Sermin Özkal

Effects of erythropoietin on hyperoxic lung injury in neonatal rats

Pulmonary oxygen toxicity is believed to play a prominent role in the lung injury that leads to the development of bronchopulmonary dysplasia (BPD). To determine whether human recombinant erythropoietin (rhEPO) treatment reduces the risk of developing BPD, we investigated the effect of rhEPO treatment on the histopathologic changes seen in hyperoxia-induced lung injury of BPD. Twenty-five rat pups were divided into four groups: air-exposed control group (n = 5), hyperoxia-exposed placebo group (n = 7), hyperoxia-exposed rhEPO-treated group (n = 6), and air-exposed rhEPO-treated group (n = 7). Measurement of alveolar surface area, quantification of secondary crest formation, microvessel count, evaluation of alveolar septal fibrosis, and smooth muscle actin immunostaining were performed to assess hyperoxia-induced changes in lung morphology. Treatment of hyperoxia-exposed animals with rhEPO resulted in a significant increase in the mean alveolar area, number of secondary crests formed, and the microvessel count in comparison with hyperoxia-exposed placebo-treated animals. There was significantly less fibrosis in rhEPO-treated animals. However, treatment of hyperoxia-exposed animals with rhEPO did not result in a significant change in smooth muscle content compared with hyperoxia-exposed placebo treated animals. Our results suggest treatment with rhEPO during hyperoxia exposure is associated with improved alveolar structure, enhanced vascularity, and decreased fibrosis. Therefore, we conclude that treatment of preterm infants with EPO might reduce the risk of developing BPD.

Effects of trimetazidine on acetic acid-induced colitis in female Swiss rats.

Induction of colitis by acetic acid (A A) in the rat is widely used experimental model of inflammatory bowel disease (IBD) and ulcerations. AA as an irritant induces colitis involving infiltration of colonic mucosa with neutrophils and increased production of inflammatory mediators, such as hydrogen peroxide (H 2 O 2 ), nitric oxide (NO), myeloperoxidase activity (MPO), and tumor necrosis factor (TNF- f ). Trimetazidine (TMZ), an antianginal compound, was administered to investigate if its cytoprotective features in cardiac tissue are also effective in AA colitis where ischemic injury contributes to colitis. Administration of TMZ intraperitoneally improved the macroscopic and microscopic score alterations produced by AA. AA administration significantly elevated colonic MPO activity; however, treatment with TMZ significantly lowered this enzyme activity compared to AA. AA administration significantly enhanced superoxide dismutase (SOD) activities, except for AA + TMZ given rectally. TMZ treatment significantly lowered nitrate levels, but A A increased these levels. AA administration markedly lowered TNF- f levels, but TMZ treatment elevated these levels to control. These findings indicate that overproduction of NO may be involved in the immunosuppression observed during acute AA-induced rat colitis. In conclusion, TMZ treatment was more effective via the intraperitoneal than rectal route, and may be beneficial in therapy of colitis.

Selective loss of B-cell phenotype in lymphocyte predominant Hodgkin lymphoma

The neoplastic Reed–Sternberg cells characteristic of classical Hodgkins lymphoma (cHL) are of B‐cell origin but they almost always show striking loss of a range of B‐cell‐associated molecules. In contrast, the neoplastic cells found in lymphocyte predominant Hodgkins lymphoma (LPHL) (L&H cells) are traditionally thought of as possessing the full repertoire of features associated with germinal centre B cells (eg BCL‐6 expression, ‘ongoing’ Ig gene mutation). In the present paper, we report an extensive phenotypic analysis of L&H cells which revealed down‐regulation of a number of markers associated with the B‐cell lineage (eg CD19, CD37) and with the germinal centre maturation stage (eg PAG, LCK). The promoter methylation status of three of these down‐regulated genes (CD10, CD19, and LCK) was further studied in microdissected L&H cells, and this revealed that their promoters were unmethylated. In contrast, these genes showed promoter methylation in cell lines derived from CHL. Further investigation of the mechanisms responsible for the deregulation of these molecules in L&H cells may provide new insights into the genetic abnormalities underlying LPHL. Copyright

The expression of IgM is helpful in the differentiation of primary cutaneous diffuse large B cell lymphoma and follicle center lymphoma

Diffuse large B-cell infiltration of the skin includes mainly primary cutaneous follicle center lymphoma (PCFCL) with diffuse architecture and diffuse large B cell lymphoma (PCDLBCL), leg type. Differentiation of these lymphomas on morphology may be troublesome. Immunohistochemistry panel, including CD20, CD79a, bcl-6, bcl-2, MUM-1, FOX-P1 is mandatory. However, in minority of cases, these markers would not suffice. In order to search the value of another marker, IgM, 30 cases of PCFCL and 10 cases of PCDLBCL, leg type were included in the study. As suggested in a recent literature, our study denoted that expression of IgM was useful as an additional tool for differentiation.

Prognostic significance of immunohistochemical classification of diffuse large B-cell lymphoma

Abstract Aim: To evaluate the clinical significance of immunoperoxidase staining for CD10, bcl-6, mum-1 and bcl-2 to subdivide DLBCL into prognostic subgroups, we analysed 50 DLBCL cases using immunohistochemical methods. Methods and results: Fifty DLBCL patients were evaluated retrospectively. The expression of CD10 was associated with better OS (p=0·04) whereas expression of mum-1 was associated with worse OS (p=0·009). There were no significance of OS in case of expression of bcl-6 (p=0·05) and bcl-2 (p=0·3). They were subclassified using CD10, mum-1, bcl-6 as germinal center B-cell like (GCB) lymphoma (30%) and non-GCB lymphoma (70%). The OS and EFS (event free survival) were longer in GCB group (p=0·002) and 5-year OS for GCB group was 92% compared with only 44% for the non-GCB group (p=0·02). The OS of the GCB group also was longer compared to that of the non-GCB group in low IPI subgroup (p=0·01). Conclusion: The existance of survival differences between GCB a non-GCB group also in the patients with low IPI score, showed the importance of prognostic classification in the risk-adaptive treatment approaches. The classification as GCB and non-GCB based immunostains may enable to define more accurate prognostic groups in DLBCL.

Articular, B-cell, non-Hodgkin’s lymphoma mimicking rheumatoid arthritis: synovial involvement in a small hand joint

Polyarticular joint manifestations as the predominant symptom of non-Hodgkin’s lymphoma (NHL) are quite rare. In the absence of peripheral lymph node and visceral involvement, lymphomas presenting as polyarthritis create a problem for the patients as another rheumatic disease. We present a case that had been diagnosed with rheumatoid arthritis because of symmetrical articular symptoms. The patient later developed severe pain and marked swelling in her right fourth finger, and a diagnosis of septic arthritis and osteomyelitis complicating rheumatoid arthritis was assumed. The final diagnosis of NHL with synovial involvement could be made only after histopathologic examination of a biopsy specimen obtained from the amputated finger. This is the first case report demonstrating direct synovial involvement of a small joint in a patient with NHL presenting with polyarthritis. Articular and periarticular involvement of multiple joints shown by MRI in this patient suggests that direct synovial involvement may be responsible for the polyarticular symptoms in such patients.

No beneficial effects of joint distraction on early microscopical changes in osteoarthrotic knees

Background Although promising results have been reported, on the use of joint distraction in osteoarthrotic joints, the mechanism behind the effects has not yet been expland. Material and methods 24 rabbits were randomly divided into 4 groups and osteoarthrosis was induced by papain injection. The first group served as control and the others were treated by simple external fixation (group 2), articulated distraction (group 3) or nonarticulated distraction (group 4). Results Histologically, there was no significant difference between the first, the second and the third groups. However, osteoarthrosis increased in group 4. Interpretation We conclude that joint distraction has no beneficial effect on the osteoarthrotic cartilage in papain-induced osteoarthrosis, and nonarticulated distraction worsens the results.

Cystic schwannoma of the maxillary sinus

OBJECTIVE Although 25-45% of all schwannomas are reported to occur in the head and neck region, nasal cavity and paranasal sinus involvement is rare, with 32 such cases described till 1999. Of these cases, only three were cystic. Herein we present a cystic schwannoma of the maxillary sinus of a 66-year-old, otherwise healthy male patient. METHODS The tumor tissue was routinely processed, embedded in paraffin, and stained with H&E. Immunostaining was performed for S-100 protein, epithelial membrane antigen (EMA) and cytokeratin. RESULTS A mass with sudden enlargement, inhomogeneous enhancement with cystic areas, S-100 positive membrane-like structures lining the cystic cavity of an otherwise classical schwannoma were the main features encountered in our case. CONCLUSION We recommend that cystic schwannoma should be kept in mind in the differential diagnosis of cystic masses of the maxilla.

Focal adhesion kinase (FAK) expression in normal and neoplastic lymphoid tissues.

Focal adhesion kinase (FAK) is a protein tyrosine kinase essential for intracellular regulatory events, such as cell growth, differentiation, migration and tumor metastasis. The aim of this study was to analyze the expression of FAK protein in a series of normal and neoplastic lymphoid tissues. An anti-FAK antibody was used to study the protein expression in paraffin-embedded samples of normal and neoplastic, hematolymphoid and non-hematolymphoid tissues by immunohistochemistry. In normal hematolymphoid tissue, the strongest expression of FAK was detected in germinal center and marginal-zone B cells; positive staining was also found in mantle zone B cells. In human lymphomas, FAK was expressed mostly in B-cell lymphomas and was predominantly negative in T-cell lymphoma. In Hodgkin lymphomas, FAK was found only in the neoplastic cells of lymphocyte predominant type, whereas the tumor cells of the classical form were FAK-negative. We demonstrate for the first time the expression of FAK in paraffin-embedded hematolymphoid tissue samples. Its differential expression in lymphomas may be of relevance for some B-cell neoplasms by using it as an additional marker to distinguish B- from T-lymphoblastic leukemia/lymphoma to further differentiate lymphocyte predominant from classical Hodgkin lymphoma.

MMP-2 and MMP-9 Alteration in Response to Collaring in Rabbits: The Effects of Endothelin Receptor Antagonism

Matrix metalloproteinases (MMPs), and, in particular, gelatinases (MMP-2 and MMP-9), have been implicated in vascular cell proliferation and/or migration, contributing to intimal thickening, an essential stage in the development of atherosclerosis and restenosis following balloon angioplasty. Endothelin, a strong chemoatractant and mitogen, has been shown to promote smooth muscle cell proliferation and migration by activating MMPs via endothelin-A (ETA) receptors. The positioning of a soft silicon collar around the left carotid artery in rabbits results in intimal thickening. In this study, we investigate the possible role of gelatinases and the effect of a nonselective ETA/ETB receptor antagonist, TAK-044 (5 mg/kg body weight/day, subcutaneously [sc]), on these enzymes. Our results demonstrated that both MMP-2 and MMP-9 activities increased in response to collaring in placebo group, while treatment with TAK-044 significantly suppressed both gelatinase activities and proMMP-2 levels, and inhibited intimal thickening in collared arteries. These results suggest that either enhanced MMP expression or endothelin receptor antagonism may be involved in the formation of intimal thickening in this model.