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Biomedical subjects

W Y Chan

Publications and source records attributed to W Y Chan.

At least 127 records · Page 7Linked to original sources

Antiproliferative and teratogenic activities of the bishemisuccinates of 7 alpha-hydroxycholesterol and 7 beta-hydroxycholesterol.

1. The bishemisuccinates of 7 alpha-hydroxycholesterol and 7 beta-hydroxycholesterol induced a dose-dependent decrease in the incorporation of [3H]thymidine into fibroblast cell line (3T3), macrophage-like cell line (P388D1) and rat hepatoma cell line (H35). Concomitantly there was a reduction in cell viability. 2. The 3T3 cells were less susceptible than P388D1 and H35 cells. 3. The aforementioned derivatives of 7 alpha-hydroxycholesterol and 7 beta-hydroxycholesterol produced malformations in cultured embryos including abnormalities in yolk sac circulation, heartbeat, body axis, otic vesicle, branchial apparatus, cranial neural tube and forelimb bud. Axial length and somite number were reduced.

3T3 Cells↗

Actions of selected proteins, peptides and amino acid derivatives on mouse embryonic development in vitro.

1. The actions of various compounds with antiproliferative and/or immunomodulatory activities including the ribosome-inactivating protein gelonin, the tetrapeptide tuftsin, the opioid peptide leucine-enkephalin, the antireproductive tripeptide Thr-Ser-Lys, the melatonin analog 6-methoxy-2-benzoxazolinone, and the amino acid derivatives 5-hydroxytryptamine and oxalysine on mouse embryonic development and organogenesis in vitro were investigated. 2. The various compounds were tested up to a concentration of 300 micrograms/ml. It was found that only 6-methoxy-2-benzoxazolinone, a derivative of tryptophan, produced an increase in the number of abnormal embryos and reductions in the final somite numbers and axial lengths of embryos. 3. 6-Methoxy-2-benzoxazolinone treatment also resulted in an increased incidence of abnormal morphogenesis of various organ primordia, including abnormal yolk sac circulation, twisting of body axis, absence of forelimb bud and opening of cranial neural tube.

Amino Acid Sequence↗

Distribution of neuropeptide Y in the developing human spinal cord.

The distribution of neuropeptide Y at different levels of the spinal cord of 23 human fetuses aged from 10-41 weeks of gestation was studied using immunocytochemical staining. Neuropeptide Y-immunoreactive neurons were identified at all levels of the spinal cord examined as early as 10 weeks of gestation. These cells were localized in the superficial layers (laminae I and II of Rexed) of the dorsal gray matter. As the age of the fetuses increased, their cell number increased and the region containing positive neurons extended from the superficial to deep layers (laminae III and VI). Immunoreactive fibers started to appear in fetuses at 10 weeks of gestation. They were found not only in the gray and white matters, but also in the pia mater lining the spinal cord. As the fetuses aged, the neuropeptide Y-immunoreactive fibers became mostly concentrated in the intermediate zones of the thoracic and sacral segments corresponding to the developing autonomic centers. Our results suggest that neuropeptide Y may play a role in the early development of the autonomic system.

Embryonic and Fetal Development↗

Invasive squamous cell carcinoma and cervical intraepithelial neoplasia III of uterine cervix. Morphologic differences other than stromal invasion.

The authors compared 69 cases of surgically proven invasive squamous cell carcinoma (ISCC) of uterine cervix with 48 cone biopsy specimens that showed cervical intraepithelial neoplasia (CIN) grade III. Histologic features that were preferentially associated with ISCC included the following: giant bizarre cells (66.7% in ISCC, 6.26% in CIN III, P < .01); large keratinized cells (87% in ISCC, 0% in CIN III, P < .01); keratin pearls (40.6% in ISCC, 0% in CIN III, P < .01); necrosis (79.7% in ISCC, 8.3% in CIN III, P < .01); and neovascularization (56.5% in ISCC, 0% in CIN III). In 51 (74%) cases of ISCC, a CIN III component was present, of which 18 (35.3%) showed large keratinized cells or keratin pearls in the in situ components. None of the CIN III cases showed more than one of the above features. In the ISCC group, the above features occurred with similar frequency in microinvasive and frankly invasive tumors. The authors' results agree with previous Papanicolaou-smear cytologic studies, which found that ISCC can be distinguished accurately from CIN III by the morphology of the neoplasm. The authors concluded that cervical biopsy specimens that show two or more of the above features are highly suggestive of ISCC, even when stromal tissue is absent or insufficient for the assessment of invasion. Furthermore, in cervical biopsy specimens showing CIN III, the presence of large keratinized cells or keratin pearls may signify the presence of invasive lesions elsewhere in the cervical mucosa.

Adult↗

Coccoid forms of Helicobacter pylori in the human stomach.

Helicobacter pylori (HP) may transform from helical bacillary forms to coccoid forms after several days' in vitro incubation. The authors examined 111 consecutive gastrectomy specimens for the presence of coccoid forms of H pylori. Tissues from 64 stomachs (57.7%) showed colonization by H pylori, including 49 cases (76.6%) of adenocarcinoma, 14 cases (21.9%) of benign peptic ulcer, and 1 case (1.6%) of malignant lymphoma. Of these, coccoid forms of H pylori were identified in 53 cases (82.8%). In hematoxylin-and-eosin-stained sections coccoid forms of H pylori appeared as solid, round, basophilic dotlike structures. Under an electron microscope, coccoid forms of H pylori appeared as U-shaped bacilli, with the ends of the two arms joined by a membranous structure. Ultrastructural findings were identical to those from cultures of H pylori. With anti-Helicobacter antibody, coccoid forms of H pylori were positively stained by immunoperoxidase. Helical bacillary forms of H pylori invariably coexisted with the coccoid forms. By semiquantitative analysis, the number of coccoid forms in adenocarcinoma was significantly (P > .01) greater than that in benign peptic ulcers. This study confirms that H pylori can exist in coccoid forms in the human stomach. Coccoid forms should be distinguished from the pathogenic or nonpathogenic bacterial cocci, fungal spores, and cryptosporidia that may colonize the human stomach.

Adenocarcinoma↗

Agonist and antagonist specificities of decidual prostaglandin-releasing oxytocin receptors and myometrial uterotonic oxytocin receptors in pregnant rats.

This paper describes further pharmacological characterization of the decidual prostaglandin-releasing oxytocin receptors and the myometrial uterotonic oxytocin receptors in the uterus of the pregnant rat. The effects of oxytocin, arginine-vasopressin and their related agonists and antagonists on the release of PGF2 alpha were studied in vitro on isolated uteri from rats on day 19-20 of pregnancy that had been incubated in Krebs buffer, pH 7.4, at 37 degrees C. The concentration of PGF2 alpha in the media was measured using specific radioimmunoassays. It was found that the decidual and myometrial oxytocin receptors exhibit different ligand specificities. Of the agonists tested, oxytocin and arginine-vasopressin stimulated PGF2 alpha release in a dose-dependent manner. Arginine-vasopressin has only 3% of the uterotonic potency of oxytocin, but was found to have 16% of its PGF2 alpha-releasing activity. [4-Threonine, 7-glycine]oxytocin, a highly potent and selective uterotonic oxytocin analogue, had no detectable prostaglandin-releasing activity at a dosage 30 times higher than oxytocin. However, 1-deamino-[8-D-arginine]vasopressin, a highly potent and selective antidiuretic arginine-vasopressin analogue, which has only 10% of the uterotonic activity of arginine-vasopressin, was as potent as arginine-vasopressin in prostaglandin-releasing activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Association of Epstein-Barr virus, human papilloma virus, and cytomegalovirus with nine nasopharyngeal carcinoma cell lines.

BACKGROUND: Epstein-Barr virus (EBV) has been proposed to be closely associated with nasopharyngeal carcinoma (NPC). To evaluate the actual relationship, EBV was analyzed in nine established NPC cell lines and in four original NPC biopsy specimens. EXPERIMENTAL DESIGN: We used Southern blot analysis alone or after polymerase chain reaction to determine whether EBV was present in our NPC cell lines. We also used in situ nucleic acid hybridization and in situ polymerase chain reaction to identify EBV in 4 original biopsy specimens. For comparison, we investigated the cell lines for the presence of human papilloma virus type 16 (HPV-16) and human cytomegalovirus (HCMV). RESULTS: Southern blots alone for detection of 3 viruses in 9 cell lines were all negative. PCR plus Southern blotting revealed that 5 cell lines contained EBV in earlier passages, and all became negative in later passages. Some cell lines also contained HPV-16 and HCMV. At earlier passages, some cell lines contained EBV, HPV-16, and HCMV concurrently. Three out of four biopsy specimens contained EBV in certain tumor cells, lymphocytes, and glandular epithelia. CONCLUSIONS: These findings indicate that EBV, HPV-16, and HCMV may be present in certain NPC cell lines and in only a small fraction of each positive cell line, and that a cell line may contain these three viruses concurrently. EBV is present not only in a fraction of tumor cells, but also in some lymphocytes and glandular epithelia in biopsy specimens. It is present as an episomal form but not as an integrated form in the infected cells, suggesting that the carcinogenesis of non-EBV containing NPC tumor cells is not related to EBV infection.

Base Sequence↗

Gastrulation in the mouse embryo: ultrastructural and molecular aspects of germ layer morphogenesis.

Ultrastructural studies and lineage analyses of gastrulating mouse embryos have revealed that different morphogenetic tissue movements are involved in the formation of the three definitive germ layers. Definitive ectoderm is formed by epibolic expansion of the pre-existing progenitor population in the embryonic ectoderm. Formation of the mesoderm and the endoderm is initiated by cellular ingression at the primitive streak. The mesodermal layer is established by cell migration and cell sheet spreading, but the endoderm is formed by replacing the original primitive endodermal population. To this date, genes that are expressed during mouse gastrulation mostly encode cell surface adhesion or signalling molecules, growth factors and their receptors, and putative transcriptional factors. Their precise role during gastrulation remains to be investigated.

Animals↗

The carboxyl-terminal domain of the human pregnancy-specific glycoprotein specifies intracellular retention and stability.

The pregnancy-specific glycoproteins (PSGs), which are members of the immunoglobulin superfamily, are the major pregnancy-associated proteins synthesized by the human placenta. Thirty or more PSG members have been identified which are encoded by at least 11 linked genes. The PSG proteins share 85-95% sequence homology in the coding region, but show variability at the carboxyl-terminal (COOH) domains. In the present study, we examined the effects of PSG COOH domains on protein secretion and stability. Using PSGs containing short (11-12 residues) hydrophilic (PSG1e, PSG11s, and PSG16a), short (22 residues) hydrophobic (PSG6r), and long (81 residues) hydrophobic (PSG11w) COOH domains, we showed that most PSG members were secretory proteins except PSG11w which was largely retained in cells. When the PSG11w COOH domain was replaced with a short COOH domain of PSG1e, the resulting PSG-N11w/C1e chimera became secreted into the medium. On the other hand, chimeras that harbored the PSG11w COOH domain, PSG-N1e/C11w and PSG-N16a/C11w, remained in cells, demonstrating that the COOH domain of PSG11w confers intracellular retention. Deletion analysis showed that mutant (PSG11w-C2) that contained the first 21 amino acids of PSG11w COOH domain or mutant (PSG11w-C3) that contained a deletion of hydrophobic residues 372-392 in the PSG11w COOH domain remained largely in cells. In contrast, the PSG11w-C1 mutant which contained the first 12 residues of the PSG11w COOH domain became a secretory protein. Studies of PSG synthesis and processing in the presence of Brefeldin A, a drug that impedes protein transport from endoplasmic reticulum to the Golgi system, showed that PSG11w resided and degraded in the endoplasmic reticulum. The endoplasmic reticulum localization of PSG11w and the cell-associated mutant PSGs was further demonstrated by their sensitivity to endoglycosidase H and indirect immunofluorescence analysis.

Amino Acid Sequence↗

Expression of pregnancy-specific beta 1-glycoprotein genes in hematopoietic cells.

The presence of PSG in blood cells has been demonstrated by immunohistochemical staining. However, the origin of those proteins is not known. This report examines the expression of the PSG genes in different types of freshly isolated blood cells. RNA isolated from bone marrow and peripheral blood cells of healthy individuals was analyzed for PSG transcripts by reverse transcriptase-polymerase chain reaction using synthetic oligonucleotide primers specific for the PSG genes. The level of expression of the PSG genes in different types of cells exhibited significant individual variation. Trace amounts of PSG transcripts could be detected in polymorphonuclear cells (PMN), monocytes and B lymphocytes while T lymphocytes always contained the highest level of transcript. The expression of PSG genes in the blood cells apparently was not affected by the method of isolation nor by overnight culturing of these cells except in the case when lymphocytes were separated by rosetting with sheep red blood cells. All reported PSG transcripts were detected in blood cells. Both type I and type II transcripts of the PSG genes were detected in blood cells with the exception of type II transcript of PSG5 and PSG11 which were only found in the placenta. Tissue specificity in the expression or alternative splicing of some of the PSG family members was implicated.

Alternative Splicing↗

Pregnancy specific beta 1-glycoprotein in human intestine.

Pregnancy-specific beta 1-glycoprotein (PSG) transcripts have been identified in a number of placental and non-placental tissues. Using a placental PSG cDNA probe to screen a normal human intestinal cDNA library we have isolated 22 hybridizing clones. These clones could be divided into four groups. Nucleotide sequence analysis showed that one group of clones correspond to functional and another group correspond to non-functional PSG cDNAs. The other two groups are homologous to the nonspecific cross-reacting antigen (NCA) and biliary glycoprotein (BGP), both of which are members of the carcinoembryonic antigen (CEA) family. Thus, PSG, NCA and BGP are co-expressed in normal human intestine. RNA and immunoblot analysis, along with polymerase chain reaction amplification further confirm the expression of PSG in human intestinal tissue.

Amino Acid Sequence↗

Histogenetic potential of rat hind-limb interdigital tissues prior to and during the onset of programmed cell death.

The histogenetic potential of interdigital tissues isolated from the autopod of rat embryonic hind-limbs between 14.5 and 16.5 days was investigated. A wedge of tissue containing ectoderm and mesoderm was excised from between the developing digits and grafted beneath the kidney capsule of adult rats for two weeks. We have previously demonstrated that the renal capsule is an excellent site for permitting limb tissues to proliferate and differentiate (Chan et al.: J. Exp. Zool., 260:74-83, 1991). At 14.5 days, when cell death (revealed with neutral red stains) within the interdigital zone was limited to the apical ectodermal ridge (AER), the interdigital mesoderm was capable of developing into bone, cartilage, and loose connective tissue in the kidney. It was estimated that the skeletal elements occupied approximately 38% of the overall area of the grafts. In addition, the ectoderm was able to produce keratinized epithelium, hair follicles, and sebaceous glands. In 15.5 day autopod, necrosis was present both in the AER and the mesoderm between the AER and marginal sinus. Interdigital mesoderm obtained from this stage of development formed cartilage but not as extensively as that derived from 14.5 day autopod (4% as compared with 38%). Necrotic cells were present in all of the interdigital zones at 16.5 days. Ten explants were introduced into the kidney at this stage, but only 4 grafts were recovered after 2 weeks. In all cases, the explants did not produce cartilage. Only a small amount of keratinized epithelium and loose connective tissue was found. In summary the interdigital mesoderm has the potential to develop bone, cartilage, and loose connective tissue, but this ability is progressively lost during morphogenesis.

Animals↗

Developmental toxicity and teratogenicity of trichosanthin, a ribosome-inactivating protein, in mice.

The embryotoxic and teratogenic effects of trichosanthin (TCS), a protein isolated from tubers of Trichosanthes kirilowii (family Cucurbitaceae), were studied both in vivo and in vitro. The protein was administered i.p. to ICR mice on day 8.0 of pregnancy, and the animals were sacrificed 1 day before parturition. The fetuses were fixed and subsequently sectioned. At the highest TCS dose employed (7.5 mg/kg body weight), the viability of fetuses declined to 70.2%, compared with 96.5% in the saline-treated control group. The number of resorbed fetuses increased, and the crown-rump length of the surviving fetuses was reduced. At the doses of 5.0 and 7.5 mg TCS/kg body weight, 2.3% and 9.0%, respectively, of the surviving fetuses were found to be abnormal. The abnormalities observed included exencephaly, micromelia, and short tail. When mouse embryos at the early organogenesis stage were cultured with TCS at a dose of 200 micrograms/ml or above, a significantly larger number of embryos were found to be abnormal as compared with the controls. The abnormalities were observed in the head, trunk, and limb regions. Hence, TCS produced adverse effects on prenatal development both in vivo and in vitro.

Abnormalities, Drug-Induced↗

Action of pineal indoleamines on the reproductive systems of the male C57 mouse and golden hamster.

Intraperitoneal administration of melatonin, methoxytryptamine and methoxytryptophol in the late afternoon to mice exposed to a 14L:10D photoperiod induced appearance of necrotic cells in seminiferious tubules and an increase in incidence of aspermic tubules. The histological appearances of the seminal vesicles and coagulating glands were, however, unaffected by the treatments. Treatment of mice with methoxyindoleacetic acid did not produce discernible changes in the testes and accessory sex organs. Subcutaneous injections of the aforementioned pineal indoles at a dose of 250 micrograms/injection for 3 months to mature male hamsters kept under a 14L:10D photoperiod did not evoke changes in the testes, seminal vesicles and coagulating glands, suggesting a down-regulation of melatonin receptors by administration of a high dose of pineal indole over a prolonged period.

5-Methoxytryptamine↗

Correlation of acid phosphatase but not alkaline phosphatase activity with myelination in the developing mouse brain.

1. Neonatal mice received subcutaneous injections of buffer, thiourea (TU) or propylthiouracil (PTU). 2. The PTU-treated mice were sacrificed on postnatal day 14 (P14) and the TU-treated mice on P28. 3. Brain weights of the TU- and PTU-treated mice were not significantly different from the controls. 4. Acid but not alkaline phosphatase activity in the brainstem decreased after TU and PTU treatment. 5. Myelination as indicated by intensity of luxol fast blue staining was weaker in the drug-treated animals. 6. The level of myelin marker enzyme, 2',3'-cyclic nucleotide 3'-phosphohydrolase, was lower in the brainstem of PTU-treated animals. 7. The results suggest a correlation between acid phosphatase but not alkaline phosphatase activity with myelination in the developing mouse brain.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗