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Biomedical subjects

W S Chan

Publications and source records attributed to W S Chan.

At least 55 records · Page 3Linked to original sources
PubMed1989

Effect of photodynamic therapy on anti-tumor immune defenses: comparison of the photosensitizers hematoporphyrin derivative and chloro-aluminum sulfonated phthalocyanine.

The effects of the two photosensitizers chloroaluminum sulfonated phthalocyanine (ClAlSPc) and hematoporphyrin derivative (HpD) on the functional activities of macrophages and natural killer (NK) cells, two immunocyte populations implicated in the control of tumor development and spread, have been investigated. Murine peritoneal macrophages treated in vivo with ClAlSPc or HpD at 10 mg/kg body weight showed no impairment of Fc-mediated phagocytic capacity and only minor disturbances of in vitro tumoricidal/tumoristatic function. The NK cell activity of splenocytes obtained from photosensitizer-treated mice, assayed 24 or 48 h after i.v. injection of ClAlSPc or HpD at 10 mg/kg was unaffected compared to controls. However significant inhibition of NK activity was observed when splenocytes obtained from mice with or without subcutaneous Colo 26 tumors, treated with ClAlSPc plus laser therapy (675 nm) were used as effector cells. The results show that impairment of some anti-tumor activity can be observed in phthalocyanine treated or phthalocyanine + laser-treated animals but this relatively minor impairment may augur well for the use of systemic phthalocyanine administration in photodynamic therapy.

Animals↗
PubMed1989

Variations in WGA-binding proteins in tumours growing in different implantation sites.

The protein/glycoprotein composition of Triton X100 extracts of four metastatic tumour lines have been compared by gel electrophoresis after the implantation into different sites of the body. No consistent differences in the patterns were noted after staining with Coomassie Blue or treating with concanavalin A. In contrast, after treating with wheat germ agglutinin (WGA), the patterns varied with site. This was most marked with the ML and M5 tumours, where the overall binding was much lower for some sites. Although WGA binding with the LL and BL6 tumours was generally higher than with the ML and M5, reduced binding was still evident for some sites. Reduced WGA binding was also observed for extracts of secondary tumour growing in the liver or lungs.

Animals↗
PubMed1988

Tissue uptake, distribution, and potency of the photoactivatable dye chloroaluminum sulfonated phthalocyanine in mice bearing transplantable tumors.

The potency of chloroaluminum sulfonated phthalocyanine (ClAlSPc) as a photosensitizing agent for photodynamic therapy of cancer was evaluated in vivo by its ability to be taken up and retained by murine tumors of diverse histological origin. Antitumor effects following laser irradiation were evaluated by measurement of the tumor weights of dissected-out tumor masses. Three tumors (Colo 26, a colorectal carcinoma; M5076, a reticulum cell sarcoma; and UV-2237, a fibrosarcoma) growing s.c. in the flank region retained substantially greater quantities of ClAlSPc than did adjacent skin and muscle achieving peak values 24-48 h after the i.v. administration of ClAlSPc (10 mg/kg). The relative magnitude of ClAlSPc retention by these tumors was Colo 26 greater than M5076 greater than UV-2237. However, normal liver and spleen were organs which retained the greatest amounts of ClAlSPc even compared to the s.c. grown tumors and other normal tissues examined. Flow cytometric analysis of tumor cell suspensions obtained from collagenase-digested tumors showed that individual neoplastic cells were capable of taking up and retaining ClAlSPc. Photodynamic therapy, undertaken by i.v. administration of dye (5 mg/kg) followed 24 h later by local laser light irradiation (675 nm, 100 J), brought about significant (Colo 26, M5076, and 3LL tumors) and obvious but nonsignificant (UV-2237 tumor) reductions in tumor weights, as assessed 5 days later. Thus, selective tumor retention of ClAlSPc coupled with a significant response to red light produced dramatic alterations in cancer growth.

Aluminum↗
PubMed1988

Maximum length sequence applied to the measurement of brainstem auditory evoked responses.

An evoked response may be assumed to consist of synchronous electrical activities of groups of neurons in response to a stimulus. Unfortunately, this response is usually weak and often masked by the background EEG activity generated spontaneously by the brain. In order to extract the embedded evoked response we have employed the theory of maximum length sequence, assuming only a temporal linearity of the system from which measurements are taken. The technique has been applied successfully with the aid of a microcomputer. The system also supports the same measurement by a conventional averaging technique. The results of the two are compared, indicating the advantages of the maximum length technique: improved signal-to-noise ratio, repeatability and speed.

Animals↗
PubMed1987

Ca2+/calmodulin-dependent phosphoprotein phosphatase activity of calcineurin in rat striatum: effect of kainic acid lesions.

Calcineurin, a Ca2+ and calmodulin (CM)-dependent phosphatase, has been shown to be present in high concentrations in the striatum. Using inhibitor-1(phosphorylated by cAMP-dependent protein kinase) as a substrate, we found Ca2+/CM-dependent phosphatase (calcineurin) to be more than 2-fold higher than non-Ca2+/CM-dependent phosphatase in the rat striatum. In order to determine the cellular localization of calcineurin, striatal kainic acid injections were used to destroy neurons whose cell bodies are present at the site of injection. Glutamic acid decarboxylase (GAD) activity was measured as an indicator of destruction of striatal GABA-ergic neurons. After intrastriatal injection of 1 and 2 ug of kainic acid, there was a significant decrease of both calcineurin and GAD. However, injection of 0.5 ug kainic acid into the striatum reduced GAD activity by 81%, but had no effect on calcineurin phosphatase activity. Thus calcineurin does not appear to be equally distributed among all types of striatal neurons, but rather may be concentrated in neurons that are less sensitive to kainic acid than the GABA-ergic neuron.

Animals↗
PubMed1986

Cell uptake, distribution and response to aluminium chloro sulphonated phthalocyanine, a potential anti-tumour photosensitizer.

The uptake, retention and effects of aluminium chloro sulphonated phthalocyanine (AlSPc) were measured in two cell lines, UV-2237 a murine fibrosarcoma and the non-tumorigenic NIH/3T3 fibroblast line. The behaviour of cells treated with AlSPc was compared with that of those treated with haematoporphyrin derivative (HpD), a photosensitizer often used in photodynamic therapy (PDT) of cancer. AlSPc absorbs light strongly in the red region, is taken up by cells in a dose dependent fashion and is retained in vitro over a period of days (5 days after exposure greater than 40% remains cell-associated versus less than 25% of HpD). Additionally AlSPc was less cytotoxic to cells, maintained in darkness or exposed to room light, compared to HpD (100% viability versus 0% viability 3 days after 60 min exposure to room light). However red light (approximately 600-700 nm) caused greater toxicity in AlSPc-treated cells (100%) than in similarly exposed HpD-treated cells (less than 60%). No significant differences were detected between the responses of the fibrosarcoma and the fibroblast cell lines. These characteristics of AlSPc suggest that it may prove to be a useful photosensitizer for PDT of cancer and this possibility is discussed.

Animals↗
PubMed1985

The binding of ConA and other lectins to surface glycoproteins: a comparison of a subcutaneous tumour and its liver metastases.

The glycoprotein composition of a transplantable subcutaneous lymphosarcoma (1 degree) and its liver metastases (2 degrees) have been examined in Triton X-100 extracts obtained from tissue, single cells and membrane preparations by using electrophoresis and treatment with radio-labelled lectins. No consistent differences could be detected in the electrophoretic patterns of 1 degree and 2 degrees tumour using RCA-60 or gorse. Small differences were detected using Concanavalin A; all but one of these were eliminated as being due to differential host contamination. A minor band of 178,000 daltons molecular weight was found in 1 degree tissue, cells and membranes that was absent in extracts from 2 degrees tumour. Percoll density gradient separations suggested that this glycoprotein belonged to a small subpopulation of cells; their identity remains uncertain. The band was still detected when tumour was grown from direct liver implants, but it disappeared when this growth metastasized to another lobe. The results provide evidence that metastasis can be accompanied by a very subtle change in the tumour glycoprotein profile. Such a change may have important consequences for host/tumour interactions and subsequent metastatic spread.

Animals↗
PubMed1984

Differences in surface expression of WGA-binding proteins of cells from a lymphosarcoma and its liver metastases.

The protein and glycoprotein compositions of a subcutaneous lymphosarcoma (1 degree) and its metastatic deposits in the liver (2 degrees) have been investigated in Triton X-100 extracts obtained from tissue, single cells and membrane preparations. No consistent differences in the electrophoretic patterns for 1 degree and 2 degrees tissue or cells were observed for separations visualized with the protein stain Coomassie Blue. Substantial and consistent reductions in the glycoprotein content of extracts from 2 degrees tissue or cells were observed if the separated proteins were treated with the radioiodinated lectin, Wheat Germ Agglutinin (WGA). Densitometric scans of autoradiographs indicated that WGA binding occurred in 4 major areas; the approximate mol. wts of these were 180,000, 102,000, 84,000 and 23,000 daltons. All these components except the 23,000 component were shown to be located in the cell membrane and to be reduced in 2 degrees preparations. Possible sources of host contamination were also investigated, but these did not show WGA binding patterns that were similar to that obtained for the tumour. If 2 degrees tumour was transplanted into the 1 degree site, the resultant growth exhibited a WGA-binding pattern normally shown by a 1 degree tumour growing in this site. Conversely, if 1 degree tumour was transplanted into the liver, the WGA binding of the resultant growth was substantially reduced. The results suggest that local and metastatic tumours do contain cells that express different glycoproteins on their surfaces but that the site of tumour growth is a very important factor in determining this difference in surface expression.

Animals↗
PubMed1976

A possible reflex mechanism of hypotensive action of extract from Cassia tora seeds.

The Chinese medicinal herb Chueh-ming-tzu, seeds of Cassia tora (Leguminosae) Linn., elicits hypotensive effects in anesthetized rats. Experimental results indicate that the hypotensive effect of the Cassia tora extract possibly involves a vagal reflex which reciprocally alters the vasomotor tone of the centrally emanating sympathetic nervous system. It is shown that the capacity of the Cassia tora extract to reduce blood pressure is significantly reduced in vagotomized rats and that hypotensive effects are greatly antagonized in rats whose sympathetic nervous systems are interrupted by transection of the spinal cord.

Animals↗
PubMedDate not supplied

The growth and metastasis of four commonly used tumour lines implanted into eight different sites: evidence for site and tumour effects.

The growth and metastasis of four commonly used experimental tumour lines have been compared after the implantation of cells into a lobe of the liver, the spleen, the left kidney, the peritoneal cavity, the thorax, the right thigh muscle, subcutaneously into the dorsolumbar region and intravenously into the tail vein or the right femoral vein. This was done to assess the importance of site in affecting metastatic distribution, and to determine whether any general conclusions could be drawn as to the role of this factor. Tumours grew at variable rates in different sites, but this did not affect the extent or distribution of metastasis. Each line gave a characteristic pattern that could be considerably modified by site. For example, in the spleen, metastasis was always extensively to the liver; in the kidney, and to some extent in the muscle, metastasis was similar to that obtained for intravenously injected cells; in the peritoneal cavity or thorax, metastasis was usually lower than from other sites; and in the liver, the metastasis to other lobes of the liver and to the lungs was modified. Many of these findings could be explained by both specific and non-specific factors operating at each site. It is suggested that interactions at the primary site of tumour growth may be very important in affecting metastasis, and that in the future more attention should be given to this factor in order to make progress in understanding tumour spread.

Animals↗
PubMedDate not supplied

Common C677T polymorphism of the methylenetetrahydrofolate reductase gene and the risk of venous thromboembolism: meta-analysis of 31 studies.

BACKGROUND: Although the common 677 C --> T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene is implicated in the development of hyperhomocysteinemia, its correlation with venous thromboembolism (VTE) remains controversial. We conducted a meta-analysis of previously published studies to clarify the role of the MTHFR 677 TT homozygous genotype in association with VTE. METHODS AND RESULTS: Relevant articles were retrieved from a systematic search of Medline and Embase from 1990 to September 2001. Two independent reviewers abstracted data on the characteristics of the cases with VTE and controls without VTE. We pooled the rates of the MTHFR 677 TT genotype in both groups, as well as the odds ratio (OR) of VTE in the presence of the TT versus CC or CT genotypes. In 31 published studies, comprising 4,901 cases and 7,886 controls, the pooled prevalence of the MTHFR 677 TT genotype was slightly higher among cases (14.3%) than controls (11.7%), conferring a borderline degree of heightened risk [pooled OR (OR(p)) 1.2, 95% confidence interval (CI) 1.1-1.4]. After excluding cases with a classic thrombophilia factor, the pooled prevalence rates of the MTHFR 677 TT genotype among 11 studies were 17.7 and 12.3%, respectively (OR(p) 1.5, 95% CI 1.2-1.9). CONCLUSIONS: The classic MTHFR C677T gene polymorphism is weakly associated with an increased risk of VTE. It is unlikely that the purported relationship between hyperhomocysteinemia and VTE is mediated by this gene defect to a substantial degree, although other undiscovered gene polymorphisms may explain this association. Until more compelling data are made available, we do not recommend that testing for the MTHFR C677T polymorphism be routinely included as part of any clinical thrombophilia assessment.

Adult↗
PubMedDate not supplied

Differential expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate glutamate receptors in the rat striatum during postnatal development.

Alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA)-type glutamate receptors (GluR1-4) are one of the most important ionotropic glutamate receptors in the striatum, a key region of the basal ganglia. The present study investigated the trend of developmental expression of AMPA receptor subunits in the striatum of rats in different developmental stages, i.e., at postnatal day 7 (PND7), PND21 and adult. Perfuse-fixed striatal sections were used. The expression of AMPA subunits was studied by immunofluorescence and reverse transcriptase-polymerase chain reaction (RT-PCR). RT-PCR revealed that the levels of expression of the GluR1 and GluR3 mRNAs were the same among the age groups. The level of GluR2 mRNA was highest in PND21 rats and lowest in adult. The highest level of GluR4 mRNA was detected in rats at PND7. Similar trends of GluR1, GluR2 and GluR2/3 immunoreactivity expression were observed using commercially available specific antibodies. In addition, a large proportion of parvalbumin-immunoreactive GABAergic interneurons in the striatum were found to display GluR1 immunoreactivity in PND21 and adult rats. In contrast, most of the choline acetyltransferase-immunoreactive cholinergic interneurons were found to display GluR2 immunoreactivity but less GluR1 and no GluR2/3 immunoreactivity in PND21 and adult rats. The present study suggests that there is a distinct pattern of expression of AMPA-type receptor mRNAs and proteins in the rat striatum at different stages of development.

Animals↗
PubMedDate not supplied

Structure-activity relationship of caffeic acid analogues on xanthine oxidase inhibition.

Caffeic acid has been reported to have activity on xanthine oxidase inhibition which is related to several diseases, e.g. gout, hepatitis and tumors. Based on this study, the alpha, beta-unsaturated COOH moiety in the molecule of caffeic acid plays a very important role on the xanthine oxidase inhibition because hydrocaffeic acid was inactive and the activities of coniferyl aldehyde and coniferyl alcohol were reduced as compared with ferulic acid. Moreover, chlorogenic acid showed a weaker activity than caffeic acid. On the other hand, the phenolic OH group present in the molecule of caffeic acid makes an important contribution to the activity, e.g. transcinnamic acid in which the absence of the phenolic OH group in the structure reduced its activity as compared with caffeic acid. Ferulic acid, isoferulic acid and 3,4-dimethoxy cinnamic acid also had reduced activity due to the methoxy groups replacing the phenolic OH group in the structures. However, m-coumaric acid displayed the strongest activity (IC50 = 63.31 microM) and induced uncompetitive inhibition with respect to the substrate xanthine (Ki = 21.568 microM). Caffeic acid (IC50 = 74.6 microM) showed the second strongest activity, followed by p-coumaric acid (IC50 = 111.09 microM).

Caffeic Acids↗