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Biomedical subjects

C Wong

Publications and source records attributed to C Wong.

At least 217 records · Page 12Linked to original sources
PubMed1993

Phosphohistidine and phospholysine phosphatase activities in the rat: potential protein-lysine and protein-histidine phosphatases?

We have detected phosphohistidine and phospholysine phosphatase activities in rat tissue extracts using partially phosphorylated, high-molecular-mass (> 10 kDa) polymers of histidine and lysine as substrates. Multiple phosphohistidine- and phospholysine-specific phosphatases were present in these extracts based on observed differences in heat stability, sensitivity to bivalent metal ions and thiol modifying reagents, and/or elution from DE-52 cellulose. The properties of these phosphohistidine and phospholysine phosphatases were distinct from those of the phosphomonoester-specific protein phosphatases or the N-P phosphohydrolases that act on the free phosphoamino acids phosphoarginine, 3-phosphohistidine or phospholysine.

Animals↗
PubMed1993

Sites of iodination in recombinant human brain-derived neurotrophic factor and its effect on neurotrophic activity.

Recombinant human brain-derived neurotrophic factor (BDNF) is now under extensive investigation because of its potential clinical applications. Radioactively labeled proteins are usually required to study receptor binding and pharmacokinetic properties of proteins. This study was undertaken to see if iodination affects the biological and conformational properties of a recombinant BDNF. BDNF was iodinated using a stoichiometric amount of nonradioactive cold NaI to minimize multiple iodinations. Of the four tyrosines present in BDNF--Tyr-52, Tyr-54, Tyr-63, and Tyr-86--only Tyr-63 and Tyr-86 were iodinated under the experimental conditions used. Iodination of Tyr-63 resulted in modification without alteration of the biological activity, whereas iodination of Tyr-86 resulted in a molecule with highly compromised biological activity. Similar inactivation was observed if both Tyr-63 and Tyr-86 were iodinated. These modified proteins exhibited conformation and dimerization apparently identical to those of the native protein, as demonstrated by analytical ultracentrifugation, gel filtration, light scattering, and circular dichroism. From these results, we concluded that Tyr-52 and Tyr-54 are not accessible to the reagent and are probably buried in the hydrophobic core, whereas Tyr-63 and Tyr-86 are exposed on the surface of the molecule; of the two exposed residues, only Tyr-86 contributes to the biological activity.

Amino Acid Sequence↗
PubMed1993

On the guidance of regenerating axons from a half-retina in the adult goldfish.

We have examined the guidance of regenerating optic axons from half-retinal fragments in the goldfish. Axons regenerating from a dorsal, ventral, or nasal half-retina showed no bias to grow through the retinotopically appropriate parts of the optic tract. By contrast, axons from a temporal half-retina did show a bias, albeit a small one, to grow through the correct part of the tract. In addition, we found evidence that axons from the temporal quadrant of dorsal or ventral half-retinas showed a similar bias. In the optic tectum, axons regenerating from a dorsal, ventral, or temporal half-retina showed strong biases to invade the retinotopically appropriate portion of the synaptic field. Of these three, temporal axons showed the sharpest restriction in their field of innervation. Nasal fibers were unique in that they invaded the entire tectum with little evidence of a preference for their appropriate field. Our results indicate that there is minimal guidance offered to regenerating optic axons in the optic tract. However, once dorsal, ventral, or temporal axons reach the tectum they appear to encounter strong organizing forces which constrain them to preferentially invade their retinotopically appropriate areas. Nasal axons appear to be exempt from these forces. In both the optic tract and tectum, axons from a temporal half-retina are the most effectively guided and constrained.

Animals↗
PubMed1993

Mutation of human short tandem repeats.

A total of 20,000 parent-offspring transfers of alleles were examined through the genotyping within 40 CEPH reference families of 28 short tandem repeat polymorphisms (STRPs) located on chromosome 19. Forty-seven initial mutation events were detected in the STRPs using DNA from transformed lymphoblastoid cell lines, but less than half (39%) could be verified using DNA from untransformed cells. None of the cases where three alleles were observed in a single individual could be verified using DNA from untransformed cells. The average mutation rate for the chromosome 19 STRPs after correction for events which would not be detectable as Mendelian errors was 1.2 x 10(-3) per locus per gamete per generation. This rate may have been inflated by somatic as opposed to germline events. Observed mutation rates for individual STRPs ranged from 0 to 8 x 10(-3). The average mutation rate for tetranucleotide STRPs was nearly four times higher than the average rate for dinucleotide STRPs. For determination of the mode of mutation, events involving STRPs on other chromosomes were also examined. Of the events which were verified using DNA from untransformed lymphocytes or which were likely among those for which DNA from untransformed cells was not available: none were located at the sites of meiotic recombination, 91% involved the gain or loss of a single repeat unit, and 15 occurred in the male germline compared to 4 in the female germline (p = 0.01).

Base Sequence↗
PubMed1993

The frequency of red cell transfusion for anemia in patients receiving chemotherapy. A retrospective cohort study.

The objective of this retrospective cohort study was to determine the frequency of red cell transfusion for anemia and risk factors. It was conducted at a regional cancer center and host hospital. All patients receiving chemotherapy in 1989 were studied. Complete data were available on 381; 26 were excluded. Age, diagnosis, baseline and nadir hemoglobin, transfusion history, chemotherapy regimen, and prior treatment were abstracted from the cancer center chart and hospital medical records. Transfusion for anemia was required in 18% of all patients with solid tumors; those with lung cancer had the highest rate (34%). Patients with anemia who entered chemotherapy were more likely to be transfused. Therefore, patients with leukemia, lung cancer, and/or prior anemia have higher transfusion rates and may benefit from such therapies as recombinant human erythropoietin.

Anemia↗
PubMed1993

Disease-specific questionnaire for patients with a renal transplant.

A disease-specific questionnaire to assess the quality of life of renal transplant recipients was developed. A list of items of potential relevance to these patients was created and 50 transplant recipients rated the importance of each item. A combination of factor analysis and clinical judgment was then used to create the final questionnaire which consists of 25 questions in 5 dimensions (physical symptoms, fatigue, uncertainty/fear, appearance and emotions). The physical symptoms dimension is patient specific. All questions are scored on a 7-point Likert scale. The reproducibility of the questionnaire when it was administered to stable transplant recipients was high (intraclass correlation coefficients between 0.82 and 0.91 for the 5 dimensions). The scores of all dimensions except appearance improved 6 months after transplantation, when compared to pretransplantation scores. Patients who had a well-functioning graft (creatinine < 250 mmol/l) had higher scores than those with poorly functioning grafts. This questionnaire is easy to administer and is valid, reproducible in stable patients and responsive to change.

Adult↗
PubMed1993

The effect of elective total hip replacement on health-related quality of life.

The effect of total hip replacement on the health-related quality of life of patients who have osteoarthrosis was examined as part of a randomized, controlled trial comparing femoral head prostheses that were inserted with or without cement. One hundred and eighty-eight patients were followed for three months: 179 of them, for six months; 156, for one year; and ninety, for two years. The health-related quality of life was assessed with use of the Harris hip score, the Merle d'Aubigné hip score, the Sickness Impact Profile, the Western Ontario and McMaster University (WOMAC) Osteoarthritis Index, the McMaster--Toronto Arthritis (MACTAR) Patient Preference Disability Questionnaire, and the time trade-off technique as a measure of utility. Patients also took the six-minute-walk test. The mean age of the patients in the study was sixty-four years (range, forty to seventy-five years); ninety-seven patients (53 per cent) were men and ninety-four (50 per cent) had a prosthesis inserted with cement. Only three of 188 patients refused to return for quality-of-life assessments. There was significant improvement in all health-related quality-of-life measures and in the six-minute-walk test after the operation (p < 0.01 for all items, except for the work dimension of the Sickness Impact Profile at three months [p = 0.07]). Most of the improvement had occurred by three months postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Coagulopathy presenting as calf pain in a racquetball player.

Most cases of lower leg pain in athletes result from musculoskeletal injury. Occasionally these patients do not respond to treatment in a timely fashion. This should alert the clinician to rethink the original diagnosis and consider more unusual causes of leg pain. Deep venous thrombosis must be considered in a young athletic person experiencing unexplained persistent calf pain after exercise. Further investigation may be necessary to rule out a hereditary or acquired hypercoagulable state.

Adult↗
PubMed1992

A role for the acidic trimer repeat region of transcription factor sigma 54 in setting the rate and temperature dependence of promoter melting in vivo.

sigma 54 is an atypical sigma factor involved in enhancer-dependent transcription in Escherichia coli. In vivo assays were developed for following the kinetics and thermodynamics of sigma 54-dependent melting of the glnAP2 promoter start site. These assays were applied to a series of three sigma 54 polymerases containing zero, one, and two copies of the highly acidic trimer repeat region. The results showed that at least one copy of this acid region is required for a complete melting transition at physiological temperature, but is not required for a low temperature melting transition. The rate of melting the promoter in vivo increased with number of copies of this region. Taken together with other observations, the experiments point to a role for the acid region in triggering conformational changes that lead to specific promoter melting. The acid region is required for these changes to occur fully at physiological temperature and influences the rate at which they occur.

Amino Acid Sequence↗
PubMed1992

Phosphorylation of the C-terminal domain of the Na+/H+ exchanger by Ca2+/calmodulin-dependent protein kinase II.

The Na+/H+ exchanger is a pH-regulatory protein that extrudes one H+ ion in exchange for one Na+ ion when intracellular pH declines. A number of studies have shown phorbol ester stimulation of activity in intact cells, leading to the idea that the exchanger is regulated by protein kinase C-mediated phosphorylation in vivo. cDNA encoding the protein has been cloned, and a recent model suggests a large internal cytoplasmic C-terminal domain that may be a site of regulation of the exchanger [Sardet, Franchi & Pouyssegur (1989) Cell 56, 271-280]. We examined this region of the protein using a rabbit cardiac Na+/H+ exchanger cDNA clone. cDNA of the Na+/H+ exchanger, coding for the C-terminal 178 amino acid residues, was cloned into the expression vector pEX-1 and expressed as a fusion protein with beta-galactosidase. The fusion protein reacted with an antibody produced against a synthetic peptide of the C-terminal 13 amino acid residues of the Na+/H+ exchanger, confirming the identity of the expressed protein. Control and experimental pEX-1-Na+/H+ exchanger protein was purified on a p-aminophenyl beta-D-thiogalactopyranoside-agarose column. Purified Ca2+/calmodulin-dependent protein kinase II readily phosphorylated the Na+/H+ exchanger protein in a Ca(2+)- and calmodulin-dependent manner in vitro, but this region of the protein was not a substrate for purified protein kinase C or for the catalytic subunit of cyclic AMP-dependent protein kinase. Control-expressed beta-galactosidase was phosphorylated to a maximal level of 0.77 +/- 0.17 mol of Pi/mol (mean +/- S.E.M., n = 6) whereas the fusion protein was phosphorylated to a maximal level of 4.09 +/- 0.39 mol of Pi/mol (n = 6), suggesting one site of phosphorylation in beta-galactosidase and three in the C-terminal domain of the Na+/H+ exchanger. Examination of the deduced amino acid sequence of this part of the exchanger reveals three consensus sequences for Ca2+/calmodulin-dependent protein kinase II. These results suggest that the exchanger may be directly regulated in vivo by calmodulin-dependent protein kinase II but not by protein kinase C or cyclic AMP-dependent protein kinase.

Amino Acid Sequence↗
PubMed1992

Hospitalization in an urban homeless population: the Honolulu Urban Homeless Project.

OBJECTIVE: To determine the rate and estimate the cost of hospitalization in a defined urban homeless population. DESIGN: Retrospective chart review. SETTING: Kalihi-Palama Health Clinic Health Care for the Homeless Project, Hawaii State Hospital and seven acute care hospitals in Honolulu, Hawaii. PATIENTS: A total of 1751 homeless clients contacted between 1 December 1988 and 30 November 1990. MEASUREMENTS AND MAIN RESULTS: A total of 1751 individuals were studied for an aggregate of 871.3 person-years. Five hundred sixty-four hospitalizations were identified: ninety-two to the state psychiatric hospital and 472 to acute care hospitals. The age- and sex-adjusted hospitalization rate for acute care hospitals was 542/1000 person-years (compared with the state rate of 96/1000 person-years). Homeless persons were admitted to acute care hospitals for 4766 days compared with a predicted 640 days. The age- and sex-adjusted rate of admission to the state psychiatric hospital was 105/1000 person-years (compared with the state rate of 0.8/1000 person-years). Homeless persons were admitted to the state psychiatric hospital for 3837 days compared with a predicted 139 days. CONCLUSIONS: Homeless individuals in this study were hospitalized in acute care and psychiatric hospitals far more frequently than were members of the general population.

Adult↗
PubMed1992

Differential effects of the simian virus 40 early genes on mammary epithelial cell growth, morphology, and gene expression.

To study the effect of SV40 T-antigen in mammary epithelial cells, a rat beta-casein promoter-driven SV40 early-region construct was stably introduced into the clonal mouse mammary epithelial cell line HC11. With the expression of the viral T-antigens under the control of a hormone-inducible promoter, it was possible to dissociate the effects of different levels of T-antigen expression on cell growth, morphology, and gene expression. Following hormonal induction, a rapid but transient induction of T-antigen was observed, followed by a delayed induction of H4 histone mRNA. In T-antigen-positive HC11 cells cultured in the absence of EGF, the expression of basal levels of T-antigen (in the absence of hormonal induction) led to a decreased doubling time and an increased cell density. In the presence of EGF, T-antigen expression resulted additionally in an altered cell morphology. Despite the effects of T-antigen on cell growth and gene expression, the cells were unable to form colonies in soft agar and were nontumorigenic when transplanted into cleared mammary fat pads. They were, however, weakly tumorigenic in nude mice. Relatively high levels of p53 protein synthesis were observed in both the transfected HC11 cells and the parental COMMA-D cells, as compared to 3T3E fibroblasts and another mammary epithelial cell line. The HC11 and COMMA-D cells synthesized approximately equal levels of wild-type and mutated p53 proteins as defined by their reactivities with monoclonal antibodies PAb246 and PAb240, respectively. Interactions between excess p53 and T-antigen may, in part, explain the failure of these cells to display a completely transformed phenotype.

Adenovirus Early Proteins↗
PubMed1992

Runners' diarrhea. Different patterns and associated factors.

One hundred and nine distance runners participated in a questionnaire survey of bowel function related to running. Thirteen (12%) had had fecal incontinence while running. Sixty-eight (62%) had stopped to have a bowel movement while training. Forty-seven (43%) had "nervous" diarrhea before competition and 13 (12%) had stopped during competition for a bowel movement. Fifty-one (47%) had experienced diarrhea after racing or hard runs and 17 (16%) had seen blood in their stool in the same situations. Runners who had nervous diarrhea before competition were more likely to have symptoms of milk intolerance and irregular bowel function when not exercising, and runners who had symptoms of the irritable bowel syndrome often had to stop for a bowel movement during training. Runners with diarrhea after racing or hard runs frequently experienced severe abdominal cramps, nausea and vomiting, and occasionally, rectal bleeding at the same time. Any form of "runners' diarrhea" was unrelated to age, previous intestinal infection or food poisoning, food allergies, or dietary fiber.

Adult↗
PubMed1992

Renal allograft scintigraphy with Tc-99M-DTPA--its role during cyclosporine therapy.

There are no accurate noninvasive methods to distinguish renal allograft dysfunction due to rejection or cyclosporine nephrotoxicity. We have studied the value of Tc-99M-DTPA renal scanning in 90 episodes of renal allograft dysfunction occurring in 44 patients subjected to 57 renal biopsies in whom a clear diagnosis could be established. Renal scintigrams were assessed qualitatively and quantitatively by a blinded observer. Rejection was diagnosed when deterioration in perfusion occurred in the presence of maintained or declining radionuclide excretion. The diagnosis of cyclosporine nephrotoxicity was made by exclusion. The final diagnosis was based on the clinical response to therapy and/or the findings on renal biopsy. The scintigraphic diagnosis of rejection had a specificity of 87.9% and significantly contributed to the exclusion of cyclosporine nephrotoxicity (negative predictive value of 90.6%). Furthermore, a scintigraphic diagnosis compatible with cyclosporine nephrotoxicity, in the presence of a drug level above the therapeutic range, indicated a 90.4% probability of true nephrotoxicity. We conclude that, even in cyclosporine-treated renal transplant patients, Tc-99M-DTPA scintigraphy is of clinical value and can be incorporated into an effective diagnostic algorithm for allograft dysfunction.

Cyclosporine↗
PubMed1992

Pheophorbide a-induced photo-oxidation of cytochrome c: implication for photodynamic therapy.

Pheophorbide a-induced photo-oxidation, in vitro, of cytochrome c oxidase and cytochrome c results in irreversible modifications to both protein components. Photo-oxidation of cytochrome c, as exhibited by change in its heme oxidation state, displays exponential kinetics and is detected with a lag period. Both the photo-induced inactivation of the enzyme, and destruction of the substrate ability of cytochrome c occur as complex multi-process events. Under similar experimental conditions, the loss of the substrate capability of cytochrome c develops approximately three times faster than inactivation of the enzyme. The slight lag in the photo-oxidation of cytochrome c is due to pheophorbide a-induced superoxide production. However, the relative amount of photo-oxidant produced is considerably more effective than the cytochrome c reducing capacity of the superoxide. Neither hydroxyl radical nor hydrogen peroxide are involved in the photo-oxidation of the heme function. The possibilities of heme oxidation by a singlet oxygen mediated pathway or direct electron abstraction involving the heme or apoprotein are not excluded. It is proposed that a multi-site oxidation of numerous reduced energy cofactors within cells may augment collateral enzyme inactivation in maximizing photosensitizer-induced cytotoxicity. Accordingly, amphipathic photosensitizers, capable of accessing both lipid and aqueous compartments containing reduced cofactors, may be more effective agents for photodynamic therapy than those which exhibit a high specificity of subcellular localization.

Chlorophyll↗