Involvement of central opioid systems in human interferon-alpha induced immobility in the mouse forced swimming test

1. We investigated the mechanism by which human interferon-alpha (IFN-alpha) increases the immobility time in a forced swimming test, an animal model of depression. 2. Central administration of IFN-alpha (0.05 - 50 IU per mouse, i.cist.) increased the immobility time in the forced swimming test in mice in a dose-dependent manner. 3. Neither IFN-beta nor -gamma possessed any effect under the same experimental conditions. 4. Pre-treatment with an opioid receptor antagonist, naloxone (1 mg kg(-1), s.c.) inhibited the prolonged immobility time induced by IFN-alpha (60 KIU kg(-1), i.v. or 50 IU per mouse. i.cist. ). 5. Peripheral administration of naloxone methiodide (1 mg kg(-1), s. c.), which does not pass the blood - brain barrier, failed to block the effect of IFN-alpha, while intracisternal administration of naloxone methiodide (1 nmol per mouse) completely blocked. 6. The effect of IFN-alpha was inhibited by a mu(1)-specific opioid receptor antagonist, naloxonazine (35 mg kg(-1), s.c.) and a mu(1)/mu(2) receptor antagonist, beta-FNA (40 mg kg(-1), s.c.). A selective delta-opioid receptor antagonist, naltrindole (3 mg kg(-1), s.c.) and a kappa-opioid receptor antagonist, nor-binaltorphimine (20 mg kg(-1), s.c.), both failed to inhibit the increasing effect of IFN-alpha. 7. These results suggest that the activator of the central opioid receptors of the mu(1)-subtype might be related to the prolonged immobility time of IFN-alpha, but delta and kappa-opioid receptors most likely are not involved.     

Prognostic value of tumor-infiltrating FOXP3 regulatory T cells in patients with hepatocellular carcinoma

Aims

CD4⁺ CD25⁺ forkhead box P3 (FOXP3)⁺ T_reg accumulate in malignant tumors and negatively regulate anti-tumor immunity. To determine the prognostic value of tumor-infiltrating regulatory T cells (T_reg), we conducted a retrospective study on 164 patients with hepatocellular carcinoma (HCC) who underwent curative hepatic resection.

Methods

We investigated the number of tumor-infiltrating FOXP3⁺ T_reg in formalin-fixed HCC specimens. The number of FOXP3⁺ T_reg for each case was calculated as the total number of positive cells per 10 high-power fields (HPF) on light microscopy. Long-term survival rate after resection according to the number of FOXP3⁺ T_reg was accessed by univariate and multivariate analyses.

Results

The mean and median numbers of tumor-infiltrating T_reg were 29.0 and 14 per 10 HPF for FOXP3⁺ T_reg. The number of FOXP3⁺ T_reg was positively correlated with preoperative serum alpha-fetoprotein levels. The disease-free survival rate was significantly lower in patients with high T_reg counts (≥14, n = 84) than in those with low T_reg counts (<14, n = 80) (13.6% vs. 25.7% at 5 years; P = 0.02). By multivariate analysis, the high T_reg counts, presence of portal vein invasion, and elevation of preoperative aspartate aminotransferase level were independent predictive factors of tumor recurrence.

Conclusions

The high number of tumor-infiltrating T_reg is an independent predictive factor of tumor recurrence after hepatic resection for HCC.     

Change of autonomic nervous activity during pregnancy and its modulation of labor assessed by spectral heart rate variability analysis

PURPOSE OF INVESTIGATION: To elucidate the sequential changes of autonomic nervous activity during pregnancy, we examined heart rate variability on two positions and whether autonomic nervous activity affected duration of labor. METHODS: Thirty-eight normal pregnant women were studied. Frequency domain parameters (HF, LF, LF/HF ratio) and heart rate were obtained by spectral HRV analysis in the supine and left recumbent position in three trimesters. RESULTS: We found HF was significantly higher in early pregnancy, while the LF/HF ratio was significantly higher in late pregnancy. The LF/HF ratio was significantly lower when the left recumbent position was assumed. The LF/HF ratio was significantly higher in the longer labor group of primiparous women. CONCLUSION: Our findings demonstrate that sympathovagal balance shifted progressively from a higher vagal modulation towards a higher sympathetic modulation, and the recumbent position activated vagal activity. It is suggested that increased sympathetic activity in late pregnancy could affect the duration of labor.     

Über das Verhalten der Phosphorsäure bei künstlicher Durchströmung von Froschmuskeln

Zusammenfassung Es wird die Phosphorsäureabgabe aus durchströmten Froschmuskeln an die Durchströmungsflüssigkeit in ihrem zeitlichen Verlauf bei Ruhe und Arbeit, bei Gegenwart und Fehlen von Sauerstoff, bei kontinuierlicher und zirkulierender Durchströmung messend verfolgt. Dabei zeigt sich eine starke Abhängigkeit der Phosphorsäurebildung und -restitution von der Sauerstoffversorgung und ein typischer Gang der Phosphorsäureabgabe, der durch das Zusammenwirken von Bildungsintensität, Diffusionsgefälle und oxydativer Restitution bedingt ist.     

Hepatitis B Virus Infection Predicts Extrahepatic Metastasis After Hepatic Resection in Patients With Large Hepatocellular Carcinoma

Background Although extrahepatic metastasis occurs rarely after hepatic resection for hepatocellular carcinoma (HCC), the prognosis of these patients is extremely poor. Predictors of extrahepatic metastasis have not been fully investigated. Methods To identify predictors of extrahepatic metastasis after resection, we retrospectively investigated 77 patients with HCC tumors >50 mm in diameter who underwent hepatic resection. We investigated correlations between postoperative extrahepatic metastasis and clinicopathologic factors as well as extrahepatic metastasis-free survival rate by log rank test and predictors of extrahepatic metastasis by univariate and multivariate logistic regression models. Results Hepatitis B surface antigen (HBs-Ag) was found in 25 (32.5%) of 77 patients, and extrahepatic metastasis occurred in 26 (33.8%). Patients with extrahepatic metastasis showed better liver function and a high occurrence of HBs-Ag positivity than those without. The 5-year extrahepatic metastasis-free survival rate was worse in patients with HBs-Ag positivity, larger tumors (≥70 mm), higher alfa-fetoprotein level (≥300 ng/mL), and lower indocyanine green retention rate at 15 minutes (ICGR₁₅) (<15%) than in those without. By univariate logistic regression analysis, HBs-Ag positivity, larger HCC tumor (≥70 mm), lower ICGR₁₅ (<15%), and lower preoperative lymphocyte count (<1000/mm³) were predictors of extrahepatic metastasis (P < .1). By multivariate analysis, HBs-Ag positivity was an independent predictor of postoperative extrahepatic metastasis (P = .04). Conclusions In patients positive for HBs-Ag, radiologic examination of extrahepatic organs should be performed as a part of the postoperative surveillance. Hepatitis B virus infection may promote establishment of extrahepatic metastasis.     

Changes in thymus- and activation-regulated chemokine (TARC) associated with allergen immunotherapy in patients with perennial allergic rhinitis.

BACKGROUND: Thymus- and activation-regulated chemokine (TARC), which is a CC chemokine receptor (CCR) 4 ligand with ability to recruit Th2 cells to inflammatory sites, is pathogenetically important in allergic rhinitis. Specific immunotherapy (IT), among the most effective therapies for allergic rhinitis, has incompletely understood mechanisms of action. TARC might be involved in some benefits of IT. METHODS: TARC in sera was assayed, obtained from 50 patients with house dust mite allergic rhinitis before and 1 year after beginning IT. Their ages ranged from 6 to 34 years (mean, 10), 30 were male and 20 were female. RESULTS: In patients whose nasal obstruction responded to IT, TARC decreased significantly with IT, while when response was defined in terms of sneezing or rhinorrhea, TARC did not change significantly. CONCLUSION: TARC might be an important target of IT in reducing obstructive allergic rhinitis.     

Malignant serous cystic neoplasm of the pancreas: report of a case and review of the literature

BACKGROUND: In general, serous cystic neoplasms of the pancreas are thought to be benign. Malignant serous cystic neoplasm of the pancreas is a rare clinical entity. CASE REPORT: We report the case of an 87-year-old woman with a serous microcystic neoplasm in the tail of the pancreas that behaved in a malignant fashion. The neoplasm had also invaded the colonic mesentery and splenic hilum. The pancreatic lesion was diagnosed as a large malignant serous cystic neoplasm, and the patient underwent distal pancreatectomy with splenectomy and segmental colectomy. The resected specimen contained a large tumor, 12 x 9 x 8 cm, which occupied the body and tail of the pancreas. Histologically, the tumor was indistinguishable from serous cystadenoma. However, the tumor had invaded surrounding tissues including the splenic vein, and there were splenic invasion and a regional lymph node metastasis. The postoperative course was uneventful. DISCUSSION: There are few reported cases of malignant serous cystic neoplasm, in which malignancy was histologically confirmed in the resected specimen. There are no reports of a negative outcome with complete resection of the tumor. Surgical treatment should be considered for serous cystic neoplasms, especially large ones, because of the malignant potential.     

Implications of arterial anatomy in patients with cancer of the periampullary region

BACKGROUND/AIMS: Preoperative information on arterial anatomy in the peripancreatic and hepatic areas is valuable to any surgeon performing pancreatoduodenectomy. METHODOLOGY: Between 1994 and 1998, 49 patients with periampullary cancer (31 distal bile duct and 18 ampullary tumors) underwent visceral angiography and radical pancreatoduodenectomy with lymphadenectomy. Surgically "significant" arterial variations and their effects on operative management and results were examined retrospectively. RESULTS: Arterial variations were found in 18 patients (37%); 15 (31%) were "significant" and 3 (6%) were "nonsignificant." All 15 patients with "significant" variants required specific type of various preservations of the hepatic arterial system. Intraoperative blood loss, transfused blood units, and operation time were greater in patients with "significant" variations than in patients without (P<0.05). Histopathologic diagnosis, tumor staging, morbidity, and mortality did not differ between the 2 groups. The 5-year survival was 33% for patients with "significant" variations and 63% for patients without (P<0.05). CONCLUSIONS: Information on arterial anatomy in the peripancreatic and hepatic areas is necessary for preoperative evaluation in patients requiring radical pancreatoduodenectomy. Presence of "significant" arterial variations may be considered as one of the negative prognostic factors in patients with periampullary cancer.