Augmentation of tumor necrosis factor family-induced apoptosis by E3330 in human hepatocellular carcinoma cell lines via inhibition of NFκB

AIM: To investigate the reduction of cell viability in human hepatocellular carcinoma (HCC) cell lines induced by inhibition of nuclear factor κB (NFκB).METHODS: HLE, SKHep1, and HepG2 were incubated and E3330 was used to compare the stimulation of some chemotherapeutic drugs with that of TNF family, Fas ligand, TNFα and TNF-related apoptosis-inducing ligand (TRAIL) at the point of the reduction of cell viability by inhibiting NFκB.RESULTS: E3330 decreased NFκB levels in HLE cells stimulated by TNF and TRAIL. The cytotoxicity of the combination of TRAIL, TNFα, Fas ligand, and E3330increased synergistically in a dose-dependent manner compared to either E3330 alone in all HCC cell lines by MTT assay. However, the combination of some chemotherapeutic drugs and E3330 did not decrease the cell viability.CONCLUSION: Inhibition of NFκB sensitizes human HCC cell lines to TNF-mediated apoptosis including TRAIL, and TRAIL-based tumor therapy might be a powerful potential therapeutic tool in the treatment of human HCC.     

Elevated levels of soluble fibrin in patients with venous thromboembolism

The fibrin-related markers (FRMs), including soluble fibrin (SF), d-dimer and fibrin and fibrinogen degradation products (FDP) are considered to be useful for the diagnosis of thrombosis; however, evidence for the diagnosis of thrombosis by SF is still not well established. The present study was designed to evaluate the usefulness of SF in the diagnosis of venous thromboembolism (VTE). The plasma concentrations of FRMs were measured in 551 in-patients suspected to have a VTE. The plasma levels of SF, d-dimer and FDP were significantly higher in patients with VTE than patients without VTE and those were significantly higher in patients without VTE than in healthy volunteers. In a receiver operating characteristic analysis for the diagnosis of VTE, the area under the curve was 0.950 for SF, 0.933 for FDP and 0.805 for d-dimer. The appropriate cut-off values for the diagnosis were as follows SF 5.9 μg/ml, FDP 2.1 μg/ml and d-dimer 4.8 μg/ml. To obtain a 100% negative predictive value for the diagnosis of VTE, the SF was less than 5.2 μg/ml, FDP was less than 1.3 μg/ml, and d-dimer was less than 0.5 μg/ml. Our findings suggest that the SF assay is useful for the diagnosis and exclusion of VTE.     

Demographic characteristics of 3,659 Japanese patients with obstructive sleep apnea–hypopnea syndrome diagnosed by full polysomnography: associations with apnea–hypopnea index

Information on obstructive sleep apnea-hypopnea syndrome (OSAHS) in Japan has been limited. The purposes of this clinical study were to evaluate the demographic characteristics of Japanese OSAHS patients and to assess how demographic factors are associated with OSAHS severity. We analyzed 3,659 OSAHS patients who underwent polysomnographic evaluation between January 2000 and December 2004 at 11 hospitals in Niigata Prefecture, Japan. Data consisted of apnea-hypopnea index (AHI) and demographic characteristics, including sex, age, and body-mass index, for statistical analysis. Levels of obesity were classified according to the WHO criteria. The male-to-female patient ratio for OSAHS was 4.6, and male patients presented more severe OSAHS than female patients. High AHI and a high proportion of moderate to serious OSAHS (AHI > or = 15) were found among the patients in their 30s, as well as female patients in their 70s and male patients in their 80s. The AHI and the proportion of moderate-to-serious OSAHS (AHI > or = 15) were greater in patients classified as underweight than in normal weight patients. In conclusion, there is a higher male predominance in the prevalence of OSAHS, and in both sexes, the results suggest different pathophysiological mechanisms of deteriorating OSAHS between adults under age 55 and adults 55 years or over. In addition, underweight patients exhibit more severe OSAHS than normal weight patients.     

Pneumothorax after diagnostic laparoscopy

Here we want to call laparoscopist's attention to pneumothorax after diagnostic laparoscopy. Diagnostic laparoscopy has less complications, compared with laparoscopic surgery. In our experience, only one case (0.04%) developed pneumothorax during routine diagnostic laparoscopic procedure. This complication is presented in a 50-year-old female. She complained of dyspnea just after the decrease of intraabdominal pressure and deflation of intraperitoneal gas. The chest roentgenogram showed a right pneumothorax, and a right chest tube was inserted with immediate relief of tension. Pneumothorax during diagnostic laparoscopy is relatively rare but a major complication; Medline literature research showed six reported cases of pneumothorax after diagnostic laparoscopy from 1983 to 1998 including our case. The etiology was idiopathy in 5 and diaphragmatic injury in 1. Hypotension, elevation of inspiratory pressure, dyspnea, a decrease in systemic oxygen saturation, and loss of breath sounds suggest tension pneumothorax. The clinical condition of the patients improved rapidly because of the easy diffusion of the gas used in laparoscopy. Diagnostic laparoscopists should be aware of this complication and treat ventilatory problems.     

Left ventricular dysfunction and remodeling in streptozotocin-induced diabetic rats.

BACKGROUND: It is not fully clarified how diabetes mellitus (DM)-induced cardiac dysfunction is associated with histopathological changes of the heart in a long lasting period of DM. METHODS AND RESULTS: Eighteen weeks after a streptozotocin injection was given to Wistar - Kyoto rats (D rats), echocardiography and hemodynamic studies including the dobutamine infusion test were performed. After perfusion fixation, immunofluorescent staining and histopathology of the heart were analyzed, and analysis with electron microscopy was also conducted. Systolic blood pressure in the conscious state and left ventricular (LV) ejection fraction by 2-dimensional echocardiography were reduced in D rats. LV mechanical responses to dobutamine assessed by maximal LV pressure derivative (+LVdP/dt) also decreased with higher dobutamine doses in D rats. Although LV and right ventricular (RV) wall thickness were smaller in D rats, there were increased RV volumes, indicating LV and RV dilatational remodeling in D rats. The cardiomyocyte transverse diameter and actin staining in cardiomyocytes in both the LV and RV were significantly reduced, and capillary tortuosity and type IV collagen were increased, indicating microangiopathy in D rats. CONCLUSIONS: Advanced insulin-dependent DM incurred not only RV remodeling but also overt resting LV systolic dysfunction and decreased LV responsiveness to beta adrenergic stimulation with dilatational remodeling, accompanied by pathological changes of capillaries and cardiomyocytes including actin filaments.     

Supraglottic subepithelial benign mass lesions: Focus on clinical features of sialolipoma-like lesion

ObjectivesSialolipoma has been classified as a benign soft tissue lesion in the 2017 World Health Organization classification of head and neck tumors. To our knowledge, only one case of laryngeal sialolipoma has been reported in the English literature. We conducted a retrospective study to identify clinical characteristics of supraglottic sialolipoma-like lesion and differentiate it from other supraglottic subepithelial masses.MethodsMedical records of 16 patients with supraglottic subepithelial benign mass lesions who underwent histological evaluation between 2003 and 2019 were retrospectively analyzed. Sialolipoma-like lesion was defined as a local finding of a well-circumscribed gross mass with pathological presence of salivary gland-like parenchymal lobules with evenly interspersed adipose tissue.ResultsEight patients showed histological positivity for sialolipoma-like lesion, 3 for amyloidosis, 2 for hemangioma, and 1 each for cyst, lymphoid hyperplasia, and chondrometaplasia. Sialolipoma-like lesion tended to be predominant among men; those affected had a mean age of 52.8 (range, 39–74) years. By contrast, among patients with amyloidosis, the ratio of men to women was 1:2 (100% vs. 33%; p = 0.055). Fiberscopic examination of all patients with sialolipoma-like lesions identified well-circumscribed, yellowish masses, closely resembling local amyloidosis findings. Sialolipoma-like lesion was associated with a significantly higher body-mass index (BMI; 27.4 ± 2.8 kg/m²) than amyloidosis (21.6 ± 1.4 kg/m²; p = 0.014). The transoral approach was used for lesion resection in all patients with sialolipoma-like lesion. No patient experienced postoperative recurrence.ConclusionLaryngeal sialolipoma-like lesion might be more prevalent than was previously reported, and histological examination is important to differentiate it from amyloidosis. Supraglottic sialolipoma-like lesion must be differentially diagnosed in patients with high BMI presenting with well-circumscribed, yellowish supraglottic masses.     

Intraoperative dorsal language network mapping by using single‐pulse electrical stimulation

The preservation of language function during brain surgery still poses a challenge. No intraoperative methods have been established to monitor the language network reliably. We aimed to establish intraoperative language network monitoring by means of cortico‐cortical evoked potentials (CCEPs). Subjects were six patients with tumors located close to the arcuate fasciculus (AF) in the language‐dominant left hemisphere. Under general anesthesia, the anterior perisylvian language area (AL) was first defined by the CCEP connectivity patterns between the ventrolateral frontal and temporoparietal area, and also by presurgical neuroimaging findings. We then monitored the integrity of the language network by stimulating AL and by recording CCEPs from the posterior perisylvian language area (PL) consecutively during both general anesthesia and awake condition. High‐frequency electrical stimulation (ES) performed during awake craniotomy confirmed language function at AL in all six patients. Despite an amplitude decline (≤32%) in two patients, CCEP monitoring successfully prevented persistent language impairment. After tumor removal, single‐pulse ES was applied to the white matter tract beneath the floor of the removal cavity in five patients, in order to trace its connections into the language cortices. In three patients in whom high‐frequency ES of the white matter produced naming impairment, this “eloquent” subcortical site directly connected AL and PL, judging from the latencies and distributions of cortico‐ and subcortico‐cortical evoked potentials. In conclusion, this study provided the direct evidence that AL, PL, and AF constitute the dorsal language network. Intraoperative CCEP monitoring is clinically useful for evaluating the integrity of the language network. Hum Brain Mapp 35:4345–4361, 2014. © 2014 Wiley Periodicals, Inc .