Impact of lymph node metastasis on survival in patients with pathological T1 carcinoma of the ampulla of vater

To determine the prognostic factors for patients with pathological T1 (pT1) carcinoma of the ampulla of Vater, 36 consecutive patients with carcinoma of the ampulla of Vater who underwent surgery were retrospectively analyzed in terms of clinicopathological features. The overall 5-year Kaplan-Meier survival in all patients was 50.2%, and the median survival of all patients was 64.0 months. Factors favorably influencing a long-term outcome were the absence of lymph node metastasis (P<0.0001), the absence of ulcer formation of the tumor (P=0.0062), and the absence of tumor invasion into the duodenum (P = 0.0025) and the pancreas (P=0.0098). In a multivariate analysis, lymph node metastasis was the only predictor of survival (P=0.0023). In the pT1 stage patients, 20% of the patients had lymph node metastasis, and their survival was statistically poor compared to the pT1 patients without lymph node metastasis (P=0.017). As for survival after the operation, there was no significant difference between pancreatoduodenectomy and pylorus-preserving pancreatoduodenectomy.     

Human T-Cell Leukemia Virus-1-positive Cell Line Established from a Patient with Small Cell Lung Cancer

A stable cell line, KHM-3S, was established from a patient with small cell lung cancer (SCLC), who had a high serum level of soluble interleukin 2 receptors (sIL2-R) and was seropositive for human T cell leukemia virus (HTLV)-l. KHM-3S cells were positive for IL2-R (Tac) and NKH-1, but negative for other lymphocytic markers such as OKT 11, OKT 4, OKT 8, T cell receptor (WT 31), B 1, and B 4. Moreover, the KHM-3S cells were negative for leukocyte common antigen and strongly positive for neuron-specific enolase (NSE). Secretion of sIL2-R and NSE by the KHM-3S line was detected by an enzyme-linked immunosorbent assay. Rearrangement of the T cell receptor gene and monoclonal HTLV-1 integration were found by Southern blot analysis of KHM-3S DNA. However, Northern blot analysis showed no T cell receptor mRNA. KHM-3S may be useful for studies on the role of HTLV-1 in carcinogenesis and IL2-R expression in SCLC.     

Effect of FK-506 on xenografted human Graves' thyroid tissue in severe combined immunodeficient mice

OBJECTIVE We studied the macrolide antibiotic FK-506, an immunosuppressive agent, in an attempt to ameliorate the lesion of autoimmune thyroid disease in human thyroid tissue xenografted into severe combined immunodeficient (SCID) mice. It was not felt appropriate to employ this agent directly in patients with autoimmune thyroid disease because adequate therapeutic modalities are available and the introduction of new, experimental agents could not be justified. Moreover, the study of the tissue before and after treatment could not have been undertaken directly in patients. DESIGN Human thyroid xenografts from four patients with Graves' disease and two normal persons were xenografted into SCID mice. Two weeks after xenograft-ing, human immunoglobulin G (IgG) was detectable in all SCID mice xenografted with Graves' thyroid tissue. Mice were divided into two groups with human IgG levels similar to each other. Mice in the first group were treated with FK-506 daily for 6 weeks; mice in the second (similar) group were given phosphate-buffered saline (PBS) only (control group). MEASUREMENTS Blood samples were taken every 2 weeks from the tail veins for human IgG, thyroid stimulating antibody, thyroperoxidase antibodies, thyroglobulin antibodies, and interferon-gamma (IFN-7). After 8 weeks treatment, animals were sacrificed; thyroid tissue was examined histologically and for thyrocyte HLA-DR expression. FK-506 was also added to thyrocytes in in-vitro tissue culture conditions. RESULTS After 4–6 weeks of FK-506 therapy, human IgG, all thyroid antibodies and IFN-7 were suppressed, while the levels remained elevated in the control group. Lymphocytic infiltration virtually disappeared in the human thyroid tissue of the FK-506-treated mice and thyrocyte HLA-DR expression markedly declined; in the control mice, lymphocytic infiltration remained heavy and HLA-DR expression remained high. On the other hand, FK-506 added directly to thyrocytes in vitro (without lymphocytes) did not reduce thyrocyte HLA-DR expression. CONCLUSIONS FK-506 appears to suppress the activation of intrathyroidal lymphocytes, but not thyrocytes. From these observations, it is concluded that this agent, by its action on intrathyroidal lymphocytes, is able to ameliorate the immunologically mediated histological and serological disturbance in human autoimmune thyroid disease, at least under these circumstances.     

Enhancement of hepatitis-B surface-antigen expression by 5-azacytidine in a hepatitis-B-virus-transfected cell line.

The human hepatoblastoma-derived cell line HB611 secretes hepatitis-B surface antigen (HBsAg) and hepatitis-B e antigen (HBeAg) into the medium. Hepatitis-B-virus (HBV) DNA integrated into the cellular genome was found to be hypermethylated. When the cells were treated with 5-azacytidine for 3 days, the level of HBsAg in the medium increased, while the level of HBeAg remained constant. The level of alpha-fetoprotein (AFP) decreased with the 5-azacytidine treatment. Southern blot analysis of DNA digested with HpaII or MspI showed that 5-azacytidine treatment resulted in hypomethylation of the integrated HBV DNA, suggesting that 5-azacytidine increased HBsAg production in the cells through hypomethylation of the HBV genomic DNA.     

The gastric antisecretory action of lipopolysaccharide is blocked by indomethacin.

We have recently found that bacterial lipopolysaccharide (LPS) at minute doses inhibits the secretion of gastric acid and pepsin in rats. The present study was performed to examine the mechanism by which LPS exerts its antisecretory action. The i.p. injection of LPS resulted in a dose-dependent (40-4000 ng/kg) decrease in gastric acid output in pylorus-ligated rats. However, preinjection of indomethacin (2-10 mg/kg s.c.), an inhibitor of prostaglandin biosynthesis, prevented the LPS-induced inhibition of gastric secretion in a dose-related manner, while these concentrations of indomethacin by themselves did not affect gastric acid output. These results suggest that LPS requires an intact prostaglandin system to exhibit its inhibitory action on gastric secretion.     

Inhibition of inward rectifier K+ currents by angiotensin II in rat atrial myocytes: lack of effects in cells from spontaneously hypertensive rats.

We examined the effects of angiotensin II (Ang II) on inward rectifier K+ currents (IK1) in rat atrial myocytes. [125I]Ang II-binding assays revealed the presence of both Ang II type 1 (AT1) and type 2 (AT2) receptors in atrial membrane preparations. Ang II inhibited IK1 in isolated atrial myocytes with an IC50 of 46 nmol/l. This inhibition was abolished by the AT, antagonist RNH6270 but not at all by the AT2 antagonist PD123319. Treatment of cells with pertussis toxin or a synthetic decapeptide corresponding to the carboxyl-terminus of Gialpha-3 abolished the inhibition by Ang II, indicating the role of a Gi-dependent signaling pathway. Accordingly, Ang II failed to inhibit IK1 in the presence of forskolin, dibutyryl-cAMP or protein kinase A catalytic subunits. In spite of the increased binding capacities for [125I]Ang II, Ang II failed to affect IKI in cells from spontaneously hypertensive rats (SHR). AT, immunoprecipitation from atrial extracts revealed decreased amounts of Gialpha-2 and Gialpha-3 proteins associated with this receptor in SHR as compared with controls. The reduced coupling of AT, with Gialpha. proteins may underlie the unresponsiveness of atrial IK1 to Ang II in SHR cells.     

Aortic valve replacement with fresh or cryopreserved aortic allograft--initial experience in Japan]

Aortic allograft valves were harvested from non-infected (bacterial or viral) cadavers within 24 hours of death with a family consent, and were sterilized by 4 degrees C antibiotic solution for 48 hours. Then, the allograft was preserved in the 4 degrees C nutrient medium (fresh; TC-199, calf serum and HEPES buffer) or in liquid nitrogen (-196 degrees C) after freezing to -80 degrees C by a programmed freezer. 10% dimethylsulfoxide (DMSO) was used for cryopreservation. Following germ-free confirmation, aortic allograft valves were implanted in 5 patients having aortic regurgitation with good results. Three fresh and two cryopreserved allograft valves were used. Although the follow-up term is very short (maximum 1 year) at the present time, the valve function is quite satisfactory, confirmed by cardiac catheterization and echocardiography. This is the first report in Japan with regard to cryopreservation of allograft valves and clinical use of fresh or cryopreserved valves. We believe that realization and progress of allograft preservation by cryo-technique and establishment of the tissue bank are important for the development of cardiovascular surgery in Japan.     

Clinical characteristics of pulmonary edema in patients with unstable angina]

To elucidate the clinical characteristics of pulmonary edema in unstable angina, 120 patients with unstable angina who admitted to the hospital within 6 hours after the onset of chest pain were studied. The criteria for the diagnosis of pulmonary edema included interstitial pulmonary edema and diffuse alveolar edema. Pulmonary edema was present in 24 patients. In these patients, the duration of chest pain was relatively longer, and the incidences of diabetes mellitus, emergency coronary revascularization and multiple-vessel coronary artery disease were higher than in those without pulmonary edema. In addition, in-hospital mortality rate in patients with pulmonary edema was higher than in those without it (21 vs 1%, p < 0.001), which is probably due to a large area of myocardial ischemia. For these patients, therefore, early diagnosis and appropriate therapy to save viable segments of the myocardium are mandatory.