Search PubMed⌕ Search

Biomedical subjects

A Chong

Publications and source records attributed to A Chong.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effect of prone sleeping on circulatory control in infants.

BACKGROUND: The mechanism of death in sudden infant death syndrome (SIDS) remains unclear. Progressive bradycardia is the pre-eminent terminal event, suggesting that circulatory failure might be a crucial factor. Vasomotor tone regulates the circulatory system by controlling blood volume distribution while maintaining venous return and blood pressure. AIM: To examine whether prone sleeping, the most consistently identified risk factor for SIDS, has a measurable influence on vasomotor/circulatory control. METHODS: 44 full term infants (mean age, 7.9 weeks) were studied during an overnight sleep. Recordings were made while the infants were horizontal and asleep in the supine and prone positions, and repeated after a head up tilt to 60 degrees, maintained for 30 minutes, while in both sleep positions. Blood pressure, heart rate, anterior shin, and anterior abdominal wall skin temperatures were measured. RESULTS: Systolic blood pressure was lower, but peripheral skin temperature and heart rate were higher during sleep, while horizontal, in the prone rather than the supine position. After tilting, there was a greater reduction in blood pressure and a greater increase in peripheral skin temperature and heart rate when in the prone position. Anterior abdominal wall skin temperature did not vary in either sleeping positions while horizontal or tilted. CONCLUSION: Prone sleeping has a measurable effect on circulatory control, with a reduction in vasomotor tone resulting in peripheral vasodilatation, a higher peripheral skin temperature, a lower blood pressure, and a higher resting heart rate. Because vasomotor tone is crucially important in circulatory control this could be a factor in increasing the risk of SIDS.

Autonomic Nervous System↗
PubMed2000

Effect of ganaxolone in a rodent model of cerebral hematoma.

BACKGROUND AND PURPOSE: Therapy with gamma-aminobutyric acid (GABA) agonists appears to improve outcome after experimental hematoma but with unacceptable side effects. We looked to synthetic GABA agonists, or positive GABA modulators, widely developed as anticonvulsants and anxiolytics, to find compounds that may be effective. Ganaxolone is a synthetic neuroactive steroid that positively modulates GABA. We sought to determine whether ganaxolone was beneficial using a model of intracerebral hematoma. METHODS: We stereotaxically injected varying doses of bacterial collagenase into the caudate nucleus of rats to induce blood-brain barrier failure and hematoma formation. Four hours later, we administered intravenously 15 or 30 mg/kg ganaxolone (n=23 each group), 20 mg/kg pregnanolone (n=21), or vehicle (n=30). Forty-eight hours after collagenase injection, we rated each animal using a standard rodent neurological examination. The ratings were compared with the amounts of injected collagenase using the quantal bioassay procedure. Other sets of animals were tested later for visuospatial learning. Brains were then prepared for histomorphometry, and brain volumes were estimated. RESULTS: We found that ganaxolone 30 mg/kg significantly increased the ED(50) in the bioassay, for a potency ratio of 1.8+/-0.41 compared with vehicle (P<0.05). Ganaxolone 15 mg/kg and pregnanolone did not affect neurological outcome. Ganaxolone 30 mg/kg did not clearly improve visuospatial learning several weeks after hemorrhage. Ganaxolone exhibited a weak effect on cerebral volumes 48 hours after stroke, but 3 months after hemorrhage no such effect could be detected. CONCLUSIONS: Ganaxolone improves neurological outcome 48 hours after intracerebral hematoma but not visuospatial learning several weeks after intracerebral hematoma. Histological evidence of damage was reduced at 48 hours but not at 3 months.

Animals↗
PubMed1999

Site-specific characterization of the N-linked glycans of murine prion protein by high-performance liquid chromatography/electrospray mass spectrometry and exoglycosidase digestions.

The murine prion protein PrP gene encodes a protein of 254 amino acids with two consensus sites for Asn-linked glycosylation at codons 180 and 196. A partial site-specific study of the N-linked glycans from hamster PrP has previously been carried out by mass spectrometry [Stahl, N., Baldwin, M. A., Teplow, D. B., Hood, L., Gibson, B. W., Burlingame, A. L., and Prusiner, S. B. (1993) Biochemistry 32, 1991-2002] and revealed that the glycosylation at Asn-181 (equivalent to mouse 180) is heterogeneous, comprising over 30 glycoforms. The identification of the glycosylated peptide spanning Asn-197 was not reported. Recent technical advances in electrospray mass spectrometry now provide the sensitivity to detect low femtomole quantities of glycopeptides with >5000 mass resolution and 30 ppm mass measurement [Medzihradszky, K. F., Besman, M. J., and Burlingame, A. L. (1998) Rapid Commun. Mass Spectrom. 12, 472-478]. This performance coupled with stepwise exoglycosidase digestion has been employed to establish the differential nature of the structural complexity (glycoforms) of the glycans at Asn-180 and Asn-196 from a single strain infected with the ME7 strain. Some sixty structures have been found characterized by neutral and sialylated bi-, tri-, and tetraantennary complex-type bearing outer-arm alpha(1-3)-fucosylation (the Lewisx and sialyl-Lewisx epitopes), core alpha(1,6) fucosylation, and the presence of terminal HexNAc residues. The Lewisx trisaccharide is the major nonreducing structure at Asn-180, and significant amounts of both Lewisx and sialyl Lewisx epitopes are observed at Asn-196. The abundance of the Lewisx and sialyl Lewisx epitopes on murine PrPSc may indicate a role for these structures in the normal function of PrPC or the pathophysiology of PrPSc.

Amino Acid Sequence↗
PubMed1999

Molecular analysis of ovine prion protein identifies similarities between BSE and an experimental isolate of natural scrapie, CH1641.

New variant Creutzfeldt-Jakob disease (vCJD) and bovine spongiform encephalopathy (BSE) are caused by the same strain of pathogen and, as sheep can develop experimental BSE, this has raised concern that humans may be at risk from eating mutton if BSE has naturally transmitted to sheep. Biochemical typing of abnormal prion proteins (PrPsc) has been suggested to detect BSE in sheep. Although this approach is ingenuous, we can now report biochemical evidence of strain variation in contemporary and archival brain tissue from cases of experimental BSE or experimental and natural scrapie in sheep. Interestingly, we found at least one isolate of natural scrapie (CH 1641) with a very similar, but not identical, PrPsc profile to BSE but which differs from BSE in its transmission characteristics to mice.

Animals↗
PubMed1999

Experimentally induced bovine spongiform encephalopathy did not transmit via goat embryos.

Goats are susceptible to experimental challenge with bovine spongiform encephalopathy (BSE). This study set out to investigate whether the transmission of BSE could occur in goats following the transfer of embryos from experimentally infected donor females into uninfected recipient females. The results showed no evidence of transmissible spongiform encephalopathy disease in any of the offspring which developed from embryos from infected donors, nor indeed in any of the recipient females used as surrogate dams. In addition, there was no indication of experimental BSE spreading as either a venereal infection to males used in mating or by maternal transmission to offspring born naturally to experimentally infected donors, although numbers were small.

Animals↗
PubMed1998

The shortest known prion protein gene allele occurs in goats, has only three octapeptide repeats and is non-pathogenic.

The prion protein (PrP) gene modulates the incidence and incubation periods of transmissible spongiform encephalopathies of sheep, goats, mice and man. Here, a new caprine PrP allele encoding the shortest naturally occurring PrP protein so far described is reported. This variant contains only three instead of the usual five copies of a short peptide repeat [Pro-Gln/His-Gly-Gly-Gly-(Gly)-TrpGly-Gln] characteristic of PrP, with an additional Trp to Gly substitution in codon 102. Fifteen out of 111 genotyped goats carried the novel PrP allele and 14 survived without signs of disease for at least 4 years. One goat heterozygous for the polymorphism was challenged experimentally with SSBP/1-scrapie and succumbed after an unusually long incubation period.

Alleles↗
PubMed1998

[Central neurocytoma].

INTRODUCTION: A central neurocytoma (CN) is a rare tumor, of neuronal origin, well-differentiated and found intraventricularly. It mainly affects young adults. Firm diagnosis is made on immunohistochemical (IHQ) and ultrastructural studies, since on optic microscopy it is similar in appearance to an oligodendroglioma or to an ependymoma. PATIENTS AND METHODS: We studied 4 cases, three after surgical resection and one on autopsy. The average age was 29, ranging from 3 to 63. Both sexes were equally affected. In all cases IHQ techniques were used (GFAP, neurofilament, synaptophysin and specific neuronal enolase) and they were studied by electron microscopy. RESULTS: IHQ was negative for GFAP and neurofilament, but intensely positive for synaptophysin and specific neuronal enolase. On ultrastructural study there were few neurofilaments, microtubules and dense central granules typical of neural differentiation. CONCLUSIONS: The findings in our cases lead to diagnosis of NC and confirm that this tumor is a distinct clinicopathological entity.

Adolescent↗
PubMed1996

Metabolic changes associated with vacuolation in murine models of scrapie using in vitro 1H-NMR spectroscopy.

In this study, metabolic changes in the 79A/C3H, ME7/VM, ME7/C3H, 87V/VM and 22A/SV scrapie mouse models were investigated during the clinical phase of the disease, using in vitro proton nuclear magnetic resonance spectroscopy. N-acetyl-aspartate was found to be significantly reduced in infected mice of the ME7/ C3H (40% reduction), ME7/VM (26%) and 79A/C3H (17%) models when compared to control mice, but not in the 87V/VM and 22A/SV models. The concentration of choline containing compounds and creatine remain unchanged in all models when compared with control murine brains. The level of N-acetyl-aspartate reduction correlated with the extent of grey-matter brain vacuolation. The levels of myo-inositol were found to be significantly increased in the ME7/VM (143%) and 79A/C3H (132%) models only and no significant changes were observed in the ME7/C3H, 87V/VM and 22A/SV models. These changes did not correspond to the severity of gliosis.

Animals↗
PubMed1996

Cytotoxicity of prion protein peptide (PrP106-126) differs in mechanism from the cytotoxic activity of the Alzheimer's disease amyloid peptide, A beta 25-35.

The abnormal form of the prion protein (PrPSc), a synthetic prion protein peptide fragment (PrP106-126) and fragments of the Alzheimer's protein precursor, APP, have been shown to be cytotoxic in vitro. We have used synchronous, clonal cell models originally developed to study the toxicity of the Alzheimer's disease amyloid peptide, A beta 25-35, to investigate the actions of PrP peptides. We found that the cytotoxicity of the PrP106-126 depends on its state of aggregation and the cellular expression of PrPc, and is independent of a loss of MTT reduction activity in the absence of cell death associated with the cellular effects of A beta 25-35. These factors may play a role in the lesion specificity of different pathological phenotypes of prion-protein related diseases.

Amino Acid Sequence↗
PubMed1996

Preservation of endothelium-dependent vasodilation with low-potassium University of Wisconsin solution.

University of Wisconsin solution has provided excellent myocardial preservation. However, the high potassium content of the currently available University of Wisconsin solution has been implicated in coronary artery endothelial damage. We placed 16 neonatal (age 1 to 3 days) Duroc piglet hearts on an isolated nonworking perfusion circuit. Endothelium-dependent and endothelium-independent vasodilation were tested by measuring coronary blood flow after intracoronary infusion of bradykinin (10(-6) mol/L) and nitroprusside (10(-6) mol/L), respectively. In addition, nitric oxide levels were measured after bradykinin infusion. The hearts were then arrested blindly with either a modified University of Wisconsin solution (group 1; n = 8, K+ = 25 mEq/L) or standard University of Wisconsin solution (group 2; n = 8, K+ = 129 mEq/L) by infusion of cardioplegic solution every 20 minutes for a total of 2 hours. After bradykinin infusion, the mean coronary blood flow increased by 237.1% +/- 14.0% of baseline valves before arrest and by 232.8% +/- 16.0% after arrest in group 1 (p = not significant). As in the first group, the mean coronary blood flow in group 2 increased by 231.1% +/- 13.7% before arrest; however, the increase in mean coronary blood flow after arrest was significantly attenuated (163.3% +/- 12.8%, p < 0.01). The loss of endothelium-dependent coronary blood flow response in group 2 correlated with a decreased capacity to release nitric oxide after arrest (prearrest 8.25 +/- 2.30 nmol/min per gram versus postarrest -2.46 +/- 2.29 nmol/min per gram, p < 0.01). Endothelium-independent vasodilatory response revealed no significant difference between groups before and after arrest. These results suggest that the low-potassium University of Wisconsin solution provides superior protection of the endothelium by preserving the endothelium-dependent vasodilatory response to nitric oxide release.

Adenosine↗
PubMed1996

Mild cervical atypia: a management dilemma.

This study examined 117 patients with mild cervical atypia or atypical squamous cells of uncertain significance; it was found that 25% had histologically proven CIN lesions by colposcopically-directed punch biopsy or cone biopsy. 18% were found to have at least CIN 2 lesions and there was 1 case of invasive cancer. These data strongly support the recommendation of early colposcopic referral in patients with mild cervical atypia.

Adolescent↗
PubMed1996

Communication problems in day to day practice.

One of the main difficulties GPs face is in communication. This is not necessarily in the doctor-patient relationship, but often in areas of practice management, and the way our work impinges on our social lives.

Communication↗
PubMed1995

Pharmacologically induced regression of chronic transplant rejection.

Chronic rejection, characterized by a progressive obliterative arteriopathy, is a major cause of graft failure in long-surviving human transplants for which there is no effective treatment. Leflunomide, an isoxazol derivative, has been shown to be a novel immunomodulatory drug that profoundly suppresses the immune response. In this study, 58 Fisher-344 rats received cardiac transplantation from Lewis rats. All the recipients were given CsA at 2.5 mg/kg for 5 days postoperatively. Without further treatments, the arterial intima was progressively injured by mononuclear cell infiltration and Ab deposition. Smooth muscle cell and fibroblast proliferation in the intima became a predominant phenomenon by day 90. CsA was ineffective in controlling the progress of arterial intimal thickening when treatment began on day 30. Leflunomide at 5 mg/kg failed to control arterial intimal thickening by day 60 when therapy began on day 30. However, the progress of arterial intimal thickening was significantly inhibited by day 90 when the dosage of leflunomide had been increased to 10 mg/kg on day 60. Combined therapy with leflunomide and CsA at 5 mg/kg for 30 days dramatically reversed the arterial thickening by day 60. After increasing the dosages of both leflunomide and CsA to 10 mg/kg on day 60, the combination therapy steadily controlled the chronic rejection. Only the combination therapy significantly down-regulated circulating antidonor IgM and IgG titers. In rat smooth muscle cell culture, this same drug combination had a synergistic inhibitory effect on proliferation. Therefore, the combination therapy of leflunomide and CsA could reverse and control the progress of chronic rejection, while leflunomide, at higher dosage as a monotherapy, could stabilize chronic rejection in this model. The mechanism of the regression of chronic rejection by leflunomide and cyclosporine may be related to their in vitro abilities to control not only lymphocyte but smooth muscle cell proliferation, as well. The synergistic effect of these two drugs on vascular smooth muscle cell proliferation in vitro may be an important part of this novel activity. This unique feature holds intriguing possibilities for treating established chronic rejection.

Animals↗
PubMed1995

Improved viability of hepatic allografts from fasted donors is associated with decreased peripheral TNF activity.

Despite improvements in preservation solutions, hepatic allografts continue to be lost from primary nonfunction. Previous work by this group and others has established that donor fasting improves the viability of hepatic allografts. We have also established an association between viability of stored organs and serum TNF levels. The purpose of this study was to determine whether improved viability of hepatic allografts from fasted donors is associated with lower peripheral serum TNF levels. TNF was measured using a bioassay employing a WEHI cell line. Transplanted livers from fasted donors displayed gross deglycogenation had less bile flow postrevascularization and increased postoperative AST, but had significant improvement in viability and were associated with significantly less TNF recovered from the peripheral circulation. The association of improved viability and diminished serum TNF and previous work that links changes in postrevascularization TNF levels with changes in Kupffer cell activity suggest a possible cause for improved survival of recipients of fasted allografts.

Animals↗
PubMed1995

Inactivation of Kupffer cells after prolonged donor fasting improves viability of transplanted hepatic allografts.

Data from recent studies suggest that donor fasting imparts a beneficial effect on the viability of transplanted hepatic allografts. Because starvation may temporarily inactivate Kupffer cells, and because these cells are the likely mediators of liver injury after prolonged preservation-reperfusion, the purpose of this study is to establish a link between improved organ viability and Kupffer cell inactivation caused by donor allograft fasting. In an in vivo rat liver transplant model, 48 hours of donor fasting (1) improved allograft viability, (2) significantly decreased Kupffer cell phagocytosis, and (3) significantly decreased cytokine (tumor necrosis factor [TNF]) production postrevascularization. These data validate work from previous studies demonstrating that donor fasting improves allograft viability and furthermore support our previous research implicating activation of Kupffer cells as a causative agent of cold ischemia-preservation injury.

Animals↗