Biomedical subjects

P L Lai

Publications and source records attributed to P L Lai.

13 recordsLinked to original sources

PubMed2001

Surgical treatment of adjacent instability after lumbar spine fusion.

STUDY DESIGN: This study is a retrospective review of 39 patients with previous instrumented lumbar fusion who underwent secondary spine surgery for lumbar adjacent instability. To the authors' knowledge, this is the largest study of surgical treatment of lumbar adjacent instability in the literature to date. OBJECT: This study evaluated the feasibility of adjacent instability treated with medial facetectomy, fusion with autologous bone grafting, and pedicle screw instrumentation. SUMMARY OF BACKGROUND DATA: The surgical treatment of adjacent instability has seldom been discussed. Revision spine fusions are challenged by high pseudarthrosis rates. METHODS: Thirty-nine patients with previous lumbar fusion underwent second lumbar spine surgery for adjacent instability. All were treated with autogenous posterolateral arthrodesis and transpedicle screw fixation in addition to decompressive laminectomy. Medical records, radiographs, and pain scores were obtained. RESULTS: The clinical results were excellent or good in 76.9% of patients, and the radiographic fusion was successful in 37 (94.9%) of patients. Flat back was noted in 8 (20.5%) of patients. In 5 patients (12.8%), neighboring segment breakdown again developed, and 2 of those patients underwent a third lumbar fusion. Dural tear during operation occurred in 2 patients. One patient experienced cauda equina syndrome but recovered bladder function 1 month later. CONCLUSION: Autogenous posterolateral arthrodesis combined with pedicle screw fixation led to successful radiologic and clinical outcome in patients with lumbar adjacent instability. Adequate decompression of the adjacent stenosis requires medial facetectomy, thus preventing aggressive nerve root manipulation and reducing the incidence of dural tear.

Aged↗

PubMed2001

Expression of mutant nuclear beta-catenin correlates with non-invasive hepatocellular carcinoma, absence of portal vein spread, and good prognosis.

beta-catenin has functions both in the cadherin-mediated cell adhesion system and in the signalling pathway that mediates dorsal axis patterning in the embryo; it has been shown to be aberrantly expressed or mutated in diverse types of human tumour, but the biological significance of this remains to be clarified. To elucidate the clinical implications of aberrant beta-catenin expression and the potential differences between mutant and wild-type beta-catenin protein expression in hepatocellular carcinoma (HCC), the protein expression was analysed by immunohistochemical staining, supplemented by the analysis of gene mutation. Among 372 unifocal primary HCCs, beta-catenin was detected in the tumour cell membrane alone in 272 tumours (group A) and also in the nuclei in 100 (group B). In group A, 148 tumours had decreased beta-catenin expression, but the reduction did not correlate with invasion or prognosis. When compared with group A, however, group B had significantly lower frequencies of hepatitis B surface antigen carrier (p=0.015), and alpha-fetoprotein elevation (p=0.0003), but more often had non-invasive HCC (p<0.001) and better survival (p=0.01). Nuclear beta-catenin expression strongly correlated with mutation of the gene (p<0.00001). In group B, HCC with mutant nuclear beta-catenin correlated positively with non-invasive (stage 1) tumour and inversely with portal vein tumour thrombi (stage 3 HCC), and had significantly better 5-year survival, p<0.001 and p<0.0003, respectively. These results suggest that beta-catenin mutation plays an important role in the tumourigenesis of a subset of HCC of good prognosis, and that mutant and wild-type nuclear beta-catenin proteins are not functionally equivalent.

Adolescent↗

PubMed2000

Beta-catenin mutations are associated with a subset of low-stage hepatocellular carcinoma negative for hepatitis B virus and with favorable prognosis.

To better understand the role of beta-catenin mutation in hepatocellular carcinoma (HCC), we correlated the gene mutation with hepatitis virus B (HBV) and hepatitis virus C (HCV) status and the clinicopathological features in 366 patients with resected primary unifocal HCC. beta-Catenin mutations were also analyzed in 55 patients with multifocal HCC (68 tumors). Of the whole series, 57 (13.1%) of 434 tumors examined had beta-catenin mutations, 34 occurred at the serine/threonine residues of the GSK-3beta region of beta-catenin. Outside the GSK-3beta phosphorylation site, codons 32 and 34 were two mutational hot spots (17 tumors). The non-HBV-related HCC that was predominantly HCV related had a higher frequency of mutation (P: < 0.00001) and more frequent mutations at codon 45 than HBV-related HCC. HBV-related HCC had a younger mean age (P: < 0.00001), and higher male-to-female ratio (P: < 0.003) and positive familial history of HCC (P: < 0.014). Among 366 unifocal HCCs selected for clinicopathological analysis, beta-catenin mutations were associated with grade I (P: = 0.005) and stage I and II HCC (P: < 0.0001), and a better 5-year survival rate (P: = 0. 00003). These findings suggest mechanisms for beta-catenin mutations differ between HBV-related and non-HBV-related HCCs, and that beta-catenin mutation is a favorable prognostic factor related to low stage. beta-Catenin mutation was associated with nuclear expression of the protein (P: < 0.00001), but we failed to detect point or large fragment deletion mutation in 39 HCCs with nuclear beta-catenin expression, presumably wild-type protein. HCCs expressing mutant nuclear beta-catenin had a better 5-year survival rate (P: < 0.007), suggesting that mutant and wild-type nuclear beta-catenin proteins are not functionally equivalent and deserve more studies for further clarification.

Base Sequence↗

PubMed2000

Kernel and nonlinear canonical correlation analysis.

We review a neural implementation of the statistical technique of Canonical Correlation Analysis (CCA) and extend it to nonlinear CCA. We then derive the method of kernel-based CCA and compare these two methods on real and artificial data sets before using both on the Blind Separation of Sources.

Algorithms↗

PubMed1998

Simultaneous anterior dislocation of the shoulder and fracture of the ipsilateral humeral shaft. Two case reports.

Two patients with anterior dislocation of the shoulder and ipsilateral fracture of the shaft of the humerus have been studied and the mechanism of their injuries has been documented. Closed reduction of the dislocations was performed under anaesthesia during surgery for humeral fixation with a dynamic compression plate. The fractures and dislocations healed without any problems at 6 to 9 months postoperatively. At recent follow-up, one patient had returned to work and regained normal mobility. The other patient had the sequelae of a brachial plexus injury. The literature on this subject is reviewed.

Adult↗

PubMed1998

Gouty os trigonum tarsi: case report.

Os trigonum tarsi is found in 7% of the world adult population. However, it rarely causes symptoms. The majority of patients with os trigonum tarsi are found incidentally. This condition is often found in ballet dancers, javelin throwers and soccer players. It rarely produces symptoms in normally active adults. The etiology of os trigonum syndrome is impingement of an unfused ossicle or a fractured posterior lateral tubercle of talus over the posterior rim of tibial plafond. We present a case of os trigonum syndrome in a young man. His posterior heel pain was due to tophaceous gout around the os trigonum tarsi, instead of the common pathogenesis of repeated hyperflexion of the ankle joint. Pictures of the specimen showed marked giant cell reaction which resulted in pseudotumor formation. We reviewed the clinical characteristics of os trigonum tarsi and gout and present the treatment of our patient.

Adult↗

PubMed1997

Cloning and expression of a developmentally regulated transcript MXR7 in hepatocellular carcinoma: biological significance and temporospatial distribution.

Using the differential display method to analyze mRNA expression in hepatocellular carcinoma (HCC) and nontumor livers, we cloned a full-length cDNA of 2263 bp, which was designated GTR2-2 and was identical with MXR7. The MXR7 mRNA was detected in 143 of 191 (74.8%) primary and recurrent HCCs taken from 154 patients but only in 5 (3.2%) nontumor livers. MXR7 mRNA was detected in one of two hepatoblastomas but not in hepatocellular adenoma, cholangiocarcinoma, or metastatic carcinomas to the liver. In human cancer of other anatomical sites, MXR7 mRNA was detected in low levels in one Wilms' tumor and in 4 of 40 gastric adenocarcinomas but not in several other types of cancer and 21 nonhepatocellular human tumor cell lines examined. MXR7 mRNA was expressed in high levels in the placenta, fetal liver, lung, and kidney, but it was undetectable in adult liver and was expressed in very low levels in adult lung and kidney. Our observations suggest that the MXR7 gene is regulated developmentally and expressed preferentially in HCC. To study its potential biological significance, we selected 113 patients who had unicentric primary HCC and had been followed for more than 4 years for further analysis. The MXR7 mRNA expression correlated closely with elevated serum alpha-fetoprotein (AFP) levels (88 versus 55%; P = 0.0001) and with expression of AFP mRNA (87 versus 55%; P = 0.005) and CD24 mRNA in HCC (80 versus 50%; P < 0.04), high tumor grade (76 versus 56%; P = 0.05), and tumor invasion (76 versus 55%; P < 0.05), but not with patient outcome. In HCC < or =3 cm, the frequency (77%) of MXR7 mRNA expression was significantly higher than that of elevated serum AFP (43%; P < 0.007) and AFP mRNA expression in HCC (41%; P < 0.004). Thus, MXR7 may serve as a sensitive early tumor marker for HCC and warrants more study to better understand its biological function.

Adolescent↗

PubMed1994

Allelotype and loss of heterozygosity of p53 in primary and recurrent hepatocellular carcinomas. A study of 150 patients.

BACKGROUND: The allelotype and loss of heterozygosity (LOH) of the p53 gene in human hepatocellular carcinoma (HCC) were studied in 150 patients with resected primary HCC and 18 with recurrent HCC. METHODS: DNA samples of paired HCC and livers were cut with BanII enzyme for the study of p53 allelotype and allele loss. The medical records of the patients were carefully reviewed. RESULTS: Sixty-four (42.7%) patients were heterozygous for the p53 gene, 69 (46%) were homozygous for the 1.5/1.4 kb small (S) allele, and 17 (11.3%) were homozygous for the 2.9 kb large (L) allele. The frequencies of the minor L allele (0.323) and of the major S allele (0.677) in this population of Chinese patients differed from the frequencies previously reported for North American Caucasians (0.13 and 0.87, respectively). The heterozygous patients tended to have lower serum hepatitis B surface- and e antigens (HBsAg and HBeAg) and higher diabetes mellitus (DM) than did homozygous patients (SS and LL). Thirty-seven (57.8%) of the 64 heterozygous patients had a tumor-specific p53 allele LOH, being two times more common in HCC tumors larger than 8 cm than in HCC tumors 2 cm or smaller. The frequency of DM was four times higher in the heterozygous patients who had p53 LOH than in those who retained both alleles. LOH of p53 did not correlate with tumor invasiveness or differentiation, hepatitis B or C virus infection, or prognosis. CONCLUSION: The allelotype of p53 gene in HCC correlates with HBsAg and HBeAg seropositivities and DM. LOH of the p53 gene is a common event in HCC, correlates with DM, and occurs less often in familial HCC. LOH can identify the clonal origin of recurrent HCC but is not a critical prognostic factor.

Adult↗

PubMed1994

Genetic alterations at the splice junction of p53 gene in human hepatocellular carcinoma.

The tumor-suppressor gene p53 may transactivate the transcription of genes that down-regulate cellular growth-related genes and may become oncogenic as a result of the production of mutant proteins or the loss of its protein expression. This study reports that alterations of the highly conserved consensus intervening sequences at the splice junctions may lead to the inactivation of the p53 gene. Analyses with the combined polymerase chain reaction and single-strand conformational polymorphism and direct DNA sequencing of DNAs amplified by means of asymmetric polymerase chain reaction demonstrated sequence alterations at the splice junctions of introns 5 and 7 in four human hepatocellular carcinomas, with a single base substitution at the splice junction in three and a 10-bp deletion starting from the dinucleotide AG of the acceptor site of intron 5 in the fourth. Restriction fragment length polymorphism analysis disclosed allele loss in all three informative cases. The p53 mRNA concentrations were remarkably reduced or undetectable in two hepatocellular carcinomas, whereas the two tumors (cases 2 and 3) that had single base changes at the acceptor site of intron 7 had both normal and abnormally sized p53 mRNAs. Immunocytochemistry failed to detect the wild-type and mutant p53 proteins in all four tumors. Western-blot analysis disclosed an abnormal, larger p53 protein of 55 kD in the tumor of case 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Expression of p53 gene in 184 unifocal hepatocellular carcinomas: association with tumor growth and invasiveness.

To elucidate the biological significance of the p53 gene expression in human hepatocellular carcinoma (HCC), the p53 protein was studied in 184 resected unifocal primary HCCs, including 102 small (< or = 5 cm) and 82 large HCCs (> 5 cm), using immunocytochemistry. The p53 mRNA expression was analyzed in 69 cases using Northern hybridization. The p53 protein, which was detected in 58 HCCs (31.5%), was overexpressed more frequently in HCC with elevated serum alpha-fetoprotein level (37.9 versus 25%, P < 0.04), in large HCC (39.0 versus 25.5%, P < 0.03), and in invasive HCC (35.1 versus 13.3%, P < 0.01). The overexpression of p53 protein closely correlated with p53 mRNA overexpression (75 versus 44.4%, P < 0.003), and p53 gene mutation (76.9 versus 19.2%, P < 1 x 10(-9)). HCCs with p53 protein expression (group A) and those negative for both p53 protein and mRNA expression (group B) had an unfavorable outcome, while HCC with no p53 protein but with p53 mRNA overexpression (group C) had the best outcome; the 4-year survival was 26.1, 26.3, and 62.5%, respectively. The p53 gene mutation was significantly higher in group A HCC (76.9%) than in groups B (27.3%) and C (23.5%), P < 0.0001. The results suggest that the p53 protein and mRNA expression patterns in HCC correlate with p53 gene mutation and tumor behavior and may serve as a molecular prognostic factor.

Blotting, Northern↗

PubMed1993

Amplification of the c-myc gene in human hepatocellular carcinoma: biologic significance.

To elucidate the prevalence and biologic significance of the c-myc gene in human hepatocellular carcinoma (HCC), DNA samples were taken from the paired tumorous and nontumorous tissues of 77 cases of resected primary HCC and were analyzed by Southern blot hybridization. We demonstrated modest, but significant c-myc amplification (group A) in 28 (36.4%) of the cases: 1.6- to 2.0-fold in 18, 2.1- to 3.0-fold in four, and > 3.0-fold in six. Compared to HCC without c-myc amplification (group B), group A HCC occurred more often in patients < 50 years old (54.5% vs 29.1%, p < 0.02) with serum alpha-fetoprotein (AFP) levels > 320 ng/mL (61.1% vs 14.6%, p < 0.00002). Group A HCC occurred more frequently in patients with hepatitis B virus infection than in those with hepatitis C virus infection (p < 0.03). Group A HCC was more likely to be poorly differentiated (44.8% vs 10.5%, p < 0.004) and associated with intrahepatic portal vein spread (57.1% vs 28.6%, p < 0.02). The c-myc amplification did not correlate with sex or tumor size. For small HCC, group A had a worse one-year survival rate than group B (72.2% vs 90.9%, p < 0.04). These findings suggest that c-myc amplification is not an uncommon event in human hepatocarcinogenesis, occurs more frequently in young patients who have an elevated serum AFP level or HBV infection, and is related to the biologic behavior of HCC.

Adult↗

PubMed1993

Expression and hypomethylation of alpha-fetoprotein gene in unicentric and multicentric human hepatocellular carcinomas.

The messenger RNA and DNA methylation of the alpha-fetoprotein gene were studied in 101 resected primary hepatocellular carcinomas, of which 93 were unicentric and 8 were multicentric. Fifty-five were 5 cm or less in diameter (small) and 46 were more than 5 cm in diameter (large). In 48.5% of the cases, we detected alpha-fetoprotein messenger RNA in hepatocellular carcinomas, more frequently in large (60.9%) than in small (38.2%; p < 0.00001) but not in any of the nontumorous livers. The alpha-fetoprotein messenger RNA was detected in 83%, 70% and 6.8% of patients with serum alpha-fetoprotein levels of 320 ng/ml or more, 100 to 319 ng/ml and less than 100 ng/ml, respectively. This finding suggests that alpha-fetoprotein gene expression in hepatocellular carcinoma contributes to the serum alpha-fetoprotein elevation in patients with hepatocellular carcinoma. alpha-Fetoprotein messenger RNA appeared as a major band of 2.4 kb, with two minor species of about 6.5 and 3.6 kb in the hepatocellular carcinoma and the fetal liver. Hypomethylation of the 5' end of the alpha-fetoprotein gene was detected in 78.3% of hepatocellular carcinomas expressing alpha-fetoprotein messenger RNA but infrequently (16.7%) in hepatocellular carcinomas with no detectable alpha-fetoprotein messenger RNA (p < 0.0003). This finding suggests that hypomethylation at the 5' region of the gene is associated with alpha-fetoprotein gene reexpression in hepatocellular carcinoma. The alpha-fetoprotein gene expression helped to differentiate unicentric from multicentric hepatocellular carcinomas and to identify other hidden alpha-fetoprotein-secreting hepatocellular carcinomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMedDate not supplied

A new assay for hepatitis C virus (HCV) core antigen detection: an alternative to nucleic acid technologies in positive or indeterminate anti-HCV subjects?

Markers of viral replication are fundamental tools for understanding the mode of transmission, diagnosis and management of hepatitis C virus (HCV) infection. A new enzyme-linked immunosorbent assay for quantitative detection of free and complexed HCV core antigen (HCV Ag) has been developed. The aim of this study is to evaluate the clinical performance of the new test and compare it with the most widely used commercially available RT-PCR-based assay. To determine the cut-off value we tested 60 samples from anti-HCV negative samples and selected a qualitative cut-off value of 3 pg/ml. To evaluate the usefulness of the new assay in confirming serologically indeterminate results we collected 62 sera. To evaluate the HCV Ag and HCV-RNA relationship we tested 245 samples from patients with different clinical conditions. The results of 61 out of 62 (98.4%) anti-HCV indeterminate samples were found to agree, whereas only one serum was found to be RT-PCR positive and HCV Ag negative. We also found the results to agree in 77.6% (190/245) of the samples from infected patients, while we observed higher agreement in untreated patients, both with and without evidence of liver damage. The correlation coefficient (r) observed between HCV Ag and HCV-RNA was 0.88. The regression line meets the cut-off value at an HCV-RNA concentration of approximately 40,000 IU/ml. In conclusion, we found that the results from the total HCV Ag test agree with the RT-PCR results and therefore we believe that this test could become a useful tool for the diagnosis and management of HCV infection.

Hepatitis C Antigens↗