• Title/Summary/Keyword: Non-responder

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Decreased CRTH2 Expression and Response to Allergen Re-stimulation on Innate Lymphoid Cells in Patients With Allergen-Specific Immunotherapy

  • Mitthamsiri, Wat;Pradubpongsa, Panitan;Sangasapaviliya, Atik;Boonpiyathad, Tadech
    • Allergy, Asthma & Immunology Research
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    • v.10 no.6
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    • pp.662-674
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    • 2018
  • Purpose: Group 2 innate lymphoid cells (ILC2s) have been implicated in the pathogenesis of allergic disease. However, the effect of allergen-specific immunotherapy (AIT) on ILCs remains to be clarified. The aim of this study was to evaluate the levels of ILC subsets in allergic rhinitis (AR) patients in response to house dust mite (HDM)-specific immunotherapy. Methods: We enrolled 37 AR patients undergoing AIT (16 responders and 11 non-responders) for 2 years, 35 HDM AR patients and 28 healthy subjects. Peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry to identify ILC subsets. Stimulation of ILC2s with recombinant allergen-specific protein was used to determine ILC2's activation (CD69 expression). Results: Responder AIT patients and healthy subjects had a decreased frequency of circulating ILC2s compared to non-responder AIT and AR patients. Conversely, ILC1s from responder AIT patients and healthy subjects showed increased frequency compared to non-responder AIT and AR patients. The frequency of ILC3s natural cytotoxicity receptor $(NCR)^+$ and $NCR^-$ in responder AIT patients was significantly lower compared to AR patients and healthy subjects. The ILC1: ILC2 proportion in responder AIT patients was similar to that of healthy subjects. PBMCs from patients who were responders to AIT had a significantly lower expression of the activation marker CD69 on ILC2s in response to allergen re-stimulation compared to AR patients, but no difference compared to non-responder AIT patients and healthy subjects. Conclusions: We propose that AIT might affect ILC responses. The activation of ILC2s was reduced in AR patients treated with AIT. Our results indicate that a relative ILC1/ILC2 skewed response is a possible key to successful AIT.

Shunt-Responsive Idiopathic Normal Pressure Hydrocephalus Patient with Delayed Improvement after Tap Test

  • Kang, Kyunghun;Hwang, Sung Kyoo;Lee, Ho-Won
    • Journal of Korean Neurosurgical Society
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    • v.54 no.5
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    • pp.437-440
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    • 2013
  • The cerebrospinal fluid tap test (CSFTT) is recommended as a key step in the diagnosis of idiopathic normal pressure hydrocephalus (iNPH). While there is no generally accepted evaluation period for ascertaining a CSFTT responder, a substantial number of patients are evaluated only once within 24 hours of the test for improvement in gait. We report an iNPH patient with a favorable response to shunt surgery, who was first judged a non-responder by this standard, though subsequently was judged a responder in virtue of repetitively testing gait over 7 days. A 68-year-old man presented with progressive impairment of gait, balance, and memory. He was diagnosed as iNPH with an Evans' ratio of 0.35. At first hospitalization, change in gait was evaluated 24 hours after the CSFTT. He didn't show any significant improvement and was judged as a non-responder. However, at the second CSFTT, we repetitively tested his change in gait over seven days. Forty-eight hours after the tap, he showed significant improvement in his gait. He was then confirmed as a responder. After the operation, the gait difficulties were almost fully resolved. Further studies developing the standard procedure of the CSFTT should be considered.

The association of genetic polymorphism between responder and nonresponder to acupuncture in smoking cessation (금연침에 대한 반응군과 비반응군의 유전자 다형성 차이 연구)

  • Youhn, Dong-Hak;Park, Hi-Joon;Kim, Seung-Tae;Jin, Soo-Hee;Lee, Su-Jin;Lee, Hye-Jung;Lim, Sa-Bi-Na
    • Korean Journal of Acupuncture
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    • v.21 no.1
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    • pp.41-50
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    • 2004
  • Objectives : This study was designed to investigate the differences of effects in smoking cessation after acupuncture treatment and we hypothesized that the discrepancies might be caused by individual genetic differences. Methods : Acupuncture treatment was given to the subjects three times a week for the 231 healthy male Korean smokers without personal or familial history of psychiatric or neurological illness. We evaluated for differentiate responder and non-responder who showed more than 50% decrease in the cigarette consumption or the desire for smoking were regarded as responder, and less than 25% decrease in the cigarette consumption or the desire for smoking were regarded as non-responder, respectively. Allele and genotype frequencies of the Taq1 A polymorphism of dopamine D2 receptor (DRD2) gene were compared in 231male smokers. Chai-square analyses were performed to test for an interactive effect between the DRD2 Taq1 A allele. Results : The allele frequencies and genotype distributions of DRD2 gene among the smokers (n = 231) showed significant the differences in their genotype distributions. The responder and non-responder showed the difference in genotype distribution with a prevalence of A1 allele. A slightly positive association of DRD2 Taq1 A1 genotypes with smoking was observed. Conclusions : This experiment results indicate that the present of DRD2 allele genotype showing significant difference in the genotype distributions between responders and non-responders could be explained by the difference in the genetic effect of DRD2 A1 allele.

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Genes Associated with Individual Variation of Electroacupuncture Anti-allodynic Effects in Rat

  • Hwang, Byung-Gil;Kim, Sun-Kwang;Han, Jae-Bok;Bae, Hyun-Su;Min, Byung-Il
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.5
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    • pp.1285-1290
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    • 2007
  • The present study aims to identify and characterize genes that cause differen genes between non-responders and responders to electroacupuncture (EA) on mechanical allodynia following peripheral nerve injury. Under sodium pentobarbital anesthesia, animals were subjected to unilateral transection of the superior caudal trunk at the level between S1 and S2 spinal nerves. EA stimulation (2Hz, 0.3 ms, 0.2-0.3 mA) was delivered to Zusanli (ST36) for 30 min 2 weeks after the surgery. The degree of mechanical allodynia was assessed quantitatively by touching the tail with von Frey hair (2.0 g) at 10 min intervals. The rats, which showed an EA-induced decrease of response frequencies under 10 %, were classified as non-responders and those displaying an EA-induced decrease of response frequencies 20 % or more were classified as responders. Results from oligonucleotide microarray, to which cDNAs from the spinal dorsal horn (DH) were applied, showed that hemoglobin beta chain complex and chondroitin sulfate proteoglycan-5 decreased and limbic system-associated membrane protein increased in the non-responder group, whereas calcium-independent alpha-Iatrotoxin receptor homolog-3 increased in the responder group. These results suggest that The functional abnormality of molecules regulating cell adhesion, intracellular signal transduction and cell differentiation in the spinal DH may be involved in the anti-allodynic effect of EA.

Earlier treatment improves the chances of complete relief from postherpetic neuralgia

  • Kang, Dong Hee;Kim, Su Young;Kim, Hyuck Goo;Park, Jung Hyun;Kim, Tae Kyun;Kim, Kyung Hoon
    • The Korean Journal of Pain
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    • v.30 no.3
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    • pp.214-219
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    • 2017
  • Background: As herpes zoster progresses via postherpetic neuralgia (PHN) to well-established PHN, it presents its recalcitrant nature to the treatment. At this point, the well-established PHN is fixed as a non-treatable, but manageable chronic painful neuropathic disorder. This study evaluated the incidence of complete relief from PHN according to PHN duration at their first visit, and the other factors influencing it. Methods: A retrospective chart review was performed on patients with PHN at a university-based pain clinic over 7 years. The responders were defined as patients who had complete relief from pain after 1 year of active treatment. Age, sex, PHN duration at their first visit, dermatomal distribution, and underlying disorders were compared in the responder and non-responder groups. Responders were also compared according to these factors. Results: Among 117 PHN patients (M/F = 48/69), 35 patients (29.9%) had complete relief from PHN. Mean ages were $64.3{\pm}10.6$ and $66.9{\pm}10.7$ years, numbers of male to female patients were 11/24 and 37/45, and mean durations of PHN at their first visit were $8.5{\pm}6.3$ and $15.3{\pm}10.7$ months in the responder and non- responder groups, respectively. In addition, PHN patients who visited the clinic before 9 months showed a better result. Dermatomal distribution and underlying disorders did not show significant differences. Conclusions: Almost 30% of PHN patients received complete relief. Those who sought treatment in a pain clinic before 9 months received a better result.

Prediction of response by FDG PET early during concurrent chemoradiotherapy for locally advanced non-small cell lung cancer

  • Kim, Suzy;Oh, So Won;Kim, Jin Soo;Kim, Ki Hwan;Kim, Yu Kyeong
    • Radiation Oncology Journal
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    • v.32 no.4
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    • pp.231-237
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    • 2014
  • Purpose: To evaluate the predictive value of the early response of $^{18}F$-flurodeoxyglucose positron emission tomography (FDG PET) during concurrent chemoradiotherapy (CCRT) for locally advanced non-small cell lung cancer (NSCLC). Materials and Methods: FDG PET was performed before and during CCRT for 13 NSCLC patients. Maximum standardized uptake value ($SUV_{max}$), mean standardized uptake value ($SUV_{mean}$), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured and the changes were calculated. These early metabolic changes were compared with the standard tumor response by computed tomograms (CT) one month after CCRT. Results: One month after the completion of CCRT, 9 patients had partial response (PR) of tumor and 4 patients had stable disease. The percent changes of $SUV_{max}$ ($%{\Delta}SUV_{max}$) were larger in responder group than in non-responder group ($55.7%{\pm}15.6%$ vs. $23.1%{\pm}19.0%$, p = 0.01). The percent changes of $SUV_{mean}$ ($%{\Delta}SUV_{mean}$) were also larger in responder group than in non-responder group ($54.4%{\pm}15.9%$ vs. $22.3%{\pm}23.0%$, p = 0.01). The percent changes of MTV ($%{\Delta}MTV$) or TLG ($%{\Delta}TLG$) had no correlation with the tumor response after treatment. All the 7 patients (100%) with $%{\Delta}SUV_{max}{\geq}50%$ had PR, but only 2 out of 6 patients (33%) with $%{\Delta}SUV_{max}$ < 50% had PR after CCRT (p = 0.009). Likewise, all the 6 patients (100%) with $%{\Delta}SUV_{mean}{\geq}50%$ had PR, but only 3 out of 7 patients (43%) with $%{\Delta}SUV_{mean}$ < 50% had PR after CCRT (p = 0.026). Conclusion: The degree of metabolic changes measured by PET-CT during CCRT was predictive for NSCLC tumor response after CCRT.

Long-Term Treatment Response to Lithium and Valproate in Patients with Bipolar 1 Disorder Treated More Than 2 Years : A Retrospective Study (1형 양극성 장애 환자에서 리튬과 발프로산의 장기간 치료 효과에 대한 후향적 평가 : 2년 이상 치료받은 환자의 효과 비교)

  • Ahn, Sung Woo;Yang, So-Yung;Choi, Yujin;Hong, Kyung Sue
    • Korean Journal of Biological Psychiatry
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    • v.23 no.4
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    • pp.185-192
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    • 2016
  • Objectives Treatment response of bipolar disorders (BDs) to long-term mood stabilizers maintenance has not been well explored because of complicated clinical and treatment courses. This study aims at investigating long-term clinical response of BDs to lithium and/or valproate in a naturalistic setting of a tertiary-care university-affiliated hospital. Methods Subjects were 65 patients with bipolar I (BD-I) disorders who had been treated with lithium and/or valproate for more than two years at single bipolar disorder clinic. Long-term response to the best treatment based on treatment algorithms and the current clinical standard of care was retrospectively evaluated using the Alda Scale and the Clinical Global Impression Scale for use in bi-polar illness (CGI-BP). Patients were classified into full responder and partial/non responder groups based on the total score of the Alda Scale with the cut-off score generated from the frequentist mixture analysis of the authors' previous study. Results The mean duration of treatment with the index medication was 69.2 months. Baseline demographic and clinical characteristics were not different among three mood stabilizer groups (valproate, lithium, and combination groups). Twenty-one subjects were classified into full responder group (32.3%). Treatment response assessed by the Alda Scale and CGI-BP scores was not different between lithium and valproate groups. The Alda Scale scores were well correlated with the CGI-BP scores (p < 0.05). Conclusions One third of the patients showed a full response to the long-term lithium and/or valproate treatment in BD-I. The degree of response was similar between lithium and valproate groups.

Hypothesis Proposal about Predictive Factors and Optimal Age for Response to Herbal Medicine Treatment for Height Gain in Children: a Retrospective Review

  • Leem, Jungtae;Kim, Jeeyeun;Suh, Kyeungsuk;Lim, Youngkwern;Lee, Junhee
    • The Journal of Korean Medicine
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    • v.39 no.4
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    • pp.16-29
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    • 2018
  • Introduction: We aimed to investigate the predictive factors and optimal age for response to herbal medicine treatment for height gain in children. Methods: This retrospective chart review included 61 children (age range, 5-16 years) treated for height gain between 2011 and 2015. A predictive model was established by multiple linear regression analysis. Dependent variables were defined by the differences in percentile before and after herbal medicine treatment. The optimal cutoff value of patient age was determined by receiver operating curve analysis. Results : The age of initiation of herbal medicine therapy (p = 0.012) and administration of Forsythiae fructus (p = 0.002) were significant variables for treatment response. The adjusted R2 value was 0.231. The mean ages of the responder and non-responder groups were significantly different (p = 0.023). The optimal cutoff value of age for predicting treatment response was 9.75 years. Treatment response was better among children below 9.75 years of age. Conclusions: Patient age and administration of Forsythiae fructus were identified as determinants of response to herbal medicine treatment. Treatment of rhinitis and initiation of height gain treatment at an early age are critical for better response. These findings will provide fundamental data for further research.

Electroacupuncture Analgesia Is Improved by Adenoviral Gene Transfer of Dopamine Beta-hydroxylase into the Hypothalamus of Rats

  • Kim, Soo-Jeong;Chung, Eun Sook;Lee, Jun-Ho;Lee, Chang Hoon;Kim, Sun Kwang;Lee, Hye-Jung;Bae, Hyunsu
    • The Korean Journal of Physiology and Pharmacology
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    • v.17 no.6
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    • pp.505-510
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    • 2013
  • Electroacupuncture (EA) is a modified form of acupuncture that utilizes electrical stimulation. We previously showed that EA stimulated rats were divided into responders that were sensitive to EA and non-responders that were insensitive to EA based on the tail flick latency (TFL) test. The dopamine beta-hydroxylase (DBH) gene was more abundantly expressed in the hypothalamus of responder rats than non-responder rats. To determine whether overexpression of DBH gene expression in the hypothalamus modulate EA analgesia, we constructed a DBH encoding adenovirus and which was then injected into the hypothalamus of SD rats. Microinjection of DBH or control GFP virus into the hypothalamus had no changes on the basal pain threshold measured by a TFL test without EA treatment. However, the analgesic effect of EA was significantly enhanced from seven days after microinjection of the DBH virus, but not after injection of the control GFP virus. DBH expression was significantly higher in the hypothalamus of DBH virus injected rat than control GFP virus or PBS injected rats. Moreover, expression of the DBH gene did not affect the body core temperature, body weight, motor function or learning and memory ability. Although the functional role of DBH in the hypothalamus in the analgesic effect of EA remains unclear, our findings suggest that expression of the DBH gene in the hypothalamus promotes EA analgesia without obvious side-effects.

Gene Expression Profile of the Responder vs. the Non-Responder to the Acupuncture Mediated Analgesic Effects (침자극에 대한 반응과 비반응군 흰쥐의 특이 유전자 발현 연구)

  • Sur Young Chan;Rho Sam Woong;Lee Gi Seog;Ko Eun Jung;Hong Moo Chang;Shin Min Kyu;Min Byung il;Bae Hyun Su
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.3
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    • pp.633-642
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    • 2003
  • A pain is the symptom which defends against noxious stimulus about a human body, it is known that if the periphery of perceptive nerve were stimulated by a physical or chemical factors, the stimulation is induced by transmission to pain center in the cerebral cortex according to pain conduction tract. The treatment of pain is to decrease a stimulus that causes a pain or block off a nerve transmitting a stimulus or puts on a way to calm down pain center, but It is for adjustment of a pain to be the most representative in acupuncture among various ways to cure a pain in Oriental medicine. However, the analgesic effect of an individual response to acupuncture stimulation shows marked individual variations, so these days genetic a few approach is attempted. On this the author determined that the responding group was appointed those whose tail flick latency (TFL) responding time delayed the minimum of 30 % comparing with basal reaction time. For those whose TFL time had shorter than 30 % was grouped as a non-responding group. And then the hypothalamus of each group was dissected and RNA was further purified. After synthesizing cDNA using oligo dT primer, products were finally applied to the PCR. The results were as follows; The ratio of responding group to non-responding group was 6:4. Ach T (acetylcholinesterase T subunit), BF-I (Brain factor-I), DBH (Dopamine β-hydroxylase) and PNM (Phosphotidylethanolamine N-Methyltransferase) were revealed significantly in the responding group. Cathepsin B and Tau were revealed significantly in the non-responding group. The PCR results show that Ach T, BF-I, DBH and PNM are expressed abundantly in the responding group, where as cathepsin B and tau are abundant in the non-responding group. These results suggest that the analgesic effect on acupuncture stimulation is related to regulation of neurotransmitter as well as neurodegeration of cerebrum.