Organ-specific Lesions Research Articles

Novel pathologic findings and viral antigen distribution in cattle and buffalo calves naturally infected with Foot-and-Mouth disease virus

The Foot-and-Mouth disease is highly contagious acute viral disease of livestock inflicting huge economic loss to the farmers. The limited knowledge regarding the pathological lesions vis-a-vis distribution of the FMDV in lesser explored endocrine glands and important vital organs other than the target organs of infected calves prompted us to take the present investigation to have detailed insight into the pathogenesis. The systematic necropsy of 37 dead calves (cattle-28 and buffalo-9) was conducted, and thin representative tissue pieces from the affected organs were collected in 10% neutral buffered formalin (NBF) for pathological and immunohistochemical investigations. The genomic detection and its serotyping were done by RT-PCR and multiplex-PCR, respectively. Necropsy examination in all cases showed myocardial lesions resembling ‘tigroid heart appearance’. Other organ specific lesions include vesiculo-ulcerative stomatitis, edema of the lungs, petechial hemorrhages, edema of the endocrines, and gastroenteritis. Histopathological examination showed varying sizes of vesicles and ulcerations in stratified squamous epithelium of the tongue, acute necrotizing myocarditis, lymphoid depletion in lymphoid tissues, hepatitis, pancreatitis, thymic hyperplasia, thyroiditis, adrenitis, and enteritis. Positive immunolabeling for viral antigens was observed in endocrine glands, lymphoid organs, lungs, liver, kidneys, and intestine, in addition to other typical locations. The thyroid, adrenal glands, and pancreas, in addition to the tongue and heart, are the tissue of choice for sampling in the field during epidemics. Further, the viral genome and serotype A was confirmed in the affected tissues. This study provides insights into novel tissue tropism and pathogenesis in young calves naturally infected with FMDV.

Chronic heart failure and COVID-19

The coronavirus pandemic has caused a rapid increase in the number of cases and high deaths worldwide. A new coronavirus infection in the presence of an initial cardiac pathology can provoke decompensation of chronic heart failure. The article shows current information on the pathogenesis of COVID-19 and organ-specific lesions that develop in this disease is presented. Data on inflammation and its biochemical markers, on the features of coagulopathy, endothelial damage and microthromboses has been reflected in detail in this article. Particular attention is paid to the role of type 2 angiotensin-converting enzyme receptors and type 2 transmembrane serine protease in the development of organ-specific lesions in COVID-19. The pathogenesis of damage to the cardiovascular system is considered in detail with the presentation of data from latest literature on changes in the myocardium in patients who underwent COVID-19.

COVID-19 and features of cardiovascular involvement

The article provides an overview of current information on the pathogenesis of COVID-19 and organ-specific lesions developing in this disease. The data on inflammation and its biochemical markers, on the features of coagulopathy, endothelial damage and microthrombosis are presented in detail. Particular attention is paid to the role of receptors for angiotensin converting enzyme type 2 and transmembrane serine protease type 2 in the development of organ-specific lesions in COVID-19. The pathogenesis of damage to the cardiovascular system is considered in detail with the presentation of data from foreign literature on changes in the myocardium and the author's results of transthoracic echocardiographic examination in patients who have undergone COVID-19.

Graft dysfunction in simultaneous pancreas kidney transplantation (SPK): Results of concurrent kidney and pancreas allograft biopsies.

Simultaneous pancreas and kidney transplants offer significant therapeutic advantages but present a diagnostic approach dilemma in the diagnosis of rejection. Because both organs are from the same donor, the kidney has been treated traditionally as the "sentinel" organ to biopsy, presumably representing the status of both allografts. Truly concurrent biopsy studies, however, are needed to confirm this hypothesis. We examined 101 concurrent biopsies from 70 patients with dysfunction in either or both organs. Results showed concurrent rejection in 23 of 57 (40%) of cases with rejection; 19 of 57 (33.5%) and 15 of 57 (26.5%) showed kidney or pancreas only rejection, respectively. The degree and type of rejection differed in the majority (13 of 23, 56.5%) of cases with concurrent rejection, with the pancreas more often showing higher rejection grade. Taking into account pancreas dysfunction, a positive kidney biopsy should correctly predict pancreas rejection in 86% of the instances. However, the lack of complete concordance between the 2 organs, the discrepancies in grade and type of rejection, and the tendency for higher rejection grades in concurrent or pancreas only rejections, all support the rationale for pancreas biopsies. The latter provide additional data on the overall status of the organ, as well as information on nonrejection-related pathologies.

Role of abdominal Ultrasonography in diagnosis of acute abdomen

Introduction: Ultrasonography has established itself as an invaluable tool in surgery. In surgical practice, abdominal pain is perhaps the most common symptom encountered and almost in every case of abdominal pain surgeon prefers to use the ultrasound to confirm the diagnosis. Although physical examination of the patient is the most important part in proper diagnosis many a time some positive help is required in the form of investigations especially ultrasonography. Methods: This was a study of hundred patients carried out at a tertiary care hospital admitted with complaints of severe abdominal pain except those with a history of trauma or with a history of chronic abdominal pain. Clinical history, physical examination, ultrasonography, per operative findings and histo-pathological examination were used to come to a final conclusion. Result: In this study ultrasonography was diagnostic in 78% of patients. Two patients were misdiagnosed and in 20 patients other investigations were required for the confirmation of diagnosis. The sensitivity and specificity of ultrasound in diagnosing acute appendicitis, renal calculus, liver abscess, mesenteric lymphadenitis, acute pancreatitis and ovarian cyst was 100% and in calculus cholecystitis it was 93.75% and 100% respectively. Conclusion: Ultrasonography is superior in organ system imaging. It helps in showing organ specific lesions and its accurate measurement which is helpful in follow up and response to treatment. Ultrasonography is also helpful in diagnosing alternative disease and to reduce negative laparotomy rate.

Etiology and pathophysiology of chronic transplant dysfunction.

Chronic transplant dysfunction (CTD) is the predominant cause of late graft failure. The common histopathological feature in all transplanted organs is intimal hyperplasia accompanied by organ specific lesions. The knowledge about CTD is incomplete, and there is no therapy to prevent or treat it. This review describes the current knowledge on the etiology of CTD, with emphasis on kidney transplants, and postulates a pathophysiologic route through which CTD may develop.

Etiology and pathophysiology of chronic transplant dysfunction

Abstract Chronic transplant dysfunction (CTD) is the predominant cause of late graft failure. The common histopathological feature in all transplanted organs is intimal hyperplasia accompanied by organ specific lesions. The knowledge about CTD is incomplete, and there is no therapy to prevent or treat it. This review describes the current knowledge on the etiology of CTD, with emphasis on kidney transplants, and postulates a pathophysi ologic route through which CTD may develop.

Involvement of Peritoneal Dendritic Cells in the Induction of Autoimmune Prostatitis

We have been working within a model of autoimmune prostatitis induced by the intraperitoneal administration of saline extract of rat male accessory glands (RAG) associated to liposomes. The intraperitoneal administration of RAG-liposomes elicits both primary and secondary cellular autoimmune responses to RAG as well as organ-specific lesions. To evaluate the participation of dendritic cells (DC) in the induction of the autoimmune response, we purified peritoneal DC (PDC) after a single injection of RAG-liposomes and we characterized this population by morphology and phenotype. Based on adherence and morphologic criteria, we determined that PDC comprised approximately 1% of the total peritoneal cells. The ultrastructure of the dendritic cell enriched fraction was assessed by electron microscopy. By FACS analysis, PDC showed a two to three-fold increase in expression of the IA molecule compared to macrophages. They expressed low but positive levels of the CD14 marker, and intermediate levels of both CD11b (Mac-1) and CD54 (ICAM-1) adhesion molecules. In addition, PDC transferred either intra-venously or intraperitoneally efficiently elicited the autoimmune response to RAG in normal receptors. These results support the involvement of peritoneal dendritic cells in the induction of autoimmune prostatitis, modifying the idea of macrophages as the single antigen presenting cell in the peritoneal cavity.

A Sudden Death Syndrome Induced in Poults and Chicks Fed Diets Containing Fusarium fujikuroi with Known Concentrations of Moniliformin

A sudden death syndrome was induced in chicks and poults fed diets containing Fusarium fujikuroi, formulated to contain 0-330 mg/kg moniliformin (M) with or without the maximum recommended therapeutic concentration of monensin. Lesions of monensin toxicosis were not observed. Clinical signs were referable to cardiac dysfunction (sudden death, dyspnea, cyanosis, depression). Poults and chicks dying early in the study had no gross lesions or had lesions of right ventricular dilation. Treated poults and chicks dying late in the study or euthanatized at termination of the study had lesions of bilateral myocardial hypertrophy, usually concentric. Absolute heart weights and relative heart weights, expressed as a percentage of body weight, were significantly greater in treated birds than controls (P < 0.05), whereas body weights were significantly less (P < 0.05). Microscopically, lesions progressed from acute myocardial degeneration to necrosis, fibrosis, and hypertrophy. Ultrastructural findings were consistent with the gross and microscopic lesions. Serum pyruvate concentrations were a useful indicator of M-induced cardiotoxicosis. Concentrations of serum pyruvate increased with increased concentration of dietary M, but were not affected by addition of monensin to the diet. In chicks ingesting 40-300 mg/kg M, serum pyruvate concentrations were significantly greater (P > 0.05) than those in controls (controls, 0.28 +/- 0.08 mmol/liter; exposed 0.38 +/- 0.11-0.55 +/- 0.13 mmol/liter). Poults ingesting 80-330 mg/kg M had significantly greater serum pyruvate concentrations than controls (controls 0.33 +/- 0.09 mmol/liter; exposed 0.43 +/- 0.13-1.00 +/- 0.006 mmol/liter). The Vetronics System was used to evaluate electrocardiographic alterations in a limited number of chicks and poults surviving to the end of the feeding trial. Electrocardiographic alterations in poults and chicks fed diets containing > or = 40 mg/kg and > or = 160 mg/kg M, respectively, were consistent with ventricular hypertrophy, myocardial injury, and hypoxia. Electrocardiographic alterations were more striking in poults than in chicks. Altered myocardial metabolism due to M toxicosis, in conjunction with the unusual susceptibility of domestic poultry to altered cardiac metabolism, is believed to be the cause of the organ-specific lesions in these birds. These findings suggest that cardiac injury with subsequent alterations in cardiac electrical conductance may be a cause of the sudden deaths observed in poultry chronically intoxicated with dietary M.

Isolation and characterisation of two haemorrhagic proteins (HTa and HTb) from the venom of Bitis gabonica (gaboon viper)

Two distinct haemorrhagic proteinases, HTa and HTb, were isolated from the venom of Bitis gabonica by gel filtration and ion-exchange chromatography with native mol. wts of 180,000 and 111,000, respectively. After reduction with dithiothreitol, smaller mol. wts of 77,600 and 69,200 were recorded for HTa and HTb, suggesting that under native conditions the haemorrhagins exist as dimeric molecules. Both toxins possessed caseinolytic and collagenase activity although HTa was 15–36 times more potent than HTb with respect to collagenase activity. No zinc could be detected in the toxins; however, dialysis against ethylenediamine tetracetic acid (EDTA) reduced caseinolytic activity, suggesting the dependence of the latter on other metal ions. HTa and HTb had a marked effect on the intrinsic cascade coagulation mechanism (factors IX, XI and XII) but no effect on the final common coagulation pathway (factor X and prothrombin). Light and electron microscopical studies demonstrated that both HTa and HTb caused organspecific lesions, with the lungs, diaphragm and body wall muscle being most affected. HTa caused widespread haemorrhage whilst HTb caused discrete focal lesions near the site of injection and elsewhere. However, both toxins appeared to cause capillary rupture by the separation of cells from one another and both caused cell detachment and cell death of bovine endothelial cells cultured in vitro, consonant with the massive disruption of capillaries seen in vivo.

Mast Cells in Accessory Glands of Experimentally Induced Prostatitis in Male Wistar Rats

We studied the histological modificatious in the accessory glands of autoimmune rats. Adult male Wistar rats were id immunized three times with saline extract of rat male accessory glands (RAG) chemically modified (MRAG) in complete Freund's adjuvaut (CFA) (groups 1, 2, and 3). Prior to the first immunization with MRAG-CFA groups 2 and 3 received peritoneal cells obtained from rats that had been injected 2 or 24 hr previously with low doses of RAG. Furthermore, an additional group (group 4) ip immunized with liposome-associated-RAG was incorporated. The delayed-type hypersensitivity response studied 10 or 15 days after first immunization was positive for rats of groups 1, 3, and 4, while it was negative for rats of group 2. Serum samples obtained on Day 45 and studied by ELISA showed high levels of autoantibodies in groups 1 and 2 and lower levels of autoantibodies in group 3, but did not show autoantibodies in group 4. The histological studies performed 10 days after the last immunization showed organ-specific lesions in the accessory glands in animals of groups 1, 3, and 4. Infiltration of mononuclear cells was the main alteration in group 1, while infiltration of mast cells and polymorphonuclear leukocytes were present in specimens of groups 3 and 4. The main finding of this study was a significant increase ( P < 0.0005) in the extent of mast cell degranulation in the specimens of accessory glands stained with toluidine blue. Our results suggest that mast cells are activated in our experimental model of autoimmune disease.

The nonobese diabetic mouse model. Independent expression of humoral and cell-mediated autoimmune features.

Nonobese diabetic (NOD) mice present concomitant signs of cell-mediated and humoral autoimmunity. Whereas the involvement of the cell-mediated manifestations in the pathogenesis of diabetes has been clearly demonstrated, the origin and the relevance of the humoral manifestations is still unclear. In the present study, we have tried to determine whether the humoral manifestations observed in NOD mice were secondary to the cell-mediated antiislet reaction, or whether they resulted from an autonomous polyclonal activation of B cells, a possibility suggested by the notorious presence of antilymphocyte antibodies with thymocytotoxic properties, in the serum of old NOD females. To discriminate between the two alternatives, we have followed the titers of thymocytotoxic autoantibodies in aging males and females, as well as in F1 hybrids where the organ-specific disease is recessive, and in back-crossed mice where the susceptibility genes responsible for insulitis and diabetes have segregated. In addition to thymocytotoxic antibodies, we have also screened the sera of these animals for hyperglobulinemia, antiinsulin, and anti-DNA autoantibodies that are classically associated with polyclonal B cell activation in autoimmune strains of mice. The results indicate that these humoral anomalies are clearly disconnected from the occurrence of diabetes and even of insulitis. Lymphocytotoxic antibodies appear several weeks after the onset of insulitis in NOD mice, are not correlated with disease occurrence and have no predictive value for its onset. The humoral manifestations that include, beside thymocytotoxic antibodies, antiinsulin antibodies, hyperglobulinemia, but no anti-DNA antibodies, are found at the same frequency in F1 mice as in parental mice in spite of the fact that the former are practically free of insulitis lesions. These anomalies are also randomly distributed among back-crossed mice independently of the presence and the severity of the organ-specific lesions. Altogether, these results suggest that NOD mice, like other autoimmune strains, suffer from a genetically inherited defect of B cell regulation resulting in the hyperproduction of natural autoantibodies.

Natural killer cells and autoimmunity.

In various autoimmune diseases it appears that NK activity is impaired, and that this phenomenon is significant in disease development. Impairment of NK activity may be the result of two different mechanisms. In systemic autoimmune diseases, in which various target organs are involved (nonorgan-specific), the peripheral blood NK level is generally lower than normal. This most likely allows the expression of autoimmune phenomena such as B cell hyperactivity and polyclonal antibody production, as is seen in SLE, due to a defect in the termination of the immune response. In autoimmune diseases with more localized, organ-specific lesions one can detect increased NK activity at the target organ itself. In these instances, the cytotoxic characteristic of the NK cell is more prominent. This theory explains why both increased and decreased NK activity may be observed in autoimmune diseases. In some disorders in which decreased NK activity was suspected of being crucial, immunomodulators, known to increase NK activity, were administered. Yet it is still difficult to separate the NK activity from the effect of the remaining immune system.