A transcrista galli, translamina terminalis approach for highly placed basilar bifurcation aneurysms

Summary Surgery for highly placed basilar bifurcation aneurysms is one of the most difficult operations in neurosurgery. Specific surgical techniques have been developed including the temporopolar, zygomatic, transzygomatic subtemporal, transclinoid trans-sellar transcavernous, and trans third ventricular approaches. The authors present some technical advances which have been developed for the transcristagalli translamina terminalis approach for the treatment of this aneurysm.     

A novel quinolinone diuretic, M12285, and its activation mechanism through sulfate conjugation.

The diuretic activity of a quinolinone oxime diuretic, M12285, was examined after renal arterial, i.v. and portal injection in rats. M12285 injected into the renal artery at a dose of 1 mg/kg caused no diuretic effect, whereas i.v. and portal injections induced marked diuresis dose dependently. The minimum effective dose with portal injection was lower (1 mg/kg) than that with i.v. injection (3 mg/kg) and the start of the effect was faster with portal injection. These results indicated that some metabolic modification in the liver is necessary for the diuretic activity to appear. Accordingly, we performed in situ rat liver perfusion with M12285 and obtained several metabolites. Renal arterial injection of each fractionated metabolite of M12285 revealed that all the diuretic activity derived from one of these metabolites. From IR and 1H-nuclear magnetic resonance (1HNMR) measurements, the chemical structure of this active metabolite was assumed to be a sulfate-conjugated form of M12285 at the oxime moiety. Based on this tentative chemical structure, we synthesized the oxime sulfate of M12285 (potassium salt, M17000) and confirmed the identity of IR and 1HNMR spectra. Administration of M17000 into the renal artery induced apparent diuresis in a dose-dependent manner in both rats and dogs. These results indicate that the oxime sulfate of M12285 is responsible for the diuretic activity of M12285. Therefore, we synthesized several derivatives of M17000 and confirmed their possible therapeutic value as a novel family of diuretics, namely quinolinone oxime sulfonic acids.     

Gene expression profiling in schizophrenia and related mental disorders.

The etiology and pathophysiology of schizophrenia and related mental disorders such as bipolar disorder and major depression remain largely unclear. Recent advances in mRNA profiling techniques made it possible to perform genome-wide gene expression analysis in a hypothesis-free manner. It was thought that this large-scale data mining approach would reveal unknown molecular cascades involved in mental disorders. Contrary to this initial expectation, however, DNA microarray results in psychiatric fields have been notoriously discordant. Here the authors review the findings of DNA microarray analysis, focusing on systematic gene expression changes in schizophrenia, as well as alterations in the expression of specific genes, that have been reported and replicated. The authors also address the probable causes for the discordance among studies, possible ways to solve the problem, and their preferred approach for data interpretation.     

Quantitative determination of N-glycolylneuraminic acid expression in human cancerous tissues and avian lymphoma cell lines as a tumor-associated sialic acid by gas chromatography-mass spectrometry

N-Glycolylneuraminic acid (NeuGc) is distributed in most animals except humans and chickens. However, human and chicken cancerous tissues often synthesize this heterophilic sialic acid as a tumor-associated Hanganutziu-Deicher antigen [M. Naiki and H. Higashi, Adv. Exp. Med. Biol., 152: 445-456, 1982; H. Higashi et al., Cancer Res., 45: 3796-3802, 1985]. In this paper, NeuGc in human cancerous tissues and chicken Marek's disease lymphoma cell lines was determined quantitatively with gas chromatography-mass spectrometry analysis using mass fragmentography. The detectable limit of NeuGc was 40 pg (0.12 pmol) in each injection using 5 ng of trideuteriomethyl ester trideuteriomethyl glycoside of the sialic acid as an internal standard sample when a pair of ions at m/e 386 and 389 was chosen for ion monitoring. NeuGc was detected in ganglioside-rich fractions of various human cancerous tissues from 5 of 8 patients examined but was not detected in glycosphingolipids of normal human tissues. The contents of NeuGc in these cancerous tissues ranged from 0.02 to 0.5% of the total sialic acid content. NeuGc was also detected in freeze-dried samples of 5 different cell lines from chicken Marek's disease lymphomas but was not detected in a cell line from chicken lymphoid leukosis lymphoma and normal chicken skeletal muscle tissue. The contents of NeuGc in the positive cell lines ranged from 0.03 to 0.11% of the total sialic acid content. These results indicate that NeuGc can be synthesized in both humans and chickens in some cancers.     

The leprosy bacillus: a microbe-dependent microbe

Since the discovery of the leprosy bacillus, cultivable mycobacteria were regularly found in lepratic tissues of humans and armadillos. Unpublished data indicate that Professor Hugo Preisz isolated and collected several cultures of unidentified cultivable strains of mycobacteria from leprosy sufferers. Recent findings suggest that Mycobacterium leprae is a microbe-dependent, mycobactin-deficient microorganism. The author proposes the concept that secondary mycobacteria found in leprosy cases are ethilogical cofactors in the pathogenesis of leprosy. Since secondary mycobacteria are rich in mycobactin, it is suggested that they provide the essential mycobactin for growth multiplication and virulence for the mycobactin deficient leprosy bacilli. The implications of this concept are discussed.     

Effect of central scotomata on pattern reversal visual evoked potentials in patients with maculopathy and healthy subjects

The effect of central scotomata on pattern reversal visual evoked potential (PVEP) was investigated in patients with maculopathy and healthy subjects. PVEP was evoked monocularly by both full-field and half-field stimulations. Since the latency of 'the major positivity at Oz' (P100-Oz) is used as the most reliable parameter in the clinical application of PVEP, special attention was focused on its changes, comparing with 'ipsilateral major positivity of half-field PVEP' (P100-IHF). Although the incidence of modification was lower in the patients, central scotomata modified PVEPs of the healthy subjects and of the affected eye of the patients in a similar manner: full-field PVEP showed prolonged latency and reduced amplitude of P100-Oz. Half-field PVEP disclosed prolonged P100-Oz latency with intact P100-IHF latency. Only difference was that amplitude reduction of both P100-Oz and P100-IHF of half-field PVEP was observed only in the healthy subjects. The prolonged P100-Oz latency of half-field PVEP was accompanied, both in the healthy subjects and in the patients, by a contralateral negative-positive complex (N105-P135) which was augmented and extended to Oz. The prolonged P100-Oz latency, thus, was due to the pronounced P135. These observations suggested that an attenuation of the afferent impulses from the central retina may cause a prolongation of the P100-Oz latency in both healthy subjects and patients, but this is not a reflection of the truly prolonged P100-IHF latency. It was concluded that, in the clinical application of PVEP, recordings of half-field PVEP from the lateral electrodes seem to be essential to distinguish true prolongation of the P100-Oz latency.     

Developmental changes in the susceptibility to long-term potentiation of neurones in rat visual cortex slices.

We investigated with intracellular recordings from rat visual cortex slices whether the susceptibility to undergo long-term potentiation (LTP) is age-dependent and whether it is correlated with the expression of synaptic responses mediated by N-methyl-D-aspartate (NMDA) receptors. Test and tetanic stimuli were applied to the white matter and post-tetanic modifications of the amplitude of postsynaptic potentials (PSPs) were assessed in regular spiking cells of supragranular layers. At 2 weeks of age, the amplitudes of early (8-10 ms post-stimulus) and late (20 ms post-stimulus) PSP-components increased after tetanic stimulation to 137.1 +/- 13.4% and 141.3 +/- 12.1% of the pretetanic controls, respectively. At 3 weeks, potentiation of both PSP-components was less pronounced but still significant, the late component being on average more potentiated than the early one. At 4 weeks, PSPs were no longer potentiated. Bath application of 25 microM DL-2-amino-5-phosphonovalerate (APV), an NMDA receptor antagonist, blocked LTP induction both at 2 and at 3 weeks. We also studied developmental changes of two synaptic responses known to influence the susceptibility of cortical neurones to LTP, the NMDA receptor-mediated excitatory PSP (EPSP) and the initial inhibitory PSP (iIPSP). The amplitude of the APV-sensitive EPSP decreased with age and reached adult values in 4-week-old animals. The iIPSPs were pronounced already at 2 weeks and showed no marked change during further development. The results suggest a close correlation between the susceptibility to undergo LTP and the extent to which NMDA receptor-gated conductances contribute to the synaptic response.(ABSTRACT TRUNCATED AT 250 WORDS)     

Autoradiographic analysis of second messenger and neurotransmitter system receptors in the gerbil hippocampus following transient forebrain ischemia.

Changes in second messenger and neurotransmitter system receptor ligand binding induced by transient forebrain ischemia were studied in the gerbil hippocampus. The animals were allowed variable periods of recovery ranging from 2 h to 7 days after 5-min bilateral carotid artery occlusion. The binding of second messenger systems ([3H]inositol 1,4,5-trisphosphate ([3H]IP3)to inositol 1,4,5-triphosphate, [3H]forskolin to adenylate cyclase and [3H]phorbol 12,13-dibutylate to protein kinase C) and neurotransmitter receptor systems ([3H]PN200-110 to L-type calcium channels. [3H]N6-cyclohexyl-adenosine to adenosine A1 and [3H]quinuclidinyl benzilate to muscarinic cholinergic receptor) were assayed using quantitative autoradiography. In the CA1 subfield, 2 h after ischemia, [3H]IP3, [3H]forskolin, and [3H]quinuclidinyl benzilate binding activities significantly decreased by 25, 17 and 13%, respectively, though no morphological abnormalities were obvious. Six hours after ischemia, the [3H]phorbol 12,13-dibutylate binding activity in the stratum oriens of the CA1 subfield increased by 15%. One day after ischemia, [3H]PN200-110 binding activity in this subfield decreased by 26%, and 7 days after ischemia, [3H]phorbol 12,13-dibutylate and [3H]N6-cyclohexyl-adenosine receptor binding activities decreased in this subfield. In particular, at 7 days after ischemia, [3H]IP3 binding activity in the CA1 subfield showed a complete decline. In the CA3 subfield, [3H]PN200-110 binding activity decreased 2 days after ischemia, and [3H]IP3 and [3H]N6-cyclohexyl-adenosine binding activities decreased 7 days after ischemia. In the dentate gyrus, the structure of which remained histologically intact after ischemic insult, [3H]IP3 and [3H]forskolin binding activities decreased 7 days after ischemia. In contrast, the [3H]phorbol 12,13-dibutylate binding activity increased in the molecular layer of the dentate gyrus 7 days after ischemia. These results indicate that marked alteration of intracellular signal transduction precedes neuronal damage in the hippocampal CA1 subfield and that the histologically intact CA3 and dentate gyrus also shows modulated neuronal transmission after ischemia.     

Age- and sex-related differences in the nerve growth factor distribution in the rat brain.

Levels of the nerve growth factor (NGF) have been measured in various brain regions of young and aged male and female rats of Wistar strain by means of a highly sensitive two-site enzyme immunoassay system for beta-NGF. Among the ten regions examined, the amount of NGF per wet weight of tissue was found to be highest in the hippocampus, irrespective of the sex and age. The NGF concentration in the hippocampus of female rats at 3 months of age was comparable to that of same aged males. Further, there was no significant difference in the NGF levels of the hippocampus between young and age males. However, the NGF level was significantly lower in aged females as compared to that in 3- or 4-month-old females, and hence the marked male-female difference was found in the NGF levels in aged Wistar rats.