Search PubMed⌕ Search

Biomedical subjects

W Y Chan

Publications and source records attributed to W Y Chan.

At least 109 records · Page 6Linked to original sources
PubMed1995

Effect of hypothyroidism induced by propylthiouracil and thiourea on male and female reproductive systems of neonatal mice.

The effect of hypothyroidism induced by 6-propyl-2-thiouracil (PTU) or thiourea (TU) on the development of the reproductive system in male and female neonatal ICR mice was investigated. PTU or TU was injected subcutaneously into experimental animals from postnatal day 1 (PD1) onward. The histological changes of the reproductive organs, formation of ovarian follicles, and spermatogenesis were examined on PD 14, 21, and 28, and the fertility of the hypothyroid mice in adulthood was followed. It was found that PTU or TU treatment did not produce an effect on the histology of the neonatal uterus and oviduct. In contrast, the drugs induced a decrease in the number of primordial follicles, multilaminar follicles, and Graafian follicles in the ovary. The number of follicles with degenerated follicular cells was increased. In the testis both PTU and TU treatments brought about a decrease in the number of seminiferous tubules with developing spermatids although the mean diameter of seminiferous tubules and the histology of the testis, epididymis, seminal vesicle, and coagulating gland was unaffected. The mating between hypothyroid females and euthyroid males and that between hypothyroid males and euthyroid females were normal with regard to the pregnancy rate, litter size, and sex ratio of offspring. The somatic growth of the resulting offspring was normal. It is concluded that the retarding effect on ovarian and testicular development in mice during neonatal period was not serious enough to adversely affect reproduction in the hypothyroid animals.

Animals↗
PubMed1995

Effects of a D-Cys6/L-Cys6 interchange in nonselective and selective vasopressin and oxytocin antagonists.

We report the solid-phase synthesis of the D-Cys6 analogues of arginine-vasopressin (AVP), peptide 1, of the selective AVP vasopressor (V1a receptor) antagonist [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid),2-O-methyltyrosine]arginine-vasopressin (d(CH2)5[Tyr(Me)2]-AVP, (A)), peptide 2, of the three nonselective antidiuretic/vasopressor (V2/V1a receptor) AVP antagonists d(CH2)5[Tyr(Et)2]VAVP (B), d(CH2)5[D-Tyr(Et)2]VAVP (C), and d(CH2)5[D-Phe2]VAVP (D) (where V = Val4), peptides 3-5, of the nonselective oxytocin (OT) antagonists d(CH2)5-[Tyr(Me)2]OVT (E) and d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT (F) (where OVT = ornithine-vasotocin), peptides 6 and 7, and of the selective OT antagonists desGly-NH2,d(CH2)5[Tyr(Me)2,Thr4]OVT (G) and d(CH2)5]D-Trp2,Thr4]OVT (H), peptides 8 and 9. We also present the repeat syntheses of the previously reported d(CH2)5[D-Trp2]AVT (peptide 10) and its D-Cys6 analogue (peptide 11) (where AVT = arginine-vasotocin). Peptides 1-11 were assayed for agonistic and antagonistic activities in in vivo V1a, V2, and oxytocic assays and in in vitro oxytocic assays without and with 0.5 mM Mg2+. With V2 and V1a agonistic potencies of 0.82 and 0.41 units/mg, [D-Cys6]AVP has retained less than 0.3% of the V2 and V1a potencies of AVP. It exhibits no oxytocic activity and is an in vitro OT antagonist. pA2 = 6.67 (no Mg2+); pA2 = 5.24 (0.5 mM Mg2+). By contrast, with one or two exceptions, a D-Cys6/L-Cys6 interchange in antagonists 2-9, although resulting in reductions of antagonistic potencies in all assays for virtually all peptides 2-9 relative to A-H, has been well tolerated. For peptides 2-5, the anti-V2 and anti-V1a pA2 values range from approximately 5.54 to 7.33 and from 7.19 to 8.06, respectively; the range of in vitro anti-OT pA2 values (no Mg2+) is 7.35-7.87; with 0.5 mM Mg2+, the range is 7.24-8.21. Peptides 2 and 4 have in vivo anti-OT pA2s = 6.60 and 7.16, respectively. For peptides 6-9, the range of in vitro anti-OT pA2 values (no Mg2+) is 7.65-7.96; with 0.5 mM Mg2+, the range is 7.41-7.65, and the in vivo anti-OT pA2 values range from 6.85 to 7.33. With an in vivo anti-OT pA2 = 7.33, peptide 6 is equipotent with its parent E. The in vivo anti-OT potencies of peptides 7-9 are significantly reduced relative to those of F-H. The in vitro anti-OT (0.5 mM Mg2+) pA2 values of 10 and 11 are 7.54 and 7.50, both significantly lower than those previously reported.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1995

Genetic heterogeneity of constitutively activating mutations of the human luteinizing hormone receptor in familial male-limited precocious puberty.

Genomic DNA from 32 unrelated families with male-limited precocious puberty was examined for the previously described Asp-578-->Gly, Met-571-->Ile, and Thr-577-->Ile mutations in transmembrane helix 6 of the human luteinizing hormone receptor (hLHR). Twenty-eight families had the inherited form of the disorder, and of these, 24 were found to have the Asp-578-->Gly mutation. Four additional mutations were found among the remaining four families with the inherited form and in four sporadic cases of the disorder: an A-->C transversion resulting in substitution of leucine for Ile-542 in the fifth transmembrane helix, an A-->G transition resulting in substitution of glycine for Asp-564 in the third cytoplasmic loop, a G-->T transversion resulting in substitution of tyrosine for Asp-578 in the sixth transmembrane helix, and a T-->C transition resulting in substitution of arginine for Cys-581 in the sixth transmembrane helix. Human embryonic kidney cells transfected with cDNAs for each of the mutant hLHRs, created by PCR-based mutagenesis of the wild-type hLHR cDNA, exhibited increased levels of basal cAMP production in the absence of agonist, indicating constitutive activation of the mutation hLHRs. Three of the additional mutations had specific features: Ile-542-->Leu and Cys-581-->Arg appeared ligand-unresponsive, whereas Asp-578-->Tyr appeared to correlate genotype with phenotype. We conclude that the region spanning nt 1624-1741 of exon 11 is a hotspot for heterogeneous point mutations that constitutively activate the hLHR and cause male-limited precocious puberty.

Amino Acid Sequence↗
PubMed1995

Mouse embryonic development and tumor cell growth under the influence of recombinant trichosanthin (a ribosome inactivating protein) and its muteins.

Trichosanthin, a ribosome inactivating protein, is known to possess embryotoxic and antiproliferative activities. In the present study recombinant trichosanthin and its muteins produced by site-directed mutagenesis were tested for these activities using whole embryo culture and cell culture. The results revealed that when Glu 160 in trichosanthin was mutated to alanine or aspartate, the two aforementioned activities underwent a substantial decrease. However, the former mutein had a higher potency than the latter mutein. When both Glu 160 and Glu 189 were mutated, the resultant mutant possessed very low antiproliferative and yet considerable embryotoxic activity, indicating the contribution from other amino acids in stabilizing the transition state complex of trichosanthin.

Animals↗
PubMed1995

Effects of pineal indoles on ovarian response to gonadotropin-induced ovulation in mice.

Ovulation was induced in immature mice by injections of pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (HCG) spaced 48 hours apart. The mice were divided into six groups: one group received intraperitoneal injections of normal saline, another group received alcoholic saline which was used as the vehicle of pineal indoles, and the remaining groups received respectively hydroxyindoleacetic acid (HIAA), melatonin (MEL), methoxytryptamine (MTA) and methoxytryptophol (MTP). The pineal indoles were administered 24 hours before, on the same day as, 24 hours after and 48 hours after the PMSG injection. The mice were sacrificed 24 hours after the HCG injection. The numbers of growing primary follicles, multilaminar primary follicles, Graafian follicles, preovulatory follicles and corpora lutea in the ovary were not altered by treatment with pineal indoles. However, there was an increased incidence of follicular atresia in the groups treated with MEL, MTA and MTP. The pineal indoles did not affect the number of ovulated oocytes, but there was a large number of degenerated and fragmented ovulated oocytes in the MTA- and MTP-treated groups. Treatment with MEL, MTA and MTP also resulted in lower plasma levels of estradiol-17 beta and progesterone.

5-Methoxytryptamine↗
PubMed1995

Adverse effect of Tripterygium wilfordii extract on mouse embryonic development.

Tripterygium wilfordii Hook f. is a medicinal plant which possesses anti-fertility activity in males and has been used in China for the treatment of rheumatoid arthritis, chronic nephritis and other pulmonary diseases for years. The effect of Tripterygium wilfordii extract on in vitro development in day 9 and day 10 mouse embryos was examined. The embryotoxicity of T. wilfordii extract was obvious on day 9 and day 10 embryos at doses of 50 and 100 micrograms/ml, respectively. The embryonic abnormalities produced included abnormal branchial apparatus, open cranial neural tube and absence of forelimb bud in day 9 embryos. In day 10 embryos, the abnormality appeared first in the branchial apparatus. At higher doses, additional abnormalities appeared: abnormal optic and otic vesicles and twisted body axis in day 9 embryos; microcephaly, hematoma in cranial region and absence of hindlimb buds in day 10 embryos. There were reductions in final somite number, yolk sac surface area and axial length. Dead cells were present all over the embryo. The blood circulation of the visceral yolk sac of the abnormal embryos became defective. Ultrastructural analysis of the visceral yolk sac revealed abnormalities including decrease in the amount of microvilli, reduction in the number of storage vesicles, appearance of large vacant vacuoles and decrease in the number of pinocytotic invaginations on the apical surface of the yolk sac epithelium. The embryotoxic effect of T. wilfordii extract was, however, destroyed by heat treatment of the extract at 80 degrees C for 6 hours.

Animals↗
PubMed1995

Changes induced by pineal indoles in post-implantation mouse embryos.

1. A subcutaneous injection of hydroxyindoleacetic acid (HIAA), melatonin (MEL), methoxytryptophol (MTP) or methoxytryptamine (MTA) (1 mg/25 g body wt/injection) at 8.5 days post-coitum (p.c.) did not produce any effect on the development of embryos in utero at 10.5 days p.c. 2. Two subcutaneous injections (3 mg/25 g body wt/injection) of MTP, but not HIAA, MEL nor MTP, at 7.5 and 8.5 days p.c. brought about a decrease in gravid uterine weight and number of live fetuses and an increased incidence of early resorptions at 17.5 days p.c. 3. MEL at doses 100 and 200 micrograms/ml, MTP at doses 50 and 100 micrograms/ml and MTA at 25, 50 and 100 micrograms/ ml brought about an increase in the number of abnormal embryos cultured in vitro and an increased incidence of abnormal yolk sac circulation, body axis, optic and otic placodes, branchial apparatus, forelimb buds and cranial neural tube. 4. The findings show than melatonin, methoxytryptamine and methoxytryptophol produced an embryotoxic effect on embryos at the early somite stage in vitro while only methoxytryptamine had an adverse effect on embryonic development in vivo.

5-Methoxytryptamine↗
PubMed1995

Acute renal failure following cardiac surgery: incidence, outcomes and risk factors.

BACKGROUND: Acute renal failure (ARF) is a recognised complication following cardiac surgery, but the incidence varies widely in the published literature and there are no Australian data available to help predict the risks of ARF in patients with pre-existing renal disease. AIM: To determine the incidence, outcome and risk factors for ARF following cardiac surgery. METHODS: A retrospective case control analysis of 903 consecutive patients who had cardiac surgery (795 CABG, 68 valve/septal surgery, 40 combined valve/CABG) in 1992-93. ARF was defined as doubling of serum creatinine concentration (Cr) to > 0.13 mmol/L if serum Cr was < or = 0.13 mmol/L pre-operatively, or else a rise in serum Cr of > or = 0.10 mmol/L after cardiac surgery. For each subject with ARF, two case control subjects were matched for date of surgery, surgeon, age, sex, type of surgery and pre-operative serum Cr to permit analysis of the influence of pre-operative factors (hypertension, diabetes mellitus, left ventricular systolic dysfunction) and for the comparison of cardiopulmonary bypass time upon the development of ARF. Subsidiary endpoints were mortality, need for dialysis and length of hospital stay. RESULTS: ARF developed in only 1.1% of patients with 'normal' pre-operative renal function (creatinine < or = 0.13 mmol/L) and none required dialysis. ARF developed in 16% of those with impaired pre-operative renal function, 20% of whom required dialysis. Mortality from ARF was 13%. The risk of ARF rose from 10.4% in those with pre-operative serum Cr 0.14-0.20 mmol/L to 36.8% if the serum Cr was > 0.20 mmol/L (p < 0.01). Mortality was higher (4.2% vs 0.7%, p < 0.01) and length of hospital stay longer (14.5 vs nine days [median], p < 0.001) in those with impaired pre-operative renal function. ARF was more likely in those over 65 years, if valve surgery was included and where there was prolonged cardiopulmonary bypass time. CONCLUSIONS: These data confirm that ARF following cardiac surgery is uncommon without pre-operative impairment of renal function but currently carries a mortality rate of 13%. Impaired renal function alone is associated with higher mortality and prolonged hospital stay. Studies to prevent ARF in this setting should focus on the high risk subsets described in this study.

Acute Kidney Injury↗
PubMed1995

Characterization of a novel, linear radioiodinated vasopressin antagonist: an excellent radioligand for vasopressin V1a receptors.

We report on the pharmacological properties of a potent and selective linear vasopressin (AVP) V1a receptor antagonist HO-Phenylacetyl1-D-Tyr(Me)2-Phe3-Gln4-Asn5-Arg6-Pro7-Arg8-NH2 (HO-LVA). Iodinated on the phenolic substituent at position 1, [125I]-HO-LVA displayed the highest affinity for rat liver V1a receptors (8 pM) ever reported. Furthermore, affinities of HO-LVA and I-HO-LVA for V1b, V2 and oxytocin (OT) receptors was 400- to 1,000-fold lower than for V1a receptors, rendering it a highly selective ligand. Both HO-LVA and its iodinated derivative are V1 antagonists, they potently inhibited AVP-induced inositol-phosphate accumulation in WRK1 cells, and also, although with a much lower potency, the AVP-induced ACTH release from freshly prepared pituitary cells. Using autoradiography [125I]-HO-LVA appeared to be the first radioligand to successfully identify and localize the presence of V1a receptors in rat liver and blood vessel walls. Moreover, several new brain regions expressing V1a receptors could be identified, in addition to those brain regions that were previously identified with other radiolabelled AVP analogues.

Adrenocorticotropic Hormone↗
PubMed1995

Examination for toxicity of a Chinese drug, the toad glandular secretory product chan su, in pregnant mice and embryos.

In order to evaluate the developmental toxicity and teratogenicity of a Chinese drug, the toad venom Chan Su, the drug was administered in a single intraperitoneal injection to pregnant ICR mice during the period of embryonic organogenesis. At the end of the gestation period, the mice were sacrificed, and the fetuses were collected, fixed and sectioned. A dose of Chan Su lower than 50 mg (dry weight)/kg body weight did not produce detectable changes in the recipient mice, but at a dose of 50 mg/kg the drug induced a decrease in body weight and structural abnormalities in livers and kidneys of the pregnant mice as well as increases in the number of resorbed and dead fetuses. There was a reduction in fetal weight although there were no changes in fetal crown-rump length nor tail length. No abnormalities were observed in the fetuses.

Abnormalities, Drug-Induced↗
PubMed1995

Effects of decoctions prepared from Aconitum carmichaeli, Aconitum kusnezoffii and Tripterygium wilfordii on serum lactate dehydrogenase activity and histology of liver, kidney, heart and gonad in mice.

Mature ICR mice were randomly divided into groups and treated with various doses (1 mg, 5 mg or 10 mg herb/25 g body weight) of a decoction of one of three following Chinese medicinal herbs: Aconitum carmichaeli, Aconitum kusnezoffi and Tripterygium wilfordii, once daily for 4 days. Twenty four hours after the last injection the animals were bled and the blood samples were stored at -20 degrees C until assay for liver lactate dehydrogenase (LDH) isozyme activity. The livers, kidneys, hearts and gonads were dissected out, immediately fixed in Bouin's fluid, and subsequently processed for histological examination. It was found that the gonads and hearts of the drug-treated mice were histologically similar to those of control animals. After treatment with the lowest dose of the herbs i.e. 1 mg/25 body weight, the liver and kidney did not undergo observable changes. However, the herbs at the doses of 5 mg and 10 mg/25 g body weight produced damaging effects on the liver and kidney, the effects produced by the higher dose being more dramatic. The tissue damage was accompanied by elevations of liver LDH isozyme activity in the serum.

Animals↗
PubMed1995

Advances in the design of selective antagonists, potential tocolytics, and radioiodinated ligands for oxytocin receptors.

Despite intensive efforts over three decades in many laboratories, attempts to design peptide antagonists of oxytocin (OT) which are more selective for OT uterine receptors than for vasopressin (AVP), vasopressor V1a receptors, have met with only limited success. We will review the current status of the field and report on studies in our laboratories which have led to the design of highly potent non-selective and selective OT antagonists. Virtually all are more potent (2-6 fold) and a number are more selective (10-12 fold) than Atosiban, currently in clinical trial as a tocolytic agent. Many of these new published and unpublished OT antagonists are thus promising candidates for development as potential tocolytic agents for the prevention of pre-term labor. We also report on promising new radioiodinatable ligands for OT receptors. All the new OT antagonists are valuable new tools for studies on the physiological roles of OT and as probes for OT and AVP receptors.

Amino Acid Sequence↗
PubMed1994

Pregnancy-specific glycoprotein gene expression and the induction by 5-bromo-2'-deoxyuridine.

The pregnancy-specific glycoproteins (PSGs) of the placenta, members of the immunoglobulin superfamily, are encoded by multiple linked genes located on chromosome 19. To study the control of PSG expression, we have immortalized differentiated human placental cells (HP-A1) temperature-sensitive for transformation by a recombinant adenovirus-(ori-)-SV40 tsA mutant virus. We now show that expression of the PSG gene in HP-A1 cells is temperature-sensitive. At the permissive temperature (33 degrees C), these cells expressed low levels of PSG mRNA and synthesized a 64-kDa PSG. Shifting HP-A1 cells to a nonpermissive temperature (39.5 degrees C) increased PSG mRNA expression and biosynthesis with preferential increase in the synthesis of a 54-kDa and a low level of a 72-kDa PSG. Moreover, PSG expression was greatly induced by 5-bromo-2'-deoxyuridine (BudR), which selectively increased synthesis of PSGs of 72 and 54 kDa. In the presence of BudR, HP-A1 synthesized PSGs of 72, 64, and 54 kDa, similar to the pattern seen with placental PSGs. Ribonuclease protection assays demonstrated that HP-A1 cells express the majority of PSG mRNAs and BudR stimulated expression of PSG1 and PSG1-like transcripts. Reverse transcription and polymerase chain reaction analysis using PSG gene-specific primers demonstrated that untreated HP-A1 cells expressed primarily PSG1, PSG2, PSG4, and PSG5 mRNAs. BudR stimulated the expression of all PSG transcripts except PSG4. Moreover, in transient expression assays, BudR increased chloramphenicol acetyltransferase (CAT) expression directed by PSG1-I, PSG4, PSG5, PSG6, and PSG11 promoter-CAT fusion genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1994

Development of pre-implantation mouse embryos under the influence of pineal indoles.

The developmental toxicity of pineal hormones on mouse embryos was examined both in vitro and in vivo. Pregnant ICR mice were divided into groups which received at 1.5 days post-coitum (p.c.) and again at 2.5 days p.c. a subcutaneous injection of one of the following pineal indoles: hydroxyindoleacetic acid (HIAA), melatonin (MEL), methoxytryptophol (MTP) or methoxytryptamine (MTA). Mice treated with the injection vehicle served as the control. The animals were sacrificed at 17.5 days p.c. The pineal indole treatment did not cause changes in the gravid uterine weight, numbers of implants, early resorption, late resorption, dead fetuses and live fetuses, fetal weight or fetal crown-rump length, and did not produce embryos with external or visceral defects. However, some mice treated with MTP or MTA produced litters in which all embryos underwent resorption. Cultured embryos at the 4-cell stage were treated with the aforementioned pineal indoles and examined after 24, 48, 72 and 96 hours. It was found that MTA retarded embryonic development at all time points studied. HIAA also produced a slight inhibitory effect on embryonic development. Some embryos underwent degeneration in response to the MTA and HIAA treatments. However, MEL- and MTP-treated embryos were in general developmentally similar to control embryos. When cultured embryos were treated at the 8-cell to compacting stage, it was found that MTA exerted only a slight retarding effect on embryonic development, while other indoles were devoid of any conspicuous effects.

5-Methoxytryptamine↗
PubMed1994

Epstein-Barr virus-associated gastric lymphoma in Hong Kong Chinese.

We report 11 cases of gastric lymphoma that harbor the Epstein-Barr virus (EBV) encoded small messenger RNA, EBER-1, detected by in situ hybridization. The cases represented 18% of 61 consecutive gastric lymphomas from three institutions in Hong Kong between 1988 and 1993. The mean age of patients was 62 years (range, 33 to 87). The male to female ratio was 5:6. Nine of the 11 (81.8%) EBER-1+ gastric lymphomas were diffuse large cell lymphomas of B-cell type without low grade components. Macroscopically these lymphomas appeared either as large noncleaved cell (centroblastic) or immunoblastic type. From the available follow-up data, five of the nine patients with B-cell lymphoma were alive and well 48, 40, 14, 13, and 12 months, respectively, after gastrectomy and chemotherapy. One patient died of postoperative pneumonia and one died of a second malignancy (esophageal squamous carcinoma) 40 months after gastrectomy. None of the EBER-1+ B-cell gastric lymphomas showed histological features characteristic of low grade lymphoma of the mucosa-associated lymphoid tissue (MALT) type reported to be common in some Western countries. Of the two patients with T-cell lymphoma, one had a pleomorphic T-cell lymphoma and the other had an angiocentric lymphoma. The former was lost to follow-up after the biopsy and the latter presented with gastric perforation and died 1.5 months after gastrectomy. It is concluded that a significant proportion of gastric lymphomas in Hong Kong Chinese are EBV-related and that they show histological features more akin to conventional node-based lymphomas than to MALT-type lymphomas.

Adult↗
PubMed1994

Changes in ovulatory and steroidogenic responses in mice after administration of the ribosome inactivating proteins momorcochin, luffaculin and luffins.

1. Immature mice were induced to ovulate by pregnant serum gonadotropin and human chorionic gonadotropin. 2. The ribosome inactivating proteins luffaculin, luffin-a, luffin-b and momorcochin were administered i.p. 3. It was found that all four ribosome inactivating proteins elicited a reduction in the circulating titer of estradiol-17 beta. 4. Both luffaculin and momorcochin brought about an increase in the number of degenerated oocytes. 5. Only momorcochin caused a decrease in the ovarian weight and the number of ovulated oocytes.

Animals↗
PubMed1994

Differential abilities of the ribosome inactivating proteins luffaculin, luffins and momorcochin to induce abnormalities in developing mouse embryos in vitro.

1. Possible teratogenic activity in the ribosome inactivating proteins luffaculin, luffin-a, luffin-b and momorcochin was tested using cultured mouse embryos. 2. At a dosage of 200 micrograms/ml culture medium, luffin-a and momorcochin did not affect organogenesis in embryos. 3. Luffin-b at a dosage of 100 micrograms/ml brought about decreases in embryo somite number and axial length and induced defects in yolk sac circulation, body axis, optic placodes, branchial apparatus, forelimb buds and cranial neural tube. 4. Luffaculin at a dosage of 100 micrograms/ml caused only reductions in embryo somite number and axial length, but at 200 micrograms/ml produced all of the aforementioned teratogenic effects and defects in otic placodes. 5. The data indicate that ribosome inactivating proteins differ in their potencies as teratogens.

Abnormalities, Drug-Induced↗