The Immunomodulating Effects of Thalidomide and Dexamethasone in a Murine Cardiac Allograft Transplantation Model

Purpose@#The immunomodulatory effects of thalidomide (TM) and dexamethasone (DX) on immune cells and their co-stimulatory, co-inhibitory molecules in vitro and in vivo have been previously reported. The current study investigated the effects of TM and the combinatorial treatment with DX on immune cells using a murine cardiac allograft transplantation model. @*Materials and Methods@#Intraabdominal transplant of cardiac allografts from BALB/c (H-2d ) donors to C57BL/6 (H-2b ) recipients was performed. After transplantation, mice were injected daily with TM or DX or a combination of both TM and DX (TM/DX) by intraperitoneal route until the time of graft loss. CD4+ T cell subsets and CD11c+ cells in the peripheral blood mononuclear cells and spleen were examined and quantified with flow cytometry. Serum IL-6 levels were measured by enzyme-linked immunosorbent assay on day 7. @*Results@#The mean graft survivals were 6.86 days in the untreated group, and 10.0 days in the TM/DX group (p<0.001). The TM/DX treatment affected the CD4+ T cell subsets without suppressing the total CD4+ T cell population. The CD4 + FOXP3+ /CD4+ CD44hi T cell ratio increased. Increase in cell counts and median fluorescence intensity on CD11c+ CD85k+ with TM/DX were observed. The inhibition of pro-inflammatory cytokine interleukin-6 was also observed. @*Conclusion@#These outcomes suggest the immunomodulating effect of the TM/DX combinatorial treatment. In conclusion, TM/ DX combination may be a promising immunomodulatory approach for preventing allograft rejection and improving graft survival by inducing tolerance in transplantation.

Systemic Immunomodulatory Effects of Combinatorial Treatment of Thalidomide and Dexamethasone on T Cells and Other Immune Cells

Purpose@#In organ transplantation, the need for immune modulation rather than immune suppression has been emphasized. In this study, we investigated whether combinatorial treatments of with thalidomide (TM) and dexamethasone (DX) might be new approaches to induce systemic immunomodulation on T cells and other immune cells that regulate the expression of co-inhibitory molecules. @*Materials and Methods@#Naïve splenic T cells from C57BL/6 mice were sort-purified and cultured in vitro for CD4+ T cell proliferation and regulatory T cell (Treg) conversion in the presence of TM or/and DX. Expression of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1) in proliferated and converted T cells was quantified by flow cytometry. We also quantified in vivo expression of CTLA-4 and PD-1 on splenic CD4+ T cells and other immune cells isolated from TM- or/and DX-treated mice. Mixed lymphocytes reactions (MLR) were performed to evaluate the capacity of immune cells in carrying out immune responses. @*Results@#CTLA-4 expressions in effector T cells in vivo and in Tregs in vivo/vitro significantly increased upon TM/DX combinatorial treatment. Corresponding to increased CTLA-4 expression in T cells, the expression of ligand molecules for CTLA-4 significantly increased in splenic dendritic cells in TM/DX-treated groups. In addition, MLR results demonstrated that splenocytes isolated from TM/DX-treated mice significantly suppressed the proliferation of T cells isolated from other strains. @*Conclusion@#Based on these results, we suggest that TM/DX combinatorial treatments might be efficient immunomodulatory methods for regulating T cell immunity.

The Relationship Between Response-Inhibitory Event-Related Potentials and Symptoms of Attention-Deficit/Hyperactivity Disorder in Adult Patients with Major Depressive Disorder

Objective@#Attention-deficit and poor impulse control have frequently been observed in major depressive disorder (MDD) and attention-deficit and hyperactivity disorder (ADHD). Altered event-related potential (ERP) performance, such as GoNogo tasks, has been regarded as a neurocognitive process associated with attention and behavioral inhibition. The aim of this study was to investigate the association between Nogo ERP and adult ADHD in MDD. @*Methods@#A total of 64 participants with MDD (32 comorbid with ADHD) and 32 healthy controls aged 19–45 years were recruited; they performed GoNogo paradigms during electroencephalogram measurement. Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), and the Adult ADHD Self-Report Scale (ASRS) were evaluated. Clinical measures and GoNogo ERP were compared between three groups: depression with ADHD, depression without ADHD, and healthy controls. @*Results@#MDD subjects with ADHD showed significantly decreased Nogo P3 amplitude at frontal electrode, compared with those without ADHD and healthy controls. MDD subjects with ADHD showed significantly longer Nogo N2 latency at frontal and frontocentral electrodes, compared with those without ADHD and healthy controls. In MDD subjects with ADHD, the Nogo P3 amplitude at the frontal electrode was negatively correlated with the ASRS score and inattention. The Nogo N2 latency at the frontal electrode was positively correlated with false alarm rate. @*Conclusion@#The decreased Nogo P3 amplitude in the frontal area might be a potential biological marker for inattention in depressed patients with ADHD.

Metabolic Reprogramming by the Excessive AMPK Activation Exacerbates Antigen-Specific Memory CD8⁺ T Cell Differentiation after Acute Lymphocytic Choriomeningitis Virus Infection

During virus infection, T cells must be adapted to activation and lineage differentiation states via metabolic reprogramming. Whereas effector CD8⁺ T cells preferentially use glycolysis for their rapid proliferation, memory CD8⁺ T cells utilize oxidative phosphorylation for their homeostatic maintenance. Particularly, enhanced AMP-activated protein kinase (AMPK) activity promotes the memory T cell response through different pathways. However, the level of AMPK activation required for optimal memory T cell differentiation remains unclear. A new metformin derivative, IM156, formerly known as HL156A, has been reported to ameliorate various types of fibrosis and inhibit in vitro and in vivo tumors by inducing AMPK activation more potently than metformin. Here, we evaluated the in vivo effects of IM156 on antigen-specific CD8⁺ T cells during their effector and memory differentiation after acute lymphocytic choriomeningitis virus infection. Unexpectedly, our results showed that in vivo treatment of IM156 exacerbated the memory differentiation of virus-specific CD8⁺ T cells, resulting in an increase in short-lived effector cells but decrease in memory precursor effector cells. Thus, IM156 treatment impaired the function of virus-specific memory CD8⁺ T cells, indicating that excessive AMPK activation weakens memory T cell differentiation, thereby suppressing recall immune responses. This study suggests that metabolic reprogramming of antigen-specific CD8⁺ T cells by regulating the AMPK pathway should be carefully performed and managed to improve the efficacy of T cell vaccine.

Endophthalmitis after Removal of an Intralenticular Foreign Body in Place without Symptoms for 20 Years

PURPOSE: We report a case of postoperative endophthalmitis in the cataract patient, associated with removal of an intralenticular foreign body that had remained in place without symptoms for 20 years. CASE SUMMARY: A 45-year-old male visited our outpatient clinic complaining of gradual visual loss in his right eye over the past 3 months. In slit-lamp examinations, anterior capsular opacification, nuclear sclerosis, and posterior subcapsular opacity were observed in the right eye. Twenty years before, a tiny metallic projectile had hit his right eye, but slit-lamp examination at the time of injury did not reveal any intraocular foreign body. We decided to undergo cataract surgery. During phacoemulsification, a metallic foreign body was found in the lens and safely removed; then an intraocular lens was implanted. As hypopyon was evident 3 days later, we injected intravitreal antibiotics and applied fortified antibiotic eye drops to the right eye. The anterior chamber inflammation improved and the best-corrected visual acuity recovered to 1.0. CONCLUSIONS: Surgeon should be aware of that endophthalmitis could develop after cataract surgery with removal of an intralenticular foreign body that had been in place for 20 years. But did not trigger inflammation or cause any symptoms as the cataract progressed.

Relationship between Early Postoperative Stereoacuity and Surgical Outcome in Intermittent Exotropia

PURPOSE: To identify the correlation between early postoperative stereoacuity and surgical outcome in intermittent exotropia. METHODS: The medical records of 74 patients who underwent unilateral lateral rectus recession or bilateral lateral rectus recession for intermittent exotropia with a minimum postoperative follow-up of 3 years were retrospectively reviewed. Postoperative stereoacuity was measured using the vectogram test and Titmus test at 1 month post-operative. The deviation angle was measured at near and at distance using a prism cover test. Patients were divided into two groups according to post-operative angle deviation, and stereoacuity was analyzed in both groups. RESULTS: Sixty patients showed no suppression at distance at 1 month post-operative follow-up. Of these, 55 patients (85.9%) belonged to the success group and 5 patients (50.0%) belonged to the recurrence group. The post-operative suppression test and the surgical outcome exhibited a significant association (p = 0.017). 53 patients showed normal stereoacuity 1 month after surgery. Of these, 49 patients (76.6%) belonged to the success group and 4 patients (40.0%) belonged to the recurrence group (p = 0.017). Post-operative stereoacuity and surgical outcome exhibited a significant association (p = 0.026). CONCLUSIONS: Post-operative suppression test results at distance and stereoacuity at near may be helpful in predicting surgical outcomes of patients with intermittent exotropia.

A Case of Miller Fisher Syndrome in a Pediatric Patient with Positive Anti-GQ1b IgG

PURPOSE: To report a case of Miller Fisher syndrome in a pediatric patient with gastroenteritis associated with seroconversion of Campylobacter jejuni titer during the development of neurological symptoms and positive anti-GQ1b IgG. CASE SUMMARY: An 8-year-old male patient visited our clinic with bilateral ophthalmoplegia, diplopia, and ptosis of the right upper lid. He had experienced gastroenteritis one week previous, and antibodies to Campylobacter jejuni were detected in his plasma. Ophthalmic examination revealed a corrected visual acuity of 20/20 in both eyes. Ocular motor examination revealed limitations in all positions of gaze. Neurologic examination demonstrated areflexia and ataxia. The serologic anti-GQ1b IgG test was positive. Intravenous immunoglobulin and steroid pulse therapy were started. Extraocular movement, ptosis, and ataxia gradually improved after one month of treatment. CONCLUSIONS: We confirmed a case of Miller Fisher syndrome in a pediatric patient with bilateral ophthalmoplegia, ptosis, and a positive anti-GQ1b antibody test.

A Case of Psoriasis Accompanied by Systemic Lupus Erythematosus

No abstract available.

An Unsuspected Case of Relapsed Multibacillary Leprosy

No abstract available.

Squamous Cell Carcinoma and Bowen Disease in Nail Apparatus / 대한피부과학회지

Squamous cell carcinoma of the nail apparatus is a rare phenomenon. Because of its indolent course and similar presentation to other benign conditions, correct diagnosis in the early stages is practically difficult. We here report two cases of periungual squamous cell carcinoma and squamous cell carcinoma in situ (Bowen's disease). These cases emphasize the importance of extra vigilance and high suspicion when facing intractable atypical lesions on the fingers. Repetitive biopsy with exploratory nail plate extraction should be considered to acquire appropriate specimens, which is critical for early and correct diagnosis.

Two Cases of Lentigo Maligna with Atypical Clinical Presentation / 대한피부과학회지

Lentigo maligna is a variant of melanoma in situ that appears on sun-exposed areas as a macule with variegated pigmentation and irregular borders. If untreated, it has a risk of progressing to lentigo maligna melanoma. Two patients presented with hyperpigmented macules or patches on atypical facial areas. The histological findings were consistent with lentigo maligna. An 80-year-old Korean woman presented with clustered hyperpigmented macules on the lower lip and oral mucosa, and a 45-year-old Caucasian presented with a lesion located on the external auditory meatus, with intermittent sun exposure. Herein, we report two interesting cases of lentigo maligna with atypical clinical presentations.

A Case of Mucinous Nevus Clinically Mimicking Nevus Lipomatosus Superficialis

No abstract available.

Four Cases of Onychomadesis after Hand-Foot-Mouth Disease

No abstract available.

An Ulcerative Amelanotic Melanoma on the Heel / 대한피부과학회지

No abstract available.

Difference in Psychiatric Comorbidity of Panic Disorder According to Age of Onset

OBJECTIVES: It is reported that panic disorder is frequently comorbid with other psychiatric illnesses. The aim of this study was to investigate differences of psychiatric comorbidity according to age of onset of panic disorder. METHODS: Three hundred-two patients participated in the study. All the patients were evaluated by clinical instruments for the assessment the presence of other comorbid psychiatric disorders and various clinical features; Korean version of Mini International Neuropsychiatric Interview, Self-report questionnaires(Beck Anxiety Inventory, Beck Depression Inventory, Anxiety Sensitivity Index and State-Trait Anxiety Inventory) and clinical rating scale (Hamilton Anxiety Scale, Hamilton Depression Scale and Global Assessment of Functional score). Chi-square test was used to determine the difference between early onset and late onset panic disorder. RESULTS: Forty percent of panic patients were found to have at least one comorbid psychiatric diagnosis. There were no differences among the groups divided by number of comorbidity in sex, agoraphobia comorbidity, duration of panic disorder, except onset age of panic disorder. Early onset group had more comorbidy with social phobia, agoraphobia, PTSD. We also found that Early onset panic disorder patients were more likely to experience derealization, nausea, parethesia than late onset panic disorder patients. CONCLUSION: The results of our study are in keeping with previous data from other parts of the world. Our finding suggest that earier onset of panic disorder related to more psychiatric comorbidity.

Annual Report on External Quality Assessment in Diagnostic Genetics in Korea (2005) / 임상검사와정도관리

Diagnostic genetics subcommitee of KSQACP has performed two trials each for cytogenetic studies and molecular genetic studies in 2005. Cytogenetic surveys were performed by 37 laboratories and answered correctly in most laboratories. And the first trial with whole blood specimen from the patient with cytogenetic abnormality (mosaic Turner syndrome) was successfully done, which could evaluate the whole process for cytogenetic studies from cell culture, harvest and karyotyping.. The molecular genetic test surveys included many kinds of tests like M. tuberculosis, HBV, HCV, HPV, leukemias/lymphomas, ApoE genotyping, MTHFR genotyping, BRCA1 & BRCA2, Duchenne muscular dystrophy, and Huntington disease. Molecular genetic surveys showed excellent results in most of participants. External quality assessment program for genetic analysis in 2005 was proved to be helpful in continuous education and evaluation of quality improvement.