Prognostic significance of serum osteoprotegerin levels in patients with bladder carcinoma

BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) plays an important role in the process of lymphocyte-mediated cytotoxicity against malignant cells. Osteoprotegerin (OPG) is a soluble decoy receptor for TRAIL, and circulating OPG has been implicated in the protection of cells from TRAIL-mediated apoptosis. Thus, OPG may protect tumor cells from lymphocyte-mediated cytotoxicity and, as a result, contribute to tumor progression. In the current study, the authors investigated this hypothesis in patients with bladder carcinoma. METHODS: Serum OPG levels for 185 patients with bladder carcinoma were determined using an enzyme-linked immunosorbent assay. These levels then were assessed for potential correlations with various disease characteristics and outcome measures. RESULTS: The mean serum OPG concentration in patients with bladder carcinoma was approximately 3 times greater than the mean concentration in healthy individuals, and among patients with bladder carcinoma, higher tumor stage and grade were found to be associated with increased serum OPG levels. Within the subpopulation of patients with superficial bladder carcinoma, after a follow-up period of 5 years, those who had low serum OPG levels tended to have a longer postoperative tumor-free interval compared with those who had high serum OPG levels. Furthermore, among patients with muscle-invasive bladder carcinoma, the 5-year disease-specific survival rate was greater for those who had low serum OPG levels than for those who had high serum OPG levels. CONCLUSIONS: To the authors' knowledge, the current study is the first to demonstrate that serum OPG concentration is correlated with both tumor stage and tumor grade and that elevated serum OPG levels are predictive of early recurrence in patients with bladder carcinoma. These findings suggest that serum OPG concentration may have utility as a prognostic parameter in this setting.     

Suicide among psychiatric patients in Fukuoka Prefecture]

To investigate suicide among psychiatric patients in Japan (mainly Fukuoka prefecture), a questionnaire survey was submitted to psychiatrists from departments of psychiatry of university hospitals in Japan, departments of psychiatry of Rosai Hospitals in Japan, psychiatric hospitals in Fukuoka prefecture, psychiatric clinics in Fukuoka prefecture, and departments of psychiatry of general hospitals in Fukuoka prefecture regarding their psychiatric patients who died from suicide (266 females and 267 males). A large proportion of the patients at completed suicide was aged within the thirties to fifties. The majority of patients suffered from either F3 (mood disorders) or F2 (schizophrenia, schizotypal and delusional disorders) categories of the ICD-10 classification. Approximately one-fifth of the patients in Fukuoka prefecture had jobs at the time of completed suicide. The main "occupational risk factors" that were found to be risks for suicide were "failure or overloaded responsibilities in their jobs" and "worsening business situation". The main "other risk factors", i.e., risk factors other than "occupational risk factors" were "worsening psychiatric conditions", "personal life events (e.g., somatic illness or marital discord)" and "life events in other family members (e.g., familial discord or familial problems)". Over 50% of all cases had both "occupational risk factors" and "other risk factors", suggestive of the necessity for multidimensional evaluation and care in the treatment of suicidal patients. Given that numerous males that suffer from psychiatric disorders commit suicide without seeing a psychiatrist, it is important to establish a system to treat them appropriately in order to prevent unnecessary deaths.     

Cortical processing of musical consonance: an evoked potential study

Cortical processes underlying perception of musical consonance were investigated by long-latency auditory evoked potentials (EPs). Subjects listened to a random sequence of dyadic pure tones paired at various pitch intervals (1, 4, 6, 7, or 9 semitones). Amplitudes of P2 and N2 components of auditory EPs were significantly modulated by pitch interval of the dyads, being most negative for 1 semitone (minor second) and least negative or most positive for 7 semitones (perfect fifth). The results indicate that neural processing of consonance depend not only on peripheral mechanisms in the inner ear but also on higher associative processing of pitch relationships in the cerebral cortex.     

CpG island hypermethylation of SOCS-1 gene is inversely associated with HBV infection in hepatocellular carcinoma

The CpG island hypermethylation of the suppressor of cytokine signaling-1 (SOCS-1) gene is frequently methylated in hepatocellular carcinoma (HCC), but its clinicopathological significance and the potential risk factors for the epigenetic change in HCC remain poorly understood. The methylation status of SOCS-1 CpG island was evaluated in fresh-frozen tissues from 284 HCC patients using the methylation-specific polymerase chain reaction. The expression of SOCS-1 protein was analyzed by immunohistochemical staining. SOCS-1 methylation was found in 163 (57%) of 284 HCCs. SOCS-1 methylation was positively associated with patient age (P = 0.002) and HCV infection status (P = 0.004), and was inversely associated with HBV infection (P = 0.0002). In the multivariate logistic regression analysis, the HB_sAg-negative HCCs showed a 2.78 (95% CI = 1.31–5.89, P = 0.007) times greater risk of SOCS-1 methylation than the HB_sAg-positive HCCs. SOCS-1 methylation also occurred at a 4.34 times (95% CI = 1.24–14.25, P = 0.02) higher prevalence in antiHCV-positive cases than in antiHCV-negative cases. No prognostic effect of SOCS-1 methylation was observed in the HCCs. In conclusion, the present study suggests that SOCS-1 methylation in HCC may be negatively associated with HB_sAg status.     

A severe outbreak of haemorrhagic colitis and haemolytic uraemic syndrome associated withEscherichia coli 0157: H7 in Japan

In 1990, an outbreak ofEscherichia coli 0157: H7 infection occurred in 174 children in a nursery school in Saitama, Japan. The organism was isolated from tap water supplied from the well in the school. Clinical manifestations varied from asymptomatic infection to non-bloody diarrhoea, haemorrhagic colitis, haemolytic uraemic syndrome (HUS) and death. Among culture-confirmed 42 cases ofE. coli 0157: H7, 7 children were asymptomatic, 21 children had only diarrhoea, and 14 children developed HUS. Bloody diarrhoea with abdominal pain following initial frequent diarrhoea appeared to be associated with subsequent HUS. In patients with HUS, both leucocyte count and lactate dehydrogenase activity continued to increase in the early phase of the disease, and on day 3 of illness attained markedly higher levels than in patients without HUS. These two parameters seemed to be important as predictors of the development of HUS.Committee for epidemiological and clinical study of epidemic diarrhoea due to pathogenicE. coli in a nursery school, Saitama, Japan     

Potential usage of liposomal 4beta-aminoalkyl-4'-O-demethyl-4-desoxypodophyllotoxin (TOP-53) for cancer chemotherapy

To enhance the therapeutic efficacy as well as to reduce the side effect, we attempted to liposomalize 4beta-aminoalkyl-4'-O-demethyl-4-desoxypodophyllotoxin (TOP-53), a novel and effective topoisomerase II inhibitor. More than 90% of TOP-53 was efficiently incorporated into the liposomes composed of dipalmitoylphosphatidylcholine and cholesterol by remote-loading method. Anti-tumor activity of liposomal TOP-53 against solid tumor was examined in vivo using colon26 NL-17 carcinoma model mice. Three doses of liposomal TOP-53 (12 mg/kg/dose) showed significant tumor growth suppression (97.5% reduction determined at day 25) and the increase in life span (33%) of tumor-bearing mice. Furthermore, one mouse out of 5 was completely cured after treatment. Since similar efficacy was observed in the free TOP-53 treated group, liposomalization does not contribute much to the enhancement of therapeutic efficacy. However, a slight but measurable damage at the injection site was observed when free TOP-53 was injected, and the damage was diminished by the liposomalization. Taken together, liposomalization reduces the side effect rather than enhancing the therapeutic efficacy when TOP-53 is used.     

Effects of red ginseng upon postoperative immunity and survival in patients with stage III gastric cancer

In this paper, we present evidence that the red ginseng powder from Panax ginseng C.A. Meyer inhibits the recurrence of AJCC stage III gastric cancer and shows immunomodulatory activities during postoperative chemotherapy, after a curative resection with D2 lymph node dissection. Flow cytometric analyses for peripheral T-lymphocyte subsets showed that the red ginseng powder restored CD4 levels to the initial preoperative values during postoperative chemotherapy. Depression of CD3 during postoperative chemotherapy was also inhibited by the red ginseng powder ingestion. This study demonstrated a five-year disease free survival and overall survival rate that was significantly higher in patients taking the red ginseng powder during postoperative chemotherapy versus control (68.2% versus 33.3%, 76.4% versus 38.5%, respectively, p < 0.05). In spite of the limitation of a small number of patients (n = 42), these findings suggest that red ginseng powder may help to improve postoperative survival in these patients. Additionally, red ginseng powder may have some immunomodulatory properties associated with CD3 and CD4 activity in patients with advanced gastric cancer during postoperative chemotherapy.     

Serum cystatin-C values in children by age and their fluctuation during dehydration

BACKGROUND: Serum creatinine level (Cr) is extensively used as an index of glomerular filtration rate (GFR) with bedside patients. As serum Cr level differ by the muscle volume, the use of serum Cr as an index of GFR has long been considered problematic in children. METHODS: The subjects of this study were 135 healthy children aged from 1 to 15-years-old. As a pathological condition, the changes in serum cystatin C (Cys-C) in the children whose blood urea nitrogen exceeded 20 mg/dL during the acute stage of dehydration were also investigated. RESULTS: The mean serum Cys-C value was 0.67 +/- 0.19 mg/L on the whole. There was not any male-female difference. The mean serum Cys-C values of the 12 cases in the acute stage and the recovery stage were 0.61 +/- 0.12 mg/L and 0.64 +/- 0.14 mg/L, respectively, indicating no significant difference. CONCLUSION: Serum Cys-C is considered as a favorable index of GFR in children because it is not influenced by age and sex. As it is not influenced by the prerenal factors either, serum Cys-C is useful in children over 1-years-old.     

APP knockout attenuates microglial activation and enhances neuron survival in substantia nigra compacta after axotomy

Focal microglial activation and progressive dopaminergic neurodegeneration in substantia nigra compacta (SNc) have characterized Parkinson's disease (PD). We have hypothesized that the microglial response may be provoked by molecular signals from chronically stressed SNc neurons. To test whether amyloid precursor protein (APP) could serve as such a signal, we evaluated microglial activation in SN after unilateral transection of the medial forebrain bundle (MFB) in mice either wild-type (WT) or null (KO) for APP. WT and KO mice displayed comparable microglial response at the MFB transection site. In WT mice microglial activation was first apparent in the ipsilateral SN at 3 days postlesion (dpl), marked by morphological change and increased isolectin immunoreactivity. The microglial response intensified at 7 dpl and persisted in the medial nigra through 14 dpl. In contrast, in KO mice activated microglia appeared predominantly at 7 dpl, with little activation at 3 dpl and none at 14 dpl. Neuron number in affected WT SNc at 14 dpl was significantly reduced compared with loss in affected KO SNc. The delayed and limited local microglial activation and increased neuron survival in response to distal axotomy of SNc neurons in APP KO mice are consistent with the important role APP in neuronal stress responses in vivo.