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Biomedical subjects

J C Pang

Publications and source records attributed to J C Pang.

31 records · Page 2Linked to original sources

Effects of TGFbeta2 on collagen synthesis in cultured normal and wounded fetal mouse palates.

OBJECTIVE: It has been demonstrated in a number of models that fetal wounds heal with little or no scar. Since collagen is an integral part of the extracellular matrix in adult scar formation, we studied the synthesis and localization of collagen in an in vitro mouse palate model for fetal wound healing. METHODS: Palates, dissected from fetal mice at 15, 16, and 17 days of gestation and from newborn mice, were cultured in medium containing serum (for 8 hours); this was followed by culture in serum-free medium (for 12 hours). One-half of the samples from each age group were wounded in the midline. All samples were placed in serum-free medium containing 20 microCi/mL 3H-proline for 8 hours. In addition, palates from 15-day gestation and from newborn mice were also incubated with transforming growth factor TGF-beta2 (10 ng/mL). Palates were washed with saline, homogenized, and radioactivity was counted. Proline uptake was calculated for each sample as counts per milligram of protein and was subjected to statistical analysis (three-way analysis of variance). Samples of the homogenate were subjected to sodium dodecyl sulfate-gel electrophoresis and Western blotting in order to determine the types of collagen that were synthesized. Immunohistochemical localization of collagen types I, III, and VI was carried out on paraffin-embedded samples from each group. RESULTS: There were no significant differences in proline uptake between wounded mouse palates and nonwounded mouse palates at any age, and there was no histological evidence of regeneration of the palate at the site of the wound. Proline uptake was significantly greater in untreated wounded palates at 15 days' gestation than it was in newborns. After treatment with TGF-beta2, proline uptake was significantly greater in both wounded and nonwounded palates in the newborn group and had no effect on collagen synthesis in palates from 15-day gestation animals. Collagen types I and III were localized in histological specimens using immunohistochemistry and on nitrocellulose using Western blotting. No type VI collagen was demonstrated by Western blotting, but it was localized around blood vessels and on basement membranes using immunohistochemistry. CONCLUSION: Treatment with TGF-beta2 significantly increased collagen synthesis, as assessed by 3H-proline uptake, in cultured palates from newborn mice as compared with palates from untreated newborn mice and from both treated and untreated palates of 15-day gestation mice. These data suggest a differential response to TGF-beta2 by mouse palates as a function of fetal development.

Analysis of Variance↗

Antisense epidermal growth factor receptor RNA transfection in human malignant glioma cells leads to inhibition of proliferation and induction of differentiation.

The epidermal growth factor receptor (EGFR) is a protooncogene that is frequently observed with alterations in late stage gliomas, suggesting an important role of this gene in glial tumorigenesis and progression. In this study we evaluated an antisense EGFR approach as an alternative therapeutic modality for glioblastomas. We transfected U-87MG cells with an antisense EGFR construct and obtained several clones stably expressing lower or undetectable levels of EGFR protein. These clones were found to have impaired proliferation as well as a reduced transforming potential to grow in soft agarose. The number of cells positive for the cell cycle-specific nuclear antigen Ki-67 was also significantly decreased (P < 0.05) in antisense EGFR-transfected clones compared with parental or empty vector-transfected cells. Flow cytometric analysis revealed that the proportion of cells in G0/G1 phases of the cell cycle in the antisense clones increased by up to 31% compared with control cells, whereas the proportion of cells in S phase decreased by up to 58%. In addition, the antisense EGFR-transfected cells showed higher expression of glial fibrillary acidic protein and a more differentiated form, with smaller cell bodies possessing fine tapering cell processes. These results suggest that EGFR plays a major role in modulating cell growth and differentiation in glioblastoma cells. Our experimental model of antisense EGFR provides a basis for future development of antisense EGFR oligodeoxynucleotides in treatment of glioblastomas.

Antibodies, Monoclonal↗

Marmoset (Callithrix jacchus jacchus) spatial memory in a foraging task: win-stay versus win-shift strategies.

The spatial memory of common marmosets (Callithrix jacchus jacchus) was explored in 3 experiments with a simulated foraging task. In Experiment 1, individual monkeys foraged among 8 baited food sites. They appeared to use spatial memory to accurately avoid revisiting previously depleted sites. There was no difference in accuracy between the adult monkeys and a juvenile monkey tested on the same task. In Experiment 2, a win-stay paradigm was used. The adult monkey subject very accurately remembered locations that had previously contained food. The monkey tended to visit adjacent correct sites when retrieving food and thus minimized the total distance travelled. In Experiment 3, a win-shift paradigm was used with 2 adult monkeys. Although both monkeys performed at above-chance levels of accuracy on the win-shift task, they made many errors. These results suggest that marmosets may prefer tasks that require a win-stay strategy.

Animals↗

Combined chemotherapy and radiotherapy versus best supportive care in the treatment of inoperable non-small-cell lung cancer.

Between October 1984 and July 1988, 119 patients with limited-stage inoperable non-small-cell lung cancer (NSCLC) were randomized to receive either active treatment (arm 1) or best supportive treatment (arm 2). Arm 1 patients received 3 courses of chemotherapy with cisplatin (100 mg/m2, day 1) and etoposide (125 mg/m2 i.v., day 1; 250 mg/m2 p.o., day 2-3), followed by radiotherapy (4,000 cGy/20 fractions/4 weeks). Arm 2 patients only received best supportive care. Fifty-three and 66 patients were randomized to arms 1 and 2, respectively. Thirty-eight patients in arm 1 and 57 in arm 2 were evaluable for survival. Median survivals of arms 1 and 2 were 12.4 and 8.7 months, respectively (p = 0.047). In the multivariate analysis, only age and histology were independent prognostic variables in predicting survival. The overall response rate after chemotherapy was 20.6% (complete remission 5.9%, partial remission 14.7%). Toxicities were mainly anemia, leukopenia, vomiting and alopecia. This study suggests that active treatment has marginal survival benefit in NSCLC though with considerable toxicities.

Actuarial Analysis↗

Poems syndrome.

A 40 year old Chinese woman presented with anasarca and later developed features of POEMS syndrome. These are peripheral neuropathy (P), organomegaly (O), endocrine dysfunction (E), monoclonal gammopathy (M), and skin changes (S) which are usually associated with plasma cell dyscrasia. In our patient, monoclonal gammopathy was not detected on immunofixation electrophoresis and was revealed only after analysis of kappa/lambda light chain ratio of the raised serum IgA immunoglobulin. Needle liver biopsy of her grossly enlarged liver showed marked accumulation of glycogen and presence of giant mitochondria in the hepatocytes, a feature not previously reported.

Adult↗

Combination cyclophosphamide and etoposide in treatment of small cell lung cancer.

Thirty-one patients with histologically proven small cell lung cancer were treated with cyclophosphamide 1 g m-2 and etoposide (VP16-213) 125 mg m-2 both intravenously on day 1 followed by etoposide 250 mg m-2 orally on days 2-3 for a maximum of six courses at 3 weekly intervals. Fourteen patients had limited and 17 patients had extensive disease. Twenty-five patients were evaluable for response. Objective response was observed in 18 patients (58%) with 6 (19%) complete and 12 (39%) partial responses. Median survival of the entire group of patients was 30 weeks. There was significant survival benefit among the responders (P less than 0.005) when compared with non-responders. One patient (3.3%) developed grade 4 while 60% of patients developed grade 1-2 haematological toxicity. Other side effects were relatively mild. We conclude that combination cyclophosphamide and etoposide was active in small cell lung cancer and relatively well tolerated.

Adult↗

Imbalance of purine nucleotides in alanosine-resistant baby hamster kidney cells.

Human DNA was used to transform adenosine kinase (AK)-deficient BHK cells followed by selection of AK+ cells in medium containing alanosine, adenosine, and uridine (AAU medium). Twenty AAUr isolates were analyzed, and none of them contained AK activity. Several purine salvage enzymes were, however, found to be affected in these cells. The levels of hypoxanthine-guanine phosphoribosyltransferase and adenylosuccinate synthetase activities were elevated, while the adenylosuccinase activity was reduced. AAU-resistance may be explained by elevated activity of adenylosuccinate synthetase to overcome the alanosine block; thus AAUr cells were able to convert exogenous adenosine----inosine----hypoxanthine----IMP----AMPS----AMP. Moreover, these AAUr cells required exogenous purines for growth. HPLC analyses of endogenous nucleotide pools of AAUr cells showed that the levels of adenine nucleotides have diminished to less than 10% of the parental levels. These results suggest that the AAU-resistant mutation, which elicits pleiotropic phenotypes in BHK cells, affects an important component in the regulation of adenine nucleotide synthesis. By including erthyro-9-(2-hydroxy-3-nonyl)adenine in the AAU medium (renamed as AAUE medium) to block deamination of adenosine, AK+ BHK cells were isolated.

Adenine↗

[Preparation and evaluation of anti-human growth hormone immunoserum].

Using small dosage of human growth hormone to immunize rabbit or guinea pig, it is able to induce anti-hGH antibody formation with high titre and high affinity that could be applied to hGH RIA. In the present study five rabbits and three guinea pigs were immunized with 125-200 micrograms and 250-285 micrograms per animal of hGH respectively, followed by boosters of 10-20 or 160-250 micrograms of hGH at 2-4 week intervals for 6 or 3 months. Blood was drown 1-2 weeks before each booster for determination of antibody formation. Antibody titre and affinity were successively observed and specificity of antibody was determined for the final bleeding. It was shown that titres of immune sera from guinea pigs were much higher than those of rabbit immune sera, but vice versa for antibody affinity. This might be due to larger immunogen dose used for guinea pigs than for rabbits. Fourteen different peptide hormones were tested in reference to cross-immunoreactivity to anti-hGH antibody. It could be demonstrated that the major cross-reactive hormones are hFSH and hLH, and hTSH also reacts to rabbit anti-hGH immune sera at a lesser degree. These cross reactivities are obviously owing to the molecular homogeneities between hGH and these hormones especially of their alpha-subunits.

Animals↗

A retrospective study of community-acquired pneumonia in Hong Kong with special reference to the choice of antibiotics.

The records of patients admitted to the Prince of Wales Hospital with a presumptive diagnosis of pneumonia over a one-year period were reviewed retrospectively. Forty-four patients fulfilled our diagnostic criteria for community-acquired pneumonia and were included in the survey. The initial choice of antibiotics was reasonably uniform: a penicillin in 75%; erythromycin in 9% and other antibiotics in 16%. Lack of clinical improvement resulted in a change of antibiotics in 15 patients (34%). Overall 23 patients (52%) responded to a penicillin, 12 patients (27%) responded to erythromycin, and 8 patients (18%) responded to other antibiotics. This suggests that the majority of the causative organisms were sensitive to penicillin, but a significant number of patients required drugs which were effective against 'atypical' and gram negative organisms. One elderly patient, who also suffered from severe chronic airflow obstruction, died after a grand mal seizure which might have been partly related to theophylline toxicity (Mortality 2%). The investigations performed confirmed or strongly suggested the identity of the causative organism in only 9 patients (21%), and had little or no influence in therapeutic decisions. Although empirical antibiotic treatment was reasonably successful, frequent changes were required, and the lack of firm data on the aetiology indicates that a detailed prospective study is needed.

Adolescent↗

Hyperosmolar urea for elective midtrimester abortion. Experience in 1,913 cases.

Intra-amniotic hyperosmolar urea (59.7 per cent) augmented by intravenous oxytocin (332 millimicron per minute), prostaglandin F2alpha (20 mg.), prostaglandin F2alpha (10 mg.), or prostaglandin F2alpha (5 mg.) was utilized for 1,913 patients requesting elective midtrimester abortion. Injection-abortion intervals ranging from 13.70 to 21.49 hours were achieved with failure rates of 0.7 to 6.7 per cent. Despite frequent pre-existing medical conditions, the complication rate compared favorably with those of other methods for terminating midtrimester pregnancy such as saline amnioinfusion or dilatation and evacuation.

Abortifacient Agents↗

Induction of labor by acupuncture electro-stimulation.

Induction of labor by acupuncture electro-stimulation was carried out in 31 patients. This was successful in 21 cases. The pattern of uterine contractions induced in these patients was similar to that in normal labor. No serious fetal or maternal complications occurred. The delay between the commencement of stimulation and the onset of contractions suggests that a humoral mechanism may be involved.

Acupuncture Therapy↗