The reliability and validity of Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version- Korean version (K-SADS-PL-K)

In order to develop a structured and objective diagnostic instrument, authors completed: (1) the translation and back translation of the Korean version of the Kiddie-Schedule for Affective Disorders and Schizophrenia - Present and Lifetime Version (K-SADS-PL) and (2) the examination of its validity and reliability of the K-SADS-PL-Korean version (K-SADS- PL) when used with Korean children. A total of 91 study subjects were recruited from child and adolescent psychiatry outpatient clinics. Clinical diagnoses were used as a gold standard for the examination of validity of K-SADS-PL-K. Consensual validity of threshold and sub-threshold diagnoses were good to excellent for attention-deficit/hyperactivity disorder (ADHD), fair for tic and oppositional defiant disorders, and poor to fair for anxiety and depressive disorders. Inter-rater and test-retest reliabilities were fair to excellent for ADHD and tic disorder. The significant correlations between the K-SADS-PL-K and Korean Child Behavior Checklist (K-CBCL) were found, which provided additional support for the concurrent validity of the K-SADS-PL-K. Sensitivities varied according to the diagnostic categories, but specificities remained high over all diagnoses, suggesting that the K-SADS-PL-K is a desirable confirmatory diagnostic tool. The results of this study suggest that the K-SADS-PL-K is an effective instrument for diagnosing major child psychiatric disorders, including ADHD, behavioral disorders and tic disorders in Korean children. Future studies will examine the validity and reliability of the K-SADS-PL-K in larger samples, including adolescents and community samples on a variety of child and adolescent psychiatric disorders.     

Fabrication and characterization of hydrophilic poly(lactic-co-glycolic acid)/poly(vinyl alcohol) blend cell scaffolds by melt-molding particulate-leaching method

Porous PLGA/PVA scaffolds were fabricated by blending poly(lactic-co-glycolic acid) (PLGA) with polyvinyl alcohol (PVA) to improve the hydrophilicity and cell compatibility of the scaffolds for tissue engineering applications. PLGA/PVA blend scaffolds with different PVA compositions up to 20wt% were fabricated by a melt-molding particulate-leaching method (non-solvent method). The prepared scaffolds were investigated by scanning electron microscopy (SEM), mercury intrusion porosimetry, the measurements of water contact angles and bi-axial tensile strengths, etc. for their surface and bulk characterizations. The scaffolds exhibited highly porous and open-cellular pore structures with almost same surface and interior porosities (pore size, 200-300 microm; porosity, about 90%). The PLGA/PVA blend scaffolds with PVA compositions more than 5% were easily wetted in cell culture medium without any prewetting treatments, which is highly desirable for tissue engineering applications. In vitro cell compatibility of the control hydrophobic PLGA and hydrophilized PLGA/PVA (5wt%) blend scaffolds was compared by the culture of human chondrocytes in the scaffolds and the following analyses by MTT assay and SEM observation. It was observed that the PLGA/PVA blend scaffold had better cell adhesion and growth than the control PLGA scaffold. For in vivo evaluation of tissue compatibility, the scaffolds were implanted into the skull defects of rabbits. The results were evaluated by histology examinations. The PLGA/PVA (5wt%) blend scaffold showed better bone ingrowth into the scaffold and new bone formation inside the scaffold than the PLGA scaffold. It seems that 5% addition of PVA to PLGA to fabricate PLGA/PVA blend scaffolds is enough for improving the hydrophilicity and cell compatibility of the scaffolds.     

Molecular and genetic characterizations of five pathogenic and two non-pathogenic monoclonal antiphospholipid antibodies

Antiphospholipid syndrome (APS) is an autoimmune disease that is characterized by thrombosis, recurrent fetal loss and thrombocytopenia. Antiphospholipid antibodies, detected by enzyme-linked immunoabsorbent assays (aCL) and/or in vitro blood clotting assays (LAC) are strongly associated with APS. Both the molecular structures used by pathogenic antiphospholipid antibodies and the genetic mechanisms leading to their production are unknown. We describe here the variable region genes of seven IgG antiphospholipid antibodies derived from two APS patients. Of these, five are pathogenic as defined in a mouse model of thrombosis and two are not. Analyses of the expressed variable region genes show no preferential V gene usage. However, similar to anti-DNA antibodies, pathogenic antiphospholipid antibodies contain an increased number of arginine residues in the third complimentarity-determining region (CDR3) of their H chains. The increased accumulation of arginine residues in the V(H) CDR3 may act to enhance antigen binding, promote disease and point to the importance of the H chain in the pathogenic potential of certain antiphospholipid antibodies.     

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.     

Systemic Administration of Immunostimulatory DNA Sequences Mediates Reversible Inhibition of Th2 Responses in a Mouse Model of Asthma

This study investigated whether immunostimulatory DNA sequences (ISS) induce a transient or sustained inhibition of Th2 responses to inhaled antigen. We sensitized mice with subcutaneous injections to develop a Th2 response to ovalbumin (ova) and then administered a dose of ISS prior to ova inhalation challenge. Mice were then rechallenged with ova by inhalation a second time at varying time points after the first ova inhalation (1 to 8 weeks later) to determine whether the ISS dose administered prior to the first ova inhalation protected against a subsequent second ova inhalation challenge. A single dose of ISS inhibited the Th2 response to the first inhalation of ova antigen, as well as 4 weeks later to the second inhalation of ova. However, ISS did not inhibit a Th2 response to the second inhalation of ova 8 weeks later. The reversible inhibition of Th2 responses at 8 weeks suggests the need for repeated ISS administration at monthly intervals.     

A proposed mechanism for the induction of cytotoxic T lymphocyte production by heat shock fusion proteins

A 65 kDa mycobacterial heat shock protein (hsp65), fused to a polypeptide that contains an octapeptide (SIYRYYGL) agonist for a particular T cell receptor (2C TCR), stimulated C57BL/6 mice as well as CD4-deficient mice to produce CD8+ cytolytic T lymphocytes (CTL) to the fusion partner's octapeptide. This and other hsp65 fusion proteins but not native hsp65 itself stimulated dendritic cells in vitro and in vivo to upregulate the levels of MHC (class I and II) and costimulatory (B7.2) molecules. The results suggest a mechanism for the general finding that hsp fusion proteins, having fusion partners of widely differing lengths and sequences, elicit CD8 CTL to peptides from the fusion partners without requiring exogenous adjuvants or the participation of CD4+ T cells.     

DNA ploidy patterns in gastric adenocarcinoma

To assess the value of DNA ploidy, flow cytometric analysis was performed on unfixed fresh materials obtained from 86 patients with gastric cancer who underwent stomach resection. We evaluated the DNA content of gastric carcinoma cells from four different sites and compared it with Ki-67 proliferating activity, and other pathologic parameters. The incidence of aneuploid and diploid was similar (48.8% vs. 51.1%). Early gastric carcinoma showed a higher rate of the diploid pattern (75%) compared to that of advanced gastric carcinoma (47.3%). DNA diploidy was noted increasingly in diffuse-type tumors according to Lauren, in signet ring cell type tumor according to WHO classification and in poorly differentiated tumors (p<0.05). Well and moderately differentiated carcinomas revealed the aneuploid pattern more frequently than poorly differentiated tumors. The aneuploidy was associated with high S phase fraction and high proliferative index. Aneuploidy was noted in the mucosa adjacent to the tumor (26%), in the close normal-looking mucosa (7%) and in the remote normal-looking mucosa (3%). This result suggest the possible role of field cancerization in the development of gastric adenocarcinoma.     

A rat model for radiation-induced proctitis

Radiation proctitis is a frequent acute complication encountered with pelvic irradiation. This study was aimed at establishing the optimal radiation dose for radiation-induced proctitis in rats. Female Wistar rats were used. The rectal specimens were examined morphologically at 5th and 10th day following 10-30 Gy irradiation in single fraction. With increasing dose, mucosal damage became worse, and there was a prominent reaction after > or =15 Gy. We selected 17.5 Gy as an optimal dose for radiation proctitis and examined specimens at day 1-14 and at week 4, 6, 8, and 12 after 17.5 Gy. The rectal mucosa revealed characteristic histological changes with time. An edema in lamina propria started as early as 1-2 days after irradiation and progressed into acute inflammation. On day 7 and 8, regeneration was observed with or without ulcer. Four weeks later, all regeneration processes have been completed with end result of either fibrosis or normal appearing mucosa. This study showed that the radiation injury of the rectum in rat develops in dose-dependent manner as it has reported in previous studies and suggested that 17.5 Gy in single fraction is the optimum dose to evaluate the protective effect of various medications for radiation proctitis in face of the clinical situation.     

Spontaneous programmed cell death of peripheral blood mononuclear cells from HIV-infected persons is decreased with interleukin-15

Interleukin 15 (IL-15) is an important regulatory cytokine in cellular immunity. In vitro replacement of IL-15 has been shown to enhance immunity in Human immunodeficiency virus type 1 (HIV-1) infected lymphocytes. We evaluated the effect of IL-15 on the survival of peripheral blood mononuclear cells of HIV patients by examining in vitro lymphocyte apoptosis, and correlated the process with Bcl-2 and Fas gene regulation. Peripheral blood mononuclear cells (PBMC) from 21 HIV-infected adults and 24 HIV-seronegative healthy individuals were isolated and cultured to determine the effect of escalating doses of IL-15 (0, 1, 10, 100, 1000 ng/mL) on apoptosis. Lymphocyte proliferation assay with (3H) TdR was measured and Bcl-2 and Fas gene regulation was observed. The results were as follows: 1) IL-15 reduced culture induced lymphocyte apoptosis in HIV patients in a dose dependent manner, and reached a plateau level at a concentration of 100 ng/ml; 2) IL-15 significantly reduced the level of apoptosis after 3 days (14%) and 5 days (15%) of culture in HIV patients, while no difference was observed in HIV (-) donors; 3) The percentage of viable cells among the total number of lymphocytes was significantly enhanced by 25% in HIV patients with IL-15; 4) Bcl-2 expression was decreased in HIV patients (53.9 +/- 12.3%) compared to HIV (-) donors (93.0 +/- 3.7%), and IL-15 increased Bcl-2 expression by 21.2 +/- 5.2% in HIV patients; 5) Fas expression was increased in HIV patients (70.2 +/- 4.6%) compared to HIV (-) donors (32.4 +/- 4.3%), and IL-15 increased Fas expression by 8.4 +/- 1.2% in HIV (-) donors. Our findings indicate that IL-15 may influence immunologic abnormalities in HIV infection, particularly its ability to prevent apoptosis of lymphocytes by suppressing the down-modulation of Bcl-2. This may provide an experimental basis for IL-15 immunotherapy.