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W H Ho

Publications and source records attributed to W H Ho.

18 recordsLinked to original sources
PubMed2001

IL-17E, a novel proinflammatory ligand for the IL-17 receptor homolog IL-17Rh1.

We report identification of interleukin (IL)-17E, a novel member of the IL-17 family of cytokines. IL-17E is a ligand for the recently identified protein termed EVI27/IL-17BR, which we term IL-17 receptor homolog 1 (IL-17Rh1) in light of the multiple reported ligand-receptor relationships. Murine EVI27 was identified through its location at a common site of retroviral integration in BXH2 murine myeloid leukemias. IL-17Rh1 shows highest level expression in kidney with moderate expression in multiple other organs, whereas IL-17E mRNA was detected at very low levels in several peripheral tissues. IL-17E induces activation of NF-kappaB and stimulates production of the proinflammatory chemokine IL-8.

Amino Acid Sequence↗
PubMed2001

Amphetamine induces differential changes in the gene expression of metabotropic glutamate receptor 5 in cultured cortical and hippocampal neurons.

Mechanisms underlying the short-term effects of amphetamine (AMPH) were examined by monitoring the expression of metabotropic glutamate receptor 5 (mGluR5) in cultured rat neurons. The cortical and hippocampal neurons were incubated with 0.1-100 microM of AMPH for 1 h or 1 microM of AMPH for 10 min to 3 h. Immunocytochemical and in situ hybridization (ISH) analyses revealed that the levels of mGluR5 immunoreactivity and mRNA in the cortical neurons were initially increased with the treatment time and dosage, to reach maximal elevations of 34 and 53% from control values following 1 h incubation of 1 microM, and then returned toward the controls. When the cortical neurons were preincubated with the antagonist, alpha-methyl-4-carboxyphenylglycine (MCPG) to mGluRs, before treated with 1 M of AMPH for 1 h, the levels of mGluR5 protein and mRNA became 120 and 116% of control values. In hippocampal neurons, the AMPH treatment persistently upregulated the mGluR5 protein by 50-62%; however, the mRNA responded with the bell-shaped pattern to the treatment times and doses, with 20-43% increases from controls. These modifications of the receptor were reversible, since removal of AMPH resulted in regular levels of the receptor. Notably, the AMPH-generated increases in mGluR5 protein and mRNA were completely blocked by the pretreatment with cycloheximide and actinomycin D, respectively. The data indicate differential responsive patterns of mGluR5 in the cortical and hippocampal neurons to the drug perturbation. The action of AMPH may involve regulation to transcriptional and translational events in the neurons, and the activation of the MCPG-sensitive receptors.

Amphetamine↗
PubMed2000

Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2-4 and IL-22R.

We report the identification of a novel human cytokine, distantly related to interleukin (IL)-10, which we term IL-22. IL-22 is produced by activated T cells. IL-22 is a ligand for CRF2-4, a member of the class II cytokine receptor family. No high affinity ligand has yet been reported for this receptor, although it has been reported to serve as a second component in IL-10 signaling. A new member of the interferon receptor family, which we term IL-22R, functions as a second component together with CRF2-4 to enable IL-22 signaling. IL-22 does not bind the IL-10R. Cell lines were identified that respond to IL-22 by activation of STATs 1, 3, and 5, but were unresponsive to IL-10. In contrast to IL-10, IL-22 does not inhibit the production of proinflammatory cytokines by monocytes in response to LPS nor does it impact IL-10 function on monocytes, but it has modest inhibitory effects on IL-4 production from Th2 T cells.

Amino Acid Sequence↗
PubMed2000

Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system.

alpha-Synuclein (alpha-Syn) is a 14 kDa protein of unknown function that has been implicated in the pathophysiology of Parkinson's disease (PD). Here, we show that alpha-Syn-/- mice are viable and fertile, exhibit intact brain architecture, and possess a normal complement of dopaminergic cell bodies, fibers, and synapses. Nigrostriatal terminals of alpha-Syn-/- mice display a standard pattern of dopamine (DA) discharge and reuptake in response to simple electrical stimulation. However, they exhibit an increased release with paired stimuli that can be mimicked by elevated Ca2+. Concurrent with the altered DA release, alpha-Syn-/- mice display a reduction in striatal DA and an attenuation of DA-dependent locomotor response to amphetamine. These findings support the hypothesis that alpha-Syn is an essential presynaptic, activity-dependent negative regulator of DA neurotransmission.

Amphetamine↗
PubMed1997

A GPI-linked protein that interacts with Ret to form a candidate neurturin receptor.

Glial-cell-line-derived neurotrophic factor (GDNF) and neurturin (NTN) are two structurally related, potent survival factors for sympathetic, sensory and central nervous system neurons. GDNF mediates its actions through a multicomponent receptor system composed of a ligand-binding glycosyl-phosphatidylinositol (GPI)-linked protein (designated GDNFR-alpha) and the transmembrane protein tyrosine kinase Ret. In contrast, the mechanism by which the NTN signal is transmitted is not well understood. Here we describe the identification and tissue distribution of a GPI-linked protein (designated NTNR-alpha) that is structurally related to GDNFR-alpha. We further demonstrate that NTNR-alpha binds NTN (K[d] approximately 10 pM) but not GDNF with high affinity; that GDNFR-alpha binds to GDNF but not NTN with high affinity; and that cellular responses to NTN require the presence of NTNR-alpha. Finally, we show that NTN, in the presence of NTNR-alpha, induces tyrosine-phosphorylation of Ret, and that NTN, NTNR-alpha and Ret form a physical complex on the cell surface. These findings identify Ret and NTNR-alpha as signalling and ligand-binding components, respectively, of a receptor for NTN and define a novel family of receptors for neurotrophic and differentiation factors composed of a shared transmembrane protein tyrosine kinase and a ligand-specific GPI-linked protein.

Amino Acid Sequence↗
PubMed1996

Sensory detection and pain thresholds in spinal cord injury patients with and without dysesthetic pain, and in chronic low back pain patients.

In an effort to understand the mechanisms involved in dysesthetic pain syndrome (DPS) in spinal cord injury (SCI) patients, four groups of 13 subjects each--SCI subjects with DPS, SCI subjects without pain, chronic low back pain subjects, and control subjects--were examined for sensory detection and pain thresholds at forearm, neck, and rostral trunk areas. Results indicated that the SCI pain group had significantly lower pain thresholds at all skin sites, compared to the SCI no-pain and chronic low back pain groups, and at the rostral trunk skin site, compared to the control group. The SCI pain group also showed a lower sensory detection threshold at the rostral trunk skin site than did the SCI no-pain group. Equally important, the SCI no-pain group had detection and pain thresholds significantly higher than those of the control group. The results suggest fundamental differences in somatosensory processing when DPS is or is not a consequence of SCI.

Adult↗
PubMed1995

Sensory and motor neuron-derived factor. A novel heregulin variant highly expressed in sensory and motor neurons.

The heregulin family of polypeptides arise as splice variants from a single gene and share a conserved epidermal growth factor (EGF)-like domain thought to be the major determinant of their biological activities. We report here the cloning of a novel member of this family, termed sensory and motor neuron-derived factor or SMDF, which is highly expressed in sensory and motor neurons in human and rodent species. It contains a C-terminal beta-type EGF-like domain and an unique N-terminal sequence which lacks an Ig-like domain and is distinct from all known heregulin variants. Mammalian cell-expressed SMDF activates tyrosine phosphorylation of a 185-kDa protein in cell lines expressing p185erbB2, indicating that it is biologically active. Analyses of expression patterns suggest that, unlike other heregulin variants, SMDF is expressed mainly in the nervous system. In situ hybridization signals with the unique SMDF sequence probe and with a probe to the conserved EGF-like domain are comparable, suggesting that SMDF is the predominant isoform expressed in sensory and motor neurons. Expression of SMDF is maintained in both adult motor neurons and dorsal root ganglion neurons. These findings suggest that SMDF may mediate biological responses such as Schwann cell proliferation and acetylcholine receptor induction in the peripheral nervous system.

Amino Acid Sequence↗
PubMed1994

Small granule-containing (SGC) cells in the hamster adrenal medulla.

In addition to adrenalin (A)- and noradrenaline (NA)-containing cells in the hamster adrenal medulla, a third type of small granule-containing (SGC) cells was identified. These cells were characterized by their small size (about 15 microns in diameter) and location adjacent to A-cells. Numerous pleomorphic dense-cored cytoplasmic granules (306 +/- 44.5 nm x 204.5 +/- 58.3 nm, mean +/- standard error) were present in their cytoplasm. The ultrastructure of these granules were similar to that of NA-containing granules but smaller in size. The granular inclusions of the granules were moderate to high in electrol density. The cytoplasm of the SGC cells contained short profiles of rough endoplasmic reticulum and some free ribosomes.

Adrenal Medulla↗
PubMed1993

Expression of relaxin mRNA and relaxin receptors in postnatal and adult rat brains and hearts. Localization and developmental patterns.

Relaxin is a polypeptide hormone best known for its role in parturition. However, high affinity relaxin receptors have been localized in the rat brain and heart in addition to the uterus. Several lines of evidence also suggest that relaxin may be involved in the regulation of blood pressure, heart rate, and the release of oxytocin and vasopressin. We now show by Northern analysis that a 1-kilobase relaxin transcript is detected in the rat brain as well as the ovary of pregnant rats. Using in situ hybridization, relaxin mRNA is localized in discrete regions of the male and female brains, including the anterior olfactory nucleus, tenia tecta, pyriform cortex, neocortex, and hippocampus. Developmental studies show that relaxin mRNA is present in the 1-day postnatal brain, while relaxin receptors are not detectable until 7 days after birth. The relaxin receptor binding affinity was similar in the developing brains, but there was a steady increase in relaxin binding sites during postnatal days 7 to 29, suggesting that relaxin may play a role in brain maturation. While relaxin mRNA is not detected in the heart, high levels of relaxin receptors are detected in the cardiac atrium as early as 1 day after birth. These atrial receptors remained at similar levels throughout postnatal development, suggesting an important role for relaxin in cardiovascular function.

Animals↗
PubMed1993

Two-point discrimination thresholds in spinal cord injured patients with dysesthetic pain.

We questioned whether deafferentation following SCI would result in an increase in somatic sensitivity possibly due to cortical reorganization. Dysesthetic pain syndrome (DPS) below the level of a spinal cord injury (SCI) is a common complication. We hypothesized that DPS patients would show increased cortical reorganization because of high levels of sensory stimulation following injury. Sixteen dysesthetic pain SCI patients, 15 SCI patients without pain, and 16 control subjects were examined for two-point discrimination thresholds (2PDT) of the forearm, neck, and spine. The SCI pain group had significantly smaller 2PDTs than either SCI no pain or control groups, particularly over the neck and spine. The SCI pain group had a significant inverse correlation between perceived degree of pain (visual analogue scale) and 2PDT in the spinal skin area. The findings indicate that SCI patients with severe DPS have a higher sensitivity to somatosensory stimuli, particularly in skin areas with projections to primary somatosensory cortex areas adjacent to the deafferentated region. The increase in 2PDT may be due to an increase in the size of the somatosensory cortical areas allotted to the corresponding skin areas.

Adult↗
PubMed1992

Molecular cloning of mouse alcohol dehydrogenase-B2 cDNA: nucleotide sequences of the class III ADH genes evolve slowly even for silent substitutions.

We have cloned and sequenced a cDNA encoding the mouse class III alcohol dehydrogenase, Adh-B2. Adh-B2 mRNA is detectable in all the mouse tissues tested. Class III ADHs are highly conserved: the deduced amino acid sequence of the mouse Adh-B2 is 91 to 97% identical to the human, horse and rat liver enzymes. The mouse Adh-B2 cDNA is 87% identical in nucleotide sequence to the human chi-ADH cDNA. Previously, a slower rate of evolutionary divergence of the amino acid sequences of class III ADH proteins was detected and ascribed to functional constraints upon the protein. Our analysis of the nucleotide sequences demonstrates that this cannot be the entire explanation, since the rate of silent (synonymous) nucleotide substitutions is also lower in the class III ADHs than in the class I ADHs.

Alcohol Dehydrogenase↗
PubMed1989

Nucleotide sequence of the ADH2(3) gene encoding the human alcohol dehydrogenase beta 3 subunit.

All nine exons of the ADH2(3) allele, which encodes the human alcohol dehydrogenase beta 3 subunit, have been cloned and sequenced. Comparison of this sequence to the ADH2(1) nucleotide sequence revealed only a single difference that results in an amino acid change, thus proving that the significant kinetic differences between these two isozymes is due to the Cys for Arg substitution at position 369. There are also two silent polymorphisms, and two changes in noncoding regions.

Alcohol Dehydrogenase↗
PubMed1982

Bacterial endocarditis in mitral leaflet prolapse syndrome.

A 25-year-old quadriplegic man with mitral leaflet prolapse syndrome was seen for complaints of intermittent fever, chills, and cough of three months' duration. Subacute bacterial endocarditis was diagnosed. Unusual complications of this disorder included hyperplenism with pancytopenia, pericardial effusion, and multiple infections in the blood and the spleen. Antibiotic therapy was begun, and splenectomy was performed. After seven weeks of treatment, the patient was free of symptoms and was discharged with advice on appropriate antibiotic prophylaxis. We believe that although bacterial endocarditis is a major complication of mitral leaflet prolapse syndrome, it can be prevented with antibiotic prophylaxis whenever dental, surgical, or other invasive procedures are performed.

Adult↗
PubMedDate not supplied

Regulation of the subcellular distribution and gene expression of GABA(A) receptor by microtubules and microfilaments in cultured brain neurons.

Mechanisms underlying the intracellular transport of gamma-aminobutyric acid(A) receptor (GABA(A)R) were examined in the cultured neurons derived from chicken embryo brains. In situ trypsinization of the cultures and (3)H-flunitrazepam (FNZ) binding assay were employed to determine the cell surface and intracellular distribution of the receptor. A 3-h treatment of the cells with 1 microM of colchicine, a microtubule depolymerizer, reversibly raised the proportion of intracellular GABA(A)R density by about 36% and decreased that of the cell surface receptors by 18% from respective control values, whereas the 3-h incubation with 2 microM of cytochalasin D, a microfilament disrupter, did not cause significant changes. These treatments failed to alter the total number of the (3)H-FNZ binding sites of the neurons and the affinity of the ligand. Moreover, the exposure to colchicine seemed to produce a stronger cytoplasmic immunostaining of the GABA(A)R alpha subunits in many neurons without affecting the total cellular level of the proteins, in accordance with the increased fraction of intracellular (3)H-FNZ binding. However, in the neurons exposed to cytochalasin D, there was an increase of around 28% in the total content of alpha(1)+51kDa proteins. In addition, the colchicine or cytochalasin D treatment inhibited approximately 21 or 18% of the rate of general protein synthesis in the culture. Notably, in situ hybridization assay showed that the GABA(A)R alpha(1) or alpha(2) mRNA was present in 92 +/- 2% or 94 +/- 2% of the cytochalasin D-treated neurons, both of which were higher than 71 +/- 2-74 +/- 3% of the control and colchicine-treated cells. The data suggest that by regulating the intracellular transport, the microtubular system participates in the maintenance of normal subcellular distribution of GABA(A)R in the neurons. By contrast, the organization of microfilaments may play a role in modulating the gene expression of GABA(A)R subunits.

Actin Cytoskeleton↗