Symposium: Current and future issues in hepatitis C treatment : New emerging therapy for hepatitis C -The rational use of specifically targeted agents against hepatitis C infection

Raymond T. Chung 대한간학회 2009 Clinical and Molecular Hepatology(대한간학회지) Vol.15 No.4(S)

The development of specifically targeted antiviral agents against hepatitis C (STAT-C) is a major therapeutic advance that promises to dramatically improve treatment response rates in patients with chronic infection. However, rapid emergence of drug resistance has already been described, the consequences of which are not yet understood. While there are important differences between HCV and HIV infection, the judicious use of candidate agents against HCV should be guided by principles that have been established in the HIV therapeutic arena. In this review, we attempt to draw useful parallels between the development of antiretroviral therapy for HIV and preliminary data on antiviral agents for hepatitis C virus infection. Applying concepts learned in HIV therapeutics will hopefully lead to a prudent and cautious path in HCV treatment paradigms, particularly with respect to drug resistance.

Treatment Options in HCV Relapsers and Nonresponders

( Raymond T. Chung ) 대한간학회 2007 Clinical and Molecular Hepatology(대한간학회지) Vol.13 No.5(S)

Photoimmunology : Past , Present and Future

Chung, Hun Taeg,Raymond A . Daynes,Lee K . Roberts 대한미생물학회 1986 大韓微生物學會誌 Vol.21 No.3

The experimental exposure of animals to sources of ultraviolet radiation (UVR) which emit their energy primarily in the UVB region (280-320nm) is known to result in a nu- mber of well-described changes in the recipients immune competence. Two such changes include a depressed capacity to effectively respond immunologically to transplants of syngeneic UVR tumors and a markedly reduced responsiveness to known inducers of delayed-type (DTH) and contact hypersensitivity (CH) reactions. The results of experiments that were designed to elucidate the mechanisms res- ponsible for UVR-induced immunomodulation have implicated: 1) an altered pattern of lymphocyte recirculation, 2) suppressor T cells(Ts), 3) deviatioris io systernic antigen presenting cell (APC) potential, 4) changes in the prod- uction of interleukin-1-like molecules, and 5) the functional inactivation of epidermal Langerhans cells in this process. The exposure of skin to UVR, therefore, eauses a number of both local and systemic alterations to the normal host immune system. In spite of this seeming complexity and diversity of responses, our recent studies have established that each of the UVR-mediated changes is probably of equal importance to creating the UVR-induced immunocompromised state. Normal animals were exposed to low dose UVR radiation on their dorsal surfaces under conditions where a 3.0cm area of skin was physically protected from the light energy. Contact sensitization of these animals with DN-FB, to either the irradiated or protected hack skin, resulted in markedly reduced CH responses. This was observed in spite of a normal responsiveness following the skin sensitization to ventral surfaces of the UVR-exposed animals. Systemic treatment of the low dose UVR recipients with the drug indomethacin (1-3 micrograms/day) during the UVR exposures resulted in a complete reversal of the depressions observed following DNFB sensitization to protected dorsal skin while the altered responsiveness found in the group exposed to the skin reactive chemical through directly UVR-exposed sites was maintained. These studies implicate the importance of EC as effective APC in the skin and also suggest that some of the systemic influences caused by UVR exposure involve the production of prostaglandins. This concept was further supported by finding that indomethacin treatment was also capable of totally reversing the systemic depressions in CH responsiveness caused by high dose UVR exposure (30K joules/ m) of mice. Attempts to analyze the cellular mechanisms responsible established that the spleens of all animals which demonstrated a1tered CH responses, regardless of whether sensitization was through a normal or an irradiated skin site, contained suppressor cells. Interestingly, we also found normal Devels of T effector cells in the peripheral lymph nodes of the UVR-exposed mice that were contact sensitized through normal skin. No effector cells were found when skin sensitizetion took place through irradiated skin sites. In spite of such an apparent paradox, insight into the probable mechanisms responsible for these observations was provided by establishing that UVR exposure of skin results in a striking and dose-dependent blockade of the efferent lymphatic vessels in all peripheral lymph nodes, Therefore, the afferent phases of immune responses can apparently take place normally in UVR exposed animals when antigen is applied to normal skin. The final effector responses, however, appear to be inhibited in the UVR-exposed animals by an apparent bloek of effector cell mobility. This contrasts with findings in the normal animals. Following contact sensitization, normal animals were also found to simultaneously contain both antigen specific suppr essor T cells and lymph node effector cells. However, these normal animals were fully capable of mobilizing their effector cells into the systemic circulation, thereby allowing a localization of these cells to peripheral sites of antigen challenge. Our results suggest that UVR is probably not a significant inducer of suppressor T-cell activity to topically applied antigens. Rather, UVR exposure appears to modify the normal relationship which exists between effector and regulatory immune responses in vivo. It does so by either causing a direct reduction in the skins APC function, a situation which results in an absence of effector cell generation to antigens applied to UVR-exposed skin sites, inhibiting the capacity of effector cells to gain access to skin sites of antigen challenge or by sequestering the lymphocytes with effector cell potential into the draining peripheral lymph nodes. Each of these situations result in a similar effect on the UVR-exposed host, that being a reduced capacity to elicit a CH response. We hypothesize that altered DTH responses, altered alloresponses, and altcred graftversus-host responses, all of which have been observed in UVR exposed animals, may result from similar mechanisms.

Cost, safety, and rehabilitation of samestage, bilateral total knee replacements compared to two-stage total knee replacements

( Raymond C. W. Wan ),( Jason C. H. Fan ),( Yuk-wah Hung ),( Ka-bon Kwok ),( Carmen K. M. Lo ),( Kwong-yin Chung ) 대한슬관절학회 2021 대한슬관절학회지 Vol.33 No.-

Background: Many patients experience bilateral knee osteoarthritis and require bilateral total knee replacement (TKR). Same-stage, bilateral TKR is proposed to be a cost-effective and safe solution compared to two-stage, but conflicting results in the literature are reported. We aim to compare the costs, safety, and rehabilitation performance of patients in same-stage versus two-stage, bilateral TKR with our centre’s perioperative protocol. Materials and methods: We retrospectively reviewed 175 patients (95 same-stage, 80 two-stage) who had undergone bilateral TKR in our centre. Patient selection for same-stage, bilateral TKR was strictly protocol-driven and required fulfilment of all criteria, including age < 75 years, American Society of Anesthesiologists (ASA) grade 1 or 2, body mass index (BMI) < 40, and having non-complex arthritis. All patients followed a standardised pre-operative, intra-operative, and post-operative Enhanced Recovery After Surgery (ERAS) protocol. The cost, safety profiles, and rehabilitation outcomes were compared between the same-stage and two-stage groups. Results: The same-stage, bilateral TKR reduced the length of hospital stays by 5.71 days per patient, decreased the operation time by 27.4 min, saved 3.34 (18.6%) physiotherapy sessions, and 3.78 (51.5%) occupational therapy sessions. The same-stage group experienced a higher haemoglobin drop but no significant difference in transfusion percentage, transfusion volume, complication rate, and readmission rate. The two-stage subgroup with anaesthetic risk, age, and BMI similar to the same-stage group showed the same results. Same-stage, bilateral TKR patients experienced no significant difference in final post-operative pain levels and rehabilitation outcomes as two-stage TKR patients. Conclusion: This study showed that same-stage, bilateral TKR can reduce costs, with similar safety profiles and rehabilitation outcomes compared to the two-stage, bilateral TKR.

Elucidation of the Mechanisms Responsible for the Immunomodulatory Influences of Ultraviolet Radiation

Chung, Hun-Taeg,Kang, Eun-Mi,Kang, Kyoung-Sook,Kim, Burnham,Lee, K. Roberts,Daynes, Raymond A. 圓光大學校 醫科學硏究所 1985 圓光醫科學 Vol.1 No.2

본 실험에서 저자들은 자외선조사에 의한 접촉성과민반응의 감소가 두 기전에 의한다는 사실을 시사하는 결과를 얻은 바 그 하나는 자외선조사에 의하여 피부의 Langerhans 씨 세포에 기능적 장애가 초래되는 것이고 다른 하나는 자외선 조사에 의한 prostaglandin 생산의 과잉으로 인한 임파구 재순환의 장애에 의한 것이다. 전자는 소량의 자외선 조사에 의한 국부적인 접촉성과민반응의 감소를 초래하나 후자는 대량의 자외선 조사에 의한 전신적 면역억제현상을 유도하며 이러한 현상은 prostaglandin 합성 억제제인 indomethacin을 투여할 경우 나타나지 아니하였다. The exposure of experimental animals to ultraviolet radiation (UVR) results in a marked reduction in their capacity to elicit contact hypersensitivity (CH) responses to epicutaneously applied skin reactive chemicals. Mice exposed to low-dose UVR (4 × 400 J/m^2/day) demonstrate a reduction in contact sensitization potential which is site specific (localized to the skin areas of direct UVR exposure) whereas high-dose exposure of mice to UVR (1 × 30,000 J/m^2) causes systemic alterations which leave the animals hyporesponsive to CH induction regardless of the skin site of hapten application. Both types of UVR-mediated alterations have been reported to associate with suppressor T-cell induction, a regulatory response which has been concluded to be responsible for the observed hyporesponsiveness to stimulation of CH reactions. Herein we report that the ability of UVR exposure to alter a recipient's capacity to elicit CH responses is mediated through two distinct mechanisms, one of which can be overridden by an inhibition of in situ prostaglandin biosynthesis by treatment with the drug indomethacin. The capacity of UVR to functionally inactivate epidermal Langerhans cells (LC) results in a markedly reduced capacity of animals that are contact sensitized directly through irradiated skin sites to elicit CH responses. This condition is associated with a lack of CH effector cells in the peripheral lymph nodes, an enhanced splenic suppressor cell activity, and cannot be reversed by indomethacin treatment. The “systemic suppression” of CH responsiveness observed in high-dose UVR-exposed animals that are sensitized through unirradiated or UVR-protected skin sites (normal LC) was found to be totaly reversible with indomethacin treatment. The mechanism responsible for the indomethacin-sensitive immunomo-dulatory effects of UVR-exposure appears to be due to the capacity of prostaglandins to sequester lymphocytes within peripheral lymph nodes via an efferent lymphatic blockade. This hypothesis was supported by our observation of a marked CH-effector cell activity in the peripheral lymph nodes of contact sensitized high-dose UVR-exposed animals which demonstrated a simultaneous presence of splenic suppressor cells. Therefore, UVR does not appear to exert its immunoregulatory activities via the preferential induction of suppressor cell activity following skin sensitization. Rather, the suppressor circuit in UVR-exposed animals appears to remain normal, with the immune modifying influences of this physical agent being due to either an inhibition of CH-effector cell generation (due to direct LC inactivation) or to a prostaglandin-mediated sequestration of CH-effector cells within peripheral lymph nodes (efferent blockade).

Herbs and Rehabilitation after Stroke Study: A Multi-center, Double-blinded, Randomized Trial in Hong Kong

Raymond Cheung,Li Xiong,Shek Kwan Chang,Choi Ting Tse,Yin Yu Pang,Vincent Mok,Thomas Leung,Tak Hong Tsoi,Richard Li,May Mok,Chee My Chang,Kwok Kwong Lau,Bun Sheng,Terrence Li,Jonas Yeung,Ping Chung Le 대한뇌졸중학회 2016 Journal of stroke Vol.18 No.3

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Photoimmunology -Past, Present and Future-

Daynes, Raymond A.,Chung, Hun-Taeg,Roberts, Lee K. The Korea Society for Microbiology 1986 大韓微生物學會誌 Vol.21 No.3

The experimental exposure of animals to sources of ultraviolet radiation (UVR) which emit their energy primarily in the UVB region (280-320nm) is known to result in a number of well-described changes in the recipient's immune competence. Two such changes include a depressed capacity to effectively respond immunologically to transplants of syngeneic UVR tumors and a markedly reduced responsiveness to known inducers of delayedtype (DTH) and contact hypersensitivity (CH) reactions. The results of experiments that were designed to elucidate the mechanisms responsible for UVR-induced immunomodulation have implicated: 1) an altered pattern of lymphocyte recirculation, 2) suppressor T cells(Ts), 3) deviations in systemic antigen presenting cell (APC) potential. 4) changes in the production of interleukin-1-like molecules, and 5) the functional inactivation of epidermal Langerhans cells in this process. The exposure of skin to UVR, therefore, causes a number of both local and systemic alterations to the normal host immune system. In spite of this seeming complexity and diversity of responses, our recent studies have established that each of the UVR-mediated changes is probably of equal importance to creating the UVR-induced immunocompromised state. Normal animals were exposed to low dose UVR radiation on their dorsal surfaces under conditions where a $3.0\;cm^2$ area of skin was physically protected from the light energy. Contact sensitization of these animals with DNFB, to either the irradiated or protected back skin, resulted in markedly reduced CH responses. This was observed in spite of a normal responsiveness following the skin sensitization to ventral surfaces of the UVR-exposed animals. Systemic treatment of the low dose UVR recipients with the drug indomethacin (1-3 micrograms/day) during the UVR exposures resulted in a complete reversal of the depressions observed following DNFB sensitization to "protected" dorsal skin while the altered responsiveness found in the group exposed to the skin reactive chemical through directly UVR-exposed sites was maintained. These studies implicate the importance of EC as effective APC in the skin and also suggest that some of the systemic influences caused by UVR exposure involve the production of prostaglandins. This concept was further supported by finding that indomethacin treatment was also capable of totally reversing the systemic depressions in CH responsiveness caused by high dose UVR exposure (30K joules/$m^2$) of mice. Attempts to analyze the cellular mechanisms responsible established that the spleens of all animals which demonstrated altered CH responses, regardless of whether sensitization was through a normal or an irradiated skin site, contained suppressor cells. Interestingly, we also found normal levels of T effector cells in the peripheral lymph nodes of the UVR-exposed mice that were contact sensitized through normal skin. No effector cells were found when skin sensitization took place through irradiated skin sites. In spite of such an apparent paradox, insight into the probable mechanisms responsible for these observations was provided by establishing that UVR exposure of skin results in a striking and dose-dependent blockade of the efferent lymphatic vessels in all peripheral lymph nodes. Therefore, the afferent phases of immune responses can apparently take place normally in UVR exposed animals when antigen is applied to normal skin. The final effector responses, however, appear to be inhibited in the UVR-exposed animals by an apparent block of effector cell mobility. This contrasts with findings in the normal animals. Following contact sensitization, normal animals were also found to simultaneously contain both antigen specific suppressor T cells and lymph node effector cells. However, these normal animals were fully capable of mobilizing their effector cells into the systemic circulation, thereby allowing a localization of these cells to peripheral

페루 꾸스코 지역 지질특성과 다금속 광화작용

류충렬 ( Chung Ryul Ryoo ),허철호 ( Chul Ho Heo ),미카엘발렌시아무노즈 ( Michael Valencia Munoz ),레이몬리베라코르네호 ( Raymond Rivera Cornejo ),알렉산더산띠스떼반안겔도니스 ( Alexander Santisteban Angeldonis ) 한국광물학회 2012 광물과 암석 (J.Miner.Soc.Korea) Vol.25 No.1

Review : New treatments for chronic hepatitis C

( Jae Young Jang ),( Raymond T. Chung ) 대한간학회 2010 Clinical and Molecular Hepatology(대한간학회지) Vol.16 No.3

Treatments for chronic hepatitis C has evolved significantly in the past 15 years. The standard of care (SOC) is peginterferon alfa-2a/-2b with ribavirin for 48 weeks or 24 weeks in patients infected with HCV genotype 1 or 2/3, respectively. The treatment duration can be individualized based on the baseline viral load and the speed of the virologic response during treatment. However, current therapies are associated with side effects, complications, and poor patient tolerability. Therefore, there is an urgent need to identify better strategies for treating this disease. An improved sustained virologic response (SVR) can be achieved with new HCV-specific inhibitors against NS3/4A and NS5B polymerases. Recent trials have found SVR rates in patients with HCV genotype 1 infection of 61~68% and 67~75% for combining the SOC with the protease inhibitors telaprevir and boceprevir, respectively. Several new HCV-specific inhibitors such as protease inhibitors and nucleoside and non-nucleoside polymerase inhibitors as well as non-HCV-specific compounds with anti-HCV activity are currently in clinical evaluation. In this review we discuss these new treatments for chronic hepatitis C. (Korean J Hepatol 2010;16:263-277)

Review : Chronic Hepatitis C

( Jae Young Jang ),( Raymond T. Chung ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2011 Gut and Liver Vol.5 No.2

The goal of antiviral therapy for patients with chronic hepatitis C virus (HCV) infection is to attain a sustained virologic response (SVR), which is defined as undetectable serum HCV-RNA levels at 6 months after the cessation of treatment. Major improvements in antiviral therapy for chronic hepatitis C have occurred in the past decade. The addition of ribavirin to interferon-alfa therapy and the introduction of pegylated interferon (PEG-IFN) have substantially improved SVR rates in patients with chronic hepatitis C. The optimization of HCV therapy with PEG-IFN and ribavirin continues to evolve. Studies are ongoing that use viral kinetics to tailor therapy to an individual`s antiviral response and determine the ideal length of treatment to maximize the chance of SVR. Improved SVR can be achieved with new specifi c inhibitors that target the HCV NS3/4A protease and the NS5B polymerase. Several long-term follow-up studies have shown that SVR, when achieved, is associated with a very low risk of virologic relapse. Furthermore, antiviral therapy can reduce the morbidity and mortality rates associated with chronic hepatitis C by reducing fi brosis progression, the incidence of cirrhosis, and hepatocellular carcinoma. (Gut Liver 2011;5:117-132)