Revealed Lymphocyte Infiltration Research Articles

Evaluation of Immune Responses and Histopathological Effects against Gamma Irradiated Avian Influenza (Sub type H9N2) Vaccine on Broiler Chicken

Abstract Vaccination is a good strategy for the prevention of avian influenza virus. In this research Gamma Irradiated Avian Influenza (Sub type H9N2) Vaccine (GAIV) was prepared by 30 kGy irradiation and used for vaccination of broiler chickens. The purpose was a comparison of immune responses in the two routes of administration for the GAIV vaccine; intranasal and subcutaneously, use of Montanide ISA70 and Trehalose accompanied with irradiated vaccine and compare with formalin vaccine. The Influenza Virus A/Chicken/IRN/Ghazvin/2001/H9N2 was irradiated and used for vaccine formulation, and formalin inactivated AIV was used as conventional vaccine. Chickens were vaccinated by GAIV with and without Trehalose, GAIV and formalin vaccines with ISA70, two routes of administration were intranasal and subcutaneously. All the vaccinated chickens showed a significant increase in antibody titration. The most significant increase of antibody titration was in irradiated vaccine plus Trehalose groups intranasal and subcutaneously. After the first and second intranasal vaccination, the amount of IFN-gamma increased in the irradiated vaccine plus Trehalose group compared to other groups. However, most of the vaccinated groups did not show any significant increase of IFN-α concentration. Histopathological examination revealed lymphocyte infiltration (++), foci dispersed of hemorrhage and edema in intranasal vaccination groups and in addition to these, thickening of alveolar septa was observed in the injection groups. GAIV vaccine can be a good candidate for vaccine preparation, and Trehalose as a stabilizer protects viral antigenic proteins, also makes more absorbance of antigen by the inhalation route. In vaccinated chickens the ulcers in injected vaccines were lower than intranasal vaccines.

The Relation of Cytotoxin-Associated Gene-A Seropositivity with Vitamin B12 Deficiency in Helicobacter pylori-Positive Patients.

Background and Aim As a worldwide infectious bacterium, H. pylori leads to stomach pathologies such as gastritis, peptic ulcer, gastric cancer, MALToma, and various extragastric manifestations. In our study, we aimed to investigate the association between serum vitamin B12 level and cytotoxin-associated gene-A (CagA) seropositivity, which is one of the virulence factors of Helicobacter pylori (H. pylori). Method This study has been conducted on 289 patients who have met the inclusion criteria. Within these patients, 213 of them were H. pylori positive and 76 were negative. Vitamin B12 and CagA-IgG levels were assessed in consecutive dyspeptic patients undergoing upper endoscopy. Results Out of 289 patients, 51.9% were women (n = 150) and H. pylori was detected in 213 (73.7%) patients. Histopathological evaluation with modified Sydney classification revealed lymphocyte infiltration in 66.8% (n = 193), activation in 46% (n = 133), metaplasia in 11.4% (n = 33), atrophy in 11.4% (n = 33), and lymphoid follicles in 21.1% (n = 61) of the patients. Within H. pylori-positive patients, the ratio of CagA positivity was 57.3% (n = 122). Low B12 vitamin level was significantly correlated with existence of H. pylori (p=0.02), CagA (p=0.002), lymphocyte (p=0.006), metaplasia (p=0.001), atrophy (p=0.001), and lymphoid follicles (p=0.006). Positivity of CagA has been detected to be statistically corelated with lymphocyte (p=0.001) and activation (p=0.005); however, the same relation was not present with atrophy (p=0.236). Conclusion In conclusion, B12 deficiency was positively correlated with CagA positivity and gastric inflammatory activity.

A case report of myocarditis combined with hepatitis caused by herpes simplex virus

BackgroundViral myocarditis presents with various symptoms, including fatal arrhythmia and cardiogenic shock, and may develop into chronic myocarditis and dilated cardiomyopathy in some patients. We report a case of viral myocarditis and hepatitis caused by herpes simplex virus.Case presentationA 20-year-old woman was admitted to our hospital with fever, fatigue, and anorexia. The initial investigation showed elevated liver enzyme levels and elevated creatine phosphokinase, and computed tomography showed diffuse swelling and internal heterogeneous image in the liver. These findings were consistent with acute hepatitis; therefore, we performed a liver biopsy, which showed parenchymal necrosis and lymphocytic infiltration. The night that the liver biopsy was performed, blood pressure gradually decreased and revealed cardiogenic shock. Electrocardiography showed diffuse ST-segment elevation, and echocardiography showed a dilated, spherical ventricle with reduced systolic function and pericardial effusion. An endomyocardial biopsy revealed lymphocyte infiltration of the myocardium, confirming acute myocarditis. After a few days, tests for immunoglobin M and immunoglobin G antibodies against herpes simplex virus were positive.ConclusionsWe presented a rare case of myocarditis combined with hepatitis that was caused by herpes simplex virus. Acute myocarditis can occur concurrently with hepatitis, pancreatitis, nephritis, and encephalitis; thus, determining the presence of other infectious lesions is necessary to provide appropriate treatment for the patient.

HISTOPATHOLOGICAL AND BIOCHEMICAL EFFECTS OF IMIPRAMINE ON LIVER, KIDNEY AND BRAIN IN ADULT MICE

This study examined the hepatic functions (Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP)), and histological changes in liver and kidney in imipramine -induced rabbits. Twenty adult mice were randomly divided into two groups comprising 10 mice each. Control group, received 1 ml normal saline 0.9%. Groups 2 received daily, 10 mg/kg of Imipramine for 21 days. Assessment of (AST,ALT, and ALP) were done by spectrophotometry, in addition to histological studies. There were significant changes in parameters for rabbits in group 2 compared to control group. The histopathological examination of renal tissue revealed lymphocyte infiltration, congestion, glomerulus and tubular damage. The tubular was containing hypertrophied epithelial cell which block the lumen. Brain tissues in groups 2 showed degeneration of pyramidal cells in the cortex, congestion of the blood vessels in the cortex and medulla. The cortex certain pyramidal cell with slight enlarged. Conclusion: Evidence of biochemical and histopath-ological affection of hepatic, renal and brain evoked by repeated administration of imipramine for long periods.

Carpal spasm in a girl as initial presentation of celiac disease: a case report

BackgroundCeliac disease is an immune-mediated disorder elicited by ingestion of gluten in genetically susceptible persons. This disorder is characterized by specific histological changes of the small intestine mucosa resulting in malabsorption. This case was written up as it was an unusual and dramatic presentation of celiac disease.Case presentationWe report the case of a 3-year-old Albanian girl who presented at our clinic with carpal spasms and hand paresthesia. A physical examination at admission revealed a relatively good general condition and body weight of 10.5 kg (10 percentile). Carpal spasms and paresthesias of her extremities were present. Neuromuscular irritability was demonstrated by positive Chvostek and Trousseau signs.Blood tests showed severe hypocalcemia with a total serum calcium of 1.2 mmol/L (normal range 2.12 to 2.55 mmol/L), ionized calcium of 0.87 (normal range 1.11 to 1.30 mmol/L), and 24-hour urine calcium excretion of 9.16 mmol (normal range female <6.2 mmol/day).Among other tests, screening for celiac disease was performed: antigliadin immunoglobulin A, anti-tissue transglutaminase, and anti-endomysial immunoglobulin A antibodies were positive. A duodenal biopsy revealed lymphocyte infiltration, crypt hyperplasia, and villous atrophy compatible with celiac disease grade IIIb according to the Marsh classification. Following the diagnosis of celiac disease, human leukocyte antigen typing was performed, giving a definite diagnosis of celiac disease. She was started on a gluten-free diet.Due to failure to follow a gluten-free diet, episodes of carpal spasms appeared again. Unfortunately, at the age of 7 years she presents with delayed psychophysical development.ConclusionsAlthough hypocalcemia is a common finding in celiac disease, hypocalcemic carpal spasm is a rare initial manifestation of the disease. Therefore, the possibility of celiac disease should be considered in patients with repeated carpal spasms that seem unduly difficult to treat. This should be evaluated even in the absence of gastrointestinal symptoms since hypocalcemia and its manifestation may present as initial symptoms of celiac disease even in young children.

Abstract A06: Development of a drug discovery platform using clinically relevant patient-derived xenograft models for cutaneous T cell lymphomas

Abstract Introduction: Cutaneous T cell lymphomas (CTCL) represent a heterogeneous group of diseases. Mycosis fungoides (MF) and Sezary syndrome (SS) are the most common subtypes of CTCL. Discovery of new therapeutic targets in T cell lymphomas has been hampered by lack of appropriate discovery platforms. Few T cell lymphoma cell lines are available; and it is likely that they have departed significantly from the original disease through long-term in vitro cultivation. Objectives: To develop patient-derived T cell lymphoma mouse xenograft models (PDX) that recapitulate the clinical presentation of human diseases and to establish a drug discovery platform using these PDX models. Materials and Methods: To establish PDX models for MF and SS, we injected lymphocytes obtained from patients into an NSG mouse (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) either subcutaneously or intravenously. Next, we investigated whether tumor derived plasma cell-free DNA can serve as a surrogate for disease burden in PDX. We first established this method in xenografts bearing a subcutaneous tumor derived from a MF cell line. We measured tumor volume by manual caliper methods twice weekly and simultaneously, we collected plasma from these mice. We measured human-actin-specific cell-free DNA concentrations in the plasma by qPCR and examined whether they can correlate with the tumor volume measured by the caliber method. After validated this method in xenografts established with a MF cell line, we examined this method in PDX. To this end, we measured human-actin-specific cell-free DNA concentrations in PDX plasma at various time points post-inoculation and investigated whether they correlated with tumor progression in PDX. Results: Three weeks after inoculation of patient-derived malignant lymphocytes, the MF PDX mouse developed clinical syndrome of MF with erythematous, scaly skin lesions and alopecia. Necropsy revealed lymphocyte infiltration in the skin, spleen, liver and lungs, resembling the disease distribution of MF in humans. The erythematous skin lesions showed atypical lymphocyte infiltration in the epidermis, a diagnostic hallmark for MF. Additionally, immunohistochemistry staining reveled malignant cells in the epidermis expressed CD3 and CD4 without co-expression of CD7, which is identical to those of the donor patient's. Furthermore, we analyzed T cell receptor (TCR) clonality by PCR and demonstrated a clonal T-cell population in both patient and mouse specimens with similar amplified peaks, consistent with successful xenograft. Similarly, the PDX mouse for SS developed the clinical syndromes with skin rashes, alopecia and was found to have Sezary cells in the blood, a diagnostic hallmark for SS. Malignant cells isolated from the spleen of a SS PDX animal had the same immunophenotype and TCR clonality as that of the donor patients, indicating successful xenografts. Importantly, we were able to passage malignant cells from one generation of PDX to the next while maintaining the clinical presentation of the disease. Finally, we were able to demonstrate that in cell-line derived xenograft mice bearing subcutaneous tumors, human-actin-specific cell-free DNA concentrations in the plasma correlated with tumor volume assessed by manual caliber measurements. Next, we extended these results to MF/SS PDX, and were able to correlate human-actin cell-free DNA concentrations with tumor progression in in these mice. Conclusion: We established PDX models that recapitulate the clinic syndrome of MF and SS with characteristic skin, nodes and blood involvement by the malignant cells. Additionally, we demonstrated that tumor-specific cell-free DNA concentration can be used as a surrogate for tumor burden in PDX. Together, our results demonstrated that we can establish a drug discovery platform using clinically relevant PDX models for T cell lymphomas. Citation Format: Wei Ai, Yen-Chen Yang Yang, Shervin Afghani, Huaxin Gao, Laura Pincus Pincus, Linlin Wang Wang, Taha Rakhshandhroo, Ronald Balassanian, James Rubenstein, Ryan Gill, Frank McCormick. Development of a drug discovery platform using clinically relevant patient-derived xenograft models for cutaneous T cell lymphomas. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr A06.

Pathology of Edwardsiella tarda infection in African catfish, Clarias gariepinus (Burchell 1822), fingerlings

Abstract Edwardsiella tarda is one of the serious fish pathogens infecting both cultured and wild fish species. This study aimed to assess the phenotypic characterization and pathogenicity of E. tarda isolated from Clarias gariepinus (Burchell) with dropsy and histopathological alterations. The causative agent was identified with Vitek 2, and its pathogenicity was determined by intramuscular injection. The challenged catfish exhibited vertical hanging, frothing, excess mucus production, listing, swollen abdomen, anorexia, fin and tail rot, and reddish operculum. The LD50 of E. tarda PBB and PBP strains was found to be 8.52 × 106 and 1.68 × 107 cells fish-1, respectively. Histopathological observations on catfish infected naturally revealed lymphocyte infiltration in muscle and focal necrosis, hyperplasia, edema, and swelling of the gill lamellar epithelium. The kidney of diseased fish exhibited ischemic type tubulopathy, necrosis of nephritic tubules, hyperplastic hematopoietic tissue, rupture of the tubular basement membrane, hydropic dystrophy of nephritic cells, neutrophil infiltration, fibrinoid necrosis of nephretic tubules, hemosiderin deposition, and edema. The liver sections revealed lymphocyte infiltration, dilation of hepatic sinusoids, expansion of space between hepatic sinusoids, and focal necrosis. The inflammatory responses observed in kidney and liver in the present study were presumably suppuration and were attributed to the potential virulence factors of E. tarda.

Behçet's Disease With Ruptured Anterior Communicating Artery Aneurysm Following Ruptured Thoracic Aortic Aneurysm

A 48-year-old Japanese woman with Behçet's disease suffered successive rupture of thoracic aortic and cerebral aneurysms within one year. The patient underwent successful surgical treatment for both aneurysms. Histological examination of the aneurysm walls revealed lymphocyte infiltration into the adventitia with smooth muscle cell hyperplasia in the thickened intima. This is an extremely unusual presentation of Behçet's disease associated with both cerebral and aortic aneurysms.

Differential immune responses to albumin adducts of reactive intermediates of trichloroethene in MRL+/+ mice.

Trichloroethene (TCE) is an industrial degreasing solvent and widespread environmental contaminant. Exposure to TCE is associated with autoimmunity. The mode of action of TCE is via its oxidative metabolism, and most likely, immunotoxicity is mediated via haptenization of macromolecules and subsequent induction of immune responses. To better understand the role of protein haptenization through TCE metabolism, we immunized MRL+/+ mice with albumin adducts of various TCE reactive intermediates. Serum immunoglobulins and cytokine levels were measured to determine immune responses against haptenized albumin. We found antigen-specific IgG responses of the IgG subtypes IgG(1), IgG(2a), and IgG(2b), with IgG(1) predominating. Serum levels of G-CSF were increased in immunized mice, suggesting macrophage activation. Liver histology revealed lymphocyte infiltration in the lobules and the portal area following immunization with formyl-albumin. Our findings suggest that proteins haptenized by metabolites of TCE may act as neo-antigens that can induce humoral immune responses and T cell-mediated hepatitis.

Rupture of the Achilles Tendon in Rheumatoid Arthritis With Histologie Evidence of Enthesitis

Spontaneous Achilles tendon rupture occurred in a 60-year-old man with a two-year history of sero-positive rheumatoid arthritis (RA). Histologic section of the ruptured Achilles tendon revealed the existence of rheumatoid granulation that consisted of lymphocytes, histiocytes, and small vascular proliferation within the tendon tissue. The enthesis of the tendon to the calcaneus also revealed lymphocyte infiltration in the bone marrow and rheumatoid granulation within the tendon. Throughout the course of his disease, the patient had not been treated with corticosteroids. These facts suggested that enthesis (attachment of tendon to bone) was one of the extraarticular sites of the rheumatoid inflammation and that enthesitis was a possible cause of Achilles tendon rupture in this RA patient.