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Biomedical subjects

C H Kuo

Publications and source records attributed to C H Kuo.

At least 109 records · Page 6Linked to original sources
PubMed1989

Isolation of a novel retina-specific clone (MEKA cDNA) encoding a photoreceptor soluble protein.

We have reported the isolation of clones which are candidates for retina-specific cDNAs. One of the cDNA clones, pCR-470, was further characterized. We found that mRNA corresponding to the pCR-470 was expressed only in the retina and encodes an unknown soluble protein whose molecular weight and pI are calculated to be 26,935 and 5.35, respectively. We designated it as a MEKA protein, because its amino acid sequence starts from M-E-K-A. It was found by in situ hybridization that MEKA mRNA was transcribed only in the photoreceptor cells and accumulated in the inner segments just like opsin mRNA. The MEKA cDNA was ligated with expression vector PEX 1, and a MEKA-fusion protein synthesized in E. coli was purified and used as an antigen. By the Western blot analysis anti-MEKA protein serum reacted with a soluble 32 kDa protein from bovine retina and 33 kDa for chick, but not with proteins from other tissues. Immunohistochemical study showed that anti-MEKA stained only the photoreceptor cells in bovine, chick, rat and mouse retinas.

Amino Acid Sequence↗
PubMed1989

A longitudinal study on the expression of the opsin gene in the degenerating retina of C3H/He mice.

By a combination of immunohistochemistry and in situ hybridization using a 35S-labeled opsin cDNA probe, it was revealed in rd mutant C3H/He mice that opsin mRNA is not detectable in photoreceptor cells which still exhibit opsin-immunoreactivity at later stages of retinal degeneration. This indicates that the photoreceptor cells of rd mutant mice cease to express the opsin gene at earlier stages of retinal degeneration.

Animals↗
PubMed1988

Presence of retina-specific proteins in the lamprey pineal complex.

The pineal complex of river lamprey reacted with the antisera raised against retina specific proteins including bovine opsin, chick visinin and frog light-sensitive cyclic GMP phosphodiesterase (PDE). Immunoreactive materials stained with anti-opsin were evenly located at the outer segment of photoreceptor cells in the pineal organ and also found in the parapineal organ. Although anti-visinin stained the pineal and parapineal photoreceptor cells, the immunopositive photoreceptor cells were observed only at the lateral portion and not at the medial portion of the pineal organ. No immunoreactive materials were found in the pineal complex by the anti-PDE, whereas the anti-PDE reacted with photoreceptor cells of the retinal tissue. The data suggest that the pineal and parapineal retinas of lamprey contain opsin- and visinin-like proteins with different distribution in their photoreceptor cell layer as found in the lamprey retinal tissue.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1987

Two types of lamprey retina photoreceptors immunoreactive to rod- or cone-specific antibodies.

The localization of structures immunoreactive to antisera against opsin (OPS; a specific marker for rods) and against visinin (VIS; a specific marker for cones in the vertebrate retina) was investigated in the retina of the river lamprey (Lampetra japonica) by means of fluorescence microscopy. Different immunoreactive structures were found with the two antisera. A vitreadly located structure in the outer nuclear layer displayed OPS-like immunoreactivity, while a scleradly located one exhibited VIS-like reactivity. Thus, the two antisera applied to the retina of the river lamprey permit the distinguishing of rod and cone immunoreactive photoreceptors such as occurs typically in all vertebrate classes. The former appears in the outer segments of a type of rod cells, and the latter in the cell bodies and axons of cones.

Animals↗
PubMed1986

Cloning and characterization of a cDNA specific for bovine retina.

A retina-specific cDNA clone (pCR18) was selected from a bovine retinal cDNA library and characterized. The clone pCR18 consisted of 905 base pairs and hybridized to the mRNA of about 12S from the bovine retina, but not that from the brain or liver. The nucleotide sequence revealed a long open reading frame which encodes a 147 amino acid polypeptide of about 15,700 Da. No significant sequence homology with the predicted protein was found in the protein sequence library of about 3500. Messenger RNA which hybridized to pCR18 translated a polypeptide of about 19,000 Da in a reticulocyte translation system. Southern blot analysis indicated that the bovine genome contains a single copy of this gene. Furthermore, RNA dot analysis showed that the poly(A)+ RNA from the human retinoblastoma cell lines (Y79 and WERI) hybridized to pCR18, whose intensity was comparable to that of the bovine retina. In situ hybridization revealed that pCR18 was expressed mostly in some ganglion cells of the rat retina. The results suggest that cDNA clone (pCR18) encodes a protein specific for the retina and mRNA for pCR18 is mostly localized in the retinal ganglion cells and also expressed in the human retinoblastoma cells, although its function remains to be elucidated.

Animals↗
PubMed1986

Multiple opsin mRNA species in bovine retina.

Two retina specific cDNAs have been isolated by differential colony hybridization to retina and brain, and one of them, pCR-394, was identified as an opsin cDNA. By Northern hybridization experiment, the opsin cDNA hybridized to two species of bovine mRNA, one approximately 18 S (1800 bp) and the other 22 S (2600 bp). Using pCR-394 as a probe two opsin clones, R-5 (about 1200 bp) and LR-8 (about 2500 bp), were isolated from a cDNA library which was prepared by the method of Okayama-Berg. Each had a different length of 3'-untranslated DNA. The nucleotide sequences of R-5 and LR-8, as well as Northern and Southern hybridization experiments suggest that at least two species of opsin mRNA are expressed from a single gene. When the effects of illumination were examined by Northern hybridization and translation assays, the ratio of the two opsin mRNA species was changed between light- and dark-adapted eyes.

Animals↗
PubMed1985

The role of p-aminophenol in acetaminophen-induced nephrotoxicity: effect of bis(p-nitrophenyl) phosphate on acetaminophen and p-aminophenol nephrotoxicity and metabolism in Fischer 344 rats.

Acetaminophen (APAP) produces proximal tubular necrosis in Fischer 344 (F344) rats. Recently, p-aminophenol (PAP), a known potent nephrotoxicant, was identified as a metabolite of APAP in F344 rats. The purpose of this study was to determine if PAP formation is a requisite step in APAP-induced nephrotoxicity. Therefore, the effect of bis(p-nitrophenyl) phosphate (BNPP), an acylamidase inhibitor, on APAP and PAP nephrotoxicity and metabolism was determined. BNPP (1 to 8 mM) reduced APAP deacetylation and covalent binding in F344 renal cortical homogenates in a concentration-dependent manner. Pretreatment of animals with BNPP prior to APAP or PAP administration resulted in marked reduction of APAP (900 mg/kg) nephrotoxicity but not PAP nephrotoxicity. This result was not due to altered disposition of either APAP or acetylated metabolites in plasma or renal cortical and hepatic tissue. Rather, BNPP pretreatment reduced the fraction of APAP excreted as PAP by 64 and 75% after APAP doses of 750 and 900 mg/kg. BNPP did not alter the excretion of APAP or any of its non-deacetylated metabolites nor did BNPP alter excretion of PAP or its metabolites after PAP doses of 150 and 300 mg/kg. Therefore, the BNPP-induced reduction in APAP-induced nephrotoxicity appears to be due to inhibition of APAP deacetylation. It is concluded that PAP formation, in vivo, accounts, at least in part, for APAP-induced renal tubular necrosis.

Acetaminophen↗
PubMed1985

Characterization of the polypeptide composition of human factor VIII:C and the nucleotide sequence and expression of the human kidney cDNA.

Human coagulation factor VIII:C has been purified approximately 5000-fold from commercial preparations with an average activity yield of 35%. Proteins of 92 kD and 77-80 kD enriched during purification are precipitated by a human serum polyclonal antibody which inhibits factor VIII:C activity. Evidence suggests that these polypeptides are linked by a calcium ion bridge. Partial amino acid sequence information from these proteins has been obtained from the intact polypeptides and from products of digestion with thrombin, endoproteinase lysC, or trypsin after citraconylation. An oligonucleotide probe designed from one of the amino acid sequences was used to isolate a partial genomic clone from a human 4X chromosome library in bacteriophage lambda. The genomic segment was used to isolate two cDNA molecules encompassing the entire human kidney factor VIII:C mRNA. Biologically active factor VIII:C has been produced in a mammalian cell line utilizing a complete cDNA construction.

Amino Acid Sequence↗
PubMed1984

Nephrotoxicity of phenolic bromobenzene metabolites in the mouse.

Bromobenzene, at doses greater than 5.7 mmol/kg, produced renal proximal tubular necrosis and renal functional changes in mice. p-Bromophenol and o-bromophenol were the major urinary phenolic bromobenzene metabolites although m-bromophenol and 4-bromocatechol were also excreted in detectable quantities. With the exception of o-bromophenol, urinary metabolites were excreted primarily as conjugates. 4-Bromocatechol and the 3 bromophenol isomers were nephrotoxicants (measured as increased blood urea nitrogen and decreased accumulation of organic anions by renal cortical slices) but not hepatotoxicants (measured as serum glutamic pyruvate transaminase) in vivo at 0.56 mmol/kg (i.v.). Preincubation of renal cortical slices with each of these bromobenzene metabolites for 90 min resulted in dose-dependent decreases in the accumulation of p-aminohippurate and tetraethylammonium. At 10 mumol/preincubation (2.4 mM), organic ion accumulation was decreased maximally by all bromobenzene metabolites examined while equimolar amounts of bromobenzene were without effect. 4-Bromocatechol was the most potent nephrotoxicant in vitro. Administration of 0.53-2.12 mmol/kg (i.v.) 4-bromocatechol to mice resulted in a dose-dependent decrease in renal function while hepatic function was altered only slightly at the higher doses. The renal cortical necrosis produced by in vivo administration of 4-bromocatechol could not be distinguished histologically from that induced by bromobenzene. These results demonstrate that 4-bromocatechol and the 3 bromophenol isomers are nephrotoxicants that can be generated from bromobenzene in mice.

Animals↗
PubMed1984

Effect of polybrominated biphenyls, beta-naphthoflavone and phenobarbital on arylhydrocarbon hydroxylase activities and chloroform-induced nephrotoxicity and hepatotoxicity in male C57BL/6J and DBA/2J mice.

Administration of chloroform (CHCl3) to male C57/6J (C57) and DBA/2J (DBA) mice produced dose-dependent hepatic and renal damage. Hepatic arylhydrocarbon hydroxylase (AHH) activity was higher in C57 than DBA mice; in kidney, AHH activity was higher in DBA than in C57 mice. CHCl3 caused the same degree of liver damage in both strains of mice; however, nephrotoxicity of CHCl3 was greater in DBA than in C57 mice. Pretreatment of C57 and DBA mice with phenobarbital (PB) markedly increased hepatic AHH activity and hepatotoxicity of CHCl3 in both strains but did not affect renal AHH or nephrotoxicity of CHCl3. Similarly, beta-naphthoflavone (BNF) enhanced AHH activity and CHCl3 hepatotoxicity in C57 mice, but had little effect on nephrotoxicity. BNF did not affect hepatic AHH nor CHCl3-induced hepatic injury in male DBA mice. Pretreatment with polybrominated biphenyl (PBB) enhanced AHH activity in liver and CHCl3 hepatotoxicity in both strains. After PBB, nephrotoxicity of CHCl3 and renal AHH activity were increased in C57 mice whereas PBB did not alter nephrotoxicity or renal AHH in DBA mice. These results suggest that CHCl3-nephrotoxicity is independent of hepatotoxicity.

Alanine Transaminase↗
PubMed1984

Sex and strain differences in mouse kidney: Bowman's capsule morphology and susceptibility to chloroform.

Chloroform (CHCl3) produces liver damage in male and female mice but renal injury only in male mice. Previous reports demonstrated that the parietal epithelium of Bowman's capsule in female mice is composed of squamous cells, whereas the parietal cells of Bowman's capsule from male mice consist of a mixture of squamous and cuboidal cells or purely cuboidal cells. These data suggested that the factor(s) associated with these histological differences may similarly be associated with factors that determine susceptibility to tubular damage from chloroform. The susceptibility of male mice to chloroform nephrotoxicity varies with animal strain. In the present study, administration of CHCl3 to male C57BL/6J (C57) and male and female DBA/2J (DBA) mice produced dose-dependent kidney tubular damage in male C57 and male DBA mice. However, CHCl3 nephrotoxicity was considerably greater in male DBA mice than in male C57 mice. Female DBA mice failed to develop renal damage following administration of CHCl3. Male DBA mice had a higher percentage of cuboidal parietal epithelial cells in Bowman's capsule whereas male C57 mice had a higher percentage of squamous cells in the parietal epithelium. The parietal epithelium in Bowman's capsule of female DBA mice was predominantly squamous. Since morphological differences between sex and strain of mice occurred in the capsular epithelium, and the differences in susceptibility to CHCl3 appear to be a tubular phenomenon, it is unlikely that there is a causal relationship between the structure of Bowman's capsule and chloroform-induced renal tubular necrosis; rather, these two independent phenomena are regulated by some common factor(s), possibly testosterone.

Alanine Transaminase↗
PubMed1984

Effect of dietary trans-stilbene oxide on hepatic and renal drug-metabolizing enzyme activities and bromobenzene-induced toxicity in male Sprague-Dawley rats.

The effect of dietary trans-stilbene oxide (TSO) on hepatic and renal xenobiotic metabolizing-enzyme activities and bromobenzene-induced toxicity was quantified in adult male Sprague-Dawley rats. Rats were fed a regular diet or the same diet supplemented with 2.5 g TSO/kg diet for 10 days. TSO treatment did not alter hepatic or renal arylhydrocarbon hydroxylase activity, but significantly increased glutathione S-transferase and uridine diphosphoglucuronyl transferase activities in both organs. In addition, TSO increased hepatic, but not renal, epoxide hydrolase activity. The same treatment did not produce adverse effects on renal or hepatic functions, but markedly potentiated bromobenzene hepatotoxicity. A single dose of bromobenzene (0.2 ml/kg) caused a slight increase in serum glutamic pyruvic transaminase (SGPT) activity and minor hepatic necrosis in animals fed the control diet; the same dose of bromobenzene markedly increased SGPT activity and produced severe hepatic necrosis in the TSO-fed animals.

Animals↗
PubMed1984

Nephrotoxicity of bromobenzene in mice.

I.p. administration of bromobenzene to male mice at doses ranging from 0 to 9.4 mmol/kg resulted in a dose-dependent increase in blood urea nitrogen (BUN) and serum glutamic-pyruvic transaminase (SGPT) activity and a decrease in renal cortical accumulation of para-aminohippurate (PAH) and tetraethylammonium (TEA). Induction of renal and hepatic mixed-function oxidases by beta-naphthoflavone (BNF) did not result in any alterations in the hepatotoxic or nephrotoxic response to bromobenzene. Renal and hepatic non-protein sulfhydryl (NPSH) concentrations were decreased significantly 1 h after administration of bromobenzene (7.5 mmol/kg) and were maximally depleted in both organs to 18% of control after 7 h. Depletion of renal NPSH by bromobenzene was dose-dependent up to 9.4 mmol/kg. Treatment of mice with diethyl maleate (DEM) (0.6 ml/kg) 60 min prior to bromobenzene administration resulted in greater hepatotoxicity, evidenced by increased SGPT, while renal toxicity was unchanged. These data demonstrate that large doses of bromobenzene produce functional alterations in the kidney.

Animals↗
PubMed1984

cis-Dichlorodiammineplatinum nephrotoxicity in rats of different ages.

In 5-, 15-, 30-, and 60-day-old rats there was a distinct decrease of body weight 24 hours after a single i.p. injection of cis-dichlorodiammineplatinum (CDDP) over a dose range from 0.25 to 2.0 mg/100 g b.w.t. Compared with a control group the kidney weights appeared nearly unchanged. The increase of blood urea nitrogen (BUN) concentrations following CDDP treatment was dose dependent and more profound in 5- and 15-day-old rats than in older animals. In higher doses, CDDP impaired the renal concentrating ability in rats of all age groups as reflected in a significant increase in urine volume with only a slightly increased renal sodium excretion. Following CDDP treatment there was a moderate proteinuria. In 30- and 60-day-old rats the renal excretion of p-aminohippurate (PAH) was more reduced by CDDP compared to younger rats.

Age Factors↗
PubMed1983

Metabolic heterogeneity of the proximal and distal kidney tubules.

Proximal and distal tubule suspensions were prepared from kidneys of Sprague-Dawley rats by an isolation procedure on a Percoll gradient. The marker enzymes alkaline phosphatase (brush border) and hexokinase (cytoplasmic) as well as p-aminohippurate transport capacity, gluconeogenic activity and electron microscopy were used to characterize the two kidney tubule suspensions. The results of this study indicate that cytochrome P-450 is localized to the proximal tubular cells and that the O-deethylation of 7-ethoxycoumarin was higher in the proximal than distal fraction. Both proximal and distal tubules showed glucuronidation and deacetylation capacities and a relatively equal distribution of non-protein sulfhydryls. These studies demonstrate metabolic heterogeneity of the nephron, the proximal tubule being the main site of renal xenobiotic metabolism. Understanding of metabolic heterogeneity of proximal and distal kidney tubules should provide important information regarding cell specific mechanisms of nephrotoxicity.

7-Alkoxycoumarin O-Dealkylase↗