A novel cognition enhancer NS-105 modulates adenylate cyclase activity through metabotropic glutamate receptors in primary neuronal culture

The effect of (+)-5-oxo-D-prolinepiperidinamide monohydrate (NS-105), a novel cognition enhancer, on adenylate cyclase activity was investigated in cultured neurons of the mouse cerebral cortex. NS-105 (10^–7 and 10^–6 M) inhibited forskolin-stimulated cyclic AMP formation, an action that was dependent on pertussis toxin-sensitive G proteins. Conversely, in pertussis toxin-pretreated neurons, NS-105 (10^–7 –10^–5 M) significantly enhanced the forskolin-stimulated cyclic AMP formation, and this action was completely reversed by cholera toxin. A metabotropic glutamate receptor agonist (1S, 3R)-1-aminocyclopentane-1, 3-dicarboxylic acid (1S, 3R-ACPD) produced similar bi-directional actions on the cyclic AMP formation. Both of these inhibitory and facilitatory actions of NS-105 and 1S, 3R-ACPD were blocked by L(+)-2-amino-3-phosphopropinoic acid (L-AP3). NS-105 (10^–6 M) and 1S, 3R-ACPD (10^–4 M) significantly enhanced isoproterenol- and adenosine-stimulated cyclic AMP formation. The enhancement of such Gs-coupled receptor agonists-stimulated cyclic AMP formation was also produced by quisqualate but not by L(+)-2-amino-4-phosphonobutanoate (L-AP4). The phosphoinositides hydrolysis was enhanced by 1S, 3R-ACPD (10^–4 M) but not by NS-105 (10^–6 M), however, 1S, 3R-ACPD-induced increase in phosphoinositides turnover was attenuated by NS-105. These findings suggest that NS-105 stimulates metabotropic glutamate receptor subclasses that are coupled both negatively and positively to adenylate cyclase, but it acts as an antagonist at the receptor subclasses that are linked to phosphoinositides hydrolysis. Received: 3 February 1997 / Accepted: 25 April 1997     

Destination after discharge from a senile dementia therapy ward before and after the implementation of long-term care insurance in Japan

Background: In Japan a new long‐term care insurance (LTCI) system, the so‐called ‘Kaigo‐Hoken’, was started in April 2000. The present study analyzes the change in the type of destination after discharge from a senile dementia therapy ward before and after the implementation of LTCI at Fukuoka Prefectural Onga Hospital, Japan. Methods: The present study examines data from 199 inpatients discharged from the Fukuoka Prefectural Onga Hospital that had been diagnosed with dementia and met the DSM IV criteria for Alzheimer's type, vascular dementia or other type of dementia. For the purposes of comparison two periods were defined, ‘the first period’ was defined as the period from 1 April 1999 to 31 March 2000, before LTCI was implemented, while ‘the second period’ was defined as the period from 1 April 2000 to 31 March 2001, after LTCI had started. Subject data was analyzed on the basis of where the subject had resided pre‐admission and their destination after discharge using the following classifications: nursing home or geriatric care facility, hospitalization, home and death. Results: While the certification rate of inpatients regarding long‐term care increased slightly in the second period, no significant change was observed based on where the subject had resided pre‐admission and their destination after discharge between the first and second periods. Conclusions: While LTCI is essential for Japan, it is necessary that people with dementia in senile dementia therapy wards are encouraged to return to their homes under the care and support of LTCI.     

Measurement of the zeta potential of human platelets by the use of laser-light scattering.

An instrument was developed to detect the shift in scattering of laser light that occurs when particles in suspension move in a chamber with an electrical load. The instrument measures the zeta potential of particles. We applied the instrument to study human blood cells. Platelet-rich plasma was used because of the stability of the suspension, without the sedimentation or autoaggregation that is often seen with red or white blood cells. The reproducibility of the measurements was satisfactory when there were enough platelets in the suspension. Platelets from healthy controls (n = 136) had a potential of -14.20 +/- 1.64 mV at the detection angle of 17.1 degrees. Platelets from patients with essential thrombocytosis (n = 16) or polycythemia vera (n = 8) had higher potentials than the healthy controls.     

A case of Raeder's syndrome caused by metastatic malignant lymphoma

A case of Raeder's syndrome caused by metastatic malignant lymphoma was reported. The patient was 67-year-old male. He had complained of diplopia, ptosis and frontal headache at the left side. Neurological examinations revealed left incomplete Horner's syndrome (miosis and ptosis, but normal facial sweating) and left abducens palsy, which was considered to be Raeder's syndrome Group 1 (Boniuk and Schlazinger's classification). CT scan, MRI and angiography demonstrated a mass lesion in the left cavernous sinus extending to the sphenoparietal sinus, and a mass lesion in the anterior part of the superior sagittal sinus. During his hospitalization, enlargement of the left cervical lymph nodes was noticed. "Malignant lymphoma (non-Hodgkin)" was diagnosed on the basis of biopsy. Group 1 of Raeder's syndrome is rare, but it is important to define the site of lesion, which is located around the paratrigeminal region at the middle cranial fossa. Because these lesions are very small and metastatic in many cases, various neuroradiological investigations, especially MRI, are necessary for early diagnosis and early treatment.     

SOLITARY PLASMACYTOMA OF THE SUBMANDIBULAR LYMPH NODE WITH STROMAL AMYLOID DEPOSITS

This report concerns a case of solitary extramedullary plasmacytoma of the left submandibular lymph node in a 56-year-old man. The tumor showed monoclonal proliferation of abnormal plasma cells which revealed highly positive stainings of both methylgreen pyronin and kappa light chain using the immunoperoxidase technique in the cytoplasms, and further revealed massive'.amyloid'deposits in the stroma, which suggested the possibility of sequential amyloid formation upon the secretion of paraprotein by tumor cells.     

FGF signaling segregates biliary cell-lineage from chick hepatoblasts cooperatively with BMP4 and ECM components in vitro.

Intrahepatic bile ducts (IHBDs) are indispensable for transporting bile secreted from hepatocytes to the hepatic duct. The biliary epithelial cells (BECs) of the IHBD arise from bipotent hepatoblasts around the portal vein, suggesting the portal mesenchyme is essential for their development. However, except for Notch or Activin/TGF-beta signaling molecules, it is not known which molecules regulate IHBD development. Here, we found that FGF receptors and BMP4 are specifically expressed in the developing IHBD and the hepatic mesenchyme, respectively. Using a mesenchyme-free culture of liver bud, we showed that bFGF and FGF7 induce the hepatoblasts to differentiate into BECs, and that BMP4 enhances bFGF-induced BEC differentiation. The extracellular matrix (ECM) components in the hepatic mesenchyme induced BEC differentiation. Forced expression of a constitutively active form of the FGF receptor partially induced BEC differentiation markers in vivo. These data strongly suggest that bFGF and FGF7 promote BEC differentiation cooperatively with BMP4 and ECMs in vivo.