous gastric cancer samples and with the culture supernatants of colonic and pancreatic cancers.
Adenocarcinoma, Scirrhous↗
Localization of radiolabeled monoclonal antibody S74 in human scirrhous type gastric cancer xenografts in nude mice.
A mouse monoclonal antibody (MoAb), S74 against a human scirrhous gastric carcinoma cell line was developed. The radioiodinated antibody bound preferentially in vivo to xenografted tumors rather than to normal tissue, whereas tumor uptake of normal mouse IgG did not occur. Thus this MoAb was able to selectively localize a human tumor in an animal model, and clinically it may enable immunotherapy against scirrhous carcinoma of the stomach.
Adenocarcinoma, Scirrhous↗
Visualization of anti-I-J antibody binding sites on bone marrow-derived macrophages.
I-J antigens on BMDM were visualized by immunofluorescence. Nonspecific binding of IgG antibody to Fc receptors was eliminated by the pretreatment of the antibody with anti-mouse IgG Fc portion antibody.
Animals↗
Regulation of coronary artery tone in relation to the activation of signal transductors that regulate calcium homeostasis.
Muscle tone of coronary arteries is regulated by free calcium concentration in the myoplasm. Various agonists, autacoids and putative peptides modify the calcium concentration directly or through actions of second messengers (signal transductors), such as cyclic guanosine monophosphate (GMP), cyclic adenosine monophosphate (AMP), inositol 1,4,5-trisphosphate, diacylglycerol or calmodulin. For example, acetylcholine (in the presence of intact endothelium cells), alpha-human natriuretic peptide or nitrate compounds increase the amount of cyclic GMP and isoproterenol, prostacyclin (prostaglandin I2) or vasoactive intestinal polypeptide increases cyclic AMP. Both cyclic nucleotides reduce free calcium concentration. On the other hand, acetylcholine (in the presence or absence of endothelium cells), norepinephrine or thromboxane A2 increases inositol 1,4,5-trisphosphate and diacylglycerol, thus causing the increase in the free calcium concentration, whereas vasoactive intestinal peptide and alpha-human natriuretic peptide reduce them. Calmodulin acts as an internal calcium receptor for regulation of the contractile machinary. Regulation of calcium homeostasis in relation to the muscle tone in the coronary arteries including other vascular tissues is discussed together with the role of second messengers.
Arteries↗
Downbeat nystagmus during eye closure.
Two patients with dizzy spells demonstrated downbeat nystagmus during eye closure. The eye movements were examined by simultaneous horizontal and vertical electro-oculography. As the eyeballs were depressed to the midline position during eye closure, downbeat nystagmus appeared. There were no remarkable neurological findings in either patient. The pathophysiology of this nystagmus remains to be defined.
Adult↗
Identification of a cDNA coding for a fifth form of myelin basic protein in mouse.
The primary sequences of four molecular mass variants (14, 17, 18.5, and 21.5 kDa) of the mouse myelin basic protein (MBP) have recently been determined through analysis of cDNA clones of their mRNAs. The mRNAs coding for the four MBP variants are thought to arise by differential splicing of two exons (exons 2 and 6) from a single gene. In contrast, exons 2 and 5 may be spliced out in the posttranscriptional processing of the human MBP gene. To investigate the possibility that a third exon (exon 5) may also be differentially spliced out in the processing of the mouse MBP gene transcript, a mouse cDNA library was screened to search for cDNAs missing exon 5. A MBP cDNA was isolated whose coding region specified a fifth mouse MBP variant with a molecular mass of approximately equal to 17 kDa. The mass of this variant (17,257 Da) is so close to that of the other 17-kDa mouse MBP (17,224 Da) that the two would be indistinguishable on NaDodSO4/polyacrylamide gels. Analysis of the sequence of the cDNA clone indicates that excision of exons 2 and 5 of the mouse MBP gene would produce the mRNA encoding this newly described 17-kDa MBP, whereas excision of exon 6 would produce the mRNA for the other 17-kDa MBP variant. Thus, the "17-kDa" mouse MBP consists of at least two molecular forms with very similar molecular masses but markedly different primary sequences. Of five full-length or near full-length cDNAs representing 17-kDa MBPs, one was missing exons 2 and 5 and four were missing exon 6.
Amino Acid Sequence↗
Serological relationships between serotype-III Streptococcus sanguis and Lancefield group-H streptococci.
Certain strains of Streptococcus sanguis and group-H streptococci have been shown to have similar physiological properties and serological specificities. Serological studies revealed that serotype-III S. sanguis shared a common antigen with the so-called "British" group-H streptococci, but not with the "American" group-H streptococci. Serotype-III antigen was extracted in cold 5% trichloroacetic acid from isolated cell walls of S. sanguis ATCC 10558, and purified chromatographically. The purified serotype-III antigen consisted of neutral and amino sugars and some phosphorus, and was negatively charged. Hapten inhibition of the quantitative precipitin reaction between serotype-III antigen and antiserum indicated the strong possibility of alpha-glucosidic linkages being an immunodeterminant of the antigen.
Antigens, Bacterial↗
Action of the 1,4-dihydropyridine derivative, KW-3049, on the smooth muscle membrane of the rabbit mesenteric artery.
1. The effect of 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid methyl 1-(phenylmethyl)-3-piperidinyl ester hydrochloride (KW-3049) on the smooth muscle membrane of the rabbit mesenteric artery was investigated using microelectrode and single electrode voltage clamp methods. 2. In whole tissue preparations KW-3049 did not alter the resting membrane potential of the artery, but did inhibit the action potential evoked by a depolarizing current in the presence of 10 mM tetraethylammonium (TEA). 3. Using the voltage clamp technique, the effects of KW-3049 on the inward current evoked in solution containing 100 mM BaCl2 were observed. When the membrane was held at -60 mV, KW-3049 inhibited the inward current in a concentration-dependent manner. The inward current evoked by a larger depolarizing pulse was inhibited to a larger extent than that evoked by a smaller one. 4. When the membrane was held at -80 mV, the inward current evoked at test potentials of -10 and 0 mV was enhanced by low concentrations of KW-3049 (below 100 nM). 5. KW-3049 accelerated the rate of inactivation of the inward current and shifted the voltage-dependent inactivation curve to the left. 6. KW-3049 has a long-lasting inhibitory action on smooth muscle cells, since the inhibition of the inward current persisted for over 1 h after the removal of KW-3049. 7. Our results suggest that KW-3049 has a selective and long-lasting action on the Ca channels of the smooth muscle cell membrane of the rabbit mesenteric artery. This agent has both facilitatory and inhibitory actions on the Ca channel, depending on the values of the holding and command potentials.
Action Potentials↗