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Biomedical subjects

L H Wu

Publications and source records attributed to L H Wu.

At least 55 records · Page 3Linked to original sources

Can determination of the proliferative capacity of the nontumor portion predict the risk of tumor recurrence in the liver remnant after resection of human hepatocellular carcinoma?

To test the hypothesis that increased proliferative capacity of cells in a liver remnant is a risk factor for tumor recurrence in patients who have undergone liver resection for hepatocellular carcinoma, DNA flow-cytometric measurement and cell-cycle analysis of the nontumor parts of resected hepatocellular carcinomas (tumor size < 5 cm) were performed. The disease-free survival rates 1, 2, 3 and 4 yr after surgery were 64%, 58%, 43%, and 36%, respectively. Proliferative capacity (fractions of synthetic, postsynthetic and mitotic phases) of the nontumor parts, irrespective of liver pathology, was higher than that of normal liver and statistically lower than that of tumor parts from resected hepatocellular carcinoma specimens. Livers with chronic active hepatitis (+) and with hepatocyte dysplasia (-) had significantly lower proliferative activity than did those with chronic active hepatitis (-) and with hepatocyte dysplasia (+), respectively [corrected]. We saw no significant difference in proliferative capacity between patients with and without cirrhosis. Disease-free-survival analysis showed that the presence of liver pathology (hepatitis B infection, cirrhosis, chronic active hepatitis and hepatocyte dysplasia) was not the factor linked to tumor recurrence in the liver remnant and that a marked increase in proliferative capacity (> or = 18%), regardless of liver pathology, was the risk factor linked to tumor recurrence after liver resection. We conclude that there is some degree of increased proliferative capacity in the nontumor parts of resected hepatocellular carcinomas and that a marked increase in the proliferative capacity (> or = 18%) of the nontumor part is a significant risk factor in predicting tumor recurrence in the liver remnant after liver resection.

Aged↗

Cloning, expression, and characterization of a gene encoding the human angiotensin II type 1A receptor.

The human angiotensin II (AII) type 1a receptor gene and its upstream control sequence has been cloned from a human leukocyte genomic library. The promoter element CAAT and TATA sequences were found at -602 and -538, respectively, upstream from the translational initiation site. The deduced protein sequence is homologous to rat and bovine AT1a receptors (94.7% and 95.3% identity). The expressed gene exhibited high-affinity AII and Dup753 binding and was functionally coupled to inositol phosphate turnover. Northern analysis of human tissues showed AT1 receptor mRNA expression in placenta, lung, heart, liver, and kidney. Using 5' untranslated and coding sequence as probes in a Southern blot analysis, it was established that another AT1 subtype exists in the human genome.

Amino Acid Sequence↗

Replacement of lysine-181 by aspartic acid in the third transmembrane region of endothelin type B receptor reduces its affinity to endothelin peptides and sarafotoxin 6c without affecting G protein coupling.

A conserved aspartic acid residue in the third transmembrane region of many of the G protein-coupled receptors has been shown to play a role in ligand binding. In the case of endothelin receptors, however, a lysine residue replaces this conserved aspartic acid residue. To access the importance of this residue in ligand binding, we have replaced it with an aspartic acid in the rat endothelin type B (ETb) receptor by PCR mediated mutagenesis. The binding characteristics and functional properties of both the wild type and mutant receptors were determined in COS-7 cells transiently expressing the cloned receptor cDNAs. Using 125I-ET-1 as the radioactive peptide ligand in displacement binding studies, the wild type receptor displayed a typical non-isopeptide-selective binding profile with similar IC50 values (0.2-0.6 nM) for all three endothelin peptides (ET-1, ET-2, and ET-3) and sarafotoxin 6c (SRTX 6c). Interestingly, the mutant receptor showed an increase in IC50 values for ET-1 (5 nM), ET-2 (27 nM), and ET-3 (127 nM) but displayed a much larger increase in IC50 value for SRTX 6c (> 10 uM). The lysine mutant receptor still elicited full inositol phosphate (IP) turnover responses in the presence of saturating concentrations of endothelins (10 nM of ET-1, 100 nM of ET-2, or 1 uM of ET-3), indicating that the mutation (K181D) did not affect the coupling of mutant receptor to the appropriate G protein. These results demonstrate that lysine-181 on the receptor is important for binding ET peptides; however, it is required for binding the ETb selective agonist-SRTX 6c.

Animals↗

Substitution of lysine-181 to aspartic acid in the third transmembrane region of the endothelin (ET) type B receptor selectively reduces its high-affinity binding with ET-3 peptide.

In the G protein-coupled receptor family, a highly conserved aspartic acid located within the third transmembrane domain has been shown to be involved in ligand binding. Within the endothelin (ET) peptide receptor family, this aspartic acid has been replaced by a lysine. To assess the importance of this residue in ET binding, the lysine (position 181) of rat ET type B receptor was replaced by an aspartic acid. The effects on ligand binding and phosphoinositide turnover of both the wild-type and K181D mutant receptors were examined using transient receptor expression in COS-7 cells. Using [125I]ET-1 as the radioactive peptide ligand in displacement binding studies, the wild-type receptor displayed a typical non-isopeptide-selective binding profile with similar IC50 values (0.2-0.6 nM) for all three ET peptides (ET-1, ET-2, and ET-3). The mutant receptor showed an increase in IC50 values for ET-1 (5 nM), ET-2 (27 nM), and ET-3 (127 nM). The K181D mutant receptor still elicited full inositol phosphate (IP) accumulation responses in the presence of saturating concentrations of ETs (10 nM of ET-1, 100 nM of ET-2, or 1 microM of ET-3), indicating that the mutation did not affect G protein coupling.

Animals↗

Prediction of relapse or survival after resection in human hepatomas by DNA flow cytometry.

To investigate the change of DNA content and the effect of synthetic phase (S-phase) fraction on hepatocytes and hepatomas, DNA content and S-phase fraction were measured by flow cytometry in human livers and hepatoma tissues. The ploidy status of nontumor parts of resected hepatoma, fetal liver, and focal nodular hyperplasia were diploid, similar to that of the normal liver. Three patterns of DNA ploidy in human hepatoma cells were newly classified, namely, pattern I, diploid tumors; pattern II, aneuploid tumors with single G0/G1 peak; and pattern III, aneuploid tumors with more than one G0/G1 peaks. Among the 130 resectable hepatomas measured for DNA ploidy status, 84 (64.6%) were pattern I, 20 (15.4%) pattern II, and 26 (20%) pattern III. Multivariate analyses for those 130 patients who underwent hepatic resection showed that, in addition to tumor size, DNA ploidy was another prognostic factor in predicting overall survival and disease-free survival. Patients with small tumors (less than 5 cm) had a significantly higher overall survival rate than those with large tumor (greater than 5 cm). Patients with pattern III hepatomas had a significantly lower overall survival rate and a higher recurrent rate than did those with pattern I or pattern II tumors. The S-phase fraction was a significant predictor of overall survival rate in patients with pattern II, but not with pattern I, tumors. We conclude that DNA flow-cytometric measurements of ploidy and S-phase fraction are potential important prognostic predictors in patients with resectable hepatomas.

Adult↗

Effect of sodium butyrate on glucocorticoid-sensitive and -resistant P1798 lymphosarcoma.

This study aims to examine the effect of sodium butyrate on the viability and the level of glucocorticoid receptors and cells cycle progression in glucocorticoid-sensitive and -resistant P1798 cells. Our results indicated that low levels of sodium butyrate had no effect on either the viability or the receptor level. However, high-level (5 mM) sodium butyrate appeared to reduce cell viability as well as the glucocorticoid receptor level. On the other hand, sodium butyrate inhibited cell cycle progression in a dose-dependent manner. This response was similar in both the glucocorticoid-sensitive and -resistant P1798 cells. Results from this study suggested that the sodium butyrate induced effect may be cell cycle related.

Butyrates↗

The rate and locus of development of rat vallate taste buds.

Several hundred taste buds develop and mature in the trench walls of the rat's vallate papilla during the first 3 months after birth. The objective of this investigation of taste bud development was to determine: (i) whether the vallate papilla has local growth zones where new taste buds form, (ii) whether new taste buds arise by the division of mature taste buds, (iii) how many days are required for a new taste bud to mature, and (iv) whether a taste pore forms as the taste bud reaches a critical volume. Camera lucida drawings were made of more than 4000 iron hematoxylin-stained, serially sectioned, vallate taste buds. The relative abundance of immature taste buds declined exponentially with age, from 18% of the mature taste buds at day 15 to 2% at day 90. At days 21, 33 and 45 most of the immature taste buds (those lacking a taste pore) were located in growth zones at the anterior and posterior extremes of the vallate trench. A mean of 10.5 days was required for the maturation of each cohort of immature taste buds present at days 15, 21, 33 and 45. Vallate taste buds were added de novo; fission of mature taste buds was rare. Taste buds varied widely in the taste bud volume at which a pore formed and in the final volume of the taste bud.

Animals↗

Neural control of ectopic filiform spines in adult tongue.

The tongue surface directly above a fungiform taste bud is flat, thinly keratinized, and free of filiform spines. We examined fungiform papillae in serial sections of rat and gerbil tongues after unilateral transection of the chorda-lingual nerve had caused many fungiform taste buds to degenerate. Such empty fungiform papillae often formed a solitary keratinized outgrowth that closely resembled the spine of an ordinary filiform papilla. By six months an ectopic spine was found on 61% of empty fungiform papillae, but never on fungiform papillae that contained a taste bud. Experimental innervation of the tongue reduced the incidence of ectopic filiform spines in proportion to the cross-sectional area of the trigeminal nerve branches tested (the mylohyoid nerve, the lingual nerve, lingual + mylohyoid or lingual + auriculotemporal nerves). The chorda tympani nerve was 60 times more effective than trigeminal nerves in preventing ectopic filiform spines. We suggest that positive and negative trophic actions are normal characteristics of taste axons, for they promote the formation of taste buds and prevent the expression of ectopic filiform spines. By preventing the outgrowth of ectopic spines on fungiform papillae, taste axons maintain a thinly keratinized apical surface that can be breached by the taste receptor cells.

Animals↗

Early and late results of total gastrectomy in treatment of advanced adenocarcinoma of the cardia.

Sixty-six patients with advanced adenocarcinoma of the cardia underwent total gastrectomy between 1978 and 1986. The operative morbidity rate was 7.5% and the hospital mortality rate (1 month) was 1.5%. The postoperative 1, 3, 4, and 5 year survival rates were 69%, 30.7%, 20% and 13.8% respectively. The quality of life after surgery was improved. Pathological type, lymph node metastasis, completeness of resection and postoperative chemotherapy were the main factors influencing postoperative survival time. Indications for total gastrectomy and the advantages of transthoracic total gastrectomy are discussed.

Adenocarcinoma↗

Isolation and characterization of myoglobin and its two major isoforms from sheep heart.

We isolated myoglobin from sheep heart by homogenizing cardiac muscle in 70%-saturated ammonium sulfate, followed by chromatography on a column containing carboxymethyl(CM)-Sephadex gel. Two major isoforms of myoglobin, designated Mb 7.9 and Mb 8.1, were separated by chromatofocusing and were distinguished by their different patterns seen on either isoelectrofocusing or on electrophoresis on polyacrylamide gel. The isoelectric points of the major bands of Mb 7.9 and Mb 8.1 were 7.4 and 7.16, respectively. Both isoforms were identical in size when examined by gel filtration chromatography but differed slightly when analyzed by polyacrylamide gradient gel in the presence of sodium dodecyl sulfate. The Mr of Mb 7.9 (15,900 Da) is slightly smaller than that of Mb 8.1 (18,400 Da). When reacted against rabbit anti-sheep myoglobin, two isoforms also appeared as two nonidentical precipitin lines on agarose gel.

Animals↗

Glucocorticoid receptors in hepatocellular carcinoma and adjacent liver tissue.

Glucocorticoid and progesterone receptors, tyrosine aminotransferase, gamma-glutamyltransferase and alpha-fetoprotein levels were determined in human hepatocellular carcinoma (HCC) and adjacent liver tissues. Glucocorticoid receptor was present in seven of ten HCC samples, values ranged from 1.9 to 66.8 fmol/mg protein. Progesterone receptor was present in two of ten HCC samples with values of 1.7 and 7.2 fmol/mg protein, respectively. In the adjacent liver tissues, no measurable progesterone receptor was found and only one sample had glucocorticoid receptor with a value of 3.0 fmol/mg protein. The increase of glucocorticoid receptor in HCC samples was coincident with a decreased level of tyrosine aminotransferase and an increased level of gamma-glutamyltransferase. No correlation was found among glucocorticoid receptor level, serum or tissue alpha-fetoprotein levels. The presence of glucocorticoid receptors in HCC suggest that hormones may play an important role in the formation of hepatoma, and hormonal therapy may be useful for patients with HCC.

Carcinoma, Hepatocellular↗

Controlled release of adriamycin HCl from polymeric needle devices.

Two types of polymeric needle devices (reservoir type and matrix type) were prepared. The release behavior and mechanism of adriamycin HCl from these needle devices were investigated and deduced. Adriamycin HCl released from reservoir type needle devices exhibited a zero order release kinetic, but a Higuchi membrane-diffusion controlled model was shown in matrix type needle devices. A lag time and burst effect were obtained in reservoir type and matrix needle devices, respectively. The release of adriamycin HCl from these needle devices was controlled and can be monitored by adding a hydrophilic or hydrophobic additive.

Biocompatible Materials↗

A method for purification of bacterial R-type lipopolysaccharides (lipooligosaccharides).

A new gel filtration method was developed for purification of R-type lipopolysaccharides (lipooligosaccharides) from some nonenteric gram-negative bacteria, including Neisseria meningitidis, Haemophilus influenzae, and Bordetella pertussis. These wild-type lipooligosaccharides are poorly extractable by the phenol-chloroform-ether extraction method of C. Galanos, O. Luderitz, and O. Westphal [1969) Eur. J. Biochem. 9, 245-249) and therefore a new procedure was developed for their isolation. The lipooligosaccharides (LOS) were first extracted by hot phenol-water, treated with RNase, then disaggregated in deoxycholic acid, and purified by gel filtration on Sephadex G-75. By comparison the conventional hot phenol-water purification method using repeated ultracentrifugations yielded less LOS. The yield of LOS by gel filtration was 30 to 108% higher and the purity was better.

Bordetella pertussis↗

Clinical and pathologic characteristics in patients with tracheobronchial tumor: report of 50 patients.

From January, 1961, to July, 1985, 50 patients in the Peking Union Medical College Hospital with intraluminal tracheobronchial tumors were operated on. There was no gender or age predominance either in the 24 patients with tracheal tumor or in the 26 patients with bronchial tumor. The 13 cell types found in these patients' specimens were divided into four groups: malignant, low-grade malignant, benign with tendency to recur and benign without tendency to recur. Squamous cell carcinoma and adenoid cystic carcinoma were the most common tumors of the trachea. Carcinoid and adenoid cystic carcinoma were the most common tumors of the bronchus in this group of patients. Conservative excision with postoperative irradiation may be sufficient for patients with advanced lesions of low-grade malignancy.

Adolescent↗

Genetic study of retinitis pigmentosa in China.

A total of 190 patients (379 eyes), from 169 families, with retinitis pigmentosa were studied in four genetic aspects in China. A large percentage (58.9%) of affected patients appear to be sporadic cases with no family history of disease. In dermatoglyphic analysis, comparing with the controls, the increment of eight or more whorls, the increase of the number of simian and the value of atd angle in 110 patients with retinitis pigmentosa were statistically significant. In addition, the incidence of G6PD deficiency in retinitis pigmentosa (7.89%) is higher than that (3.5%) of a nonaffected population in the same area. However, there is no significant difference of ABO blood typing between 176 patients with retinitis pigmentosa and the normal population of China.

ABO Blood-Group System↗

Study of aging macular degeneration in China.

Studies of the epidemiology, pathogenetic factors and visual function of aging macular degeneration (AMD) show that it has become an ocular disease worth noticing in China. Although most AMD cases were of the dry type and the patients had rather good visual acuity, various determinations of visual function showed different degrees of impairment. Controlling light exposure and improving trace metal metabolism may be helpful for early prevention and treatment of AMD. It will also be an important factor in the prevention of blindness in Asian nations.

Aged↗