Histopathological findings in filtering blebs with recurrent blebitis.
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Aged↗
Biomedical subjects
H Obata
Publications and source records attributed to H Obata.
Bone defects in latent TGF-beta binding protein (Ltbp)-3 null mice; a role for Ltbp in TGF-beta presentation.
The latent transforming growth factor (TGF)-beta binding proteins (LTBP)-1, -3 and -4 bind the latent form of the multipotent cytokine TGF-beta. To examine the function of the LTBPs, we made a null mutation of Ltbp-3 by gene targeting. The homozygous mutant animals developed cranio-facial malformations by 12 days. By three months, there was a pronounced rounding of the cranial vault, extension of the mandible beyond the maxilla, and kyphosis. The mutant animals developed osteosclerosis of the long bones and vertebrae as well as osteoarthritis between 6 and 9 months of age. These latter phenotypic changes were similar to those described for mice that have impaired TGF-beta signaling. Thus, we suggest that Ltbp-3 plays an important role in regulating TGF-beta bioavailability as the phenotype of the Ltbp-3 null mouse appears to result from decreased TGF-beta signaling. Histological examination of the skulls from null animals revealed no effects on calvarial suture closure. However, the synchondroses in the skull base were obliterated within 2 weeks of birth. This is in contrast to the wild-type synchondroses, which remain unossified throughout the life of the animal and enable growth of the skull base through endochondral ossification. Histological changes in mutant basooccipital-basosphenoid synchondrosis were observed 1.5 days after birth. Compared with wild-type or heterozygous littermates, the basooccipital-basosphenoid synchondrosis of Ltbp-3 null mice contained increased numbers of hypertrophic chondrocytes. The expression of bone sialoprotein-1 (a marker for osteoblasts) was observed in cells surrounding the synchondrosis at postnatal day 1.5 indicating ectopic ossification. The expression of Indian hedgehog (Ihh) (a marker for chondrocytes committed to hypertrophic differentiation) was found through the basooccipital-basosphenoid synchondrosis, whereas the expression of parathyroid hormone related protein (PTHrP), which inhibits chondrocyte differentiation, appeared to be diminished in Ltbp-3 null mice. This suggests that Ltbp-3 may control chondrocyte differentiation by regulating TGF-beta availability. TGF-beta may regulate PTHrP expression either downstream of Ihh or independently of Ihh signaling.
Adaptor Proteins, Signal Transducing↗
Dye terminator re-cycle-sequencing method: phage plaque direct sequencing.
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Bacteriophage lambda↗
Apolipoprotein J/clusterin is induced in vascular smooth muscle cells after vascular injury.
BACKGROUND: Understanding the precise molecular mechanisms underlying the phenomenon of restenosis after PTCA may help us to develop a new strategy for the treatment of restenosis after PTCA. The purpose of this study was to identify the genes involved in vascular restenosis. METHODS AND RESULTS: Applying a differential hybridization method to a model of the balloon-injured rabbit aorta, we identified 6 cDNA clones that were upregulated after injury. Northern blot showed that 5 genes, but not apolipoprotein J (apoJ)/clusterin, were constitutively expressed in noninjured aorta and upregulated after balloon injury. ApoJ mRNA was not detectable in noninjured aorta (control), began to be expressed at 6 hours after injury, showed a peak level at 24 hours (a 48-fold increase), gradually declined, and returned to the control level at 24 weeks. Western blot and immunohistochemistry demonstrated no expression of apoJ protein in noninjured aorta, an expression of apoJ at 2 days after balloon injury, and a peak level (a 55-fold increase) at 2 to 8 weeks. The expression of apoJ protein continued until 24 weeks after injury. In situ hybridization revealed that apoJ mRNA was expressed in smooth muscle cells (SMCs) of media at 2 days after injury and in SMCs of media and neointima at 2 weeks. To analyze the function of apoJ, stably transfected rabbit SMCs were created. The expression of apoJ stimulated proliferation and migration of SMCs. CONCLUSIONS: ApoJ is dramatically induced in media and neointima after vascular injury, suggesting that apoJ contributes to restenosis after angioplasty.
Angioplasty, Balloon, Coronary↗
Effects of 5-HT2 and 5-HT3 receptors on the modulation of nociceptive transmission in rat spinal cord according to the formalin test.
We used the formalin test to clarify the 5-hydroxytryptamine (5-HT) receptor subtypes involved in the modulation of spinal nociceptive transmission in rats. Intrathecal administration of a 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)-tetraline (8-OH-DPAT; 1, 10, and 30 microg), or a 5-HT1B receptor agonist, 1, 4-dihydro-3-(1, 2, 3, 6-tetrahydro-4-pyridinyl)-5H-pyrrol (3, 2-b) pyridin-5-one (CP 93129; 1 and 10 microg), produced no significant change in the number of flinches. A 5-HT(2) receptor agonist, (+/-)-2, 5-dimethoxy-4-iodoamphetamine (DOI; 10, 30, and 100 microg), and a 5-HT3 receptor agonist, 2-methyl-5-HT (100 and 300 microg), produced dose-dependent decreases in the number of flinches in phases 1 (1 to 6 min) and 2 (10 to 61 min) of the test. The antinociceptive effects of DOI and 2-methyl-5-HT were antagonized by intrathecal pretreatment with a 5-HT2 receptor antagonist, ketanserin, and a 5-HT3 receptor antagonist, 3-tropanyl-3, 5-dichlorobenzoate (MDL-72222), respectively. These results suggest that 5-HT2 and 5-HT3 receptors in the spinal cord mediate antinociception to chemical stimuli.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Determination of picomolar levels of iron in seawater using catalytic cathodic stripping voltammetry.
A new procedure for the direct determination of picomolar levels of iron in seawater is presented. Cathodic stripping voltammetry (CSV) is preceded by adsorptive accumulation of the iron(III)-2,3-dihydroxynaphthalene (DHN) complex from seawater, containing 20 microM DHN at pH 8.0, onto a static mercury drop electrode, followed by reduction of the adsorbed species. The reduction current is catalytically enhanced by the presence of 20 mM bromate. Optimized conditions include a 60-s adsorption period at -0.1 V and a voltammetric scan using sampled dc modulation at 10 Hz. In these conditions, a detection limit of 13 pM iron in seawater was achieved which can be lowered further by extending the adsorption time to 300 s. The new catalytic CSV method is approximately 5 times more sensitive than existing CSV methods and was tested on samples from the Atlantic Ocean.
Journal Article↗
Antiallodynic effect of intrathecally administered 5-HT(2) agonists in rats with nerve ligation.
We examined the antiallodynic effect of intrathecally administered serotonin receptor agonists including 5-HT(1A), 5-HT(1B), 5-HT(2) and 5-HT(3) receptor subtypes in a rat model using spinal nerve ligation at L5 and L6. Administration of the 5-HT(2) receptor agonist, alpha-methyl-5-hydroxytryptamine maleate (alpha-m-5-HT; 3-100 microg) or (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI; 10-100 microg), showed dose-dependent antiallodynic actions with no associated motor weakness. The antiallodynic action of alpha-m-5-HT was more potent than that of DOI. The effects of 5-HT(2) agonists on tactile allodynia were reversed by intrathecal pretreatment with the selective 5-HT(2) antagonist ketanserin and with the mixed 5-HT(1) and 5-HT(2) antagonist methysergide. Neither the mixed 5-HT(1A) and 5-HT(1B) antagonist cyanopindolol nor the selective 5-HT(3) antagonist MDL72222 attenuated antiallodynic effects induced by 5-HT(2) agonists. In contrast, the selective 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)-tetralin hydrobromide (8-OH-DPAT; 1-50 microg), the 5-HT(1B) agonist 5-methoxy-3-(1,2,5,6-tetrahydro-4-pyridinil)-1H-indol (RU-24969; 10-100 microg) and the 5-HT(3) agonist 2-methyl-5-hydroxytryptamine maleate (2-m-5-HT; 30-300 microg) all lacked significant antiallodynic action with intrathecal administration. These results indicate that the 5-HT(2) receptor plays an essential role in spinal suppression of neuropathic pain by 5-HT.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Selection and timing of liver transplantation in primary biliary cirrhosis.
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Journal Article↗
Twenty-seven-year follow-up of arrhythmogenic right ventricular dysplasia.
This case report describes clinical features, especially of surface ECG changes, observed for 27 years in a patient with arrhythmogenic right ventricular dysplasia (ARVD). The course of this patient was characterized by progressive deterioration of right ventricular function and progression of delayed potentials (so-called epsilon waves) following QRS complexes. However, the relation between ventricular arrhythmias and ECG changes or the degree of right ventricular abnormality was difficult to discern.
Adult↗
Direct neurotoxicity of tetracaine on growth cones and neurites of growing neurons in vitro.
BACKGROUND: Local anesthetics have direct neurotoxicity on neurons. However, precise morphologic changes induced by the direct application of local anesthetics to neurons have not yet been fully understood. Also, despite the fact that local anesthetics are sometimes applied to the sites where peripheral nerves may be regenerating after injury, the effects of local anesthetics on growing or regenerating neurons have never been studied. METHODS: Three different neuronal tissues (dorsal root ganglion, retinal ganglion cell layer, and sympathetic ganglion chain) were isolated from an age-matched chick embryo and cultured for 20 h. Effects of tetracaine were examined microscopically and by a quantitative morphologic assay, growth cone collapse assay. RESULTS: Tetracaine induced growth cone collapse and neurite destruction. Three neuronal tissues showed significantly different dose-response, both at 60 min and at 24 h after the application of tetracaine (P < 0.01). The ED50 values (mean +/- SD) at 60 min were 1.53+/-1.05 mM in dorsal root ganglion, 0.15+/-0.05 mM in retinal, and 0.06+/-0.02 mM in sympathetic ganglion chain cultures. The ED50 values at 24 h were 0.43+/-0.15 mM in dorsal root ganglion, 0.07+/-0.03 mM in retinal, and 0.02+/-0.01 mM in sympathetic ganglion chain cultures. Concentration of nerve growth factor in the culture media did not influence the ED50 values. The growth cone collapsing effect was partially reversible in dorsal root ganglion and retinal neurons. However, in the sympathetic ganglion culture, no reversibility was observed after exposure to 1 mM tetracaine for 10 or for 60 min. Bupivacaine had similar neurotoxicity to the three types of growing neurons. (The ED50 values at 60 min were 2.32+/-0.50 mM in dorsal root ganglion, 0.96+/-0.16 mM in retinal, and 0.18+/-0.05 mM in sympathetic ganglion chain cultures. The ED50 values at 24 h were 0.34+/-0.09 mM in dorsal root ganglion, 0.21+/-0.06 mM in retinal, and 0.45+/-0.10 mM in sympathetic ganglion chain cultures.) CONCLUSIONS: Short-term exposure to tetracaine produced irreversible changes in growing neurons. Growth cones were quickly affected, and neurites degenerated subsequently. Sensitivity varied with neuronal type and was not influenced by the concentration of nerve growth factor. Because a similar phenomenon was observed after exposure to bupivacaine, the toxicity to growing neurons may not be unique to tetracaine.
Anesthetics, Local↗
[The trends of Vibrio parahaemolyticus foodborne outbreaks in Tokyo: 1989-2000].
The total number of foodborne outbreaks due to Vibrio parahaemolyticus in Tokyo during the last 12 years between 1989 and 2000 were 710. The number of outbreaks in a year was 55 in 1989, 75 in 1990, and there was a gradual decrease to 24 outbreaks in 1993 which was the smallest number during those 12 years. After 1994, the number of outbreaks increased dramatically year by year until 1998 (107 outbreaks). Then they had decreased slightly to 74 in 1999, 65 in 2000. The monthly incidence of V. parahaemolyticus foodborne outbreaks showed a peak in August (44.2%) each year. In the last 12 years, 88.7% of V. parahaemolyticus foodborne outbreaks occurred during the 3 months between July and September, while 99.9% occurred between June and October. The most prevalent serotype of V. parahaemolyticus also changed, the most prevalent was O4:K4 in 1989, O4:K8 in both 1990 and 1991, O1:K56 in 1992, and O4:K8 from 1993 through 1995. Serotype O3:K6 became the most prevalent in 1996 and has remained so to date. In addition, the new serotype O4:K68 had also appeared in 1998. The number of outbreaks due to serotype O4:K68 followed that of O3:K6. Thus, the trends of V. parahaemolyticus foodborne outbreaks during the last 12 years in Tokyo showed various characteristics and dramatic changes in causal organisms.
Disease Outbreaks↗
[Colony and phage-plaque direct sequencings by dye-terminator methods].
Direct sequencing using lambda phage DNA and E. coli colonies with plasmid DNA is a very powerful technique. Almost all of the reported direct sequencing methods involve either radioactive sequencing or fluorescent dye-primer sequencing. We present a direct colony sequencing strategy that uses a dye terminator (BigDye terminator kit) together with dye primer sequencing. We found that single-colony sequencing with the terminator yielded about 500 base pairs of sequence information. Signal strength was not improved when the number of cycles increased to 40. The colony used for the sequencing was estimated to contain about 5.6 x 10(7) cells. In addition, although a single plaque consisted of 2 x 10(6) cells, the pfu was not high enough to read with single-cycle sequencing, and only about 300 base pairs of sequence information were obtained from a single plaque using two cycle-sequencing reactions (re-cycle sequencing). The optimal amounts of the template were 500 ng of purified lambda DNA and 1 x 10(7) pfu of the lambda phage suspension, but with BigDye terminator it was possible to detect as little as 50 ng of purified lambda DNA and 2 x 10(6) pfu for lambda phage suspensions. Thus, colony direct sequencing and plaque direct sequencing are estimated to be very useful for rapid and high-throughout screening of genomic and cDNA libraries.
Coloring Agents↗
A novel cryoprotective protein (CRP) with high activity from the ice-nucleating bacterium, Pantoea agglomerans IFO12686.
The ice-nucleating bacterium, Pantoea agglomerans IFO12686, induces the cryoprotective protein (CRP) by cold acclimation at 12 degrees C. The CRP was purified to apparent homogeneity by various chromatographies. We found that the purified CRP was a monomer of approximately 29,000 according to gel filtration chromatography and SDS-PAGE, and was a heat-stable protein. The CRP could protect freeze-labile enzymes, lactate dehydrogenase (LDH), alcohol dehydrogenase (ADH) and isocitrate dehydrogenase (iCDH), against freezing-thawing denaturation. The activity of the CRP was about 3.5 x 10(4) times more effective than bovine serum albumin (BSA) and 2 x 10(6) times than COR26 from the ice-nucleating bacterium Pseudomonas fluorescens KUIN-1. We confirmed that the CRP was a novel protein, as judged by the a different molecule mass from the already-known cryoprotectants, and has an extremely high cryoprotective activity.
Ammonium Sulfate↗
[Endoventricular circular patch plasty (dor operation) for postinfarction left ventricular aneurysm and ischemic cardiomyopathy].
The determination of purse-string suture line is one of the most important point in endoventricular circular patch plasty (Dor operation) for postinfarction left ventricular aneurysm (LVAN), especially for ischemic cardiomyopathy (ICM). We suggest following three points to decide appropriate suture line. First, the purse-string suture on the basal side should be placed on the 1-2 cm level under diagonal branch. Secondly, lateral wall should not be over excluded to maintain left ventricular function. And the third, akinetic or dyskinetic lesion of apex and septal wall should be excluded as much as possible. Nine cases of five LVAN and four ICM were underwent Dor operation in our institute from Dec. 1999 to Jan. 2000. All patients were weaned from cardiopulmonary bypass easily except one patient, who was operated under IABP support, because of his preoperative severe heart failure. All patients recovered well without any serious complications and postoperative left ventricular graphies were satisfactory. Left ventricular ejection fraction and stroke volume index were increased from 34 +/- 17 to 55 +/- 16% and from 38 +/- 7 to 47 +/- 6 ml/m2, end-diastric and systric volume index decreased from 141 +/- 37 to 88 +/- 19 ml/m2 and from 96 +/- 41 to 41 +/- 23 ml/m2 respectively. The Dor procedure adopted our idea led to satisfactory result in hemodynamic and also in morphologic study.
Aged↗
[Detection of visceral ischemia with doplex scanning method of mesenteric arteries: in patients with acute type B aortic dissection].
Between March, 1997 and January, 1999, 11 patients with acute type B aortic dissection underwent doplex scanning evaluation of mesenteric arteries for the early detection of visceral ischemia. Peak systolic velocity (PSV) of the celiac artery (CeA) and superior mesenteric artery (SMA) was measured on their admission. Mean PSV of CeA in the non-ischemic group (8 patients) and in the ischemic group (3 patients) was 1.66 +/- 0.34 m/sec and 3.60 +/- 0.49 m/sec (p = 0.0481), respectively. Mean PSV of the SMA in the non-ischemic group and in the ischemic group was 1.93 +/- 0.52 m/sec and 3.33 +/- 0.37 m/sec (p = 0.00768), respectively. All patients with PSV of the mesenteric arteries above 3.00 m/sec presented visceral ischemia that required emergency operation. If PSV of the mesenteric arteries exceeds 3.00 m/sec, urgent surgical repair should be considered.
Aged↗
[Colony and phage-plaque direct sequencing by dye terminator method].
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Bacteriophages↗
Antinociception in rat by sarpogrelate, a selective 5-HT(2A) receptor antagonist, is peripheral.
The antinociceptive effect of sarpogrelate, a new selective 5-hydroxytriptamine (5-HT)(2A) receptor antagonist, in the formalin test was examined in rats. Sarpogrelate was administered intraperitoneally, locally (subcutaneously at the formalin test site) or intrathecally 10 min before formalin injection. Intraperitoneal (1-100 mg/kg) and local (0.01-1 mg) administration of sarpogrelate suppressed flinching behavior in both phases 1 (0-9 min) and 2 (10-60 min) in a dose-dependent manner. Intraperitoneal (100 mg/kg) and local (1 mg) injection 7 min after formalin injection reduced phase 2 flinches to the same degree as with the pre-treatment. Intrathecal administration (1-100 microg) showed no antinociceptive action, and facilitated phase 2 flinches at 10 microg. The plasma concentration of sarpogrelate after local administration of 1 mg was lower than after intraperitoneal administration of 10 mg/kg, although local administration produced more potent antinociception. The data imply that the antinociceptive effect of sarpogrelate results mainly from an action at peripheral sites.
Analgesics↗
A novel human HER2-derived peptide homologous to the mouse K(d)-restricted tumor rejection antigen can induce HLA-A24-restricted cytotoxic T lymphocytes in ovarian cancer patients and healthy individuals.
A mouse HER2-derived peptide, HER2p63 (A) (TYLPANASL), can induce K(d)-restricted mouse cytotoxic T lymphocytes (CTL) and also function as a tumor rejection antigen in an in vivo assay. Since the anchor motif of mouse K(d) for peptide binding has much similarity to that of human HLA-A2402, we asked if human HER2p63 (T) (TYLPTNASL) could induce HER2-specific CTL in HLA-A2402-positive individuals. Peripheral blood mononuclear cells (PBMC) of HLA-A2402-positive individuals were sensitized in vitro with HER2p63-pulsed autologous dendritic cells prepared from PBMC. CTL clone derived from these specifically lysed HER2-expressing cell lines bearing HLA-A2402. Cytotoxic activity of the CTL clone against the HER2-expressing cell line bearing HLA-A2402 was blocked by antibodies against CD3, CD8, HLA-A24 or MHC class I, and was also inhibited by the addition of excess HER2p63-pulsed C1R bearing HLA-A2402. Killer cells were generated from PBMC of seven healthy individuals and five ovarian cancer patients, all of HLA-A2402 type, by in vitro sensitization with HER2p63-pulsed autologous antigen presenting cells. These killer cells selectively lysed HER2-expressing SKOV3 transfected with HLA-A2402 cDNA, indicating high immunogenicity of HER2p63 in all 12 individuals examined.
Animals↗