An investigation of bovine papillomaviruses from ocular squamous cell carcinomas in cattle.

Background: Ocular squamous cell carcinomas (OSCCs) in cattle has been studied for many years, but no definite etiology has been established. Squamous cell carcinomas (SCCs) may occur in different body parts of cattle. Depending on the location, it can cause an economic loss of varying degrees. Aims: The aim of this study was to investigate the causes of OSCCs in the eye region of cattle. Methods: Sixty tumoral masses taken form 60 cattle with proliferation in the eye region that were collected between the years 2012-2022 were used. These cases were admitted to our department for routine diagnosis. The tissues were diagnosed as OSCC using histopathological methods. The presence of bovine papillomavirus (BPV), one of the causative factors, was investigated using immunohistochemical and polymerase chain reaction (PCR). Results: Macroscopically masses were nodular or cauliflower-like and fragile and had hemorrhagic surfaces. Considering the keratin pearls, tumoral islands, and squamous differentiation, 20 out of 60 cases were classified as well, 20 as moderately, and 20 as poorly-differentiated OSCCs. 47 of the 60 cases were BPV positive using immunohistochemical methods. However, BPV nucleic acid was detected in only two cases with PCR. Only one of the cases could be sequenced. After phylogenetic analysis, virus strain was identified as BPV-1. Conclusion: Our results indicated that papillomaviruses can contribute to the development of OSCCs, in both precursor lesions and also advanced stage OSCCs. We found that BPV-1 has a possible causative role; however, more studies are needed to investigate the role of other viral agents and their interaction with secondary factors.

The comparison of efficacy of single intraarticular steroid injection versus the combination of genicular nerve block and intraarticular steroid injection in patients with knee osteoarthritis: a randomised study.

OBJECTIVES: The aim of this study is to evaluate the efficacy of genicular nerve block (GNB) and intraarticular corticosteroid injection (IACSI) in patients with knee osteoarthritis (OA). METHODS: Forty patients with Kellgren-Lawrence grade 2-4 knee OA were included for the study. Patients were divided into two groups randomly as IACS and IACS + GNB groups. All patients were evaluated with ultrasound for cartilage thickness, patellar tendon thickness, quadriceps tendon thickness and quadriceps muscle cross-sectional area (QMA). Pain intensity of the patients was evaluated with visual analogue scale and the Leeds Assessment of Neuropathic Symptoms and Signs pain scale. Functional status of the patients was evaluated with Western Ontario and Mc Master Universities Osteoarthritis Index. Quality of life of the patients was assessed with Nottingham Health Profile (NHP). All assessments were measured and compared at baseline, 1st month and 3rd month after treatment. RESULTS: All evaluation parameters were significantly improved in IACSI and IACSI + GNB groups. However, the improvement was better in IACSI + GNB group compared to those in IACSI group in terms of all evaluation parameters except QMA (0.10 ± 0.18 and 0.11 ± 0.22, respectively) and NHP scores in 1st month evaluation (- 3.11 ± 6.99 and - 3.54 ± 1.74, respectively). CONCLUSIONS: When combined with IACSI, GNB yields better analgesic effect and improves function in patients with knee OA compared to only IACSI.

The treatment effect on peripheral B cell markers in antibody positive myasthenia gravis patients.

B cells play a major role in the pathophysiology of myasthenia gravis (MG) with their ability to produce disease specific, pathogenic antibodies. However, their status during disease development and follow-up stages of the disease in the peripheral blood may need further studies to determine useful markers. In this study, we aimed to detect B cell associated factors concerning immunosuppressive treatment in generalized non-thymomatous MG patients. Although CD19+ B cell distribution did not vary among disease subgroups, expressions of both CD38 and BAFFR were altered on B cells in MG patients under immunosuppressive therapy. Serum levels of BAFF were elevated in untreated MG patients as compared to treated MG patients and healthy controls. B cell activation factors may show profound alterations due to immunosuppression.

Living donor kidney transplantation after desensitization in cross-match positive high sensitized patients.

BACKGROUND: We aimed to evaluate the long-term results of the patients who had positive cross-match (XM) test results and underwent living donor renal transplantation after desensitization with different combinations of intravenous immunoglobulin (IVIG), plasmapheresis (PP), and rituximab. MATERIAL AND METHODS: Forty-nine patients who were positive for complement-dependent cytotoxicity (CDC), flow cytometric (FC), and Luminex-XM test were included in the study. Renal transplantation was performed in 16 patients who had XM (-) test after desensitization with different combinations of IVIG (n =15), PP (n =13), and rituximab (n =10). Anti-human leukocyte antigens (HLA) antibodies (anti-HLA Abs) were detected by the Luminex single antigen bead assay. Anti-thymocyte globulin was used for induction, and tacrolimus, mycophenolic acid, and prednisolone were used for maintenance therapy. Also, we evaluated the relationship between different donor-specific anti-HLA Abs and the parameters mentioned above. RESULTS: Antibody-mediated rejection (AMR) and acute T cell-mediated rejection rates were 18.8 % and 6.3 %, respectively. Graft survival rates at the first, third, and fifth years post-transplantation were 93.8 %, 85.2 %, and 85.2 %, respectively, and the patients' survival rates were found to be 100 %. Serum creatinine level and glomerular filtration rate were 1.5 ± 1.2 mg/dl and 69.9 ± 30.4 ml/min, respectively. The mean follow-up time was 39 ± 24 months. CONCLUSIONS: Our study showed that kidney transplantation could be performed by effective desensitization in XM test positive patients. It was also shown that donor-specific anti-HLA DQ Ab and non-HLA Ab determination might be useful in diagnosing patients with positive cross-test and/or diagnosis of AMR. HIPPOKRATIA 2020, 24(4): 182-190.

Cardiovascular and Neurologic Complications in Kidney Transplant Recipients: A Focused Appraisal of Symptoms.

BACKGROUND AND OBJECTIVE: After a kidney transplantation, all efforts are focused on graft function. However, cardiovascular and neurologic complications might lead to decreased quality of life and shortened life expectancy. Early recognition of related symptoms might be critical to successfully manage these complications. METHODS AND PATIENTS: We retrospectively reviewed the medical records of patients who had undergone kidney transplantation in a tertiary center between January 2014 and December 2017. Demographic data and past medical history were systematically gathered. Symptoms related to cardiac or neurologic disorders and final diagnoses were recorded. RESULTS: One hundred eighty-six patients were evaluated by a cardiologist or a neurologist in the early post-operative period or long-term follow-up. Chest pain (n = 17; 9.1%) and palpitations (n = 13; 7.0%) were the most prevalent symptoms. Coronary artery disease was diagnosed in 70.6% (n = 12) of the patients presenting with chest pain. All of the patients were treated successfully, with either antianginal drugs or percutaneous angioplasty. Atrial fibrillation was diagnosed in 53.9% (n = 7) of the patients presenting with palpitations. Headache was the most prevalent chronic neurologic symptom (n = 16; 8.6%). Transient ischemic attack occured in 7 patients (3.8%) and 5 (2.7%) patients experienced ischemic stroke. CONCLUSION: Kidney transplantation is associated with short- and long-term cardiac and neurologic complications. Our findings underscore the crucial role of questioning symptoms that might be related to severe disorders. Asymptomatic patients with high risk factors must also be under scope. Attending physicians should have a low threshold for referring these patients to cardiologists and neurologists.

Relation of HLA-DRB1 to IgG4 autoantibody and cytokine production in muscle-specific tyrosine kinase myasthenia gravis (MuSK-MG).

A small subset of myasthenia gravis (MG) patients develop autoantibodies against muscle-specific kinase (MuSK), which are predominantly of the immunoglobulin (Ig)G4 isotype. MuSK-MG is strongly associated with HLA-DRB1*14, HLA-DRB1*16 and HLA-DQB1*05. In this study, the possible effects of these HLA associations on MuSK IgG autoantibody or cytokine production were investigated. Samples from 80 MG patients with MuSK antibodies were studied. The disease-associated HLA types were screened in the DNA samples. The IgG1, IgG2, IgG3 and IgG4 titres of the MuSK antibodies and the levels of interleukin (IL)-4, IL-6, IL-17A and IL-10 were measured in the sera. Comparisons were made among the groups with or without HLA-DRB1*14, HLA-DRB1*16 or HLA-DQB1*05. The IgG4 titres of the MuSK antibodies were higher than those of the IgG1, IgG2 and IgG3 isotypes among the whole group of patients. DRB1*14 (+) DRB1*16 (-) patients had higher levels of IgG4 antibodies than those of DRB1*14 (-) DRB1*16 (+) patients. DRB1*14 (+) DRB1*16 (+) patients also had higher levels of IgG4 antibodies than those of DRB1*14 (-) DRB1*16 (+) and DRB1*14 (-) DRB1*16 (-) patients. Higher IL-10 and lower IL-17A levels were measured in DRB1*14 (+) DRB1*16 (-) patients than in DRB1*14 (-) DRB1*16 (-) patients. The higher IgG4 titres of MuSK autoantibodies in patients carrying HLA-DRB1*14 than those in the other patients suggest a role for HLA in the production of the antibodies. The differences in IL-10 and IL-17A support the role of DRB1 in the etiopathogenesis of this autoimmune response.

Correlations between biochemical composition and biogas production during anaerobic digestion of microalgae and cyanobacteria isolated from different sources of Turkey.

Twenty one species of microalgae and Cyanobacteria were isolated from different ecosystems in Turkey to investigate the relation between biochemical methane potential (BMP) and biochemical characterization. Since the highest dry weight (X), specific growth rate (µ) and maximum productivity (Pmax) were obtained from the five species, identification of species and BMP tests with the composition analyzes were examined. BMP values were determined 308, 293, 242, 229 and 230 mLCH4/gVS for Desertifilum tharense, Phormidium animale, Chlorella sp., Anabeana variabilis and Chlorophyta uncultured. The Pearson correlation and principal component analysis (PCA) were applied to extract and clarify the correlation between composition of species and their methane production. Pearson correlation shows that glucose, Kjeldahl nitrogen and chlorophyll are highly and positively correlated with BMP. PCA revealed that Chlorella sp., Chlorophyta uncultured and Desertifilum tharense were placed against Phormidium animale distinguished by its extreme and different profile because of Kjeldahl nitrogen and glucose content.

Renoportal anastomosis in living donor liver transplantation.

BACKGROUND:  In advanced cirrhotic patients, extensive mesenteric vein thrombosis extends the operative time, causes peri- and postoperative complications, and increases the mortality and morbidity in liver transplantation (LT). The anastomosis between the left renal vein and graft portal vein is one of the crucial options in such patients. However, especially in living donor liver transplantation (LDLT) practice, limited cases are published in the literature. CASE REPORT: A thirty-seven years old female patient with hepatitis B virus (HBV) associated liver cirrhosis underwent LDLT. Her body mass index, graft weight, and graft-recipient weight ratio (GRWR) were noted 19.3 kg/m2, 990 g, and 1.9 %, respectively. During the surgical procedure, she had renoportal anastomosis (RPA) due to extensive portal vein thrombosis to provide an efficient portal inflow to the transplanted graft. No complication was observed in the early postoperative period, and the one year follow up passed without any problem. CONCLUSIONS: In LT, for providing efficient portal flow to the graft, the RPAs should be considered as an option in case of extensive splanchnic vein thrombosis and large splenorenal shunt. Ensuring that graft volume is close to the recipient standard liver volume, RPA can be performed safely and effectively in LDLT as an acceptable and life-saving procedure. HIPPOKRATIA 2019, 23(3): 140-142.

Effects of hepatitis B surface antigen (HBsAg) positivity of donors in HBsAg(+) renal transplant recipients: comparison of outcomes with HBsAg(+) and HBsAg(-) donors.

AIM: The aim of this study was to determine the effects of hepatitis B surface antigen (HBsAg) positivity of the donors on graft survival and liver complications in HBsAg(+) renal transplant recipients. PATIENTS AND METHOD: A group of 55 patients who underwent renal transplantation (RTx) in our hospital between 2001 and 2012 were included in the study. Patients were divided into 2 groups. Group 1 (n = 50) consisted of HBsAg(+) renal transplant recipients (RTR) whose donors were HBsAg(-). In Group 2 (n = 5), RTR and donors were both HBsAg(+). Lymphocyte cross matches, number of mismatches, donor types, renal replacement treatment modalities, drugs of induction treatment, and preoperative hepatitis B virus DNA titers of the groups were similar. In Group 1, 42 patients were taking lamivudine, 3 patients were taking entecavir, and 5 patients were taking tenofovir. All of the patients in Group 2 were taking lamivudine. Patient and graft survival rates, graft functions, acute hepatitis rates, acute rejection rates, and other clinical outcomes of the groups were compared. RESULTS: Demographic data of the groups were similar. Acute rejection rates (P = 0.458), graft survival rates (P = 0.515), and patient survival rates (P = 0.803) were also similar. No significant difference was found between the groups in terms of acute hepatitis rate (P = 0.511), glomerular filtration rate (calculated by Modification of Diet in Renal Disease formula) in the last follow-up (P = 0.988), alanine aminotransferase levels (P = 0.069), or delayed graft function rate (P = 0.973). Rates of chronic allograft dysfunction and new onset diabetes mellitus after transplantation were similar. CONCLUSION: Our study revealed that, RTx from HBsAg(+) donors to HBsAg(+) recipients is safe with antiviral treatment.

A Successful Renal Transplantation Case After Stem Cell Transplantation.

Renal transplantation is the most effective treatment method for end-stage renal disease (ESRD). However, new treatment modalities are being investigated, such as immunotoleration, to avoid the acute and chronic side effects of immunosuppressant drugs. We report a case in which a man had undergone allogenic stem cell transplantation from his brother 16 years ago due to chronic myeloid leukemia, and who then developed ESRD due to arterial hypertension and underwent renal transplantation (Rtx) from the same brother. The patient was followed up without immunosuppression due to full chimerism.

Outcomes of Renal Transplantation in Patients With Alport Syndrome.

AIM: We evaluated the outcomes of patients who underwent renal transplantation (Rtx) due to end-stage renal disease (ESRD) related to Alport syndrome in our study. MATERIALS AND METHODS: Twenty-five patients (female/male: 9 [36%]/16 [64%]) who underwent Rtx at our center between 2002 and 2014 were enrolled in the study. Mean ages of patients and donors (cadaveric/living: 8 [32%]/17 [68%]) were 28.2 ± 11.6 and 42.3 ± 15.8 years, respectively. As immunosuppressive therapy, tacrolimus plus mycophenolic acid were used for 17 (68%) patients and cyclosporin plus mycophenolic acid were used for 8 (32%) patients where induction therapy was basiliximab 20 mg (day 0 and 4) for 11 (44%) patients and anti-thymocyte globulin for 8 (32%) patients. Acute rejection was diagnosed using biopsy and evaluated with Banff classification. Analyses were performed by using SPSS 20.0 software with outcomes of mean 75.4 ± 31.4 months follow-up. Patient and graft survival were measured by using Kaplan-Meier survival curve and compared by using log-rank test. RESULTS: Graft survival rate was 89%, patient survival rate was 92.9%, and acute rejection rate was 12% (3 cases; 1 was cellular and 2 were antibody-mediated). Delayed graft function was observed in 4 (16%) cases, 1 patient (4%) had BK virus nephropathy and 2 (8%) patients required hemodialysis and had cytomegalovirus infection. At the last follow-up, mean serum creatinine level was 1.57 ± 1.23 mg/dL, spot urine protein creatinine ratio was 0.13 (0.04-1.84), and glomerular filtration rate was 71.7 ± 34.9 mL/min. CONCLUSION: Rtx is an effective and successful treatment modality for ESRD cases related to Alport syndrome.

Equine herpes virus type 1 (EHV-1) and 4 (EHV-4) infections in horses and donkeys in northeastern Turkey.

The herpesviruses infections in equides are caused by five different serotypes of viruses, belonging to family Herpesviridae. The goal of this study was to conduct a seroepidemiological investigation of equine herpesvirus type 1 (EHV-1) and type 4 (EHV-4) in horses and donkeys raised in two provinces and their villages in northeastern Turkey. A total of 666 samples from 423 horses and 243 donkeys that were not immunized against these infections were tested with ELISA. While 52.48% of tested horse sera was found to carry specific antibodies to EHV-1, 83.69% of these serums were found to carry specific antibodies to EHV-4. 51. Eighty-five percent of analyzed donkey samples tested positive for EHV-1 and 64.20% of these samples tested positive for EHV-4 antibodies. When the horse and donkey samples were evaluated together, 52.25% were seropositive for EHV-1 and 76.58% were seropositive for EHV-4. This study showed that EHV-1 and EHV-4 infections are quite common in the horses and donkeys being raised in the areas where the study was carried out. In addition, since the area where the study was carried out in the borders of Armenia and Georgia, the high level of seropositive results for these infections leads to the conclusion that we should consider the risk of diseases spreading to neighboring countries. This is the first study to serologically identify EHV-1 and EHV-4 infections in donkeys raised in Turkey.

Activation of the JAK/STAT pathway in Behcet's disease.

Th1/Th17-type T-cell responses are upregulated in Behcet's disease (BD). However, signaling pathways associated with this aberrant immune response are not clarified. Whole-genome microarray profiling was performed with human U133 (Plus 2.0) chips using messenger RNA of isolated CD14(+) monocytes and CD4(+) T cells from peripheral blood mononucleated cell (PBMC) in patients with BD (n = 9) and healthy controls (HCs) (n = 9). Flow cytometric analysis of unstimulated (US) and stimulated (phytohaemagglutinin) signal transducer and activator of transcription (STAT3) and pSTAT3 expressions of PBMCs were also analyzed (BD and HC, both n = 26). Janus family of kinase (JAK1) was observed to be upregulated in both CD14(+) monocytes (1.95-fold) and CD4(+) T lymphocytes (1.40-fold) of BD patients. Using canonical pathway enrichment analysis, JAK/STAT signaling was identified as activated in both CD14(+) monocytes (P = 9.55E-03) and in CD4(+) lymphocytes (P =8.13E-04) in BD. Interferon signaling was also prominent among upregulated genes in CD14(+) monocytes (P = 5.62E-05). Glucocorticoid receptor signaling and interleukin (IL-6) signaling were among the most enriched pathways in differentially expressed genes in CD14+ monocytes (P = 2.45E-09 and 1.00E-06, respectively). Basal US total STAT3 expression was significantly higher in BD (1.2 vs 3.45, P < 0.05). The JAK1/STAT3 signaling pathway is activated in BD, possibly through the activation of Th1/Th17-type cytokines such as IL-2, interferon (IFN-γ), IL-6, IL-17 and IL-23.

mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake.

How adult tissue stem and niche cells respond to the nutritional state of an organism is not well understood. Here we find that Paneth cells, a key constituent of the mammalian intestinal stem-cell (ISC) niche, augment stem-cell function in response to calorie restriction. Calorie restriction acts by reducing mechanistic target of rapamycin complex 1 (mTORC1) signalling in Paneth cells, and the ISC-enhancing effects of calorie restriction can be mimicked by rapamycin. Calorie intake regulates mTORC1 in Paneth cells, but not ISCs, and forced activation of mTORC1 in Paneth cells during calorie restriction abolishes the ISC-augmenting effects of the niche. Finally, increased expression of bone stromal antigen 1 (Bst1) in Paneth cells­an ectoenzyme that produces the paracrine factor cyclic ADP ribose­mediates the effects of calorie restriction and rapamycin on ISC function. Our findings establish that mTORC1 non-cell-autonomously regulates stem-cell self-renewal, and highlight a significant role of the mammalian intestinal niche in coupling stem-cell function to organismal physiology.

Molecular characteristics of bovine virus diarrhoea virus 1 isolates from Turkey: approaches for an eradication programme.

Forty pestivirus isolates sampled from cattle in Turkey between 2002 and 2007 were characterized according to 5' untranslated region (5'UTR) sequences and autoprotease (N(pro) ) gene sequences. The sampling of Bovine virus diarrhoea viruses (BVDVs) from 15 farms in five different regions indicated that BVDV 1-l (18/40, 45%) was the predominant genotype in Turkey; the samples also contained the genotypes 1-f (10/40, 25%), 1-b (7/40, 17.5%), 1-d (3/40, 7.5%), and 1-a (2/40, 5%), respectively.

The role of HLA-DRB1 shared epitope alleles in predicting short-term response to leflunomide in rheumatoid arthritis.

OBJECTIVES: To investigate the role of shared epitope (SE) alleles in the short-term clinical response to leflunomide for the treatment of active RA. METHODS: In an open-label, multi-centre study of 16-weeks duration, 93 patients (82% female) fulfilling ARA 1987 RA criteria were treated with leflunomide (100 mg loading dose for 3 days, then 20 mg/day as the maintenance dose). The primary efficacy criterion was the response status according to the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score-28 (DAS28) activity measure. SE determinations have been undertaken by polymerase chain reaction and sequence-specific oligonucleotide genotyping methods. RESULTS: The mean (s.d.) Disease Activity Score-28 (DAS28) was 5.1 (1.3) before the treatment, which was significantly decreased after 16 weeks [3.0 (1.1), P < 0.001]. According to the EULAR response criteria, 55 patients (59.1%) were classified as good responders. SE was positive in 51 (54.8%) of the patients, with 13 (13.9%) having SE homozygosity or carrying any two SE alleles. Among SE-positive patients, 68.6% (35/51) were good responders, compared with 47.6% (20/42) in SE negatives (P = 0.04). No difference was present according to SE hetero- or homozygosity (68.4 vs 69.2%). RF was also present significantly more frequently in the SE-positive group compared with negatives (78.4 vs 57.1%, P = 0.03). However, no significant difference was observed in the prevalence of RF positivity in patients with a good clinical response (72.7 vs 63.2%, P = 0.32). CONCLUSIONS: The results suggest that HLA-DRB1 SE presence may favourably affect the outcome of leflunomide monotherapy in an unselected group of RA patients with an active disease and naive to leflunomide.

Clinical comparison of anti-MuSK- vs anti-AChR-positive and seronegative myasthenia gravis.

We compared 65 anti-acetylcholine receptor (AChR)-negative myasthenia gravis (MG) patients, including 32 anti-muscle-specific tyrosine kinase (MuSK)-positive (49%) and 33 anti-MuSK-negative (seronegative) (51%) patients, with 161 anti-AChR-positive MG patients. The anti-MuSK-positive group had a higher frequency of bulbar involvement and respiratory crises. The seronegative group was in between the anti-MuSK positive and the anti-AChR positive groups, being closer to the latter, with regard to the severity of the disease. At the end of follow-up, the outcome of the anti-MuSK-positive patients was not different from that of the anti-AChR-positive patients, although their maintenance corticosteroid dose was higher. The seronegative patients had better outcome than the other two groups.

Interleukin (IL)-12, IL-2, and IL-6 gene polymorphisms in Takayasu's arteritis from Turkey.

Takayasu's arteritis (TA) is a chronic arterial inflammation of unknown etiology involving mainly the aorta and its major branches. Genetic polymorphisms of cytokines are screened as susceptibility factors for TA in Turkey. A total of 94 patients with TA were investigated for the genetic polymorphisms of the interleukin genes IL12, IL2,and IL6 and were compared with 108 healthy control subjects using polymerase chain reaction-sequence-specific primer method. The frequencies of IL12B 1188 C allele (p = 0.03, OR = 1.7) and CC genotype (p = 0.007, OR = 3.7) were both higher in TA patients than in control subjects. TT genotype at IL2-330 (p = 0.006, OR = 2.4) and GG genotype at IL6-174 (p = 0.04, OR = 1.9) were more frequent in TA patients. Lower prevalence of GT genotype at IL2-330 (p = 0.005, OR = 0.4), CG genotype at IL6-174 (p = 0.001, OR = 0.4), and AG genotypes at IL6-598 (p = 0.01, OR = 0.4) were also detected. The polymorphism of IL-12 as well as IL-6 and IL-2 genes may contribute to susceptibility and pathogenesis of TA by altering cytokine production and inducing inflammation.

Serological evidence of West Nile Virus (WNV) in mammalian species in Turkey.

In this study, the sera collected from a variety of mammalian species (ass-mules, cat, cattle, dog, horse, human and sheep) in 10 representative provinces of Turkey, were surveyed for the presence of neutralizing antibodies to West Nile virus (WNV). Overall, 1 of 40 (2.5%) ass-mules, 4 of 100 (4%) cattle, 43 of 114 (37.7%) dogs, 35 of 259 (13.5%) horses, 18 of 88 (20.4%) humans and 1 of 100 (1%) sheep, tested positive for WNV-neutralizing antibodies. The results indicate that a wide range of mammals are exposed to a West Nile-related virus and this could contribute to the long-term survival of this virus in the absence of overt disease.