Matrigel‐Based Sprouting Endothelial Cell Culture System from Mouse Corpus Cavernosum Is Potentially Useful for the Study of Endothelial and Erectile Dysfunction Related to High‐Glucose Exposure

IntroductionA proper cavernous endothelial cell culture system would be advantageous for the study of the pathophysiologic mechanisms involved in endothelial dysfunction and erectile dysfunction (ED).AimTo establish a nonenzymatic technique, which we termed the “Matrigel‐based sprouting endothelial cell culture system,” for the isolation of mouse cavernous endothelial cells (MCECs) and an in vitro model that mimics in vivo situation for diabetes‐induced ED.MethodsFor primary MCEC culture, mouse cavernous tissue was implanted into Matrigel and sprouting cells from the tissue were subcultivated. To establish an in vitro model for diabetes‐induced ED, the primary cultured MCECs were exposed to a normal‐glucose (5 mmoL) or a high‐glucose (30 mmoL) condition for 48 hours.Main Outcome MeasuresThe purity of isolated cells was determined by fluorescence‐activated cell sorting analysis. MCECs incubated under the normal‐ or the high‐glucose condition were used for Western blot, cyclic guanosine monophosphate (cGMP) quantification, and in vitro angiogenesis assay.ResultsWe could consistently isolate high‐purity MCECs (about 97%) with the Matrigel‐based sprouting endothelial cell culture system. MCECs were subcultured up to the fifth passage and no significant changes were noted in endothelial cell morphology or purity. The phosphorylation of Akt and eNOS and the cGMP concentration were significantly lower in MCECs exposed to high glucose than in those exposed to normal glucose. MCECs exposed to the normal‐glucose condition formed well‐organized capillary‐like structures, whereas derangements in tube formation were noted in MCECs exposed to high glucose. The protein expression of transforming growth factor‐β1 (TGF‐β1) and phospho‐Smad2 was significantly increased by exposure to high glucose.ConclusionThe Matrigel‐based sprouting endothelial cell culture system is a simple, technically feasible, and reproducible technique for isolating pure cavernous endothelial cells in mice. An in vitro model for diabetic ED will be a valuable tool for evaluating the angiogenic potential of novel endogenous or synthetic modulators. Yin GN, Ryu J‐K, Kwon M‐H, Shin SH, Jin HR, Song K‐M, Choi MJ, Kang D‐Y, Kim WJ, and Suh J‐K. Matrigel‐based sprouting endothelial cell culture system from mouse corpus cavernosum is potentially useful for the study of endothelial and erectile dysfunction related to high‐glucose exposure. J Sex Med 2012;9:1777–1789.     

High Shear Stress at the Surface of Enhancing Plaque in the Systolic Phase is Related to the Symptom Presentation of Severe M1 Stenosis

The computational fluid dynamics methods for the limited flow rate and the small dimensions of an intracranial artery stenosis may help demonstrate the stroke mechanism in intracranial atherosclerosis. We have modeled the high wall shear stress (WSS) in a severe M1 stenosis. The high WSS in the systolic phase of the cardiac cycle was well-correlated with a thick fibrous cap atheroma with enhancement, as was determined using high-resolution plaque imaging techniques in a severe stenosis of the middle cerebral artery.     

Microglandular Adenosis

Microglandular adenosis (MGA) of the breast is a very rare and benign proliferative lesion. Most patients complain of a palpable breast mass that may arouse a clinical suspicion of breast cancer. Histopathologically, it is hard to distinguish MGA from breast cancer because of the lack of a myoepithelial layer and infiltrative proliferation. Several studies have reported a strong relationship between MGA and carcinoma arising in MGA, so the mass should be excised completely in cases of MGA determined from a core needle biopsy rather than observation. A 72-years-old woman presented with a palpable breast mass. On physical examination, a mass was palpable in the right upper outer quadrant area and somewhat fixed to the surrounding tissues and pectoralis major muscle. We could not detect any mass or dense lesion on mammography because of a grade 4 dense breast. Ultrasonographic findings revealed a low echoic lesion with indistinct margins. The result of a core needle biopsy was MGA, which was confirmed by excision. We report one case of MGA, which was believed to breast cancer clinically.     

Nardostachys jatamansi extract protects against cytokine-induced β-cell damage and streptozotocin-induced diabetes

AIM: To investigate the anti-diabetogenic mechanism of Nardostachys jatamansi extract (NJE). METHODS: Mice were injected with streptozotocin viaa tail vein to induce diabetes. Rat insulinoma RINm5F cells and isolated rat islets were treated with interleukin1β and interferon-γ to induce cytotoxicity. RESULTS: Treatment of mice with streptozotocin resulted in hyperglycemia and hypoinsulinemia, which was conf irmed by immunohistochemical staining of the islets. The diabetogenic effects of streptozotocin were c...     

A novel videoendoscopy system by using autofluorescence and reflectance imaging for diagnosis of esophagogastric cancers

BACKGROUND: Image quality of the prior autofluorescence (AF) imaging systems, including the fiber-optic endoscope, was not feasible for general clinical use. The use of AF image alone resulted in low specificity. The objective of the study was to evaluate the resolution and the sensitivity of the novel videoendoscopy system by using AF and reflectance imaging (AFI) in the diagnosis of early esophagogastric cancers. METHODS: This was a case series study. The setting was a pretreatment examination at a cancer center. Five patients with superficial esophageal cancers (SEC) and 21 patients with 22 early gastric cancers (EGC) were included in the study. The extent of the tumors was diagnosed by white light (WL), AF and chromoendoscopic observations. The main outcome measurement was the diagnostic accuracy of each observation in relation to the histologic mapping as a criterion standard. RESULTS: Two of 5 SECs (40%) were correctly diagnosed in the WL image and all (100%) in the AF image as purple or magenta color in a green background. EGCs in atrophic mucosa were observed as purple or magenta areas in a green background, while diffuse-type EGCs in fundic mucosa were observed as green areas in a purple background. Of the 22 EGCs, diagnostic accuracy of WL, AF, and chromoendoscopic observations were 36%: 95% CI [16%, 56%], 68%: 95% CI [49%, 88%], and 91%: 95% CI [79%, 100%], respectively. AFI could reveal flat or isochromatic extensions that were not detected in the WL images. The limitations of the study were ulcerations or inflammation that caused overdiagnosis in the AF observation. CONCLUSIONS: The resolution of the AFI at present is limited, but the image quality was acceptable. The current system of AFI does not equal to chromoendoscopy in sensitivity but has an advantage over standard WL videoendoscopy.     

Therapeutic Decision-Making Using Endoscopic Ultrasonography in Endoscopic Treatment of Early Gastric Cancer

Background/Aims

We evaluated the effectiveness of an endoscopic ultrasonography (EUS)-based treatment plan compared to an endoscopy-based treatment plan in selecting candidates with early gastric cancer (EGC) for endoscopic submucosal dissection based on the prediction of invasion depth.

Methods

We reviewed 393 EGCs with differentiated histology from 380 patients who underwent EUS from July 2007 to April 2010. The effectiveness of the EUS-based and endoscopy-based plans was evaluated using a simplified hypothetical treatment algorithm.

Results

The numbers of endoscopically determined mucosal, indeterminate, and submucosal cancers were 253 (64.4%), 56 (14.2%), and 84 (21.4%), respectively. Overall, the appropriate treatment selection rates were 75.3% (296/393) in the endoscopy-based plan and 71.5% (281/393) in the EUS-based plan (p=0.184). For endoscopic mucosal cancers, the appropriate treatment selection rates in the endoscopy-based plan were 88.1% (223/253), while the use of an EUS-based plan significantly decreased this rate to 81.4% (206/253) (p=0.036). For endoscopic submucosal cancers, the appropriate selection rates did not differ between the endoscopy-based plan (46.4%, 39/84) and the EUS-based plan (53.6%, 45/84) (p=0.070).

Conclusions

EUS did not increase the likelihood of selecting the appropriate treatment in differentiated-type EGC. Therefore, EUS may not be necessary before treating differentiated-type EGC, especially in endoscopically presumed mucosal cancers.     

Thrombopoietin-producing hepatocellular carcinoma

A 66-year-old man with hepatocellular carcinoma (HCC) showed marked thrombocytosis (110.7 x 10(4)/microl). Bone marrow (BM) aspirates demonstrated an increase of mature megakaryocytes (MgK). The serum thrombopoietin (TPO) level was increased to about 100-fold that of the normal level in the terminal stage. However, the platelet count gradually decreased to 13.5 x 10(4)/microl. The autopsy specimen revealed normoplastic BM with decreased MgK, mainly consisting of the immature type, and it was negative for tumor cells. Liver specimen showed markedly fatty metamorphosis. Immunohistochemical staining of TPO demonstrated that hepatocytes were weakly stained and HCC cells strongly stained, suggesting TPO-producing HCC.     

Occult Diffuse Neoplasm in the Lungs: Intravascular Large B-Cell Lymphoma

BackgroundIntrathoracic involvement with lymphomas is common and manifests lymphadenopathy as well as a wide spectrum of imaging abnormalities in the lungs. Intravascular large B-cell lymphoma (IVLBCL) is a rare extranodal subtype of large B-cell lymphoma that typically involves small blood vessels and is difficult to detect.MethodsUsing a computer-assisted search, we identified patients with histopathologically proven IVLBCL in the lungs at Mayo Clinic from 2001 through 2018. Medical records, imaging studies, and pathologic specimens were reviewed.ResultsA total of 5 patients were diagnosed with a median age at diagnosis of 68 years (range, 44-73); 4 patients were male. The diagnosis of IVLBCL was achieved by surgical lung biopsy in 3 and at autopsy in 2. At presentation, all 5 patients had dyspnea and systemic symptoms including fever, fatigue, night sweats, and/or weight loss. Chest radiography and computed tomography (CT) failed to demonstrate the diffuse infiltrative process; positron emission tomography (PET) scan performed in 2 patients did not show fluorodeoxyglucose (FDG) uptake in the lungs. Pulmonary function tests obtained in 3 patients showed reduced diffusing capacity in all; transthoracic echocardiography yielded evidence of pulmonary hypertension in 2 of 4 patients. All 3 patients diagnosed antemortem underwent chemotherapy with 1 patient remaining alive at 4 years after diagnosis.ConclusionsIVLBCL is difficult to diagnose given variable and nonspecific clinical presentations. Microvascular disease processes such as IVLBCL should be kept in mind in cases of undiagnosed progressive dyspnea accompanied by systemic symptoms even when imaging studies are unrevealing.     

Successful defibrotide treatment of a patient with veno-occlusive disease after living-donor liver transplantation: A case report

Rationale:Veno-occlusive disease (VOD) is characterized by painful hepatomegaly, ascites, weight gain, and jaundice with nonthrombotic, fibrous obliteration of the centrilobular hepatic veins. VOD after liver transplantation is a rare complication, with an incidence of approximately 2%; however, it can be life-threatening in severe cases. The precise etiology and mechanism of VOD after liver transplantation remains unclear. Acute cellular rejection, antibody-mediated rejection, and treatment with tacrolimus or azathioprine may be associated with the development of VOD after liver transplantation. Additionally, the optimal treatment of VOD after liver transplantation has not yet been established and focuses on supportive care. Defibrotide is an anti-ischemic and antithrombotic drug with no systemic anticoagulant effects. Moreover, only a few reports have investigated the use of defibrotide for VOD after liver transplantation, which has shown promising results.Patient concerns:A 39-year-old woman with primary biliary cholangitis underwent living-donor liver transplantation at our center. She experienced right upper quadrant pain with increased ascites, pleural effusion, and weight gain on postoperative day 14.Diagnoses:Imaging and pathological tests showed no evidence of rejection or vessel complications. VOD was diagnosed clinically based on the findings of weight gain, ascites, jaundice, and pathological biopsy.Interventions:Defibrotid, 25 mg/kg/day, was administered intravenously for 21 days.Outcomes:She showed complete clinical resolution of the VOD.Lessons:Herein, we report a case of successful defibrotide treatment of VOD after living-donor liver transplantation.