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Biomedical subjects

H Ueda

Publications and source records attributed to H Ueda.

At least 55 records · Page 3Linked to original sources

Functional characterization of organic cation drug transport in the pigmented rabbit conjunctiva.

PURPOSE: To characterize carrier-mediated organic cation drug transport in the rabbit conjunctiva. METHODS: The transport of [14C]guanidine, the model substrate, in the excised pigmented rabbit conjunctiva was evaluated in the modified Ussing chamber. Tetraethylammonium (TEA) transport also was investigated to determine substrate specificity. RESULTS: The apparent permeability coefficient for guanidine and TEA in the mucosal-to-serosal (ms) direction was 5.4 and 49.6 times greater than that in the serosal-to-mucosal (sm) direction, respectively. Guanidine transport in the ms (but not sm) direction revealed temperature and concentration dependency over 0.02 to 10 mM with an apparent Michaelis-Menten constant of 3.1 mM and a maximal flux of 11.4 nmol/(cm2 x h). Net guanidine transport measured at 0.1 mM across the conjunctiva was decreased by 71% or 82%, respectively, on the addition of 1 microM valinomycin (a K+ ionophore) in both bathing fluids or in a high K+ buffer in the mucosal fluid. Interestingly, net guanidine transport was reduced, rather than enhanced, by 63% upon acidifying the mucosal bathing fluid. By contrast, net guanidine transport was not affected by the serosal presence of 0.5 mM ouabain (a Na+, K+-ATPase inhibitor), by the mucosal and serosal presence of 0.1 microM monensin (a Na+ ionophore) or 0.3 microM carbonyl cyanide p-(trifluoromethoxy)phenyl-hydrazone (FCCP, a H+ ionophore). Guanidine transport in the ms direction was polyspecific, as indicated by the 48% to 82% inhibition by structurally diverse amines. In particular, guanidine ms transport was inhibited by the antiglaucoma drugs dipivefrine (72%), brimonidine (70%), and carbachol (78%). CONCLUSIONS: A carrier-mediated organic cation transport process appears to exist in the conjunctiva, mediating the absorption of organic amines, including certain amine-type ophthalmic drugs. This process may be driven by an inside-negative apical membrane potential difference.

Animals↗

Pyogenic arthritis of a lumbar facet joint.

We herein report the case of a 68-year-old man with diabetes who developed pyogenic arthritis of a lumbar facet joint after spinal injection. We performed magnetic resonance imaging (MRI), computed tomography (CT), technetium 99 methylene diphosphonate scintigraphy, and single photon emission computed tomography (SPECT) for this patient. MRI showed a lesion in the facet joint and no evidence of spondylodiscitis. CT showed a swelling of periarticular soft tissue around the facet joint. Bone scintigraphy showed a characteristic vertical uptake. In particular, SPECT was able to clearly confirm the location of the infection. An infection of the facet joint has only been rarely reported, but we recommended that this area should be carefully evaluated whenever a patient develops an infection of the lumbar spine after a spinal injection.

Aged↗

Protein kinase C-mediated acute tolerance to peripheral mu-opioid analgesia in the bradykinin-nociception test in mice.

We studied the acute tolerance liability of peripheral opioid analgesia in mice. The analgesia was assessed by the inhibition of bradykinin (BK)-induced nociceptive action by using a newly developed flexor reflex paradigm. Morphine [intraplantarly (i.pl.)] given ipsilaterally to BK showed a dose-dependent reduction of the BK (2 pmol) responses, whereas the administration of 10 nmol of morphine into the contralateral side failed to show any significant analgesic effects. Furthermore, DAMGO ([D-Ala(2),MePhe(4), Gly-ol(5)]-enkephalin), a mu-opioid receptor (MOR) agonist, and U-69593, a kappa-opioid receptor (KOR) agonist, but not DSLET ([D-Ser(2)]Leu-enkephalin-Thr(6)), a delta-opioid receptor agonist, showed similar analgesia on the BK responses. The morphine- or U-69593 [(5alpha,7alpha, 8beta)-(+)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4,5]dec -8yl] benzeneacetamide]-induced analgesia was markedly attenuated by the intrathecal injection of each antisense oligodeoxynucleotide for the MOR or KOR, respectively, suggesting that these peripheral analgesia are mediated through MORs and KORs located on nociceptor endings, respectively. As BK response was completely recovered to the control level 4 h after morphine (3 nmol i.pl.) or U-69593 (10 nmol i.pl.) administration, these compounds were challenged again to see the inhibition of BK responses. Although morphine analgesia by the second challenge was markedly attenuated, U-69593 analgesia was not. The attenuated morphine analgesia was completely reversed by the pretreatment of calphostin C, Go6976, or HBDDE, a protein kinase C inhibitor, but not by KT-5720, a protein kinase A inhibitor. These results suggest that selective acute tolerance of peripheral morphine analgesia, but not U-69593 analgesia, through MORs and KORs located on polymodal nociceptors, respectively, in the bradykinin-nociception test in mice was mediated through protein kinase C activation.

Analgesics, Opioid↗

[A case of epithelial cancer of the alveoli which responded favorably to the additional administration of UFT for refractory cancer after administration of carboplatin and docetaxel].

Epithelial cancer of the alveoli is considered to be a pulmonary non-small cell carcinoma which responds poorly to carcinostatics. In one case of epithelial cancer of the alveoli which metastasized to both lungs and caused breathing to deteriorate rapidly, chemotherapy was applied with 500 mg of carboplatin (CBDCA) and 90 mg of docetaxel (TXT). Although the tumor was reduced initially, it was found to have been aggravated again three weeks after the start of the chemotherapy. In the second and third courses of the chemotherapy, CBDCA and TXT were administered in the same dosage as in the initial course, but with the oral administration of UFT (600 mg/day). The results were favorable, as evidenced by the absence of recurring aggravation. Currently, the patient has been followed on an outpatient basis for over six months with the administration of UFT. Good QOL is being maintained without any repeated aggravation of the tumor.

Administration, Oral↗

[Four cases with latex allergy followed by anaphylaxis to chestnut].

It is well known that patients with latex allergy have cross-reactions to various fruits, which is called a latex fruit syndrome. We report four cases with latex allergy followed by anaphylaxis to chestnut. They are all nurses of our hospital, who has personal history of atopic diseases. There were varieties in the methods of processing chestnut, presence of epicutaneous contact to chestnut, and clinical courses among the cases. All cases had positive skin prick test reactions while only two cases showed specific IgEs measured with AlaSTAT to chestnut. This fact suggests that we have to warn the risk of anaphylaxis even if one had not shown a serum specific IgE. We could follow the clinical courses and study specific IgEs to chestnut and latex in the two cases for more than two years. The titer of specific IgE was increased in the one, who could not avoid eating chestnut and contact to latex, while it was decreased in the other who could avoid the exposure to the antigens. Hevein is one of the panallergens among latex and related fruits. We studied specific IgEs to hevein on these four cases and 12 normal controls. The results showed that the former had significantly higher values of sIgEs to hevein compared to the latter (p < 0.05). We conclude that a patient with latex allergy has a high risk of contact urticaria or even anaphylaxis to the related fruits such as chestnut so that we recommend the patient with latex allergy to avoid them.

Adult↗

[30 cases of occupational latex allergy].

We experienced 30 patients with occupational latex allergy (LA) in a 4-year period between 1995 and 1998 in Fujita Health University Hospital. All of them were medical personnel. We studied clinical symptoms and the clinical relevance of latex specific IgE and skin test (prick test and use test) in 30 cases. As a result, skin test result was most related of the diagnosis and the severity of LA. The average of the duration to decide LA diagnosis was 21.2 months. The reasons of the delayed diagnosis were that they were left and treated as an unexplained urticaria or asthma. Therefore, we have to warn about LA to the medical personnel who are frequently exposed to latex in Japan.

Adult↗

[A case of xanthogranulomatous pyelonephritis presenting with the flank subcutaneous mass].

A 51-year-old female exhibited fever, left flank pain and left flank mass in March, 1993. Drip infusion pyelography (DIP) revealed a non-functioning left kidney with shadows of calculi, and abdominal computerized tomography (CT) showed renal calculi and multilocular cystic lesions in the left kidney extending through the perinephric space into the mass on the left flank. Percutaneous nephrostomy and percutaneous drainage were performed, followed by left nephrectomy. Histopathological findings revealed xanthogranulomatous pyelonephritis. There have been a few case reports of xanthogranulomatous pyelonephritis forming nephrocutaneous fistula in the back.

Cutaneous Fistula↗

Intracranial aneurysms and autosomal dominant polycystic kidney disease: followup study by magnetic resonance angiography.

PURPOSE: Intracranial aneurysms are known to complicate autosomal dominant polycystic kidney disease. We assess the value of magnetic resonance angiography to detect intracranial aneurysms early in patients with autosomal dominant polycystic kidney disease. MATERIALS AND METHODS: We evaluated 15 patients with asymptomatic autosomal dominant polycystic kidney disease treated at our hospital between 1992 and 1998. Magnetic resonance angiography was performed at presentation and was repeated 18 to 72 months after treatment. RESULTS: On the initial magnetic resonance angiogram 3 intracranial aneurysms were detected in 3 patients. The intracranial aneurysms ranged from 4 to 8 mm. in diameter, and were in the anterior communicating artery in 1, in the vertebral artery in 1, and at the bifurcation of the internal carotid artery and ophthalmic artery in 1 case. Repeat magnetic resonance angiography 18 to 72 months after treatment revealed new intracranial aneurysms in 2 patients. In 1 case the lesion was 7 mm. in diameter, in the internal carotid artery and posterior communicating artery, and detected 69 months after the initial angiogram. In the other patient the lesion was 4 mm. in diameter, in the anterior communicating artery and detected 71 months after treatment. CONCLUSIONS: Since new intracranial aneurysms were demonstrated in patients followed for a long time periodic repeat magnetic resonance angiography is important.

Adult↗

Homology between Fas and nicotinic acetylcholine receptor protein in a thymoma with myasthenia gravis--immunohistochemical and biochemical study.

Nicotinic acetylcholine receptor (nAChR) protein and Fas were detected in a cortical type thymoma from a patient with myasthenia gravis (MG). Immunohistochemical study showed the presence of these two antigens in the neoplastic thymic epithelial cells. This was confirmed by immunoblot analysis of the thymoma extract using polyclonal anti-nAChR (FCT) antibody and two monoclonal anti-Fas antibodies. A homology search between each of five subunits of nAChR and Fas in sequences of nucleotides and amino acids were performed. In nucleotides the percent identity revealed 44.1 and 44.4 in the alpha and gamma subunits, respectively. The places of homology in amino acids sequences between nAChR and Fas were found in alpha 316-355 and Fas 232-271, gamma 321-352 and Fas 3-34. These portions with homology include previously reported T-cell epitopes, alpha 320-337 and gamma 321-340. These two antigens may play a role in triggerring autoimmunity in MG.

Autoimmunity↗

Large vestibular aqueduct syndrome treated by hyperbaric oxygen.

We report the case of a 14-year-old girl with a large vestibular aqueduct (LVA) in whom hyperbaric oxygen (HBO) therapy was effective for the treatment of sensorineural hearing loss. The patient was referred to Nagoya University Hospital for the treatment of hearing loss on 14 September, 1998, because her right hearing level had declined abruptly on 22 August, 1998, and had not changed for 3 weeks since then in spite of steroid and prostaglandin therapy. Her audiogram revealed bilateral profound deafness of more than 110 dB. She had had profound hearing loss on the left side since she was 9 years old. HBO therapy was performed on 22 occasions from 17 September until 19 October, 1998. During the HBO therapy, her right hearing ability returned almost to the level determined prior to the abrupt loss, 60 dB. We therefore recommend HBO therapy for the treatment of sensorineural hearing loss associated with large vestibular aqueduct syndrome if the hearing ability does not recover following conventional treatment.

Adolescent↗

Rat optic nerve oligodendrocytes develop in the absence of viable retinal ganglion cell axons.

Retinal ganglion cell axons and axonal electrical activity have been considered essential for migration, proliferation, and survival of oligodendrocyte lineage cells in the optic nerve. To define axonal requirements during oligodendrogenesis, the developmental appearance of oligodendrocyte progenitors and oligodendrocytes were compared between normal and transected optic nerves. In the absence of viable axons, oligodendrocyte precursors migrated along the length of the nerve and subsequently multiplied and differentiated into myelin basic protein-positive oligodendrocytes at similar densities and with similar temporal and spatial patterns as in control nerves. Since transected optic nerves failed to grow radially, the number of oligodendrocyte lineage cells was reduced compared with control nerves. However, the mitotic indices of progenitors and the percentage of oligodendrocytes undergoing programmed cell death were similar in control and transected optic nerves. Oligodendrocytes lacked their normal longitudinal orientation, developed fewer, shorter processes, and failed to form myelin in the transected nerves. These data indicate that normal densities of oligodendrocytes can develop in the absence of viable retinal ganglion axons, and support the possibility that axons assure their own myelination by regulating the number of myelin internodes formed by individual oligodendrocytes.

Animals↗

A synthetic peptide derived from human immunodeficiency virus type 1 gp120 downregulates the expression and function of chemokine receptors CCR5 and CXCR4 in monocytes by activating the 7-transmembrane G-protein-coupled receptor FPRL1/LXA4R.

Because envelope gp120 of various strains of human immunodeficiency virus type 1 (HIV-1) downregulates the expression and function of a variety of chemoattractant receptors through a process of heterologous desensitization, we investigated whether epitopes derived from gp120 could mimic the effect. A synthetic peptide domain, designated F peptide, corresponding to amino acid residues 414-434 in the V4-C4 region of gp120 of the HIV-1 Bru strain, potently reduced monocyte binding and chemotaxis response to macrophage inflammatory protein 1beta (MIP-1beta) and stromal cell-derived factor 1alpha (SDF-1alpha), chemokines that use the receptors CCR5 and CXCR4, respectively. Further study showed that F peptide by itself is an inducer of chemotaxis and calcium mobilization in human monocytes and neutrophils. In cross-desensitization experiments, among the numerous chemoattractants tested, only the bacterial chemotactic peptide fMLF, when used at high concentrations, partially attenuated calcium mobilization induced by F peptide in phagocytes, suggesting that this peptide domain might share a 7-transmembrane, G-protein-coupled receptor with fMLF. By using cells transfected with cDNAs encoding receptors that interact with fMLF, we found that F peptide uses an fMLF receptor variant, FPRL1, as a functional receptor. The activation of monocytes by F peptide resulted in downregulation of the cell surface expression of CCR5 and CXCR4 in a protein kinase C-dependent manner. These results demonstrate that activation of FPRL1 on human moncytes by a peptide domain derived from HIV-1 gp120 could lead to desensitization of cell response to other chemoattractants. This may explain, at least in part, the initial activation of innate immune responses in HIV-1-infected patients followed by immune suppression.

Acquired Immunodeficiency Syndrome↗

Lysophosphatidic acid-induced, pertussis toxin-sensitive nociception through a substance P release from peripheral nerve endings in mice.

The intraplantar injection of lysophosphatidic acid (LPA) at doses of 0.1-100 pmol into the hind limb of mice showed dose-dependent nociceptive flexor responses. Repeated challenges of LPA at 100 pmol every 5 min showed constant responses at least for 30 min. The prior application of pertussis toxin (PTX) at a dose of 10 ng markedly reduced the following LPA (100 pmol) actions. In addition, the intraplantar application of CP-99994 (1 pmol), a substance P (NK1) receptor antagonist, but not CP-100263 (1 pmol), an inactive derivative, also markedly reduced the LPA responses. These findings suggest that LPA has a nociception-producing activity on sensory neurons through G(i/o) activation and substance P release from nociceptor endings.

Animals↗

Selective association of G protein beta(4) with gamma(5) and gamma(12) subunits in bovine tissues.

The beta and gamma subunits of G proteins are tightly bound under physiological conditions, and so far, seven beta and 11 gamma subunit isoforms have been found. The relative abilities of the beta and gamma subunits to associate with each other have been studied using transfected cell assays, in vitro translation and the yeast two-hybrid system, but have not been fully characterized in various tissues. In the present study, we demonstrated the selectivity of association of the beta with gamma isoforms in bovine tissues. Immunoprecipitation of betagamma complexes from tissue extracts with antibodies against various gamma subunits and subsequent analyses revealed that beta(4) associated with the gamma subunits with the following rank order of selectivity: gamma(5) > gamma(12) > gamma(2) > gamma(3), while beta(2) bound to gamma(2), gamma(3), and gamma(12) more selectively than to gamma(5). By contrast, beta(1) associated with all gamma subunits without significant selectivity. Analyses of purified betagamma complexes containing various gamma isoforms revealed beta subunit compositions similar to those found in the immunoprecipitates. Particular combinations of beta and gamma subunit isoforms may contribute to maintaining efficient and specific signal transduction mediated by G proteins.

Amino Acid Sequence↗

Selective coupling of mouse brain metabotropic sigma receptor with recombinant Gi1.

Various sigma (sigma) ligands including (+)-pentazocine stimulated [35S]GTPgammaS binding in synaptic membranes from the mouse cerebellum. The (+)-pentazocine-stimulated [35S]GTPgammaS binding was blocked by the treatment of membranes with pertussis toxin (PTX), but completely recovered by the reconstitution of PTX-treated membranes with recombinant Gi1, but not with GoA. These findings suggest that metabotropic sigma receptors are selectively coupled to Gi1 protein.

Animals↗

Low dose of kyotorphin (tyrosine-arginine) induces nociceptive responses through a substance P release from nociceptor endings.

The intraplantar injection of kyotorphin (Kyo) elicited nociceptive flexor responses in mice in a dose-dependent manner between 0.1 and 100 fmol. These actions were completely blocked by substance P (NK1) receptor antagonists, such as CP-96345 and CP-99994, but not by their inactive derivatives, CP-96344 or CP-100263, nor by MEN-10376, an NK2 antagonist. Kyo-responses were also abolished by the local pretreatment with capsaicin to deplete substance P from nociceptor endings, and in tachykinin 1 gene K/O mice. These findings suggest that Kyo indirectly stimulates nociceptor endings through a local substance P release.

Animals↗

Activation of Gi1 by lysophosphatidic acid receptor without ligand in the baculovirus expression system.

Lysophosphatidic acid (LPA) receptor has been attracting many neuroscientists' concerns, since it was reported to have a potential role in the neurogenesis, which occurs in the ventricular zone of the developing and adult brain. In the present experiments using baculovirus expression system, the LPA receptor encoded by ventricular zone gene 1 (Edg-2/Vzg-1) was found to be functionally coupled to Gi1, Goa, and G11, but not to GS. The coexpression of LPA receptor markedly decreased the expression of G protein alphai1 or alphaoa subunit, while the basal [35S]GTPgammaS binding significantly increased in the Gi1-preparation. The Scatchard Plot analysis indicates that the expression of LPA-receptor (Edg-2/Vzg-1) showed stimulation of Gi1 without agonist. These results suggest the Edg-2/Vzg-1 has an intrinsic acctivity on Gi1.

Animals↗