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Biomedical subjects

H H Ho

Publications and source records attributed to H H Ho.

At least 37 records · Page 2Linked to original sources
PubMed1999

The N terminus of Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor is necessary for high affinity chemokine binding but not for constitutive activity.

Kaposi's sarcoma-associated herpesvirus (KSHV) contains a gene encoding a G protein-coupled receptor (KSHV-GPCR) that is homologous to mammalian chemokine receptors. KSHV-GPCR signals constitutively (in an agonist-independent manner) via the phosphoinositide-inositol 1,4,5-trisphosphate pathway. Because it has been proposed that the N terminus (N-TERM) of other GPCRs may act as tethered agonists, we determined whether the N-TERM of KSHV-GPCR is necessary for constitutive signaling activity or ligand binding, or both. We show that replacement of the entire N-TERM of KSHV-GPCR with those of two other GPCRs, deletion of residues within the N-TERM, and disruption of a putative disulfide bond that may hold the N-TERM in close proximity to extracellular loop 3 do not affect constitutive signaling activity but decrease chemokine binding. There were differences in the effects of mutation of the N-TERM on binding of the chemokines growth-related oncogene alpha, which is an agonist, and interferon-gamma-inducible protein-10, which is an inverse agonist. The effects on chemokine binding were accompanied by changes in chemokine regulation of KSHV-GPCR signaling. We conclude that the N-TERM is not necessary for constitutive KSHV-GPCR signaling, i.e. the N-TERM is not a tethered agonist, but plays a crucial role in binding of chemokine ligands and of chemokine regulation of KSHV-GPCR signaling.

Animals↗
PubMed1999

Glycosylation is important for binding to human calcitonin receptors.

Human calcitonin receptor (hCTR) subtypes contain three or four potential Asn-linked glycosylation sites in their extracellular amino termini. The role of glycosylation in hCTR function has not been identified, but it has been suggested that inhibition of glycosylation does not affect binding or signaling. To determine the role of glycosylation in hCTR biology, we studied the effects of inhibition of glycosylation and of substitution of Asn residues that are potential glycosylation sites. Native and mutated hCTRs were studied after transient expression in monkey kidney COS-1 cells. Tunicamycin, administered as part of a treatment protocol that inhibited glycosylation of all expressed receptors, decreased salmon calcitonin (sCT) binding affinities and signaling potencies at hCTRs with three or four potential glycosylation sites. In hCTR3, which contains three potential glycosylation sites at positions 26, 78, and 83, site-specific substitution of Asn-26 by Ala had no effect on sCT binding affinity or potency, whereas substitution of Asn-78 or Asn-83 lowered sCT affinity and potency. A mutant hCTR3 in which all three Asn residues were substituted with Ala exhibited no high-affinity sCT binding and potencies of several calcitonin analogues that were more than 100-fold lower than that of native hCTR3. Our data show that glycosylation is important for high-affinity binding and potency of calcitonin analogues at hCTRs.

Alanine↗
PubMed1999

Chelation therapy for patients with elevated body lead burden and progressive renal insufficiency. A randomized, controlled trial.

BACKGROUND: Nephropathy is known to occur in persons exposed to high levels of lead, but the question of whether long-term exposure to low levels of environmental lead is associated with impaired renal function remains controversial. OBJECTIVE: To examine whether chelation therapy slows the progression of renal insufficiency in patients with mildly elevated body lead burden. DESIGN: Randomized, controlled trial. SETTING: Academic medical center in Taiwan. PATIENTS: 32 patients with chronic renal insufficiency (serum creatinine level > 132.6 micromol/L [1.5 mg/dL] and < 353.8 micromol/L [4.0 mg/dL]), mildly elevated body lead burden (> 0.72 micromol [150 microg] of lead per 72-hour urine collection and < 2.90 micromol [600 microg] of lead per 72-hour urine collection [EDTA mobilization tests]), and no history of heavy lead exposure. INTERVENTION: The treatment group received 2 months of chelation therapy; the control group received no therapy. MEASUREMENTS: The reciprocal of serum creatinine (1/Cr) was used as an index of progressive renal insufficiency. RESULTS: Rates of progression of renal insufficiency were similar in the treatment group and the control group during a 12-month baseline observation period (1/Cr, 0.000054 L/micromol per month compared with 0.000046 L/micromol per month; P > 0.2). After the 2-month treatment period, improvement in renal function was greater in the treatment group than in the control group. In the 12 months after the treatment period, renal insufficiency progressed more slowly in the treatment group than in the control group (1/Cr, 0.000033 +/- 0.00038 L/micromol per month compared with 0.000045 +/- 0.000038 L/micromol per month; P = 0.0030). CONCLUSION: Chelation therapy seems to slow the progression of renal insufficiency in patients with mildly elevated body lead burden. This implies that long-term exposure to low levels of environmental lead may be associated with impaired renal function in patients with chronic renal disease.

Adult↗
PubMed1999

The correlates of depressed mood in adolescents in Hong Kong.

PURPOSE: Most studies of depressed mood and its correlates in adolescents have been conducted in Western countries. This study examined the relationship between a broad range of stressors and depressed mood in a community sample of Hong Kong adolescents. METHODS: Secondary school students (n = 996) completed the Chinese Beck Depression Inventory (C-BDI), provided demographic information, and indicated their perceptions of family and peer relationships, school function and pressures, and subjective health, and some measures salient to the Hong Kong environment: triad gang pressure, religiosity, and intent to emigrate. The correlation between C-BDI and these variables was assessed in bivariate and multivariate analyses. RESULTS: Hong Kong adolescents reported higher levels of depressive symptoms than a comparison group of Western teenagers. Girls showed more symptoms than boys. All stressors correlated in bivariate analyses with C-BDI, indicating similar influences on depressed mood in Western and Hong Kong teenagers. In multivariate analyses, the stressors contributed cumulatively to the C-BDI score. Perceptions of a lack of parental understanding and peer acceptance appeared as the strongest variables in predicting depressed mood. CONCLUSIONS: Depressed mood is highly prevalent among Hong Kong teenagers. Stressors play a cumulative role in their relationship to mood. Our findings point to the importance of broad screening of this vulnerable population.

Adolescent↗
PubMed1999

Ankylosing spondylitis with severe chondrocalcinosis: case report.

The term chondrocalcinosis is often used to describe the radiological or pathological features of calcified joint cartilage, and it usually indicates the deposition in cartilage of calcium pyrophosphate dihydrate. The prevalence of chondrocalcinosis increases with age, with dramatic increases occurring in the decades past age 60. In younger patients with chondrocalcinosis, either clinical evidence of associated metabolic diseases leading to the chondrocalcinosis or familial disease occurrence usually can be detected. We report a 42-year-old Chinese woman with ankylosing spondylitis and arthritis involving multiple peripheral joints. Severe chondrocalcinosis was detected incidentally in this patient, however, subsequent studies revealed no associated metabolic disease or familial susceptibility and the clinical features of this patient were different from those of ankylosing chondrocalcinosis (pseudoankylosing spondylitis). The cause of chondrocalcinosis in this patient remains unknown, but joint damage and repair could have been initiating or aggravating factors of the chondrocalcinosis.

Adult↗
PubMed1998

Salmonella septic arthritis in systemic lupus erythematosus and other systemic diseases.

Salmonella infection is an important problem in immunocompromised patients. The synovium is a particular metastatic focus of Salmonella infection and can result in many disabilities of life. Systemic lupus erythematosus (SLE) patients were highly susceptible to Salmonella infection. In the past 6 years, 41 patients with Salmonella septic arthritis have been treated in our hospital. Eleven patients had an underlying systemic disease of SLE which presented with a distinctive clinical course. Alcoholic liver disease (six cases) was another common underlying systemic disease. The most frequent predisposing articular factor was avascular necrosis (16 cases). The hip joint was the most commonly involved site. Salmonella group B was the most common serotype (30/41). Seventy-three per cent (8/11) of the SLE group had involvement of two or more joints compared with only three out of 30 patients in the non-SLE group. The sex differentiation shows a predominance of young females (10/11) in the SLE group and middle-aged males in the non-SLE group. Moreover, in the SLE group, all 11 patients shared the risk of lupus nephritis and steroid use. Ten patients had Salmonella group B bacteraemia and five had urinary tract infections simultaneously. In the non-SLE group, there were 10 patients with a history of steroid use, three with antecedent enteritis, 12 with bacteraemia, and three with necrotising fasciitis. Seven patients in each of the groups had a recurrent course. However, three patients in the non-SLE group had died during the episode of septic arthritis.

Adolescent↗
PubMed1997

A synopsis of the occurrence and pathogenicity of Phytophthora species in mainland China.

To date, 26 species of Phytophthora have been reported in mainland China but only 23 are accepted as good taxa. Phytophthora nicotianae (P. parasitica) is the single most important species causing over 40 different plant diseases; P. boehmeriae is widespread attacking Gossypium, Boehmeria, Citrus, Broussonetia papyrifera and Pterocarya stenoptera; P. "fragariae var. oryzo-bladis" is unique to mainland China causing blight of Oryza sativa seedlings; P. megasperma sensu lato has been isolated from Glycine max, Asparagus officinalis and Spinacia oleracea. In Hainan Province, P. heveae is present in the soil without causing apparent diseases to Hevea brasiliensis there.

Journal Article↗
PubMed1997

Kabuki make-up (Niikawa-Kuroki) syndrome: cognitive abilities and autistic features.

Kabuki make-up syndrome (KMS), also known as Niikawa-Kuroki syndrome, is a rare malformation complex characterized by a peculiar facies with long palpebral fissures and partially everted lower eyelid, mental retardation, dwarfism, and skeletal and dermatoglyphic abnormalities. Four children from different ethnic groups presented with phenotypic manifestation of KMS. They showed variable degrees of learning disabilities, mental retardation, and autistic behavior. Two boys declined in IQ in early adolescence. In addition to being aware of the variable presentation of cognitive and behavioral characteristics in those already diagnosed, it is important to consider KMS when assessing dysmorphic children with learning disabilities and/or autism.

Abnormalities, Multiple↗
PubMed1997

Characterization of human chorionic gonadotropin peptide variants with a radio-receptor assay using recombinant human luteinizing hormone/chorionic gonadotropin receptors.

There are potential interactions between various human chorionic gonadotropin (hCG) isoforms at the level of luteinizing hormone/chorionic gonadotropin (LH/CG) receptor. The objective of this study was to characterize the receptor-binding activities of the primary peptide variants of hCG including intact hCG, free beta subunit, beta-core fragment and nicked hCG, and to test the effects of these hCG variants on the binding of intact hCG. A radio-receptor assay based on cell membranes expressing recombinant human LH/CG receptors was validated and used in this study to avoid species differences in the receptor-binding specificity. The results showed that none of the hCG variants that we studied had sufficient binding affinity to compete with binding of intact hCG, nor were they able to antagonize the binding of intact hCG. These results suggest that hCG variants with either abbreviated polypeptide structures or incomplete peptide linkage are products or metabolites which do not have the tropic biological activity of the whole hormone, the intact heterodimeric hCG.

Cells, Cultured↗
PubMed1997

Characterization of human chorionic gonadotropin in normal and abnormal pregnancies.

In this study circulating human chorionic gonadotropin (hCG) levels in the peri-implantation period of natural cycles of normal women were characterized. The hypothesis that the bioactivity of hCG in abnormal pregnancies is different from that in normal pregnancies was tested daily through serum hCG measurements in two immunoenzymometric assays, a radioreceptor assay and a human luteinizing hormone/human chorionic gonadotropin--cyclic adenosine monophosphate--luciferase bioassay. In normal pregnancies, the levels of immunoreactive and bioactive hCG were higher than in abnormal pregnancies (p < 0.05). In addition, the slopes of the rise in concentration of hCG as measured in all four assays were significantly greater for normal pregnancies than for abnormal pregnancies (p < 0.01). The rate of rise of hCG bioactivity was significantly greater than the rise of immunoreactivity or receptor-binding activity in normal pregnancies, but this difference was not observed in abnormal pregnancies. These results indicate that: (1) A steep rise of bioactive hCG is a consistent feature of the peri-implantation period of normal pregnancies. (2) Abnormal pregnancies had a deficiency in the production of hCG, which was reflected in both the hCG levels and the rate of increase, even in the first week of implantation. (3) Some abnormal pregnancies produced hCG with lower biological activity than the hCG of normal pregnancies.

Abortion, Spontaneous↗
PubMed1997

The relationship between trophoblast differentiation and the production of bioactive hCG.

We previously showed that a significant number of failing pregnancies are associated with production of human chorionic gonadotropin (hCG) having relatively low bioactivity. The present study was designed to compare the secretion of intact, immunoreactive hCG to the secretion of bioactive hCG during trophoblast differentiation, and to test the hypothesis that the lower bioactive: immunoreactive hCG ratios in failing pregnancies are related to reduced or impaired trophoblast differentiation. Cytotrophoblast cells were isolated from term placentas and cultured under conditions that induced or did not induce syncytiotrophoblast formation. Culture media were collected at regular intervals up to 72 h and levels of immunoreactive and bioactive hCG were measured. The differentiation of cytotrophoblast cells to multinucleated syncytiotrophoblast was monitored by immunocytochemistry and electron microscopy. During the 72 h culture period, concentrations of immunoreactive and bioactive hCG increased in both differentiating and non-differentiating cells. However, the concentrations of immunoreactive and bioactive hCG were higher under culture conditions that promoted trophoblast differentiation. Furthermore, the ratio of bioactive hCG to immunoreactive hCG was higher in differentiating cultures. When differentiation was inhibited by dimethyl sulfoxide, the secretion of bioactive hCG was reduced and the bioactive: immunoreactive hCG ratio did not change. These findings are consistent with the idea that production of bioactive hCG accompanies syncytiotrophoblast formation.

Administration, Topical↗
PubMed1996

Major groove recognition elements in the middle of the T7 RNA polymerase promoter.

T7 RNA polymerase recognizes a relatively small promoter extending only 17 base pairs upstream from the start site for transcription. A model for this recognition suggests that the enzyme interacts with the major groove of duplex DNA in the region centered at position -9 [Muller, D.K., et al. (1989) Biochemistry 28, 3306-3313], and recent kinetic analyses of promoters containing base analogs at positions -10 and -11 have provided support for this model [Schick, C., & Martin, C.T. (1993) Biochemistry 32, 4275-4280; Schick, C., & Martin, C.T. (1995) Biochemistry 34, 666-672]. In the current work, we extend this analysis across the proposed major groove, identifying specific base functional group contacts at positions -9 through -5. Specifically, the 6-carbonyl of guanine at positions -9 and -7, the 6-amino group of adenine at position -8, the 5-methyl group of thymine at position -6 and the 2-amino group of guanine at position -5 are identified as primary contacts. The results strongly support the model for duplex recognition in this region of the promoter and suggest that recognition continues along one face of the helix beyond the major groove and into the adjoining minor groove at position -5, where helix melting begins.

Bacteriophage T7↗
PubMed1994

Subtypes of autism by cluster analysis.

Multidisciplinary data from 166 children with autistic spectrum disorders were subjected to cluster analysis. Cross-validation between random halves of the sample showed acceptable consistency of the clustering method. Four clinically meaningful subtypes emerged from the analysis. They did not differ in demographic characteristics but did show, on average, distinct differences in behavioral and cognitive areas. Over half of the sample fell into a subtype described as typically autistic with abnormal verbal and nonverbal communication, aloofness, impaired social skills, and sensory disturbances. Another 19% were similarly autistic but with moderate to severe mental handicap. The remaining children formed two subtypes: a high-functioning Asperger-like group who were overactive and aggressive, and a small group who were impaired in social and language skills, had restricted interests, and a family history of learning problems. This study highlights important differences among children with autism and emphasizes relationships between cognitive functioning and subtypes of the disorder.

Attention Deficit Disorder with Hyperactivity↗
PubMed1994

Parent-professional agreement on diagnosis and recommendations for children with developmental disorders.

Twenty-eight children with developmental disorders underwent an interdisciplinary assessment for diagnosis and recommendations about management. Following this assessment, the degree of agreement on diagnosis and recommendations between parents and the team was determined. There was substantial agreement for diagnosis of clearly identifiable conditions such as genetic disorders, autism, and mental retardation but less agreement for milder disorders such as learning disabilities, attention deficit disorder, and emotional disorders. Agreement on management varied, being higher for speech therapy and psychosocial interventions but lower for use of stimulant medication and diet. The parents identified additional diagnostic labels in their child and mentioned more recommendations than the clinicians prescribed. The results suggest the need for careful attention to parent perceptions following interdisciplinary assessment.

British Columbia↗