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Biomedical subjects

K Iizuka

Publications and source records attributed to K Iizuka.

At least 55 records · Page 3Linked to original sources
PubMed1998

Genetic control of natural killing and in vivo tumor elimination by the Chok locus.

The molecular mechanisms underlying target recognition during natural killing are not well understood. One approach to dissect the complexities of natural killer (NK) cell recognition is through exploitation of genetic differences among inbred mouse strains. In this study, we determined that interleukin 2-activated BALB/c-derived NK cells could not lyse Chinese hamster ovary (CHO) cells as efficiently as C57BL/6-derived NK cells, despite equivalent capacity to kill other targets. This strain-determined difference was also exhibited by freshly isolated NK cells, and was determined to be independent of host major histocompatibility haplotype. Furthermore, CHO killing did not correlate with expression of NK1.1 or 2B4 activation molecules. Genetic mapping studies revealed linkage between the locus influencing CHO killing, termed Chok, and loci encoded within the NK gene complex (NKC), suggesting that Chok encodes an NK cell receptor specific for CHO cells. In vivo assays recapitulated the in vitro data, and both studies determined that Chok regulates an NK perforin-dependent cytotoxic process. These results may have implications for the role of NK cells in xenograft rejection. Our genetic analysis suggests Chok is a single locus that affects NK cell-mediated cytotoxicity similar to other NKC loci that also regulate the complex activity of NK cells.

Alleles↗
PubMed1998

InsP3, but not novel Ca2+ releasers, contributes to agonist-initiated contraction in rabbit airway smooth muscle.

1. To examine the contributions of the putative Ca2+ releasers, inositol 1,4,5-trisphosphate (InsP3), cyclic ADP ribose (cADPR), and nicotinate adenine dinucleotide phosphate (NAADP), to carbachol (CCh)-induced contraction in airway smooth muscle, we measured force development of permeabilized rabbit tracheal smooth muscle, human bronchial smooth muscle and guinea-pig ileum longitudinal smooth muscle. 2. In the presence of 50 microM GTP, CCh and InsP3 contracted alpha-toxin-permeabilized tracheal smooth muscle dose dependently; the EC50 values for CCh and InsP3 were 1.84 microM and 363 microM, and the maximum responses (normalized to the 30 mM caffeine response) to 100 microM CCh and to 800 microM InsP3 were 206 +/- 13.4 % (mean +/- S.E.M.) and 84.4 +/- 5.3 %, respectively. 3. However, cADPR (10-300 microM), beta-NAD+ (2.5 mM), FK506 (30 microM) and NAADP (100 microM) neither contracted the strip by themselves nor affected the subsequent CCh (1 microM) response. alpha-Toxin-permeabilized bronchial smooth muscle and ileum smooth muscle also responded to caffeine, InsP3 and CCh but not to cADPR. 4. Both 100 microM 8-amino-cADPR, a selective cADPR antagonist, and 100 microM thionicotinamide-NADP, a selective NAADP antagonist, failed to inhibit the CCh response, although procaine abolished the caffeine, InsP3 and CCh responses in the permeabilized tracheal smooth muscle. 5. Although inhibition of the caffeine response by 30 microM ryanodine was nearly complete, approximately 30 % of the InsP3 (300 microM) plus GTP (50 microM) response was retained, and the resultant response disappeared after the caffeine response was evoked in the presence of ryanodine. 6. Heparin (300 microg ml-1) blocked InsP3 (300 microM) and CCh (3 microM) responses in beta-escin-permeabilized tracheal smooth muscle, while Ruthenium Red (100 microM) partially inhibited the CCh response. 7. Collectively, InsP3 but not cADPR or NAADP plays a key role in CCh-initiated contraction, and InsP3 utilizes a single compartment of the caffeine/ryanodine-sensitive stored Ca2+ in airway smooth muscle.

Adenosine Diphosphate Ribose↗
PubMed1998

Increased mRNA expression of cardiac renin-angiotensin system and collagen synthesis in spontaneously hypertensive rats.

Hypertensive cardiac hypertrophy is associated with the accumulation of collagen in the myocardial interstitium. Previous studies have demonstrated that this myocardial fibrosis accounts for impaired myocardial stiffness and ventricular dysfunction. Although cardiac fibroblasts are responsible for the synthesis of fibrillar collagen, the factors that regulate collagen synthesis in cardiac fibroblasts are not fully understood. We investigated the effects of angiotensin II on cardiac collagen synthesis in cardiac fibroblasts. Cardiac fibroblasts of 10 week old spontaneously hypertensive rats and age-matched Wistar-Kyoto rats were prepared and maintained in culture medium supplemented with 10% fetal calf serum. The expression of mRNA of the renin-angiotensin system (renin, angiotensinogen, angiotensin converting enzyme) was determined by using a ribonuclease protection assay. Basal collagen synthesis in cardiac fibroblasts from spontaneously hypertensive rats was 1.6 fold greater than that in the cell of Wistar-Kyoto rats. Angiotensin II stimulated collagen synthesis in cardiac fibroblasts in a dose-dependent manner. The responsiveness of collagen production to angiotensin II was significantly enhanced in cardiac fibroblasts from spontaneously hypertensive rats (100 nM angiotensin II resulted in 185 +/- 18% increase above basal levels, 185 +/- 18 versus 128 +/- 19% in Wistar-Kyoto rats p < 0.01). This effect was receptor-specific, because it was blocked by the competitive inhibitor saralasin and MK 954. These results indicate that collagen production was enhanced in cardiac fibroblasts from spontaneously hypertensive rats, that angiotensin II had a stimulatory effect on collagen synthesis in cardiac fibroblasts, and that cardiac fibroblasts from spontaneously hypertensive rats were hyper-responsive to stimulation by angiotensin II. Level of angiotensin and renin mRNA expressed in ventricles, and angiotensinogen mRNA expressed in fibroblasts from SHR were higher than those from WKY. These findings suggest that the cardiac renin-angiotensin system may play an important role in collagen accumulation in hypertensive cardiac hypertrophy.

Angiotensin II↗
PubMed1998

Surgical techniques for benign parotid tumors: segmental resection vs extracapsular lumpectomy.

In 80 patients surgical techniques for benign parotid gland tumor have been reviewed and evaluated. Segmental resection was introduced during partial superficial parotidectomy. The superficial lobe of the parotid gland was divided into four sections according to the distribution of the tumors. Total parotidectomy was applied to remove deep lobe and recurrent tumors, together with the superficial lobe, followed by retrograde dissection of the facial nerve. This technique was termed the hamburger technique. Furthermore, with a margin of normal tissue, extracapsular lumpectomy was used. Segmental resection is at method of extirpation by dissecting the facial nerve, whereas extracapsular lumpectomy is a method of extirpation by dissecting the tumor itself with a safety margin.

Adenolymphoma↗
PubMed1998

Kimura's disease associated with bronchial asthma presenting eosinophilia and hyperimmunoglobulinemia E which were attenuated by suplatast tosilate (IPD-1151T).

A 29-year-old man developed atopic bronchial asthma in association with eosinophilia and hyperimmunoglobulinemia E (hyper-IgE). A biopsy specimen from an inguinal lymph node showed changes consistent with Kimura's disease. IPD-1151T (suplatast tosilate), an anti-allergy drug, attenuated eosinophilia and hyper-IgE as well as the serum level of eosinophil cationic protein (ECP). The drug, however, did not affect the positivity for specific IgE antibodies against common allergens or the bronchial hyperresponsiveness to acetylcholine. Interleukin (IL)-2, IL-4, IL-5, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha were measured to be undetectable in serum before or during therapy. However, the expressions of mRNAs for IL-2, IL-4, IL-5, IFN-gamma, and TNF-alpha in peripheral blood T-lymphocytes and the expression of IL-5 mRNA in peripheral blood eosinophils were detected before and during therapy, which were unchanged by therapy with IPD-1151T. The present results suggest that different mechanisms other than the predominance of type 2 helper (T(H2))-like T-lymphocytes may underlie Kimura's disease and atopic bronchial asthma regarding the findings of eosinophilia and hyper-IgE, which could be modulated by IPD-1151T.

Adult↗
PubMed1997

Effects of two familial hypertrophic cardiomyopathy-causing mutations on alpha-tropomyosin structure and function.

Missense mutations in alpha-tropomyosin can cause familial hypertrophic cardiomyopathy. The effects of two of these, Asp175Asn and Glu180Gly, have been tested on the structure and function of recombinant human tropomyosin expressed in Escherichia coli. The F-actin affinity (measured by cosedimentation) of Glu180Gly was similar to that of wild-type, but Asp175Asn was more than 2-fold weaker, whether or not troponin was present. The mutations had no apparent effect on the affinity of tropomyosin for troponin. The mutations had a small effect on the overall stability (measured using circular dichroism) but caused increased local flexibility or decreased local stability, as evaluated by the higher excimer/monomer ratios of tropomyosin labeled with pyrene maleimide at Cys 190. The pyrene-labeled tropomyosins differed in their response to myosin S1 binding to the actin-tropomyosin filament. The conformations of the two mutants were different from each other and from wild-type in the myosin S1-induced on-state of the thin filament. Even though both mutant tropomyosins bound cooperatively to actin, they did not respond with the same conformational change as wild-type when myosin S1 switched the thin filament from the off- to the on-state.

Actins↗
PubMed1997

Host F1 mice pretreated with granulocyte colony-stimulating factor accept parental bone marrow grafts in hybrid resistance system.

In the setting of hybrid resistance, parental C57BL/6 bone marrow (BM) grafts are vigorously rejected by lethally irradiated (C57BL/6xDBA/2) F1 mice. However, F1 mice pretreated by continuous administration of granulocyte colony-stimulating factor (G-CSF) with a miniosmotic pump before BM grafting developed day-8 splenic colonies of donor origin. This inhibitory effect on rejection was reversible because F1 mice regained the capacity to reject parental BM when the pump ceased functioning. The appearance of only a small number of colonies with the administration of G-CSF soon after BM grafting suggested the importance in producing this inhibitory effect of pre-exposure of host mice to G-CSF. Because G-CSF administration with a syngeneic combination did not influence the number of colonies, an altered distribution of grafted precursors was unlikely. The absence of a reduction in the number of NK1.1-positive cells in G-CSF-treated mice suggested functional impairment of natural killer cells, major effectors in hybrid resistance, but further study is necessary to elucidate the mechanism underlying this phenomenon. However, our results indicate the importance of G-CSF as a regulator in a certain type of immune response and raise the possibility of clinical application in transplantation medicine.

Adjuvants, Immunologic↗
PubMed1997

Receptor-dependent G protein-mediated Ca2+ sensitization in canine airway smooth muscle.

To determine the mechanisms of receptor-dependent Ca2+ sensitization in airway smooth muscle, canine tracheal smooth muscle (CTSM) was permeabilized with alpha-toxin or beta-escin. Although the effects of 5-hydroxytryptamine (100 microM), histamine (100 microM), and the thromboxane A2 analogue U-46619 (100 microM) were negligible, carbachol (100 microM) and endothelin-1 (ET-1, 1 microM) evoked additional contractions of 47.0 +/- 5.90% and 25.0 +/- 5.37% (n = 6) at pCa 6.7 with GTP (3 microM) (normalized to the maximum contraction at pCa 4.5) in alpha-toxin-permeabilized CTSM. GDP-beta-S (1 mM) reversed the carbachol and ET-1 responses completely. GTP-gamma-S (30 microM) and 4 beta-phorbol 12,13-dibutyrate (PDBu, 3 microM) increased the Ca2+ sensitivity (median effective pCa) of contraction by 1.8- and 4.4-fold, respectively (n = 4-11, P < 0.05). The effects of saturating concentrations of GTP-gamma-S and PDBu were additive. A synthetic peptide (T2) corresponding to the actin-binding site of calponin caused a dose-dependent contraction of beta-escin permeabilized CTSM, with the peak effect (25 +/- 4%, n = 4) at 1200 microM, PDBu (3 microM) caused contraction of the T2 peptide-treated CTSM. In conclusion, Ca2+ sensitization of CTSM depends on receptor type and is mediated by G proteins and protein kinase C whose effects are additive, with a partial contribution by calponin.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

Targeted ablation of the murine alpha-tropomyosin gene.

We created a mouse that lacks a functional alpha-tropomyosin gene using gene targeting in embryonic stem cells and blastocyst-mediated transgenesis. Homozygous alpha-tropomyosin "knockout" mice die between embryonic day 9.5 and 13.5 and lack alpha-tropomyosin mRNA. Heterozygous alpha-tropomyosin knockout mice have approximately 50% as much cardiac alpha-tropomyosin mRNA as wild-type littermates but similar alpha-tropomyosin protein levels. Cardiac gross morphology, histology, and function (assessed by working heart preparations) of heterozygous alpha-tropomyosin knockout and wild-type mice were indistinguishable. Mechanical performance of skinned papillary muscle strips derived from mutant and wild-type hearts also revealed no differences. We conclude that haploinsufficiency of the alpha-tropomyosin gene produces little or no change in cardiac function or structure, whereas total alpha-tropomyosin deficiency is incompatible with life. These findings imply that in heterozygotes there is a regulatory mechanism that maintains the level of myofibrillar tropomyosin despite the reduction in alpha-tropomyosin mRNA.

Animals↗
PubMed1996

Effect of KMD-3213, an alpha 1a-adrenoceptor-selective antagonist, on the contractions of rabbit prostate and rabbit and rat aorta.

KMD-3213, (-)-(R)-1-(3-hydroxypropyl)-5-[2-[[2-[2-(2,2,2-trifluoroethoxy) phenoxy]ethyl]amino]propyl]indoline-7-carboxamide, a newly synthesized alpha 1-adrenoceptor antagonist, has been shown to have potent action toward, and to be selective for human cloned and native alpha 1-adrenoceptors. In the present study, we characterized the inhibitory effect of KMD-3213 on the phenylephrine (alpha 1-adrenoceptor-selective agonist)-induced contraction of rabbit prostate, rabbit thoracic aorta and rat thoracic aorta to functionally confirm the tissue selectivity of KMD-3213. The mean pA2 value for KMD-3213 for the inhibition of the rabbit prostatic contraction was 10.05, whereas the values for the rabbit and rat aortic contractions were 9.36 and 8.13, respectively. The order of mean pA2 values for the inhibition of the rabbit prostatic contraction was KMD-3213 > or = tamsulosin >> prazosin, whereas that for the rabbit and rat aortic contractions was tamsulosin > KMD-3213 > prazosin and tamsulosin > or = prazosin >> KMD-3213, respectively. KMD-3213 produced a sigmoidal inhibition curve for single-dose phenylephrine-induced contractions of rabbit prostate, whereas it produced a non-sigmoidal curve for that of rabbit aorta. KMD-3213 had no effect on isoproterenol-induced chronotropic action in guinea-pig atria, and 5-hydroxytryptamine-, histamine- and acetylcholine-mediated contractions of rabbit aorta. These results indicate that the potency of the inhibitory activity of KMD-3213 depends on the tissue subtype expression and that KMD-3213 preferentially antagonizes prostatic contraction.

Adrenergic alpha-Antagonists↗
PubMed1996

Role of guanine nucleotide-binding proteins--ras-family or trimeric proteins or both--in Ca2+ sensitization of smooth muscle.

The purpose of this study was to identify guanine nucleotide-binding proteins (G proteins) involved in the agonist- and guanosine 5'-[gamma-thio]triphosphate (GTP[gamma-S])-induced increase in the Ca2+ sensitivity of 20-kDa myosin light chain (MLC20) phosphorylation and contraction in smooth muscle. A constitutively active, recombinant val14p21rhoA.GTP expressed in the baculovirus/Sf9 system, but not the protein expressed without posttranslational modification in Escherichia coli, induced at constant Ca2+ (pCa 6.4) a slow contraction associated with increased MLC20 phosphorylation from 19.8% to 29.5% (P < 0.05) in smooth muscle permeabilized with beta-esein. The effect of val14p21rhoA.GTP was inhibited by ADP-ribosylation of the protein and was absent in smooth muscle extensively permeabilized with Triton X-100. ADP-ribosylation of endogenous p21rho with epidermal cell differentiation inhibitor (EDIN) inhibited Ca2+ sensitization induced by GTP [in rabbit mesenteric artery (RMA) and rabbit ileum smooth muscles], by carbachol (in rabbit ileum), and by endothelin (in RMA), but not by phenylephrine (in RMA), and only slowed the rate without reducing the amplitude of contractions induced in RMA by 1 microM GTP[gamma-S] at constant Ca2+ concentrations. AlF(4-)-induced Ca2+ sensitization was inhibited by both guanosine 5'-[beta-thio]diphosphate (GDP[beta-S]) and by EDIN. EDIN also inhibited, to a lesser extent, contractions induced by Ca2+ alone (pCa 6.4) in both RMA and rabbit ileum. ADP-ribosylation of trimeric G proteins with pertussis toxin did not inhibit Ca2+ sensitization. We conclude that p21rho may play a role in physiological Ca2+ sensitization as a cofactor with other messengers, rather than as a sole direct inhibitor of smooth muscle MLC20 phosphatase.

Animals↗
PubMed1996

Expression of epidermal growth factor and its receptor in rabbits with ischaemic acute renal failure.

Urinary immunoreactive epidermal growth factor (EGF) levels decrease, and renal immunoreactive EGF levels increase in rats with ischaemic acute renal failure (ARF). We investigated the immunohistochemical localization of EGF and EGF receptor in rabbits with ischaemic ARF to clarify the significance of renal EGF. Male New Zealand White rabbits underwent right nephrectomy prior to a 60 min renal artery clamp. At 3, 6, 24, 48, 72 and 96 h after ischaemia, serum urea nitrogen and serum creatinine were determined. Guinea pig anti-rabbit EGF antibody and monoclonal anti-EGF receptor antibody were used for the primary incubation. EGF was immunolocalized to the ascending limb of Henle and the distal convoluted tubule in the normal right kidneys. However, in the post ischaemic left kidneys at 6, 24, 48 and 72 h, immunoreactivity of EGF was associated with proximal tubules. In the normal kidneys, antibody to EGF receptor reacted with distal tubules and collecting ducts. In the ischaemic kidneys, EGF receptor was localized in the basolateral membrane in the proximal tubules. The expression of EGF and EGF receptor in renal tubules may play an important role in repair following ischaemic renal damage.

Acute Kidney Injury↗
PubMed1996

An electrical knee lock system for functional electrical stimulation.

An electrical knee lock system that can be combined with functional electrical stimulation was designed for paraplegic patients. This knee system unlocks the knee electrically and allows knee flexion during the swing phase of the gait. When the knee is extended by electrical stimulation of the knee extensors, the knee is automatically locked by the weight of the locking bar, and the stimulation of the knee extensors is stopped. Since the knee extensors are stimulated for only a short period, muscle fatigue of the knee extensors seldom occurs. We applied this system to a T8 completely paraplegic patient. Standing-up, standing, walking, and sitting-down motions were all restored by our hybrid system. No electrical stimulation was necessary during standing, and the knee extensors were stimulated during only a small percentage of the 1-gait cycle.

Adult↗
PubMed1996

Effect of cetirizine on antigen-induced tracheal contraction of passively sensitized guinea pigs.

BACKGROUND: Cetirizine dihydrochloride (cetirizine), a potent histamine H1-receptor antagonist, has been developed as an anti-allergy drug. OBJECT: The anti-allergic effects and mechanism of cetirizine were studied using in vitro assay systems. METHODS: We investigated the effect of cetirizine on antigen-induced contractions of isolated tracheal strips and on chemical mediator release from antigen-stimulated lung chips taken from passively sensitized guinea pigs. We examined the antigen-induced mobilization of Ca2+ in MC/9 mast cells sensitized with IgE. RESULTS: Cetirizine inhibited the antigen-induced contraction of isolated guinea-pig trachea concentration dependently. Pyrilamine, another histamine H1-receptor antagonist, delayed the response but did not change the maximum amplitude. Cetirizine at the concentration of 3 microM also inhibited the antigen-induced release of histamine, leukotriene D4, and leukotriene E4 from guinea pig lung chips. Furthermore, it inhibited the antigen-induced Ca2+ increase in MC/9 mast cells, whereas pyrilamine did not. CONCLUSION: These findings suggest that one anti-allergic mechanism of cetirizine may inhibit mediator release which is, at least partially, mediated by a decrease in the transient Ca2+ influx in mast cells.

Animals↗
PubMed1996

Total replacement of urethral mucosa with oral mucosa in dogs.

PURPOSE: If the urethral mucosa is replaced by another mucosa, urethral recurrence might decrease in patients who undergo neobladder construction for bladder cancer. We determined whether such replacement is possible. MATERIALS AND METHODS: Six dogs underwent an operation consisting of a longitudinal urethral incision at its full length and immediate closure. In 6 other dogs, after the urethral mucosa was totally removed, a tubularized sublingual mucosa was closely set inside the urethral lumen. Postoperatively, the urinary stream and external meatus were observed every day. To measure urine leakage, a 10-minute pad test was performed once a month. All dogs were sacrificed 3 to 12 weeks after the operation for histological examination of the urethra. The excised urethras were examined with a 12F catheter for urethral patency. RESULTS: All dogs were continent postoperatively. The results of the 10-minute pad test showed no significant difference in the weight increase of the pad among the control, sham-operated and mucosa-replaced dogs. Urethral stricture developed in 1 mucosa-replaced dog. Histological examination revealed that all of the grafted oral mucosa survived in the urethra. CONCLUSION: These results indicate that the urethral mucosa can be replaced by oral mucosa without damaging the continence mechanism in female dogs.

Animals↗
PubMed1996

Allergic responses reduce the relaxant effect of beta-agonists but not potassium channel openers in guinea-pig isolated trachea.

This study was conducted to determine whether the relaxant effect of adenosine triphosphate (ATP)-sensitive potassium channel (KATP) openers on airway smooth muscle are reduced during the hyporesponsiveness of beta-adrenergic receptors. Isometric tension was measured and dose-response curves were constructed for levcromakalim (a KATP opener), Y-26763 (another KATP opener), isoprenaline and theophylline in guinea-pig isolated trachea that was challenged with ovalbumin or pretreated in vitro with either isoprenaline or the KATP openers. Antigen challenge in vitro significantly reduced the potency but not the efficacy of isoprenaline in tracheal strips from actively sensitized guinea-pigs. The concentration of drug that produced a half-maximum inhibition (IC50) was 0.014 +/- 0.004 microM in the challenge group versus 0.006 +/- 0.001 microM in the control group (p < 0.05; n = 9). The IC50 of levcromakalim (1.73 +/- 0.17 microM; n = 6) and of theophylline (110 +/- 3.1 microM; n = 6) were unaffected. Exposure to 4 microM isoprenaline for 30 min evoked beta-adrenergic hyporesponsiveness: the IC50 of isoprenaline rose significantly from 0.010 +/- 0.001 to 0.017 +/- 0.002 microM (p < 0.01; n = 6). No effect was observed on the relaxant actions of levcromakalim and theophylline. In contrast, prior incubation with either levcromakalim or Y-26763 (300 microM for 30 min) significantly reduced the subsequent potency and efficacy of levcromakalim, but did not alter the effects of isoprenaline and theophylline. We conclude that the relaxant effect of the adenosine triphosphate-sensitive potassium channel openers was independent of beta-adrenergic hyporesponsiveness in airway smooth muscle of guinea-pigs.

Adrenergic beta-Agonists↗
PubMed1996

Lack of CD54 expression and mutation of p53 gene relate to the prognosis of childhood Burkitt's lymphoma.

Expression of the intercellular adhesion molecule-1 (CD54) as well as the mutations of p53 gene were studied in childhood Burkitt's lymphoma (BL). Expression of CD54 was identified in 6 of 15 fresh BL cases. Mutations of p53 gene, analyzed by polymerase chain reaction-single stranded chain polymorphism followed by sequencing, were found in 5 of 14 cases examined. Interestingly, all the cases with p53 mutation were CD54 negative. This high frequency of p53 mutation in the CD54 negative group prompted us to analyze the clinical features of these cases. Six of 15 cases died within 21 months after initiation of therapy and five of these were CD54 negative. In addition, four of these had p53 mutation. These results suggest that the lack of CD54 by BL cells may provide the background for the mutation of p53 gene to occur which could result in the transformation to a more aggressive phenotype.

Adolescent↗