The distinctive effects of acute and chronic psychological stress on airway inflammation in a murine model of allergic asthma.

BACKGROUND: Psychological stress has long been recognized to be associated with asthma symptoms. There appear to be individual differences in the susceptibility to even the same kind of stress, and furthermore, stress responses are different between the types of the stress, acute and chronic, even in the same person. However, the mechanisms linking stress to asthma are not well defined. Psychological stress upregulates the expression of endogenous opioids. The opioids stimulate the hypothalamus-pituitary-adrenal axis and sympathetic and adrenomedullary system, through the activation of mu-opioid receptor (MOR) to release stress hormones, such as cortisol and catecholamines, respectively. These hormones can modulate immune responses via the induction of Th1 immunity. METHODS: Female BALB/c and C57BL/6, wild and MOR-deficient, mice sensitized with ovalbumin (OVA) were exposed to OVA with or without either acute or chronic restraint stress. Airway inflammation was evaluated by the measurement of the number of inflammatory cells and cytokine contents in bronchoalveolar lavage fluids. RESULTS: In BALB/c mice, but not in C57BL/6 mice, the number of total cells, eosinophils and lymphocytes in the acute stress group were significantly decreased compared with those in the non-acute stress group. In contrast, chronic stress significantly increased the cell numbers and the contents of IL-4 and IL-5 in both mouse strains. Furthermore, these exacerbations were abolished in MOR-deficient mice. CONCLUSIONS: These results suggest that acute stress modifies the allergic airway responses distinctively depending on the genetic background, and MOR is involved in the chronic psychological stress-induced exacerbation of allergic airway inflammation.     

Increased circulating CD16+ CD14dim monocytes in a patient with pulmonary alveolar proteinosis

Pulmonary alveolar proteinosis (PAP) is characterized by filling of the alveoli with a periodic acid-Schiff-positive proteinaceous material. Although the pathogenesis of primary or idiopathic PAP remains unknown, it has been proposed that a deficiency or loss of responsiveness of the monocyte/macrophage lineage to granulocyte-macrophage colony stimulating factor (GM-CSF) is involved in PAP. Secondary PAP is associated with haematological malignancies, especially in myeloid disorders. Herein, we report on an adult with PAP associated with myelodysplastic syndrome (MDS). The CD16+ CD14dim monocytes comprise 5-10% of circulating monocytes in healthy volunteers. Flow cytometric analysis of the patient in the present study revealed increased CD16+ CD14dim monocytes in the peripheral blood. It has been demonstrated that the expression of CD16 and CD14 is regulated by macrophage colony stimulating factor (M-CSF) and GM-CSF. Hence, serum cytokines were analysed in our patient and the concentration of serum GM-CSF was found to be less than the lower limit of the assay. In addition, serum M-CSF and granulocyte colony stimulating factor levels were only slightly increased above the normal range. These results suggest that the increase in the CD16+ CD14dim subpopulation in the circulation of our patient indicates another pathogenetic mechanism for secondary PAP, such as hyperresponsiveness of the monocyte/macrophage lineage to these cytokines.     

Adjuvant therapy with protein-bound polysaccharide K and tegafur uracil in patients with stage II or III colorectal cancer: randomized,controlled trial

PURPOSE: Intravenous fluorouracil and leucovorin for six to eight months is currently a standard adjuvant treatment for Stage III colon cancer; however, this regimen is complex, inconvenient, and has a high intolerability. Adjuvant chemotherapies are claimed for objective response rates with an acceptable safety profile and complexity. We investigated the benefits of oral protein-bound polysaccharide K added to oral tegafur/uracil on curatively resected Stage II or III colorectal cancer. METHODS: We prospectively randomized 207 patients to treatments of either oral 3.0 g protein-bound polysaccharide K plus 300 mg tegafur/uracil or 300 mg tegafur/uracil alone for two years following 12 mg/m² and 8 mg/m² mitomycin treatment on postoperative Days 1 and 2, respectively. The primary end points were disease-free and overall survival, and recurrence rates. RESULTS: Three (1.4 percent) patients were declared ineligible, and three patients did not start treatment. In total, 201 patients were analyzed. The three-year, disease-free survival rate was 80.6 percent (standard error = 3.4 percent) in the protein-bound polysaccharide K group (P = 0.02) compared with 68.7 percent (SE = 5.7 percent) in the control group after a median follow-up of 3.7 years. The estimated relative risk of recurrence in the control group was 1.87 (95 percent confidence interval, 1.10–3.20) at three years. The three-year, overall survival rate was 87.3 percent (standard error = 2.9 percent) in the protein-bound polysaccharide K group and 80.6 percent (standard error = 4.8 percent) in the control group (P = 0.24). The three-year, overall survival rate in 80 pathological TNM Stage III patients was 83.0 percent (standard error = 5.2 percent) in the protein-bound polysaccharide K group and 59.3 percent (standard error = 9.5 percent) in the control group (P = 0.02). Protein-bound polysaccharide K prevented distant metastases (P = 0.05), particularly lung metastases (P = 0.01). The incidence of adverse effects was minimal, and compliance was good. CONCLUSION: Adjuvant therapy using a combination of oral protein-bound polysaccharide K and tegafur/uracil is highly effective in preventing the recurrence of colorectal cancer in Stage II or III patients, and increases overall survival in pathological TNM Stage III. These results will be a sufficient proof to conduct a larger study to compare tegafur/uracil/protein-bound polysaccharide K with 5-fluorouracil/ leucovorin.     

Successful treatment of cytomegalovirus enteritis after unrelated allogeneic stem cell transplantation by the infusion of ex vivo‐expanded CD4+ lymphocytes derived from the recipient's peripheral blood donor cells

Adoptive immunotherapies have been developed for antiviral agent‐refractory cytomegalovirus (CMV) disease after stem cell transplantation (SCT). However, the application of such strategies is limited, particularly in terms of need for donor cooperation regarding blood sampling and inaccessibility in the setting of cord blood transplantation. Herein, we describe the first successful treatment of antiviral agent‐refractory CMV enteritis after allogeneic SCT by the infusion of ex vivo‐expanded donor‐derived CD4⁺ lymphocytes obtained from the recipient's peripheral blood.     

Specificity of vascular reactivity and remodeling after repeated endothelial injury in a swine model

We investigated the difference in vascular responses and remodeling between coronary and iliac arteries after repeated endothelial denudation. Endothelial denudation of the left anterior descending coronary artery (LAD) and the right common iliac artery (RIA) was repeated 4 times twice a month using a Fogarty catheter in 21 pigs. Vascular responses to vasoactive drugs were evaluated as % luminal diameter changes on contrast angiography 2 weeks after the last denudation. Corresponding nondenuded sites, ie, the left circumflex coronary artery (LCX) and the left common iliac artery (LIA), were used as references. Acetylcholine (1 microg/kg) did not constrict the LCX (0 +/- 1%) and the LAD (1 +/- 1%, P < 0.05), whereas it constricted the RIA (20 +/- 6%) but not the LIA (-3 +/- 3%, P < 0.01). Alternatively, serotonin (10 microg/kg) constricted the LAD strikingly (88 +/- 5%, P < 0.01 versus LCX and RIA), as well as the RIA (35 +/- 10%, P < 0.05 versus LIA). Vasodilator responses to substance P and isosorbide dinitrate were not different after injury in both arteries. The intima-to-media ratio and adventitia-to-media ratio of the relevant site in cross section of tissue sample from LAD were greater than those from LCX, and were more prominent than those from RIA. The results show that vascular tone regulation after the endothelial injury and vascular remodeling might be altered in a vessel-specific manner.     

Immunohistochemistry for the differentiation of peritoneal disseminated carcinoma of unknown origin

We report a woman with ascites, hydrothorax, pancreatic tumor, left cystic ovarian tumor, and an elevated serum cancer antigen 125 level. Exploratory laparotomy was performed to determine peritoneal disseminated carcinoma of unknown origin. Immunohistochemical analysis demonstrated positive staining for carcinoembryonic antigen, trypsin, and progesterone receptor and nonspecific or negative reaction for calretinin, estrogen receptor, amylase, lipase, Wilms tumor gene 1 protein, and inhibin or chromogranin A. These results together with the morphology of tubular structure suggested the pathological diagnosis of adenocarcinoma with pancreatic characteristics and contradicted ovarian cancer or mesothelioma. Immunohistochemistry is an adjunct tool to differentiate the primary site of carcinomatous peritonitis.     

Jejunal pouch interposition with an antiperistaltic conduit as a pyloric ring substitute after standard distal gastrectomy: a comparison with the use of an isoperistaltic conduit

BACKGROUND/AIMS: We performed jejunal pouch interposition with a short antiperistaltic conduit as a pylorus substitute after gastrectomy for gastric cancer and compared the outcome with an isoperistaltic conduit. METHODOLOGY: After a standard distal gastrectomy and lymph node dissection, a 15-cm-long pouch was formed using 3 linear staples (Endo-GIA) and interposed between the residual stomach and duodenum. The distal jejunal limb was made into a 3-cm-long isoperistaltic conduit in the isoperistaltic group (n = 17), and the proximal jejunal limb was made into a 3-cm-long antiperistaltic conduit in the antiperistaltic group (n = 8). Postoperatively, the patients were interviewed periodically to document any complaints. A dual-phase, dual-isotope radionuclide gastro-pouch-emptying study was performed 1 and 6 months after surgery. RESULTS: None of the patients developed postoperative complications and showed discomforts of dumping, stasis or reflux esophagitis. The dietary volume and body weight of patients gradually increased in both groups after 6 months. The combined radioisotope retention rate for the pouch and residual stomach was 31% for liquid food and 35% for solid food in the isoperistaltic group after 120 min, and 41% and 57%, respectively, in the antiperistaltic group. The pattern and emptying rate for solid food in the antiperistaltic group were more similar to those in healthy individuals than in the isoperistaltic group. CONCLUSIONS: The gastro-pouch-emptying test in the antiperistaltic group demonstrated acceptable emptying for a pyloric ring substitute. A reasonably good quality of life has been obtained for patients having an antiperistaltic jejunal conduit.     

Hypokalemia with syncope caused by habitual drinking of oolong tea.

A 61-year-old woman developed hypokalemia, atrioventricular block and ventricular tachycardia with syncope after habitual drinking 2 to 3 liters of oolong tea per day. She had been suffering from rheumatoid arthritis and Sj?gren's syndrome and her serum albumin was decreased (2.9 g/dl). Oolong tea contains caffeine at approximately 20 mg/dl. Great quantities of caffeine can induce hypokalemia. The serum protein binding caffeine is albumin. Accordingly, in patients with hypoalbuminemia, caffeine is apt to induce hypokalemia. This case suggested that great quantities of oolong tea, one of the so-called "healthy" drinks, result in serious symptoms for patients with hypoalbuminemia.     

Gonadal vein graft for hepatic artery reconstruction.

BACKGROUND/AIMS: Resection of hepatic arteries is often obligatory on resecting pancreatic, gastric and hepatobiliary malignancies. Hepatic artery reconstruction is required to preserve liver function and blood flow to the bile duct. We applied the gonadal vein to hepatic artery reconstruction. METHODOLOGY: Hepatic artery reconstruction using a gonadal vein graft was performed in two patients: one with gallbladder cancer and the other with recurrent gastric cancer. RESULTS: The right ovarian vein, 2 mm in diameter and 4 cm in length, was grafted for reconstruction between the proper hepatic and the posterior hepatic artery in one patient who underwent modified central hepatic bisegmetectomy and common bile duct resection. The left spermatic vein, 3 mm in diameter and 6 cm in length, was grafted for reconstruction between the celiac artery and the right hepatic artery in the other, who underwent upper abdominal exenteration. The former graft was occluded due to tumor invasion at 4 months after surgery, the latter one was patent at 8 weeks after surgery. CONCLUSIONS: The gonadal vein had an ideal diameter and sufficient length to accomplish hepatic arterial reconstruction. The gonadal vein graft will be a new and preferable addition to the selection of an optimal graft for hepatic arterial reconstruction.