Expression of protocadherin-γC4 protein in the rat brain

It has been proposed that the combinatorial expression of γ-protocadherins (Pcdh-γs) and other clustered protocadherins (Pcdhs) provides a code of molecular identity and individuality to neurons, which plays a major role in the establishment of specific synaptic connectivity and formation of neuronal circuits. Particular attention has been directed to the Pcdh-γ family, for which experimental evidence derived from Pcdh-γ-deficient mice shows that they are involved in dendrite self-avoidance, synapse development, dendritic arborization, spine maturation, and prevention of apoptosis of some neurons. Moreover, a triple-mutant mouse deficient in the three C-type members of the Pcdh-γ family (Pcdh-γC3, Pcdh-γC4, and Pcdh-γC5) shows a phenotype similar to the mouse deficient in whole Pcdh-γ family, indicating that the latter is largely due to the absence of C-type Pcdh-γs. The role of each individual C-type Pcdh-γ is not known. We have developed a specific antibody to Pcdh-γC4 to reveal the expression of this protein in the rat brain. The results show that although Pcdh-γC4 is expressed at higher levels in the embryo and earlier postnatal weeks, it is also expressed in the adult rat brain. Pcdh-γC4 is expressed in both neurons and astrocytes. In the adult brain, the regional distribution of Pcdh-γC4 immunoreactivity is similar to that of Pcdh-γC4 mRNA, being highest in the olfactory bulb, dentate gyrus, and cerebellum. Pcdh-γC4 forms puncta that are frequently apposed to glutamatergic and GABAergic synapses. They are also frequently associated with neuron-astrocyte contacts. The results provide new insights into the cell recognition function of Pcdh-γC4 in neurons and astrocytes.     

Effectiveness of Live-Attenuated Genotype III Japanese Encephalitis Viral Vaccine against Circulating Genotype I Viruses in Swine

Expansion of genotype I (GI) Japanese encephalitis viruses (JEV) has resulted in the replacement of the dominant genotype III (GIII) viruses, raising serious public health concerns for using GIII virus-derived vaccines to effectively control JEV epidemics. Therefore, this study used swine as the model to estimate the effectiveness of GIII live-attenuated vaccine against GI virus infection by comparing the incidence of stillbirth/abortion in gilts from vaccinated and non-vaccinated pig farms during the GI-circulation period. In total, 389 and 213 litters of gilts were recorded from four vaccinated and two non-vaccinated pig farms, respectively. All viruses detected in the aborted fetuses and mosquitoes belonged to the GI genotype during the study period. We thus estimated that the vaccine effectiveness of GIII live-attenuated vaccine against GI viruses in naive gilts based on the overall incidence of stillbirth/abortion and incidence of JEV-confirmed stillbirth/abortion was 65.5% (50.8–75.7%) and 74.7% (34.5–90.2%), respectively. In contrast to previous estimates, the GIII live-attenuated vaccine had an efficacy of 95.6% (68.3–99.4%) to prevent the incidence of stillbirth/abortion during the GIII-circulating period. These results indicate that the vaccine effectiveness of GIII live-attenuated JEV vaccine to prevent stillbirth/abortion caused by GI viruses is lower than that against GIII viruses.     

Astragalus membranaceus flavonoids (AMF) ameliorate chronic fatigue syndrome induced by food intake restriction plus forced swimming

Aim of the study

Alteration of immune function may be associated with chronic fatigue syndrome (CFS) and this study reveals the immunoregulatory effect of Astragalus membranaceus flavonoids (AMF).

Materials and methods

CF rats were induced by food intake restriction plus forced swimming for 6 weeks.

Results

An atrophied spleen associated with a significantly decreased spleen/body weight ratio and a reduced spleen cells proliferation was found in CF rats when compared with home cage controls. AMF given orally at 20, 50 and 100 mg/kg body weight once a day consecutively for 6 weeks could recover the reduced cell proliferation. A switch to Th1-dominated immune regulation was observed in CF rats as the cultured splenocytes produced more interleukin-2 (IL-2) but less IL-4 when compared with controls. Supplementation with AMF could significantly counteract the aberrant cytokine production and rats received AMF exhibited higher endurance capacity to swim when compared with those without AMF administration. Checking the spectrum signals confirmed that the three major isoflavones contained in AMF were ononin, formononetin, and demethylhomopterocarpin.

Conclusion

Alterations of immune function may be associated with CFS and the tonic effects of AMF against CF may be attributable to balance the abnormal cytokine level by isoflavones.     

Microsatellite Instability Is Associated With a Better Prognosis for Gastric Cancer Patients After Curative Surgery

Background

Microsatellite instability (MSI) is one of the leading mechanisms for the carcinogenesis of gastric cancer. Its prognostic value is controversial.

Methods

Between May 1988 and Oct 2003, a total of 214 gastric cancer patients undergoing curative surgery were enrolled, and their MSI statuses were classified as MSI-H (high) or MSI-L/S (low/stable). The clinicopathologic characteristics of MSI-H and MSI-L/S gastric cancers were compared.

Results

The MSI-H tumors accounted for 11.7?% (n?=?25) of the 214 total gastric cancers. Although not statistically significant, the MSI-H gastric cancers were more frequently located in the lower third of the stomach (64?% vs. 49.2?%) and were more often the intestinal type (72?% vs. 61.4?%) compared to the MSI-L/S gastric cancers. The MSI-H gastric cancers had a significantly better 5-year overall survival (OS) rate (68?% vs. 47.6?%, p?=?0.030) and a trend of a better 3-year disease-free survival rate (71.8?% vs. 55.2?%, p?=?0.076) compared to the MSI-L/S gastric cancers. A multivariate analysis revealed that pathologic TNM stage and MSI status were the independent prognostic factors for OS after curative surgery.

Conclusions

Compared to MSI-L/S tumors, MSI-H tumors are associated with a better OS rate for gastric cancer patients after R0 resection.     

Factors Associated with Recurrence Within 2 Years After Curative Surgery for Gastric Adenocarcinoma

Background

Despite curative surgery for gastric cancer, many patients die of recurrent cancer. Few studies have investigated the time to recurrence after curative resection for gastric cancer.

Methods

Data were collected prospectively between December 1987 and December 2006. A total of 1,549 patients underwent curative resection of adenocarcinoma of the stomach at Taipei Veterans General Hospital. Among them, 419 patients had recurrence; they were divided into early recurrence (<2?years) and late recurrence (??2?years). The clinicopathological characteristics, survival time after recurrence, and recurrence patterns were compared between the two groups.

Results

Multivariate analysis showed that stage III gastric cancer patients with early recurrence had larger tumors and more lymph node metastasis than patients with late recurrence, while no difference between early and late recurrence was observed in stage I and II patients. Early recurrence was associated with more distant metastasis than was late recurrence. Patients with advanced TNM stage tended to die within 2?years after recurrence.

Conclusions

Gastric cancer patients with larger tumors and more lymph node metastasis tended to have early recurrence, especially stage III patients. Advanced TNM stage was associated with early cancer death after recurrence.     

Performance Status Enhances the Selection of Treatment for Patients with Hepatocellular Carcinoma Within the Milan Criteria

Background

Performance status (PS) is closely linked with survival in patients with hepatocellular carcinoma (HCC). We investigated its impact on treatment strategy for small HCC(s).

Methods

A total of 360 and 362 HCC patients within the Milan criteria undergoing surgical resection (SR) and radiofrequency ablation (RFA), respectively, were prospectively enrolled. Patients were classified into PS 0 (n = 558) and PS ≥1 (n = 164) groups. Propensity score analysis was performed, and 168 and 35 matched pairs were selected from patients with PS 0 and ≥1, respectively.

Results

The SR group was younger and had a higher male-to-female ratio, higher prevalence of hepatitis B, lower prevalence of hepatitis C, better PS, better liver functional reserve, and larger tumor burden than the RFA group (all p < 0.05). Among patients with PS 0, the SR group was consistently younger, less cirrhotic, and had larger tumor burden (all p < 0.05). The long-term survival was comparable between SR and RFA group in patients with PS 0. After propensity score matching, SR provided significantly better long-term survival than RFA for patients within the Milan criteria classified as PS 0 (p = 0.016); the Cox proportional hazards model showed consistent results. There was no significant difference of overall survival between the SR and RFA group in patients with PS ≥1 before or after propensity score matching (both p > 0.05).

Conclusions

For HCC patients within the Milan criteria and classified as PS 0, SR provides a better long-term survival compared with RFA. Performance status may enhance treatment selection and stratify the risk of survival in these patients.     

Graft patency is not the only clinical predictor of success after exclusion and bypass of popliteal artery aneurysms

PURPOSE: The traditional measure of success after exclusion and bypass of popliteal artery aneurysm (PAA) is graft patency. In addition to fate of the bypass, we hypothesize that late outcome after surgical treatment of PAA is influenced by completeness of exclusion. METHODS: Thirty patients who underwent 41 reconstructions for PAA over a 10-year period were reviewed. RESULTS: Excluded PAAs were examined with duplex ultrasound scan for size, patency, and patent feeding branches; bypass grafts and native inflow and outflow arteries were examined for patency and size. Thirty-six limbs were available for follow-up (mean follow-up period, 46 +/- 42 months). Only two aneurysms (5.6%) appeared patent on duplex ultrasound scan, but five limbs had patent arterial branches communicating with thrombosed excluded PAAs. PAA diameter decreased from 2.5 +/- 0.8 cm to 1.7 +/- 0.5 cm (P <.0001) in most. However, 12 excluded PAAs (33%) showed significant enlargement from 2.2 +/- 0.9 cm to 2.8 +/- 1.0 cm (P =.002). A quarter of enlarging excluded PAA were associated with new compressive symptoms. Three methods of PAA exclusion were used: proximal and distal ligation with short segment isolation (type 1), proximal and distal ligation with long segment isolation (type 2), and single ligature (type 3). In univariate analysis, type of exclusion significantly influenced late size of excluded PAA (P =.004). Type 1 exclusion was superior to both type 2 and 3 exclusions in producing aneurysm diameter reduction. Type 3 exclusion resulted in aneurysm growth. In addition, excluded aneurysms with visualized feeding branches were associated with significant growth compared with PAAs without feeding branches (P =.006). Graft primary and assisted primary patency rates at 5 years were 86% +/- 9.4% and 92% +/- 7.4%, respectively. Although graft diameter and native donor artery diameter significantly increased, this did not adversely affect graft patency. CONCLUSION: Enlargement of excluded PAA after surgical treatment can cause compressive symptoms. Exclusion requires adequate vascular isolation to prevent late PAA enlargement, with proximal and distal arterial ligation best performed adjacent to the aneurysm. Vein graft enlargement occurs, but this enlargement does not adversely influence patency.