Suppressive effects ofl-5-hydroxytryptophan in a feline model of photosensitive epilepsy

We recently demonstrated that long-lasting photosensitivity is acquired as a result of kindling of the lateral geniculate nucleus (LGN), and that the LGN-kindled cat pretreated withd,l-allylglycine represents a useful model of epilepsy for drug studies. The present experiments studied anticonvulsant effects of a serotonin precursor,l-5-hydroxytryptophan (5-HTP), on photosensitivity in the LGN-kindled cat underd,l-allylglycine and on LGN-kindled seizures. 5-HTP suppressed both myoclonic responses and paroxysmal EEG discharges induced by photic stimulation in a dose-related manner. Photically-induced seizures were completely blocked 1.5–2 h after injection of 20 mg/kg 5-HTP. 5-HTP was also effective in reducing the afterdischarge duration and behavioral seizure stage in LGN-kindled seizures; following 40 mg/kg administration, no electroclinical seizures were elicited in the LGN-kindled cats. Serotonergic mechanisms may play an important role in epileptic photosensitivity; the 5-HTP suppressive effect on photosensitivity is at least partly due to reduced neuronal activity at the level of the LGN via serotonergic inhibition.     

Systemic Delivery of Synthetic MicroRNA-16 Inhibits the Growth of Metastatic Prostate Tumors via Downregulation of Multiple Cell-cycle Genes

Recent reports have linked the expression of specific microRNAs (miRNAs) with tumorigenesis and metastasis. Here, we show that microRNA (miR)-16, which is expressed at lower levels in prostate cancer cells, affects the proliferation of human prostate cancer cell lines both in vitro and in vivo. Transient transfection with synthetic miR-16 significantly reduced cell proliferation of 22Rv1, Du145, PPC-1, and PC-3M-luc cells. A prostate cancer xenograft model revealed that atelocollagen could efficiently deliver synthetic miR-16 to tumor cells on bone tissues in mice when injected into tail veins. In the therapeutic bone metastasis model, injection of miR-16 with atelocollagen via tail vein significantly inhibited the growth of prostate tumors in bone. Cell model studies indicate that miR-16 likely suppresses prostate tumor growth by regulating the expression of genes such as CDK1 and CDK2 associated with cell-cycle control and cellular proliferation. There is a trend toward lower miR-16 expression in human prostate tumors versus normal prostate tissues. Thus, this study indicates the therapeutic potential of miRNA in an animal model of cancer metastasis with systemic miRNA injection and suggest that systemic delivery of miR-16 could be used to treat patients with advanced prostate cancer.     

A Study on the Prognostic Evaluation of Carbon Ion Radiotherapy for Head and Neck Adenocarcinoma with C-11 Methionine PET

Purpose  

Carbon ion radiotherapy (CIRT) has been developed, and a phase I/II CIRT trial has been conducted in patients with adenocarcinoma in the head and neck region. We evaluated whether the l-methyl [11C]-methionine (MET) uptake could be an early predictor for local recurrence, metastasis, and the prognosis in patients with adenocarcinoma in the head and neck region.     

Analysis of Killer Cell Activities in Epstein-Barr Virus Infections

Using spontaneously established autologous lymphoblastoid B cell lines (LCL), killer cell activities were studied in children with severe infectious mononucleosis (IM), chronic IM, and acute IM, and compared with those in EBV-seropositive normal controls. Natural killer (NK) cell activity of fresh peripheral blood mononuclear cells (PBMC) was normal in acute IM patients, but it was low in four of six patients with severe or chronic IM. Recombinant inter-leukin 2 (rIL-2)-activated PBMC from normal controls showed lymphokine-activated killer (LAK) cell activity against the respective autologous LCL. The levels of LCL lysis by LAK cells were significantly higher in acute IM patients, lower in chronic IM patients, and much lower in severe IM patients. In contrast to the fact that PBMC stimulated in vitro with autologous LCL (IVS cells) from normal controls and acute IM patients showed potent killing of autologous LCL, IVS cells from severe or chronic IM patients showed lower levels of LCL lysis, which were markedly augmented in three patients by rIL-2 addition to the cultures. These killer cell dysfunctions appear to be responsible for the severe or chronic course of EBV infection.     

Descriptive Epidemiology of Diabetes Prevalence and HbA1c Distributions Based on a Self-Reported Questionnaire and a Health Checkup in the JPHC Diabetes Study

Background

The present study examined the prevalence of diabetes in Japan during the late 1990s and early 2000s using the Japan Public Health Center-based Prospective Diabetes cohort. We also investigated the distributions of HbA1c values in noncompliant diabetic participants in the cohort.

Methods

A total of 28 183 registered inhabitants aged 46–75 years from 10 public health center areas were included in the initial survey. The 5-year follow-up survey included 20 129 participants. The prevalence of diabetes was estimated using both a self-reported questionnaire and laboratory measurements. Among the participants who reported the presence of diabetes on the questionnaire (self-reported diabetes), the distributions of HbA1c values were described according to their treatment status.

Results

The age-standardized prevalence of diabetes in 55- to 74-year-old adults was 8.2% at the initial survey and 10.6% at the 5-year follow-up. At the initial survey, among participants with self-reported diabetes, the mean HbA1c values in the participants who had never and who had previously received diabetes treatment were 7.01% (standard deviation [SD] 1.56%) and 6.56% (SD 1.46%), respectively. Approximately 15% of the participants who had self-reported diabetes but had never received diabetes treatment had an HbA1c ≥ 8.4%.

Conclusions

The prevalence of diabetes increased in the JPHC cohort between the late 1990s and early 2000s. A certain proportion of participants who were aware of their diabetes but were not currently receiving treatment had poor diabetic control. Efforts to promote continuous medical attendance for diabetes care may be necessary.Key words: diabetes mellitus, prevalence, self-report, HbA1c     

Attitudes toward dementia‐related aggression among staff in Japanese aged care settings

Aim and objective. This study investigated attitudes of Japanese aged care staff toward aggression by people with dementia. Relationships between staff attitudes, professional characteristics and clinical practice were explored. Background. Aggressive behaviour is often demonstrated by people with dementia and may be influenced by many factors including an inability by the individual to appropriately express their needs, difficulties with assessment, as well as organisational and practice issues. Design. Survey. Method. Twenty‐seven facilities/organisations located in the western and middle parts of Japan were surveyed. Staff (n = 675) employed in these facilities provided personal and professional information and completed the Attitudes Towards Aggression Scale. Results. Staff who were older, had more clinical experience, higher education and/or a higher position reported more positive attitudes towards patient aggression. Staff with negative attitudes towards patients who are aggressive reported using chemical and/or physical restraint more often than staff with positive attitudes. Conclusions. Dementia education as well as restraint policy will be useful in addressing negative staff attitudes, in particular it may help to reverse the myth that restraint is necessary for staff protection. Furthermore, staff counseling may help to reduce stressors and to change staff negative attitudes towards people with dementia who display aggression. Relevance to clinical practice. The findings show that negative staff attitudes may adversely affect clinical decision making and patient care. Measuring attitudes can identify areas requiring education or skill development and enable changes in attitudes to be monitored over time.     

Retrovirus-mediated Gene Transfer Targeted to Malignant Glioma Cells in Murine Brain

A murine model for meningeal metastasis of malignant glioma was developed to study selective gene transfer into tumor cells and to establish a reliable means of determining the rate of tumor cell infection. A murine ecotropic retroviral vector was created in which the Escherichia coli β-galactosidase gene served as a marker for gene expression from the integrated retrovirus. This retrovirus exhibited a high rate of infectivity in RSV-M mouse glioma cells in vitro . The recombinant retrovirus was injected directly into the cisterna magna of the mice. Staining of β-galactosidase showed that the rate of gene integration was high in the disseminated glioma cells. These results suggest the possibility of retrovirus-mediated gene therapy for meningeal dissemination of malignant glioma.