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Biomedical subjects

S M Li

Publications and source records attributed to S M Li.

68 records · Page 4Linked to original sources

Effects of individual terphenyls and polychlorinated terphenyls on rat hepatic microsomal cytochrome P-450-dependent monooxygenases: structure-activity relationships.

The effects of o-, m- and p-terphenyl, 2,4-dichloro-, 2,4,6-trichloro-, 2,3,5,6-tetrachloro-, 2,3,4,6-tetrachloro-, 2,4,4''',6- tetrachloro- and 2,3,4,5-tetrachloro-p-terphenyl, 2,3,4,5-tetrachloro-m- and o-terphenyl as inducers of hepatic drug-metabolizing enzymes were determined in immature male Wistar rats. o-Terphenyl, 2,4-dichloro-, 2,4,6-trichloro-p-terphenyl and 2,3,4,5-tetrachloro-o-terphenyl induced 4,4'-dimethylamino antipyrine N-demethylase at total dose levels of 300 mumol/kg and the 2,3,4,5-tetrachloro-p-terphenyl induced ethoxyresorufin O-deethylase (EROD). In contrast, none of the other terphenyls or polychlorinated terphenyls (PCTs) induced these enzyme activities. Previous studies have demonstrated that 2,3,4,5-tetrachloro-p-terphenyl did not exhibit a high affinity for the 2,3,7,8-tetrachlorodibenzo-p-trachlorodibenzo-p-dioxin (TCDD) receptor protein (EC50 = 6.6 X 10(-6) M). In contrast, this study showed that 2,3,4,5-tetrachloro-p-terphenyl was more active than either 2,3,4,5-tetrachloro-o- or m-terphenyl as an inducer of EROD. Moreover, the competitive receptor binding EC50 values for the latter two isomers were greater than 10(-5) M and this result was also consistent with their lack of EROD induction activity. Previous studies showed that analysis of the data for a series of 4'-substituted-2,3,4,5-tetrachlorobiphenyls indicated that the p-terphenyl structural moiety (i.e. 4'-substituent = phenyl) did not interact with high affinity with the receptor protein binding site. Since the 2,3,4,5-tetrachloro o- and m-terphenyls are also poor ligands for the receptor protein, this data and results from other studies indicate that PCT congeners (and commercial mixtures) are therefore unlikely to elicit significant 2,3,7,8-TCDD-like biologic or toxic effects in target species.

Animals↗

Hexachlorobenzene and substituted pentachlorobenzenes (X-C6Cl5) as inducers of hepatic cytochrome P-450-dependent mono-oxygenases.

Hexachlorobenzene (HCB) and 2,3,4,4',5-pentachlorobiphenyl induced a similar spectrum of cytochrome-P-450-dependent mono-oxygenase activities in the rat, including 4-dimethylaminoantipyrine N-demethylase, aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD). Levels of individual cytochrome P-450 isozymes and various mono-oxygenase activities in liver microsomes from rats treated with substituted pentachlorobenzene (X-C6Cl5) and 4'-substituted-2,3,4,5-tetrachlorobiphenyl (X-C12 H5Cl4) analogues demonstrated the remarkable effects of substituent structure on induction activities. The chloro- and bromopentachlorobenzenes induced hepatic microsomal 4-dimethylaminoantipyrine N-demethylase, AHH and EROD; the iodo-, fluoro-, acetamino- and nitropentachlorobenzene analogues together with pentachlorobenzene weakly induced both AHH and EROD (approximately 2-fold or less); and the remaining substituted pentachlorobenzenes tested (X = CH3, OCH3 and OH) were relatively inactive as inducers of microsomal mono-oxygenases. Substituent effects were observed for the induction of liver microsomal cytochromes P-450a, P-450b + e, P-450c, P-450d and total cytochrome P-450 by the X-C6Cl5 and X-C12H5Cl4 analogues. The chloro- and bromopentachlorobenzene analogues in both series induced total cytochrome P-450 and cytochromes P-450a to P-450d, whereas the hydroxy-, methyl- and methoxy-substituted analogues in both series were relatively inactive as inducers of cytochrome P-450. Iodo-, fluoro- and nitropentachlorobenzene were weak 3-methylcholanthrene-type inducers and, in contrast to the corresponding biphenyl analogues, had little or no effect on the induction of cytochromes P-450a, P-450c and P-450d.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Polychlorinated biphenyls: correlation between in vivo and in vitro quantitative structure-activity relationships (QSARs).

The in vivo quantitative structure-activity relationships (QSARs) for several polychlorinated biphenyls (PCBs) were determined in the immature male Wistar rat. The ED25 and ED50 values for hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) induction as well as for body weight loss and for thymic atrophy were determined for nine PCB congeners and 4'-bromo-2,3,4,5-tetrachlorobiphenyl. The most active compounds were the coplanar PCB congeners, 3,3',4,4',5-penta- and 3,3',4,4',5,5'-hexachlorobiphenyl; for example, their ED50 values for body weight loss were 3.25 and 15.1 mumol/kg, respectively. The in vivo toxicity of the coplanar PCB, 3,3',4,4'-tetrachlorobiphenyl, was significantly lower (ED50 for body weight loss = 730 mumol/kg) than the values observed for the more highly chlorinated homologs, and this was consistent with the more rapid metabolism of the lower chlorinated congener. The dose-response biologic and toxic effects of several mono-ortho-chloro-substituted analogs of the coplanar PCBs, including 2,3,4,4'5-, 2,3,3',4,4'-, 2',3,4,4',5- and 2,3',4,4',5-penta-, 2,3,3',4,4',5- and 2,3,3',4,4',5'-hexachlorobiphenyl were also determined, and members of this group of compounds were all less toxic than 3,3',4,4',5-penta and 3,3',4,4',5,5'-hexachlorobiphenyl. There was a good rank order correlation between the in vivo QSAR data and the in vitro QSARs for PCBs that were developed from their relative receptor binding affinities and potencies as inducers of AHH and EROD in rat hepatoma H-4-II E cells in culture. These results are consistent with the proposed receptor-mediated mechanism of action for PCBs. In addition, for this series of halogenated biphenyls there was a linear correlation between their in vivo toxicity in rats and their in vitro monooxygenase enzyme induction results. Assuming that the in vivo toxic responses in the rat are representative toxic responses to PCBs, then these results support the predictive utility of the in vitro bioassay with rat hepatoma H-4-II E cells as a short-term test system for the potential toxicity of this class of halogenated aryl hydrocarbons.

Animals↗

Early vascular grafting to prevent upper extremity necrosis after electrical burns.

Presented in this paper are the surgical considerations in the management of 8 electrically injured patients, with special reference to the care for wrist damage associated with impaired blood flow, and the prospect for effective recovery. Sound surgical principles, such as early diagnosis and repair of artery damage, complete débridement of dead tissue and affective wound closure, in conjunction with intensive general treatment and overall planning, are necessary for maximally rehabilitated limbs. The electrically injured seem to have benefited a great deal from the procedures outlined, with a lowered incidence of amputation and a better functional recovery.

Amputation, Surgical↗

Giant-cell tumor of bone: analysis of two hundred and eight cases in Chinese patients.

Giant-cell tumor of bone seems to occur more frequently in Chinese people than in those residing in Western countries. The estimated incidence is about 20 per cent of all primary tumors of bone. Of 208 surgically treated and pathologically proved giant-cell tumors, 194 were benign. We excluded patients with primary or secondary amputation unrelated to recurrence and those followed for less than two years or lost to follow-up. Of the remaining 111 patients who were followed for more than two years, twenty-nine had a recurrence, giving a recurrence rate of 26.1 per cent. The rate of recurrence was highest following curettage and bone-grafting (41.2 per cent) and was much lower in patients who were treated by resection and fusion (7.1 per cent). Since resection of this tumor with reconstructive procedures, either by massive homogenous bone-grafting or artificial joint replacement, is complicated and might cripple the patient if it fails, we propose excision and curettage with bone-grafting as the most suitable method of treatment in the majority of patients with giant-cell tumor of bone.

Adolescent↗

Actin inclusions in stromal cells of fibroepithelial tumor of breast: immunohistochemical and ultrastructural studies.

An uncommon occurrence of actin inclusions in the stromal cells of a benign fibroepithelial tumor of breast is reported. Histologically, many of the stromal cells contained round and eosinophilic intracytoplasmic inclusions identical to those seen in inclusion body fibromatosis. Ultrastructurally, these inclusions represented dense spherical clumps of microfilaments derived from rough endoplasmic reticulum. The literature was reviewed and follow-up data showed that the clinical course of these morphologically distinctive benign fibroepithelial tumors was relatively indolent if completely excised, in contrast to inclusion body fibromatosis, which commonly recurs. The pathogenesis may be related to abnormal production of truncated actin filaments or alteration in microenvironment.

Actins↗