CD5 Expression Dynamically ChangesDuring the Differentiation of Human CD8+ T Cells Predicting Clinical Response to Immunotherapy

Defining the molecular dynamics associated with T cell differentiation enhances our understanding of T cell biology and opens up new possibilities for clinical implications. In this study, we investigated the dynamics of CD5 expression in CD8+ T cell differentiation and explored its potential clinical uses. Using PBMCs from 29 healthy donors, we observed a stepwise decrease in CD5 expression as CD8+ T cells progressed through the differentiation stages. Interestingly, we found that CD5 expression was initially upregulated in response to T cell receptor stimulation, but diminished as the cells underwent proliferation, potentially explaining the differentiation-associated CD5 downregulation. Based on the proliferationdependent downregulation of CD5, we hypothesized that relative CD5 expression could serve as a marker to distinguish the heterogeneous CD8+ T cell population based on their proliferation history. In support of this, we demonstrated that effector memory CD8+ T cells with higher CD5 expression exhibited phenotypic and functional characteristics resembling less differentiated cells compared to those with lower CD5 expression. Furthermore, in the retrospective analysis of PBMCs from 30 non-small cell lung cancer patients, we found that patients with higher CD5 expression in effector memory T cells displayed CD8+ T cells with a phenotype closer to the less differentiated cells, leading to favorable clinical outcomes in response to immune checkpoint inhibitor (ICI) therapy. These findings highlight the dynamics of CD5 expression as an indicator of CD8+ T cell differentiation status, and have implications for the development of predictive biomarker for ICI therapy.

Shaping Heterogeneity of Naive CD8+ T Cell Pools

Immune diversification helps protect the host against a myriad of pathogens. CD8+ T cells are essential adaptive immune cells that inhibit the spread of pathogens by inducing apoptosis in infected host cells, ultimately ensuring complete elimination of infectious pathogens and suppressing disease development. Accordingly, numerous studies have been conducted to elucidate the mechanisms underlying CD8+ T cell activation, proliferation, and differentiation into effector and memory cells, and to identify various intrinsic and extrinsic factors regulating these processes. The current knowledge accumulated through these studies has led to a huge breakthrough in understanding the existence of heterogeneity in CD8+ T cell populations during immune response and the principles underlying this heterogeneity. As the heterogeneity in effector/memory phases has been extensively reviewed elsewhere, in the current review, we focus on CD8+ T cells in a “naïve” state, introducing recent studies dealing with the heterogeneity of naive CD8+ T cells and discussing the factors that contribute to such heterogeneity. We also discuss how this heterogeneity contributes to establishing the immense complexity of antigen-specific CD8+ T cell response.

Deletion Timing of Cic Alleles during Hematopoiesis Determines the Degree of Peripheral CD4+ T Cell Activation and Proliferation

Capicua (CIC) is a transcriptional repressor that regulates several developmental processes. CIC deficiency results in lymphoproliferative autoimmunity accompanied by expansion of CD44hiCD62Llo effector/memory and follicular Th cell populations. Deletion of Cic alleles in hematopoietic stem cells (Vav1-Cre-mediated knockout of Cic) causes more severe autoimmunity than that caused by the knockout of Cic in CD4+CD8+ double positive thymocytes (Cd4-Cre-mediated knockout of Cic). In this study, we compared splenic CD4+ T cell activation and proliferation between whole immune cell-specific Cic-null (Cicf/f;Vav1-Cre) and T cell-specific Cic-null (Cicf/f;Cd4-Cre) mice. Hyperactivation and hyperproliferation of CD4+ T cells were more apparent in Cicf/f;Vav1-Cre mice than in Cicf/f;Cd4-Cre mice. Cicf/f;Vav1-Cre CD4+ T cells more rapidly proliferated and secreted larger amounts of IL-2 upon TCR stimulation than did Cicf/f;Cd4-Cre CD4+ T cells, while the TCR stimulation-induced activation of the TCR signaling cascade and calcium flux were comparable between them. Mixed wild-type and Cicf/f;Vav1-Cre bone marrow chimeras also exhibited more apparent hyperactivation and hyperproliferation of Cic-deficient CD4+ T cells than did mixed wild-type and Cicf/f;Cd4-Cre bone marrow chimeras. Taken together, our data demonstrate that CIC deficiency at the beginning of T cell development endows peripheral CD4+ T cells with enhanced T cell activation and proliferative capability.

Dexmedetomidine Improves Locomotor Function and Alleviates Thermal Hyperalgesia Following Sciatic Nerve Crush Injury in Rats / 대한배뇨장애요실금학회지

Purpose@#The effects of dexmedetomidine on locomotor function and thermal hyperalgesia in sciatic nerve crush injury (SNCI) were investigated using rats. @*Methods@#After exposing the right sciatic nerve, the sciatic nerve was crushed for 1 minute by a surgical clip. One day after nerve injury, dexmedetomidine (5, 25, and 50 µg/kg) was directly applied to the injured sciatic nerve once a day for 14 days. Walking track analysis was used to assess locomotor function and plantar test was conducted to assess thermal pain sensitivity. Immunohistochemistry was performed to determine the expression of c-Fos in the ventrolateral periaqueductal gray (vlPAG) and paraventricular nucleus (PVN). Western blot was used to evaluate the expression level of nerve growth factor (NGF) and myelin basic protein (MBP) in the sciatic nerve. @*Results@#SNCI resulted in deterioration of locomotor function and increased thermal pain sensitivity. The level of c-Fos expression in the PVN and vlPAG was increased and the level of NGF and MBP expression in the sciatic nerve was enhanced by SNCI. Dexmedetomidine treatment improved locomotor function and upregulated expression of NGF and MBP in the sciatic nerve of SNCI. Dexmedetomidine treatment alleviated thermal hyperalgesia and downregulated expression of c-Fos in the vlPAG and PVN after SNCI. @*Conclusions@#Dexmedetomidine may be used as a potential new treatment drug for recovery of locomotion and control of pain in peripheral nerve injury.

Deletion Timing of Cic Alleles during Hematopoiesis Determines the Degree of Peripheral CD4+ T Cell Activation and Proliferation

Capicua (CIC) is a transcriptional repressor that regulates several developmental processes. CIC deficiency results in lymphoproliferative autoimmunity accompanied by expansion of CD44hiCD62Llo effector/memory and follicular Th cell populations. Deletion of Cic alleles in hematopoietic stem cells (Vav1-Cre-mediated knockout of Cic) causes more severe autoimmunity than that caused by the knockout of Cic in CD4+CD8+ double positive thymocytes (Cd4-Cre-mediated knockout of Cic). In this study, we compared splenic CD4+ T cell activation and proliferation between whole immune cell-specific Cic-null (Cicf/f;Vav1-Cre) and T cell-specific Cic-null (Cicf/f;Cd4-Cre) mice. Hyperactivation and hyperproliferation of CD4+ T cells were more apparent in Cicf/f;Vav1-Cre mice than in Cicf/f;Cd4-Cre mice. Cicf/f;Vav1-Cre CD4+ T cells more rapidly proliferated and secreted larger amounts of IL-2 upon TCR stimulation than did Cicf/f;Cd4-Cre CD4+ T cells, while the TCR stimulation-induced activation of the TCR signaling cascade and calcium flux were comparable between them. Mixed wild-type and Cicf/f;Vav1-Cre bone marrow chimeras also exhibited more apparent hyperactivation and hyperproliferation of Cic-deficient CD4+ T cells than did mixed wild-type and Cicf/f;Cd4-Cre bone marrow chimeras. Taken together, our data demonstrate that CIC deficiency at the beginning of T cell development endows peripheral CD4+ T cells with enhanced T cell activation and proliferative capability.

A Case of Mucinous Gastric Adenocarcinoma Mimicking Submucosal Tumor / 대한소화기학회지

A gastric carcinoma with the endoscopic features resembling a submucosal tumor (SMT) is rare, and reportedly accounting for 0.1% to 0.63% of all resected gastric carcinomas in Japan. A diagnosis of a SMT-like gastric carcinoma is often difficult as the tumors are almost entirely covered with normal mucosa. Furthermore mucinous gastric adenocarcinoma is uncommon histologic subtype of gastric cancer. These tumors are detected mostly in an advanced stage and rarely in an early stage. Early mucinous gastric adenocarcinoma is characterized as an elevated lesion resembling SMT due to abundant mucin pools in the submucosa. Here we report one case of SMT-like mucinous gastric adenocarcinoma, diagnosed by the usual endoscopic biopsy and treated with surgery.

A Case of Pseudohypoparathyroidism with Graves' Disease

Pseudohypoparathyroidism is a rare disease that is characterized by target cell resistance to the effects of parathyroid hormone and this disease is classified into various types depending on the phenotypic and biochemical findings. The patients with pseudohypoparathyroidism present with the clinical and biochemical features of hypoparathyroidism, but they have an increased serum level of parathyroid hormone. We experienced a case of pseudohypoparathyroidism in a 24 years old woman who had Graves' disease at that time. She had hypocalcemia, hyperphosphatemia, an elevated serum parathyroid hormone level and a normal urinary basal cyclic AMP(adenosine monophosphate) level. She also had a normal phenotypic appearance. Therefore, she was classified as suffering with pseudohypoparathyroidism type II. The clinical and laboratory abnormalities were improved by calcium supplementation in addition to vitamin D. To the best of our knowledge, this is the first case of pseudohypoparathyroidism combined with Graves' disease in Korea.

A Case of Colonic Intussusception Occurring after Colonoscopic Polypectomy / 대한소화기내시경학회지

Intestinal intussusception in adults is a rare disease. Most of the cases of adult intussusception are secondary to a definable lesion, and so surgical treatment generally needed. Intussusception that occurs after colonoscopic polypectomy is apparently a rare malady. A 77-year old man undergoing colonoscopic polypectomy was diagnosed as having colonic intussusception at the hepatic flexure. As there was no clinical improvement with conservative treatment, he underwent segmental resection of the ascending and transverse colon. Pathologic examination revealed that the colonoscopic polypectomy site was a leading point of the intussusception.

Clinical Evaluation of Anterolateral Surgical Decompression and Instrumentation in Thoracolumbar Bursting Fracture

The authors report clinical results of fifty-two traumatic thoracolumbar bburstfractures treated by internal fixation with Kaneda device after anterior decompression during recent six years. The burst fractures occurred most frequently at the age of twenties and thirties. The main causes of injury were vehicle accident and fall.In all cases, spinal decompression, internal instrumet fixation and bone fusion(rib, iliac bone) were performed. No patient showed neurological deterioration after surgery and almost all patients improved post operatively by on grade of Frankel's(classification). Thirty-three patients(85%) with Denis type I and II showed the correction of the fracture deformities with good bony fusion and 9 of 13 patients(70%) with Denis type IV showed bony fusion in serial follow-up. It if thus concluded that anterolateral internal fixation combined with bony fusion provide good mechanical stability and decompression of protruding ventral bone fragments above conus medullaris level.

Prognostic Factors in Patients with Severe Head Injury

OBJECTIVE: To elucidate the problems that must be dealt with in the prognosis of patients with severe head injury and to find out the prognosis factors related to severe head injury. METHODS: A clinical analysis was carried out retrospectively with 292cases of severe head- injured patients (Glasgow coma scale score 3-8) admitted to the our department for 10 years from January 1987 to December 1996. RESULTS: Patients who were classified as having severe brain injury belonged to 13.1% of all craniocerebral trauma cases among which sixty-three cases had diffuse brain injury. The causes of head injuries were motor vehicle accident, falls from heights, bicycle and other causes in order of frequency. Pediatric patients showed better outcome(51.4%), compared with only 28.1% of all adult cases(p<0.0001). The patients with high initial GCS score(6-8, 47.9%) had significantly better outcome than the patients with low initial GCS socre(3-5, 16.9%) (p<0.0001). Fifty point three percents of patients with good motor response had good outcome, whereas only 15.8 percent in patients with poor motor response. The cases with diffuse head injury without basal cistern compression had significantly higher percentage of good outcome(74.0%) than those with basal cistern compression(16.9%, p<0.0001). The cases with normal pupillary reaction had significantly higher percentage of good outcome(50.3%) than those with bilateral oculomotor nerve palsy(18.4%, p<0.0001). The patients with skull fracture had good outcome(48.1%), compare to 20.3% of patients without skull fracture(p<0.0017). CONCLUSION: The good prognostic factors in this study were young age, initial high Glasgow coma scale, good motor response, diffuse brain injury type I, II, bilaterally intact light reflex, with skull fracture. Individual prognostic factor is significant to indicate the patient's outcome and may be utilized for assessing the relative efficacy of the alternative treatment and prognosis.

Result of MAST in bronchial asthma in Pusan area / 알레르기

OBJECTIVES: Allergen is closely related with local features and cultural environment and a new approach method regarding causes triggering aggravation is especially required due to complex and variety of ordinary residence and pollution of living environment recently. We, therefore, performed this study to inspire the necessity of identification of causative afeuts in aothmatic patients in pusan area. METHODS: We measured serum specific IgE antibody by means of chemiluminescent analyzer employing MAST, classified the level from class 0 to 4 and interpreted the result in order to identify allergen on total 262 patients consisted of inpatients and outpatients who had been presumed as extrinisic asthma and treated in this hospital during 2 and a half years from June of 1994 to December of 1996. RESULTS: 1. With regard to sex and age distribution, the rate of men versus women was 1 : 1.3, while in the distribution by age, the twenties and the thirties were the most as 29% and 26% respectively. 2. The result of interpretation of the test showed positive in 75%, 78% of which showed positive reaction compounded of 2 kinds or more. 3. If we take a look at the distribution of total IgE class in the positive area, we can find that ; Class III and class II showed the highest frequency as 47% and 37% respectively. 4. If we take a look at the distribution by age and allergen, the twenties(32%) and the thirties(30%) showed the highest frequency, the fifties, the forties and the teens showed middle frequency as 10~13% and the sixties and the seventies showed the lowest frequency as about 1%. The causative allergen appeared in the order of pollen(40%), dust(20%), food(18%), fungus(13%) and epidermis(8%). 5. The distribution of allergen by season generally showed high rate of positive appearance in spring and fall as pollen appeared in spring(44%) and fall(27%), dust appeared in fall(32%) and summer(23%), food appeared in spring(34%) and fall(29%), fungus appeared in fall(30%) and spring(28%) and epidermis appeared in spring(30%) and fall(28%). 6. With regard to the allergen: (1) In pollen allergens, trees showed higher positive frequency than weeds and trees were in the order of birch(14%), alder(13%) and hazelnut mix(12%) and weeds showed similar positive values. (2) In dust allergens, mite(D. pteronyssinus and D. farinae) showed high positive rate as 39% each. (3) In epidermal allergens, it also showed relatively even positive value among which cat's halr-dandruff was the highest as 40%. (4) In food allergens, shrimp showed the highest as 22% and others were similar as evenly positive values. (5) In fungus allergens, Candida and Stemphylium showed the highest value as 19% each. CONCLUSION: The analysis of allergen by means of MAST could be used as a valuable guide post for identifing cousative antigens for active treatment of extrinsic asthma.

Comparative Analysis of Results by Operative Approaches for Thoracolumbar or Lumbar Fractures

A retrospective study of 100 cases with thoracolumbar fractures was performed to compare the results from different surgical approaches and to provide a guide line for surgical treatment. Fifty-three patients were operated through anterior approach and forty-two patients were through posterior approach. All patients were evaluated according to changes in the following parameters: kyphotic angles, compression heights, degrees of canal compromise, neurologic deficits, pain levels, delayed kyphosis and complications. There were no significant differences in kyphotic angles, compression heights, degrees of canal compromise, neurologic deficits, and pain levels between two approaches. Delayed kyphosis occurred in one(2.4%) of 42 cases treated by posterior approach and six(11.3%) of 53 cases treated by anterior approach. Dural lacerations were noted in fourteen(43.8%) of 32 cases associated with lamina fractures and were repaired in all of nine cases approached posteriorly but none of five cases approached anteriorly. In conclusion, posterior approach is simple, less extensive, is associated with lower incidence of delayed kyphosis and better dural repair than the anterior approach. Posterior approach could be, therefore, considered initially for those cases where surgery is indicated for thoracolumbar or lumbar fractures.

Radioisotope Cisternographic Analysis of Post-operative Subdural Hygroma after Aneurysmal Surgery

Authors analyzed the post-operative subdural hygroma using radioisotope(RI) cisternography in 30 cases following aneurysmal surgery with pterional approach from October, 1995 to March, 1996. Age, CSF flow from basal cisterns, and etent of opening of Liliequist's membrane during operation were significantly related to the development of post-operative subdural hygroma. Computed tomography(CT) scan of brain and RI cisternography were performed in all patients at three weeks following operations. RI diffusion time from the interpeduncular cistern to the cerebral convexity of ipsilateral side with surgically opened Liliequist's membrane was compared with contralateral nonoperated normal side. Diffusion time of ipsilateral side(mean 5.2+/-8.4hr) was faster than that of contralateral one. Age, cerebrospinal fluid(CSF) from basal cistern, and extent of opening of Liliequist's membrane during operation were significantly related to development of post-operative subdural hygroma. Development of subdural hygroma after pterional approach for aneurysmal operations in our series is believed to be caused by stagnation of CSF in the convexity until its absorption into the arachnoid villi. Increased CSF flow from the infratentorial space to the supratentorial space through extensively opened Liliequist's membrane is considered to contribute development of its formation.

Popliteal pterygium syndrome: A Case Report / 대한정형외과학회잡지

Popliteal pterygium syndrome is rare, with 60 cases described in the literature. The syndrome includes a popliteal web extending from the ischium to the heel and other abnormalities including toenail dysplasia, deformities of the foot and toes, and oral cavity abnormalities. The main orthopedic problem is a flextion contracture of the knee and an equinus foot. We experienced a six-month-old girl with popliteal pterygium, in whom resection of abnormal fibrotic muscle belly, Achilles tendon legnthening, and Z-plastic lengthening of the skin resulted in partial correction of flexion deformity of the knee and equines contracture of the foot at one year follow-up.

A Case of Percutaneous Intracavitary Amphotericin B Injection for the Treatment of Hemoptysis due to Pulmonary Aspergilloma / 결핵

Pulmonary Aspergillomas usually arise from proliferation of Aspergillus in preexisting parenchymal cavities.202 college students (99 men, 103 women) aged 18% 26 years. Fasting blood samples were. The most common symptom in this disorder is hemoptysis, which may be minimal in amount or it may be massive & life threatening. The optimum therapy for pulmonary aspergilloma is controversial. The major options available include surgical resection of the lesion, a number of medical therapies, or simple observation of the patient for a time. Surgery is the most effective treatment but it is limited to some patient because most patients haute underlying pulmonary disease. Thus the various form of medical therapy was available with successful result. The authors present a case of percutaneous intracavitary amphoterician B injection for the treatment of pulmonary aspergilloma & its successful effect for the repetitive hemoptysis.

Co-culture of mouse 2 - cell embryos / 대한산부인과학회잡지

No abstract available.

A case of pseudotumor of the maxillary sinus / 대한이비인후과학회지

No abstract available.