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Biomedical subjects

K Wong

Publications and source records attributed to K Wong.

252 records · Page 14Linked to original sources
PubMedDate not supplied

Phagocyte-produced free radicals: roles in cytotoxicity and inflammation.

The production of superoxide free radical, O2-, by metabolically activated phagocytes results in damage to the phagocyte which is manifested by the premature death of the cell in vitro. The cytotoxic agent appears to be formed by the reaction of superoxide with hydrogen peroxide, and is thought to be hydroxyl radical or a secondary radical thereof. In vivo two animal models of induced inflammation also appear to be largely dependent on superoxide production by phagocytes for the development of tissue damage manifested as oedema. Intravenously administered superoxide dismutase shows anti-inflammatory activity in these models, but only when so derivatized that it can remain in the circulation for longer periods of time. Catalase, or a catalase derivative, on the other hand, shows no anti-inflammatory activity in vivo.

Blood Bactericidal Activity↗
PubMedDate not supplied

Management of metastatic breast cancer.

Systemic treatment almost certainly prolongs the median survival of women with metastatic breast cancer, and it may prolong the survival of a small number of patients substantially. Even with conventional therapy, 10% or more patients may live into the second decade after recurrence. However, the disease cannot be eradicated, and the primary goal of treatment remains palliation and improvement of the quality of life. Because of the great variability in the pattern and course of the disease from one patient to another, therapy should be selected judiciously to maximize response and minimize toxicity. In some clinical situations, such as pathologic fractures and brain metastases, local therapies alone, such as surgery or irradiation, are the treatments of choice. Patients who will respond to endocrine therapy are well defined, and all patients with the characteristics of an endocrine responder deserve a chance at palliation with this modality alone because of its limited toxicity. A number of new forms of endocrine therapy with more specific targets at estrogen and progesterone receptor sites are now in clinical trials. When used appropriately, chemotherapy significantly improves patient quality of life despite its toxicity. No drug combinations, schedules, or doses have been shown to prolong survival or provide better net palliation than classic CMF (oral cyclophosphamide with intravenous methotrexate and 5-fluorouracil) or CAF (intravenous cyclophosphamide, doxorubicin, and 5-fluorouracil). Treatment with these combinations in excess of 6 to 9 months provides only marginal additional benefits and no survival advantage. The role of high dose chemotherapy with autologous bone marrow transplantation remains a promising area of investigation, but the available survival data are entirely compatible with the possibility that this modality will eventually prove inferior to conventional therapy. Many new cytotoxic agents with unique mechanisms of action are currently under investigation, including taxol, taxotere, Topotecan, and amonafide. Taxol may be the most promising therapy now available for patients whose disease has become refractory to doxorubicin. Biologic therapies using monoclonal antibodies against a specific oncogene or its product have entered clinical trials, and novel drug delivery systems using liposomes are under evaluation.

Antineoplastic Agents↗
PubMedDate not supplied

In vitro activity of second and third generation cephalosporins against ampicillin susceptible and resistant haemophilus influenzae.

One hundred seventy-five clinical isolates of Haemophilus influenzae (including 74 beta-lactamase-producing strains) were examined for susceptibility to ampicillin, cefonicid, cefamandole, cefuroxime and cefotaxime. Cefonicid and cefamandole exhibited similar activity against ampicillin-susceptible strains (MIC90 = 0.2 mg/l for both antibiotics); cefuroxime was slightly less active (MIC90 = 0.01 mg/l). However, cefonicid, cefuroxime and cefotaxime were all more active against beta-lactamase-producing H. influenzae than cefamandole (MIC90 = 1.0 mg/l for cefonicid, MIC90 = 2.0 mg/l for cefuroxime, MIC90 = 0.01 mg/l for cefotaxime, MIC90 = 5.0 mg/l for cefamandole). One hundred twenty-five of the 175 isolates were also tested for susceptibility to cefonicid and cefamandole by disc diffusion technique and a plot of zone diameter vs. MIC was analyzed for the beta-lactamase-producing strains.

Ampicillin↗
PubMedDate not supplied

Novel point mutation (W184R) in neonatal type 2 Gaucher disease.

Gaucher disease is the most prevalent inherited sphingolipidosis and results from deficient glucocerebrosidase activity. Three clinical forms of Gaucher disease have been described: type 1, or non-neuronopathic; type 2, or acute neuronopathic; and type 3, or subacute neuronopathic. We have identified a novel mutation in a patient of Russian-British descent who died of type 2 Gaucher disease a few hours after birth. A heterozygous T --> C transition mutation in exon 6, cDNA nucleotide position 667, results in the substitution of tryptophan by arginine at amino acid residue 184 (W184R) of glucocerebrosidase. This mutation creates a new cleavage site for the restriction endonuclease Hinf1. We developed a method that utilizes Hinf1 restriction endonuclease analysis to confirm the presence of the mutation and test family members. The second mutation identified in the other glucocerebrosidase allele of the patient is mutation L444P, a severe mutation frequent in type 2 and 3 Gaucher disease. Since the patient died very shortly after birth, we postulate that the W184R/L444P genotype may result in little or no detectable glucocerebrosidase activity and thus a poor prognosis.

Base Sequence↗
PubMedDate not supplied

Proteomic investigation of metabolic shift in mammalian cell culture.

Mammalian cells, under typical cultivation conditions, produce large quantities of lactate and ammonia that affect cell growth adversely and result in low cell concentration. Controlled nutrient feeding to maintain low concentrations of glucose and glutamine reduces metabolite production drastically, altering the metabolism of the cells. This metabolic shift results in higher cell concentration in continuous cultures and does not affect the specific productivity of the cells. We have taken a proteomics approach to investigate the differential protein expression with metabolic shift. Using two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS), we have found at least eight differentially expressed spots; two proteins were down-regulated, and the others were up-regulated with metabolic shift. These included metabolic enzymes, the brain form of phosphoglycerate mutase, which was down-regulated, and the precursor of the 23 kDa subunit of NADH-ubiquinone oxidoreductase, which was up-regulated. Another enzyme, the L1 isozyme of ubiquitin carboxyl-terminal hydrolase, which is involved in protein turnover and degradation, was also up-regulated in the metabolically altered cells. The remaining down-regulated spot had been identified as two isoforms of cytoplasmic actins, while three of the up-regulated spots were viral GAG polyproteins from various murine viruses. An unidentified protein was also up-regulated in the cells with altered metabolic state. This study shows the potential of using a proteomics approach in deciphering the intracellular changes in cells with physiological changes such as metabolism shift. The new insight into cell metabolism afforded by this analysis will greatly facilitate process optimization of continuous cell cultures.

Alkylation↗
PubMedDate not supplied

High-pressure liquid chromatographic quantitation of rifampin and its two major metabolites in urine and serum.

Rifampin and two of its major metabolites, 25-O-desacetylrifampin and 3-formylrifamycin SV, were quantitated in serum, urine, and aqueous solutions by high-pressure, reverse-phase liquid chromatography. This rapid, precise, and simple method utilizes a single-step extraction, dual-wavelength monitoring, and quantitation by comparison of the absorbance of the drug or metabolite with that of an internal standard; the wavelengths used are 337 nm and 254 nm. The degrees of precision are +/- 1.3% and + 4.0% for rifampin only (within run and run to run); recovery in the assay is linear, with concentrations of up to 20 micrograms/ml. Comparison of this method with the reference bioassays yielded a good correlation (r = .975). Short turnover time and small sample size make the assay ideal for the monitoring of therapeutic drug concentrations and for pharmacokinetic studies.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Tracking the use and impact of a community social report: where does the information go?

The purpose of this paper is to report on a study evaluating the extent to which a social report (entitled "Hamilton-Wentworth Profile on Children and Youth") was read and used by recipients. Subjects were divided into two groups: an Active Group which had worked on producing the Profile and/or requested copies of it once it had been released, and a Passive Group which had received copies of the Profile through a general mailing list used for other research reports. Approximately one year later, 90% of the Active Group recalled the Profile compared to 21% of the Passive Group. Similarly, 83% of Active Group respondents had read the Profile compared to 8% of Passive Group subjects. 80% of Active Group respondents and 5% of Passive Group respondents used the Profile. The results suggest that if social reports are read by local community agencies and individuals, they will be used to help improve conditions for children and youth. Social reports at the local level are more likely to be read if potential users are engaged in the process of report production and if the reports are disseminated to the appropriate target audience.

Attitude of Health Personnel↗
PubMedDate not supplied

Disposition of the flame retardant, tris(1,3-dichloro-2-propyl) phosphate, in the rat.

The metabolism, distribution, and excretion of the flame retardant, tris(1,3-dichloro-2-propyl) phosphate (TDCP), were studied in the rat. Five days after iv administration of 14C-TDCP, 92% of the administered radiolabel had been excreted in the urine (54%), feces (16%), and expired air (22% as 14CO2); 4% was recovered in the body. The major urinary, fecal, and biliary metabolite was identified as bis(1,3-dichloro-2-propyl) phosphate (BDCP). In disposition studies performed 5 days after iv administration of TDCP, 63% of the administered phosphate was recovered as BDCP. Other metabolites included the mono ester, 1,3-dichloro-2-propyl phosphate, and the bacterial mutagen, 1,3-dichloro-2-propanol. Less than 0.1% of the administered radiolabel was recovered as TDCP in the excreta. Kinetic and distribution studies demonstrated that TDCP was eliminated primarily by rapid metabolism whereas the slowly metabolized BDCP was eliminated by excretion. A major portion of the radiolabel excreted in bile underwent enterohepatic recirculation. In the presence of phenobarbital-induced liver homogenates, TDCP was mutagenic to Salmonella typhimurium (TA100), whereas its major metabolite, BDCP, and a minor metabolite, 1,3-dichloro-2-propyl phosphate, were nonmutagenic. Another metabolite, 1,3-dichloro-2-propanol, was mutagenic in the same system without liver homogenate activation.

Animals↗
PubMedDate not supplied

Thanatogen expression during involution of the rat ventral prostate after castration.

After castration the rat ventral prostate undergoes regression. This process occurs due to the induction of apoptosis, or active cell death, in the epithelial cells of the gland. Several genes, including TRPM-2, (testosterone repressed prostate message), RVP.1, fos, and myc, have been shown to be induced in the prostate during this process. We have investigated the expression of several other genes that may be associated with apoptosis, including tissue transglutaminase (TGase), poly(ADP)ribose polymerase (PARP), and heat shock protein 27 (Hsp27). Northern hybridization has been used to determine the steady-state mRNA levels of these genes in the ventral prostate after castration, and the time course of induction has been compared to the changes in the steady-state levels of prostate steroid binding protein (PSBP), alpha-tubulin, and TRPM-2 mRNAs. The results show that the mRNAs for PARP, transglutaminase, and Hsp27, in addition to TRPM-2, are induced by androgen ablation in the rat ventral prostate and reach maximum levels between days 3 and 4 after castration. Using in situ hybridization we have established that these genes are expressed in the epithelial cells of the prostate that are known to undergo active cell death; this result suggests that their gene products may be required in the dying cells to ensure that the biochemical and morphological processes of apoptosis are completed appropriately.

Androgen-Binding Protein↗
PubMedDate not supplied

The role of spermatozoa in the pathogenesis of Chlamydia trachomatis salpingitis in a primate model.

BACKGROUND AND OBJECTIVES: The role of spermatozoa in carrying microorganisms from the cervix to the fallopian tubes and promoting infection was examined in eight pig-tailed macaques. GOAL OF THIS STUDY: The aim of this study was to determine whether spermatozoa play a role in the transport of Chlamydia trachomatis into the upper reproductive tract and in the pathogenesis of chlamydial salpingitis. STUDY DESIGN: Five monkeys were inoculated with Chlamydia trachomatis in the cervix and mated, and three other monkeys were infected in the cervix but not mated. RESULTS: Culture positive results were obtained for cervical samples from all animals. After cervical inoculation, no mated animals and one unmated animal had positive culture results for samples from the fallopian tubes. After mating, no spermatozoa examined in samples taken from the upper tract or cul de sac had elementary bodies (EBs) on their surfaces, and only one sample obtained from the cervix showed C. trachomatis attached to the spermatozoa, as determined by fluorescent antibody (FA) staining. Two of the mated monkeys became pregnant; one spontaneously aborted late in gestation, and the other delivered a normal female infant. The fallopian tubes of all eight monkeys were challenged directly with serovar D and examined for evidence of salpingitis. Repeat laparoscopy was performed to monitor the inflammatory response. Tubal specimens for isolation and polymerase chain reaction (PCR) were obtained. Hysterectomies were performed between 3 and 4 weeks after tubal inoculation. Histopathologic examination of the fallopian tubes revealed widespread inflammation consisting of focal collections of lymphocytes and plasma cells in the submucosa. Peritubal adhesions were observed in four of five mated monkeys and in two of three unmated monkeys. CONCLUSION: This study failed to confirm that spermatozoa play a role in the pathogenesis of C. trachomatis infection.

Animals↗
PubMedDate not supplied

Immediate implantation of endosseous dental implants in the posterior maxilla and anatomic advantages for this region: a case report.

A procedure is presented whereby treatment planning for the long-term restoration of imminent loss of well-rooted posterior maxillary teeth by immediate endosseous dental implant placement may aid the patient in avoiding major surgical reconstruction. The clinical case report presented illustrates the advantages of an immediate dental implant placement technique that is especially relevant and unique to the posterior maxilla. Anatomic advantages are discussed.

Adult↗