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Biomedical subjects

C S Yang

Publications and source records attributed to C S Yang.

At least 199 records · Page 11Linked to original sources
PubMed1996

Nitrite, N-nitroso compounds, and other analytes in physiological fluids in relation to precancerous gastric lesions.

Levels of gastric juice nitrite, several urinary N-nitroso compounds, and other analytes were examined among nearly 600 residents in an area of Shandong, China, where precancerous gastric lesions are common and rates of stomach cancer are among the world's highest. Gastric juice nitrite levels were considerably higher among those with gastric juice pH values above 2.4 versus below 2.4. Nitrite was detected more often and at higher levels among persons with later stage gastric lesions, especially when gastric pH was high. Of those with intestinal metaplasia, 17.5% had detectable levels of gastric nitrite, while this analyte was detected in only 7.2% of those with less advanced lesions. Relative to those with undetectable nitrite, the odds of intestinal metaplasia increased from 1.5 (95% confidence interval = 0.6-4.1) to 4.1 (95% confidence interval = 1.8-9.3) among those with low and high nitrite concentrations, respectively. Urinary acetaldehyde and formaldehyde levels also tended to be higher among those with more advanced pathology, particularly dysplasia. However, urinary excretion levels of total N-nitroso compounds and several nitrosamino acids differed little among those with chronic atrophic gastritis and intestinal metaplasia and dysplasia, consistent with findings from recent studies in the United Kingdom, France, and Colombia. The data from this high-risk population suggest that elevated levels of gastric nitrite, especially in a high pH environment, are associated with advanced precancerous gastric lesions, although specific N-nitroso compounds were not implicated.

Adult↗
PubMed1996

Reproducibility of an esophageal biopsy sampling procedure in a high-incidence area for esophageal cancer in northern China.

The objective of this study was to evaluate the reproducibility of the biopsy sampling procedure in research on esophageal lesions. Biopsies were taken from the middle and lower thirds of the esophagus, one from each site, from 25 subjects in a high-incidence area for esophageal cancer in Xinye County of Henan Province, China. The biopsy sampling procedure was repeated on the same subjects 10 days later. When the biopsies were analyzed together and those with worse pathologies were used for diagnosis, 52% of the subjects had the same grade of lesions in the second biopsy examination, 32% had lower-grade lesions, and 16% had higher-grade lesions.

Adult↗
PubMed1995

Effect of ageing on human plasma glutathione concentrations as determined by high-performance liquid chromatography with fluorimetric detection.

A convenient method for the determination of reduced glutathione (GSH) and oxidized glutathione (GSSG) in human plasma by high-performance liquid chromatography with fluorescence detection is reported. This assay involves direct addition of human plasma to methanolic monobromobimane, for simultaneous protein precipitation and thiol derivatization. The assay was validated by addition of authentic GSH and GSSG to plasma samples. Plasma glutathione levels in Chinese male and female volunteers were found to decrease with increasing age (age groups 20-30, 30-40, 40-50, 50-60, and > 60; mean +/- S.E.M. 0.95 +/- 0.03, 0.77 +/- 0.02, 0.67 +/- 0.03, 0.51 +/- 0.02, 0.48 +/- 0.02 microM for male volunteers and 1.11 +/- 0.06, 0.76 +/- 0.03, 0.61 +/- 0.03, 0.53 +/- 0.04 and 0.43 +/- 0.04 microM for female volunteers). GSSG levels, in both males and females, did not show a correlation with age. There were no significant differences in GSH or GSSG levels among male and female volunteers of the same age group. These results suggest that elderly persons might be more susceptible to oxidative injury due to decreased plasma glutathione levels.

Adult↗
PubMed1995

Activation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in human lung microsomes by cytochromes P450, lipoxygenase, and hydroperoxides.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent tobacco-specific carcinogen, has been demonstrated to induce lung tumors in animals and is suspected to be a human carcinogen. Cytochromes P450 are the major enzymes responsible for the activation of NNK in microsomes from the lung and liver of rat and mouse, as well as human liver. The present study investigated the enzymes responsible for the metabolic activation of NNK in human lung microsomes. In the presence of a NADPH-generating system, the formation of keto aldehyde and keto alcohol (alpha-hydroxylation products, measured together), keto acid, hydroxy acid, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol was observed in human lung microsomes. Carbon monoxide (90%) decreased the rate of NNK oxidation by 5-49%, depending on the human lung microsomal samples analyzed. Coumarin decreased the oxidation of NNK by 9-34%, and an antibody against human P450 2A6 decreased the metabolism of NNK by 8-37%, suggesting the involvement of P450 2A6 in NNK oxidation. alpha-Napthoflavone inhibited NNK oxidation by 6-26%, possibly due to the inhibition of P450 1A1. P450 1A1-expressed microsomes catalyzed the formation of keto aldehyde and keto alcohol, exhibiting Km values of 1400 microM and 371 microM, respectively. In the absence of NADPH, NNK metabolism resulted in the formation of keto acid, keto aldehyde, and keto alcohol, and the activities in different lung samples were decreased by indomethacin (100 microM; cyclooxygenase inhibitor) or nordihydroguaiaretic acid (100 microM; lipoxygenase inhibitor) by 0-27% or 30-66%, respectively. The addition of arachidonic acid (10-100 microM) increased the rate of the formation of keto aldehyde and keto alcohol approximately 2-fold but inhibited the formation of keto acid. Soybean lipoxygenase increased the rate of formation of keto aldehyde and keto alcohol in a concentration-dependent manner. The increased rate in NNK oxidation by arachidonic acid or lipoxygenase was inhibited completely by nordihydroguaiaretic acid. Catalase, thiourea, and conjugated linoleic acid decreased the rate of NNK oxidation by 47, 20, and 45%, respectively. tert-Butyl-hydroperoxide, cumene hydroperoxide, and hydrogen peroxide increased the rate of formation of keto aldehyde and keto alcohol by 210, 40, and 50%, respectively. The results suggest that P450 enzymes are only partially responsible for the activation of NNK in human lung microsomes, and P450 2A6 or a P450 2A6-related enzyme seems to be involved in the activation. Furthermore, lipoxygenase and lipid hydroxperoxides may play important roles in the oxidation of NNK in human lung microsomes.

Aldehydes↗
PubMed1995

Roles of histidine-194, aspartate-163, and a glycine-rich sequence of NAD(P)H:quinone oxidoreductase in the interaction with nicotinamide coenzymes.

NAD(P)H:(quinone-acceptor) oxidoreductase (NQOR, EC 1.6.99.2), an enzyme catalyzing the obligatory two electron reduction of quinones, can utilize both NADH and NADPH as electron donors at similar efficiencies. Based on site-directed mutagenesis studies, we previously suggested that the glycine-rich region of rat liver NQOR is important for the binding of NAD(P)H (Ma et al., J. Biol. Chem. 267, 22298-22304, 1992). However, the mode of interactions between the active site and NADH or NADPH is not clearly known. In this study, we conducted site-directed mutagenesis experiments and identified H194 and D163 of NQOR as key residues affecting the Km of NADPH. Steady-state kinetic analysis for the reduction of dichloroindophenol (DCIP) showed that Km(NADPH) values of purified mutant proteins H194D, H194A, and D163V were 288-, 14-, and 96-fold higher, respectively, than that of NQOR; but the Km(NADH) values were only slightly higher. The kcat(NADPH) values were almost the same as that of NQOR in the reduction of DCIP at the respective pH optima which were affected by the mutations. The kcat(NADH) values of these mutant enzymes were 30 to 60% that of NQOR. In the reduction of menadione, the mutations also caused much larger increases in km(NADPH) than Km(NADH). The results suggest that H194 and D163 are important for the interaction with the 2'-phosphate group of NADPH. NAD(P)H analogues, N-methyldihydronicotinamide and dihydronicotinamide mononucleotide, can also serve as electron donors for NQOR, but the Km values were 4.5- and 495-fold higher, respectively, than that with NADH. Mutations at H194 and D163 and at the glycine-rich region of NQOR, which increased Km(NADH) and Km(NADPH), did not substantially affect the Km values of these two analogues. This result is consistent with the suggested roles of these amino acid residues in the interaction with nicotinamide coenzymes. Based on these results, a model of the NAD(P)H binding site is proposed showing the interaction of the pyrophosphate group with the glycine-rich region and the interaction of 2'-phosphate group with H194 and D163.

Animals↗
PubMed1995

Lowered brain glutathione by diethylmaleate decreased the glutamate release induced by cerebral ischemia in anesthetized rats.

The effect of lowered brain glutathione content on the glutamate release following cerebral ischemia was investigated. Diethylmaleate (4 mmol/kg, i.p.), a commonly used chemical reagent for tissue glutathione depletion, significantly reduced the ischemia-induced glutamate release. The release of another excitatory amino acid aspartate was not affected by the diethylmaleate administration. These results suggested that part of the elevated glutamate content induced by ischemia might result from the cellular GSH.

Anesthetics↗
PubMed1995

Core antigen mutations of human hepatitis B virus in hepatomas accumulate in MHC class II-restricted T cell epitopes.

Despite the extensive molecular information on serum-derived human hepatitis B viruses (HBV), liver-derived replicative HBV genomes have remained largely uninvestigated. We have examined the sequences of the entire core antigen (nucleocapsid) of liver-derived HBVs in 15 different hepatoma patients. Bona fide mutations, rather than subtype polymorphism, have been identified based on the high-frequency occurrence of structural differences from wild type at the highly evolutionarily conserved positions, instead of at the positions known to contain genetic heterogeneity among different isolates from different geographic locations. The distribution of these naturally occurring mutations of HBV core gene appears to be nonrandom and is found predominantly within three major (I, IV, and V) and four minor domains (II, III, VI, and VII). In general, domain IV mutations correlate with domain V mutations. The replicative HBV DNAs tend to accumulate a higher number of mutated core domains than the integrated HBV DNAs. At the domain level, there is no significant difference in HBV core mutation frequencies between the liver tumors and the adjacent nontumorous livers. Strikingly, domains I, III, and V coincide with three major known T cell epitopes within the core protein in acute and chronic hepatitis B patients. Furthermore, these domains coincide with HLA class II-restricted T cell epitopes, rather than with the conventional HLA class I-restricted epitopes of cytotoxic T lymphocytes. Our results support the hypothesis that HBV core antigen variants can accomplish immunoevasion via accumulated escape mutations. In addition, they also provide a potential molecular explanation for the maintenance of persistent infection of human hepatitis B virus in chronic carriers.

Adult↗
PubMed1995

Determination of extracellular glutathione in livers of anaesthetized rats by microdialysis with on-line high-performance liquid chromatography.

An on-line analytical system for the continuous in vivo monitoring of extracellular glutathione (gamma-glutamyl-cysteinylglycine) (GSH) concentrations in the livers of anaesthetized rats was developed. Microdialysates perfused through implanted microdialysis probes were collected with a loading loop of an on-line injector for direct and automatic injection into a high-performance liquid chromatographic system equipped with an electrochemical detector with Au-Hg electrodes. This method shortened the analysis time and circumvented the sample preparation process which is essential for accurate determination of GSH levels in biological samples. Additionally, this method provided continuous and real-time monitoring of extracellular GSH levels. Basal extracellular GSH concentrations in the livers of anaesthetized rate were found to vary over a wide range (from 4.16 to 76.5 microM). The method was applied to study the effect of global liver ischaemia on extracellular GSH concentrations and it was found that extracellular GSH levels in livers increased immediately with the onset of ischaemia and remained elevated for the 30-min ischaemic period. Ensuing reperfusion did reduce the GSH increase; however, the GSH levels did not return to the basal value.

Anesthesia↗
PubMed1995

Characterization of Epstein-Barr virus DNase and its interaction with the major DNA binding protein.

Bacterially expressed Epstein-Barr virus (EBV) DNase was purified to 98% purity and used as the source for characterization of the enzyme activities. Complete digestion of DNA by EBV DNase yielded 5'-monophosphate nucleosides as the final products. During the logarithmic phase of the reaction, EBV DNase acted processively on dsDNA but distributively on ssDNA. Both 5' to 3' and 3' to 5' exonuclease activities were present, although the former was shown to be 10-fold stronger. No significant discrepancy was seen in the liberation of end-labeled nucleotides by DNase when substrates with 5'-protruding, blunt, or 3'-protruding ends were used. EBV DNase was demonstrated also to have an endonuclease activity using supercoiled plasmid DNA as substrate. Two preferential dsDNA cleavage sites were mapped on pBS-TR, a pBlueScript vector containing one copy of the EBV terminal repeat; both are in vector sequences. Finally, an N-terminally truncated EBV major DNA binding protein, but not EA-D, was shown to inhibit EBV DNase activity. This inhibitory effect may due to direct protein-protein interactions between EBV DNase and the major DNA binding protein. The biological significance of these characteristics is discussed.

Antigens, Viral↗
PubMed1995

Vegetable consumption, serum retinol level, and risk of hepatocellular carcinoma.

A cohort of 8436 men in Taiwan was recruited with personal interview and blood sample collection between 1984 and 1986. During the 5-year follow-up period, 50 incident cases of hepatocellular carcinoma (HCC) were identified. Retinol levels were measured for 35 HCC patients whose serum samples were available and 140 matched controls randomly selected from cohort members without HCC. Lower vegetable intake was significantly associated with an increased risk of HCC after adjustment for other HCC risk factors (P = 0.006). The effect of low vegetable intake on HCC risk was limited to hepatitis B virus chronic carriers and cigarette smokers. As compared with subjects who had a weekly vegetable consumption frequency of six or more meals, the multivariate-adjusted relative risk of HCC for subjects who had a frequency of less than six meals was 4.7 (95% confidence interval, 2.0-11.1; P = 0.0004) among chronic hepatitis B virus carriers and 3.8 (95% confidence interval, 1.7-8.5; P = 0.001) among cigarette smokers. There was an inverse dose-response relationship between the prediagnostic serum retinol level and the development of HCC (trend test, P = 0.003). The odds ratio of HCC for men with a retinol level in the lowest tertile was 9.0 (95% confidence interval, 2.1-39.1) compared with those with a level in the highest tertile. The relation remained after multivariate adjustment for cigarette smoking, habitual alcohol drinking, and either the seropositivity of hepatitis B virus surface antigen and/or anti-hepatitis C virus antibody or the past history of liver diseases through conditional logistic regression analysis. The association was more striking for men 55 years or younger and for those who smoked 10 or more cigarettes/day. There was a significant synergistic effect of hepatitis B virus surface antigen carrier status and low serum retinol level on the development of HCC. These data suggest a potential role of retinol in the chemoprevention of HCC.

Adult↗
PubMed1995

Probing the active sites of rat and human cytochrome P450 2E1 with alcohols and carboxylic acids.

Cytochrome P450 2E1 (P450 2E1) catalyzes the biotransformation of many low-molecular-weight compounds including industrial solvents, indoor pollutants, alcohol, and drugs. In order to understand the nature of the P450 2E1 active site, we studied the competitive inhibition of the P450 2E1-catalyzed N-nitrosodimethylamine demethylation by alcohols and carboxylic acids with different alkyl chain lengths. Using microsomes from acetone-treated rats as the enzyme source of P450 2E1, the Ki value for each compound was measured. With primary alcohols and secondary alcohols, the Ki decreased with the increase in the carbon chain length until the carbon number reached 6 or 7; the free energy increment of binding was 0.28 kcal/mol CH2 group. Similar inhibitory effects were also observed with human P450 2E1 heterologously expressed in Hep G2 cells. These results suggest that both rat and human P450 2E1 contain a pocket with hydrophobicity that serves as a binding site for low-molecular-weight substrates. Among a series of carboxylic acids and omega-hydroxycarboxylic acids investigated, dodecanoic acid was the strongest inhibitor (Ki = 22 microM), and 12-hydroxydodecanoic acid had the lowest Ki (320 microM) within the series of omega-hydroxycarboxylic acids. The free energy increment of binding for carboxylic acids was 0.35 kcal/mol CH2 group. 1,10-Decanedicarboxylic acid, which contains a carboxylic group at each end, showed a Ki > 20 mM. We suggest that for optimal interaction of a carboxylic acid moiety with the active site of P450 2E1, the hydrocarbon end of the molecule binds to the substrate binding site, leaving the carboxylic acid group outside of a proposed substrate access channel. The length of optimal substrates such as dodecanoic acid may reflect the length of the substrate access channel and the size of the active site. We estimate that the distance from the opening of the access channel to the oxygenation site is about 15 A. Based on the structural features of P450 2E1 substrates and competitive inhibitors, we propose a conceptual model to illustrate the binding of these molecules in the active site of P450 2E1.

Alcohols↗
PubMed1995

No point mutation but decreased expression of the p16/MTS1 tumor suppressor gene in nasopharyngeal carcinomas.

Nasopharyngeal carcinoma (NPC) is a malignancy which occurs at high incidence in southern China and southeast Asia. The molecular mechanism of this disease, however, is not well understood. Recently, a homozygous deletion and/or loss of heterozygosity on chromosome 9p21-22 was found in several primary NPCs (Huang et al., Cancer Res. 54: 4003-4006, 1994), suggesting that a potential tumor suppressor gene(s) residing in this region may play a role in nasopharyngeal carcinogenesis. Since p16/MTS1, a potential tumor suppressor gene, whose mutations/deletions are frequently found in variety of tumor cells, was mapped to chromosome 9p21, we investigated the possible involvement of this gene in the development of NPC by mutational and Northern blot analysis. SSCP-direct sequencing revealed no point mutations of the p16/MTS-1 gene in any of 42 primary NPC biopsies from three geographical regions nor in two NPC cell lines. We did, however, observe a codon 140ala-->thr polymorphism in the gene, which has been previously reported as a point mutation. Furthermore, Northern analysis revealed a decreased expression of the p16/MTS1 gene in two out of two NPC cell lines as compared with immortalized/nontransformed cell lines. These results suggest that down regulation rather than a point mutation of the p16/MTS1 gene may play a role in the genesis of NPC.

Base Sequence↗
PubMed1995

Subunit functional studies of NAD(P)H:quinone oxidoreductase with a heterodimer approach.

NAD(P)H:quinone oxidoreductase (NQOR; EC 1.6.99.2) is a homodimeric enzyme which catalyzes the reduction of quinones, azo dyes, and other electron acceptors by NADPH or NADH. To pursue subunit functional studies, we expressed a wild-type/mutant heterodimer of NQOR in Escherichia coli. The wild-type subunit of the heterodimer was tagged with polyhistidine and the other subunit contained a His-194-->Ala mutation (H194A), a change known to dramatically increase the Km for NADPH. This approach enabled us to efficiently purify the heterodimer (H194A/HNQOR) from the homodimers by stepwise elution with imidazole from a nickel nitrilotriacetate column under nondenaturing conditions. The composition of the purified heterodimer was confirmed by SDS and nondenaturing polyacrylamide gel electrophoresis and immunoblot analysis. The enzyme kinetics of the purified heterodimer were studied with two two-electron acceptors, 2,6-dichloroindophenol and menadione, and a four-electron acceptor, methyl red, as the substrates. With two-electron acceptors, the Km(NADPH) and Km(NADH) values of the heterodimer H194A/HNQOR were virtually identical to those of the wild-type homodimer, but the kcat-(NADPH) and kcat(NADH) values were only about 50% those of the wild-type homodimer. With the four-electron acceptor, the Km and kcat values of H194A/HNQOR for NADPH and NADH were similar to those of the low-efficiency mutant homodimer. These results suggest that the subunits of NQOR function independently with two-electron acceptors, but dependently with a four-electron acceptor. This heterodimer approach may have general applications for studying the functional and structural relationships of subunits in dimeric or oligomeric proteins.

Azo Compounds↗
PubMed1995

The roles of reactive oxygen species and endogenous opioid peptides in ischemia-induced arrhythmia of isolated rat hearts.

Although the formation of oxygen-derived free radicals (or reactive oxygen species; ROS) and the release of endogenous opioid peptides (EOP) have been independently reported to be the major arrhythmogenic factors in ischemic hearts, possible relations between these two factors have seldom been investigated. Thus, we studied whether the ROS and EOP were related in the progression of ischemia-induced arrhythmias. Isolated rat hearts perfused in the Langendorff mode were treated with dynorphin A1-13 (kappa EOP receptor agonist), and/or allopurinol (xanthine oxidase inhibitor), before the onset of ischemia induced by ligating the left coronary arteries. Ischemic period lasted for 30 min, during which cardiac rhythms were recorded. At the end of ischemia, hearts were analyzed for the glutathione and ascorbate levels. Allopurinol (100 nmoles/heart) was effective in reducing the severity of arrhythmia (arrhythmia score: Mean +/- SEM 3.00 +/- 0.80 for allopurinol, 5.75 +/- 0.41 for placebo, p < 0.01), while dynorphin (10 micrograms/heart) potentiated the arrhythmia (6.71 +/- 0.52, p < 0.05 vs. placebo). Coadministration of allopurinol and dynorphin was capable of reducing arrhythmia (5.57 +/- 0.65) when compared with the administration of dynorphin alone (6.71 +/- 0.52, p < 0.05). Tissue oxidative stress was evaluated by the concentrations of glutathione (GSH) and ascorbate. Allopurinol did not significantly elevate tissue GSH concentrations (1.46 +/- 0.05 mumoles/g wet wt) in ischemic hearts, while dynorphin alone significantly decreased the GSH concentrations (0.96 +/- 0.08, p < 0.05) when compared with the placebo (1.32 +/- 0.03). The dynorphin-induced GSH decrease cannot be reversed by coadministration with allopurinol (0.90 +/- 0.104). Allopurinol significantly elevated tissue ascorbate levels (0.16 +/- 0.01) when compared with placebo (0.10 +/- 0.01, p < 0.05). Interestingly, dynorphin alone also elevated the tissue ascorbate concentrations (0.16 +/- 0.02). Coadministration of allopurinol and dynorphin further spiked the ascorbate levels (0.28 +/- 0.05, p < 0.01). In conclusion, the results suggested that ischemia-induced arrhythmia mechanisms might involve the formation of superoxide and other ROS, which were probably generated from the release of EOP (or EOP/EOP receptor interactions). Superoxide, the formation of which can be inhibited by allopurinol that exerted antiarrhythmic effect, was probably scavenged by ascorbate in myocardial ischemia. The ROS resulting from EOP/EOP receptor interactions were probably scavenged by glutathione system. Elevated ascorbate levels in dynorphin-treated hearts might result from the compensatory synthesis induced by decreased glutathione levels.

Allopurinol↗
PubMed1995

Elevated extracellular glutamate levels increased the formation of hydroxyl radical in the striatum of anesthetized rat.

Results from various in vitro experiments have indicated that excitotoxicity and oxidative stress are two interrelated major mechanisms in causing neuronal damage in brain disorders such as cerebral ischemia/reperfusion. Thus, we have conducted experiments to investigate whether in the striatum of anesthetized rats the elevated brain extracellular concentrations of glutamate could increase the formation of hydroxyl radical. Elevation of glutamate levels and trapping of hydroxyl radical were accomplished by perfusing Ringer solutions containing both glutamate and salicylic acid through microdialysis probes implanted in rat striatum. The formation of hydroxyl radical was quantitated as the increased amounts of 2,3 and 2,5 dihydroxybenzoic acid (DHBA) which were the hydroxylative products of salicylic acid. Eluted microdialysates were directly injected onto high performance liquid chromatography (HPLC) with electrochemical detector via an on-line automatic injector. This method was authenticated by in vitro studies employing Fenton-type hydroxyl radicals generation system. Our results indicated that elevated glutamate concentrations (15 mM, 1.5 mM, and 150 microM glutamate in perfusing solutions) would significantly increased both the concentrations of 2,3 and 2,5 DHBA. In conclusion, we have obtained direct evidence showing that the elevated glutamate concentrations in brain extracellular space would increase the formation of hydroxyl radical, and these results implied that oxidative stress occurring in brain disorders might be induced by excitotoxicity.

Anesthesia↗
PubMed1995

Chlorambucil therapy in sympathetic ophthalmia.

PURPOSE: We used chlorambucil therapy in a 28-year-old man with sympathetic ophthalmia, which was incompletely controlled with systemic corticosteroids, and the patient developed serious side effects. METHODS: The patient sustained a penetrating injury with an intraocular metal foreign body. Attempts to remove it with a magnet failed. Vitrectomy with lensectomy successfully removed the intraocular foreign body. Five weeks after the injury and one week after the vitrectomy, sympathetic ophthalmia developed, with severe visual impairment and inflammation and serous retinal detachment in the fellow eye. Sympathetic ophthalmia was poorly responsive to topical cycloplegics, topical corticosteroids, and systemic corticosteroid therapy. The patient developed side effects to the corticosteroids, which were reduced to prednisolone 60 mg daily. Chlorambucil therapy was begun at 2 mg daily, increased by 2 mg per day each week to the maximum of 8 to 12 mg per day. The total dose of chlorambucil was 793 mg; the duration of therapy was 23 weeks. RESULTS: Successful treatment was achieved with chlorambucil therapy. There was clinical remission of inflammation and absorption of exudative retinal detachment. The neurosensory retina sealed down; the retinal pigment epithelium demonstrated severe destruction, with the characteristic sunset-glow and moth-eaten appearance. No malignancy and no serious side effect developed during one year of follow-up. After termination of therapy, the patient had sustained remission of ocular disease. CONCLUSION: Chlorambucil immunosuppressive therapy is an alternative to corticosteroids for the treatment of corticosteroid-resistant sympathetic ophthalmia; however, because chlorambucil has potentially serious late side effects, prolonged follow-up is necessary.

Adult↗