Relationship between the in vitro response of dendritic cells to Lactobacillus and prevention of tumorigenesis in the mouse

BACKGROUND: Some strains of lactobacilli stimulate immune cells, yet little is known about their potency in cancer prevention. We have previously reported that Lactobacillus casei Shirota (LcS) suppresses murine tumorigenesis through immune modulation. In this study, differences were compared among six representative strains of lactobacilli in regard to their ability to stimulate bone marrow cell-derived dendritic cells (BMDCs) in vitro and tumor suppression in vivo. METHODS: BM-DCs were cocultured with a Lactobacillus strain in vitro, and the interleukin (IL)-12 released into the culture supernatant was measured by enzyme-linked immunosorbent assay. Tumors were chemically induced by a single subcutaneous injection of 3-methylcholanthrene (MC) in BALB/c mice. The test diets containing Lactobacillus were given from the day of the MC injection, and the tumor incidences were monitored. Peyer's patches were dissected from Lactobacillus-fed mice, and the status of c-Src, a regulator of DCs, in Peyer's patch cells was examined by Western blotting. RESULTS: In the coculture system, L. fermentum FERM P-13857 and LcS potently elicited IL-12 production. LcS but not the other strains of lactobacilli showed tumor suppression. The inactive form of c-Src, phosphorylated at Tyr527, was dominantly detected in Peyer's patches resected from L. fermentum FERM P-13857-fed mice compared with LcS-fed mice. CONCLUSIONS: The responses of DCs may be associated with tumor suppression by an ingested Lactobacillus strain.     

Natural killer cell may impair liver regeneration in fulminant hepatic failure

The authors established a new experimental model of fulminant hepatic failure (FHF) with prolonged hepatocellular necrosis and impaired liver regeneration, and evaluated the immunological mechanisms related to the impaired liver regeneration in this model. A novel lipid A analogue, FS-112, was injected intravenously into male Balb/c mice, followed by a 70% partial hepatectomy 2 days later. Serum levels of T.Bil. and ALT rose 7 days after the partial hepatectomy, as compared with controls. In mice pretreated with FS-112, labeling indices of both BrdU and PCNA 36 hrs after the partial hepatectomy were significantly lower than those in the controls. Splenic lymphocytes harvested from the FHF mice 1–5 days after the partial hepatectomy showed a cytotoxic activity against regenerating hepatocytes with a peak effect on day 5. Cytotoxic activity against YAC-1 cells was also found up to 5 days after the partial hepatectomy, and resembled that directed against the regenerating hepatocytes. On the 5th day of FS-112 administration, there was a marked rise in the production of IFN-γ from splenocytes. When FK-506, an immunosuppressive agent, was given intracutaneously daily for 7 days, serum levels of T.Bil. and ALT significantly decreased, as compared with controls. Furthermore, the PCNA-labeling index 36 hrs after the partial hepatectomy was enhanced by the administration with FK-506 in the FHF mice. These results strongly suggest that the NK cells activated by IFN-y may be involved in killing the regenerating liver cells, and thus play a role in the pathogenesis of the impaired liver regeneration in FHF. Furthermore, it has been suggested that FK-506 may be beneficial for recovery from the impaired liver regeneration in FHF. This work was supported in part by grant (01-03-3) from the Research Group of Intractable Hepatitis sponsored by the Ministry of Health and Welfare of Japan, and by Grant-in-Aid for Co-operative Research (A) (01304038) from the Ministry of Education, Science and Culture of Japan.     

Evaluation of lung volume reduction surgery (LVRS) based on long-term survival rate analysis

OBJECTIVE: Lung volume reduction surgery (LVRS) is an effective therapy for some patients with end-stage emphysema. In most cases, functional improvement is maximized during the first 6 months after surgery and decreases steadily afterwards. This study was aimed at gaining further understanding of the optimal candidates for LVRS and survival rates. METHODS: 62 patients with LVRS were selected according to the inclusion criteria. Changes in lung function were evaluated by FEV1, VC, RV, TLC, DLCO, PaO2, and PaCO2, and survival rates were analyzed at 12, 24, 36, and 48 months. Patients with LVRS were divided into two groups--those surviving after 48 months and those not surviving after 48 months--and analyzed according to group. RESULTS: The overall survival rate at 2 years and 4 years was 81.0 % and 67 %, respectively, with LVRS. VC, FEV1, TLC, DLCO, PaO2, and PaCO2 were potential factors leading to mortality according to univariate analysis. Multivariate analysis demonstrated that DLCO was the only independent factor that could predict the post-LVRS prognosis; the other factors failed as independent factors. Preoperatively, the FEV1 percentage predicted gave a good index for post-LVRS survival. CONCLUSIONS: Patients with higher preoperative FEV1 values had higher survival rates. These favorable long-term survival rates might justify LVRS for treating selected patients with severe emphysema. Additionally, DLCO turned out to be the only predictive factor for high mortality risk 4 years after LVRS. DLCO may thus be a very important marker in surgical planning.     

Suppression by thyrotropin-releasing hormone (TRH) of human growth hormone release induced by L-dopa.

Oral administration of L-dopa (600 mg) significantly raised plasma human growth hormone (hGH) in 6 of 7 normal subjects examined. This L-dopa induced hGH release was significantly suppressed by the intravenous infusion of 1 mg of thyrotropin-releasing hormone (TRH). TRH administration alone had no significant effect on plasma hGH. In contrast, plasma human prolactin (hPRL) consistently increased following TRH infusion. L-dopa significantly lowered basal plasma hPRL levels and also significantly blunted TRH-induced hPRL release. These results suggest that TRH plays an inhibitory role in the regulation of hGH secretion in normal subjects, whereas it stimulates hPRL release.     

Decreased amplitude of left ventricular posterior wall motion with notch movement to determine the left posterior septal accessory pathway in Wolff-Parkinson-White syndrome

OBJECTIVE—To determine preoperatively, by analysing asynchronous left ventricular wall motion, whether to approach through the right ventricle or the left ventricle when carrying out catheter ablation of the accessory pathway in Wolff-Parkinson-White syndrome, especially in patients with the pathway located on the septum.
METHODS—73 patients with manifest Wolff-Parkinson-White syndrome who underwent successful catheter ablation were studied. Location of accessory pathway was classified as right ventricular side: right anterior paraseptum, right anterior, right lateral, right posterior, anterior septum, midseptum, right posterior septum; left ventricular side: left posterior septum, left posterior, left lateral, left anterior. Asynchronous systolic wall motion was analysed by cross sectional echocardiography.
RESULTS—Echocardiography showed that the amplitude of left ventricular posterior systolic wall motion was reduced when the pathway was located on the left ventricular side as opposed to the right ventricular side (mean (SD), 11.1 (1.7) v 12.9 (1.1) mm, p < 0.001), especially in patients with left posterior septal accessory pathway (9.7 (0.8) mm). There were no overlapping values between the left posterior septal accessory pathway and the right ventricular side accessory pathway. Posterior wall notch motion was observed in all patients with a left posterior septal accessory pathway (9/9), but not at all in patients with pathways located on the right ventricular side of the septum. In patients with a septal accessory pathway, an ECG algorithm provided poor information (relatively low sensitivity, specificity, and predictive value) for determining whether the subsite faced either the left (left posterior septum) or the right ventricle (anterior septum, midseptum, right posterior septum).
CONCLUSIONS—Decreased amplitude of left ventricular posterior wall motion with notch movement is an important finding for accessory pathways located on the left posterior septum. These findings provided clinically useful information for determining whether to approach catheter ablation from the right or the left ventricle.


     

Coronary artery stenting with high-pressure post-dilation followed by adjunctive thrombolysis after failed coronary angioplasty for acute myocardial infarction: Report of three cases

We successfully implanted coronary stents into refractory reoccluded lesions after failed coronary angioplasty in three patients with acute myocardial infarction (AMI). Lesion location was the proximal left anterior descending coronary artery in two patients and the dominant right coronary artery in one patient. The reference diameters of the lesions were 3.64, 3.33, and 3.50 mm, respectively. A stent with a luminal diameter of 3.0 mm was implanted in all patients. Poststenting dilation of the stent was performed at high pressure (18 atm), and urokinase was administered immediately thereafter. Heparin was administered for 24 h with maintenance of activated coagulation time within 180–200 s. Warfarin was then administered to keep the international normalized ratio within 2.5–3.5. Luminal diameters immediately after stenting were 3.14, 2.89, and 3.26 mm, and those at 1 month after stenting were 3.09, 2.81, and 3.12 mm, respectively, indicating good patency. Our experience in these cases suggests that coronary stenting can be applied after unsuccessful coronary angioplasty in selected patients with AMI. The present report includes informative reference data on diameter, postdilation, adjunctive thrombolytic agent administration, and adequate anticoagulation therapy in coronary stenting in this acute application.     

Effects of prolactin and growth hormone on proliferation and survival of cultured trout leucocytes

The in vitro effects of prolactin (PRL) and growth hormone (GH) on the proliferation and survival of leucocytes isolated from the blood of the rainbow trout (Oncorhynchus mykiss) were examined, with special reference to the immunosuppression by cortisol. Both PRL and GH induced a mitogenic effect in trout leucocytes. Contrary, the frequencies of annexin V-positive apoptotic cells and propidium iodide-positive dead cells were decreased by the administration of PRL, but were uninfluenced by GH. Administration of cortisol suppressed the mitotic activity and induced cell death of leucocytes. PRL inhibited the decrease in mitosis and the increase in cell death due to cortisol. GH significantly assisted recovery of cortisol-suppressed mitosis but did not influence the survival of leucocytes. These results suggest that PRL and GH are involved in the maintenance of specific immune functions in fish through a prevention of immunosuppression by cortisol.