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Biomedical subjects

T Ho

Publications and source records attributed to T Ho.

At least 55 records · Page 3Linked to original sources
PubMed1996

Mutations in the B2 bradykinin receptor reveal a different pattern of contacts for peptidic agonists and peptidic antagonists.

The B2 bradykinin receptor, a seven-helix transmembrane receptor, binds the inflammatory mediator bradykinin (BK) and the structurally related peptide antagonist HOE-140. The binding of HOE-140 and the binding of bradykinin are mutually exclusive and competitive. Fifty-four site-specific receptor mutations were made. BK's affinity is reduced 2200-fold by F261A, 490-fold by T265A, 60-fold by D286A, and 3-10-fold by N200A, D268A, and Q290A. In contrast, HOE-140 affinity is reduced less than 7-fold by F254A, F261A, Y297A, and Q262A. The almost complete discordance of mutations that affect BK binding versus HOE-140 binding is surprising, but it was paralleled by the effect of single changes in BK and HOE-140. [Ala9]BK and [Ala6]BK are reduced in receptor binding affinity 27,000- and 150-fold, respectively, while [Ala9]HOE-140 affinity is reduced 7-fold and [Ala6]HOE-140 affinity is unchanged. NMR spectroscopy of all of the peptidic analogs of BK or HOE-140 revealed a beta-turn at the C terminus. Models of the receptor-ligand complex suggested that bradykinin is bound partially inside the helical bundle of the receptor with the amino terminus emerging from the extracellular side of helical bundle. In these models a salt bridge occurs between Arg9 and Asp286; the models also place Phe8 in a hydrophobic pocket midway through the transmembrane region. Models of HOE-140 binding to the receptor place its beta-turn one alpha-helical turn deeper and closer to helix 7 and helix 1 as compared with bradykinin-receptor complex models.

Adrenergic beta-Antagonists↗
PubMed1996

RS-66271, a C-terminally substituted analog of human parathyroid hormone-related protein (1-34), increases trabecular and cortical bone in ovariectomized, osteopenic rats.

It was predicted from the amino acid sequence of the bone anabolic peptides, parathyroid hormone (PTH) (1-34) and PTH related protein (PTHrP) (1-34), that the C-terminal amino acids form an amphipathic alpha-helix. Therefore, we substituted a model amphipathic alpha-helical peptide (MAP) sequence in the C-terminal region of hPTHrP(1-34), obtaining RS-66271 ([MAP1-10]22-31 hPTHrP(1-34)-NH2). The anabolic activities of RS-66271 and hPTHrP(1-34) were evaluated in 3-month-old, ovariectomized (OVX) osteopenic rats. Subcutaneous injection of hPTHrP(1-34) at 80 micrograms/kg/day partially reversed estrogen depletion trabecular bone loss but was ineffective in the cortex. In contrast, RS-66271 dose-relatedly reversed loss at both sites and, at 80 micrograms/kg/day, returned both trabecular and cortical bone calcium to the level of sham-operated controls. Histomorphometric analysis showed significantly elevated bone formation rates over vehicle-treated OVX in both trabecular and cortical tibial bone following treatment with RS-66271. Electron microscopy showed an increase in the relative surface area of vertebral trabeculae covered by osteoblasts in animals treated with RS-66271. These studies demonstrate that the C-terminal amino acids of hPTHrP(1-34) can be replaced by a model amphipathic helix and that the new chemical entity has greater anabolic activity than the parent peptide. The results suggest that RS-66271 may be a candidate molecule for the treatment of human osteoporosis.

Amino Acid Sequence↗
PubMed1996

Isolation of Coxiella burnetii from children with influenza-like symptoms in Japan.

The prevalence of Coxiella burnetii antibodies was investigated by indirect immunofluorescence (IF) test in 55 paired sera (acute and convalescent phases) of school children who had influenza-like symptoms. Of the convalescent serum samples examined, 18 (32.7%) sera reacted positively to phase II antigen of C. burnetii. Coxiella-like organism was isolated from the sera of 13 children after injection of the 18 acute phase sera into mice. The organism was identified as C. burnetii by Giemsa staining and the IF antigen test of mouse spleen smears, the polymerase chain reaction (PCR) method, electron microscopic observations of the mouse spleen cells, and the IF antibody test of mouse sera. This is the first report of isolation of C. burnetii from serum specimens of children having influenza-like symptoms. The evidence that C. burnetii was isolated from people indigenous to Japan at a considerably high incidence suggested that C. burnetii may be widespread as a cause of influenza-like symptoms in Japan.

Acute Disease↗
PubMed1996

Cervical screening in elderly women in Singapore.

The study was conducted to determine the pick-up rate of abnormal cervical smears and the prevalence rate of cervical cancer in women aged 60 years and above and the demographic characteristics of the women screened. The pick-up rate of abnormal cervical smears was 1.65%. The prevalence rate for cervical intraepithelial neoplasia and frank carcinoma was 6.4 and 5.0 per thousand women screened respectively. The study group comprised 89.7% Chinese, 4.7% Malays, 3.6% Indians and 2.0% Others. The pick-up rate of abnormal smears was 1.9% in the Chinese and 1.3% in the Indians. There were no abnormal smears in the Malays and Others. The results demonstrate the importance of a routine cervical cancer screening programme among elderly women aged 60 years and above in Singapore.

Age Factors↗
PubMed1996

Limited value of routine followup CT scans in nonoperative management of blunt liver and splenic injuries.

The objective was to determine the utility of a second CT scan in nonoperative management of blunt liver and splenic trauma. The design was a retrospective review of consecutive cases over a 2-year period in two trauma centers. Subjects were 152 patients with blunt abdominal trauma and isolated injuries to liver and/or spleen. Thirty patients received immediate laparotomy, whereas 122 patients (80%) underwent CT scanning that showed splenic (n = 64), liver (n = 44), or combined (n = 14) injuries. Nonoperative management was undertaken in 99 of the 122 (81% of the patients who received CT scans; 65% of the overall series) and was ultimately successful in 94 (95%). Second CT scans were used in 26 patients (26%), one of whom received laparotomy for drainage of a bile leak and three for ongoing bleeding. None of the followup scans showed major progression of injury, and scan findings did not influence decisions for operation in any patients. Routine followup CT scanning is not a justifiable component of nonoperative management protocols for blunt liver and splenic injuries.

Adolescent↗
PubMed1995

Evidence for gene silencing by DNA methylation in normal human diploid fibroblasts.

Human diploid fibroblasts, strain MRC-5, were permeabilized by electroporation and treated with 5-methyl deoxycytidine triphosphate (5-methyl dCTP) in the S phase of the cell cycle. The frequency of TGR HPRT- cells was increased up to 20-fold in comparison to control untreated cultures. Representative TGR clones were unable to grow in HAT, and these were treated with 5-azacytidine (5-aza-CR). In many cases subsequent growth in HAT medium was observed, but in others it is likely that the cells had run out of growth potential. The results provide the first evidence of the silencing and reactivation of a gene in normal diploid mammalian cells.

Azacitidine↗
PubMed1995

Is there more than one prostaglandin E receptor subtype mediating hyperalgesia in the rat hindpaw?

Five synthetic prostaglandin E analogs (11-deoxyPGE1, 17-phenyl-ol-trinor prostaglandin E2, enisoprost, MB28767 and misoprostol) have been evaluated for their ability to produce mechanical hyperalgesia in rats. The Randall-Selitto paw withdrawal model of mechanical hyperalgesia was used. Following intradermal injections (2.5 microliters) into the dorsal surface of the hindpaw, each prostaglandin E analog produced a dose-dependent (1-1000 ng) decrease in nociceptive threshold (i.e. hyperalgesia). Hyperalgesia produced by 17-phenyl-ol-trinor prostaglandin E2 and MB28767, was inhibited by the prostaglandin E1 antagonist SC19220 (7.5 ng), while the hyperalgesia produced by 11-deoxyprostaglandin E1, enisoprost and misoprostol was not inhibited by this antagonist. Hyperalgesia produced by all five analogs was significantly attenuated or completely blocked by inhibiting stimulatory guanine nucleotide-binding regulatory protein with guanosine 5'-O-(2-thiodiphosphate), adenylyl cyclase with 2'5'-dideoxyadenosine and protein kinase A with WIPTIDE. These results suggest the presence of more than one prostaglandin E-receptor subtype, which mediate hyperalgesia, predominantly via the cAMP second messenger system, in the hindpaw of the rat.

Alprostadil↗
PubMed1995

The role of microtubule dynamics in growth cone motility and axonal growth.

The growth cone contains dynamic and relatively stable microtubule populations, whose function in motility and axonal growth is uncharacterized. We have used vinblastine at low doses to inhibit microtubule dynamics without appreciable depolymerization to probe the role of these dynamics in growth cone behavior. At doses of vinblastine that interfere only with dynamics, the forward and persistent movement of the growth cone is inhibited and the growth cone wanders without appreciable forward translocation; it quickly resumes forward growth after the vinblastine is washed out. Direct visualization of fluorescently tagged microtubules in these neurons shows that in the absence of dynamic microtubules, the remaining mass of polymer does not invade the peripheral lamella and does not undergo the usual cycle of bundling and splaying and the growth cone stops forward movement. These experiments argue for a role for dynamic microtubules in allowing microtubule rearrangements in the growth cone. These rearrangements seem to be necessary for microtubule bundling, the subsequent coalescence of the cortex around the bundle to form new axon, and forward translocation of the growth cone.

Animals↗
PubMed1995

Modulation of Saccharomyces cerevisiae DNA double-strand break repair by SRS2 and RAD51.

RAD52 function is required for virtually all DNA double-strand break repair and recombination events in Saccharomyces cerevisiae. To gain greater insight into the mechanism of RAD52-mediated repair, we screened for genes that suppress partially active alleles of RAD52 when mutant or overexpressed. Described here is the isolation of a phenotypic null allele of SRS2 that suppressed multiple alleles of RAD52 (rad52B, rad52D, rad52-1 and KlRAD52) and RAD51 (KlRAD51) but failed to suppress either a rad52 delta or a rad51 delta. These results indicate that SRS2 antagonizes RAD51 and RAD52 function in recombinational repair. The mechanism of suppression of RAD52 alleles by srs2 is distinct from that which has been previously described for RAD51 overexpression, as both conditions were shown to act additively with respect to the rad52B allele. Furthermore, overexpression of either RAD52 or RAD51 enhanced the recombination-dependent sensitivity of an srs2 delta RAD52 strain, suggesting that RAD52 and RAD51 positively influence recombinational repair mechanisms. Thus, RAD52-dependent recombinational repair is controlled both negatively and positively.

Alleles↗
PubMed1995

Isolation of Coxiella burnetii from dairy cattle and ticks, and some characteristics of the isolates in Japan.

Coxiella burnetii was isolated from raw milk (36/214, 16.8%) and uterus swab samples (13/61, 21.3%) originating from dairy cattle with reproductive disorders, aborted bovine fetus samples (2/4, 50%), mammary gland samples (4/50, 8%) originating from healthy dairy cattle, and tick samples (4/15, 26.7%) originating from 2 pastures. Fifty-nine strains had various degrees of pathogenicity, high (8; 13.6%), moderate (28; 47.5%) and low (23; 39%), for guinea pigs. The results of isolation suggested a high prevalence of Coxiella infection in dairy cattle with reproductive problems in Japan. Twelve strains (7, 2 and 3 strains from cattle, ticks and humans, respectively) and the reference Nine Mile strain of phases I and II were propagated in both yolk sacs of embryonated hen eggs and Buffalo green monkey (BGM) cell cultures. Protein profiles of these strains were similar to those of the reference strain of phase I. Lipopolysaccharide (LPS) profiles of 12 strains were similar to those of the reference strain of phase I and different from those of the reference strain of phase II. The LPS profiles of 12 strains suggested that these strains are associated with an acute form of Q fever.

Acute Disease↗
PubMed1994

Comparison of prostaglandin E1- and prostaglandin E2-induced hyperalgesia in the rat.

We have studied prostaglandin E1-induced mechanical hyperalgesia in the rat hindpaw, by assessing paw-withdrawal thresholds, before and after injecting prostaglandin E1 alone or with other agents, in normal and streptozotocin-induced diabetic rats. In normal and diabetic rats, prostaglandin E1 (1-1000 ng) produced a dose-dependent decrease in mechanical nociceptive threshold. In diabetic rats, prostaglandin E1 was more potent than in normal rats, in producing hyperalgesia, whereas prostaglandin E2 hyperalgesia was not changed in normal and diabetic rats. Prostaglandin E1-induced hyperalgesia was not inhibited by E-type 1 prostaglandin receptor antagonists, SC19220 or SC51089, either in normal or diabetic rats. In fact, in the presence of SC19220, prostaglandin E1 produced enhanced hyperalgesia, in normal rats. Prostaglandin E1 hyperalgesia was not significantly modified by sympathectomy or indomethacin. Unlike prostaglandin E2, prostaglandin E1 hyperalgesia was not blocked by the inhibitor of the stimulatory guanine nucleotide-binding regulatory protein, guanosine 5'-O-(2-thiodiphosphate). It is suggested that prostaglandin E1 decreases primary afferent nociceptive threshold directly, by activating a prostaglandin receptor other than the E-type 1 prostaglandin receptor, and that this receptor is not coupled to a stimulatory guanine nucleotide-binding regulatory protein.

Alprostadil↗
PubMed1994

Dementia in elderly patients: can the 3R mental stimulation programme improve mental status?

The aim of this study was to determine whether the 3R mental stimulation programme can improve the mental status score (MSS) of a group of patients with dementia attending a day care centre. Fifteen patients with dementia attending a day care centre were exposed to the 3R stimulation programme over eight weeks while 15 controls were not. All patients from both groups were subjected to pre- and post-exposure questionnaires modified from the Mental Status Questionnaire of Kahn et al. A mental status score (MSS) was thus calculated on both occasions. All patients in the exposed group showed an improved mental status score, with the mean 'pre-exposure' and 'post-exposure' scores of 4.4 and 7.3, respectively (p < 0.001; paired t test). In contrast, the mental status scores of 12 control patients had deteriorated and mean 'pre-exposure' and 'post-exposure' scores were 4.1 and 3.4, respectively (p < 0.05; paired t test). Using multiple covariance analysis, the adjusted 'post-exposure' mean mental status score was 7.1 for the exposed and 3.6 for the controlled group (p < 0.001). The 3R programme appears to be effective for short-term mental stimulation of demented elderly people.

Aged↗
PubMed1993

Therapeutic effects of a synthetic peptide of C-reactive protein in pre-clinical tumor models.

Previous studies have shown that multilamellar vesicles (MLV) or other carriers containing purified human C-reactive protein (CRP) have therapeutic activity in preclinical tumor models. Here we evaluated the therapeutic effects of MLV containing novel synthetic peptides, derived from the structure of CRP, on the extent of (a) established lung metastases of fibrosarcoma T241 in C57Bl/6 mice, (b) survival of C57Bl/6 mice bearing established liver metastases of colon carcinoma MCA-38, and (c) primary tumor growth of Renca renal carcinoma in Balb/c mice. In all cases, a single synthetic CRP peptide, RS-83277, demonstrated significant antitumor effects comparable to that seen with intact CRP. Two other synthetic CRP peptides, RS-83287 and RS-83147, showed no therapeutic activity and were comparable to control MLV containing only buffer. None of the peptides contained sequences homologous with that of the phagocyte stimulant, tuftsin. Activity of MLV-encapsulated RS-83277 was dose-dependent, and a comparable dose of the soluble peptide, given either alone or following injection of buffer-MLV, was ineffective. These results demonstrate immunotherapeutic potential for a novel synthetic peptide derived from CRP, and endogenous acute-phase protein.

Adenocarcinoma↗
PubMed1992

Maximal mydriasis evaluation in cataract surgery.

We propose the maximal mydriasis test (MMT) as a simple and safe means to provide the cataract surgeon with objective and dependable preoperative information on the idiosyncratic mydriatic response of the pupil. The MMT results of a consecutive series of 165 eyes from 100 adults referred for cataract evaluation are presented to illustrate the test's practical applications and value. The results enable the surgeon to anticipate problem eyes preoperatively so he or she can plan an appropriate and effective surgical strategy. The MMT has also improved out cost-effectiveness by cutting down unnecessary delays in the operating room and enabling better utilization of restricted costly resources.

Administration, Topical↗
PubMed1992

Sequential argon-YAG laser iridotomies in dark irides.

Laser iridotomies in dark coloured irides are associated with higher complication and failure rates. A prospective clinical study to evaluate the use of the argon and Nd:YAG laser in sequential combination for iridotomy was carried out on 20 eyes of 13 patients with dark irides. Patent iridotomies were achieved in single treatment sessions for all the eyes. Iridotomy closure was observed in one eye during a mean follow-up period of 14 months (range 6-20 months). Complications from the treatment occurred in five eyes and were minor. Total mean energy used for the argon and Nd:YAG stages respectively were a third of most studies on pure argon and Nd:YAG iridotomies. Sequential argon-YAG laser iridotomy combines most of the advantages of both laser types while avoiding some of their disadvantages. We find it a safe and effective tool for iridotomy in otherwise difficult dark irides.

Aged↗
PubMed1992

Localization of transforming growth factor-alpha in human appendageal tumors.

Transforming growth factor-alpha (TGF alpha) is a potent mitogen for epithelial cells that has been localized to normal human appendageal epithelia. To further understand the role of TGF alpha in human appendages, we examined TGF alpha expression immunohistochemically in 17 types of human appendageal tumors differentiating toward hair follicles, eccrine, apocrine, and sebaceous glands. In order of decreasing degrees of differentiation, tumors could be divided into hyperplasias, adenomas, benign epitheliomas, and primordial epitheliomas. Using an antibody that recognizes primarily the 6-kd and 13-kd forms of TGF alpha, TGF alpha immunostaining in 16 of 17 tumor types analyzed was found to follow a similar pattern, with expression in hyperplasias greater than adenomas greater than benign epitheliomas greater than primordial epitheliomas. Within a given tumor, TGF alpha expression also correlated well with the known differentiation state of the tumor cell types. The results suggest that TGF alpha expression is directly correlated with the differentiation state of hair follicle, eccrine, apocrine, and sebaceous tumors in human skin, and raises the possibility that TGF alpha may play a role in the differentiation of appendageal epithelia.

Apocrine Glands↗