Bilateral Orbital Inflammation as a Manifestation of Paraneoplastic Syndrome

Paraneoplastic neurologic syndromes (PNS) constitute a rare group of disorders whose optimal treatment is yet to be established. We report a patient with bilateral orbital inflammation associated with PNS, who responded well to surgical resection of the primary tumor. An 83-year-old woman was referred to our department for treatment of a progressive reduction in visual acuity and palpebral swelling in both eyes for the past 2 months. She was scheduled to undergo thoracic surgery for lung cancer. The best-corrected visual acuity (BCVA) in the right and left eye had worsened from 0.3 to 0.5 one month before she was referred to our department to 0.03 and 0.07, respectively. A slit-lamp examination revealed edema in both eyelids. Goldmann perimetry revealed several paracentral scotomas with constriction of the peripheral visual fields of both eyes, along with central absolute scotomas in V-4e isopter in the right eye. Magnetic resonance imaging revealed swelling of the bilateral extraocular muscles, which compressed the bilateral optic nerves at the orbital apex. Seven days after the resection of the lung cancer, the BCVA improved to 0.07 and 0.15 in the right and left eyes, respectively, without concomitant immunotherapy. Intravenous methylprednisolone (500 mg/day) was administered for 3 days to treat the residual orbital inflammation. Fourteen days after surgery, the BCVA further improved to 0.4 and 0.5 in the right and left eyes, respectively. Swelling of the bilateral extraocular muscles and the visual field abnormalities improved dramatically. Early diagnosis is crucial for the management of PNS

Palmitate induces reactive oxygen species production and β-cell dysfunction by activating nicotinamide adenine dinucleotide phosphate oxidase through Src signaling.

[Aims/Introduction]Chronic hyperlipidemia impairs pancreatic β-cell function, referred to as lipotoxicity. We have reported an important role of endogenous reactive oxygen species (ROS) overproduction by activation of Src, a non-receptor tyrosine kinase, in impaired glucose-induced insulin secretion (GIIS) from diabetic rat islets. In the present study, we investigated the role of ROS production by Src signaling in palmitate-induced dysfunction of β-cells. [Materials and Methods]After rat insulinoma INS-1D cells were exposed to 0.6 mmol/L palmitate for 24 h (palmitate exposure); GIIS, ROS production and nicotinamide adenine dinucleotide phosphate oxidase (NOX) activity were examined with or without exposure to10 μmol/L 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2), a Src inhibitior, for 30 or 60 min. [Results]Exposure to PP2 recovered impaired GIIS and decreased ROS overproduction as a result of palmitate exposure. Palmitate exposure increased activity of NOX and protein levels of NOX2, a pathological ROS source in β-cells. Palmitate exposure increased the protein level of p47phox, a regulatory protein of NOX2, in membrane fraction compared with control, which was reduced by PP2. Transfection of small interfering ribonucleic acid of p47phox suppressed the augmented p47phox protein level in membrane fraction, decreased augmented ROS production and increased impaired GΙIS by palmitate exposure. In addition, exposure to PP2 ameliorated impaired GIIS and decreased ROS production in isolated islets of KK-Ay mice, an obese diabetic model with hyperlipidemia. [Conclusions]Activation of NOX through Src signaling plays an important role in ROS overproduction and impaired GΙIS caused by chronic exposure to palmitate, suggesting a lipotoxic mechanism of β-cell dysfunction of obese mice

Protein kinase C (Pkc)-δ mediates arginine-induced glucagon secretion in pancreatic α-cells

The pathophysiology of type 2 diabetes involves insulin and glucagon. Protein kinase C (Pkc)-δ, a serine-threonine kinase, is ubiquitously expressed and involved in regulating cell death and proliferation. However, the role of Pkcδ in regulating glucagon secretion in pancreatic α-cells remains unclear. Therefore, this study aimed to elucidate the physiological role of Pkcδ in glucagon secretion from pancreatic α-cells. Glucagon secretions were investigated in Pkcδ-knockdown InR1G9 cells and pancreatic α-cell-specific Pkcδ-knockout (αPkcδKO) mice. Knockdown of Pkcδ in the glucagon-secreting cell line InR1G9 cells reduced glucagon secretion. The basic amino acid arginine enhances glucagon secretion via voltage-dependent calcium channels (VDCC). Furthermore, we showed that arginine increased Pkcδ phosphorylation at Th

Photoinduced swing of a diarylethene thin broad sword shaped crystal:a study on the detailed mechanism

We report a swinging motion of photochromic thin broad sword shaped crystals upon continuous irradiation with UV light. By contrast in thick crystals, photosalient phenomena were observed. The bending and swinging mechanisms are in fact due to molecular size changes as well as phase transitions. The first slight bending away from the light source is due to photocyclization-induced surface expansion, and the second dramatic bending toward UV incidence is due to single-crystal-to-single-crystal (SCSC) phase transition from the original phase I to phase IIUV. Upon visible light irradiation, the crystal returned to phase I. A similar SCSC phase transition with a similar volume decrease occurred by lowering the temperature (phase IIItemp). For both photoinduced and thermal SCSC phase transitions, the symmetry of the unit cell is lowered; in phase IIUV the twisting angle of disordered phenyl groups is different between two adjacent molecules, while in phase IIItemp, the population of the phenyl rotamer is different between adjacent molecules. In the case of phase IIUV, we found thickness dependent photosalient phenomena. The thin broad sword shaped crystals with a 3 mu m thickness showed no photosalient phenomena, whereas photoinduced SCSC phase transition occurred. In contrast, large crystals of several tens of mu m thickness showed photosalient phenomena on the irradiated surface where SCSC phase transition occurred. The results indicated that the accumulated strain, between isomerized and non-isomerized layers, gave rise to the photosalient phenomenon

Post‐transplant Lymphoproliferative Disorders After Liver Transplantation: A Retrospective Cohort Study Including 1954 Transplants

Post-transplant lymphoproliferative disorders (PTLDs) are life-threatening neoplasms after organ transplantation. Because of their rarity and multiple grades of malignancy, the incidence, outcomes, and clinicopathological features affecting patient survival after liver transplantation (LT) remain unclear. We reviewed 1954 LTs in 1849 recipients (1990-2020), including 886 pediatric (<18 years of age) and 963 adult recipients. The following clinicopathological factors were studied: age, sex, liver etiologies, malignancy grades, Epstein-Barr virus status, performance status (PS), Ann Arbor stage, international prognostic index, and histopathological diagnosis. Of 1849 recipients, 79 PTLD lesions (4.3%) were identified in 70 patients (3.8%). After excluding 3 autopsy cases incidentally found, 67 (45 pediatric [5.1%] and 22 adult [2.3%]) patients were finally enrolled. Comorbid PTLDs significantly worsened recipient survival compared with non-complicated cases (P < 0.001). The 3-year, 5-year, and 10-year overall survival rates after PTLD diagnosis were 74%, 66%, and 58%, respectively. The incidence of PTLDs after LT (LT-PTLDs) was significantly higher (P < 0.001) with earlier onset (P = 0.002) in children, whereas patient survival was significantly worse in adults (P = 0.002). Univariate and multivariate analyses identified the following 3 prognostic factors: age at PTLD diagnosis ≥18 years (hazard ratio [HR], 11.2; 95% confidence interval [CI], 2.63-47.4; P = 0.001), PS ≥2 at diagnosis (HR, 6.77; 95% CI, 1.56-29.3; P = 0.01), and monomorphic type (HR, 6.78; 95% CI, 1.40-32.9; P = 0.02). A prognostic index, the “LT-PTLD score, ” that consists of these 3 factors effectively stratified patient survival and progression-free survival (P = 0.003 and <0.001, respectively). In conclusion, comorbid PTLDs significantly worsened patient survival after LT. Age ≥18 years and PS ≥2 at PTLD diagnosis, and monomorphic type are independent prognostic factors, and the LT-PTLD score that consists of these 3 factors may distinguish high-risk cases and guide adequate interventions

Minute ampullary carcinoid tumor with lymph node metastases: a case report and review of literature

<p>Abstract</p> <p>Background</p> <p>Carcinoid tumors are usually considered to have a low degree of malignancy and show slow progression. One of the factors indicating the malignancy of these tumors is their size, and small ampullary carcinoid tumors have been sometimes treated by endoscopic resection.</p> <p>Case presentation</p> <p>We report a case of a 63-year-old woman with a minute ampullary carcinoid tumor that was 7 mm in diameter, but was associated with 2 peripancreatic lymph node metastases. Mild elevation of liver enzymes was found at her regular medical check-up. Computed tomography (CT) revealed a markedly dilated common bile duct (CBD) and two enlarged peripancreatic lymph nodes. Endoscopy showed that the ampulla was slightly enlarged by a submucosal tumor. The biopsy specimen revealed tumor cells that showed monotonous proliferation suggestive of a carcinoid tumor. She underwent a pylorus-preserving whipple resection with lymph node dissection. The resected lesion was a small submucosal tumor (7 mm in diameter) at the ampulla, with metastasis to 2 peripancreatic lymph nodes, and it was diagnosed as a malignant carcinoid tumor.</p> <p>Conclusion</p> <p>Recently there have been some reports of endoscopic ampullectomy for small carcinoid tumors. However, this case suggests that attention should be paid to the possibility of lymph node metastases as well as that of regional infiltration of the tumor even for minute ampullary carcinoid tumors to provide the best chance for cure.</p

Genome-wide DNA methylation profiles in both precancerous conditions and clear cell renal cell carcinomas are correlated with malignant potential and patient outcome

To clarify genome-wide DNA methylation profiles during multistage renal carcinogenesis, bacterial artificial chromosome array-based methylated CpG island amplification (BAMCA) was performed. Non-cancerous renal cortex tissue obtained from patients with clear cell renal cell carcinomas (RCCs) (N) was at the precancerous stage where DNA hypomethylation and DNA hypermethylation on multiple bacterial artificial chromosome (BAC) clones were observed. By unsupervised hierarchical clustering analysis based on BAMCA data for their N, 51 patients with clear cell RCCs were clustered into two subclasses, Clusters AN (n = 46) and BN (n = 5). Clinicopathologically aggressive clear cell RCCs were accumulated in Cluster BN, and the overall survival rate of patients in Cluster BN was significantly lower than that of patients in Cluster AN. By unsupervised hierarchical clustering analysis based on BAMCA data for their RCCs, 51 patients were clustered into two subclasses, Clusters AT (n = 43) and BT (n = 8). Clinicopathologically aggressive clear cell RCCs were accumulated in Cluster BT, and the overall survival rate of patients in Cluster BT was significantly lower than that of patients in Cluster AT. Multivariate analysis revealed that belonging to Cluster BT was an independent predictor of recurrence. Cluster BN was completely included in Cluster BT, and the majority of the BAC clones that significantly discriminated Cluster BN from Cluster AN also discriminated Cluster BT from Cluster AT. In individual patients, DNA methylation status in N was basically inherited by the corresponding clear cell RCC. DNA methylation alterations in the precancerous stage may generate more malignant clear cell RCCs and determine patient outcome