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Immunotactoid glomerulopathy (ITG) is a rare form of glomerulonephritis for which our understanding is limited to case reports and small case series. Herein we describe the clinical, pathologic, and outcome characteristics of 73 patients with ITG who typically presented with proteinuria, hematuria, and renal insufficiency. Hematologic disorders were present in 66% of patients, including lymphoma in 41% (mainly chronic lymphocytic leukemia/small lymphocytic lymphoma), monoclonal gammopathy in 20%, and multiple myeloma in 6%. Light microscopy revealed endocapillary proliferative (35%), membranoproliferative (29%) and membranous (29%) patterns of glomerular involvement. Electron microscopy revealed characteristic microtubular deposits with a diameter of 14-60 nm, hollow cores, frequent parallel alignment, and a predominant distribution outside of the lamina densa of the glomerular basement membrane. Importantly, immunofluorescence revealed IgG-dominant staining which was light chain and IgG subclass restricted in 67% of cases, indicating monoclonal composition. This finding was used to distinguish monoclonal and polyclonal variants of ITG. As compared to polyclonal, monoclonal ITG had a higher incidence of lymphoma (53% vs. 11%), multiple myeloma (8% vs. 0), and monoclonal gammopathy (22% vs. 16%). Monoclonal ITG was more commonly treated with clone-directed therapy, which was associated with more frequent remission and less frequent end stage kidney disease. Thus, a third of ITG cases are polyclonal but a quarter of these cases are associated with hematologic conditions, underscoring the need for hematologic evaluation in all patients with ITG. Hence, based on these distinctions, ITG should be subclassified into monoclonal and polyclonal variants. Prognosis of ITG is good if the underlying hematologic condition is treated.

The clinicopathologic characteristics and long-term outcome of non-hepatitis-associated cryoglobulinemic glomerulonephritis (CryoGN) are not well-defined and cases with undetectable serum cryoglobulin (seronegative CryoGN) have not been investigated. To resolve this, we retrospectively identified 81 patients with biopsy-proven non-hepatitis CryoGN, including 22 with seronegative CryoGN. The median age was 61 years and 76% presented with nephritic syndrome. A hematologic condition was found in 89% of patients, including monoclonal gammopathy of renal significance (65%) and symptomatic lymphoproliferative disorder (35%). In the seropositive group, 56% had type II, 29% type I, and 8% type III cryoglobulin. Extrarenal manifestations, mostly of skin, were present in 64% and were significantly less common in seronegative CryoGN. Glomerular deposits by immunofluorescence were IgM dominant (84%) and polytypic (70%) in the seropositive group, whereas 52% of seronegative cases had monotypic deposits (i.e., type I cryoglobulin). Ultrastructurally, the deposits were organized in 77% of cases. Substructure appearance significantly differed according to the type of CryoGN, forming most commonly short cylindrical structures in type II and other organized substructures in type I CryoGN. Most patients were treated with clone-directed therapy. On follow up (median 33 months), 77% had partial or complete remission, 10% reached kidney failure and 14% died. Predictors of kidney failure on univariate analysis were AKIN stage 3, positive rheumatoid factor and biclonal gammopathy at diagnosis. We conclude that most CryoGN cases (types I and II) are due to a hematologic condition and are associated with favorable outcome after clone-directed therapy. Seronegative CryoGN accounts for about a quarter of cases and is mostly a kidney-limited disease. Thus, further investigations are needed to unravel the pathophysiology of seronegative CryoGN.

Myxoid hepatic adenomas are a rare subtype of hepatic adenomas with distinctive deposition of extracellular myxoid material between the hepatic plates. A total of 9 cases were identified in 6 women and 3 men with an average of 59±12 years. The myxoid adenomas were single tumors in 5 cases and multiple in 4 cases. In 1 case with multiple adenomas, the myxoid adenoma arose in the background of GNAS-mutated hepatic adenomatosis. Myxoid hepatic adenomas had a high frequency of malignant transformation (N=5 cases). They were characterized at the molecular level by HNF1A inactivating mutations, leading to loss of LFABP protein expression. In addition, myxoid adenomas had recurrent mutations in genes within the protein kinase A (PKA) pathway or in genes that regulate the PKA pathway: GNAS, CDKN1B (encodes p27), and RNF123. In sum, myxoid adenomas are rare, occur in older-aged persons, have a high risk of malignant transformation, and are characterized by the combined inactivation of HNF1A and additional mutations that appear to cluster in the PKA pathway.

Die Logistik ist eine systemrelevante Querschnittsfunktion und bildet das Ruckgrat der Wirtschaft. Die Herausforderungen der Logistikbranche erweisen sich als vielfaltig und enorm, denn ohne eine funktionierende Logistik wird es keine Versorgung der Privathaushalte, keine rapide Verteilung von Medikamenten oder anderen wichtigen medizinischen Gutern und schlussendlich keine leistungsfahige Wirtschaft geben. Somit steht auch die Logistikbranche durch die Corona-Krise vor einer Reihe grosen Herausforderungen und die Auswirkungen der Pandemie sind schon jetzt deutlich abbildbar.

Die Vorstellung einer vernetzten und digitalen Produktion geht weit zuruck in die Geschichte der industriellen Fertigung. Die industrielle Revolution ist gepragt durch neue technologische Entwicklungen und effiziente Produktionsprozesse. Aufgrund der Vielzahl an historischen Ereignissen ist es hilfreich, sich die Entwicklung der Industrie naher anzuschauen, um Industrie 4.0 mit diesem Hintergrundwissen besser zu verstehen.

Platelet transmission electron microscopy (PTEM) is considered the gold standard test for assessing distinct ultrastructural abnormalities in inherited platelet disorders (IPDs). Nevertheless, PTEM remains mainly a research tool due to the lack of standardized procedures, a validated dense granule (DG) count reference range, and standardized image interpretation criteria. The aim of this study was to standardize and validate PTEM as a clinical laboratory test. Based on previously established methods, we optimized and standardized preanalytical, analytical, and postanalytical procedures for both whole mount (WM) and thin section (TS) PTEM. Mean number of DG/platelet (plt), percentage of plts without DG, platelet count (PC), mean platelet volume (MPV), immature platelet fraction (IPF), and plt light transmission aggregometry analyses were measured on blood samples from 113 healthy donors. Quantile regression was used to estimate the reference range for DG/plt, and linear regression was used to assess the association of DG/plt with other plt measurements. All PTEM procedures were standardized using commercially available materials and reagents. DG interpretation criteria were established based on previous publications and expert consensus, and resulted in improved operator agreement. Mean DG/plt was stable for 2 days after blood sample collection. The median within patient coefficient of variation for mean DG/plt was 22.2%; the mean DG/plt reference range (mid-95th %) was 1.2-4.0. Mean DG/plt was associated with IPF (p = .01, R

The aim of this study was to compare feed intake, nutrients digestibility, protein fractions entering into the duodenum, and ruminal fermentation parameters of sheep fed Medicago sativa (alfalfa) and Prangos pabularia, locally called kerkol hays. In the study three ruminally and duodenally cannulated Morkaraman sheep were used. It was carried out as two periods within a 2x3 crossover experimental design. Daily intake of crude protein (CP) was higher (P less than 0.05) in sheep fed alfalfa than those fed kerkol hay. Digestibility of NDF and ADF were lower (P less than 0.05) in sheep fed alfalfa hay than those fed kerkol hay (P less than 0.05). The percentage of protein escaping ruminal degradation was higher (P less than 0.05) in sheep fed kerkol hay (30.73%) than those fed alfalfa hay (15.05%). Ruminal fermentation parameters were similar between groups, except ruminal NH3-N concentration. It is concluded that kerkol hay can be used as forage for sheep feeding.

Objective We used transcriptomic profiling and immunohistochemistry (IHC) to search for a functional imaging strategy to resolve common problems with morphological imaging of cystic neoplasms and benign cystic lesions of the pancreas. Methods Resected pancreatic cancer (n = 21) and normal pancreas were laser-capture micro-dissected, and transcripts were quantified by RNAseq. Functional imaging targets were validated at the protein level by IHC on a pancreatic adenocarcinoma tissue microarray and a newly created tissue microarray of resected intraductal papillary mucinous neoplasms (IPMNs) and IPMN-associated adenocarcinomas. Results Genes encoding proteins responsible for cellular import of pyruvate, export of lactate, and conversion of pyruvate to lactate were highly upregulated in pancreatic adenocarcinoma compared to normal pancreas. Strong expression of MCT4 and LDHA was observed by IHC in >90% of adenocarcinoma specimens. In IPMNs, the pyruvate-to-lactate signature was significantly elevated in high grade dysplasia (HGD) and IPMN-associated adenocarcinoma. Additionally, cores containing HGD and/or adenocarcinoma exhibited a higher number of peri-lesional stromal cells and a significant increase in peri-lesional stromal cell staining of LDHA and MCT4. Interestingly, the pyruvate-to-lactate signature was significantly upregulated in cores containing only low grade dysplasia (LGD) from patients with histologically confirmed IPMN-associated adenocarcinoma versus LGD cores from patients with non-invasive IPMNs. Conclusion Our results suggest prospective studies with hyperpolarized [1– 13 C]-pyruvate magnetic resonance spectroscopic imaging are warranted. If these IHC results translate to functional imaging findings, a positive pyruvate-to-lactate imaging signature might be a risk factor for invasion that would warrant resection of IPMNs in the absence of other worrisome features.

ASCL1 is an important regulatory transcription factor in pulmonary neuroendocrine (NE) cell development, but its value as a biomarker of NE differentiation in lung adenocarcinoma (AD) and as a potential prognostic biomarker remains unclear. We examined ASCL1 expression in lung cancer samples of varied histologic subtype, clinical outcome and smoking status and compared with expression of traditional NE markers. ASCL1 mRNA expression was found almost exclusively in smokers with AD, in contrast to non-smokers and other lung cancer subtypes. ASCL1 protein expression by immunohistochemical (IHC) analysis correlated best with synaptophysin compared with chromogranin and CD56/NCAM. Analysis of a compendium of 367 microarray-based gene expression profiles in stage I lung adenocarcinomas identified significantly higher expression levels of the RET oncogene in ASCL1-positive tumors (ASCL1(+)) compared with ASCL1(-) tumors (q-value

Malignant peripheral nerve sheath tumors (MPNSTs) arising from cranial nerves or their branches are very uncommon. The literature consists mainly of isolated case reports and small series. We identified 17 such cases in 14 males and 3 females. With one exception, the tumors affected adults (age range 5 to 69y, mean 39, median 32). Sites of involvement included vestibular nerves (n = 6). vagal nerves (n = 4), facial nerves (n = 3) (1 centered in the geniculate ganglion), and 2 unspecified cranial nerves in the posterior fossa. In addition, I tumor involved the optic chiasm (n = 1). Only I tumor arose in brain parenchyma of (frontal lobe). All but 3 lesions were intracranial, live tumors arose in patients who satisfied clinical criteria for neurofibromatosis type 1 (NNI). One patient with a vestibular tumor and presumed NF2 had previously undergone resection of a contralateral vestibular cellular schwannoma. One posterior fossa tumor was a malignant melanotic schwannoma. Four patients had postirradiation malignant peripheral nerve sheath tumors, 2 having been treated for optic chiasm glioma, both being NNI affected. One patient was irradiated for hypothalamic pilocytic astrocytoma and another for cervical Hodgkin disease. Identifiable precursor lesions included schwannoma (n = 4), plexiform neurofibroma (n = 2), and solitary intraneural neurofibroma (n = 2). All tumors were histologically high grade (6 grade III and 10 grade IV). Three tumors showed heterologous elements, 2 osscous, and 1 rhabdomyoblastic. More often scattered than diffuse, S-100 protein staining was noted in 11 of 16 tumors and variable collagen IV staining in 10 of the 16. Immunoreactivity for p53 protein was diffuse and strong in 7 of 11 tumors. Twelve patients died within 17 months to 3 years of diagnosis, 1 was lost to follow-up, 2 are very recent cases, and 2 patients are currently alive, I after 2 recurrences, and another with spinal leptomeningeal metastases. Malignant cranial nerve sheath tumors :ire rare and are associated with the same poor prognosis as those of spinal nerves at other sites.

We used a target-centric strategy to identify transporter proteins upregulated in pancreatic ductal adenocarcinoma (PDAC) as potential targets for a functional imaging probe to complement existing anatomical imaging approaches. We performed transcriptomic profiling (microarray and RNASeq) on histologically confirmed primary PDAC tumors and normal pancreas tissue from 33 patients, including five patients whose tumors were not visible on computed tomography. Target expression was confirmed with immunohistochemistry on tissue microarrays from 94 PDAC patients. The best imaging target identified was SLC6A14 (a neutral and basic amino acid transporter). SLC6A14 was overexpressed at the transcriptional level in all patients and expressed at the protein level in 95% of PDAC tumors. Very little is known about the role of SLC6A14 in PDAC and our results demonstrate that this target merits further investigation as a candidate transporter for functional imaging of PDAC.

We present computed tomography, magnetic resonance imaging and pathologic findings of a 52-year-old female with a giant dedifferentiated retroperitoneal liposarcoma in which well differentiated lipoma-like and dedifferentiated components are found together. Dedifferentiated components of the mass showed various degrees of enhancement and revealed no suppression with fat saturation techniques. The diagnosis of dedifferentiated liposarcoma should be kept in mind when a mass is found with retroperitoneal localization, intense of contrast enhancement, calcifications, invasion of adjacent tissues, necrosis and haemorrhage, and the absence of fat suppression. © 2004 Elsevier Ireland Ltd. All rights reserved.

In patients with gastric carcinomas, the role of the alteration of mucin expression in overall survival has been a matter of some speculation, but few studies have been reported. The aim of our study was to determine the relationship between MUC1, MUC2, and MUC5AC expression and patient survival, with a secondary aim designed to investigate the alteration of MUC expression within various clinicopathologic parameters. Forty-four specimens from gastric carcinoma patients were immunohistochemically evaluated using the monoclonal antibodies for MUC1 (EMA, clone E29), MUC2 (CCP58), and MUC5AC (human gastric mucin, clone 45M1). MUC1 expression increased in gastric carcinoma. MUC1 positivity was determined to be statistically significant, with poor clinicopathological parameters and decreased long-term survival. MUC5AC expression decreased in gastric carcinoma. In addition, patients with MUC5AC-positive tumors also had poor clinicopathological parameters and showed shorter survival than those with MUC5AC-negative tumors. MUC2 expression was not significantly associated with patient survival. We confirmed that the expression of mucins is associated with characteristics of differentiation in gastric carcinoma. Poor patient outcomes were seen in gastric carcinomas with MUC1 mucin expression and MUC5AC positivity.

Overexpression and alterations in the glycosylation of gastric mucins have been described in colorectal carcinoma. The purpose of our study was to confirm aberrant expression of MUC5AC in colorectal carcinoma, to investigate relationships between clinicopathological parameters and MUC5AC expression, and to determine if MUC5AC expression may be a prognostic factor for colorectal carcinoma. Immunohistochemical staining using an antibody against MUC5AC tandem repeat epitopes was performed on colorectal tumor specimens (n = 41), their metastatic tumors in regional lymph nodes (n = 21) and normal colonic mucosa (n = 41). We also documented clinicopathological parameters such as the age and sex of the patient, location, size, Dukes stage, histological type and grade of the tumor, pre-sence and number of metastatic lymph nodes, lymphatic, venous and perineural invasion, presence of preoperative and postoperative metastatic tumors and tumor recurrence. MUC5AC was expressed in 34.1% of tumor samples, 24.4% of normal colonic mucosa samples and 19% of lymph node metastases. MUC5AC showed ectopic expression in colorectal carcinoma and was also expressed strongly in mucinous carcinoma (60%). The number of tumors that expressed MUC5AC was lower in patients older than 60 years, in rectum-localized tumors and in patients who had evidence of recurrence and/or metastasis in the postoperative period. The patients with MUC5AC-negative tumors had a lower incidence of being disease free and of overall survival. In conclusion, the patients with MUC5AC-negative tumors had poor clinicopathological parameters and showed worse survival than patients with MUC5AC-positive tumors. Absence of MUC5AC expression in tumors can be a prognostic factor for more aggressive colorectal carcinoma.

BACKGROUND Improved tests are needed for detection and management of prostate cancer. We hypothesized that differential gene expression in prostate tissue could help identify candidate blood biomarkers for prostate cancer and that blood from men with advanced prostate disease could be used to verify the biomarkers presence in circulation. METHODS We identified candidate markers using mRNA expression patterns from laser-capture microdissected prostate tissue and confirmed tissue expression using immunohistochemistry (IHC) for the subset of candidates having commercial antisera. We analyzed tissue extracts with tandem mass spectrometry (MS/MS) and measured blood concentrations using immunoassays and MS/MS of trypsin-digested, immunoextracted peptides. RESULTS We selected 35 novel candidate prostate adenocarcinoma biomarkers. For all 13 markers having commercial antisera for IHC, tissue expression was confirmed; 6 showed statistical discrimination between nondiseased and malignant tissue, and only 5 were detected in tissue extracts by MS/MS. Sixteen of the 35 candidate markers were successfully assayed in blood. Four of 8 biomarkers measured by ELISA and 3 of 10 measured by targeted MS showed statistically significant increases in blood concentrations of advanced prostate cancer cases, compared with controls. CONCLUSIONS Seven novel biomarkers identified by gene expression profiles in prostate tissue were shown to have statistically significant increased concentrations in blood from men with advanced prostate adenocarcinoma compared with controls: apolipoprotein C1, asporin, cartilage oligomeric matrix protein, chemokine (C-X-C motif) ligand 11 (CXCL11), CXCL9, coagulation factor V, and proprotein convertase subtilisin/kexin 6.

Prostate cancer (PCa) field effect alterations provide important clues regarding the initiation of these tumors and suggest targets for prevention or biomarkers for early detection. However, biomarkers of PCa field effects that have passed independent validation are lacking, largely because these alterations are subtle and difficult to distinguish from unrelated small changes in gene expression. We hypothesized that shared expression alterations in PCa and benign prostates containing PCa (BPCs) would have a higher potential for independent validation than alterations identified in BPCs alone. Expression analyses were performed on 37 PCas and 36 unmatched BPCs and were contrasted with 28 benign prostates (BPs) from patients free of PCa. Most of the protein-coding genes and nonexonic RNAs selected according to the hypothesis were validated by quantitative RT-PCR in an independent set of 51 BPCs and BPs. A statistical model based on two markers distinguished BPCs from BPs in the RT-PCR set and in an external microarray (area under the curve = 0.84 and 0.90, respectively). In addition, genes with predominant expression in stroma were identified by expression profiling of pure stroma and epithelial cells. Pathway analysis identified dysregulated platelet-derived growth factor receptor signaling in BPC stroma. These results validate our approach for finding PCa field effect alterations and demonstrate a PCa transcriptome fingerprint in nonneoplastic cells in prostates containing cancer.

Background The methods used for sample selection and processing can have a strong influence on the expression values obtained through microarray profiling. Laser capture microdissection (LCM) provides higher specificity in the selection of target cells compared to traditional bulk tissue selection methods, but at an increased processing cost. The benefit gained from the higher tissue specificity realized through LCM sampling is evaluated in this study through a comparison of microarray expression profiles obtained from same-samples using bulk and LCM processing. Methods Expression data from ten lung adenocarcinoma samples and six adjacent normal samples were acquired using LCM and bulk sampling methods. Expression values were evaluated for correlation between sample processing methods, as well as for bias introduced by the additional linear amplification required for LCM sample profiling. Results The direct comparison of expression values obtained from the bulk and LCM sampled datasets reveals a large number of probesets with significantly varied expression. Many of these variations were shown to be related to bias arising from the process of linear amplification, which is required for LCM sample preparation. A comparison of differentially expressed genes (cancer vs. normal) selected in the bulk and LCM datasets also showed substantial differences. There were more than twice as many down-regulated probesets identified in the LCM data than identified in the bulk data. Controlling for the previously identified amplification bias did not have a substantial impact on the differences identified in the differentially expressed probesets found in the bulk and LCM samples. Conclusion LCM-coupled microarray expression profiling was shown to uniquely identify a large number of differentially expressed probesets not otherwise found using bulk tissue sampling. The information gain realized from the LCM sampling was limited to differential analysis, as the absolute expression values obtained for some probesets using this study's protocol were biased during the second round of amplification. Consequently, LCM may enable investigators to obtain additional information in microarray studies not easily found using bulk tissue samples, but it is of critical importance that potential amplification biases are controlled for.

Recently, the fusion gene EML4-ALK was identified in non-small cell lung carcinoma, which could be a potential therapeutic target. We investigated the prevalence of anaplastic lymphoma kinase protein expression in these tumors by immunohistochemistry and correlated the results with data from ALK molecular studies. Gene expression profiling was performed on 35 adenocarcinomas to identify cases with ALK gene up-regulation, which was correlated with protein overexpression by immunohistochemistry. Immunohistochemistry was also performed on an independent cohort consisting of 150 adenocarcinomas and 150 squamous cell carcinomas to evaluate the utility of anaplastic lymphoma kinase immunostaining as a screening tool. Florescence in situ hybridization for the ALK locus and reverse transcriptase-polymerase chain reaction for EML4-ALK were performed on tumors positive for anaplastic lymphoma kinase by immunohistochemistry. Transcriptional up-regulation of ALK was identified in 2 (6%) of 35 adenocarcinomas by gene expression profiling. These 2 cases were positive for anaplastic lymphoma kinase by immunohistochemistry, whereas the remaining 33 cases were completely negative. In the independent cohort, anaplastic lymphoma kinase immunostaining was positive in 1 of 150 squamous cell carcinomas and in 3 of 150 adenocarcinomas. The 6 cases positive for anaplastic lymphoma kinase by immunohistochemistry showed evidence of ALK locus rearrangement by florescence in situ hybridization but were negative for EGFR and KRAS mutation. The presence of EML4-ALK fusion transcript was confirmed in 2 cases by reverse transcriptase-polymerase chain reaction. In conclusion, anaplastic lymphoma kinase immunoreactivity in non-small cell lung carcinomas was associated with transcriptional up-regulation, ALK locus rearrangement, and the presence of EML4-ALK fusion transcript. Anaplastic lymphoma kinase immunohistochemistry may have utility as a screening tool or as a surrogate marker for the molecular techniques to detect the EML4-ALK fusion gene in these tumors.

WOS: 000246135600021 PubMed: 17460467 Malignant tumors of myoepithelial origin have been increasingly recognized at a variety of sites. Herein, we describe an example of malignant myoepithelioma arising in intracranial dura. The patient is a 47-year-old woman who presented with intracranial hemorrhage and on magnetic resonance imaging was found to have an enhancing tumor. No extracranial primary tumor was identified. A gross total resection was performed. Histologically, it varied in pattern from diffuse to focally (< 10%) ductular and consisted of epitheloid to spindle cells showing marked mitotic activity. Prominent infiltration of the dura was noted. Immunohistochemical stains showed convincing expression of cytokeratins (AE1/AE3 and CAM 5.2), S-100 protein, smooth muscle actin, and glial fibrillary acidic protein. Electron microscopy performed on formalin-fixed, paraffin-embedded tissue demonstrated cohesive cells with focal intermediate filament content and surface basal lamina formation at stromal interfaces. Occasional desmosomes with tonofilaments surrounded intercellular lumina containing masses of filamentous material. This example of malignant myoepithelioma is the first convincing primary salivary gland type tumor to arise in an intracranial location outside the sellar region or ear. Intracranial dura should be added to various sites at which this morphologically heterogenous tumor may arise.

WOS: 000237600700020 PubMed: 16771732 Objective: We aimed to detect the preventive effects of trapidil in ischemia reperfusion (IR) injury due to testicular torsion and detorsion. Methods: Forty prepubertal albino rats were used. In the IR group, torsion was created by rotating the left testis over 2 h, and detorsion was done by untwisting the testis. Bilateral orchiectomies were performed after 4 h. In study group, 2-h torsion was performed and trapidil was administered as a single dose I h before detorsion. Bilateral orchiectomies were performed after 4 h. In the sham group, a sham operation was done. In the sham plus trapidil group, a sham operation was done and trapidil was administered as a single dose. Testicular tissue malondialdehyde (MDA), nitric oxide (NO) and total sulfhydryl (T-SH) levels were determined for each group. The grades of interstitial injury were determined in histopathologic examination. Results: The NO and MDA levels in the IR group were significantly higher than the study, sham and sham plus trapidil groups in the left testis (P < 0.05 P < 0.001 and P < 0.001, respectively). A statistical difference was not found among Study, sham and sham plus trapidil groups in the left testis in NO and MDA levels (P > 0.05). The T-SH level in the study group was significantly higher than in the IR. sham and sham plus trapidil groups in left testis P < 0.05). In the IR group (left testis), grade I interstitial injury was 30% (3/10), grade 2 injury was 60% (6/10) and grade 3 injury was 10% (1/10). In the study group (left testis), grade I interstitial injury was 30% (3/10) and there was no injury in 70% (7/10). Conclusion: Trapidil decreased free oxygen radical formation in testicular torsion and detorsion, and attenuated histopathological damage in the ipsilateral twisted testis.

WOS: 000232286600004 PubMed: 16210831 Corrosive esophageal burn is a common health problem in the pediatric age group and causes serious esophageal injuries. The medical treatment In acute phase of corrosive esophageal injury is of particular importance for prevention of esophageal stricture. We therefore aimed to investigate the possible beneficial effect of trapidil (triazolopyrimidine), an inhibitor for phosphodiesterase and platelet-derived-growth-factor, during acute phase of esophageal corrosive injury. Wistar albino rats were randomly allocated to untreated, treated, and sham-operated groups (n = 10 for each group). Corrosive esophageal burn was generated with 10% NaOH solution. The rats were left untreated (untreated group) or treated with trapidil as a single dose of 40 mg/kg intraperitoneally after one hour of the injury (treated group). Abdominal esophageal segment was isolated and tied in sham-control group. The studied esophageal segment was removed from each animal after 24 hours. Malondialdehyde (MDA) and nitric oxide (NO) levels were measured in the esophageal tissues. The ulcer depth was graded by histopathologic examination. MDA and NO levels were significantly higher in the untreated group than in the treated group. Namely, trapidil treatment significantly decreased MDA and NO levels in the injured tissues, the levels of which are similar to those in the tissues of control animals. The grades of ulcer depth were significantly improved in the treated group. These results indicate that the reactive oxygen radicals increase in the early phase of corrosive esophagitis and cause tissue damage. We suggest that trapidil treatment may be useful in acute phase of corrosive esophageal injury.

WOS: 000233630000008 PubMed: 16244863 We aimed to investigate the protective effects of trapidil after the occlusion of abdominal aorta and the reperfusion injury in lung. Eighteen New Zealand albino rabbits were used in the study. In six animals [group 1, ischemia-reperfusion (IR) group], the abdominal aorta was exposed and a microvascular clamp was placed in the infrarenal abdominal aorta for 60 min. After the ischemic period, the microvascular clamp was removed and reperfusion was provided for 2 h. After the reperfusion period, the lungs were removed carefully and specimens were prepared for histopathological and biochemical studies in appropriate conditions. In group 2 (study group), trapidil (Rocarnal, Rentschler-UCB GmbH, Kerpen, Germany) was administered intraperitoneally as a single dose 1 h prior to trial, the IR procedure was performed and lung specimens were prepared similar to group 1. In group 3 (sham group), the infrarenal abdominal aorta was exposed and lung specimens were prepared for histopathological and biochemical studies at the end of the study. Histopathological changes, malondialdehyde (MDA), nitric oxide (NO) and total sulfhydryl group (T-SH) levels were evaluated. There was a statistical difference between the IR group and study group regarding NO and MDA levels (P < 0.05 and P < 0.01, respectively), but this was not detected between the IR group and the sham group (P > 0.05). There was no statistical difference among the three groups regarding T-SH levels (P > 0.05). While a statistical difference was found between the sham group and study group in the NO level (P < 0.05), no statistical difference was found in the MDA level (P > 0.05). There was a statistical difference in interstitial edema, PMN infiltration and hemorrhage scores among the groups (P < 0.05). There was a statistical difference between the IR group and study group in PMN infiltration (P < 0.05), but this was not detected between the groups in interstitial edema and hemorrhage scores (P > 0.05). There was a statistical difference between IR group and sham group in interstitial edema, PMN infiltration and hemorrhage scores (P < 0.05). Statistical difference was found between the sham group and study group in interstitial edema and hemorrhage scores (P < 0.05), but not in PMN infiltration (P > 0.05). Conclusions: Infrarenal abdominal aortic occlusion and reperfusion causes lung injury. We conclude that trapidil has preventive effects in the lung tissue after IR injury.

PubMed: 15293068 [No abstract available]

Helicobacter pylori (H. pylori) infection is associated with the development of gastritis and peptic ulcer and is presumed to be a risk factor for low-grade B-cell lymphoma and gastric cancer. H. pylori also causes critical alterations in gastric mucin structure. Our aim was to determine the effect of H. pylori on MUC1, MUC2, and MUC5AC expression.Thirty H. pylori-positive and 15 H. pylori-negative antral gastric endoscopic biopsy specimens were evaluated for MUC1, MUC2, and MUC5AC expression with immunohistochemical staining. From the same specimens, we scrutinized the presence of H. pylori infection by hematoxylin and eosin and immunohistochemical staining.In H. pylori infected patients, the expression of MUC5AC was found to be localized to the cells in the superficial epithelium and upper parts of the gastric glands. The number of MUC5AC-expressing cells and the staining intensity of MUC5AC were shown to decrease in patients with H. pylori infection. Histopathology and immunostaining patterns of gastric mucins implied that H. pylori was physically associated with extracellular MUC5AC and MUC5AC-producing cells. H. pylori infection does not significantly affect staining intensity and patterns of MUC1 and MUC2 expressions. MUC1 was not found in dysplastic tissues or intestinal metaplasia areas. MUC5AC was expressed in dysplastic areas, but not in intestinal metaplasia. MUC2 was expressed in both dysplastic and intestinal metaplasia areas.H. pylori decreases the amount of MUC5AC expression. With reducing MUC5AC-producing cells and MUC5AC mucin, H. pylori may potentially cause significant alterations of the structure and function of gastric mucins. H. pylori-dependent inhibition of mucin synthesis deserves more investigations to clarify the role of H. pylori and gastric MUC5AC interaction.

Background Platelet dense granule (DG) deficiencies, including Hermansky-Pudlak syndrome, are relatively common and frequently under-diagnosed hereditary platelet hypofunctional disorders. Among various laboratory tests, platelet whole mount (WM) transmission electron microscopy (TEM) is considered the gold standard method for diagnosing DG deficiencies. Nevertheless, platelet DG TEM testing is still largely a research tool and has not been thoroughly validated and standardized as a clinical test. Furthermore, reference ranges (RR) of DG count/platelet (DGC) have not been adequately established. Aim Our goals were to validate and standardize platelet WM TEM testing and establish reference ranges for platelet DGC. Methods Based on previously established methods (Blood, 33:598-606), we first optimized and standardized various pre-analytical, analytical and post-analytical procedures including sample matrix, sample stability, platelet-rich plasma (PRP) preparation, platelet mounting procedure and DG counting criteria. Then whole blood samples in ACD-B tubes were collected from a total of 128 healthy donors (64 males and 64 females). Platelet DGC, percentage of platelets without any DG (empty platelets), platelet count (PC), mean platelet volume (MPV) and immature platelet fraction (IPF) were measured. In addition, platelet aggregometry analyses were performed on citrated PRP samples from the same donors. Standard statistical analyses were employed in this study. Results DGC and platelet ultra-structure were stable when whole blood samples were stored at room temperature (RT) for up to 4 days. Reproducible DGC and adequate preservation of platelet ultrastructure depended on an optimized mounting method. The DG counting criteria were developed based on previous publications and guidance from Dr. James G. White. Using the same WM TEM images and DG counting criteria, agreements among different technologists (n=5) improved from 60% to 95%. Finally, DGC reference range study using 128 healthy donor samples (age range 18, 72 years) and scoring 100-200 platelets from each donor showed that the DGC distribution of each donor sample was left-skewed with a median of 15% of empty platelets (range: 3, 40). The median DGC was 2.6 with a range of 1.0—5.1. Reference ranges established at the lower 95th percentile for DGC empty platelets is ≤ 31% (95% CI 28, 34) and for the mid-95th percentiles of DGCs between 1.5 and 4.0. DGCs were weakly associated with MPV and IPF (ρ between 0.22 and 0.28); and inversely associated with the percentage of empty platelets (ρ between -0.26 and -0.25). DGC showed no significant association with PC, platelet maximum aggregation or primary slope of aggregation, nor age or gender. Conclusion We validated platelet WM TEM procedures and for the first time established an adult reference range for platelet DGC. The results of association analyses implied that immature platelets may have slightly more DGs. Disclosures: No relevant conflicts of interest to declare.

The frequent observations of heterogeneous tumor foci in prostate cancers indicate that the molecular changes induced by carcinogenic insult take place over wide areas within the diseased prostate. These ‘field effect’ alterations provide important clues regarding the initiation of prostate cancer (PCa) and suggest targets for cancer prevention or biomarkers for early detection. However, PCa field effect biomarkers that have passed independent validation are lacking largely because these alterations are subtle and difficult to distinguish from unrelated small changes in gene expression in the benign prostate. We postulated that shared expression alterations in PCa and in benign prostate tissue in prostate glands that contain prostate cancer (BPC) would have a higher potential for independent validation than alterations identified in BPC alone. Expression analyses was performed on PCa (n = 37) and unmatched BPC (n = 36) and contrasted with benign prostate glands (BP) from patients free of prostate cancer (n =28). These analyses identified gene alterations that were concomitantly present in both PCa and BPC. The majority of the selected markers were validated by quantitative RT-PCR in an independent set of BPC (n = 33) and BP (n =18). Validated markers included genes and non-exonic sequences not previously associated with PCa field effect. A statistical model based on CCNB1 and non-exonic NACA locus discriminated between BPC and BP in the RT-PCR set and in an external microarray dataset with accuracies of 0.84 and 0.90, respectively. Genes with predominant expression in prostate stroma were identified by expression profiling of stroma and epithelial cells collected by laser captured microdissection. Pathway analysis identified enriched GO categories in BPC stroma including PDGFR signaling. These results validate our approach for finding PCa field effect alterations and demonstrate a prostate cancer transcriptome fingerprint in the adjacent non-neoplastic cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3008. doi:1538-7445.AM2012-3008