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Biomedical subjects

C L Chan

Publications and source records attributed to C L Chan.

At least 73 records · Page 4Linked to original sources
PubMed1991

Expression of human O6-methylguanine-DNA methyltransferase in Chinese hamster ovary cells and restoration of cellular resistance to certain N-nitroso compounds.

We have constructed a plasmid in which the expression of human O6-methylguanine-DNA methyltransferase (MGMT) cDNA is driven by the Rous sarcoma virus promoter sequence. Transfection of this plasmid into Chinese hamster ovary (CHO) cells results in expression of MGMT and in cellular resistance to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 1-(2-chloroethyl)-1-nitrosourea (CNU), but not to N-nitroso-N-ethylurea. The specific activity of MGMT in transfected CHO cells correlated well with their resistance to MNNG and CNU. Southern analysis showed that the plasmid had been integrated into the CHO cell genome. Western analysis of extracts from transfected CHO cells using an antibody against a peptide corresponding to the carboxyl-terminal end of the human MGMT protein demonstrated a single band with a molecular size of 24-25 kDa; no such band was observed in extracts from wild-type CHO cells. These transfected cells may therefore be used to study the role of MGMT in the repair of alkylating DNA lesions and to determine its importance in carcinogenesis as well as in chemotherapy.

Alkylating Agents↗
PubMed1991

Immunocytochemical analysis of glial cells in the hypomyelinated optic nerve of the BW mutant rat.

The Browman-Wyse (BW) rat is a mutant with structural defects of the visual system, including a failure of the proximal (retinal) end of the optic nerve to myelinate. This latter abnormality is correlated with an absence of CAII+ oligodendrocytes, but we have previously shown that astrocytes are normally distributed, as judged by morphological characteristics of GFAP+ cells in vivo. We have further examined in vitro the immunohistochemical characteristics of macroglia isolated from the BW optic nerve, either as cell suspensions or after 4 days in culture. Cell cultures derived from the hypomyelinated proximal segment of BW optic nerves contained very few 0-2A progenitor cells (from which oligodendrocytes and cells with the GFAP+/A2B5+ phenotype develop), whereas over 90% of the glia were Schwann cells. A proportion of these few 0-2A progenitor cells differentiated normally after 4 days in vitro into both progeny phenotypes in appropriate media. Accordingly, we conclude that the myelination deficiency in the BW optic nerve could be explained as a failure of 0-2A progenitor cells to populate fully the proximal extremity of the nerve during development. Since most glia isolated from adult optic nerves did not adhere to the culture substrate, we analysed the phenotypes of freshly isolated cells in suspension. Comparing optic nerves of normal adult rats with those of BW mutants, a significantly higher fraction of the GFAP+ cells reacted with A2B5 in cell suspensions of the latter. The double-labelled cells which are present in abnormally high numbers may be the differentiated progeny of 0-2A progenitors in the hypomyelinated segment of nerve. One explanation for these findings is that Schwann cells within the BW nerve induce the differentiation of 0-2A progenitor cells to the GFAP+/A2B5+ phenotype. We investigated this possibility using conditioned medium from cultured Schwann cells which increased tenfold the frequency of GFAP+/A2B5+ cells in normal neonatal rat optic nerve cultures. Oligodendrocyte numbers showed a concomitant decline with increasing concentration of Schwann cell conditioned medium. Hypomyelination in the BW rat optic nerve may therefore arise because Schwann cells, present in the proximal segment of the nerve, not only impede the migration of 0-2A progenitor cells but also release a factor which induces those 0-2A progenitor cells which arrive in the proximal segment of the nerve to differentiate into GFAP+ cells at a critical stage in oligodendrocyte development.

Animals↗
PubMed1991

Vergence orthoptics: validity and persistence of the training effect.

The validity and permanence of orthoptic treatment for vergence deficiencies requires investigation due to the subjective nature of determining success in most clinical cases, i.e., the amelioration of symptoms and increases in vergence ranges. The relation between Risley prism vergences, a subjective measure, and vergence tracking rate, an objective index, is investigated. The course of orthoptics progress is compared in cases of clinical vergence dysfunction. Vergence-deficient control subjects showed no significant change in either index. However, trained subjects demonstrated rapid increases in both indices. The persistence of the training effect was monitored for up to 9 months. No regression was observed in subjects who met all release criteria, but one subject who chose to terminate therapy early showed a slow regression in tracking rate and recurrence of symptoms. These data support the validity of vergence training and increase the plausibility of previous clinical reports of orthoptics success.

Adult↗
PubMed1991

The controversy of heparin therapy as an adjunct to thrombolysis in acute myocardial infarction.

Heparin is used routinely in the US as adjunct therapy for prevention of reocclusion after thrombolysis during acute myocardial infarction. A review of the literature shows controversy over the efficacy of heparin following thrombolysis. Both beneficial and a lack of beneficial effects have been reported with heparin. From a pathophysiologic viewpoint, there appears to be a need for full heparinization in the postlytic period because the residual stenosis is highly thrombogenic. However, optimal dose, time, and mode of heparin therapy has not been defined. Despite a lack of definitive data, it seems reasonable to administer intravenous heparin immediately after thrombolytic therapy to achieve a partial thromboplastin time 1.5-2.0 times control that is concurrent with an antiplatelet agent such as aspirin. These recommendations are consistent with the consensus opinion of the American College of Cardiology and the American Heart Association.

Drug Therapy, Combination↗
PubMed1990

Oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells from neonatal and adult rat optic nerve differ in their responsiveness to platelet-derived growth factor.

We have investigated, in vitro, the mitogenic responsiveness to platelet-derived growth factor (PDGF) of oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells isolated from adult rat optic nerve and their differentiation into oligodendrocytes. Progenitor cells from adult optic nerves differentiate into oligodendrocytes in a limiting concentration of foetal calf serum more slowly than in cultures of neonatal cells. Nevertheless, differentiation of oligodendrocytes from progenitors is nearly complete by 6 days in vitro, with 50% expressing galactocerebroside by 4-5 days. In these experiments, adult optic nerve cells were grown in medium containing PDGF, a potent mitogen for neonatal O-2A progenitor cells, and yet the decline in numbers of O-2A progenitor cells matches the rise in oligodendrocyte numbers. We suggest that this is because adult O-2A progenitor cells differ from their neonatal counterparts and do not show the same proliferative response in the presence of exogenous PDGF. We tested this hypothesis by a quantitative autoradiographic analysis of tritiated thymidine-labelled nuclei, comparing percentages of labelled adult and neonatal O-2A lineage glial cells in low-serum medium, in the presence of absence of PDGF, with their response to a monolayer of neonatal rat cortical type 1 astrocytes or astrocyte-conditioned medium. Whereas, adult O-2A progenitors responded to astrocyte monolayers and to conditioned medium from astrocyte cultures, there was no dose-dependent response to PDGF-BB over a wide range of concentrations. Antibodies to human PDGF neutralise the growth-promoting activity of astrocyte-conditioned medium for neonatal O-2A cells but do not neutralise astrocyte-conditioned medium stimulation of adult O-2A progenitor cells. This indicates that the principal astrocyte-derived growth factor(s) for adult O-2A progenitor cells is unlikely to be PDGF.

Animals↗
PubMed1990

Induction and purification of O6-methylguanine-DNA-methyltransferase from rat liver.

O6-Methylguanine-DNA-methyltransferase (OMMT) is a DNA repair protein that plays an important role in chemotherapy, mutagenesis and carcinogenesis. The sp. act. of OMMT in rat liver can be induced by approximately 12- to 20-fold by treatment of the rats with ionizing radiation. The effects of dose and time were investigated in this study. We have found that OMMT sp. act. can be increased, although to a lower extent, in kidney, spleen and brain in addition to liver. However, the sp. act. of OMMT in lung was reduced by irradiation. OMMT has been purified from the livers of irradiated rats by solubilization in high-salt-containing buffer, ammonium sulfate precipitation and a series of column chromatographic steps, including phenyl-Sepharose, heparin-agarose, double-stranded DNA-cellulose and FPLC. A 3000-fold enrichment of OMMT was achieved from the induced liver preparations. However, with regard to the sp. act. of this protein in normal rat liver, the fold purification was approximately 35,000. After methylation, OMMT during the course of its action exhibited a mol. wt of 28 kd under SDS-PAGE conditions.

Animals↗
PubMed1990

Hepatocellular carcinoma in Hong Kong: clinical study on 340 cases.

Three hundred and forty cases of hepatocellular carcinoma in Hong Kong were studied for their clinical features, and various factors were analysed for their prognostic values. The clinical presentation was often vague and rather non-specific and a majority of patients were presented late and often unresectable. The overall median survival was 8 weeks. The Karnofsky performance scale and bilirubin level were the most important prognostic factors. The treated group survived longer than the untreated group.

Adolescent↗
PubMed1990

Future of assisted reproductive technologies.

Within a decade, from the birth of Louise Brown in 1978, there has been tremendous advances in the field of assisted reproduction. These advances are the collective result of techniques known as Assisted Reproductive Technologies (ART). ART is defined as techniques in which the oocyte is handled in-vitro before replacement either as oocytes or embryos. The techniques in ART include in-vitro fertilisation and embryo replacement (IVF-ER), gamete intra-fallopian transfer (GIFT), tubal embryo (TET), donor oocytes and embryos, and freezing of embryos and oocytes. The most recent has been assisting fertilisation by micro-manipulation, including zonal procedures and micro-insemination, e.g. micro-insemination sperm transfer (MIST). There has also been many ethical issues in ART, and little advance in the "take home" baby rate. There is now major interest in co-culture of embryos with ampullary, endometrial and fibroblast mono-layers, to improve the quality of these embryos before their return into the mother. Because of the public's interest in ART, its usefulness has been "oversold". In time to come, ART may be limited to patients who really need it.

Forecasting↗
PubMed1989

The Salmonella typhimurium his operon leader region contains an RNA hairpin-dependent transcription pause site. Mechanistic implications of the effect on pausing of altered RNA hairpins.

The Salmonella typhimurium his leader region contains a well documented transcription attenuator. We report here the results of in vitro transcription studies that characterized a transcription pause site in the his leader region. The pause occurred after synthesis of the first his leader secondary structure (A:B) and immediately preceding addition of G103 to the nascent transcript. RNA polymerase pausing at this site would allow a ribosome synthesizing the his leader peptide to release the paused polymerase and synchronize transcription and translation of the his leader region. The half-life of transcription complexes paused in the his leader was enhanced by NusA, but not guanosine 5'-diphosphate 3'-diphosphate. Nuclease digestion and RNA modeling studies were consistent with a compact three-dimensional structure for the his pause RNA. The half-life of the his leader paused transcription complex was decreased greatly on altered templates in which the C71-G93 base pair was disrupted but was unchanged when the C65-G100 base pair was disrupted. This result is consistent with a model for the structure of paused transcription complexes in which a portion of the RNA:DNA elongation heteroduplex is retained.

Base Sequence↗
PubMed1989

Birth from replacement of frozen-thawed embryos after failure of gamete intra-fallopian transfer: a successful pregnancy case.

The patient was 8 years subfertile and had failed other forms of treatment when she was enrolled in the GIFT program. Of the total of 16 oocytes recovered 4 were transferred and the remaining 12 inseminated with her husband's sperm. Four resulting embryos were frozen. When she did not conceive, the 4 embryos were thawed 3 months later and replaced into her. She conceived and recently delivered a pair of twins. The protocol will be discussed in detail. Cryopreservation of embryos therefore may increase the patient's chance of pregnancy in a GIFT program.

Adult↗
PubMed1989

Importance of antenatal karyotyping in the management of a case with vestigial radii.

An uncommon presentation of vestigial radii in a Trisomy E fetus was detected prenatally with ultrasound scanning. Appropriate counselling and obstetric management were thus carried out avoiding an unnecessary caesarean section. The importance of identifying high risk pregnancy and prenatal diagnosis by a qualified personnel cannot be overstressed.

Abnormalities, Multiple↗
PubMed1989

Management of unexplained infertility.

Unexplained or idiopathic infertility means no cause can be found to account for the infertility. This depends on the enthusiasm to look for the subtle causes like luteal phase defect (LPD), luteinizing unruptured follicle syndrome (LUFS), abnormal prolactin secretion, psychogenic, environmental, nutritional and immunological factors. Sometimes, these subclinical conditions can be corrected. Failing to identify these treatable conditions, various empirical treatments, laboratory manipulation or assisted reproductive techniques (ART) can be attempted to achieve conception.

Female↗
PubMed1988

Gamete intrafallopian transfer (GIFT): an alternate method of conception in couples with unexplained infertility, endometriosis and oligo-asthenospermia.

138 treatment cycles of GIFT were carried out in couples with mainly unexplained infertility, endometriosis and male factor. The overall pregnancy rate was 24.6%, abortion 29.2%, multiple pregnancy 20.6% and ectopic pregnancy 0%. Four oocytes seem to be the optimal number of oocytes to be transferred. Patients with male factor infertility fared the worse in comparison with the other groups. Successful in-vitro fertilization of excess eggs did not correlate with a positive outcome of the GIFT procedure.

Endometriosis↗
PubMed1987

Synthesis, biological evaluation, and quantitative structure-activity relationship analysis of 2-hydroxy-1H-isoindolediones as new cytostatic agents.

A series of 16 derivatives of 2-hydroxy-1H-isoindole-1,3-diones was designed and synthesized as potential antitumor agents. The cytostatic activity against L1210 cell growth of these compounds was studied, and their IC50 values were found to be in the range of 10(-4) to 10(-8) M. Quantitative structure-activity relationship analysis of these compounds showed that the inhibitory effect was well correlated with the electronic and the lipophilic parameters. Derivatives having a substituent with strongly electron-donating properties at the 6-position showed enhanced inhibitory activity while compounds having an electron-withdrawing group at the same position showed lower activity.

Animals↗