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Biomedical subjects

Y S Lai

Publications and source records attributed to Y S Lai.

14 recordsLinked to original sources

Synthesis and protein kinase C inhibitory activities of balanol analogs with replacement of the perhydroazepine moiety.

Balanol is a potent protein kinase C (PKC) inhibitor that is structurally composed of a benzophenone diacid, a 4-hydroxybenzamide, and a perhydroazepine ring. A number of balanol analogs in which the perhydroazepine moiety is replaced have been synthesized and their biological activities evaluated against both PKC and cAMP-dependent kinase (PKA). The results suggested that the activity and the isozyme/kinase selectivity of these compounds are largely related to the conformation about this nonaromatic structural element of the molecules.

Azepines

Which pressure sore risk calculator? A study of the effectiveness of the Norton scale in Hong Kong.

This study aimed to evaluate the effectiveness of the Norton score in predicting the likely occurrence of pressure sores compared to the Waterlow scale in Hong Kong. Two elderly care wards (one male and one female) were chosen, the sample size was 185 and the mean age of subjects was 80.4. Each newly admitted patient was assessed using both the Norton calculation and the Waterlow calculation. At the end of the research, there were eight patients who had sore formation. The results indicated that the Norton score identified six out of the eight patients while the Waterlow identified seven of them. The Waterlow calculation, however, seems to have misidentified 72 patients as being in the 'at risk group'. In view of a fear of the misdirection of resources the Norton score was found to be the better of the two and its use in the elderly care units in this study should be continued until a better scoring system is found.

Aged

Light-induced changes in frog pineal gland N-acetyltransferase activity.

N-Acetyltransferase (NAT) activity was determined in the pineal gland of frogs (Rana tigrina) of different ages using 2-aminofluorene and p-aminobenzoic acid as substrates, and assayed by high-pressure liquid chromatography. Frogs of different ages were either killed during the light phase or exposed to darkness or light for 1 min during the dark phase of the lighting cycle, then returned to their cages in darkness for 30 min before being killed. The pineal gland NAT activity of 1-month-old frogs was inhibited when the animal was nocturnally exposed to 1 min of light. Nocturnal light exposure did not inhibit NAT activity in 1-month-old frogs, even though these animal displayed clear light-dark differences in pineal gland NAT activity. Nocturnal light exposure did not inhibit night-time levels of NAT activity in 1-month-old animals which had been bilaterally enucleated, thus suggesting that this effect is retinally mediated. Pretreatment of 1-month-old and 6-month-old animals with isoproterenol (a beta-adrenoceptor agonist drug) prevented the nocturnal light-induced inhibition of NAT activity. From the different sensitivity of 1-month-old and 6-month-old animals to different intensities or durations of nocturnal light exposure it was found that the duration or intensity of light exposure was not able to inhibit nocturnal NAT activity. The NAT activity was at least 4-5-fold greater in 1-month-old frogs than in 6-month-old frogs. This is the first demonstration of the retino-pineal gland pathway that appears to produce light-induced changes in pineal glands of frogs 1-month-old or older, but this pathway only functions in 1-month-old frogs, and does not appear to function in 6-month-old frogs.

Aging

The alteration of cytokeratin 18 molecule and its mRNA expression during tumor transformation in hepatoma.

The cytokeratin 18 related molecules of human hepatocellular carcinoma have been previously recognized through a series of biochemical and immunological approaches. It is suggested that these molecules undergo modulation from human hepatocyte cytokeratin 18. To prove whether these molecules are produced by modulation or protein degradation, we checked the cytokeratin profile of human hepatoma cell line PLC/PRF/5 with the methods used before. These results revealed that the PLC cells have the same cytokeratin 18 related molecules as human hepatocellular carcinoma tissue. The gene expression of the cytokeratin 18 in non-tumor liver tissues, hepatocellular carcinoma and PLC/PRF/5 cells were investigated. First, the mRNAs of non-tumor liver tissues, hepatocellular carcinoma tissues and PLC/PRF/5 cells were collected by the acid guanidinium thiocyanate phenol chloroform method. After transcription into cDNA by reverse transcriptase polymerase chain reaction, the cDNAs of each specimen were amplified by PCR and then digested by SmaI and BamHI restriction enzymes. The digested cDNA fragments were electrophoresed in agarose gel and the base pairs were found to be the same in length between neoplastic and non-neoplastic hepatocytes.

Carcinoma, Hepatocellular

The dimerization domain upstream binding factor contains multiple helical structures.

The upstream binding factor, UBF, is an RNA polymerase I transcription factor which contains multiple DNA binding domains and a novel protein dimerization domain. Active UBF forms homodimers in vivo through the intramolecular interactions of its dimerization domain, which spans a hundred amino-terminal residues. In the presence of both UBF dimerization domain and its immediately adjacent lysine-rich basic DNA binding domain, the E. coli expressed recombinant polypeptide, dbUBF (dimerization plus basic motifs of UBF), forms homodimers in vitro and binds to double-stranded DNA nonselectively. In gel retardation assay, dbUBF dimers make multiple shift-ladders corresponding to numerous protein dimer-DNA complexes. The UBF dimerization domain contains multiple helical structures, as predicted by EMBO-PHD program. Most of hydrophobic residues in the dimerization domain are confined in the hydrophobic phase of these hypothetic helices. Mutating these hydrophobic residues to glutamate prohibits dbUBF association and gives a different shift pattern in gel retardation assay. The results we present here argue that UBF association is largely exerted by the hydrophobic interactions between the multiple helices to bring two molecules together.

Amino Acid Sequence

Mucinous biliary cystadenoma with mesenchymal stroma: expressions of CA 19-9 and carcinoembryonic antigen in serum and cystic fluid.

A case of mucinous biliary cystadenoma with mesenchymal stroma (CMS tumor) in a 64-year-old woman is reported. The patient presented with acute abdominal pain and a palpable mass in the upper abdomen. Computed tomography and abdominal sonography showed characteristic multilocular cysts in the left lobe of the liver. Serum CA 19-9 was elevated to 108 U/ml with normal carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) levels. The levels of CA 19-9 and CEA in the cystic fluid were high at 7430 U/ml and 576 ng/ml, respectively. The serum CA 19-9 returned to 35 U/ml 4 weeks after tumor resection. These corresponding findings of both tumor markers in the serum and cystic fluid imply that (1) CA 19-9 and CEA both exist in the epithelial component of CMS tumors as evidenced by immunohistochemical stain, (2) serum CA 19-9 is a valuable marker in the diagnosis and monitoring of CMS, and (3) in cystic fluid, there are more significantly high levels of CA 19-9 in CMS compared with levels in simple cyst and polycystic liver disease. Therefore, measurement of CA 19-9 in cystic fluid and serum may be helpful in the differential diagnosis of hepatic cystic lesions.

Angiography

Toxic effects of grass carp, snake and chicken bile juices in rats.

To evaluate the toxic effects of different animal bile juices, male Long-Evans rats were used and treated orally with different doses (0.03-0.6 ml) of grass carp, snake and chicken bile juices. After treating with one high dose (0.6 ml) for 6 and 24 h, the levels of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), alkaline phosphatase (ALP), blood urea nitrogen (BUN) and creatinine in the plasma of rats in the grass carp bile juice group became higher than those of the other two bile treated groups. After 3-days periodic treatment with 0.3 ml of each animal bile juice for 28 days, the levels of GOT, GPT, BUN and creatinine in the plasma of rats were significantly increased, especially the grass carp bile juice-treated rats. It appeared that the rats administered with snake and chicken bile juices for a much longer time were poisoned and had the same symptoms as those treated with grass carp bile juice.

Alanine Transaminase

Kinetics of acetyl coenzyme A:arylamine N-acetyltransferase from rapid and slow acetylator frog tissues.

N-acetyltransferase (NAT) activity was determined in 100 frog (Rana tigrina) livers using 2-aminofluorene and p-aminobenzoic acid as substrates. Overall, the liver NAT activity of the 50 females was higher than the liver NAT activity of the 50 males. The activities (mean +/- SD) of NAT from the bladder, blood, colon, and liver of males was 0.30 +/- 0.11, 0.05 +/- 0.03, 0.09 +/- 0.05, and 0.93 +/- 0.56 nmol/min/mg protein for the acetylation of aminofluorene and 0.29 +/- 0.06, 0.36 +/- 0.04, 0.26 +/- 0.02, and 0.32 +/- 0.14 nmol/min/mg protein for the acetylation of p-aminobenzoic acid. In the bladder, blood, colon, and liver from female frogs, the activities obtained were 1.00 +/- 0.41, 0.52 +/- 0.07, 0.08 +/- 0.05, and 1.27 +/- 0.49 nmol/min/mg protein for aminofluorene and 0.34 +/- 0.12, 0.36 +/- 0.04, 0.34 +/- 0.07, and 0.48 +/- 0.21 nmol/min/mg protein for p-aminobenzoic acid. Kinetic constants for arylamine NAT activity in the blood, liver, bladder, and colon from frogs with rapid, intermediate, and slow acetylator activities were determined. KM and Vmax values for aminofluorene were 2- to 6-fold higher for liver than for the other tissues. KM and Vmax values for p-aminobenzoic acid showed a smaller variation among the tissues examined, with values obtained for the liver and bladder being somewhat higher than the values for the blood and colon. An apparent KM difference for aminofluorene was found in the liver from frogs with high and low acetylator activity. Based on the aminofluorene NAT activity of liver, there seems to be a polymorphism in NAT activity with 4 rapid, 21 intermediate, and 75 slow acetylators among the 100 frogs assayed. Distribution of acetylator phenotypes was similar among the 50 males and 50 females in this study. This is the first demonstration of acetyl coenzyme A:arylamine NAT activity in an amphibian and could lead to the development of a frog model for monitoring the effect of pollution of wetland environments on native species.

Acetyl Coenzyme A

Could the cytokeratin molecule be modulated during tumor transformation in hepatocellular carcinoma?

The stability of cytokeratin during tumor transformation in hepatocellular carcinoma was studied. We applied biochemical methodology to look into the switching of cytokeratin molecules in tumor transformation. First, by centrifugation the cytokeratin molecules were extracted from both liver and hepatoma tissues. The extracts were then soaked with cyanogen bromide-activated Sepharose 4B beads previously coated by monoclonal anti-cytokeratin antibody. The bound molecules were then released from the resin with salt. Second, the isolated molecules of both were treated with lysosomal enzyme and analyzed on two-dimensional gels. The results demonstrated that there was a modulation in cytokeratin molecules, and the hepatoma cytokeratin was generated from the hepatocyte cytokeratin.

Blotting, Western

Ulceronodular gastritis in secondary syphilis.

Syphilitic gastric ulcers are rarely diagnosed and are almost always a manifestation of the tertiary stage. We describe the case of a 21-year-old man who developed such an ulcer during the secondary stage.

Adult

Small cell lung carcinoma: clinicopathological, immunohistochemical, and ultrastructural study.

Sixty-seven cases of small cell lung carcinoma (SCLA) in Tri-Service General Hospital (TSGH) during the past 16 years were studied. For patients with extensive stage of disease, the mean survival time and 2-year survival rate were 7.2 months and 3.1% versus 13.4 months and 16.7% for patients with limited stage. A better prognosis was obtained by treatment with a combination of intensive chemotherapy and radiotherapy. Immunohistochemical studies were performed by the peroxidase-antiperoxidase method. The positive rates in descending order were bombesin (80%), synaptophysin (74.3%), neurofilament (68.6%), neuron-specific enolase (60%), low molecular weight cytokeratin (54.3%), high molecular weight cytokeratin (25.7%), chromogranin-A (22.9%), adrenocorticotrophic hormone (0). Seven cases were examined and found to be ultrastructure; only 3 cases were found to contain neurosecretory granules. We emphasize that electron microscopy is not necessary as a routine diagnostic procedure, while light microscopy should be employed whenever possible; the immunohistochemical study should be considered within this context.

Adrenocorticotropic Hormone

Expression of cytokeratins in normal and diseased livers and in primary liver carcinomas.

Hepatocytes and bile duct epithelium express several types of cytokeratins, the characteristic intermediate-filament proteins of epithelial cells. The cytokeratin antigen expression was studied in normal and diseased livers, intrahepatic cholangiocarcinomas, and hepatocellular carcinomas by immunohistochemical methods using a panel of polyclonal and monoclonal antibodies to cytokeratins. Ten percent formaldehyde solution-fixed, paraffin-embedded sections obtained from ten patients without liver disease, 18 patients without liver disease, 18 patients with different stages of primary biliary cirrhosis, 14 patients with alcoholic hepatitis, ten patients with fatty liver hepatitis secondary to diabetes mellitus or morbid obesity, five patients with hepatocellular carcinomas, and five patients with cholangiocarcinomas were examined. The results suggested that hepatocytes and bile duct epithelium retain their distinct cytokeratin profiles in liver disease, including malignant transformation. Therefore, demonstration of cytokeratins in the liver is useful in establishing the cellular origin of neoplasms and understanding the pathogenesis of liver diseases.

Adenoma, Bile Duct