• Journal of Veterinary Science
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• v.25 no.1
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• pp.15.1-15.15
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• 2024

Background: The anti-programmed death 1 (PD-1) antibody has led to durable clinical responses in a wide variety of human tumors. We have previously developed the caninized anti-canine PD-1 antibody (ca-4F12-E6) and evaluated its therapeutic properties in dogs with advance-staged oral malignant melanoma (OMM), however, their therapeutic effects on other types of canine tumors remain unclear. Objective: The present clinical study was carried out to evaluate the safety profile and clinical efficacy of ca-4F12-E6 in dogs with advanced solid tumors except for OMM. Methods: Thirty-eight dogs with non-OMM solid tumors were enrolled prospectively and treated with ca-4F12-E6 at 3 mg/kg every 2 weeks of each 10-week treatment cycle. Adverse events (AEs) and treatment efficacy were graded based on the criteria established by the Veterinary Cooperative Oncology Group. Results: One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6. Treatment-related AEs of any grade occurred in 13 out of 37 cases (35.1%). Two dogs with sterile nodular panniculitis and one with myasthenia gravis and hypothyroidism were suspected of immune-related AEs. In 30 out of 37 dogs that had target tumor lesions, the overall response and clinical benefit rates were 6.9% and 27.6%, respectively. The median progression-free survival and overall survival time were 70 days and 215 days, respectively. Conclusions: The present study demonstrated that ca-4F12-E6 was well-tolerated in non-OMM dogs, with a small number of cases showing objective responses. This provides evidence supporting large-scale clinical trials of anti-PD-1 antibody therapy in dogs.

• Clinical and Experimental Reproductive Medicine
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• v.41 no.3
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• pp.108-114
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• 2014

Male factors account for 20%-50% of cases of infertility and in 25% of cases, the etiology of male infertility is unknown. Effective treatments are well-established for hypogonadotropic hypogonadism, male accessory gland infection, retrograde ejaculation, and positive antisperm antibody. However, the appropriate treatment for idiopathic male infertility is unclear. Empirical medical treatment (EMT) has been used in men with idiopathic infertility and can be divided into two categories based on the mode of action: hormonal treatment and antioxidant supplementation. Hormonal medications consist of gonadotropins, androgens, estrogen receptor blockers, and aromatase inhibitors. Antioxidants such as vitamins, zinc, and carnitines have also been widely used to reduce oxidative stress-induced spermatozoa damage. Although scientifically acceptable evidence of EMT is limited because of the lack of large, randomized, controlled studies, recent systematic reviews with meta-analyses have shown that the administration of gonadotropins, anti-estrogens, and oral antioxidants results in a significant increase in the live birth rate compared with control treatments. Therefore, all physicians who treat infertility should bear in mind that EMT can improve semen parameters and subsequent fertility potential through natural intercourse.

• Journal of International Academy of Physical Therapy Research
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• v.5 no.2
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• pp.718-722
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• 2014

The cerebellum is known to control balance, equilibrium, and muscle tone. If the cerebellum becomes damaged, the body is unable to retain its balancing functions or involuntary muscle movement. This is why, in stroke patients, there is a high risk of functional disability, as well as a myriad of other disabilities secondary to stroke. Ischemia was induced in SD mice by occluding the common carotid artery for 5 minutes, after which blood was reperfused. Needle electrode electrical stimulation(NEES) was applied to acupuncture points, at 12, 24, and 48 hours post-ischemia on the joksamri. Protein expression was investigated through caspase-3 antibody immuno-reactive cells in the cerebral nerve cells and Western blotting. The results were as follows: The number of caspase-3 reactive cells in the corpus cerebellum 12 and 24 hours post-ischemia was significantly (p<.05) smaller in the NEES group compared to the GI group. caspase-3 expression 12 and 24 hours post-ischemia was significantly(p<.05) smaller in the NEES group compared to the GI group. Based on these results, NEES seems to have a significant effect on Caspase-3 in the cerebellum in an ischemic state at 12 and 24 hours post ischemia, NEES delays the occurrence of early stage apoptosis-inducing Caspase-3, delaying and inhibiting apoptosis. Further systematic studies will have to be conducted in relation to the application of this study's results on stroke patients.

• Biomedical Science Letters
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• v.17 no.3
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• pp.197-202
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• 2011

Mitosis count is one of the most helpful morphologic features for distinguishing pulmonary typical carcinoid (TC) from atypical carcinoid (AC). However, identifying areas of highest mitotic activity is tedious and time-consuming, and mitosis count may vary substantially among pathologists. Anti-phosphohistone H3 (PHH3) is an antibody that specifically detects histone H3 only when phosphorylated at serine 10 or serine 28, an event that is concurrent with mitotic chromatin condensation and not observed during apoptosis. In this study, immunohistochemical staining for PHH3 was performed to determine whether PHH3 was a reliable and objective mitosis-specific marker for pulmonary carcinoid tumors. Seventeen cases of surgically resected pulmonary carcinoid tumors (12 TCs and 5 ACs) were obtained and classified according to the 2004 World Health Organization classification. Mitotic counts determined by PHH3 correlated to ones determined by hematoxylin and eosin (H&E) staining; however, PHH3 mitotic counts (mean mitotic counts: 1 in TCs and 3.2 in ACs) were slightly higher than H&E mitotic counts (mean mitotic counts: 0.25 in TCs and 1.8 in ACs). The mitotic counts determined by experienced observer were more correlated to those determined by inexperienced observer with the PHH3-based method (R=0.968, P<0.001) rather than H&E staining (R=0.658, P<0.001). These results suggest that the PHH3 mitotic counting method was more sensitive and simple for detecting mitoses compared to traditional H&E staining. Therefore, PHH3 immunohistochemistry may contribute to more accurate and reproducible diagnosis of pulmonary carcinoid tumors and may be a valuable aid for administrating appropriate clinical treatment.

• Molecules and Cells
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• v.24 no.3
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• pp.431-436
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• 2007

Stem cell-based therapy is being considered as an alternative treatment for cardiomyopathy. Hence understanding the basic molecular mechanisms of cardiomyocyte differentiation is important. Besides BMP or Wnt family proteins, $TGF-{\beta}$ family members are thought to play a role in cardiac development and differentiation. Although $TGF-{\beta}$ has been reported to induce cardiac differentiation in embryonic stem cells, the differential role of $TGF-{\beta}$ isoforms has not been elucidated. In this study, employing the DMSO-induced cardiomyocyte differentiation system using P19CL6 mouse embryonic teratocarcinoma stem cells, we investigated the $TGF-{\beta}$-induced signaling pathway in cardiomyocyte differentiation. $TGF-{\beta}1$, but not the other two isoforms of $TGF-{\beta}$, was induced at the mRNA and protein level at an early stage of differentiation, and Smad2 phosphorylation increased in parallel with $TGF-{\beta}1$ induction. Inhibition of $TGF-{\beta}1$ activity with $TGF-{\beta}1$-specific neutralizing antibody reduced cell cycle arrest as well as expression of the CDK inhibitor $p21^{WAF1}$. The antibody also inhibited induction of the cardiac transcription factor Nkx2.5. Taken together, these results suggest that $TGF-{\beta}1$ is involved in cardiomyocyte differentiation by regulating cell cycle progression and cardiac gene expression in an autocrine or paracrine manner.

• The Journal of Internal Korean Medicine
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• v.23 no.2
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• pp.306-312
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• 2002

Systemic Lupus Erythematosus(SLE) is a autoimmune disease characterized by combined symtoms of malar rash, discoid rash, neuropsychiatric disorder, renal disorder, hematologic disorder, photosensitivity immunologic disorder, oral ulcer, anti-nuclear antibody, arthritis, pleuritis and pericarditis, etc. Multiple genetic or environmental causes are supposed to facilitate antiboby production to autoantigen such as ds-DNA, histone, phospholipid, red blood cell, platelet, etc. And defective complementary system fail to remove autoantigen-antibody complex, which deposit in multiple organs and result in inflammatory damages. SLE does not correctly correspond to any specific category of oriental medicine. But, accoring to previous reports, it can be controlled by herb medications used differently patients-to-patients. So we are to report this one SLE case being successfully controlled by classic corticosteroids with herb medications based on oriental diffrential diagnosis of symptoms and signs.

• Journal of International Academy of Physical Therapy Research
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• v.6 no.2
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• pp.846-851
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• 2015

This neurological damage accelerates the infection reaction of cells and apoptosis at the time of reperfusion after ischemia occurs. BCL-2/BCL-2 allogeneic begeminum has a function of suppressing the apoptosis of cells, and thus it is inferred that the susceptibility of cells to apoptosis is determined by the amount of allogeneic begeminum present which is determined based on the amount of BAX. Ischemia was induced in SD mice by occluding the common carotid artery for 5 minutes, after which blood was re-perfused. NEES was applied to acupuncture points, at 12, 24, and 48 hours post-ischemia on the joksamri, Hapgok. Protein expression was investigated through BAX antibody immuno-reactive cells in the cerebral nerve cells and Western blotting. The results were as follows: In the present study as well, as a result of observation of the change in the number of the BAX reaction cells after the inducement of GI, there was the aspect of most of the BAX reaction cells being observed in the corpus striatum area of the GI group 24 hours after the inducement of ischemia. This revealed the same results as those of previous studies in which the change in the number of BAX reaction cells occurred in all areas while ischemia was in progress. The change in the expression of BAX protein after 24 hours showed that there was a very significant reduction in the NEES group compared to the GI group (p<.01). As a result, a greatest amount of change in the number of BAX immunoreactive cells related to apoptosis 24 hours after ischemia appeared in the NEES group. This study that ischemia increases the expression of BAX that induces apoptosis. Thus, it is determined that ischemia is the main cause of the apoptosis of neurons, and this study reveals that low frequency needle electrode electrical stimulation has the effect of blocking the apoptosis of neurons by reducing protein related to the apoptosis of cells that has increased after ischemia has occurred.

• Parasites, Hosts and Diseases
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• v.56 no.4
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• pp.325-334
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• 2018

Toxoplasma gondii is an apicomplexan zoonotic protozoan parasite that infects most species of warm-blooded animals, including humans. The heavy incidence and severe or lethal damage caused by T. gondii infection clearly indicate a need for the development of an effective vaccine. T. gondii GRA8 is a member of the dense granules protein family and is used as a marker of acute infection. In the present study, we evaluated the protective immunity induced by DNA vaccination based on a recombinant eukaryotic plasmid, pDsRed2-GRA8, against acute toxoplasmosis in mice. BALB/c mice were intramuscularly immunized with the pDsRed2-GRA8 plasmid and then challenged by infection with the highly virulent GFP-RH strain of T. gondii. The specific immune responses and protective efficacy against T. gondii of this vaccine were analyzed by measuring cytokine and serum antibody titers, splenocyte proliferation assays, and the survival times of mice after challenge. Our results showed that mice immunized with pDsRed2-GRA8 demonstrated specific humoral and cellular responses, induced higher IgG antibody titers with predominant IgG2a production; increased levels of IL-10, IL-12 (p70), $IFN-{\gamma}$, $TNF-{\alpha}$, and splenocyte proliferation; and prolonged survival times compared to those of control mice. The present study showed that DNA immunization with pDsRed2-GRA8 induced humoral and cellular immune responses, and all immunized mice showed greater Th1-type immune responses and longer survival times than those of control mice. These results indicated that T. gondii GRA8 DNA immunization induces a partial protective effect against acute toxoplasmosis.

• Korean Journal of Veterinary Research
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• v.46 no.4
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• pp.395-398
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• 2006

A 2-month-old female Shih-tzu dog was referred because of lameness, exercise intolerance, depression, elbow and stifle joint swelling. Physical examination, complete blood counts, serum-chemistry, radiography, synovial fluid analysis, antinuclear antibody test, and rheumatoid factor measurement were initiated. On radiography, soft tissue swelling of elbow and stifle joints without erosiveness were founded. The results of synovial fluid analysis revealed severe neutrophilic pleocytosis (nondegenerative), decreased viscosity, increased turbidity, positive on mucin-clot test, and negative on bacterial culture. The results of rheumatoid factor measurement and antinuclear antibody test were negative and below 1 : 40, respectively. Based on all tests, we diagnosed this case as juvenile onset type I immune-mediated polyarthritis. Azathioprine (1 mg/kg body weight, per os q 24 h, for 4 weeks) was then administered and clinical signs improved gradually. Four weeks after azathioprine administration, clinical signs were disappeared. This report describes the clinical findings, imaging characteristics, synovial fluid findings, and other laboratory results of type I immune-mediated polyarthritis and successful management with azathioprine therapy.

• Microbiology and Biotechnology Letters
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• v.50 no.3
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• pp.430-435
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• 2022

The infectious bursal disease (IBD) is a highly contagious and acute poultry disease caused by Birnavirus. However, the vaccination is the only disease prevention, but several factors impeded vaccine development. Thus, a need for time to develop a novel technique for managing and treating respiratory diseases in poultry birds. Passive immunization is a hope and a possible alternative used in birds to meet this need. The current research attempted to produce egg yolk-based polyclonal antibodies against the IBD virus. The benefits of IgY include ease of extraction, lack of reaction with mammalian Fc receptors, and low production cost. Commercial layers were immunized with inactivated IBD virus subcutaneously according to the treatment regimen. The eggs were gathered daily, and yolk antibodies were extracted with the ammonium sulfate precipitation technique. The use of an indirect hemagglutination test demonstrated that IgY was IBD-specific. Until the end of the experiment, the specific IgY immunoglobulins did not lose activity when stored at 4℃. The specific immunoglobulin (IgY) treated challenged birds were demonstrated 92% recovery in comparison to the control group. The study implies that the IBDV specific IgY is an easily prepared and rich source of antibodies and offers an alternative therapeutic agent to cure IBD-infected birds.