Tubulointerstitial nephritis and uveitis syndrome (TINU) with Fanconi's syndrome.

We report a 57-year-old woman with concurrent tubulointerstitial nephritis and uveitis syndrome (TINU) and Fanconi's syndrome. She presented with sudden onset of bilateral ocular pain, blurred vision, acute renal failure, glucosuria and proteinuria. Slit lamp examination revealed acute bilateral anterior uveitis. Tubulointerstitial nephritis was confirmed by kidney biopsy. Laboratory examination revealed normoglycemic glucosuria, proteinuria, normal anion-gap metabolic acidosis, phosphaturia, urinary uric acid wasting and kaliuresis leading to hypokalemia. Her vision and renal function improved gradually after systemic steroid therapy. There have been rare reports of TINU syndrome which had features of Fanconi's syndrome. The prevalence of TINU syndrome may be underestimated, and its association with Fanconi's syndrome requires further investigation.

Comparing the ethical challenges of forgoing tube feeding in American and Hong Kong patients with advanced dementia.

OBJECTIVES: To develop a cross-cultural dialogue for enriching our understanding of how an ethical environment can be constructed in fostering tube-feeding decisions in patients with advanced dementia (AD). DESIGN AND DATA SOURCE: Drawing on the findings of two prospective case studies conducted in Boston and Hong Kong, this paper compares the decision-making patterns of forgoing tube feeding for AD patients and their emergent ethical dilemmas typified in a special dementia care unit in Boston (BCU) and a long-term care unit in Hong Kong (HKCU). FINDINGS: Differences in forgoing tube feeding decision are delineated in the two places. No-tube-feeding practice was sustained in BCU in two ways: advance decision-making with respect paid to the patient's wishes and advance proxy decision-making focused on patient comfort. With life preservation as the prevailing value in the Hong Kong medical system, only strong family request coupled with medical evidence of patient's ability to continue hand-feeding that tube feeding would be discontinued. All patients died with some form of artificial feeding. CONCLUSION: A paradigm shift of values underpinning the practice of forgoing tube feeding in the context of palliative care is observed in three aspects. First, the emphasis on prognostication based on biomedical markers in predicting the length of survival is shifted to a focus on the "diagnosis of dying". Second, the overriding concern in conventional medical practice with preserving life is shifting to an overriding concern of "what is best for the patient." Third, in the last days of life, the conventional approach of "trying to do everything for the patient" had shifted from a technological to a relational one. Palliative measures for relieving discomfort and providing a peaceful and dignified environment in which the patient could die are the primary concern. Although the predominant medical culture in Hong Kong is biomedical, voices from the patients and family members challenge this conventional practice, and suggest that the alternative model may be a better choice.

The activity of 2'-benzoyloxycinnamaldehyde against drug-resistant cancer cell lines.

This study investigated the inhibitory effects of 2'-benzoyloxycinnamaldehyde (BCA) on cancer cells, including various drug-resistant cancer cell lines. To observe this activity, the anticancer drug-resistant cell lines were established by continuously exposing the parental cells to 5-fluorouracil (5-FU) and cyclophosphamide (CDDP), and examining the cells with the MTT assay and flow cytometric analysis. The BCA treatment produced similar growth inhibitory effects and apoptotic cell death on the drug-resistant cancer cells as their parental cells. The activation of the p38-mitogen activated protein kinase, an increased level of reactive oxygen species (ROS) generation and downregulation of Bcl-2 were observed in both the drug resistant and non-drug resistant cell lines. The GSH treatment effectively inhibited BCA-induced apoptosis by blocking ROS generation, suggesting that ROS is a major regulator in BCA-induced apoptotic cell death. These results suggest that BCA can be a useful drug candidate for treating drug-resistant cells.

Increased expression of peroxiredoxin II confers resistance to cisplatin.

Peroxiredoxin II (Prx II) has been known to be induced by various oxidative stimuli and to play an important protective role from oxidative damage by hydrogen peroxide (H2O2). In this study, we observed that cisplatin as well as H2O2 induced Prx II expression. To examine the correlation between the increased expression of Prx II and chemoresistance, we prepared a Prx II-overexpressing cell line, SNU638 cells, and found it to be more resistant to cell death induced by cisplatin and H2O2 than neo-transfectant cells. We also observed that enhanced expression of Prx II inhibited cisplatin- and H2O2-induced apoptosis, demonstrating that resistance to these cytotoxic agents was due to inhibition of apoptosis. The above results led us to suggest that the overexpressed Prx II protein inhibits cisplatin-induced apoptosis, thereby contributing to chemoresistance of tumor cells, especially to oxidative stress producing anticancer drugs.

Hepatitis C virus core protein potentiates TNF-alpha-induced NF-kappaB activation through TRAF2-IKKbeta-dependent pathway.

Previous work has implicated that the core protein of hepatitis C virus (HCV) may play a modulatory effect on NF-kappaB activation induced by TNF-alpha. However, it is unclear how HCV core protein modulates TNF-alpha-induced NK-kappaB activation. Here we show that overexpression of HCV core protein potentiates NF-kappaB activation induced by TNF-alpha. Expression of dominant negative form of TRAF2 inhibits the synergistic effects of HCV core protein on NF-kappaB activation, suggesting that HCV core protein potentiates NF-kappaB activation through TRAF2. Moreover, we demonstrate that HCV core protein potentiates TRAF2-mediated NF-kappaB activation via IKKbeta. In addition, HCV core protein associates with TNF-R1-TRADD-TRAF2 signaling complex, resulting in synergistically activation of NF-kappaB induced by TNF-alpha. Thus, these observations indicate that HCV core protein may play an important role in the regulation of the cellular inflammatory and immune responses through NF-kappaB.

Caspase-cleaved TRAF1 negatively regulates the antiapoptotic signals of TRAF2 during TNF-induced cell death.

Tumor necrosis factor (TNF) signaling leads to pleiotropic responses in a wide range of cell types, in part by activating antiapoptotic and proapoptotic pathways. Previous studies have suggested that TNF receptor-associated factor (TRAF) 2 can mediate crucial antiapoptotic signals during TNF stimulation. However, it is unclear how the antiapoptotic signals via TRAF2 in TNF-R1 signaling is regulated. Here we show that TRAF1 is cleaved by caspase-8 into two fragments during apoptosis induced by TNF. Overexpression of the C-terminal cleavage product, TRAF1-c, increased TNF-induced cell death of hybridoma T cells. Importantly, we demonstrate that the cleavage product of TRAF1 coimmunoprecipitates with TRAF2 that is released from the TNF-R1 complex in response to prolonged TNF treatment. These results indicate that caspase-dependent cleavage of TRAF1 generates TRAF1-c fragments that are able to bind TRAF2, and then sequester TRAF2 from the TNF-R1 complex, rendering cells, at least in part, sensitive to TNF.

Establishment and characterization of 5-fluorouracil-resistant gastric cancer cells.

Two 5-fluorouracil (5-FU)-resistant cell lines from a Korean gastric cancer cell line were established by incubation of the cells with increasing concentration of 5-FU, and the resultant cell lines showed an over 800-fold increased resistance to 5-FU. To identify the mechanism of 5-FU resistance, the expressions of genes involved in 5-FU metabolism were examined by reverse transcriptase-polymerase chain reaction (RT-PCR). Expressions of orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP), and uridine phosphorylase (UP) were significantly downregulated in these cell lines, resulting in low incorporation of 5-FU into nucleic acids. In contrast, an increased expression of thymidine kinase (TK) was observed in 5-FU-resistant cells. These results strongly indicate that blocking of 5-FU incorporation into nucleic acids and TK overexpression may play a major role in 5-FU resistance in these cells. Interestingly, these cell lines showed cross-resistance to paclitaxel, cisplatin, and doxorubicin, suggesting that other factors such as HSP27 and Mn-SOD could be also involved in the mechanism of multidrug resistance in these cell lines.

Antisense of human peroxiredoxin II enhances radiation-induced cell death.

Human peroxiredoxin II (Prx II) has been known to function as an antioxidant enzyme in cells. Using head-and-neck cancer cell lines, we investigated whether Prx II expression is related to the resistance of cells to radiation therapy in vivo and in vitro, and whether a Prx II antisense serves as a radiosensitizer. Increased expression of Prx II was observed in tissues isolated from the patients who did not respond to radiation therapy, whereas Prx II expression was weak in tissues from the patients with regressed tumors. Enhanced expression of Prx II in UMSCC-11A (11A) cells was also observed after treatment with gamma radiation. This increased expression conferred radiation resistance to cancer cells because overexpression of Prx II protected 11A cells from radiation-induced cell death, suggesting that blocking Prx II expression could enhance radiation sensitivity. Treatment of 11A cells with a Prx II antisense decreased induction of Prx II, enhancing the radiation sensitivity. From these results, we suggest that stress-induced overexpression of Prx II increases radiation resistance via protection of cancer cells from radiation-induced oxidative cytolysis and that a Prx II antisense can be used as a radiosensitizer.

Choroidal involvement in Wegener's granulomatosis: a case report.

Wegener's granulomatosis is a necrotizing, granulomatous vasculitis. It usually causes sinusitis, pneumonitis and glomerulonephritis. The common ocular manifestations include conjunctivitis, scleritis, peripheral keratitis and orbital inflammation. We report the case of a 50-year-old woman with Wegener's granulomatosis and very severe ocular complications who underwent bilateral enucleation. The pathologic findings of the eyeballs revealed granulomatous necrotizing scleritis, perivasculitis and granulomatous choroiditis. The last, as far as we know, has not yet been reported.

Endogenous Candida endophthalmitis after induced abortion.

PURPOSE: To report two young healthy women who developed endogenous Candida endophthalmitis after undergoing surgically induced abortion. METHOD: Case reports. RESULTS: In two eyes of two patients, a diagnosis of Candida endophthalmitis was established by typical fundus appearance, positive vaginal culture, and, in one case, positive vitreous culture. After vitrectomy and intravitreal amphotericin B injection, one eye of one patient had a best-corrected visual acuity of 20/200, whereas one eye of one patient, who had systemic corticosteroid treatment before the correct diagnosis, developed recurrent retinal detachment and a best-corrected visual acuity of counting fingers. CONCLUSIONS: Induced abortion may cause endogenous Candida endophthalmitis in young healthy pregnant women. Systemic corticosteroid treatment may increase the risk of endophthalmitis.

PIP: Reported, in this article, are the cases of two young women who developed endogenous Candida endophthalmitis after induced abortion. Both women experienced transient fever, chills, and abdominal pain after the abortion and were given antibiotics. The diagnosis of endophthalmitis was established on the basis of typical fundus appearance, positive vaginal culture, and (in one case) positive vitreous culture. In the first woman, who received vitrectomy and intravitreal amphotericin B injection, the affected eye had a best corrected visual acuity of 20/200. In the second woman, who was given systemic corticosteroid treatment before the correct diagnosis was reached, recurrent retinal detachment developed and the best corrected visual acuity was counting fingers. It appears that Candida organisms harbored in the genital tract are directly inoculated into the venous system during induced abortion. Once in the blood, if sufficient fungal load is present, Candida albicans tends to localize in the choroid and to spread toward the retina and vitreous cavity. The immunosuppressive effect of corticosteroids further increases the risk of endophthalmitis.

Effects of dopamine antagonists and agonist on cultured human Tenon's fibroblast cells.

It was found that long-term therapy with topical antiglaucoma drugs may increase the number of fibroblasts and inflammatory cells in the conjunctiva and Tenon's capsule then decrease the success of glaucoma filtering surgery. Since some dopamine antagonists and agonists are reported to have ocular hypotensive effects, they could potentially be used as clinical antiglaucoma agents in future. In this study, several dopamine antagonists and agonists were evaluated in their effects on the fibroblast proliferation of ocular tissues with cultured human ocular Tenon's fibroblast cells. It was found that dopamine antagonists inhibited [3H]-thymidine uptake to 10.8%, 14.4%, 42.2% and 72.4% of control in domperidone, 28.6%, 67.7%, 96.9% and 99.2% in haloperidol, 9.8%, 18.9%, 103.5% and 104.6% in moperone and 9.8%, 24.7%, 70.8% and 96.9% in loxapine respectively, while the 0.5% concentration of drugs were dissolved in dimethyl sulfoxide (DMSO) followed by dilution in culture medium to final concentrations ranging from 0.05%, 0.005%, 0.0005% to 0.00005%. In the case of dopamine agonist, bromocriptine, the proliferation of cultured human Tenon's fibroblast cells was also inhibited for 25.1% of the control at 0.05% concentration and 92.3% of the control at 0.00005% concentration. These results indicate that these dopamine drugs have a potential long-term application in the treatment of glaucoma without having the stimulating effect on the proliferation of human Tenon's fibroblast cells.

Transfusion-acquired AIDS in Taiwan.

Human immunodeficiency virus type 1 (HIV-1) can be transmitted through blood transfusion. The first transfusion-acquired immunodeficiency syndrome (AIDS) patient in Taiwan was a 46-year-old woman who received two units of whole blood during a hysterectomy at a provincial hospital in 1985. In 1991, she experienced a herpes zoster infection. In March 1993, she had extensive herpetic gingivostomatitis and another herpes zoster attack, and was treated at the same hospital. Two months later, she had oral candidiasis and was treated at a medical center. She was not tested for HIV-1 infection until she developed Pneumocystis carinii pneumonia in June 1993. In February 1994, and developed cytomegalovirus retinitis and died 6 months later. Donor blood given to the patients during the hysterectomy was HIV-1 positive. The donor's HIV infection was discovered in 1991 and he died of AIDS in 1993. As blood centers in Taiwan did not start screening for HIV-1 until January 1988, it is urgently recommended that any individual who received a blood transfusion between 1984 and 1987 in Taiwan and who currently experiences repeated episodes of opportunistic infections have an HIV-1 blood test. The receipt of a blood transfusion between 1984 and 1987 should be listed by the Department of Health as an indication for HIV-1 screening.

PIP: In June 1993, in Taiwan, a woman admitted to a local hospital with cough, fever, chills, and difficult breathing who tested positive for HIV-1 infection was transferred to Taipei Veterans General Hospital. In January 1985, at a provincial hospital, then 46 years old, she underwent an anterior total hysterectomy and bilateral salpingo-oophorectomy during which she received two units of whole blood. One of the blood donors was an AIDS patient who had been treated at the same hospital in 1991 and who had died in 1993. In the interim between hospitalizations, she had two episodes of herpes zoster infection, including oral ulcers diagnosed as herpetic gingivostomatitis, and an episode of oral candidiasis. Physicians at the Taipei Veterans General Hospital diagnosed oral candidiasis, herpes simplex type 1 virus infection forming ulcers on her lips, and Pneumocystis carinii pneumonia in June 1993. Her CD4 count was 0 and her CD8 count was 20%. Treatment consisted of intravenous (IV) trimethoprim/sulfamethoxazole (TMP/SMX) and oral zidovudine, fluconazole, and acyclovir. She continued this medication after discharge in August 1993. She was readmitted to Taipei Veterans General Hospital in February 1994 for blurred vision. She was diagnosed with cytomegalovirus retinitis. Her CD4 count was up to 1% and her CD8 count was down to 8%. The candidiasis infection had extended from her oral cavity to the esophageal mucosa. She was put on IV ganciclovir, TMP/SMX, and fluconazole. She was discharged 3 weeks after admission. Her condition deteriorated thereafter, resulting in her death in August 1994. Up until this study, this HIV/AIDS case was listed with 79 other HIV/AIDS patients as unknown cause. During the 8 years between HIV exposure and her diagnosis of AIDS, she had unprotected sexual intercourse with her husband. Neither the husband nor any of her four children have AIDS. Screening for HIV-1 in Taiwan began in January 1988. The authors urgently recommend that anyone who received a blood transfusion between 1984 and 1987 in Taiwan and who currently suffers repeated episodes of opportunistic infections undergo an HIV-1 blood test.

Digital indocyanine green angiography in chorioretinal diseases.

BACKGROUND: Fluorescein angiography (FA) is important in the diagnosis of chorioretinal diseases; however, it has some limitations. We conducted this study to evaluate whether digital indocyanine green (ICG) angiography can offer enhanced image in chorioretinal diseases. METHODS: Digital indocyanine green angiography with scanning laser ophthalmoscope (SLO) was performed in 314 patients with various chorioretinal diseases. This coupled digital imaging system can offer instant images, process and store data by computer, and give convenient hardcopy generation. RESULTS: The digital ICG angiography provided enhanced image resolution of the choroid compared with FA. The disease categories included choroidal neovascularization (CNV), choroidal tumor, inflammatory choroidal disease, ischemic choroidal disorder, idiopathic central serous chorioretinopathy and retinal macroaneurysm. CONCLUSIONS: ICG angiography is a useful adjunctive diagnostic technique to fluorescein angiography for various chorioretinal diseases. It is especially useful in the diagnosis of occult and recurrent CNV, as well as choroidal tumor and choroiditis. With greater clinical experience, ICG angiography is promising in giving additional clinical information for many other chorioretinal diseases.

Intraocular lens implantation following extracapsular cataract extraction in uveitis.

We reviewed the results of intraocular lens (IOL) implantation in the posterior chamber following extracapsular cataract extraction (ECCE) in 70 cataractous eyes with various types of endogenous uveitis, predominantly acute anterior uveitis, Fuchs' heterochromic cyclitis, Harada's disease, and Behçet's disease. During an average of 23.1 months' follow-up (range, 13 to 48 months) there was no exacerbation of the preexisting uveitis in any of the eyes. Postoperative visual acuity in all eyes was better than it was preoperatively, although further procedures were required in some eyes: a pars plana vitrectomy in one, a surgical peripheral iridectomy in one, and Nd:YAG laser capsulotomy in 10. Our results suggest that selected uveitis patients can tolerate and benefit from an ECCE and IOL implantation.

Formosanin-C, an immunomodulator with antitumor activity.

Paris formosana Hayata (Liliaceae) grown in the mountain areas of Taiwan, has been used as a folk remedy for snake bite, and as an anti-inflammatory or anti-neoplastic agent. The effects of formosanin-C, a diosgenin saponin isolated from Paris formosana, on immune responses and transplantable murine tumor were studied. In culture systems, formosanin-C (0.03-0.16 microM) displayed significant enhancement of the blastogenic response of human peripheral blood cells to phytohemagglutinin. Formosanin-C also significantly increased the 3H-thymidine incorporation of ConA-stimulated lymphocytes at concentrations of 0.1 and 0.01 microM. The responsiveness of the granulocyte/macrophage colony-forming cells (GM-CFC) to mouse fibroblast cells L929 conditioned medium was altered in the presence of 0.01 and 0.001 microM of formosanin-C. In addition, formosanin-C given intraperitoneally activated natural killer cell activity at doses of 1-2.5 mg/kg. An intraperitoneal injection of 2.5 mg/kg of formosanin-C markedly induced interferon production, the peak blood level of which was observed 24 h after formosanin-C injection. Growth of subcutaneously transplanted MH134 mouse hepatoma was retarded by intraperitoneal treatment with 1-2.5 mg/kg of formosanin-C. The activity of 5-fluorouracil against MH-134 mouse hepatoma was potentiated by intraperitoneal treatment with formosanin-C. These results suggest that formosanin-C might display antitumor activity in association with modification of the immune system.

Modulation of experimental autoimmune uveitis with formosanin-C in guinea pigs.

Formosanin-C, a diosgenin saponin, was isolated from a perennial herb, Paris formosana Hayata (Liliaceae) which has been used as a folk remedy for snake bite and as an anti-inflammatory or anti-neoplastic agent. Its effect on the development of S-antigen-induced experimental autoimmune uveitis (EAU) in guinea pigs was studied. Guinea pigs treated with formosanin-C (1.5 mg/kg/2 days and 0.5 mg/kg/2 days) were compared with untreated guinea pigs in regard to the development of EAU, lymphocytic proliferative responses, and anti-S-antigen serum antibodies. The higher dosage of formosanin-C (1.5 mg/kg) obviously delayed the onset of EAU. Treatment of this drug, 1.5 mg/kg and 0.5 mg/kg doses, significantly inhibited the specific lymphocytic response of lymph node and spleen cells to S-antigen. On the contrary, treatment in 1.5 mg/kg dose significantly increased the response of lymph node and spleen cells to the polyclonal T cell mitogen, phytohemagglutinin (PHA). Treatment with formosanin-C in both the 1.5 mg/kg and 0.5 mg/kg doses had a minimal effect on the lymphocytic response of lymph node to concanavalin-A (ConA), while a noticeable suppressive effect on the response of spleen cells to ConA was observed in the 1.5 mg/kg dose. This agent in 1.5 mg/kg and 0.5 mg/kg doses significantly inhibited the anti-S-antigen antibody production by days 14 and 18 postimmunization. This study suggests that formosanin-C, an immunomodulator, may offer a new approach to modulate the development of EAU.

[Sarcoidosis with ocular involvement].

A 28-year-old Chinese woman having sarcoidosis with ocular involvement was reported. She demonstrated bilateral hilar lymphadenopathy in a chest X-ray which was taken for a cough. Transbronchial lung biopsy revealed noncaseating epithelioid granulomas. Blurred vision occurred 8 months later when conjunctival follicle-like masses, granulomatous keratic precipitates, iridocyclitis, "snow-ball" vitreous opacity, and retinal periphlebitis developed in both eyes. Biopsy of the conjunctival follicle-like masses revealed noncaseating granulomas composed of epithelioid cells and multinuclear giant cells, typical of sarcoidosis. The ocular lesions waned under topical steroid treatment and vision improved. This is the only case with an ocular involvement among the 10 cases of sarcoidosis seen during the past 20 years at the Taipei Veterans General Hospital.

Conjunctival involvement of lymphomatoid granulomatosis.

Lymphomatoid granulomatosis is an angiocentric and angiodestructive lympho-proliferative disorder involving multisystems but rarely conjunctiva. We present a 62-year-old Chinese female with lymphomatoid granulomatosis who had an ulcerative conjunctival nodule. Conjunctival biopsy revealed pathological findings important for diagnosis and indicating progression of disease severity. To our knowledge, this is the first report to demonstrate pathological findings characteristic of lymphomatoid granulomatosis with conjunctival involvement.