Diffuse Mononuclear Cell Infiltration Research Articles

A case of Mikulicz’s disease complicated with severe interstitial nephritis associated with IgG4

A 48-year-old woman who had bilateral swelling in the eyelids and submandibular region was admitted. Clinical findings suggested that her renal function had deteriorated. Laboratory data showed renal insufficiency (2.52 mg/dl), hypergammaglobulinemia (IgG 3,729 mg/dl, IgA 124 mg/dl, IgM 73 mg/dl). Gallium-67 scintigram indicated abnormal uptake in bilateral lacrimal glands, submandibular glands, and kidneys. A diagnosis of Mikulicz's disease and interstitial nephritis was made, since biopsy specimens of her lacrimal gland and minor salivary gland showed diffuse infiltration of lymphocytes. In addition, renal biopsy specimens showed diffuse severe interstitial infiltration of IgG4-positive mononuclear cells. Symptoms and laboratory data normalized in response to methylprednisolone semi-pulse therapy and prednisolone 50 mg/day. Mikulicz's disease was recently reported to be IgG4 associated disease. In our case, Mikulicz's disease complicated with diffuse severe interstitial nephritis was successfully treated by corticosteroid. The present case supports the hypothesis that IgG4-related autoimmune disease could be causes of Mikulicz's disease and interstitial nephritis.

Screening of vesicoureteral reflux in pediatric patients with kidney transplantation showing non‐specific interstitial fibrosis and tubular atrophy with interstitial Tamm–Horsfall protein deposits in protocol allograft biopsy

Interstitial fibrosis and tubular atrophy (IF/TA) in kidney allografts are induced by multiple factors, and although much effort has been devoted on the classification of IF/TA, clarification of the causes of non-specific IF/TA is equally important for appropriate therapy. Tamm-Horsfall protein (THP) in renal tissue can be a useful marker for the histological expression of urine backflow and suspected vesicoureteral reflux (VUR). Here, we examined the presence of VUR in pediatric recipients with interstitial THP deposits in kidney allografts to clarify the cause of non-specific IF/TA. Ten pediatric patients showing interstitial THP deposits with non-specific IF/TA were enrolled and voiding cystourethrography was performed. Major histological findings of these patients were interstitial mononuclear cell infiltration and fibrosis associated with interstitial THP deposits. The semiquantitative grading scores of IF/TA were as follows: (i) mild IF/TA (n = 3); (ii) moderate IF/TA (n = 3); and (iii) severe IF/TA (n = 4). In the severe grade, diffuse interstitial mononuclear cell infiltrates were prominent with the appearance of thyroidization classically observed in chronic pyelonephritis. Eight of ten patients (80%) had VUR into the graft. Although symptomatic pyelonephritis was not observed in any of the patients, asymptomatic bacteriuria was detected in 40.0% of the patients. There was no significant correlation between VUR grade and IF/TA histological score. The patients without VUR also showed mild or severe IF/TA. Therefore, VUR and urinary flow stasis accompanied by asymptomatic urinary tract infection appear to be the causes of interstitial mononuclear cell infiltration and fibrosis associated with interstitial THP deposits in kidney allografts.

IL-17A-Expressing T Cells Are Essential for Bacterial Clearance in a Murine Model of Hypersensitivity Pneumonitis

Hypersensitivity pneumonitis (HP) is an inflammatory lung disease characterized by a diffuse mononuclear cell infiltrate in the lung that can progress to pulmonary fibrosis with chronic exposure to an inhaled Ag. We previously reported that C57BL/6 mice repeatedly exposed to the ubiquitous microorganism Bacillus subtilis develop mononuclear infiltrates in the lung that contain Vgamma6/Vdelta1(+) gammadelta T cells. In the absence of this T cell subset, mice treated with B. subtilis had significantly increased collagen deposition in the lung, suggesting a regulatory role for Vgamma6/Vdelta1(+) gammadelta T cells. To further investigate the role of Vgamma6/Vdelta1(+) gammadelta T cells in B. subtilis-induced lung fibrosis, we exposed transgenic Vgamma6/Vdelta1 mice to this microorganism and found decreased collagen content in the lung compared with wild-type C57BL/6 mice. Cytokine analysis of lung homogenates from wild-type C57BL/6 mice demonstrated increased IL-17A concentrations with repeated exposure to B. subtilis. In the absence of IL-17 receptor signaling, IL-17ra(-/-) mice had delayed clearance of B. subtilis with increased lung inflammation and fibrosis. Although IL-17A was predominantly expressed by Vgamma6/Vdelta1(+) T cells, a compensatory increase in IL-17A expression by CD4(+) T cells was seen in the absence of gammadelta T cells that resulted in similar levels of IL-17A in the lungs of TCRdelta(-/-) and wild-type C57BL/6 mice. In combination, our data suggest an important role for IL-17A-expressing T lymphocytes, both gammadelta and alphabeta T cells, in eliminating this microorganism that prevents excessive inflammation and eventual lung fibrosis in this murine model of B. subtilis-induced hypersensitivity pneumonitis.

Th17-Polarized Immune Response in a Murine Model of Hypersensitivity Pneumonitis and Lung Fibrosis

Hypersensitivity pneumonitis is an environmental lung disease characterized by a diffuse mononuclear cell infiltrate in the lung that can progress to pulmonary fibrosis with chronic exposure to an inhaled Ag. Using a well-established murine model of hypersensitivity pneumonitis, we repeatedly exposed C57BL/6 mice to Saccharopolyspora rectivirgula to investigate whether T cells are required for lung fibrosis. In the absence of alphabeta T cells, TCRbeta(-/-) mice exposed to S. rectivirgula for 4 wk had markedly decreased mononuclear infiltrates and collagen deposition in the lung compared with wild-type C57BL/6 mice. In contrast to CD8(+) T cells, adoptive transfer of CD4(+) T cells reconstituted the S. rectivirgula-induced inflammatory and fibrotic response, suggesting that the CD4(+) T cell represents the critical alphabeta T cell subset. Cytokine analysis of lung homogenates at various time points after S. rectivirgula exposure failed to identify a predominant Th1 or Th2 phenotype. Conversely, IL-17 was found in the lung at increasing concentrations with continued exposure to S. rectivirgula. Intracellular cytokine staining revealed that 14% of CD4(+) T cells from the lung of mice treated with S. rectivirgula expressed IL-17A. In the absence of IL-17 receptor signaling, Il17ra(-/-) mice had significantly decreased lung inflammation and fibrosis compared with wild-type C57BL/6 mice. These data are the first to demonstrate an important role for Th17-polarized CD4(+) T lymphocytes in the immune response directed against S. rectivirgula in this murine model of hypersensitivity pneumonitis and pulmonary fibrosis.

Contrasting levels of in vitro cytokine production by rheumatoid synovial tissues demonstrating different patterns of mononuclear cell infiltration.

Synovial membrane samples obtained at knee arthroplasty from 22 patients with rheumatoid arthritis (RA) were characterized histologically. Two groups were identified. Tissue samples from 15 patients demonstrated multiple focal lymphoid aggregates of mononuclear cells (group A). Samples from the remaining seven patients demonstrated diffuse mononuclear cell infiltration (group B). Samples of each synovial membrane (0.25 g) were cultured for cytokine production. The highest levels of IL-1 beta and IL-6 were produced by group A tissues: 19.1 +/- 19.6 ng/ml IL-1 beta (mean +/- s.d.) and 264.4 +/- 301.9 ng/ml IL-6, versus 3.8 +/- 6.6 ng/ml and 54.7 +/- 42.6 ng/ml respectively. Small quantities of IL-2 and IL-4 were measured in both groups: the levels of IL-2 in group A cultures were highest (P = 0.04). Moreover, using MoAbs, the most intense cytokine staining in the tissues was detected in group A. Similar total numbers of each cell subpopulation and similar quantities of immunoglobulin and rheumatoid factor synthesis were measured in both groups. It is suggested that the presence of multiple focal lymphoid aggregates associated with higher levels of cytokine production observed in group A represent a greater degree of immunological activation, and may represent a subgroup of patients with a greater potential for articular destruction.

Atypical B‐cell infiltrate in a pediatric patient: diagnostic and pathogenetic considerations

Pediatric primary central nervous system lymphoma (PCNSL) represents1–1.5% of all PCNSL. Pediatric PCNSL are usually high grade B‐cell lymphoma (30%) or anaplastic large cell lymphomas. Herein we report a 15 year‐old male with a well‐circumscribed, enhancing mass centered on the right thalamus with mass effect on the 3rd ventricle and obstructive hydrocephalus. Endoscopic biopsy produced only hemorrhage; repeat biopsy three months later produced multiple fragments of pink‐tan soft tissue including pineal gland, grey matter, granulation tissue, choroid plexus, and a diffuse mononuclear cell infiltrate composed of a mixture of small round and large atypical lymphoid cells with irregular vesicular nuclei, 2 to 3 nucleoli attached to the nuclear membrane, and moderately abundant eosinophilic cytoplasm. The large lymphoid cells showed immunoreactivity for CD20, PAX‐5, and CD79a (B‐cell markers) but were negative for epithelial and germ cell markers; small T lymphocytes were also present. The lymphocytic process infiltrated brain tissue containing atypical astrocytes and large binucleated neurons. Immunoglobulin heavy chain (Ig‐VDJ; B‐cell) and T‐cell receptor (TCR) beta and gamma gene rearrangement studies showed a monoclonal B‐cell population. This atypical B‐cell infiltrate with features of lymphoma may have arising in an inflammatory infiltrate accompanying a pre‐existing glio‐neuronal tumor.

Reversible acute renal failure associated with clomipramine-induced interstitial nephritis

We describe a 41-year old man with obsessive-compulsive neurosis who developed acute renal failure (ARF) due to acute interstitial nephritis (AIN) during 6 weeks of treatment with clomipramine hydrochloride (CPH). He had a slight fever, mild arthralgia, appetite loss, and diarrhea after taking CPH. On admission, he showed serum creatinine (sCr) of 7.31 mg/dl, and creatinine clearance (Ccr) of 2.5 ml/min. He subsequently became anuric and required hemodialysis. Renal biopsy revealed AIN with diffuse mononuclear cell infiltration. After the withdrawal of CPH and treatment with prednisolone (PSL) 0.5 mg/kg per day, his urinary output improved, along with improvement of his renal function; therefore hemodialysis was finally discontinued. To our knowledge, this is the first case report of AIN induced by clomipramine.

Expression of BAFF and BAFF‐R in the synovial tissue of patients with rheumatoid arthritis

Objective: The elevated expression of B‐cell‐activating factor belonging to the TNF family (BAFF) is associated with systemic autoimmune disease, including rheumatoid arthritis (RA). The present study was undertaken to determine the distribution of BAFF and its receptor BAFF‐R in the cells residing in the rheumatoid synovium.Methods: The expression of BAFF and BAFF‐R in synovial tissues obtained from 12 RA patients was examined by immunohistochemistry and flow cytometry. The mRNA expression of these molecules was determined by reverse transcriptase polymerase chain reaction (RT‐PCR). Soluble BAFF levels were measured with an enzyme‐linked immunosorbent assay (ELISA). Fibroblast‐like synoviocytes (FLS) purified from the RA (RA‐FLS) were co‐cultured with peripheral B cells. The degree of apoptosis in the B cells was measured to assess the effects on the viability of the B cells.Results: The RA synovium showed focal or diffuse infiltration of mononuclear cells (MNCs), and one specimen showed germinal centre (GC)‐like structures. Synovial sublining cells, but not lining cells, expressed BAFF. These sublining cells were negative for BAFF‐R. BAFF and BAFF‐R were expressed in B and T cells extracted from the RA synovium. Notably, RA‐FLS spontaneously expressed cytoplasmic BAFF after 4–6 passages; however, they did not express BAFF or BAFF‐R on their cell surface. RA‐FLS could support the survival of B cells by preventing their apoptosis, but its effect on B cells might not be BAFF dependent.Conclusions: BAFF and BAFF‐R are widely expressed in the RA synovium. The cells residing in the RA synovium might affect each other through BAFF.

Antihypertensive therapy induces compartment-specific chemokine expression and a Th1 immune response in the clipped kidney of Goldblatt hypertensive rats

The present study examined the pathogenesis of interstitial inflammation and fibrosis in antihypertensively treated rats with two-kidney, one-clip hypertension. Hypertensive rats were randomized into four groups: no treatment and moderate, intermediate, and intensified lowering of blood pressure with increasing doses of a vasopeptidase inhibitor for 6 wk. The vasopeptidase inhibitor dose dependently lowered blood pressure. The tubulointerstitial damage was accompanied by a diffuse infiltration of mononuclear cells and circumscript mononuclear inflammatory cell cluster formation consisting mainly of T cells and to a lesser degree of macrophages and B cells. Real-time PCR analyses showed a dose-dependent induction of MCP-1 and the Th1-type chemokines IP10 and Mig as well as their receptor CXCR3 and the Th1 cytokine IFN-gamma. In situ hybridization and laser microdissection revealed a strong expression of these Th1-associated transcripts in the clusters and, in the case of MCP-1, also diffusely in the interstitium. The inflammation was accompanied by the appearance of myofibroblasts and synthesis of the fibrogenic factor plasminogen activator inhibitor-1 as well as the collagenase matrix metalloproteinase-2, leading to collagen I upregulation and interstitial scarring. No inflammation or fibrosis was found in normotensive rats treated with the vasopeptidase inhibitor. The renal injury in the clipped kidney is accompanied by compartment-specific chemokine expression and cell cluster formation of Th1 specificity associated with upregulation of fibrogenic proteins and matrix metalloproteinases. These findings suggest that the Th1 chemokines IP10 and Mig as well as their receptor CXCR3 are potential targets for therapeutic interventions in ischemic nephropathy.

Tubulointerstitial nephritis and uveitis syndrome associated with hyperthyroidism

We report a 17-year-old male patient with tubulointerstitial nephritis and uveitis (TINU) associated with hyperthyroidism. He presented with a 2-month history of fatigue, loss of appetite, low-grade fever, and a 12-kg weight loss when he was admitted to our hospital. He had iritis, which was complicated by fibrin in the anterior chamber, diagnosed by slit-lamp examination. On laboratory examinations, deteriorated renal function (blood urea nitrogen level was 25.9 mg/dl and creatinine level was 2.82 mg/dl) and elevated urinary levels of N-acetyl-beta-D-glucosaminidase (33.1 U/l) and beta2-microglobulin (78,600 microg/l) were observed. Serum thyroid-stimulating hormone (TSH) was undetectable, at less than 0.01 microIU/ml, and free triiodothyronine and free thyroxine were elevated, up to 5.23 pg/ml and 2.85 ng/dl, respectively. The titers of antithyroglobulin and antithyroid microsomal and TSH-receptor antibodies were not elevated. Abdominal and thyroidal ultrasonography showed evident bilateral enlargement of the kidneys and diffuse enlargement of the thyroid gland. Iodine-123 scintigraphy showed low uptake in the thyroid gland. The biopsied renal specimen showed mild edema and severe diffuse infiltration of mononuclear cells and few eosinophils in the interstitium, without any glomerular or vascular abnormalities. Based on the clinical features and pathological findings, a diagnosis of TINU syndrome with associated hyperthyroidism was made. Treatment was started with 30 mg/day of prednisolone. The iritis disappeared, and the patient's clinical status improved remarkably. This case suggests the possibility of thyroid dysfunction in some patients with TINU syndrome, and we believe thyroid function should be measured in all TINU patients. Moreover, histopathological diagnosis of the thyroid glands before treatment is necessary for TINU patients with thyroid dysfunction.

Efficacy of Mycophenolic Acid Combined With KRP-203, a Novel Immunomodulator, in a Rat Heart Transplantation Model

To explore a more effective and less toxic immunosuppressive strategy in organ transplantation, we recently developed the novel sphingosine-1-phosphate receptor agonist KRP-203. This study examined the efficacy of KRP-203 combined with mycophenolic acid (MPA), an active metabolite of mycophenolate mofetil, in rat heart allografts. Heterotopic heart transplantation was performed in a rat combination of DA (MHC haplotype: RT1(a)) to Lewis (RT1). The recipients were divided into 12 groups (n = 5-7): Syngeneic (Lewis to Lewis), Vehicle, KRP-203 (0.3 and 1 mg/kg), MPA (10 and 20 mg/kg), 10 mg/kg MPA with KRP-203 (0.03, 0.3, 1, and 3 mg/kg), and 20 mg/kg MPA with KRP-203 (0.3 and 1 mg/kg). MPA, KRP-203, and vehicle were given orally. The mean days of survival were 5.8 (vehicle), 7 and 7.9 (0.3 and 1 mg/kg KRP-203, respectively), 12.7 and >54.4 (10 and 20 mg/kg MPA), >39.6 and >30.5 (10 mg/kg MPA with 1 and 3 mg/kg KRP-203), >100 and >87.8 (20 mg/kg MPA with 0.3 and 1 mg/kg KRP-203). Histologic and immunohistochemical analysis revealed that diffuse mononuclear cell infiltration (macrophages and T cells), hemorrhage, myocardial necrosis and fibrosis, and expression of endothelin-1, transforming growth factor-beta1, monocyte chemoattractant protein-1, interleukin-8, and E-selectin were markedly diminished in the allografts treated with MPA combined with KRP-203. Pharmacokinetic experiments indicated no interaction between MPA and KRP-203, and both combination regimens were well tolerated. Combination therapy of MPA with KRP-203 has a therapeutic potential as a novel immunosuppressant strategy in clinical transplantation.

Nephrotic Syndrome and Renal Failure After Allogeneic Stem Cell Transplantation: Novel Molecular Diagnostic Tools for a Challenging Differential Diagnosis

Sudden onset of nephrotic syndrome after allogeneic stem cell transplantation is rare and has been associated mostly with membranous glomerulonephritis related to chronic graft-versus-host disease (cGVHD). We report a case of nephrotic syndrome and rapidly progressive renal failure occurring in a young woman 3 years after allogeneic stem cell transplantation from her HLA-identical brother. In the renal biopsy, a diffuse mononuclear cell infiltrate was observed. Furthermore, histological analysis, immunofluorescence, and electron microscopy of the kidney specimen defined the diagnosis as minimal change disease, a T-cell-mediated glomerulopathy associated with lymphoproliferative disorders, but that has never been described as an isolated manifestation of cGVHD. The differential diagnosis was performed by using immunohistochemistry and laser capture microdissection combined with Taq-Man quantitative polymerase chain reaction. Infiltrating mononuclear cells in renal tissue consisted of T cells expressing DNA levels of a Y chromosome-specific gene quantitatively similar to those observed in a male subject, showing that these cells derived from the transplant donor and definitely excluding leukemia relapse. However, the large number of infiltrating T cells allowed the possibility that in this patient, minimal change disease could be related to an atypical form of GVHD. This is the first study to use molecular techniques to show the differential diagnosis of nephrotic syndrome after allogeneic stem cell transplantation. This novel method approach might represent a key tool to characterize kidney infiltrate after allogeneic stem cell transplantation.

Predominant tubulointerstitial nephritis in a patient with systemic lupus nephritis

In most cases of systemic lupus erythematosus (SLE), glomerular lesions are the main renal complication. Although tubulointerstitial lesions are often associated with severe glomerular lesions, predominant or isolated tubulointerstitial injury in the presence of minimal glomerular abnormalities with SLE, so-called predominant tubulointerstitial lupus nephritis, is rare. Only ten cases are reported in the English literature. Herein, we describe the case of a 64-year-old man with SLE who presented with acute renal deterioration attributable to acute tubulointerstitial nephritis. Renal biopsy showed diffuse infiltration of inflammatory mononuclear cells in the interstitium and tubulitis without significant glomerular lesions. Immunofluorescence study revealed positive staining for IgG, C3, and C1q along the renal tubular basement membrane (TBM). Electron microscopy also showed electron-dense deposits in the TBM. Other causes of tubulointerstitial injury, such as drug use and infection, were ruled out. Taking these findings together with the presence of antitubular basement membrane antibody, predominant tubulointerstitial lupus nephritis was diagnosed. Treatment with oral corticosteroids for 6 weeks improved renal function. Even after tapering of the corticosteroid, renal function and serological markers of SLE activity have remained stable in this patient for more than 12 months.

Development of gastric adenocarcinoma in Mongolian gerbils after long-term infection with Helicobacter pylori.

The experimental evidence that long-term colonization of Helicobacter pylori results in the development of gastric cancer in Mongolian gerbils has been reported only by two Japanese groups to date. This study aimed to investigate the carcinogenicity of H. pylori infection in a Mongolian gerbil model. Thirty-six Mongolian gerbils (inner Mongolian origin) were divided into two groups (male to female ratio, 1:1) and orally inoculated with a standard H. pylori strain (ATCC43504) or H. pylori161 (isolated from a Chinese patient with gastric adenocarcinoma), respectively, once a week for 5 weeks. Another 10 control gerbils were given phosphate-buffered saline. The animals were killed 8, 20, 28 and 84 weeks after inoculation for bacterial and histological examination. Seven inoculated gerbils died at the week 42. Overall, H. pylori colonization was detected in 24 (83%) of the 29 available inoculated gerbils. The gastric lesions were aggravated gradually over time. At week 84, moderate to severe gastritis, characterized by diffuse infiltration of mononuclear cells and formation of multiple lymphoid follicles in mucosa and submucosa, and even the lymphoepithelial lesions, were observed. Epithelial hyperplasia were dominant in almost all gerbils. Four (24%) of the 17 animals had hyperplastic polyps. Intestinal metaplasia were rarely seen (in three gerbils). Well-differentiated gastric adenocarcinomas developed in three (18%) of the 17 gerbils after 84 weeks. Of the three gerbils, one female gerbil was infected with H. pylori161 and the others (one male and one female) were infected with ATCC43504. The present study reconfirms that H. pylori infection alone can induce gastric adenocarcinoma in Mongolian gerbils and suggests that different species of gerbil and both standard and clinically isolated H. pylori strains can be used for investigating the carcinogenesis of H. pylori. This is the first report of the development of gastric cancer in female gerbils, which highlights the importance of using both sexes to investigate the pathogenesis of H. pylori and whether host susceptibility is influenced by sex.

Chronic rejection of murine cardiac allografts discordant at the H13 minor histocompatibility antigen correlates with the generation of the H13-specific CD8+ cytotoxic T cells.

Minor histocompatibility antigen (mHag) discordances have been shown to play a critical role in graft-versus-host disease after bone marrow transplantation. However, the role of mHag in rejection of solid-organ allografts remains unknown. Therefore, the goal of this study was to define the role of a single mHag discordance derived from the polymorphic H13 allele in the development of cardiac allograft rejection in mice. The H13a and H13b alleles encode for the SSVVGVWYL (SVL9) and SSVIGVWYL (SIL9) mHag bound to the H2Db molecule, respectively. C56BL/10SnJ (H13a) cardiac allografts were transplanted into congenic B10.CE-H13b Aw(30NX)/Sn (H13b) mice. Allograft function was monitored daily and rejection was defined by cessation of heart beat. Rejection was confirmed histologically. The phenotypic and functional characteristics of the graft-infiltrating cells were analyzed by in situ and in vitro staining with H13a-specific tetramers and by chromium-51 (51Cr)-release assay, respectively. Sixty-five percent of H13-incompatible allografts were rejected in 37.0+/-14.5 days. Sixty-eight percent of the H13a allografts transplanted into H13a-sensitized mice were rejected earlier, in 27.6+/-15.9 days. Rejected allografts showed histopathologic signs of chronic rejection with diffuse mononuclear cell infiltration, concentric intimal hyperplasia, and fibrosis. Both CD8+ (87%) and CD4+ (13%) T cells were observed in rejected allografts. In addition, 60% of the graft-infiltrating CD8+ T cells recognized a H2Db/SVL9 tetramer. Graft-infiltrating CD8+ T cells showed a significant H2Db-restricted, SVL9-specific cytotoxic activity. A single mHag discordance, as demonstrated with H13 disparity, results in the pathogenesis of chronic rejection of major histocompatibility complex-matched vascularized solid-organ allograft.

Miocardiopatia dilatada em pacientes com infecção chagásica crônica: relato de dois casos fatais autóctones do Rio Negro, Estado do Amazonas

Two fatal cases of human chronic chagasic cardiomyopathy are reported, for the first time, in autochthonous patients from Rio Negro, Amazonas state. Both cases, (45 year old man and 44 year old woman) who were born and lived their whole lives in the Rio Negro region, in the northern part of the state of Amazonas, reported having been bitten several times by triatomine bugs in their camping huts while gathering pia ava fibers. The patients, who had confirmed positive serology for Trypanosoma cruzi antibodies (indirect immunofluorescence, ELISA and Western blot), developed in the last 5-7 years a progressive cardiac failure, with global enlargement of the heart, atrioventricular and left bundle branch block, ventricular extrasystoles, both dying from irreversible cardiac insufficiency. The histopathology of a post-mortem surgical cardiac biopsy performed in one of the cases showed chronic myocarditis with diffuse mononuclear cell infiltrates, with areas of focal cell accumulation, fibrosis, lytic necrosis of myocardial fibers, suggestive of chronic chagasic myocarditis. An in situ PCR was positive for Trypanosoma cruzi.

Overexpression of cardiotrophin-1 and gp130 during experimental acute Chagasic cardiomyopathy

Cardiotrophin-1 (CT-1), a cytokine with structural similarities to interleukin-6, has been shown to signal through gp130-dependent pathways. In vitro, CT-1 promotes the survival and induces hypertrophy of neonatal cardiomyocytes. Since acute Chagas' disease involves an inflammatory response followed by chamber dilation, with subsequent compensatory hypertrophy, we hypothesized CT-1 and gp130 may participate in this disease process. Thus, we investigated expression and localization of these moieties during acute Chagasic cardiomyopathy. Lewis rats ( n=6/group) were either inoculated with cell culture-derived T. cruzi trypomastigotes or saline, and sacrificed 15 days later. Hearts were collected for histology, immunohistochemistry (IHC), mRNA, and protein analyses. Histology showed dense myocardial infection with amastigotes and diffuse mononuclear cell infiltrate. Northern blot analysis showed low level expression of CT-1 mRNA in controls, which was markedly elevated in infected animals (2.5-fold; P<0.001). Similarly, Western blotting showed a twofold elevation of CT-1 protein in infected animals ( P<0.025). Likewise, levels of both gp130 mRNA and protein were low in controls, but were approximately threefold higher in infected animals. IHC showed weak and diffuse staining for CT-1 in control myocardium, while intense staining especially localized to the cytoplasmic region of cardiomyocytes, was found in infected animals. Although gp130 immunoreactivity was observed in both normal and infected myocardium, more intense staining was found in infected animals. Unlike CT-1, gp130 staining was granular, and was present in both the cytoplasm as well as in the perinuclear region. These data suggest that there is substantial overexpression of both CT-1 and gp130 in the heart during acute Chagasic carditis. Their overexpression may provide a mechanism for myocyte protection, and for development of compensatory cardiac hypertrophy following myocardial damage in this form of cardiomyopathy.

Gastritis and gastric perforation due to Habronema spp. in the horse

A three-year-old horse was admitted to the Tehran Veterinary faculty teaching hospital with colic symptoms. The horse died with severe pain after two hours. Necropsy findings revealed a heavy worm infestation in the stomach. Parasitological examinations identified massive in vasion of Habronema muscae on the stomach mucosal surface and Draschia megastoma in the deep layer of mucosa and muscles. Histopathological sections showed two separate lesions including diffuse infiltration of mononuclear inflammatory cells with a number of eosinophils in the mucosa and submucosa that suggested eosinophilic gastritis. Another finding was a large granulation mass in the deep layer of the submucosa that contained granulomatous necrotic tissue and cross sections of D. megastoma.

Salivary glands in alcoholism: a histologic and sialographic study.

A qualitative and quantitative histological analysis of minor salivary glands was carried out in 60 alcoholics (20 alcoholics with liver damage, 20 without liver damage, 20 young alcoholics) and 20 matched control patients. A sialographic study was carried out in the same 60 alcoholic patients and in 40 non-alcoholic control individuals. Minor salivary gland biopsies were obtained and samples were processed for light microscopy. A quantitative morphometrical assessment was carried out by counting the number of acinar cells with a squared grid eye-piece. Both experimental and control samples presented very similar results demonstrating that, at least in this study, minor salivary glands do not develop hypertrophic, atrophic or hyperplastic changes. We detected a statistical difference between adult alcoholics without liver damage and adult alcoholics with liver damage. A diffuse mononuclear inflammatory cell infiltrate was distributed through the stroma or concentrated around the salivary ducts in both experimental and control samples. Acinar degeneration and hyperaemia were common changes observed in both experimental and control samples. Sialographic images from alcoholics demonstrated a similar morphology when compared with control patients, perhaps a reduction in secondary ducts diameter was observed in alcoholic patients. From this study we may conclude that minor salivary glands are scarcely affected by alcoholism, even when this disease has progressed to liver damage.

Histopathologic Findings in the Clinically Uninvolved Skin of Patients with Mycosis Fungoides

Several of the methods of treating plaque-stage mycosis fungoides (MF) advocate treatment of the whole skin, although relatively little information exists on the histologic appearance of clinically uninvolved MF skin. Our study was performed to elucidate the histologic appearance of the clinically uninvolved skin of plaque-stage MF patients. Biopsies were taken from the clinically uninvolved skin of 18 untreated patients with plaque-stage MF, 1 cm (near) and > or = 10 cm (far) from the MF plaques, and from 23 normal, healthy controls. Eight to 12 serial sections from each specimen were examined. The most common histologic finding, which was observed in six (33%) biopsies of near skin and four (22%) biopsies of far skin compared with only one (4%) biopsy of normal control (p = 0.02 and 0.1, respectively), consisted of mononuclear-cell infiltrate around a blood vessel in the papillary dermis, with extension of some of these cells into the overlying epidermis. More diffuse and epidermotropic mononuclear cell infiltrates were seen in an additional three (17%) biopsies of near skin, whereas mild nonepidermotropic superficial perivascular or perifollicular mononuclear cell infiltrates were observed in an additional four (17%) biopsies of the normal controls. In conclusion, the most common histologic finding in our study, which was observed predominantly in the MF group, might represent an earlier stage and clinically undetectable involvement of the normal-looking skin in MF patients.