5-HT(2) receptor-mediated phosphoinositide hydrolysis in bovine ciliary epithelium.

The serotonin 2 (5-HT(2)) receptor antagonists, MCI-9042 (Anplag) and ketanserin, have been shown to lower intraocular pressure in rabbits (1) and humans (2). The mechanism of action of these drugs has not been determined, but it is hypothesized that 5-HT(2) receptors, and possibly alpha-adrenergic receptors, (3) may regulate in part aqueous humor production via an intracellular signal transduction pathway in the ciliary body. We therefore examined whether 5-HT(2) receptors were coupled to phosphoinositide hydrolysis in an organ culture system of isolated bovine ciliary epithelium. 5-HT stimulated [(3)H]inositol phosphates ([(3)H]InsPs) accumulation in a dose-dependent manner with a maximum increase approximately twice over the basal level. The mean EC(50) value was 1.1 microM, which was calculated from four dose-response curves. The 5-HT stimulated accumulation of [(3)H]InsPs was inhibited by spiperone (5-HT(2A/1A) and dopamine 2 (D(2)) antagonists), M-1 (a major metabolite of MCI-9042), ketanserin (5-HT(2A) antagonist), SB-206553 (5- HT(2B/2C) antagonist), and mesulergine (5-HT(2C) antagonist and D(2) agonist). It was not inhibited by chlorpromazine, which is a D(2) receptor antagonist. Accordingly, our study demonstrates that 5-HT(2) receptors are coupled to phospholipase C in bovine ciliary epithelium.     

Uptake of dehydroascorbic acid in high-GSH and normal-GSH dog erythrocytes

Uptake of dehydroascorbic acid (DHA) was studied in two types of dog erythrocytes with high GSH and normal GSH levels. Compared with ascorbic acid uptake, DHA produced a much greater ascorbic acid accumulation in dog erythrocytes. Both dog erythrocytes showed a concentration dependence of DHA uptake, and cellular ascorbic acid concentrations were significantly higher in high-GSH cells than in normal-GSH cells. Glucose and cytochalasin B inhibited DHA uptake. This suggests that DHA enters dog erythrocytes predominantly by the facilitated glucose transporter, particularly by the Glut 1 glucose transporter. The rate of glucose uptake was quite similar in the two types of cells. Compared with normal-GSH cells, high-GSH cells were more resistant to oxidative stress induced by high concentration of DHA. As a rapid entry of DHA inflicts on cells a heavy demand for GSH for its reduction to ascorbic acid, high-GSH cells containing a larger reserve of GSH have an advantage over normal-GSH cells in both ascorbic acid accumulation and resisting oxidative stress produced by DHA.     

Malignant fibrous histiocytoma of the temporal bone with endocranial extension.

Cranial malignant fibrous histiocytomas are rare tumors. Most are hypervascular, destructive masses that are similar to other malignant lesions and to malignant fibrous histiocytomas found elsewhere in the body. We describe a myxoid malignant fibrous histiocytoma of the temporal bone, possibly of dural origin, with features that more closely resembled a meningioma at CT, MR imaging, and angiography.     

Kanji-predominant alexia with agraphia in opticospinal multiple sclerosis]

Alexia with agraphia is very rare symptom in multiple sclerosis. We present a patient of opticospinal multiple sclerosis with kanji-predominant alexia with agraphia. A 55-year-old, right-handed man was admitted to our hospital because of difficulty in reading and writing in August 2001. The patient had been diagnosed as having relapsing-remitting opticospinal multiple sclerosis eight years prior to admission. Language examination showed alexia with agraphia predominantly affecting kanji and also mild naming difficulties, but a good comprehension and a normal repetition. T2-weighted MRI demonstrated hyperintensity area in the left temporo-parietal lobe, involving the white matter beneath the postero-inferior temporal lobe and inferior parietal lobule. On brain SPECT, low blood perfusion was observed in the left temporo-parietal regions. Although agraphia for kana and alexia for both kana and kanji improved after steroid therapy, agraphia for kanji did not improve. After the treatment, high intensity area of inferior parietal lobule was disappeared on MRI, and the hypoperfusion of inferior parietal lobule on brain SPECT was also improved, but the lesion of left postero-inferior temporal lobe did not show any remarkable changes. We considered that the kanji-predominant alexia with agraphia was due to the lesions of left inferior parietal lobule and postero-inferior temporal lobe, and agraphia for kanji was due to the lesion of left postero-inferior temporal lobe.     

Clinical usefulness of the frontal assessment battery (FAB) for elderly in memory clinic]

To investigate the usefulness of the frontal assessment battery (FAB) as a brief assessment for diagnosis in patients with dementia, we examined cognitive function using the FAB, Mini-mental state examination (MMSE), Kana-hiroi test, and Raven's colored progressive matrices (RCPM). Subjects were 82 senile patients having amnesia as a complaint including 28 Alzheimer's disease (AD), 14 frontotemporal dementia (FTD), 17 vascular dementia (VD), 13 mild cognitive impairment (MCI), and 10 healthy persons. We discussed the difference of scores in different types of dementia. In the FAB, the scores of healthy persons and MCI were much higher compared with the scores of all types of dementia. There were high correlation between FAB and MMSE, Kana-hiroi test, and RCPM. Although some subjects showed normal score in MMSE and/or RCPM, they showed low score in FAB. Based on this, FAB is efficient for the differential diagnosis of dementia as brief screening tool.     

Actions of second messengers synthesized by various spasmogenic agents and their relation to mechanical responses in dog tracheal smooth muscle.

1. The effects of the spasmogenic agents, carbachol (CCh), histamine, 5-hydroxytryptamine (5-HT) and 9,11-epithio-11,12-methano-thromboxane A2 (STA2) were investigated on smooth muscle tissues of the dog trachea. 2. CCh (10 microM) produced a larger contraction than high K (128 mM), 10 microM histamine, 5-HT or STA2. Histamine and 5-HT produced the same amplitude of contraction as each other. In Ca-free solution containing 0.2 mM EGTA, only a phasic contraction was evoked by the above agents (except for K which induced no contraction at all). 3. In skinned muscle tissues, the maximum amplitude of contraction that could be induced by Ca (10 microM) was slightly larger than the maximum CCh-induced contraction (also at 10 microM) evoked in intact muscle tissues. Caffeine and inositol 1,4,5-trisphosphate (IP3) both produced contraction. 4. CCh, histamine and 5-HT (10 microM) produced a sustained contraction for over 30 min and also increased phosphorylation of the 20 kD protein of myosin light chain (MLC20) for over 30 min with no attenuation. Greater concentrations of the above agents caused more phosphorylation of MLC20. 5. CCh (above 1 nM), histamine (above 10 nM) and 5-HT (above 100 nM) increased the amount of IP3, in a concentration-dependent manner. Synthesis of IP3 induced by the above agents reached its peak value within 30 s and lasted for about 3 min. The potencies for the synthesis of IP3 were in the following order: CCh greater than histamine greater than 5-HT greater than STA2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dual concentration-dependent effects of phorbol 12, 13-dibutyrate on spontaneous and acetylcholine-induced electrical responses recorded from isolated circular smooth muscle of the guinea-pig stomach antrum.

Intracellular recordings of electrical activity were made from circular smooth muscle cells in small segments of tissue isolated from the guinea-pig stomach antrum. Every cell that was impaled exhibited a rhythmic generation of slow potentials. Experiments were carried out to test the effects of three different concentrations (1, 10 and 100 nM) of phorbol 12, 13-dibutyrate (PDBu) on these slow potentials and on the responses produced by acetylcholine (ACh), in the presence of nifedipine and N(omega)-nitro-L-arginine (nitroarginine), known inhibitors of L-type Ca-channels and nitric oxide synthase, respectively. The resting membrane potential was -62 +/- 7 mV, while the frequency and amplitude of the slow potentials were 1.6 +/- 0.1 cycle per min (cpm) and 33 +/- 1 mV, respectively. Application of 1 nM PDBu increased the frequency of slow potentials, with no significant change in the membrane potential and amplitude of slow potentials. At a concentration of 100 nM, PDBu depolarized the membrane by about 6 mV, and either decreased the amplitude and frequency of the slow potentials or abolished them. The amplitude and frequency of the slow potentials were not significantly changed in the presence of 10 nM PDBu. In the presence of chelerythrine (1-2 microM), a known inhibitor of protein kinase C (PKC), the increase in frequency of slow potentials by 1 nM PDBu and depolarization produced by 100 nM PDBu were not elicited. The increase in frequency of slow potentials by 100 nM ACh was inhibited by PDBu, in a concentration-dependent manner, and ACh-responses were abolished in the presence of 100 nM PDBu. These results indicate that PDBu has dual actions on the spontaneous activity of antral circular muscle, with low concentrations increasing and high concentrations inhibiting the frequency of the slow potentials. The former may be produced by activation of protein kinase C (PKC). As the ACh-induced excitation of slow potentials is inhibited by PDBu, a possible causal relationship between the inhibition and over-activation of PKC is considered.     

A case of ectopic large pituitary adenoma

Ectopic pituitary adenomas are very rare and only 17 cases have been reported. In this paper we present a case of large pituitary adenoma originating in the suprasellar region. A 26-year-old man was admitted to our clinic with a chief complaint of headaches. Neurological examination revealed slight disorientation and bilateral choked disk. Hormonal study revealed that the serum prolactin level was 3300ng/ml and serum growth hormone level was 29.5ng/ml. Computed tomography showed a large mass in the suprasellar region extending upward to the third ventricle and backward to the pons. T1-weighted MR imaging revealed that the intensity of the mass was the same as that of the cerebral cortex and the pituitary gland was showing high intensity in the pituitary fossa. The tumor was radically removed via the transpetrosal transtentorial approach. Histologically, the tumor was a prolactin-growth hormones producing pituitary adenoma. The literature was reviewed and the origin of the tumor was discussed.