Inhibition of the expression and function of chemokine receptors on human CD4+ leukocytes by HIV-1 envelope protein gp120.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
H Ueda
Publications and source records attributed to H Ueda.
Immunocytochemical study of endocytotic structures accumulated in HeLa cells transformed with a temperature-sensitive mutant of dynamin.
Dynamin is a 100-kD GTPase, which is required for clathrin-mediated endocytosis. Recent studies have revealed that dynamin is closely involved in clathrin-coated vesicle formation. In this study we investigated the ultrastructure of endocytotic structures accumulated in HeLa cells that were transformed with a temperature-sensitive (ts) mutant of dynamin to clarify which step was blocked in dynts cells. Endocytosis of transferrin receptors was restricted at the level of surface-connected membrane structures. Tubular and vesicular membrane invaginations were accumulated in the cells' peripheral regions, suggesting that the endocytosis was blocked just before the pinching-off steps in coated vesicle formation. The "collared" tubes, which were reported to be localized in nerve terminals in shibirets1 flies and GTPgammaS-treated synaptosomes, were not observed in the dynts cells even at nonpermissive temperature. The distribution pattern of dynamin in deeply invaginated coated pits in dynts cells was similar to that in dynwt cells but not to that in dynK44A cells, which are other endocytosis-defective mutant cells. These morphological data suggest that dynts blocked the pinching-off steps in clathrin-coated vesicle formation, which may be caused by a different mechanism from that of dynK44A cells.
Cell Membrane↗
Comparisons between hemodynamics, during and after bathing, and prognosis in patients with myocardial infarction.
The purpose of this study was to establish the safest way to bathe patients with myocardial infarction (MI) through measuring the hemodynamics during and after bathing. Seventy patients with MI were bathed supine in a Hubbard tank filled with 42 degrees C tap water for 5 min. The subjects were divided into 2 groups depending on their hemodynamic values 10 min after bathing: pulmonary capillary wedge pressure unchanged even after bathing (group A), and decreased pressure after bathing (group B). The left ventricular ejection fraction of group B was significantly higher than that of group A: 53.6% vs. 39.7%, respectively (p<0.01). The physical work capacity of group B was significantly higher at 5.6 METs, than that of group A with 4.5 METs (p<0.05). During the average of their 37-month follow-up period, there were 3 cardiac events in group B and 6 in group A. There were 2 cardiac events during bathing, both of which occurred in group A. When patients with MI take a bath, it is essential to closely monitor them, especially to those patients with lower cardiac function, because they have a higher possibility of a cardiac event.
Aged↗
Promoter polymorphism of the beta2 bradykinin receptor gene is associated with essential hypertension.
The present study examined the genetic contribution of the human beta2 bradykinin receptor gene in Japanese subjects with essential hypertension, and identified a -58T/C polymorphism of the core promoter that might be responsible for essential hypertension in Japanese. The study consisted of 100 hypertensive subjects and 100 age- and sex-matched controls. The allelic frequencies were 0.575 for the C allele and 0.425 for the T allele in hypertensive subjects, and 0.465 for the C allele and 0.535 for the T allele in normotensive subjects. The allelic frequencies were in Hardy-Weinberg equilibrium. Significant differences between hypertensive and normotensive subjects were seen in the genotypes distribution (p=0.049) and allelic frequencies (p=0.028), and the beta2 bradykinin receptor gene variant was associated with human essential hypertension in this Japanese population. This new marker may provide a valuable tool for assessing the risk for putative bradykinin-associated common diseases, such as hypertension, and cardiovascular diseases with genetic determinism. These results suggest that the -58 polymorphism of the human beta2 bradykinin receptor gene is an independent risk factor for essential hypertension in the Japanese population.
Adult↗
[Molecular pharmacology and physiology of nociceptin].
The family of the G protein-coupled opioid receptors was recently extended by a novel member that did not bind any of the typical opioid receptor ligands. Identification of the orphan receptor in this way led to the advent of "reverse pharmacology" to identify the corresponding physiological ligands. Nociceptin, a heptadecapeptide, which was discovered as an endogenous ligand, first, attracted us by its reported nociceptive or anti-opioid actions. However, following studies revealed that this peptide has both nociceptive and antinociceptive actions under different conditions; e.g., administration routes or doses affect its actions. In our recent studies using a unique peripheral peripheral nociception test, nociceptin given locally at lower doses was found to produce nociception through substance P release from nociceptor endings, while at higher doses, it produced antinociceptive actions through an inhibition of phospholipase C activity stimulated by nociceptive substances. Such hypothetical mechanisms can be applied to the mechanisms of nociceptin-induced paradoxical actions in the central nervous system. The physiological role of nociceptin has recently been reported using nociceptin receptor knock-out mice. Following the report of a hearing problem in such mice, the nociceptin receptor was found to be involved in the development of morphine analgesic tolerance. In this review, more findings on the physiological roles of nociceptin or its receptor, such as pain control and memory-learning, are discussed on the basis of reports using nociceptin receptor knock-out mice.
Animals↗
In vivo molecular signal transduction of peripheral mechanisms of pain.
Although we have obtained a number of pharmacological tools and mutant mice lacking specific genes related to the pain, the distinct molecular basis of the pain-producing mechanism has remained to be fully clarified since we have been using conventional paradigms of the nociception test that may drive multiple endogenous molecules affecting nociception at the same time. Here, I will introduce a new paradigm of the nociception test. In this test, we focused on polymodal C-fibers by measuring nociceptive flexor responses induced by the peripheral application of a single species of nociceptive molecule. In addition, we identified the site of drug actions on nociceptor endings by the fact that the nociception was abolished by the intrathecal pretreatment with antisense oligodeoxynucleotide for receptors. Throughout experiments using this paradigm of the nociception test, it was firstly revealed that substance P, a major neurotransmitter of polymodal C-fibers, directly stimulates nociceptor endings through activation of Gq/11 and phospholipase C, followed by Ca2+ influx through plasma membrane-bound inositol trisphosphate receptors, and that bradykinin and histamine, both endogenous representative pain-producing substances, share this mechanism. Another unique mechanism is through Gi-coupled receptors such as receptors for nociceptin (orphanin FQ) or kyotorphin (tyrosine-arginine). The latter mechanism was found to be mediated through a substance P release from nociceptor endings. Future studies including some modifications of this paradigm should be also clinically useful for neuropathic pain research as well as understanding of pain physiology.
Animals↗
Changes in the levels of mRNAs for GH/prolactin/somatolactin family and Pit-1/GHF-1 in the pituitaries of pre-spawning chum salmon.
Changes in the levels of pituitary mRNAs encoding GH, prolactin (PRL) and somatolactin (SL) were determined in pre-spawning chum salmon (Oncorhynchus keta) caught at a few key points along their homing pathway in 1994 and 1995. Furthermore, we analyzed relationships between expression of pituitary-specific POU homeodomain transcription factor (Pit-1/GHF-1) and GH/PRL/SL family genes. In 1994, seawater (SW) fish and matured fresh-water (FW) fish were sequentially captured at two points along their homing pathway, the coast and the hatchery. In addition to these two points, maturing FW fish were captured at the intermediate of the two points in 1995. The levels of hormonal mRNAs were determined by a quantitative dot blot analysis using single-stranded sense DNA as the standard. Relative levels of Pit-1/GHF-1 mRNAs were estimated by Northern blot analysis. In 1994, the levels of GH/PRL/SL family mRNAs except for PRL mRNA in the male FW fish were 1.8-4 times higher than those in the SW fish. In 1995, the level of PRL mRNA was somewhat sharply elevated in the maturing FW fish soon after entry into the FW environment, while that of SL mRNA was gradually increased during upstream migration from the coast to the hatchery. The levels of 3 kb Pit-1/GHF-1 mRNA in the FW fish were higher than those in the SW fish in both 1994 and 1995. The present results indicate that expression of genes for the GH/PRL/SL family and Pit-1/GHF-1 is coincidentally enhanced in homing chum salmon. Moreover, the present study suggests that expression of the SL gene is elevated with sexual maturation, whereas that of PRL gene is elevated with osmotic change during the final stages of spawning migration.
Animals↗
Homogeneous noncompetitive immunoassay based on the energy transfer between fluorolabeled antibody variable domains (open sandwich fluoroimmunoassay).
The antigen-dependent stabilization of an anti-hen egg lysozyme (HEL) antibody HyHEL-10 variable region was monitored with fluorescence resonance energy transfer (FRET) between fluorolabeled heavy chain (VH) and light chain (VL) fragments. The VH and VL fragments labeled with succinimide esters of fluorescein and rhodamine-X, respectively, were mixed in a cooled cuvette, and the change in fluorescence spectra upon antigen addition was monitored. When excited at 490 nm, significant decrease in the fluorescence at 520 nm and its increase at 605 nm were observed when an increasing amount of HEL was added to the mixture in the concentration range of 1-100 micrograms/mL. The assay, named open sandwich fluoroimmunoassay (FIA), is noncompetitive and homogeneous and can be conducted with one clone of antibody. With the use of appropriate antibodies, it is thought to be a quick and inexpensive alternative to the conventional laborious and/or expensive immunoassays.
Energy Transfer↗
Peripheral arterial coil embolization for hepatic arteriovenous malformation in Osler-Weber-Rendu disease; useful for controlling high output heart failure, but harmful to the liver.
A 55-year-old Japanese housewife, who had Osler-Weber-Rendu disease, was admitted to our hospital because of frequent epistaxis and worsening exertional dyspnea. The computed tomography and hepatic arteriography revealed large hepatic arteriovenous malformation, which was considered to be the leading cause of her high output heart failure. Two series of hepatic arterial coil embolization procedures were performed to reduce hepatic shunt flow. They temporarily improved her cardiac condition, but gradually induced progressive hepatic failure due to intrahepatic cholangitis. Hepatic dysfunction restricted her quality of life and lead to a fatal clinical course one year after the second coil embolization.
Arteriovenous Malformations↗
Dermoid cysts of the ovary with malignant transformation: MR appearance.
OBJECTIVE: This study presents the MR appearances of five women with a total of six proven dermoid cysts of the ovary with malignant transformation. To our knowledge, the MR findings of this entity have not been reported. CONCLUSION: The lesions appeared to be fat-containing tumors with a solid component (4/6) that extended transmurally (4/6) and extensively invaded neighboring pelvic organs (3/6). The supervening malignancy was squamous cell carcinoma in four tumors, melanoma in one, and transitional cell carcinoma in one. The mode of spread differed from that of common ovarian tumors in that it included transmural extension and local invasion, reflecting squamous cell carcinoma.
Carcinoma, Squamous Cell↗
MR imaging of endometrial stromal sarcoma: correlation with pathologic findings.
OBJECTIVE: This study describes MR imaging of eight patients with endometrial stromal sarcoma and correlates the imaging findings with histopathologic findings. To our knowledge, the radiologic findings of this entity have not been reported in the literature. CONCLUSION: Endometrial stromal sarcoma typically presents with extensive myometrial involvement, which is either sharply demarcated or diffusely infiltrative. Bands of low signal intensity are observed within the areas of myometrial involvement on T2-weighted images. These bands correspond to the preserved bundles of myometrium on pathologic examination. Tumor extension along the vessels or ligaments is another characteristic of MR imaging of endometrial stromal sarcoma.
Adult↗
Genetic analysis of late-onset type 2 diabetes in a mouse model of human complex trait.
Type 2 diabetes is a complex trait with both genes and environmental factors contributing to susceptibility. Except for rare subtypes with monogenic inheritance, the genetic basis of type 2 diabetes is unknown because of the complex and heterogeneous nature of the disease. By using the NSY mouse, an inbred mouse model of type 2 diabetes, we genetically dissected late-onset type 2 diabetes and demonstrated age-dependent changes in the genetic control of type 2 diabetes as well as polygenic inheritance. Three major loci (Nidd1nsy, Nidd2nsy, Nidd3nsy) were mapped on mouse chromosomes (Chr) 11, 14, and 6, respectively. The existence of a fourth locus (Nidd4nsy) with an age-dependent effect was suggested by longitudinal, but not cross-sectional, analysis of linkage data. Nidd1nsy and Nidd4nsy appear to affect insulin secretion, whereas Nidd2nsy and Nidd3nsy appear to affect insulin sensitivity. A locus on Chr 6 was significantly linked to epididymal fat weight. A candidate disease gene (Tcf2) on Chr 11, encoding hepatic nuclear factor-1beta, was shown to have a rare sequence variant in the DNA binding domain in the model. The mouse model we used will serve as a useful model for future studies on the etiology of late-onset polygenic type 2 diabetes in humans.
Adipose Tissue↗
Renal tubular function affects glycosuria-related urinary excretion of 1,5-anhydroglucitol.
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Aged↗
[A case report of organic solvent abuse with amotivational syndrome].
We investigated an organic solvent abuser who developed amotivational syndrome employing neuropsychological examination (Rorschach test, Bender Gestalt test and Benton visual retention test), electroencephalography, magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT). The patient manifested a disability to maintain a goal-orient mental activity, immature reality testing and poor set shifting, which suggest frontal lobe dysfunction, as we have reported before in neuropsychological examination. In this case, single photon emission computed tomography (SPECT) also revealed a decrease of regional cerebral blood flow (rCBF) in the medial frontal lobe. These results may suggest a contribution of frontal lobe (especially medial frontal lobe) dysfunction to the pathogenesis of amotivational syndrome due to organic solvent abuse.
Adult↗
Instability of chromosome 7 in colony forming cells of patients with aplastic anemia.
Monosomy 7 in isolated bone marrow mononuclear cells and colony forming cells from patients with aplastic anemia who later developed myelodysplastic syndrome/leukemia with monosomy 7 were examined by fluorescence in situ hybridization. Colonies derived from bone marrow mononuclear cells of the aplastic anemia patients consisted of a mixture of cells of normal karyotype and monosomy 7, ranging from 0 to 97.2%. This result suggests that colony forming cells initially had a normal karyotype but then lost chromosome 7 during growth in the semisolid culture. This finding suggests the genetically unstable condition of chromosome 7 in colony forming cells in aplastic anemia patients. This chromosome instability of colony forming cells may lead to malignant transformation.
Anemia, Aplastic↗
Nucleotide stimulation of Cl(-) secretion in the pigmented rabbit conjunctiva.
We evaluated the role of extracellular UTP and other nucleotides in the regulation of active ion transport across the pigmented rabbit conjunctiva. When added to the mucosal side of the conjunctiva, UTP (0.01-1000 microM), increased the short-circuit current by up to 14. 6 +/- 2.1 microA/cm(2). The half-maximal concentration was 11.4 +/- 2.3 microM. The serosal absence of Cl(-), serosal presence of 10 microM bumetanide, and mucosal presence of 0.3 mM N-phenylanthranilic acid significantly reduced the change in the short-circuit current (DeltaIsc) induced by 10 microM UTP by 78, 77, and 42%, respectively. Mucosal 10 microM UTP significantly increased (36)Cl flux in the serosal-to-mucosal direction by 0.17 microEq/cm(2)/h, while not affecting mucosal-to-serosal (36)Cl flux. By contrast, (22)Na transport in either direction was unaffected. The rank order of DeltaIsc elicited by adenosine and nucleotides was consistent with the predominant involvement of P2Y purinergic receptors in the UTP effect on conjunctival ion transport. Moreover, the DeltaIsc elicited by UTP was inhibited by 0.05 and 1 mM suramin (a P2-purinergic receptor antagonist), resulting in a rightward shift of the half-maximal concentration to 106.7 +/- 1.3 microM. In conclusion, the primary effect of UTP on ion transport in the pigmented rabbit conjunctiva is stimulation of Cl(-) secretion, possibly at the P2Y(2) and/or the P2Y(4) receptor on the mucosal side of the tissue. Because of the coupling of fluid flow with Cl(-) secretion, UTP or its analogs may be considered for stimulating transconjunctival fluid flow in the dry-eye state.
Adenosine↗
Dose-related opposite modulation by nociceptin/orphanin FQ of substance P nociception in the nociceptors and spinal cord.
We previously reported that the intraplantar (i.pl.) application of nociceptin/orphanin FQ (N/OFQ) at extremely low doses elicited a nociception through a substance P (SP) release from nociceptor endings. In the present study, the nociception induced by SP (and N/OFQ) was abolished by intrathecal (i.t.) injection of neurokinin(1) (SP receptor) antagonist, suggesting the involvement of the stimulation of nociceptive primary SP neuron and SP release into spinal synapses. On the other hand, similar low doses of N/OFQ (i.t.) exerted nociceptive responses, characterized by scratching, biting, and licking, and these responses were blocked by an neurokinin(1) antagonist (i.t.) or capsaicin pretreatment or in tachykinin 1 gene knockout mice (tac1(-/-) mice), suggesting that N/OFQ receptor (NOR) also exists on the spinal terminals of SP neurons. When wide ranges of N/OFQ doses were used, a typical bell-shaped dose-response relationship was observed in both peripheral and central nociception tests. Furthermore, N/OFQ (1 nmol) administered i.pl. blocked SP (i.pl.)-induced flexor responses, which were abolished by pertussis toxin pretreatment or in NOR gene knockout (NOR(-/-)) mice. On the other hand, N/OFQ administered i.t. blocked SP (i.t.)-induced scratching, biting, and licking in capsaicin-pretreated and tac1(-/-) mice, and this antinociception was abolished in NOR(-/-) mice. All these findings suggest that N/OFQ has biphasic actions depending on doses in the nociceptors and spinal synapses and has postsynaptic antinociceptive actions in spinal cord by modulating SP signaling.
Analgesics↗
Upstream element of the sea urchin arylsulfatase gene serves as an insulator.
Insulator DNAs functionally isolate neighboring genes by blocking interactions between distal cis-regulatory elements and promoters. Here we report that a DNA fragment located in the upstream region of sea urchin, H. pulcherrimus, arylsulfatase (HpArs) gene blocks the interaction of the Ars enhancer when positioned between the enhancer and the target promoter, in an orientation dependent manner. The Ars insulator works only 3' to 5' direction and has no significant stimulatory or inhibitory effects on its own promoter. In transgenic Drosophila, the Ars insulator blocks the interaction between even-skipped stripe enhancer and its target promoter. The insulation mechanism operates also unidirectionally in Drosophila. We also show that the efficiency of transformation of HeLa cells is enhanced when the integrated gene is flanked by the Ars insulator, suggesting the sea urchin insulator overcomes the position-dependent transgene expression in mammalian cells. These results demonstrate that the mechanism of action of the insulator has been conserved throughout evolution.
Animals↗