Adoptive Transfer of Human Papillomavirus E7-specific CTL Enhances Tumor Chemoresponse Through the Perforin/Granzyme-mediated Pathway

Adoptive cytotoxic T lymphocyte (CTL) therapy has an important implication in treating cancer patients. Here, we investigate whether adoptive transfer of human papillomavirus (HPV) E7-specific CTL can enhance tumor chemoresponse using an established cervical cancer animal model. Cisplatin-based chemotherapy plus CTL therapy showed an improved therapeutic effectiveness, along with antitumor protective responses to a parental tumor cell rechallenge. Cisplatin treatment dose-dependently increased the expression of Fas, intercellular adhesion molecule (ICAM)-1, and major histocompatibility complex (MHC) class I antigens (Ags) on tumor cells in vitro. However, CTL-expressing FasL failed to improve antitumor activity in vitro and in animals, resulting from nonfunctional Fas expressed on tumor cells. In contrast, ethylene glycol tetraacetic acid (EGTA) treatment blocked increased sensitivity of cisplatin-treated tumor cells to CTL-mediated killing in vitro, suggesting an important role of the perforin/granzyme-mediated pathway for improved therapeutic effectiveness. This notion was further confirmed by perforin knockout animal studies. Thus, this study shows that (i) modulation of Ag (Fas, ICAM-1) expression by tumor cells has little effect on their increased sensitivity to CTL-mediated killing, (ii) improved therapeutic effectiveness is mediated mainly through the perforin/granzyme-mediated tumor killing pathway, and (iii) a combination of chemotherapy and adoptive E7-specific CTL transfer augments antitumor therapeutic activity in vivo. This finding may have important implications for treating HPV-associated cervical cancer.     

Exodeviated Ophthalmoplegia in a Patient with Progressive Supranuclear Palsy

We report a patient with progressive supranuclear palsy (PSP) with his serial photographs before the onset of ocular symptoms and after the onset with two year intervals. These photographs show his progressive eyeball deviations toward complete exotropia. There were no effective voluntary eyeball movements, Bell''s phenomenon, doll''s eye movements, and vestibulo-ocular reflexes. These signs indicate the involvement of the oculomotor nuclear complex by the disease. We suggest that PSP may cause not only ''supranuclear'' but also ''nuclear'' complete ophthalmoplegia with exodeviation of the eyes.     

Additive Effect of Vitamin C to Statin in Improving the Endothelial Function in Hypercholesterolemic Patients

Lipid lowering agents and anti-oxidants are known to improve endothelial dysfunction in hypercholesterolemic patients, respectively. The objective of this study is to investigate whether vitamin C has additional benefit on endothelial function of statin-treated hypercholesterolemic patients. The endothelial function was estimated using venous occlusion plethysmography (VOP) in 13 hypercholesterolemic patients and 9 healthy volunteers. The patients in the HC group were treated with the statin, then examined again. The change of the forearm blood flow (FBF) was measured with the acetylcholine infusion through brachial artery and also with intra-arterial vitamin C. Endothelium-dependent vasodilatation was significantly impaired in the HC group compared to the control group (p < 0.01). The FBF increased significantly after statin therapy (8.4 ± 1.3 25.2 ± 3.1 ml/min/100 mg forearm tissue, p < 0.01). Vitamin C infusion in these patients results in additional improvement in FBF (25.2 ± 3.1 31.9 ± 4.9, p < 0.05). Vitamin C seems to have additional benefit on the endothelial function of statin-treated hypercholesterolemic patients.     

Characteristics of cytomegalovirus enterocolitis in patients with or without inflammatory bowel diseases

Objectives: Cytomegalovirus (CMV) disease is more common in immunocompromised patients but may occur in people with normal immune function. In addition, CMV enterocolitis can aggravate inflammatory bowel diseases (IBD), but there was little knowledge of differences in clinical and endoscopic features of CMV enterocolitis between patients with IBD and without IBD. The aim of this study was to determine the difference in clinical implication in CMV enterocolitis between the IBD patients and non-IBD patients.

Methods: This was a retrospective study of 82 patients with CMV enterocolitis based on the pathologic findings at two tertiary referral hospitals from 2003 to 2013. Clinical and endoscopic characteristics and clinical course were analyzed according to the presence of IBD.

Results: Of the 82 patients, 25 (30.5%) had IBD and 57 (69.5%) did not have IBD. Hematochezia was more common in IBD patients (84.0% vs. 35.1%; p = .001), but fever and positive CMV antigenemia were more common in non-IBD patients (50.9% vs. 12.0%; p = .001; 54.4% vs. 28.0; p = .027). Endoscopic findings showed more ulcer with inflammation in IBD patients (68.0% vs. 35.2%; p = .005). Sixty-four patients were treated with antiviral agents and 12 patients who did not receive antiviral agents recovered spontaneously. All naturally healed patients were in normal immune status.

Conclusions: Hematochezia is more common in IBD patients and fever/CMV antigenemia is more common in patients without IBD. In patients without IBD, the natural resolution of CMV enterocolitis is expected at least in normal immune function.     

Ghrelin increases food intake in obese as well as lean subjects

OBJECTIVE: To investigate whether effects on food intake are seen in obese subjects receiving exogenous administration of ghrelin. DESIGN: Randomised, double-blind, placebo-controlled study of intravenous ghrelin at doses 1 pmol/kg/min and 5 pmol/kg/min. SUBJECTS: In all, 12 healthy lean subjects (mean body mass index (BMI) 20.5+/-0.17 kg/m(2)) and 12 healthy overweight and obese subjects (mean BMI 31.9+/-1.02 kg/m(2)). MEASUREMENTS: Food intake, appetite and palatability of food, ghrelin and other obesity-related hormones, growth hormone. RESULTS: Low-dose infusion of ghrelin increased ad libitum energy intake at a buffet meal in the obese group only (mean increase 36.6+/-9.4%, P<0.01.) High-dose ghrelin infusion increased energy intake in both groups (mean increase 20.1+/-10.6% in the lean and 70.1+/-15.5% in the obese, P<0.01 in both cases.) Ghrelin infusion increased palatability of food in the obese group. CONCLUSION: Ghrelin increases food intake in obese as well as lean subjects. Obese people are sensitive to the appetite-stimulating effects of ghrelin and inhibition of circulating ghrelin may be a useful therapeutic target in the treatment of obesity.     

Efficacy of lamivudine re-treatment for relapsed patients after an initial lamivudine therapy in HBeAg-positive chronic hepatitis B

The efficacy of lamivudine re-treatment in chronic hepatitis B (CHB) patients who relapse after HBeAg seroconversion with lamivudine has not been investigated. The aim of this study was to evaluate the efficacy of lamivudine re-treatment in relapsed patients. Among 192 patients who had achieved HBeAg seroconversion with lamivudine at a dose of 100 mg/day, 121 patients discontinued lamivudine. Relapse occurred in 49 patients (40.5%). Thirty-three relapsed patients received lamivudine re-treatment for at least 6 months. The mean duration of lamivudine re-treatment was 16 months and the follow-up period was 8.9 months. HBeAg seroconversion was achieved in 23 patients (69.7%). The cumulative HBeAg seroconversion rates at 5, 9, and 12 months were 60, 64, and 67%, respectively. The mean time to HBeAg seroconversion in lamivudine re-treatment was shorter than that in the initial therapy (4.7 months vs. 9.7 months). Viral breakthrough occurred in six (18.2%) patients. All patients with viral breakthrough were accompanied by elevation of serum alanine aminotransferase (ALT) levels. Among 15 patients who discontinued lamivudine re-treatment after HBeAg seroconversion, relapse occurred in six patients (40%). All relapses occurred within 9 months after the discontinuation of lamivudine re-treatment. In conclusion, lamivudine re-treatment in relapsed patients after initial lamivudine therapy had a higher response rate and shorter duration to HBeAg seroconversion than during the initial therapy. However, HBeAg seroconversion induced by lamivudine re-treatment was not durable.     

Preventive Effect of the Flavonoid, Wogonin, Against Ethanol-Induced Gastric Mucosal Damage in Rats

Whether wogonin (5,7-dihydroxy-8-methoxyflavone), a flavonoid originated from the root of Scutellaria baicalensis Georgi, which has been shown to have antiinflammatory and antitumor activities in various cell types, possesses a gastric cytoprotective effect was investigated in an ethanol-induced gastric damage model in rats. Ethanol administration alone induced evident gastric damage including gastric hemorrhages and edema, while this gastric damage was significantly attenuated by wogonin pretreatment (30 mg/kg B.W.) 1 hr before ethanol administration. As major protective mechanisms of wogonin on ethanol-induced gastric damage, we found that wogonin showed either antiinflammatory effects through dual actions on arachidonic acid metabolism, i.e., induction of prostaglandin D2 and suppression of 5S-hydroxyeicosatetraenoic acid (5S-HETE), or preventive induction of profuse apoptosis in the stomach. Conclusively, the flavonoid wogonin could be used as a preventive agent of alcohol-induced gastropathy, whose actions were proven to be strong antiinflammation and apoptosis induction.     

Aging reduces neural specialization in ventral visual cortex

The present study investigated whether neural structures become less functionally differentiated and specialized with age. We studied ventral visual cortex, an area of the brain that responds selectively to visual categories (faces, places, and words) in young adults, and that shows little atrophy with age. Functional MRI was used to estimate neural activity in this cortical area, while young and old adults viewed faces, houses, pseudowords, and chairs. The results demonstrated significantly less neural specialization for these stimulus categories in older adults across a range of analyses.     

A Pilot Exploratory Study of Oral Electrical Stimulation on Swallow Function following Stroke: An Innovative Technique

This pilot study investigated the effect of oral electrical stimulation on swallow function in stroke patients with chronic dysphagia. The purpose was to determine whether an innovative technique could make an improvement in swallow function that might be developed as a potential treatment for patients with persistent dysphagia. Four stroke patients with chronic dysphagia were recruited on the basis of videofluoroscopic findings of a delayed swallow reflex. A single case design was used. Oral electrical stimulation of swallowing was carried out using a palatal prosthesis starting at an output pulse of 0.5 mA, with a fixed duration of 200 μsec, repeated at 1-sec intervals. Barium paste (1 × 5 ml) was introduced at the level of the patient's maximum tolerance of stimulation and any effect on swallow function was recorded by videofluoroscopy. The findings from the pilot study indicated that oral electrical stimulation resulted in an improvement in swallow function in 2 of the 4 patients. The stimulation was well tolerated in all cases with no serious adverse effects. These early results are promising, but further research is needed.