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Biomedical subjects

P Chow

Publications and source records attributed to P Chow.

35 records · Page 2Linked to original sources

Clinical profile of stage D carcinoma of the prostate--a ten-year experience.

Carcinoma of the prostate has become one of the top ten malignancies in Singapore but to date, there has been little local clinical data available on the disease. This study aims to establish the clinical profile of Stage D carcinoma of the prostate in the local population. Forty-seven patients with Stage D disease treated by the department over a ten-year period, 1981-90, were studied. The majority (47.7%) fell in the age-group 66-75 years and the most common presenting symptom was bone pain (36.2%). Both acid and alkaline phosphatases were found to be poor diagnostic markers of the extent of the disease. Acid phosphatase was not elevated in 25.0% and alkaline phosphatase not elevated in 39.1% of our patients. Forty of these patients had orchidectomy and of these, ten were also treated with oral stilbesterol. Five-year survival for the orchidectomy group was 22.7% and that for the orchidectomy-plus-stilbesterol group was 23.0%. This compares well with other studies done in the West. Eight patients died within the first year of diagnosis but of those who survived, all remained symptom-free within this first year. The proportion of those who remained symptom-free fell to 25.0% of the survivors for subsequent years.

Acid Phosphatase↗

Isolation of a cDNA encoding a human serum marker for acute pancreatitis. Identification of pancreas-specific protein as pancreatic procarboxypeptidase B.

A human pancreas-specific protein (PASP), previously characterized as a serum marker for acute pancreatitis and pancreatic graft rejection, has been identified as pancreatic procarboxypeptidase B (PCPB). cDNAs encoding PASP/PCPB were isolated from a human pancreas cDNA library using a combination of nucleic acid hybridization screening and immunoscreening with antisera raised against native PASP. The deduced amino acid sequence of PASP/PCPB cDNA predicts the translation of a 416-amino acid preproenzyme with a 15-amino acid signal/leader peptide and a 95-amino acid activation peptide. The proenzyme portion of this protein has 76% identity with rat PCPB and 84% identity with bovine carboxypeptidase B. DNA and RNA blot analyses indicate that human PCPB mRNA (1,400 nucleotides) is transcribed from a single locus in the human genome in a tissue-specific fashion. N-terminal sequencing of native PASP and the specific immunoreactivity of bacterially expressed PASP/PCPB with native PASP antibodies confirm the identification of PASP as human pancreatic PCPB.

Acute Disease↗

Multiple basal cell carcinoma in tropical Australia.

No association between HLA DR1 and the development of multiple basal cell carcinomas (BCC) was found among patients who had lived at least two-thirds of their lives in the tropics. The percentage of patients with multiple BCCs increased with age; this was different from what has been found in people living in the temperate zone of Australia.

Adult↗

CD4-binding regions of human immunodeficiency virus envelope glycoprotein gp120 defined by proteolytic digestion.

The gp120 envelope glycoprotein of human immunodeficiency virus type 1 binds the cell surface protein CD4 with high affinity. Here we report the use of proteolysis to define regions of gp120 involved in CD4 binding. Cleavage of gp120 with Staphylococcus aureus V8 protease at residue 269 or with trypsin at residue 432 destroys CD4 binding. These same sites are protected from proteolytic cleavage by bound CD4. Cleavages at 64, 144, 166, 172, and 315 do not affect binding and are not protected by bound CD4, indicating that these regions are not critical for binding CD4. All proteolytic fragments found in coprecipitates with CD4 were covalently associated via disulfides and comprised complete gp120 molecules. Previous conclusions by Nygren et al. [Nygren, A., Bergman, T., Matthews, T., Jornvall, H. & Wigzell, H. (1988) Proc. Natl. Acad. Sci. USA 85, 6543-6546] that both large and small (95-kDa and 25-kDa) V8 proteolytic fragments bind CD4, independently, are not distinguished by their experiments from the result found here that the small fragment immunoprecipitates with CD4 while disulfide-linked to the larger fragment.

Amino Acid Sequence↗

Population pharmacokinetics of rectal theophylline in neonates.

The population pharmacokinetics of theophylline were studied in 35 neonates receiving aminophylline suppositories for the treatment of apnoea of prematurity. Routinely measured theophylline serum concentrations (n = 138, range 3-20 mg/L) were modelled in NONMEM according to a one-compartment model. The influence of a number of clinical and demographic factors, e.g., weight (range 0.8-2.5 kg) and postnatal age (2-80 days), on clearance/bioavailability (CL/F) and volume/bioavailability (V/F) was investigated. Both these parameters were found to significantly correlate to weight alone in a directly proportional manner: CL/F = 40 +/- 2 ml/h/kg and V/F = 1.3 +/- 0.2 L/kg. The absorption was best described by a first-order process, having a half-life of 1.6 +/- 0.7 h. The interindividual variability in CL/F was 25%, whereas the same estimates in V/F and in the first-order absorption rate constant could not be obtained. The residual variability in theophylline concentrations was modelled with additive error with an estimated standard deviation of 1.78 mg/L. From these results, it was concluded that rectal administration of aminophylline in neonates is a therapeutically acceptable alternative to oral administration. The convenience gained by rectal, compared to oral, administrations may compensate, in many instances, for the possibly slightly higher variability in CL/F of the former.

Administration, Rectal↗

Detection of transforming growth factor-alpha messenger RNA in normal and chemically transformed hamster oral epithelium by in situ hybridization.

We have recently demonstrated the consistent detection of transforming growth factor alpha (TGF-alpha) in chemically transformed hamster oral tumors. By Northern blot analysis, no TGF-alpha mRNA can be detected in normal cheek pouch mucosa. The consistent expression of TGF-alpha associated with the malignant transformation in the well-defined hamster oral cancer model prompted us to hypothesize that the aberrant expression of this important cellular gene could be related to a specific stage of epithelial alteration. In situ hybridization was used to test this hypothesis. We now report that by in situ hybridization we can detect TGF-alpha mRNA in normal hamster oral epithelium and also at all stages of transformation. In all epithelium, labeling of TGF-alpha mRNA in the basal layer is more pronounced than that observed in the spinous and squamous layers. There is a significant increase of TGF-alpha mRNA labeling early in 7,12-dimethylbenz(a)anathracene-induced oral carcinogenesis. This increase is associated with morphological changes of epithelial hyperplasia or dysplasia. Although lesions exhibiting full-thickness epithelial dysplasia (carcinoma in situ) showed more labeling of TGF-alpha mRNA than do areas of lesser dysplasia, the transition to full-fledged papillary or invasive squamous cell carcinoma is not associated with further elevations of TGF-alpha expression.

9,10-Dimethyl-1,2-benzanthracene↗

Detection of Ki-ras messenger RNA in normal and chemically transformed hamster oral keratinocytes.

The cheek pouch of the Syrian hamster is an excellent model for the experimental study of oral carcinogenesis. The carcinogenic chemical 7,12-dimethylbenz[a]anthracene consistently produces epidermoid carcinomas in the cheek pouch of the Syrian hamster, giving rise to characteristic histopathological lesions in a time-dependent manner. We now present experimental evidence that c-Ki-ras mRNA can be detected in all 7,12-dimethylbenz[a]anthracene-induced tumors examined (in vivo and in vitro) in this experimental oral cancer model while no detectable c-Ki-ras mRNA can be found in the normal hamster cheek pouch epithelium. Cellular synchronization experiments using a cell line (hamster cheek pouch carcinoma cell line 1) derived from one of these 7,12-dimethylbenz[a]anthracene-induced hamster oral tumors revealed that the c-Ki-ras protooncogene is expressed during the G1 phase of the cell cycle (proliferation dependent). Serum starvation and RNA synthesis inhibition experiments using hamster cheek pouch carcinoma cell line 1 cells suggest that the c-Ki-ras protooncogene is indeed quiescent in the normal hamster cheek pouch epithelium and that failure to detect its mRNA is not related to the slower proliferation of the normal epithelial cells. These results suggest that the transcription of the c-Ki-ras protooncogene is associated with malignant transformation in the cheek pouch of the Syrian hamster.

9,10-Dimethyl-1,2-benzanthracene↗

Studies of chemical components of Angora goat seminal plasma.

Ejaculates were collected by artificial vagina from 11 Angora goats, once or twice weekly, between April and July in two successive years. The mean +/- SEM ejaculate volumes each year were 0.8 +/- 0.30 and 0.98 +/- 0.52 ml; the sperm concentrations were 3.33 +/- 0.49 and 2.94 +/- 0.45 x 10(9)/ml, and the pH values were 7.01 +/- 0.34 and 7.20 +/- 0.17. The concentrations (mg/100ml) of fructose (875 +/- 97) and lactic acid (73 +/- 17) in goat seminal plasma were sufficiently high to be important substrates for maintenance of sperm motility. Only trace amounts of glucose were present in seminal plasma. The glycerylphosphorylcholine (GPC) concentration of seminal plasma (809 +/- 154 mg 100 ml ) was correlated with whole semen sperm concentration (P < 0.001), indicating that GPC is of epididymal origin. Goat sperm are not likely to utilize GPC as a substrate and its metabolizable derivatives, glycerophosphate (3.3 +/- 1.1 mg 100 ml ) and glycerol (1.8 +/- 1.0 mg 100 ml ), were not present in sufficiently high concentrations to be significant as energy sources for the sperm. The mean concentration of citric acid was 331 mg 100 ml seminal plasma. Colored semen was consistently produced by eight bucks, and in yellow, light yellow and white ejaculates, the seminal plasma riboflavin (mug/ml) concentrations were 5.38 +/- 2.89, 3.09 +/- 0.85 and 1.73 +/- 0.88, respectively. This suggests that the color is due to riboflavin, which is probably produced by the vesicular glands since the concentration of riboflavin in the seminal plasma was correlated with fructose and citric acid levels.

Journal Article↗

TGF-alpha and EGF-receptor mRNAs in human oral cancers.

Transforming growth factor alpha (TGF-alpha) and epidermal growth factor receptor (EGFR) have been shown to be present in most squamous cell carcinomas. Using the Syrian hamster oral cancer model, we have recently demonstrated the consistent presence of TGF-alpha and EGFR mRNAs in chemically transformed hamster oral keratinocytes. We now present evidence that in human oral cancer (in vivo and in vitro), TGF-alpha and EGFR mRNAs can also be consistently detected. No TGF-alpha mRNA can be detected in normal human oral epithelium by Northern blot analysis. These findings reinforce the use of the hamster cheek pouch as an experimental model for the study of oral cancer development, at least in reference to the possible participation of TGF-alpha in the malignant transformation process.

Animals↗

Convulsant doses of penicillin shorten the lifetime of GABA-induced channels in cultured central neurones.

The influence of sodium benzylpenicillin (PCN) on membrane channels activated by gamma-aminobutyric acid (GABA) was studied in cultured spinal neurones of the mouse by the extracellular patch clamp technique. In whole-cell, current clamp recordings, concentrations of PCN above 0.2 mM significantly reduced the amplitude of the GABA response. Single channel currents activated by GABA were studied in outside-out patches of neuronal membrane. In both the absence and presence of PCN, cumulative open time distributions for GABA-activated channels were well fitted by the sum of two exponential terms, characterized by fast (tau f) and slow time constants (tau s). PCN (2mM) reduced the mean value of tau s from 4.29 +/- 0.56 ms (mean +/- s.e. mean) to 1.12 +/- 0.09 ms but had no significant effect on tau f. The mean open time of GABA-activated channels, calculated from the double exponential fits, decreased from 1.39 +/- 0.35 ms to 0.53 +/- 0.02 ms in the presence of 2 mM PCN. The reduced mean open time of GABA-sensitive channels seen in the presence of PCN may contribute to the convulsant action of the drug in vivo.

Animals↗

4-Methylumbelliferyl 2-acetamido-2-deoxy-alpha-D-glucopyranoside, a fluorogenic substrate for N-acetyl-alpha-D-glucosaminidase.

Condensation of dimeric 3,4,6-tri-O-acetyl-2-deoxy-2-nitroso-alpha-D-glucopyranosyl chloride with 4-methylumbelliferone gave crystalline 4-methylumbelliferyl 3,4,6-tri-O-acetyl-2-deoxy-2-oximino-alpha-D-arabino-hexopyranoside. Acetylation of this adduct, reduction of the resulting crude O-acetyloxime with borane in oxolane, and acetylation gave the 3,4,6-tri-O-acetyl derivative of 4-methylumbelliferyl 2-acetamido-2-deoxy-alpha-D-glucopyranoside (1). A new sensitive assay of N-acetyl-alpha-D-glucosaminidase (EC 3.2.1.50) is made possible by fluorometric measurement of 4-methylumbelliferone liberated by enzymic hydrolysis of glycoside 1. Such assays are illustrated by results obtained with enzyme preparations from pig liver and human-blood serum.

Acetylglucosamine↗

Manitoba barium enema efficacy study.

Claims analysis and efficacy study are two new methods of evaluating medical services. In Manitoba, with a 1974 population of 1,053,382, approximately 100,000 patient-physician interfaces resulted in 16,594 barium enema examinations; 1,000 significant abnormalities were discovered, and the referring physician was unusally perceptive in predicting the likelihood of these abnormalities. It is estimated that a 10% reduction in the use of barium enemas could be achieved by referring physicians with no deterioration in the care of patients.

Adolescent↗

Clinical and laboratory assessment of the pathogenicity of serotyped enteropathogenic Escherichia coli.

Only one of 167 separate isolates of enteropathogenic Escherichia coli (EEC) was shown to produce enterotoxin, and none of the 167 isolates were invasive. Clinical features of 123 hospitalized children with EEC were compared with those of 917 infants with nonbacterial gastroenteritis and 145 infants infected with Shigella. The average duration of diarrhea (five or more stools per day) in hospitalized children with EEC, nonbacterial gastroenteritis, Shigella flexneri, and Shigella sonnei was 4.6, 2.4, 5.1, and 2.5 days, respectively. The average duration of fever in these four groups was 1.4, 1.2, 2.1, and 1.2 days, respectively. The difference in duration of diarrhea between children with EEC and those with nonbacterial gastroenteritis was significant (P less than 0.001), even when age and rural/urban origin were controlled by analysis of variance. Nevertheless, the EEC group tended to be younger and to have a higher proportion of infants of rural origin. Although it appears that EEC serotypes rarely identify invasive or enterotoxin-producing organisms, clinical features of infants with EEC-associated gastroenteritis suggest that these infants may represent a distinctive and clinically important group with gastroenteritis of greater severity than nonbacterial gastroenteritis.

Child↗