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     

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.     

Rare Case of Small-Cell Carcinoma Arising from the Endometrium with Paraneoplastic Retinopathy

We present the fourth known case of endometrial carcinoma, and the second case of endometrial small-cell carcinoma, to be associated with paraneoplastic retinopathy. Initial symptoms were decreased visual acuity and a narrowing of the visual field. Endometrial carcinoma was diagnosed several months later. An antibody to 34-kDa bovine retinal antigen was detected in the patient's serum. Thus, autoimmunity was suspected as the cause of the retinopathy. In patients with endometrial carcinoma with visual disturbance of unknown cause, paraneoplastic retinopathy should be suspected.     

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.