Multifunctional initiation of lactide polymerization by stannous octoate/pentaerythritol

L -Lactide was polymerized with stannous 2-ethylhexanoate (stannous octoate) in the presence of pentaerythritol to investigate multifunctional initiation. The prepared oligomers contain starshaped 4-arm molecules when the mole ratio of [lactide]/[pentaerythritol] is above 32. The molecular weight of oligomers coincides with the [lactide]/[pentaerythritol] ratio, indicating that pentaerythritol in conjugation with stannous octoate is an initiator for the “living” polymerization of L-lactide.     

Immobilized IgG immune complex induces secretion of tumor necrosis factor-alpha by porcine alveolar macrophages.

Tumor necrosis factor-alpha (TNF-alpha) is an important inflammatory mediator produced by activated monocytes and macrophages. We have previously shown that porcine alveolar macrophages (PAM) mediate bystander cytotoxicity through hydrogen peroxide production following activation with immobilized IgG immune complex (IIC) (J. Immunol. 1983; 131:1438-1442). In this report, we have investigated whether IIC induces TNF-alpha secretion by PAM. Isolated PAM from Minnesota miniature swine were cultured for 18 h with and without recombinant human interferon-gamma (rhIFN-gamma). Cultured PAM were then incubated with IIC or IgG immune complex in suspension (SIC). The supernatants generated were assessed for cytotoxic activity using a TNF-alpha-sensitive WEHI-164 cell line. Anti-recombinant human TNF-alpha (rhTNF-alpha) monoclonal antibody neutralized the observed cytotoxicity of IIC-activated PAM supernatant completely, indicating that this cytotoxicity is mediated by TNF-alpha. IIC induced TNF-alpha secretion by PAM after 3 h of incubation, reaching a plateau from 6 to 12 h and decreasing thereafter. TNF-alpha release was enhanced by pretreatment of PAM with rhIFN-gamma. SIC did not induce significant levels of TNF-alpha secretion by PAM; however, SIC with cytochalasin B-pretreated PAM induced equivalent levels of TNF-alpha secretion as IIC-activated PAM. We conclude that IIC or SIC with cytochalasin B pretreatment, both of which prevent internalization of IgG immune complex-bound Fc receptor (FcR), provide a signal for PAM to generate TNF-alpha through FcR modulation. This suggests that in vivo, deposited (immobilized) IgG immune complexes-bound FcR may be a stimulus for activation of PAM to generate TNF-alpha rather than circulating (mobilized) immune complexes, which may contribute to the pathogenesis of diffuse interstitial fibrosis of the lung, especially in idiopathic pulmonary fibrosis.     

An acute pleuropneumonia in a pig caused by Chromobacterium violaceum

A 2.5-month-old, 30 kg Duroc pig died 10 days after showing clinical signs of dyspnoea and diarrhoea. Acute necrotizing and fibrinous pleuropneumonia with locally extensive lesions was found. Chromobacterium violaceum was isolated from pneumonic lung tissues and intratracheal inoculation of a pure culture into two SPF pigs reproduced lesions similar to those found in the natural infection.     

Cytoplasmic crystalline inclusions in a anaplastic oligoastrocytoma

A 41-year-old male presented with an ill-demarcated mass involving the left fronto-temporal lobe and the basal ganglia. Light microscopically the tumor was diagnosed as an anaplastic oligoastrocytoma. Electron microscopy revealed several cytoplasmic crystalline inclusions in tumor cells of oligodendroglial lineage. No crystalline inclusions were membrane bound. The morphologic features with unique ultrastructural findings are presented.     

Adjuvant-dependent modulation of Th1 and Th2 responses to immunization with beta-amyloid

The role of adjuvant on the T(h)1 and T(h)2 immune responses to Abeta-immunotherapy (Abeta(42 )peptide) was examined in wild-type mice. Fine epitope analysis with overlapping oligomers of the Abeta(42) sequence identified the 1-15 region as a dominant B cell epitope. The 6-20 peptide was recognized only weakly by antisera from mice administrated with Abeta(42) peptide formulated in complete Freund's adjuvant (CFA), alum or TiterMax Gold (TMG). However, mice immunized with Abeta(42) mixed with QS21 induced a significant antibody response to the 6-20 peptide. The only T cell epitope found was within the 6-28 sequence of Abeta(42). QS21 and CFA induced the strongest humoral response to Abeta, alum was intermediate, and TMG the weakest adjuvant. Analysis of antibody isotypes specific for Abeta indicates that alum induces primarily T(h)2-type immune response, whereas TMG, CFA and QS21 shift the immune responses toward a T(h)1 phenotype. Stimulation of splenocytes from Abeta-immunized mice with Abeta(40) peptide induced strikingly different cytokine expression profiles. QS21 and CFA induced significant IFN-gamma, IL-4 and tumor necrosis factor-alpha expression, whereas alum induced primarily IL-4 production. As T(h)1-type immune responses have been implicated in many autoimmune disorders, whereas T(h)2-type responses have been shown to inhibit autoimmune disease, the choice of adjuvant may be critical for the design of a safe and effective immunotherapy for Alzheimer's disease.     

Different corticostriatal projections from two parts of the cortical masticatory area in the rabbit

The cortical masticatory area (CMA) elicits rhythmic jaw movements in response to repetitive stimulation and is involved in the control of mastication. Based on jaw movement patterns, the CMA is divided into two parts. One is the part of the CMA in which a T-pattern similar to jaw movements during food transport in natural mastication is evoked by electrical stimulation. The other is more dorsomedially located, and during chewing a C-pattern similar to jaw movements can be induced. However, it is still not known which region of the putamen receives projections from the CMA and whether projections originate from both parts of the CMA. In this study, electrophysiological and histological experiments were undertaken in rabbits to investigate projections from the CMA to the putamen. Both experiments showed that the ventral region of the putamen received projections from the CMA. The density of the projections from the CMA area inducing the T-pattern seemed to be higher than that from the area inducing the C-pattern. Furthermore, the peak latency of the evoked potentials from stimulation of the CMA area inducing the T-pattern was shorter than that from stimulation of the area inducing the C-pattern. The data obtained from the present study indicate the functional role of the ventral region of the putamen in the regulation of mastication, and further suggest that the corticostriatal pathway is involved in the transition between behavioral jaw movement patterns.     

Description and characterization of two new HLA alleles, B*4051 and DRB1*1364, identified by sequence-based typing

Human leukocyte antigen (HLA)-B and HLA-DRB1 typing in two female individuals revealed reaction patterns that did not correspond to any known HLA-B specificity and appeared to identify a very rare HLA-DRB1 allele, respectively. Sequence-based analysis of these samples revealed two new HLA alleles, one similar to B*4023 and the other to DRB1*1308. The new HLA-B allele, which was assigned the name HLA-B*4051, could have been generated by a double crossing over recombination between B*4001 and B*1401 or 1402, whereas DRB1*1364, the new DRB1 allele, could have been generated either by a double crossing over recombination between DRB1*1308 and DRB1*1201, 1202, or 1203 or by two independent crossing over events between DRB1*1401, DRB1*1201, 1202, or 1203 and DRB1*1301.     

Veno-occlusive disease (VOD) of the liver in Korean patients following allogeneic bone marrow transplantation (BMT): efficacy of recombinant human tissue plasminogen activator (rt-PA) treatment.

Veno-occlusive disease (VOD) of the liver is a clinical syndrome characterized by hyperbilirubinemia, painful hepatomegaly, and fluid retention. In the bone marrow transplantation (BMT) setting, VOD is caused by dose-intensive chemotherapy and/or radiotherapy used to prepare patients for transplant. VOD occurs in up to 50% of the patients who undergo BMT and is usually associated with a high mortality rate. Until recently, there was no proven effective medical therapy for this condition once it was clinically apparent. We report here on the frequency and treatment result of VOD with rt-PA in our allogeneic BMT patients. Eight patients (median age 28.5 years) underwent allogeneic BMT from December, 1993 to June, 1995 in Asan Medical Center. Six leukemia patients were prepared for BMT with busulfan and cyclophosphmide, while two aplastic anemia patients received cyclophosphamide and antithymocyte globulin. VOD was defined as having two of the following features before day 20 posttransplant: jaundice (bilirubin > or = 2 mg/dL), tender hepatomegaly and/or right upper quadrant pain, ascites and/or unexplained weight gain (> 2% from baseline). All patients who were diagnosed with VOD received rt-PA (10-20 mg/day) and heparin (10,000 U/day). Three (37.5%) of the eight patients developed VOD that occurred between 6 and 10 days posttransplant. All three patients developed jaundice, weight gain, and tender hepatomegaly. Ascites and renal insufficiency occurred in two patients and pleural effusion in one patient. rt-PA and heparin were begun 6 to 26 days posttransplant and rt-PA was administered for 7 to 14 days. All three patients responded to the therapy; bilirubin levels began to decrease at 4 to 13 days from the start of therapy. They are all alive at day 111, 316, and 548 days posttransplant. None of the patients had significant hemorrhagic complications after rt-PA treatment. Prolonged administration of rt-PA was feasible without bleeding episode and it seems that rt-PA may alter the natural course of VOD.     

The tumor necrosis factor beta * 1 allele is linked significantly to HLA-DR8 in Koreans with atrophic autoimmune thyroiditis who are positive for thyrotropin receptor blocking antibody.

The localization and functional characteristics of tumor necrosis factor(TNF) beta gene raise the possibility that it may be involved in the susceptibility to autoimmune thyroid diseases. To investigate whether a TNF beta gene polymorphism is associated with autoimmune thyroiditis, we analyzed the TNF beta gene polymorphism with the restriction enzyme NcoI in 48 Korean patients with atrophic autoimmune thyroiditis [23 were found to be thyrotropin binding inhibitor immunoglobulin(TBII) positive, 25 TBII negative], 52 goitrous autoimmune thyroiditis, and 129 healthy controls. Two TNF beta alleles were identified from the restriction fragment length polymorphism studies of amplified genomic DNA. In atrophic autoimmune thyroiditis patients positive for TBII, 7 of 23 patients were homozygous for the TNF beta * 1 allele, 3 were homozygous for the TNF beta * 2 allele, and 13 were TNF beta * 1/2 heterozygous compared to controls(P = 0.20). Also, there were no associations between the TNF beta gene polymorphism and either TBII-negative atrophic autoimmune thyroiditis or goitrous autoimmune thyroiditis. Of the HLA-class II antigens, the frequency of HLA-DR8 was significantly greater among the 23 Korean patients with TBII-positive atrophic autoimmune thyroiditis compared to control subjects (Pc = 0.003). When the HLA-DR8 positive patients with TBII-positive atrophic autoimmune thyroiditis and controls were analyzed separately, the DR8 positive patients with TBII-positive atrophic autoimmune thyroiditis had more homozygotes for the TNF beta * 1 allele(6/12, 50.0%) and no homozygotes for the TNF beta * 2 allele, as compared to the DR8 negative patients with TBII-positive atrophic autoimmune thyroiditis and DR8 positive controls(P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Procoagulant activity and thrombelastography in korean hemorrhagic fever

Twenty male patients with Korean hemorrhagic fever were evaluated with thrombelastography (TEG) to assess the changes in coagulation system, and the results were compared with those of conventional coagulation tests. Procoagulant activity in the plasma was determined by comparing the reaction time "r" of the normal plasma and that of the mixture of equal parts of the normal plasma and the patient's plasma. The TEG was found to be a useful measure of the changes in the coagulation profile, and provided instant accurate assessment of the patient's hemostatic function. Presence of the procoagulant activity was demonstrated in the plasma of the patients and indicated occurrence of active intravascular coagulation during the early stage of the disease.