Search PubMed⌕ Search

Biomedical subjects

C Wong

Publications and source records attributed to C Wong.

At least 343 records · Page 19Linked to original sources

Preparation and in vitro antifungal activities of some quinolizidine derived hemiaminals and beta-tert-amino sulfides.

New alpha-thiohemiaminals, 7alpha-phenylthio-7-epideoxynupharidin-6-ol, the diasteriomeric 7beta-phenylthiodeoxy-nupharidin-6-ol, and 3-methyl-3-methylthio-4-hydroxyquinolizidine, were prepared and reduced to the corresponding beta-tert-amino sulfides. The configuration at C-7 of the beta-tert-amino sulfides was determined by observing the direction of the solvent-induced shift of the C-7 methyl proton resonance. The configuration at C-7 of the new alpha-thiohemiaminals was established by correlations with the beta-tert-amino sulfides and confirmed, in the case of the deoxynupharidine derivatives, by circular dichroism and ascertaining the sterochemistry of deuteride incorporation upon sodium borodeuteride reduction of the alpha-thiohemiaminal. The in vitro antifungal activities of six compounds possessing the quinolizidine skeleton, including all the newly synthesized compounds as well as some previously reported ones, and amphotericin B were tested against several human pathogenic fungi. Besides amphotericin B, only the two deoxynupharidine alpha-thiohemiaminals were active, especially against Histoplasma capsulatum and Blastomyces dermatitidis. The observations indicate activity is derived from the 3-furyl group and the functionality from which alpha-thioimmonium ions can be produced.

Antifungal Agents↗

Effects of the diethyl and dimethyl esters of glutamic acid on morphine anti-nociception in the rat.

The effects of pretreatments with various doses of glutamic acid diethyl or dimethyl esters on morphine-induced anti-nociception in the hot-plate and tail-flick tests on rats were examined. While neither substance alone altered control reaction times, they both antagonized the effects of morphine, suggesting the possible involvement of glutamate receptors in narcotic "analgesia". However, several aspects of the data inveigh against the significance of the findings with regard to narcotic mechanisms.

Analgesics↗

Pressure-flow curves in infancy.

Calibrated pressure-flow (P-V) curves were plotted by computer using data from both the plethysmographic method for measuring airway resistance and the esophageal balloon technique for measuring lung resistance. P-V curves from 100 sick, healthy, and convalescent infants (age range 2 days to 19 months, weight range 0.9-10.4 kg) were classified into five distinctive types according to shape and direction of looping. Two of these patterns, one with a virtually closed, the other with a narrow figure-of-eight loop, reflected the normal physiologic changes in airway caliber that may occur during tidal breathing. The remaining three patterns, with far more marked changes in resistance, were associated with particular pathophysiologic mechanisms of airway obstruction. A wide figure-of-eight configuration, in which the expiratory loop rotated clockwise with marked flow limitation toward end expiration, was found for infants with chronic lung disease. By contrast, a rise in initial expiratory resistance due to dynamic glottic narrowing, with an anticlockwise rotated expiratory P-V loop, occurred in infants with reduced or unstable lung volumes. A clockwise inspiratory loop was observed only for infants intubated during the neonatal period, many of whom had clinical evidence of extrathoracic airway obstruction. Inspection and analysis of P-V curves provides more information about the state of the airways than does a single numerical expression of resistance. However, since normal patterns of P-V curves are not restricted to infants with healthy airways, a combined qualitative and quantitative approach to these measurements is recommended.

Airway Resistance↗

Possible prebiotic significance of polyamines in the condensation, protection, encapsulation, and biological properties of DNA.

Some properties of DNA condensed with spermidine have been compared with the properties of DNA condensed with Co3+(NH3)6 to determine whether condensation of DNA with these trivalent cations protects DNA against the action of DNase I and increases transcription and encapsulation of DNA into liposomes. It was shown that DNA condensed with Co3+(NH3)6 was resistant to the action of the endonuclease DNase I such as DNA condensed with spermidine was. However, DNA condensed with Co3+(NH3)6 was significantly less active in transcription with the E. coli RNA polymerase than DNA-spermidine condensed forms. In addition, it was demonstrated that both compacted forms of DNA were more efficiently encapsulated into neutral liposomes; however, negatively, charged liposomes were scarcely formed in the presence of DNA condensed with Co3+(NH3)6. These experiments and the well documented properties of polyamines increasing the resistance to radiations and hydrolysis of nucleic acids, as well as their biological activities, such as replication, transcription, and translation, together with the low concentration of Co3+ in the environment, lead us to propose spermidine as a plausible prebiotic DNA condensing agent rather than Co3+ and the basic proteins proposed by other authors. Then, we consider the possible role and relevance of the polyamine-nucleic acids complexes in the evolution of life.

Animals↗

NMR studies in the relapsing experimental allergic encephalomyelitis (EAE) model of multiple sclerosis in the strain 13 guinea pig.

Juvenile strain 13 guinea pigs sensitized with an emulsion of whole isologous central nervous system (CNS) tissue in complete Freund's adjuvant in the first two weeks of life develop a relapsing-remitting form of experimental allergic encephalomyelitis (EAE) which resembles multiple sclerosis (MS) both clinically and pathologically. In order to determine if this experimental model could be used to identify the tissue factors which contribute to the magnetic resonance imaging (MRI)-detected lesions in MS, we measured T1 and T2 relaxation times, tissue specific gravity and histology throughout the entire CNS in vitro in eighteen animals during the acute phase (first attack), and twenty-one animals during further periods of clinical worsening (relapses) and recovery (remissions). The neuropathological findings of spinal cord meningeal inflammation, perivascular and parenchymal infiltration (myelitis and encephalitis) and demyelination were more marked during periods of clinical worsening than when the animal had recovered clinically. Even though the histological changes of EAE were present in all experimental animals, NMR relaxation times and tissue specific gravity could not distinguish experimental (first attack, subsequent relapses and remissions) from control animals due to a wide range of values for each of these parameters. Although relapsing EAE in the strain 13 guinea pig has been an instructive model of MS, we have found that in vitro NMR relaxometry cannot be used to predict the presence or degree of pathological change in the nervous system of these experimental animals.

Animals↗

Determination of non-bilayer phospholipid arrangements and their antibodies in placentae and sera of patients with hypertensive disorders of pregnancy.

Studies suggest that preeclampsia (PE) originates in the placenta and is associated with deficient trophoblast invasion of spiral arteries. The direct cause remains unknown, but preeclampsia is often associated with circulating factors that can induce generalized endothelial dysfunction. Antiphospholipid antibodies (APA) in circulation are also associated with vascular diseases. Although the quantification of APA is not currently used as a prognostic of the risk of PE, studies suggest that thrombophilias play a role in PE pathogenesis. In fact, the pathology of placentae from PE and Antiphospholipid syndrome patients is similar; atherosis, thrombosis and infarction, and endothelium activation represent the pathological mechanisms. We identified a new antibody which recognizes non-bilayer phospholipid arrangements (NPA) in membrane models and in cell membranes in vivo, and which triggered an autoimmune-like disease in mice. We evaluated the presence of NPA in the placentae and in sera, and whether NPA induced NPA antibodies in patients with hypertensive disorders of pregnancy (HDP). Results showed increased levels of NPA in the syncytiotrophoblast, extravillous cytotrophoblast, syncytial knots and the amnion epithelial cell membranes of the placenta, as well as increases in NPA and NPA antibodies in sera from HDP patients, when compared with controls. This suggests that NPA derived from placenta could be one of multiple factors associated with pregnancy pathologies.

Antibodies, Antiphospholipid↗

Distinct processing of endogenous and overexpressed recombinant presenilin 1.

The presenilin 1 (PS1) gene has been identified by positional cloning. More than 30 mutations were detected in this gene which cosegregate with Alzheimer's disease (AD). Understanding their role in disease pathogenesis requires a characterization of the PS1 protein. We have generated a set of antibodies against the three major hydrophilic domains of the deduced amino acid sequence. Analyzing cultured cells and brain samples, we identified the endogenous PS1 polypeptide as well as amino- and carboxy-terminal fragments. These metabolites were much more abundant than the full-length molecule, indicating substantial processing. Overexpression of human PS1 markedly increased the full-length polypeptide but hardly altered the amount of the metabolites. Instead, additional proteolytic fragments appeared suggesting a different metabolism of the excess PS1, which may impede studies in transfected cells. Our results indicate a tight regulation of the endogenous PS1 metabolites. PS1 and its fragments are shown to be integral membrane proteins of the endoplasmic reticulum. The mechanisms regulating the generation of the metabolites, their potential function, and role in AD remain to be studied.

Blotting, Western↗

Characterization of beta-thalassaemia mutations using direct genomic sequencing of amplified single copy DNA.

Direct sequencing of specific regions of genomic DNA became feasible with the invention of the polymerase chain reaction (PCR) which permits amplification of specific regions of DNA. Recently, human mitochondrial DNA was amplified and directly sequenced. Using a thermostable DNA polymerase of T. aquaticus (Saiki, R.K. et al., manuscript in preparation) in the PCR, we have applied a combination of PCR and direct sequence analysis of the amplified product to a human single-copy gene. We studied the genomic DNA of five patients with beta-thalassaemia whose mutant alleles were uncharacterized, and found two previously undescribed mutations, along with three known alleles. One new allele is a frameshift at codons 106-107 and the other is an A-C transversion at the cap site (+1) of the beta-globin gene. This latter is the first natural mutation observed at the cap site and it occurs in a gene which is poorly expressed.

Base Sequence↗

Endotoxin is not an essential mediator in toxic shock syndrome.

The hypothesis that toxic shock syndrome toxin 1 (TSST-1) exerts its deleterious effects in toxic shock syndrome (TSS) primarily by enhancing the lethality of small amounts of endogenous endotoxin derived from mucosal colonization with gram-negative bacteria was assessed by evaluating two means of inactivating endotoxin in rabbit models of TSS. In both of these models, toxins and TSST-1 are allowed to diffuse constantly from a subcutaneous depot. Immunologic inactivation of endotoxin with antiserum to the core lipopolysaccharide did not change the clinical course or mortality among animals infected with live TSS-associated staphylococci or among animals with a subcutaneous depot of TSST-1. Anti-TSST-1 was successful in preventing disease and death in these models. Pharmacologic inactivation of endotoxin by pretreatment or continuous treatment with polymyxin B did not prevent illness or mortality in the toxin depot model. Endotoxin thus appears not to be an essential mediator in TSS, since TSS-like illness develops and progresses despite inactivation of endotoxin in animal model systems that are faithful both physiologically and clinically to TSS in humans.

Animals↗

Pentoxifylline preloading reduces endothelial injury and permeability in cardiopulmonary bypass.

Pentoxifylline (PTX), a methyl xanthine derivative, reduces endothelial permeability. A double blind, prospective, randomized, placebo controlled, parallel study was undertaken to assess the effect of PTX on leukotriene B4, complement fragment C3a, interleukin 6 (IL6), endothelial injury as measured by von Willebrand factor (vWf), and endothelial permeability as measured by urinary albumin excretion (expressed as excreted urinary albumin to creatinine ratio [ACR]) in patients undergoing cardiopulmonary bypass (CPB) for elective coronary artery bypass grafting. Twenty patients were recruited into each treatment arm and given either PTX 400 mg or placebo three times daily for 1 week before surgery. Patients were well matched. All operations were performed using one anesthetic, CPB, and a myocardial protection technique. Blood and urine samples were taken after anesthetic induction (baseline); 20 min after the start of CPB; 5 min after removal of the cross clamp; and 5 min and 2, 6, and 24 hr after the end of CPB. Pentoxifylline did not reduce IL6, C3a, and LTB4 release but reduced Factor VIIIRAg and urinary albumin excretion preoperatively (PTX vs placebo, ACR 1q.0 vs 2.1 mg/mmol, vWf 0.8 vs 1.3 IU/ml, p < 0.05) and peak levels (PTX vs placebo, ACR 8.9 vs 16.2, vWf 1.2 vs 2.2, p < 0.05) after CPB. These results suggest that PTX may attenuate the endothelial injury and permeability seen in CPB.

Albuminuria↗

Glucose metabolic changes in nontumoral brain tissue of patients with brain tumor following radiotherapy: a preliminary study.

PURPOSE: Our goal was to measure the effect of radiotherapy on the brain glucose metabolism of tumoral and nontumoral tissue of patients with brain malignancies. METHOD: Fifteen patients with primary or metastatic brain tumors were studied with 2-deoxy-2-[18F]fluoro-D-glucose and PET prior to radiotherapy, and nine of them were rescanned 1 week after completing radiotherapy. RESULTS: Brain metabolism in patients (all brain regions except for tumoral and edematous tissue) was lower than that of matched controls (34.0 +/- 8.3 vs. 46.5 +/- 6.4 mumol/100 g/min; p < or = 0.0001). Five of the nine patients retested after radiotherapy showed decrements in tumor metabolism (47 +/- 10%; p < or = 0.05) and increases in brain metabolism (10 +/- 4%; p < or = 0.004), and the other four showed no changes in tumor or in brain metabolism. Radiotherapy-induced changes in tumor metabolism were negatively correlated with changes in brain metabolism (r = 0.85, p < or = 0.004), but not with changes in tumor volume (assessed with MR images). CONCLUSION: The study indicates that radiotherapy-induced increases in metabolism of nontumoral tissue are secondary to decreased tumor metabolic activity and not just due to volume reduction.

Adult↗

A comparison of diagnostic tests to determine Helicobacter pylori infection.

Twenty-five Helicobacter pylori positive and 25 H. pylori negative subjects as defined by culture and phase contrast microscopy of antral biopsy specimens obtained from routine upper endoscopy were studied. Antral biopsies were examined by rapid urease test, phase contrast microscopy, culture and histology. Venous blood was tested for H. pylori specific IgG antibodies by an ELISA technique. Within 7 days of endoscopy the patients also had a [14C]-urea breath test. The sensitivity and specificity of the rapid urease test was 92%, the breath test 96% and 100%, histopathology 96% and 91% and serology 96% and 88%, respectively. The [14C]-urea breath test performed over 1 h with sampling of subjects at 0, 0.5 and 1 h was an accurate and reliable method. Results expressed as counts per minute of the expired 14CO2 proved to be a simple method of assessing H. pylori status. A significant correlation between severity of histological antral gastritis and the amount of 14CO2 expired was observed. This study has shown that the non-invasive 14C-urea breath test and serology are highly sensitive and specific for the diagnosis of H. pylori infection.

Breath Tests↗

A review of liver transplantation for the dentist and guidelines for dental management.

The number of recipients of liver transplants has grown rapidly in the last few years and is likely to continue to do so in the future. The dentist should be prepared to see individuals who are contemplating or have had liver transplants. The major goal of dental intervention, before and after liver transplantation, is the prevention of bacteremia from an oral source that could lead to systemic infection. In addition, pre-transplant medical conditions of concern to the dentist include poor drug metabolism, bleeding disorders, poor wound healing, and an inability to metabolize swallowed blood. Post-transplant dental treatment must take into consideration immunosuppressive drugs and the potential for infections. Dental treatment should include a thorough dental examination, elimination of dental problems that could cause medical problems, and an intensive preventive dentistry program to minimize the occurrence of dental disease.

Anti-Bacterial Agents↗