Search PubMed⌕ Search

Biomedical subjects

W Y Chan

Publications and source records attributed to W Y Chan.

At least 91 records · Page 5Linked to original sources
PubMed1997

Polysaccharopeptide from the mushroom Coriolus versicolor possesses analgesic activity but does not produce adverse effects on female reproductive or embryonic development in mice.

1. Coriolus versicolor polysaccharopeptide has been reported to exert immunomodulatory and antitumor actions. The present study showed that it exhibits analgesic activity in the hot-plate test upon intraperitoneal administration to ICR mice. 2. It did not affect ovarian steroidogenesis, ovulation and midterm gestation in mice. It did not exert an adverse effect on mouse embryonic development either, as evidenced by the lack of an effect on somite number, axial length and the incidence of abnormalities in heartbeat, yolk sac circulation, optic vesicle, otic vesicle, shape of body axis, forelimb buds, branchial apparatus, cranial neural tube and head size. 3. Its analgesic activity would add to its attribute as an immunomodulatory and antitumor drug.

Analgesics↗
PubMed1997

Characterization and cellular localization of PSG in rat testis.

In order to establish the rat testis as a model system for studying the human pregnancy-specific beta1-glycoprotein (PSG), expression and cellular distribution of PSG in rat testis were examined. Three partial PSG cDNAs, namely, rnCGM6, rnGCM7, and rnCGM8 were obtained when rat testis cDNA libraries were screened with a human placental PSG cDNA probe. Unlike the human PSGs, the rat PSGs show less nucleotide and amino acid sequence homology among family members. The rat PSGs also have multiple truncated leader sequences followed by immunoglobulin variable-like N domains while human PSGs have a single N domain. Examination of the testis, intestine, kidney, liver, lung, and muscle of male rats by reverse transcription-polymerase chain reaction (RT-PCR) with nested gene-specific primers showed that rnCGM6 was present only in the testis, while rnCGM8 was present in the testis, intestine and lung. On the other hand rnCMG7 was found in all tissues examined. Furthermore, rnCGM7 transcript was present in all somatic cells examined whereas rnCGM6 was predominantly in myoid cells and rnCMG8 in Leydig cells. These results suggest that there is cell-specificity in the expression of PSGs in the rat testis and that the rat testis is a good model for studying the biological activities of the PSGs.

Amino Acid Sequence↗
PubMed1997

The mechanism of Epstein-Barr virus infection in nasopharyngeal carcinoma cells.

To investigate the relationship between Epstein-Barr virus (EBV) and nasopharyngeal carcinoma (NPC) cells, we examined the pathway of EBV infection in NPC cell lines. We used immunolocalization to investigate the EBV receptor (C3d-R) and polymeric immunoglobulin receptor [secretory component (SC) protein]. We incubated IgA anti-EBV and EBV particles with NPC cells and observed the EBV DNA signal by in situ polymerase chain reaction hybridization and polymerase chain reaction plus Southern blotting. We also colocalized SC protein and EBV RNA in NPC biopsy specimens. Results showed that: 1) NPC cells did not express the EBV receptor but did express SC protein in each line; 2) SC protein was also expressed in some tumor cells but not in untransformed squamous metaplastic epithelia in NPC biopsy specimens; 3) EBV could infect NPC cells through an EBV-IgA and SC complex and retained an EBV viral genome in their nuclei; SC expression could be down-regulated by EBV proteins; and 4) in biopsy specimens, a fraction of tumor cells showed SC protein expression; only a portion of tumor cells contained EBV, and of these cells only a few expressed SC protein. These findings indicate that EBV cannot infect untransformed nasopharyngeal squamous metaplastic epithelia but can enter NPC cells through IgA-mediated endocytosis.

Carcinoma↗
PubMed1997

Segregation of Allgrove (triple-A) syndrome in Puerto Rican kindreds with chromosome 12 (12q13) polymorphic markers.

Allgrove syndrome (AS), also known as triple-A syndrome, is a rare cause of congenital adrenal insufficiency due to adrenocorticotropic hormone resistance. It is inherited in an autosomal recessive manner and is associated with achalasia, alacrima, and other neurological abnormalities, including autonomic, sensory, and upper- and lower-motor neuropathy, deafness, and mental retardation. Although the etiology of AS remains unknown, recently the disease was linked to a chromosome 12 locus (corresponding cytogenetic band 12q13) in consanguineous families of European ancestry. In the present study, we investigated four nonconsanguineous families with documented inheritance of AS for linkage with the reported 12q13 locus. Eighteen subjects were studied, of whom five were affected by AS. DNA was extracted from peripheral blood lymphocytes and amplified by standard methods with primers from polymorphic sequence tagged sites (STSs) located in the chromosome 12q13 region. Two-point logarithm-of-odds (LOD) score analysis revealed a maximum LOD score of 1.7 for STSs D12S361 and D12S368 without any recombinants [recombination distance (theta) = 0]. Multipoint linkage analysis defined an area of estimated genetic distance less than 0.5 cM (approximately 500,000 bp) between STSs D12S361 and D12S359 that is most likely to contain the AS gene(s). We conclude that, in Puerto Rican families, AS segregates with polymorphic markers that have been mapped to the chromosome 12q13 locus, revealing the absence of heterogeneity for this syndrome in a genetically distinct population. Candidate genes in the region include those that code for several of the keratin proteins, transcription factors, and others.

Abnormalities, Multiple↗
PubMed1996

Importance of the Glu 160 and Glu 189 residues to the various biological activities of the ribosome inactivating protein trichosanthin.

Site-directed mutagenesis of trichosanthin (TCS), a ribosome inactivating protein with a broad spectrum of biological activities, was carried out to ascertain the importance of the Glu 160 and Glu 189 residues to the protein synthesis-inhibitory, antiproliferative, immunosuppressive and embryotoxic activities of TCS. Replacement of Glu 160 with alanine and with aspartate produced muteins, designated [E160A] and [E160D] respectively, with considerably attenuated protein synthesis-inhibitory, antiproliferative, immunosuppressive and embryotoxic activities, indicating that Glu 160 in TCS plays a role in its biological activity. [E160A] was, however, more potent than [E160D] because in the former mutein, Glu 189 constitutes a back-up of the carboxylate group but in the latter mutein, the negative charge from Asp is at a suboptimal position. The mutein [E160A, E189A] formed by mutation of both Glu 160 and Glu 189 retained considerable embryotoxic activity, suggesting that other amino acids in the active site were able to partially replace the role of Glu 160 and Glu 189. The TCS muteins also exhibit higher toxicity toward cultured embryos than cultured cells (spleen cells and tumor cells).

Animals↗
PubMed1996

SPARC, an extracellular matrix protein with tumor-suppressing activity in human ovarian epithelial cells.

SPARC, also termed osteonectin, BM-40 and 43K protein, is an acidic, cysteine-rich component of the extracellular matrix that has been shown to be directly regulated by progesterone and dexamethasone and indirectly by cytokines. By RNA fingerprinting technique, we cloned a SPARC homolog from the normal human ovarian surface epithelial (HOSE) cells and demonstrated that it is expressed at high levels in the normal HOSE cells but at much lower levels in ovarian carcinoma cells in vitro and in vivo. Subsequently, we transfected the full length SPARC cDNA into an ovarian carcinoma cell line SKOV3 and showed that it reduced the growth rate of the cancer cell line in culture and reduced the cell's ability to induce tumours in nude mice. These results suggest that SPARC may play an important role in growth and and differentiation of the HOSE cells and support the hypothesis that SPARC functions as a tumor suppressor.

Animals↗
PubMed1996

Heterogeneity of activating mutations of the human luteinizing hormone receptor in male-limited precocious puberty.

Male-limited precocious puberty (MPP) is a gonadotropin-independent disorder that occurs sporadically or is inherited in an autosomal dominant, male-limited pattern. Recent studies have identified constitutively activating missense mutations in the human luteinizing hormone receptor (hLHR) gene leading to Leydig cell activation and precocious puberty. Patients with sporadic MPP (SMPP) or with different ethnic backgrounds appear to have a greater likelihood of having novel mutations. In the current study we examined genomic DNA from two unrelated cases of SMPP of African-American descent for novel mutations of the hLHR gene. A heterozygous A to C transversion at nucleotide 1723 resulting in substitution of Leu for lle575 in transmembrane helix 6 was identified. Human embryonic kidney cells transfected with cDNA for the mutant hLHR-I575L, created by polymerase chain reaction-based mutagenesis of the wild-type (hLHR-wt) cDNA, exhibited increased basal levels of cAMP production in the absence of agonist, indicating constitutive activation. Surface expression of hLHR-I575L, as reflected by human chorionic gonadotropin binding, was diminished compared to hLHR-wt, while agonist affinity was unaffected. With the exception of two polymorphic bases, no mutation was identified within the coding sequence of the hLHR in the second case of SMPP. We conclude that I575L is a unique constitutively activating mutation that impairs cell surface expression of the receptor but does not alter agonist affinity. Furthermore, mutations of the hLHR gene causing SMPP are highly heterogeneous and may be found in regions other than exon 11 of the hLHR. Last, patients with MPP from different ethnic backgrounds are likely to have novel mutations.

Amino Acid Sequence↗
PubMed1996

The role of oxytocin receptors and vasopressin V1a receptors in uterine contractions in rats: implications for tocolytic therapy with oxytocin antagonists.

OBJECTIVE: The objective of the study was to determine in the rat model whether the uterotonic action of vasopressin is mediated by the vasopressin V1a receptor in the uterus, by the oxytocin receptor, or by both. The purpose is to assess whether the anti-V1a activity of oxytocin antagonists is a desirable pharmacologic property in tocolytic therapy for preterm labor. STUDY DESIGN: Dose-response characteristics of the uterotonic action of oxytocin and arginine vasopressin were compared and analyzed by the in vitro cumulative dose-response curve technique. A nonselective oxytocin-V1a receptor antagonist, a selective oxytocin receptor antagonist, and a selective V1a receptor antagonist were selected for this study. Their relative effectiveness in inhibiting the uterine contractile responses induced by oxytocin and by arginine vasopressin in the isolated rat uterus was examined. RESULTS: The uterotonic dose-response curves for oxytocin and arginine vasopressin were parallel and had the same maximal response. The nonselective oxytocin/V1a receptor antagonist and the selective oxytocin receptor antagonist were equally potent in inhibiting the uterine contractions induced by either oxytocin or arginine vasopressin, whereas the selective V1a receptor antagonist had no antiuterotonic activity. Inhibition by the selective oxytocin antagonist caused a similar parallel shift to the right of the dose-response curves for oxytocin and arginine vasopressin. CONCLUSIONS: The parallel dose-response curves for oxytocin and arginine vasopressin suggest that the uterotonic action of vasopressin is also mediated by the oxytocin receptor. Arginine vasopressin binds to both oxytocin and V1a receptors in the uterus, but the activation of V1a receptors appears not to be a mechanism involved in the uterine-stimulating action of vasopressin. The anti-V1a activity of oxytocin antagonists does not contribute to tocolytic efficacy and may represent an undesirable side effect. By blocking the vascular V1a receptors, it may compromise the patient's ability to maintain arterial blood pressure during hemorrhage.

Animals↗
PubMed1996

The role of the placenta in fetal nutrition and growth.

The placenta plays a key role in the nutrition of the fetus. It mediates the active transport of nutrients and metabolic wastes across the barrier separating maternal and fetal compartments, as well as modifying the composition of some nutrients through its own metabolic activity. The function of the placenta is essential to the growth of a healthy fetus; it is becoming apparent that the activities of the placenta are in turn modulated by signals originating from the fetus. Communication between placenta and fetus is especially critical in intrauterine growth retardation. The importance of the interaction of factors like insulin-like growth factor and epidermal growth factor with their receptors is becoming increasingly clear.

Amino Acids↗
PubMed1996

Scanning electron microscopic study of monofilament suture knots.

AIMS/BACKGROUND: Interrupted corneal sutures are used routinely by many cataract and corneal surgeons. A slim compact knot facilitates burial and allows atraumatic suture removal, with decreased risk of wound dehiscence. The size and morphology of knots tied in different configurations were investigated. METHODS: 10-0 nylon suture material was used to tie knots on porcine corneal cataract sections using 2/1/1 (reef and granny), 3/1/1, and 1/1/1/1 (slip knot) configurations. 10-0 Mersilene was used to tie 2/1/1 reef knots. Scanning electron micrographs of the knots were digitised and their maximal lengths and widths estimated. In addition, the area of each knot was calculated and used as an index of its volume. RESULTS: 2/1/1 reef knots were significantly smaller in all dimensions compared with the other knots (all p < 0.03) except for the maximal width of 2/1/1 granny knots which were no wider than the 2/1/1 granny knots. The Mersilene knots were larger than the nylon ones. CONCLUSION: The use of 2/1/1 reef knots is recommended for corneal suturing.

Animals↗
PubMed1996

Compound heterozygous mutations of the luteinizing hormone receptor gene in Leydig cell hypoplasia.

The human LH receptor (hLHR) is a member of the G protein-coupled receptors characterized by the presence of seven-transmembrane (TM) helices. Inactivating mutations of the hLHR lead to Leydig cell hypoplasia (LCH), a form of male pseudohermaphroditism resulting from the failure of fetal testicular Leydig cell differentiation. We have identified three mutations of the hLHR in a patient with LCH: deletion of exon 8 (delta Exon 8), A872G transition resulting in Asn291Ser substitution in the extracellular domain, and C1847A transversion resulting in Ser616Tyr substitution in the seventh TM helix. Nucleotide sequencing, gene dosage, and allele-specific amplification analyses revealed that exon 8 deletion and the two missense mutations are present in different alleles of the hLHR. Constructs of mutated hLHR (hLHR-delta Exon8, hLHR-872/1847, hLHR-1847, and hLHR-872) were used to transfect 293 cells, and the properties of the hLHR expressed were examined. Ligand-binding assays failed to detect the expression of hLHR-delta Exon8. Transfectants expressing hLHR-872/1847 demonstrated greatly reduced ligand binding and ligand-induced cAMP accumulation in comparison to those expressing wild type hLHR. Similar reduction in cAMP accumulation was observed in transfectants expressing hLHR-1847, but not hLHR-872 alone. These findings suggest that, in addition to the 7-TM helices, the polypeptide encoded by exon 8 plays an important role in LHR expression and signal transduction. On the other hand, glycosylation of Asn291 may not be critical for these activities. These results also establish that LCH can result from impaired signal transduction due to compound heterozygous mutations. Implications of these mutations on structure-function relationship of the hLHR and the genotype-phenotype correlation in LCH are discussed.

Alleles↗
PubMed1996

Mucosal lymphangiectasia in gastric adenocarcinoma.

OBJECTIVE: To describe the occurrence and significance of mucosal lymphangiectasia in gastric adenocarcinoma. DESIGN: One hundred consecutive gastrectomies for adenocarcinoma were reviewed, using 25 consecutive gastroscopically biopsied gastrectomy specimens with peptic ulcers as negative controls. SETTING: The specimens were collected over a period of 25 months in two general hospitals and processed according to a standard protocol. PATIENTS: Chinese living in Hong Kong. RESULTS: Twenty cases of adenocarcinoma were found to show mucosal lymphangiectasia, which was arbitrarily defined as the presence of ectatic lymphatic channels in the lamina propria having maximum dimensions greater than that of a foveolar gland. The ectatic lymphatics were lined by simple endothelium, devoid of fibromuscular wall, and they either were optically empty or contained scant mononuclear leukocytes. None of the patients had preoperative evidence of malabsorption syndrome or protein-losing enteropathy. Lymphangiectasia was most readily seen in the superficial lamina propria near the main tumor. In 10 cases (50%), lymphangiectasia extended to the nonneoplastic part of the gastric mucosa, at a distance of at least 2 cm away from the main tumor. Tumor emboli were seen in the ectatic lymphatics in 11 cases (55%). In two cases (10%), the distal line of resection was involved by intramucosal lymphatic spread. The tumor permeating the lymphatics did not evoke any inflammatory or desmoplastic reaction in the perilymphatic lamina propria, similar to the phenomenon of so-called lymphangitis carcinomatosa. In eight cases (40%), there were foci beyond the main tumor where mucosal lymphangiectasia was present, but without tumor in its immediate vicinity. All (100%) of the 20 stomachs with mucosal lymphangiectasia had metastases in regional lymph nodes, whereas only 59 of the 80 cases (73.75%) without lymphangiectasia were node-positive (P < .025). All node-negative cases did not show lymphangiectasia. Twenty-five consecutive gastrectomies for peptic ulcer disease that had undergone preoperative mucosal biopsies showed no lymphangiectasia, suggesting that mucosal biopsy was not the cause of mucosal lymphangiectasia. CONCLUSIONS: (1) Gastric mucosal lymphangiectasia is associated with carcinoma but not peptic ulcer, (2) Mucosal lymphangiectasia in gastric carcinoma signifies lymph node metastases, and (3) Gastric carcinoma can spread along the mucosa via intramucosal lymphatics.

Adenocarcinoma↗
PubMed1996

Isosteric substitution of Asn5 in antagonists of oxytocin and vasopressin leads to highly selective and potent oxytocin and V1a receptor antagonists: new approaches for the design of potential tocolytics for preterm labor.

Substitution of Asn5 in oxytocin (OT) or vasopressin (VP) invariably leads to a dramatic loss of the biological activities of the peptides. Because of this observation, few structure-activity-relationship studies of OT and VP peptides have involved modifications in the 5 position. It is now recognized that peptide agonists and antagonists may use different structural and conformational features in their interactions with the receptors. Our prior studies showed that OT and VP antagonists, unlike the agonists, tolerate amino acid substitutions in the 5 position. This opens new approaches for the design of antagonists. We describe the effects of isosteric replacement of Asn5 by diaminopropionic acid (Dap) or diaminobutyric acid (Dab) in three OT and VP antagonists: (1) the V1a (vasopressor receptor) antagonist d(CH2)5[Tyr(Me)2]AVP; (2) the OT (uterine OT receptor) antagonist d(CH2)5[Tyr(Me)2, Thr4, Tyr-NH29] OVT and (3) three selective OT antagonists, desGly-NH2,d(CH2)5[D-Tyr2, Thr4]OVT, desGly-NH2, d(CH2)5[D-Phe2, Thr4]OVT and desGly-NH2, d(CH2)5- [D-Trp2, Thr4]OVT. The Dap5 and Dab5 substitutions were tolerated remarkably well, with the less isosteric Dap5 substitution leading to a greater retention of anti-OT potency than the Dab5 substitution. Furthermore, the Dap5 and Dab5 and OT and VP antagonist analogues were surprisingly shown to be much more selective than their respective parent compounds. The Dab5 analogue of (1) was devoid of anti-OT activity. The three Dap5 analogues of (3) were devoid of anti-V1a activities. These appear to be the first single-receptor-type-selective OT and VP antagonists discovered to date. These findings could provide new leads for the development of single-receptor-type-selective receptor probes for the localization and characterization of OT and VP receptors and potential selective tocolytics for the treatment of premature labor.

Animals↗
PubMed1995

Mouse preproendothelin-1 gene. cDNA cloning, sequence analysis and determination of sites of expression during embryonic development.

Endothelin-1 (ET-1) is a peptide implicated in a wide variety of functions involving vascular and non-vascular systems. We have cloned the cDNA encoding the mouse prepro-endothelin-1 (PPET-1) and determined its nucleotide sequence. The putative PPET-1 peptide processing sites are all conserved and the deduced 21-amino-acid mature ET-1 peptide is identical to that of the rat, human, bovine, porcine and rabbit. Using the cloned cDNA as a probe for in situ hybridization, we detected PPET-1 mRNA in different tissues at different stages of mouse embryonic development. Embryos at a stage as early as 9.5 days postcoitum (E9.5) have very strong expression in the branchial epithelium, optic vesicle and the endothelial cells of large blood vessels, including the dorsal aorta and aortic arches. While the expression level in the branchial epithelium was decreasing towards the later stage of embryogenesis, the expression in the endothelial cells increased with age. At E10.5, PPET-1 mRNA was also detected in the otic vesicle as well as in the developing gut epithelium. At later stage of development, the expression of PPET-1 was primarily found in the vascular endothelial cells, cochlea, eye and the gut, with the highest level of PPET-1 mRNA in the endothelial cells of the lung. These data will be useful for analyzing the function of ET-1 in these organs.

Amino Acid Sequence↗
PubMed1995

Differential expression of glial fibrillary acidic protein (GFAP) in the retinae and visual cortices of rats with experimental renal hypertension.

To examine the expression of the GFAP protein in the retina and visual cortex under normal and pathological conditions, hypertension was induced in adult male Sprague-Dawley rats by applying silver clips onto renal arteries and the change in GFAP expression was followed by Western blotting and immunocytochemical staining. One week after operation when the induced hypertension was at the initial stage, GFAP expression in the retina was reduced to half of the sham control. By 4 weeks, when consistent hypertension was developed, a further decrease in the level of GFAP expression in the retina to one third of the sham control was observed. Immunocytochemical staining showed that the number of GFAP-positive cells in the nerve fiber layer of the retina of the hypertensive rat was reduced to less than one third of the sham control. However, similar changes in GFAP expression in the visual cortex of hypertensive rats were not observed. This study represents the first report to date on GFAP expression in the retina and visual cortex and includes discussion of the possible mechanisms through which GFAP expression is mediated.

Animals↗