Immunohistochemical study about the Flt-1/VEGFR1 expression in the gastrointestinal tract of mouse, rat, dog, swine and monkey

Fms-like tyrosine kinase 1 (Flt-1) performs a subordinate effector role in mesenchymal angiogenesis and potentially serves an equally important functional role as a self-contained receptor in epithelial cells. In both endothelial cells and epithelial cells, Flt-1/vascular endothelial growth factor receptor 1 (VEGFR1) downstream signalling is involved in regulating cellular processes such as cytoskeletal changes and cellular survival protection. Cellular renewal of the gastrointestinal mucosa is based on these processes and might involve Flt-1/VEGFR1 pathway activities; the molecular mechanisms regulating these cellular dynamics remain unclear. This study was performed to investigate the presence and distribution of Flt-1/VEGFR1 in epithelial cells of the gastrointestinal tract by immunohistochemistry (IHC). Gastrointestinal tissues were taken from eight anatomical sites from mouse, rat, dog, swine and monkey. Present results revealed a cytosolic Flt-1/VEGFR1 staining pattern in mucosal epithelial cells for all investigated species. Non-epithelial structures also displayed a distinct Flt-1/VEGFR1 positivity and included vascular smooth muscle walls, enteric smooth muscle layers, the enteric nervous system and capillary endothelial cells. Diverse intensities of the Flt-1/VEGFR1 binding reaction within each species were observed in the intestinal mucosa with a strong immunoreaction in enterocytes and with a low protein expression in the ileum in most species. Crypt cells in the large intestine were mostly negative for Flt-1/VEGFR1. A peculiar and mainly intranuclear antibody binding reaction was found in Brunner's gland epithelial cells of mouse and rat whereas Brunner's glands of dog, swine and monkey remained completely negative. These results indicate a potential involvement of Flt-1/VEGFR1 in normal restitution of gastrointestinal structures in the species studied. Additionally, intranuclear Flt-1/VEGFR1 antibody binding in Brunner's glands of rodents may suggest a nuclear translocation of the transmembrane VEGFR1 which has not previously been described.     

A der(14)t(1;14)(q12;p11) in chronic myelomonocytic leukemia

Duplication of the long arm of chromosome 1 (1q) is widely reported in human neoplasia, including the myelodysplastic syndromes (MDS). So far, it has not been described as a single aberration in the chronic myelomonocytic leukemia (CMML), a subtype of MDS. Rather, trisomy 1q was always a part of complex chromosome changes affecting the subtypes of MDS other than CMML. We report on a patient with CMML with an unbalanced translocation of the entire 1q onto the short arm of chromosome 14 as a sole cytogenetic abnormality. Fluorescence in situ hybridization (FISH) analysis with an alpha-satellite probe for the paracentric region of the long arm of chromosome 1 confirmed the presence of trisomy 1q in a derivative chromosome, der(14)t(1;14)(q12;p11). The discrepant results between the metaphase cytogenetics (100% abnormal) and interphase cytogenetic (71% nuclei with 3 signals) suggest that trisomy 1q, even in the absence of additional cytogenetic changes, has a sufficient leukemogenic potential to confer a proliferative advantage on hematopoietic cells committed to monocyte stemline both in vitro and in vivo. The literature data on partial and complete trisomy 1q in CMML is reviewed.     

The effect of two different bracket types on the salivary levels of S mutans and S sobrinus in the early phase of orthodontic treatment

Objective:To determine the difference in the levels of Streptococcus mutans and S sobrinus in stimulated saliva in orthodontic patients with different bracket types (stainless steel and esthetic brackets) using polymerase chain reaction and cultivation method.Materials and Methods:Thirty-two patients, aged 13 to 30 years, were selected following these criteria: 1) orthodontic treatment indication, 2) systemic health, and 3) no tobacco and antibiotic consummation for three months prior to the commencement of the study. Patients were divided into two groups according to the bracket type; 16 patients formed the conventional bracket group (stainless steel brackets), and 16 patients formed the esthetic bracket group (plastic brackets). The levels of S mutans and S sobrinus in stimulated whole saliva samples were collected prior to fixed orthodontic appliance placement (T1) and 12 weeks after placement (T2), as were the Decayed, Missing, and Filled Surface Index (DMFS) and Oral Hygiene Index-Simplified (OHI-S). Mann-Whitney, Wilcoxon, and chi-square tests were used for statistical analysis.Results:Statistical analysis (chi-square test) showed no difference in S mutans and S sobrinus counts among patients with different brackets at either T1 or T2. There was no difference in total bacteria counts after fixed orthodontic appliance placement.Conclusion:The number of colony-forming units of S mutans and S sobrinus in stimulated saliva samples does not seem to be significantly different between patients with stainless steel brackets and patients with plastic brackets.     

Contractile reserve assessed by dobutamine test identifies super-responders to cardiac resynchronization therapy

Introduction

In this study, we sought to determine whether myocardial contractile reserve (CR) assessed by dobutamine stress echocardiography (DSE) can identify patients who experience nearly complete normalization of left ventricular (LV) function after the implantation of a cardiac resynchronization therapy (CRT) pacemaker.

Material and methods

The study group consisted of 55 consecutive patients with non-ischemic dilated cardiomyopathy, LV ejection fraction (LVEF) < 35%, and prolonged QRS complex duration, who were scheduled for CRT pacemaker implantation. The DSE (20 µg/kg/min) was performed in all patients. The CR assessment was based on a change in the wall motion score index (ΔWMSI) and ΔLVEF during DSE. Super-response was defined as an increase in LVEF to > 50% and reduction in left ventricular end-systolic dimension to < 40 mm 12 months following the CRT implantation.

Results

A total of 7 patients (12.7%) were identified as super-responders to CRT. When compared to non-super-responders, these patients had significantly higher values of the dobutamine-induced change in ΔWMSI (1.031 ±0.120 vs. 0.49 ±0.371, p < 0.01), and ΔEF (17.9 ±2.2 vs. 8.8 ±6.2, p < 0.01). Receiver operating characteristic analysis showed that dobutamine-induced changes in ΔWMSI ≥ 0.7 and ≥ 14% for ΔEF are the best discriminators for a super-response. Patients with ΔWMSI ≥ 0.7 and ΔEF ≥ 14% are significantly less often hospitalized (p < 0.01) for worsening of heart failure during 28.5 ±3.0 months of the follow-up.

Conclusions

Contractile reserve assessed by DSE can identify patients with dilated cardiomyopathy who are likely to experience near normalization of LV function following CRT.     

Developmental delay associated with normal thyroidal function and long-term amiodarone therapy during fetal and neonatal life

We reported a case of a child with neurodevelopment delay induced by long-term amiodarone exposure due to a treatment of fetal supraventricular tachycardia (FSVT), subtype permanent junctional reciprocating tachycardia (PJRT) with the normal thyroidal function. Refractory persistent FSVT was treated intrautero with digoxin (0.5 mg QD) until delivery and amiodarone (100 mg QD) from 26 to 35 weeks of gestation. A baby weighing 3550 g with normal acid-base status was delivered at 38 weeks of gestation. The PJRT recurred 28 hours after delivery and reverted to sinus rhythm with amiodarone and propranolol for another 24 months. The neurological disturbances were manifested at the age of 12 months, when hypotonia and delayed motor milestones were recognised. At the age of 18 months, the child had mildly neurological development delay with hypotonia, ataxia and foot deformities. At the age of 24 months, motor milestones were mildly delayed with the usage of a few words without the ability to connect them into the sentence. The developmental quotient (DQ) was 68. Electroencephalogram and magnetic resonance imaging of the central nervous system were all normal. At the age of 30 months, motor milestones were still delayed together with speech development and language delay, only some words were used, not distinctly, DQ was 78. Thyroid function was normal on each examination. All blood and urine analyses were in normal ranges. Chromosome analysis did not show any abnormalities. Since we excluded all possible reasons, we could only bring an indirect link between the long-term amiodarone exposure during fetal and postnatal life and neurodevelopment delay.     

TP53, Bcl-2 and growth hormone receptor expression in cutaneous squamous cell carcinoma

The incidence and prevalence of premalignant and malignant skin lesions including squamous cell carcinoma (SCC) of the skin are increasing worldwide. The aim of the study was to determine TP53, Bcl-2 and growth hormone receptor (GHR) expression in SCC and to investigate relative importance of these proto-oncogenes in its biological behavior. Expression of TP53, Bcl-2 and GHR was determined by immunohistochemistry in 27 SCC specimens and adjacent perilesional skin. The relative proportion of immunoreactive cells was counted with semiquantitative method. TP53 positivity was detected in 24 (89%), Bcl-2 in 18 (67%) and GHR in 25 (93%) of 27 SCC specimens investigated. In comparison with perilesional skin, TP53 and GHR positivity was significantly increased, and Bcl-2 positivity significantly decreased in SCC. Increased TP53 expression in SCC lesions implies that Tp53 mutation is an early and crucial event in its development. Increased GHR expression suggests a role of growth hormone in the development of SCC.     

Heel reconstruction with an iliac osteocutaneous free flap: 10-year follow-up

During the Homeland War in Croatia, many civilians suffered from war wounds of the extremities. Explosive war wounds create composite and devastating injuries mainly by high-energy transfer to the tissue. We present an early reconstruction of explosive heel wound with an iliac osteocutaneous free flap with late follow-up result.     

MALT lymphoma of the parotid salivary gland

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphoma was described for the first time in 1983 by Isaacson and Wright. It was classified into extranodal non-Hodkin's lymphomas of B-cell lymphocytes of the marginal zone of reactive lymphe follicles. It is characterized by both hyperplasia and colonization of plasmocytic, centrocytoid and monocytoid cells, by the infiltration of interfollicular and parafollicular parts of interstitium, as well as by the invasion of clusters of neoplastic lymphoid cells of the glandular epithelium, forming the pathognomic lymphoepithelial MALT limphoma lesions. CASE REPORT: In this paper we presented the two female patients, 59 and 75 years of age, with MALT lymphomas, associated with Miculicz's and Sj?gren's syndromes. The paper also underlined rather many-month-long, indolent clinical course, evalution of both tumors, massive in size, as well as two-sided localization in the case of the Miculicz's syndrome. After the subtotal parotidectomy, using conservation of nerve facialis, the tissue blocks were fixed in 10% formaldehyde. The paraffine sections were stained by routine histochemical and an immunohistochemical method by using monoclonal antibodies for both B-cell and T-cell lymphomas, due to the verification of lymphoepithelial lesions. The MALT lymphoma diagnosis was based on the histological criteria and confirmed by an immunohistochemical method. After the surgical therapy accompanied by chemotherapy, the patients were controlled at regular intervals, and residual MALT lymphoma did not appear. CONCLUSION: MALT lymphoma is a rare tumor of the salivary glands, with the most frequent localization in the parotide gland. It had a slow clinical course, without metastases in both patients. The diagnosis was made pathohistologically and confirmed immunohistochemically. The surgical therapy was accompained by adjuvant chemotherapy.