Analysis of children with type 1 diabetes in Korea: high prevalence of specific anti-islet autoantibodies, immunogenetic similarities to Western populations with "unique" haplotypes, and lack of discrimination by aspartic acid at position 57 of DQB

This study analyzed the expression of anti-islet autoantibodies and HLA-DR and -DQ genotypes in Korean children with type 1 diabetes mellitus (T1DM). The positivity of the anti-ICA512, anti-GAD65, and anti-insulin autoantibodies in the newly onset T1DM patients (n = 15) was 66.7%, 86.7%, and 46.7%, respectively, and all of them had one or more of the autoantibodies. HLA analysis showed higher frequencies of HLA-DRB1*0301, *0405, *09012 and -DQB1*0201, *0401, *03032 alleles in T1DM patients compared to controls (P(c) < 0.05). Because HLA-DQB1*0401, *03032 alleles carry aspartic acid at position 57 of DQB, susceptibility to T1DM in Korean children was not related to the presence of aspartic acid at position 57 of DQB1 locus. We suggest this unique HLA-DR, -DQ allele distribution might be an important factor for the low incidence of T1DM in Korea, and the combined anti-islet autoantibody assays could be valuable screening markers for the early detection of T1DM in Korea.     

Altered GABAB receptor immunoreactivity in the gerbil hippocampus induced by baclofen and phaclofen, not seizure activity

The present study was performed to determine whether the effects induced by GABA(B) receptor-acting drugs would be related with the alteration in GABA(B) receptor expression in the hippocampus using Mongolian gerbil, a genetic epilepsy model. The distribution patterns of both GABA(B) receptor 1A/B and GABA(B)receptor 2 immunoreactivities were similarly detected in the hippocampi of normal and seizure-prone gerbils. Following baclofen (GABA(B) receptor agonist) or phaclofen (GABA(B) receptor antagonist) treatment, GABA(B) receptor immunoreactivities were decreased or increased by dose-dependent manners, respectively. Vigabatrin (GABA transaminase inhibitor) or 3-mercaptopropionic acid (GAD inhibitor) treatment did not affect GABA(B) receptor expressions. These findings suggest that GABA(B) receptor expression in the gerbil hippocampus may be altered by baclofen or phaclofen treatment.     

Applications of the pulsatile flow versatile ECLS: in vivo studies

INTRODUCTION: T-PLS (Twin-Pulse Life Support) is the first commercial pulsatile ECLS (Extra Corporeal Life Support) device (1). The dual sac structure of T-PLS can effectively reduce high membrane oxygenator inlet pressure and hemolysis. To verify both the use of T-PLS for ECLS and the advantages of T-PLS, we tested various models. METHOD AND RESULTS: In the partial CPB (cardio pulmonary bypass) model (swine), T-PLS (N = 6), and Biopump (N = 2), a single pulsatile pump (N = 2), were compared. In the case of single pulsatile flow, during pump systole, pressure increased to 700 - 800 mmHg at the inlet port of the membrane oxygenator. fHb, a hemolysis measurement value, was about 80 mg/dL at 3 hours. On the contrary, because of T-PLS's dual sac system, the pressure of T-PLS had a maximum value of about 250 mmHg and fHb was similar to that of the commercial centrifugal pumps. In the total CPB model (bovine, N = 6), the heart was stopped via cardioplegia (Kcl). T-PLS flow was maintained at 3.0-4.5 L/min. T-PLS functioned like a natural heart, having a pulse pressure of 26-43 mmHg and a pulse rate of 40-60 bpm (beats per minute). In the emergency case model (canine, N = 6), T-PLS was started 10 minutes after cardiac arrest from electronic shock. In spite of cardiac arrest for a period of 40 minutes, the heart was recovered after defibrillation. In the ARDS (Acute Respiratory Distress Syndrome) model (canine, N = 6), minimal ventilator parameters were set: tidal volume 130 ml, respiration rate = bpm, FiO2 = 10%. Three hours after starting T-PLS, PO2 of the carotid artery blood (after 2 hours: 195 +/- 89.4; after 3 hours: 258 +/- 99.3 mmHg) was above half the value of the femoral artery but was within normal range. CONCLUSION: It is suggested that a portable pulsatile ECLS like T-PLS may be used as a CPB device and as an alternative CPR (cardiopulmonary resuscitation) device in the case of cardiac arrest. Due to the pulsatile flow, oxygenated blood is delivered to the patient without overloading the ARDS patients heart.     

Prognostic factors of the long-term survival after transjugular intrahepatic portosystemic shunt in the treatment of gastric and esophageal variceal bleeding

Transjugular intrahepatic portosystemic shunt (TIPSS) is a promising method of treatment for gastric or esophageal variceal bleeding. This study was performed to determine the prognostic factors contributing to the survival of patients after TIPSS for gastric or esophageal variceal bleeding. One hundred and fifty-five patients who underwent TIPSS between September 1991 and March 2001 were followed up by clinical examination, upper gastrointestinal endoscopy, and Duplex sonography. The mean portohepatic pressure gradient prior to TIPSS was 20.5+/-9.93 mmHg and dropped to 10.7+/-6.62 mmHg after TIPSS (p<0.001). The cumulative survival rate was 75.1% at 6 months, 66.6% at 1 yr, 58.4% at 2 yr, and 38.1% at 5 yr. Survival after TIPSS was inversely related to the Child-Pugh classification (p<0.05). The rebleeding rate was 18.3% at 6 months, 21.0% at 1 yr, 32.8% at 2 yr, and 53.1% at 5 yr. The causes of deaths were hepatic failure (53.5%), recurrent variceal bleeding (11.6%), pneumonia (4.6%), sepsis (3.5%), hepatic encephalopathy (2.3%), and unknown (17.4%). Multivariate analysis (Cox proportional hazard model) revealed that the Child-Pugh classification and age were statistically significant independent prognostic factors. In conclusion, TIPSS is an effective method of treatment for variceal bleeding in cases where other treatment modalities including endoscopic therapy are unsuccessful and the most important prognostic factors are preprocedural hepatic reserve (Child-Pugh class) and age.     

Debate on annual influenza vaccination in healthcare workers for the same subtype under the vaccine shortage.

BACKGROUND: Influenza vaccination is the primary method for preventing influenza and its severe complications. Healthcare workers (HCWs) are one of the priority groups for the influenza vaccination. OBJECTIVES: To determine whether healthy HCWs, who were vaccinated with the same subtype for the two previous years, could be given less priority for influenza immunization under the vaccine shortage. STUDY DESIGN: We measured hemagglutination-inhibition antibody titers from sequential serum samples in 50 pre-immune subjects and 50 age-matched vaccine-naive subjects: immediately prior to the administration of the vaccine, 4-6 weeks, and 6 months after the vaccination. RESULTS: Prevaccination titers were maintained above protective level and high protection rates were observed for all three strains in pre-immune subjects: A/H1N1, A/H3N2, and B strains. As for the sequential changes, the protection rates for all three strains still remained above 70% until 6 months following the vaccination. CONCLUSION: Skipping influenza vaccination for a year could be considered in healthy pre-immune HCWs under the epidemic of the same subtype as two previous years.     

PD-1-Expressing SARS-CoV-2-Specific CD8+ T Cells Are Not Exhausted,but Functional in Patients with COVID-19

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Myelomatous effusion with poor response to chemotherapy

While pleural effusion in multiple myeloma is relatively infrequent, myelomatous pleural effusion is extremely rare. We experienced a 61-year-old woman with IgD-lambda multiple myeloma and pleural effusion. The diagnosis was made originally by pleural biopsy, pleural fluid cytology and immunoelectropheresis of pleural fluid. Transient improvement of the pleural effusion was observed after administration of combination chemotherapy of vincristine, melphalan, cyclophosphamide, prednisone (VMCP)/vincristine, cyclophosphamide, adriamycin, prednisone (VCAP). Two months later, myelomatous pleural effusion recurred and no response to salvage therapy was observed. We reviewed the clinical feature of this case and literature concerning myelomatous pleural effusion.     

CM1 ligation initiates apoptosis in a caspase 8-dependent manner in Ramos cells and in a mitochondria-controlled manner in Raji cells

Burkitt lymphoma (BL) is a tumor with the characteristics of germinal center B cells. We previously reported that the CM1 (centrocyte/-blast marker 1) molecule is expressed only in germinal center B cells, specifically, in a subpopulation of centroblasts and centrocytes. In the present study, we investigated the apoptosis induced by anti-CM1 in the Ramos and Raji human BL cell lines. The Ramos is protected from apoptosis by the crosslinking of sIgM and the calcium ionophore by the ligation of CD40 with anti-CD40 monoclonal antibodies (mAb) or soluble CD40 ligand (sCD40L). In this investigation on the effect of CM1 on apoptosis in BL cell lines, we found that cellular signaling by CM1 induces apoptosis and decreases cell viability, in BL cell lines cultured for 24 hours with protein-G agarose beads conjugated anti-CM1 mAb. Stimulation by CD40 ligated with sCD40L protected Raji cells from CM1-induced apoptosis, but did not protect Ramos cells. Furthermore, after anti-CM1 mAb stimulation, CD95 expression was upregulated and CD40 expression was unaltered or slightly decreased in Ramos cells, whereas CD95 was downregulated and CD40 was slightly upregulated in Raji cells. The engagement of CD40 by sCD40L enhanced CD95 expression, but the level of CM1 expression was unchanged in Ramos. However, sCD40L downregulated both CD95 and CM1 expression in Raji. In addition, the caspase-8 specific inhibitor blocked CM1-induced apoptosis in Ramos cells, but not in Raji cells. Increased mitochondrial membrane permeabilization was observed only in Raji cells. Moreover, the effector caspase inhibitor, z-DEVD, blocked CM1-mediated apoptosis in both cell lines. We found that CM1-induced apoptosis is achieved via different initiation pathways, which are cell-type dependent.     

Alterations in extracellular matrix components in transplant glomerulopathy

The distribution pattern of extracellular matrix (ECM) components in transplant glomerulopathy was studied in relation to light microscopic features, actin expression of mesangial cells, and intraglomerular inflammatory cells. Nine cases of mild (group I) and nine cases of severe (group II) transplant glomerulopathy were stained with antisera against fibronectin (FN), tenascin (TN), collagen types III and IV, smooth muscle actin, CD45RO, CD68, and Ki-67 antigen. The composition of ECM was similar in the two groups. The expanded mesangium was diffusely stained by type-IV collagen, FN and TN, and focally and weakly stained by type-III collagen and smooth muscle actin. Type-IV collagen was linearly stained along the capillary walls, imparting a double-contour feature, whereas FN and TN showed granular staining along the capillary walls. CD68 positive cells were increased in severe transplant glomerulopathy, but this increase was not related to ECM deposition. These findings suggest that increased glomerular deposition of normal and abnormal ECM components participate in the evolution of transplant glomerulopathy. Received: 5 October 1999 / Accepted: 17 January 2000