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Biomedical subjects

K W Lo

Publications and source records attributed to K W Lo.

At least 91 records · Page 5Linked to original sources
PubMed1993

Nasopharyngeal carcinoma: genetic changes, Epstein-Barr virus infection, or both. A clinical and molecular study of 36 patients.

BACKGROUND: The pathogenesis of nasopharyngeal carcinoma has been under intense investigation, especially of its peculiar predominance in southern China. The authors previously reported consistent loss of genetic material on the short arm of chromosome 3 in a few nasopharyngeal carcinoma cases. In this study, the authors examined the genetic changes as well as the presence of Epstein-Barr virus (EBV) genome on 36 nasopharyngeal carcinoma primary biopsy specimens of the undifferentiated type and the correlation of the findings to patients' clinical status. METHODS: The authors examined the DNA from tumor tissue and from matched blood leukocytes of 36 patients who suffered from nasopharyngeal carcinoma by the restriction fragment length polymorphism analysis. The genotyping for EBV was carried out by polymerase chain reaction using primers complementary to both types of EBV and probes specific to EBNA-2A (EBV-A) or EBNA-2B (EBV-B). RESULTS: A consistent deletion at two specific locus of the short arm of chromosome 3 was observed in all informative cases. The authors also found that EBV genome, especially type A, was present in 35 of 36 cases. In the remaining one case, EBV-B was detected. CONCLUSIONS: As the same tumor tissue was used for both genetic and viral studies in each case, the results may represent sequential genetic lesions in the pathogenesis and/or summation of genetic events. Moreover, 7 of 32 informative tumors were from patients of early staging (Stages I and II), which suggests the genetic changes may occur in the early development of nasopharyngeal carcinoma. Difference in allele frequency in specific locus was also noted between Asian and white patients for the first time.

Adult↗
PubMed1993

A controlled trial of amnioinfusion: the prevention of meconium aspiration in labour.

The purpose of this study was to examine the effect of amnioinfusion on the incidence of meconium aspiration syndrome, perinatal asphyxia and obstetrical intervention rate amongst patients with moderate and thick meconium-stained liquor. A total of 112 patients were studied in a prospective fashion; 60 received amnioinfusion and 52 served as controls. We have shown that amnioinfusion is a simple, relatively inexpensive and safe procedure. It benefits the patient in terms of reduction in the likelihood of operative intervention (specifically Caesarean section) for fetal distress and improvement in neonatal outcome with reduced frequency of neonatal acidaemia.

Acidosis↗
PubMed1993

Direct cycle sequencing of mutated alleles detected by PCR single-strand conformation polymorphism analysis.

A rapid protocol for direct sequencing of a mutated allele, detected by combining polymerase chain reaction with single-strand conformation polymorphism (PCR-SSCP) analysis and cycle sequencing using a thermal cycler, is described. End-labeled radioactive primers were used both for PCR-SSCP analysis for the detection of p53 gene mutation and for cycle sequencing using delta Taq Version 2.0 DNA Polymerase. The point mutations along the various exons of the p53 gene can be rapidly determined by this sequencing method. This protocol requires only a small amount of DNA template (0.1 microgram) and produces sequencing images with low backgrounds and very uniform band intensity. It has also been used successfully in the study of other gene mutations including ras and NF-1 (neurofibromatosis 1) genes.

Alleles↗
PubMed1992

Absence of p53 gene mutations in primary nasopharyngeal carcinomas.

Alterations in the p53 tumor suppressor gene and Epstein-Barr virus status were investigated in 15 nasopharyngeal carcinoma (NPC) biopsies, 4 xenografts, and 2 cell lines from the Cantonese region of southern China. One other established NPC cell line obtained from a northern Chinese patient was also studied. Restriction fragment length polymorphism analysis revealed a loss of heterozygosity for chromosome 17p, where the p53 gene resides, in only one of 15 NPC biopsies. Polymerase chain reaction-single-stranded conformational polymorphism analysis and direct sequencing failed to detect sequence alterations in exons 5 through 8 of the p53 gene in the 15 tumors and in the 4 NPC xenografts, all of which tested positive for Epstein-Barr virus. In contrast, the 3 NPC cell lines were all negative for Epstein-Barr virus and contained G----C transversions in the p53 gene, with cell lines CNE-1 and CNE-2 harboring identical AGA (arginine) to ACA (threonine) changes at codon 280. These results suggest that p53 inactivation is not a necessary component of nasopharyngeal carcinogenesis in Cantonese but may be important in the establishment of cell lines derived from these tumors.

Base Sequence↗
PubMed1991

Loss of heterozygosity on the short arm of chromosome 3 in nasopharyngeal carcinoma.

A consistent loss of constitutional heterozygosity within a specific chromosome locus in a tumor type is suggestive of a tumor suppressor gene important in the genesis of that tumor. We studied whether such genetic alterations are involved, in the development of nasopharyngeal carcinoma (NPC). Tumor and matched blood leukocytes DNA from eleven Hong Kong Chinese patients with primary NPC stages I to IV were subjected to restriction fragment length polymorphism (RFLP) analysis using chromosome 3-specific polymorphic probes. Such probes are assigned to chromosomal region 3p25 (RAF-1), 3p24-22.1 (ERBA beta), 3p21 (DNF15S2), 3p14 (D3S3), and 3q12 (D3S1). The breakpoint varied among tumors, ranging in extent from 3p21-14. However, 100% frequency of complete loss of heterozygosity was observed at two chromosomal loci: RAF-1 locus (ten of ten cases at 3p25) and D3S3 locus (nine of nine cases at 3p14), in all evaluable NPC patients, suggesting the presence of putative tumor suppressor gene(s) within or close to these defined regions. The observed consistent deletion of alleles on the short arm of chromosome 3 in the NPC cases, which is in line with our previously reported and present cytogenetic findings, may represent a critical event in the multistep genesis of NPC. The present report also identifies defined loci for linkage studies on NPC families.

Carcinoma↗
PubMed1986

Occurrence and distribution of halophilic vibrios in subtropical coastal waters of Hong Kong.

The summer occurrence and distribution of halophilic vibrios in the subtropical coastal waters of Hong Kong were investigated. The density of vibrios in six sample sites ranged from 90 to 6,700 per ml, which made up 0.41 to 40% of the total bacterial populations of these sample sites. The sucrose-positive vibrios were found to be much more common (88% of total vibrios) than the sucrose-negative ones. A total of 48 strains belonging to six Vibrio species were fully characterized. Among these, Vibrio alginolyticus was the most frequently isolated, followed by V. parahaemolyticus, V. harveyi, V. vulnificus, V. campbellii, and V. fluvialis. The finding that eight of the nine strains of V. harveyi showed a positive Kanagawa reaction warrants further study.

Hong Kong↗
PubMed1984

5'-Nucleotide phosphodiesterase isozyme-V as a marker for liver metastases in breast cancer patients.

A 2-year prospective study testing 258 breast cancer patients for the presence of 5'-nucleotide phosphodiesterase isozyme-V (5'-NPD-V) as a marker for liver metastases was undertaken. Despite the difficulty associated with such a study in obtaining data from biopsy (only 12 patients) and autopsy (only 18 patients), the 5'-NPD-V test correctly predicted confirmed liver metastases in 39 of 41 patients (95%). Of this group, 25 patients had abnormal liver scans at the time the 5'-NPD-V test was positive (64%). In 11 of 39 patients 5'-NPD-V was found positive before liver scans. In the majority of patients, 5'-NPD-V fluctuated between positive and negative during follow-up. While such transiently positive values may be related to treatment, they should be interpreted conservatively as liver proliferation until confirmed otherwise. Throughout the 2-year study only seven patients with nonmalignant hepatic diseases had consistent positive values (2.7%). As an indicator of liver metastases 5'-NPD-V is more specific than other liver function tests. It is also important to note that 14 patients received early chemotherapy because attention was directed toward the diagnosis of liver metastases by this test.

Breast Diseases↗
PubMed1982

Evaluation of 5'-nucleotide phosphodiesterase isozyme-V as a predictor for liver metastasis in breast cancer patients.

5'-nucleotide phosphodiesterase isozyme-V (5'-NPD-V) was evaluated in 85 biopsy proven breast cancer patients as a potential marker for early liver metastasis. It correctly predicts liver metastasis in 6/7 (85.7%) patients with abnormal radiologic liver scan and 2/2 other patients with palpable liver. Serum glutamic-oxaloacetic transaminase (SGOT), lactic dehydrogenase (LDH), alkaline phosphatase (AP) and total bilirubin (B) were also determined in 79 of these patients as routine liver function tests (LFT). Forty-one out of 79 from this group had all four markers all within normal limits. Yet of the 41 patients, 12 patients were found positive for 5'-NPD-V. Of these 12, one was found to have liver metastasis at surgery and one had abnormal liver scan. Five other patients had liver dysfunction and one had been diagnosed as an alcoholic. Four others had no evidence of either liver problems or liver metastasis, but follow-up data were lacking. This retrospective study, therefore suggests that there is a definite advantage to include the 5'-NPD-V in the liver profile studies for breast cancer patients, although a positive 5'-NPD-V may only indicate liver repair or liver regeneration. Long-term prospective studies of these tests with breast cancer patients should be worthwhile. No relation was found between 5'-NPV-V and axillary lymph node involvement or the estrogen receptor status of the excised tumor. Thus there is no evidence currently that the appearance of the 5'-NPD-V in serum is related to lymph node metastases or hormonal control.

Adult↗
PubMed1982

Cell cycle and 5'-Nucleotide phosphodiesterase activities in rat liver.

The postnatal developments of liver and serum 5'-nucleotide phosphodiesterase (5'-NPD) in Fischer 344 rats were studied. The liver enzyme activities were found to correlate well with the growth of the liver as measured by the wet weight and percentages of liver cells in the G2/M phases of the cell cycle as determined by flow cytofluorometry. Therefore, this enzyme may be intimately related to the growth of the liver. Although the specific activities of the serum enzyme are three orders of magnitude less than that of the liver enzyme, very good correlation was obtained between the total serum and liver enzyme activities. This finding, therefore, suggest that the main origin of the serum enzyme is from liver. Multiple isozymes were detected in both liver and serum 5'-nucleotide phosphodiesterase after polyacrylamide gel electrophoresis.

Aging↗
PubMed1981

Anti-tumor effect of (S)-10-hydroxycamptothecin on mouse hepatoma BW7756 and its possible mode of action.

(S)-10-Hydroxycamptothecin (OPT), an analog of camptothecin (CPT), was found to inhibit the growth of the mouse hepatoma BW7756, when given at 1.0 mg/kg/day for 14 days. Cell cycle studies using flow cytofluorometry indicated that this drug inhibited the S-Phase of the tumor cells in vivo and the S and G2/M phases in vitro. Similar studies on host liver showed little or no effect. In spite of the narrow range of the effective dose of this drug against mouse hepatoma BW7756, the use of OPT in combination with other antitumor agents may be useful in primary hepatoma or liver metastases in view of its low toxicity towards host liver. A simple cytofluorometric method useful for live cell cycle study has been adapted for this investigation and can be adopted for other drug studies.

Animals↗
PubMed1980

5'-Nucleotide phosphodiesterase isozyme-V in health, in cancer, and in viral hepatitis.

An abnormal, fast-moving 5'-nucleotide phosphodiesterase isozyme was found in 90.0% of 20 Malaysian patients with primary hepatoma and in 23.5% of 391 Malaysian patients with various malignant diseases; it was also discovered in 42.9% of 14 Malaysian and American patients with clinically active hepatitis B infection; in 16.7% of 18 healthy American blood bank donors who were positive for hepatitis B surface antigen (HBsAg); in 13.9% of 287 healthy Malaysian blood bank donors, some positive for HBsAg; and in none of 160 healthy American donors who were negative for HBsAg. A correlation of this abnormal isozyme with hepatoma and with infectious hepatitis B is clearly evident.

Adult↗
PubMed1980

Serum 5'--nucleotide phosphodiesterase isozyme--V test for human liver cancer.

2,131 coded sera were obtained and tested according to the new 5'-NPDase-V isozyme test. On decoding, 99/126 (79%) samples of primary hepatoma, from the United States and other countries, were positive. In the U. S. group, 51/58 (88%) were positive, 23/58 (40%) had AFP higher than 20 ng/ml. In the non-U. S. group, 48/68 (71%) were positive for 5'-NPDase-V, as compared with AFP elevation in 45/68 (66%). 236/268 (88%) cases of cancer with known liver metastases were positive for 5'-NPDase-V. Of 1,040 cancer patients without liver scan or biopsy evidence of metastasis, 316 were positive. In a follow-up of this group of 316 cases, 109 underlying liver metastases were demonstrated by repeat scan or at autopsy within 3--6 months. All 166 sera from normal healthy persons were negative for 5'-NADase-V. Based on this large panel, 5'-NPDase-V test is a sensitive and an important diagnostic aid for cancer patients, both as an early predictor for liver metastases, and a useful marker for primary hepatoma when no other primary sites are found and when there is no evidence of severe chronic liver disease such as cirrhosis.

Carcinoma, Hepatocellular↗
PubMed1980

Detection of liver metastases with 5'-nucleotide phosphodiesterase isozyme-V in gastrointestinal cancer patients.

An evaluation of the 5'-nucleotide phosphodiesterase isozyme V (5'-NPD-V) test for liver metastases in gastrointestinal (GI) cancer patients was undertaken with a coded serum panel provided by NCI Mayo Clinic. Upon decoding, 28 of 30 patients (93%) with known liver metastases and 11 or 32 patients (36%) with no known liver metastases were positive. In 20 patients with various benign GI diseases, there were 6 (30%) positive for 5'-NPD-V. 2 of these positive patients with benign GI diseases had identifiable liver disorders. Statistical analysis of the data supports 5'-NPD-V can discriminate between GI cancer patients with and without liver metastases and patients with benign GI diseases.

Clinical Enzyme Tests↗
PubMed1979

Serum 5'-nucleotide phosphodiesterase as a predictor of hepatic metastases in gastrointestinal cancer.

Isoenzyme V of 5'-nucleotide phosphodiesterase (5'-NPD-V) is present in the peripheral sera of patients with hepatic metastases. A total of 122 patients underwent prospective serologic analysis followed by operation for primary tumors of the gastrointestinal tract and careful evaluation of the liver. A positive 5'-NPD-V assay was found in fifty-nine of sixty patients with liver metastases. A negative 5'-NPD-V assay was found in forty-three of sixty-two patients with no evidence of hepatic metastases. The accuracy of the test was 84 per cent, and the predictive value was 75 per cent. Serum 5'-NPD-V was abnormal significantly more frequently in patients with metastatic liver disease than were liver scans or carcinoembryonic antigen (CEA), alpha fetoprotein, serum glutamic oxalacetic transaminase (SGOT), and total serum bilirubin or serum alkaline phosphatase levels.

Evaluation Studies as Topic↗
PubMed1978

Nucleases and adenosine 3',5'-cyclic monophosphate phosphodiesterase activities in murine sarcoma virus (Moloney)-infected mice.

To provide information on the role of nucleases in oncogenic virus infection, the activities of 3'-nucleotide phosphodiesterase (3'-NPDase), 5'-nucleotide phosphodiesterase (5'-NPDase), acid deoxyribonuclease (DNase II), and 3',5'-cyclic AMP phosphodiesterase (cAMPDase) in spleen extracts of murine sarcoma virus-infected C57BL/6 inbred mice were studied. At the peak of tumor growth and of the cell-mediated cytotoxic response (CMC) against tumor-associated antigens, 3'-NPDase, 5'-NPDase, and DNase II all showed depressed activities in the spleen, whereas the activity of cAMPDase in the spleen increased at the peak of CMC and remained elevated thereafter. Serum enzyme activities of the infected mice were also determined, and only 3'-NPD-ase in serum correlated well with CMC. Inasmuch as the correlation of the tumor growth with CMC was established in this system, further study on tumors with variance between CMC and growth is necessary to determine if serum 3'-NPDase is a useful biochemical marker for CMC in vivo.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1976

5'-nucleotide phosphodiesterase activity of floxuridine-resistant mouse glioma.

In tissue culture experiments, cells derived from glioma 26, a transplantable tumor of C57B1/6 mice, were sensitive to both floxuridine (5-fluorodeoxyuridine) and 5-fluorodeoxyuridine-5'-(5-iodo-3-indolyl)phosphate, an enzyme-mediated drug activated by 5'-nucleotide phosphodiesterase. When these compounds were tested on the tumor in animals at a level of 5 mg/kg for 5 days, tumor growth was inhibited approximately 20% by both compounds. When higher levels of 5-fluorodeoxyuridine, 100 mg/kg four times weekly throughout the lifespan of the mouse, were given, the tumor, although inhibited at first, developed resistance and continued to grow until it killed the animal. Phosphodiesterase levels in the tumor rose as the tumor grew. On the other hand, thymidine kinase levels dropped as anticipated from the known 5-fluorodeoxyuridine-resistant hepatoma tissue culture data. This enzyme pattern was maintained in transplantable mouse glioma lines established from the resistant tumors. One of these lines, tested at a level of 5 mg/kg for 5 days, showed no response to 5-fluorodeoxyuridine but was still sensitive to 5-fluorodeoxyuridine-5'-(5-iodo-3-indolyl) phosphate. These experiments, therefore, offer a model system and a rationale for the design and study of more compounds that could be activated by the enzyme phosphodiesterase. Such compounds might be used alternatively when resistance to 5-fluorodeoxyuridine develops, a common clinical experience in the use of this anticancer drug.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗