Coincidence of ipsilateral ocular dominance peaks with orientation pinwheel centers in cat visual cortex.

Geometrical relationships among multiple cortical maps, such as those between ocular dominance and orientation maps, are a prominent feature of the brain's functional architecture. It is also well known that there is a strong bias of cortical responses toward the contralateral eye during early postnatal development. We wondered therefore whether and how such an imbalance of cortical responsiveness in a developing animal might influence the mutual geometrical relationships between orientation and ocular dominance maps in adult animals. The results of our study indicate the existence of a strong tendency for the peaks of the ipsilateral eye domains to coincide with the location of point singularities (pinwheel centers) in orientation maps. No such relationship was found for the peaks of contralateral eye domains. Computational studies reproduced similar asymmetry in the coincidence under the contralateral eye bias of inputs. Our study raised the idea that the pinwheel centers play an important role for retaining the weaker ipsilateral eye inputs during normal development.

Arrangement of orientation pinwheel centers around area 17/18 transition zone in cat visual cortex.

In the primary visual cortex of higher mammals, orientation preferences are represented continuously except for singular points, so-called pinwheel centers. In spite of the uniqueness of orientation pinwheel centers, very little is known about the pattern of their arrangement. In this study we examined the arrangement of orientation pinwheel centers in the cat visual cortex by optical imaging of intrinsic signals. Our results demonstrate that orientation pinwheel centers are arranged in a unique geometric pattern around the area 17/18 transition zone: pinwheel centers of the same type are arranged in rows parallel to the transition zone, and rows of clockwise and counterclockwise pinwheel centers are arranged alternately. We suggest that the areal border imposes a strong restriction on the pattern formation of orientation preference maps in the visual cortex.

Geometrical and topological relationships between multiple functional maps in cat primary visual cortex.

The mammalian striate cortex is organized such that the receptive field properties of neighboring neurons change gradually across the cortical surface, forming so-called cortical maps. The presence of such maps has been demonstrated in different species of mammals for several parameters characterizing the visual space: retinotopy, ocular dominance, orientation, direction of motion and spatial frequency. In this study we used the optical imaging of intrinsic signals to simultaneously record the multiple functional maps in the same animal in order to obtain a comprehensive set of rules that govern mutual dependencies among the functional maps. Our results indicate that while orientation, direction and ocular dominance are represented on the cortex in a mutually dependent manner, the representation of spatial frequency is independent of the other types of cortical representations. The presence and/or absence of mutual dependence among the multiple functional maps are suggested to provide an important clue for the understanding of the development of visual cortical information representation in neonatal animals.

GABA-mediated representation of temporal information in rat barrel cortex.

Temporal sequences of inputs to the rat whiskers are thought to be important to recognize the environment of the rat. In this study, we applied combined stimulations to neighboring whiskers D1 and D2, and the cortical activities evoked in the rat barrel cortex were measured using the intrinsic optical imaging technique. The timing of stimulation to neighboring whiskers affected the evoked cortical activities: the cortical activity evoked by in-phase stimulation to D1 and D2 was significantly stronger than that evoked by out-of-phase stimulation. In order to elucidate the mechanism underlying this phenomenon, the effect of blockade of cortical inhibitory circuits was examined. Iontophoretic application of bicuculline or saclofen (GABA-A or GABA-B antagonist) increased the evoked cortical activities and diminished the difference in activities obtained with in-phase and anti-phase stimulation. These results suggest that local inhibitory circuits play a critical role in coding temporal information of whisker stimulation.

[Effective splenectomy in a patient with HIV-associated thrombocytopenia].

A 31-year-old man presented with a 3-month history of petechial hemorrhages. Physical examination revealed no splenomegaly. The patient's platelet count was 1.0 x 10(9)/l and bone marrow aspiration showed an elevated number of megakaryocytes. A diagnosis of HIV-associated thrombocytopenia was made on the basis of HIV seropositive results. The CD4 cell count was 400 x 10(6)/l. No opportunistic infections indicating AIDS were detected. Initially the patient was treated with predonisolone, but showed only a transient response. He also failed to respond to zidovudine, lamivudine, or indinavir. Following splenectomy, however, his platelet count rose above 80 x 10(9)/l (normal level: 150-350 x 10(9)/l).

A unique role of protein phosphatases in cerebellar long-term depression.

In order to investigate phosphorylation-dephosphorylation processes underlying long-term depression (LTD) in cerebellar Purkinje cells, the protein phosphatase inhibitors calyculin A and microcystein-LR were applied to Purkinje cells in guinea pig cerebellar slices either by bath application or by intracellular pressure injection. Under the influence of these protein phosphatase inhibitors, excitatory post-synaptic potentials evoked by stimulation of parallel fibres exhibited marked depression which developed at a rate dependent on the rate of parallel fibre stimulation. The protein phosphatase inhibitors thus substitute climbing fibre signals which induce LTD when combined with parallel fibre signals. Peculiarly, this is opposite to the effect in pyramidal cells, where protein phosphatase inhibitors block LTD.

NE-100, a novel sigma receptor ligand: in vivo tests.

It has been suggested that sigma receptor antagonists may be useful as antipsychotic drugs. N, N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100) is a novel compound with high affinity for the sigma receptor (IC50 = 4.16 nM), but low affinity (IC50 > 10,000 nM) for D1, D2, 5-HT1A, 5-HT2 and phencyclidine (PCP) receptors. The head-weaving behavior induced by either (+)SKF10047 or PCP was dose-dependently antagonized by NE-100 with oral ED50 at 0.27 and 0.12 mg/kg, respectively. NE-100 did not affect dopamine agonists-induced stereotyped behavior and/or hyperactivity. NE-100 failed to induce catalepsy in rats. These findings indicate that NE-100 may have antipsychotic activity without the liability of motor side effects typical of neuroleptics.

Differential blocking action of Joro spider toxin analog on parallel fiber and climbing fiber synapses in cerebellar Purkinje cells.

Synaptic potentials were recorded intracellularly from Purkinje cells in guinea pig cerebellar slices. EPSPs evoked by stimulation of parallel fibers were effectively blocked by perfusion of a slice with the synthetic analog of Joro spider toxin, 1-naphthylacetyl-spermine (NAS) at 250 microM. However, it did not influence those responses evoked by stimulation of climbing fibers. This action of NAS is in contrast to other commonly used glutamate antagonists, CNQX or APV: CNQX (5 microM) blocked both parallel fiber- and climbing fiber-induced responses, while APV (up to 1 mM) did not influence either except for a weak reduction observed in climbing fiber responses. NAS thus provides a useful tool for pharmacologically distinguishing parallel fiber and climbing fiber synapses.

Modulation of acetylcholine release by D1, D2 dopamine receptors in rat striatum under freely moving conditions.

Using in vivo brain dialysis under freely moving conditions, we have studied the effects of dopamine (DA) agonists and antagonists on acetylcholine (ACh) and DA release in rat striatum. The striatal infusion of the D1 DA receptor specific agonist, SKF38393, increased striatal ACh release in a dose-dependent manner (10(-6) to 10(-4) M), and 3 x 10(-5) M SKF38393 elicited a 60% augmentation in the level of ACh release. The level of ACh was increased with perfusion of 10(-4) M SCH23390, a D1 specific antagonist, but decreased with 10(-3) M SCH23390. The D2 specific agonist, LY171555, and the antagonist, sulpiride, slightly altered the level of ACh in the striatum. On the other hand the level of DA dramatically increased in a dose-dependent manner with SKF38393 or SCH23390 and decreased with LY171555. LY171555 inhibited the effect of 10(-4) M SKF38393 on ACh release, and enhanced the effect of SKF38393 on DA release. These results suggest that the D1 DA receptor mainly mediates ACh release and the D2 DA receptor modifies the effects of the D1 receptor.

Brain dialysis: detection of acetylcholine in the striatum of unrestrained and unanesthetized rats.

A dialysis cannula was implanted into rat striatum while the animals were anesthetized, and after at least one day following the surgery the area was perfused with Ringer solution under the unrestrained and unanesthetized conditions. Concentration of acetylcholine (ACh) in the perfusate was determined by high-performance liquid chromatography (HPLC)-electrochemical detection (ECD) with the enzyme-column on which acetylcholine esterase and choline oxidase were immobilized. ACh in the dialysate was only detectable when the Ringer solution containing eserine, an inhibitor of acetylcholinesterase, was perfused. ACh peak on HPLC-ECD could be detected at least for 4 h under these conditions. The level of ACh increased 2-3 fold with the perfusion of 1 mM atropine sulfate, a blocker of ACh receptor. These data indicate that brain dialysis in the presence of eserine is useful for study on the neurochemical activity of ACh neurons in the brain.

An attempt to determine lipid peroxides with polyethylene glycol-modified hemin.

Hemin, having two carboxyl groups, was coupled with alpha-(3-aminopropyl)-omega-methoxypoly(oxyethylene) through the acid-amide bond formed with carbodiimide. The modified hemin catalyzed the peroxidase reaction in 1,1,1-trichloroethane using benzoyl peroxide or peroxides in unsaturated fatty acids as the hydrogen acceptor and leuco crystal violet as the hydrogen donor. A basic study on quantitative microanalysis of the lipid peroxides was attempted.

Ester-exchange catalyzed by lipase modified with polyethylene glycol.

Lipoprotein lipase was modified with 2,4-bis(O-methoxypolyethylene glycol)-6-chloro-s-triazine; forty-six percent out of seven amino groups in the molecule were substituted. The modified lipase catalyzed ester-exchange reactions between an ester and an alcohol, between an ester and an acid, and between two esters. The modified enzyme catalyzed these reactions not only in organic solvents, but also in straight hydrophobic substrates. As the modified enzyme was extremely stable at elevated temperature, for example at 70 degrees C, this can find many practical applications.

Activation and stabilization of asparaginase by anti-asparaginase IgG and its Fab.

Modified asparaginase, in which 4 tryptophan residues were modified with 2-hydroxy-5-nitrobenzyl bromide, had little enzymic activity and retained immunoreactivity [(1976) FEBS Lett. 65, 11-15]. Addition of IgG or its Fab towards asparaginase to the modified asparaginase gave rise to marked enhancement of the enzymic activity. Native asparaginase (4 subunits) lost the enzymic activity due to dissociation into subunits by dilution of the enzyme solution. However, in the presence of Fab, asparaginase did not lose enzymic activity on dilution, probably due to no dissociation into subunits occurring.

Polyethylene glycol-modified catalase exhibits unexpectedly high activity in benzene.

Bovine liver catalase with molecular weight of 248,000, which consists of four subunits, was modified with 2,4-bis(o-methoxypolyethylene glycol)-6-chloro-s-triazine(activated PEG2). The modified catalase became soluble in organic solvents such as benzene by increasing the degree of modification of amino groups in the enzyme with activated PEG2. The enzymic activity of the modified catalase in benzene, in which 42% of the total amino groups were coupled with the modifier, was unexpectedly high in comparison with the activity of non-modified catalase in aqueous system. The absorption spectrum of the modified catalase in benzene showed the characteristic pattern of a haem protein with Soret band at 405 nm. The temperature-activity profile of the modified catalase in benzene was clarified and its activation energy was estimated to be 1900 cal/mol.

Modified lipoprotein lipase catalyzes ester synthesis in benzene. Substrate specificity.

Modified lipoprotein lipase catalyzed the synthesis of trilaurin from mono- or diacylglycerol and fatty acid and also the synthesis of ester from fatty acid and alcohol in benzene. In the ester synthesis reaction, the longer the chain length of fatty acid or alcohol, the higher the ester synthesis activity. The ester synthesis was competitively inhibited by fatty acids with branch of carbon chain at the position neighboring the carboxyl group. Other substrates including secondary and tertiary alcohols and carboxylic acids having benzene ring were tested and discussed in relation to the ester synthesis.