Nasal-type extranodal natural killer (NK)/T-cell lymphoma (ENKL) is a highly invasive cancer with a poor prognosis. More effective and safer treatment regimens for ENKL are needed. Pegaspargase (PEG-Asp) has a similar mechanism of action to L-asparaginase (L-Asp), but presents lower antigenicity. The aim of the present research was to evaluate the safety profile and the latent efficacy of a PEG-Asp-based treatment regimen in patients with ENKL. Data collected from 20 patients with histologically confirmed ENKL, admitted to the Third Affiliated Hospital of Sun Yat-Sen University from January 2009 to August 2013, were included in the study. All patients received $2500IU/m^2$/IM PEG-Asp on day 1 of every 21-day treatment cycle. Patients received combination chemotherapy with CHOP (n=5), EPOCH (n=7), GEMOX (n=7) or CHOP with bleomycin (n=1). After 2-5 treatment cycles (median, 4 cycles) of PEG-Asp-based chemotherapy, five patients (25%) showed a complete response (CR), and the overall response rate (ORR) was 60%. Grade 3/4 neutropenia occurred in fourteen patients (70%). Grade 3 alanine aminotransferase (ALT) elevation was observed in two. Grade 1-2 non-hematological toxicity consisted of activated partial thromboplastin time (APTT) elongation (n=9), hypofibrinogenemia (n=6), hypoproteinemia (n=17), hyperglycemia (n=3), and nausea (n=6). No allergic reactions were detected. No treatment related death was reported. Our results suggested that PEG-Asp-based chemotherapy presented an acceptable tolerance and a potential short-term outcome in patients with nasal-type ENKL.
Recently three proteins, playing central roles in the bidirectional transport of urate in renal proximal tubules, were identified: two members of the organic anion transporter (OAT) family, OAT1 and OAT3, and a protein that designated renal urate-anion exchanger (URAT1). Antibodies against these transporters are very important for investigating their expressions and functions. With the cytokine gene as a molecular adjuvant, genetic immunization-based antibody production offers several advantages including high specificity and high recognition to the native protein compared with current methods. We fused high antigenicity fragments of the three transporters to the plasmids pBQAP-TT containing T-cell epitopes and flanking regions from tetanus toxin, respectively. Gene gun immunization with these recombinant plasmids and two other adjuvant plasmids, which express granulocyte/macrophage colony-stimulating factor and FMS-like tyrosine kinase 3 ligand, induced high level immunoglobulin G antibodies, respectively. The native corresponding proteins of URAT1, OAT1 and OAT3, in human kidney can be recognized by their specific antibodies, respectively, with Western blot analysis and immunohistochemistry. Besides, URAT1 expression in Xenopus oocytes can also be recognized by its corresponding antibody with immuno-fluorescence. The successful production of the antibodies has provided an important tool for the study of UA transporters.
During the recent epidemic period ($1995{\sim}1996$), seven strains of rubella virus were isolated in Korea. To analyze phylogenetic relationship between seven Korean strains and rubella virus strains from other different geographical areas, structural genes (E1, E2 and C) of Korean strains were enzymatically amplified and automatically sequenced. The sequence similarities of the E1, E2 and C genes of the cosmopolitan types were $95.8{\sim}98.1%$, $92.6{\sim}99.2%$ and $96.4{\sim}99.3%$ based on 1,441, 122 and 139 nucleotides and $96.9{\sim}98.5%$, $90{\sim}100%$ and $97.8{\sim}100%$ based on 480, 40 and 46 amino acids compared to the sequences of strain RA27/3, respectively. In contrast, the sequence similarities of the E1, E2 and C genes of the Asian types were $91.5{\sim}92.1%$, $83.6{\sim}88.5%$ and 91.4% based on nucleotides and $96.9{\sim}97.7%$, 85.5% and 97.8% based on amino acids compared to the sequences of strain RA27/3, respectively. However, immunodominent epitopes of the E1 gene of the cosmopolitan and Asian types were well conserved, and the growth patterns in cell culture and immunofluorescent antibody titers in cross-reaction test showed no differences between two different types. In phylogenetic analysis based on nucleotide sequences of each gene regions, the cosmopolitan and Asian types formed two distinct phylogenetic lineages. These data showed two distinct genotypes of rubella viruses cocirculated in Korea, but no significant differences in the antigenicity of two different rubella virus strains were found.
The studies were conducted on the allergic skin reaction of bovine eurytremiasis. In order to confirm the appearance of allergic skin reaction in this disease, a protein fraction of Eurytrema SPP(EPF) was extracted, and it's antigenicity was studied by means of intradermal reaction on the rabbits, goats and bovine. Rabbits used in this studies were divided into three groups: the first group was sensitized with EPF, the second group was sensitized with EPF, and the third group was served as control which is consisted with 5 non-sensitized and 2 saline injected rabbits. Three healthy native goats and bovine also used. Among these, 86 cases were eurytremiasis, 31 cases were fascioliasis and 71 cases non-infected. A protein fraction was also made from adult worm of Fasciola SPP(FPF) and tested the cross reaction between these two different fluke infestations. The results obtained were as follow: 1. Intradermal reaction was appeared in the infected cattle(bovine eurytremiasis) as well as in the EPF sensitized rabbits and goats. 2. In the EPF sensitized rabbits, the wheal of the intradermal reaction reacted the maximum size (increased wheal size of 5.0 to 9.0 mm) in 40 to 60 minutes and erythema in 60 minutes after intradermal injection of EPF antigen. In the EPF sensitized goats, the size of wheal reacted the maximum(increased wheal size of 5.5 to 8.0 mm) in 30 to 40 minutes, and then disappeared in 120 to 180 minutes after injection of EPF antgen. On the contrary, in the control groups of rabbits and goats, the wheal (7.0 mm) produced following antigen injection reached only to 7.5 to 8.5 mm. in 10 minutes without developing erythema, and then perished in 40 to 60 minutes after injection of EPF antigen. In the infected cattle, the wheal of the intradermal reaction reached the maximal sizes(increased wheal size of 4.0 to 11.0 mm) in 15 to 20 minutes and perished in 60 to 90 minutes after injection of EPF antigen. 3. It would be standardized that the positive reaction is above 4.0 mm, the negative below 2.0 mm and the suspective is 3.0 mm of the infected cattle. In the results of intradermal reaction, 87.2%(75 of 86 cases) was positive, 4.7%(4 of 86 cases) negative and 8.1% (7 of 86 cases) was suspective. However, in the non-infected control cattle, the wheal produced following injection disappeared in 30 to 40 minutes without increasing the wheal size in the most subjects or with incresing only to 1.0 to 2.0 mm in a few cattle. 4. In the results of intradermal reaction which were reciprocally tested in EPF sensitized rabbits by FPF antigen and in FPF sensitized. rabbits by EPF antigen, there were cross reacted. In the 31 cases if fascioliasis tested by EPF antigen, 11 cases were not specifically reacted with EPF antigen. Judging from the results of cross reaction in experimental rabbits and natural bovine fascioliasis, it would be expected when both EPF and EPF antigens are given intracutaneously on the same bovine patients of eurytremiasis or fascioliasis, the former antigen will produce the larger wheal in eurytremiasis, while the latter antigen will produce also the larger wheal in fascioliasis.
In March 1987, a bacterial disease occured among cultured tilapia (Oreochromis niloticus), in the aquarium of Fish Pathology Laboratory of National Fisheries University of Pusan. The diseased fish showed abdominal inflamation of ascites. The causative organisms isolated from the kidney were Gram negative rods. On SS agar colonies developed within 48 hours at $25^{\circ}C$. On the basis of the morphological and biochemical characteristics the organisms were identified as Edwardsiella tarda. They were sensitive to chloramphenicol, ampicilline and oxytetracycline. The pathogenicity was proved positive by intraperitoneal injection. Three kinds of antigen were prepared with E. tarda for the immune response in tilapia : i.e., by inactivating the strain with 0.4% formalin for 24 hrs at $25^{\circ}C$ ultrasonicating it 3 times with 5 watts for 30 seconds each time and filtrating it through millipore filter. The formalin killed antigen showed good efficacy at the injection concentration of over $10^7$ cells per fish of 50g. All the immunized tilapia showed only a little agglutination titer to the three antigens. The highest survival rate was recorded in challenged tilapia immunized with formalin killed cells.
Characterization of a purified proteinase from T4chomoncs uoginalis was carried out using bacitracin-sepharose affinity chromatography. Trichomonos uqginolis KT-9 isolate was used as a source of eye study Proteinase activity was determined using Bz-Pro- Phe-Arg-Nan as the substrate. Optimum pH for the purified proteinase activity was 7.0 and 6.0, 9.0 with DTT. Optimum temperature was 37℃ and isoelectric point was 7.2 Activity of this proteinase was inhibited by E-64, antipain, leupeptin, Hg2+ and Zn2+ and activated by DTT and cysteine. Activity of the purified proteinase was visualized by gelatin SDS- PAGE. The gelatinolytic activity of the purified proteinase was inhibited by E-64, antipain, leupeptin, and IAA, but not by PMSF and EDTA. On SDS-PAGE, the molecular weight of the purified proteinase was 60,000 daltons. Sera of rabbits infected with T. vaginalis reacted specifically in immunoblots with this proteinase. These results indicate that 60 kDa of purified proteinase was cysteine proteinase with antigenicity.
Saso, Luciano;Valentini, Giovanni;Mattei, Eleonora;Panzironi, Claudio;Casini, Maria Luisa;Grippa, Eleonora;Silvestrini, Bruno
Archives of Pharmacal Research
/
v.22
no.5
/
pp.485-490
/
1999
The mechanism of action of fish oil (FO), currently used in different chronic inflammatory conditions such as rheumatoid arthritis (RA), is not completely understood, although it is thought that it could alter the metabolism of endogenous autacoids. In addition, we hypothesized that the known capability of fatty acids (FA) of stabilizing serum albumin and perhaps other proteins, may be of pharmacological relevance considering that it is shared by other anti-rheumatic agents (e.g. nonsteroidal antiinflammatory drugs). Thus, we studied the effect of oral administration of FO and corn oil (CO), a vegetable oil with a different composition, on the stability of rat serum proteins, evaluated buy a classical in vitro method based on heat-induced protein denaturation. FO, and, to a lower extent, CO inhibited heat-induced denaturation of rat serum (RS): based on the inhibitory activity (EC50) of the major fatty acids against heat-induced denaturation of RS in vitro, it was possible to speculate the in vivo effects of palmitic acid (C16:0) and eicosapentaenoic acid (EPA, C20:5, n-3) may be more relevant than that of linolenic acid (C18:2). To better investigate this phenomenon, we extracted albumin from the serum of animals treated or not with FO with a one-step affinity chromatography technique, obtaining high purity rat serum albumin preparations (RSA-CTRL and RSA-FO), as judged by SDS-PAGE with Coomassie blue staining. When these RSA preparations were heated at $70^{\circ}C$ for 30 min, it was noted that RSA-FO was much more stable than RSA-CTRL, presumably due to higher number of long chain fatty acids (FA) such as palmitic acid or EPA. In conclusion, we provided evidences that oral administration of FO in the rat stabilizes serum albumin, due to an increase in the number of protein bound long chain fatty acids (e.g. palitic acid and EPA). We speculate that the stabilization of serum albumin and perhaps other proteins could prevent changes of antigenicity due to protein denaturation and glycosylation, which may trigger pathological autoimmune responses, suggesting that this action may be involved in the mode of action of FO in RA and other chronic inflammatory diseases.
Park, Mi-Yeon;Moon, Bo-Mi;Gang, Su-Jin;Lee, Jong-Ha;Park, Jin-Woo;Cho, Sung-Woo;Her, Cheol-Ho
Korean Journal of Veterinary Service
/
v.44
no.2
/
pp.73-83
/
2021
Although many swine farms continuously vaccinated to sow to prevent Porcine epidemic diarrhea(PED), PED has occurred annually in swine herds in Jeonbuk province, Korea. In the present study, the small intestine and feces samples from 17 farms where severe watery diarrhea and death of newborn piglets occurred in 2019 were collected, amplified by RT-PCR and determined the complete nucleotide sequences of the spike (S) glycoprotein genes of nine Jeonbuk PEDV isolates. The spike (S) glycoprotein is an important determinant for molecular characterization and genetic relationship of PEDV. These nine complete S gene isolates were compared with other PEDV reference strains to identify the molecular diversity, phylogenetic relationships and antigenicity analysis. 9 field strains share 98.5~100% homologies with each other at the nucleotide sequence level and 97.3~100% homologies with each other at the amino acid level. The nine Jeonbuk PEDV isolates were classified into G2b group including a genetic specific signal, S-indels (insertion and deletion of S gene). In addition, comparisons the neutralizing epitopes of S gene between 9 field strains and domestic vaccine strains of Korea mutated 12-15 amino acids with SM-98-1 (G1a group) and mutated 0-3 amino acids with QIAP1401 (G2b group). Therefore, the development of G2b-based live vaccines will have to be expedited to ensure effective prevention of endemic PED in Korea. In addition, we will need to be prepared with periodic updates of preventive vaccines based on the PEDV variants for the re-emergence of a virulent strain.
A worldwide effort is underway to utilize urban parks as a means ofresponding to climate change, providing various benefits to citizens. However, it also has several negative effects, such as an increase in pollen allergies. These negative impacts have been defined as ecosystem disservices and discussed globally, although the discussion remains insufficient domestically. In particular, pollen allergies have been discussed as a typical ecosystem disservice, with negative impacts such as an increase in symptoms attributed to higher pollen production or the growth of trees with higher antigenicity. The WHO reports that approximately 30% of the world's population suffers from pollen allergies. Many recent studies indicate that the harm induced by pollen allergies is expected to increase due to changes in the climate and thermal environment. In this context, we aim to diagnose the allergenicity of current urban parks and assess changes according to climate change scenarios. To achieve this goal, we assess pollen allergenicity in Seoul Children's Grand Park using the Urban Green Space Allergenicity Index (IUGZA) as the first step towards discussing ecosystem disservices. We found that the IUGZA value in the target area exceeds the threshold suggested in previous research, causing harm due to pollen allergies and is expected to increase according to climate change scenarios. We conclude that this result indicates that social harm from pollen allergies in urban parks may increase due to climate change. Therefore, we emphasize the necessity of discussing ecosystem disservices in the composition of urban parks.
The poxvirus group is considered to be a typical cytoplasmic inclusion forming virus. Every poxvirus has been reported to produce only one kind of inclusion in the infected tissues. A vague concept that inclusions of poxviruses are eosinophilic or acidophilic has prevailed. Although many papers and theories about the nature of the inclusion have been presented, most of them are not quite convincing on the point of the relations with virus multiplication, and an analysis of papers published showed that there seem to be many discrepancies in the descriptions of the nature of the poxvirus inclusions. Comparative studies on host-virus interaction with cowpox, orf, swinepox and fowlpox viruses which selected from each Group (I-IV) of poxviruses were performed from the morphological and virological standpoints. At first, in cowpox virus-FL cell system, as a comparative model, cytoplasmic inclusion, nucleic acid metabolism by autoradiography and detection of viral antigen by immunofluorescence were studied and obtained the results as follows: 1. The focus-like cytopathic effect (CPE) at early stage developed to entire culture at terminal stage of infection, and also the developing status of CPE was correlated to viral doses for inoculation. Two kinds of cytoplasmic inclusions which named A and B type were easily observed by Giemsa, hematoxylin-eosin (H & E) and May-Greenwald Giemsa (MGG) stainings in the infected cells. The B type inclusions were formed at early stage of infection and the A type inclusions were produced subsequently the B type formation. The B type which common type inclusion in poxviruses was a small compact or aggregate at early stage and developed to a large diffuse body at terminal stage of infection. On the other hand, the A type inclusion which depend upon the kind of virus was appeared as round and discrete shape, and its size and number was increased gradually during the culture period. It was characteristic to form distinct halos around the both types of inclusions in acid fixed, H & E stained preparations of infected cultures. The B type inclusion was always positive in Feulgen reaction and showed as DNA containing body but the A type inclusion was not. 2. In the relationship between inclusion and DNA metabolism of infected cells by the qualitative autoradiography using 3H-thymidine, the appearance of silver grains was coincided with B type inclusion but not with A type inclusion. This showed that the DNA synthesis was proceeded in all B type inclusions except those in the terminal stage with a diffuse form. This suggested that the B type inclusions are only sites of DNA synthesis and this was proceeded after the cell infection independently. The activity of DNA synthesis of the inclusions was nearly the same as that of the nucleic of normal cells and non-inclusion bearing cells. and non-inclusion bearing cells. Regardless of the size of the degree of DNA synthesis of the B type inclusion, inclusion bearing cells all showed remarkable suppression of nuclear DNA synthesis. 3. By the direct fluorescent antibody technique viral antigen in infected cells was detected. The B type inclusions have been proved to contain a great deal of viral antigen, whereas the basic substance of A type inclusion did not show antigenicity except the round edge. It was suggested that the round edge fluorescence might be caused by the glare of cytoplasmic viral antigen which pushed out and concentrated by the A type inclusion development. 4. Hemorrhagic red pock formations on chorioallantoic membrane of embryonated chicken egg had proved the characteristic of used viral strain. 5. By the above studies on the nature of two types of inclusions and the role they play in virus multiplication, it was concluded that the B type inclusion must be the site of the synthesis of viral DNA and protein as well as the site of the virus.
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