Effects of dopamine antagonists on neuronal activity related to a delayed response task in monkey prefrontal cortex

1. Using iontophoretic techniques, we investigated the influence of dopamine (DA) antagonists [haloperidol (HAL), a non-selective DA antagonist; sulpiride (SUL), a selective antagonist for D2 receptors; and fluphenazine (FLU), a potent antagonist for D1 receptors] on neuronal activity related to a delayed response (DR) task in the monkey prefrontal cortex (PFC). The DR task was initiated by the rotation of a handle to a central zone and consisted of seven distinct periods: an initial intertrial interval of 0.3 s, a precue period of 1 s (a center green lamp), a cue period of 1 s (left or right lamp), a delay period of 4 s, a go period (red lamp in the center; rotation of the handle to either the left or right zone), a hold period (holding of the handle in either the left or right zone), and a final reward period. Because it was shown, as described in the companion paper (Sawaguchi et al. 1990), that DA augments the increased activity of prefrontal neurons related to the cue, delay, and go periods of the DR task, effects of the DA antagonists were examined in a total of 61 neurons that showed increases in activity related to these periods and a response to DA. 2. Consistent with previous studies (Sawaguchi et al. 1988a, 1990), iontophoretically applied DA increased DR task-related activity in prefrontal neurons. Iontophoretically applied HAL and FLU antagonized the increased effect of DA on the task-related activity. By contrast, SUL did not have any clear effects on the influence of DA. 3. By themselves, HAL and FLU reduced prefrontal neuronal activity related to the cue, delay, and go periods of the DR task. The ratio of the reduction by HAL and FLU was significantly larger for activity during the cue, delay, or go period than for background activity during the precue period; and, as a result, the signal-to-noise (S/N) ratio of the task-related activity to background activity was reduced during the application of HAL and FLU. In contrast, SUL did not have any clear effects on activity related to the cue, delay, and go periods of the DR task, and the S/N ratio during the application of SUL did not significantly differ from that before the application of the drug.(ABSTRACT TRUNCATED AT 400 WORDS)     

Histological properties and biological significance of pouch in red kangaroo, Macropus rufus

2 embryos, 4 youngs, 4 older youngs and the pouch of 2 mothers of the red kangaroos were examined. The results obtained are as follows: 1. The initial muscle spindles are already observed light microscopically in the vertebral, dorsal neck and forelimb muscles of the newborn baby and a little bit later in the masticatory muscles of the young of 68 mm in craniorump length and 28 g in body weight. 2. In the skin with less hair lining the inner surface of the pouch, abundant apocrine large sweat glands are observed, especially surrounding the basal region of the nipple and in the pleat formation of the skin. 3. The lactiferous mammary gland is enlarged, the lobules being divided by the interlobular muscle fiber tissue and enwrapped by the muscular capsule. The milk is squirted automatically by the muscle fiber contraction from the gland to the nipple, to which the baby attaches itself. 4. The musculature of the pouch wall is developed to form the sphincter muscle in the pouch orifice. The sphincter muscle plays an important role in conditioning the optimum temperature for the naked baby inside the pouch. 5. The apocrine perfume plays an important role in guiding the baby on the journey to the pouch after birth and the apocrine products also in maintaining the optimum humidity of the pouch to accomodate the baby. 6. During the long period of stay in the pouch, the masticatory and locomotive systems and their neuromuscular mechanism related to the herbivorous mastication become fully established and then the young leaves the pouch to feed on the animal's proper diet.     

Infrequent genetic alterations of the PTEN gene in Japanese patients with sporadic prostate cancer

Prostate cancer is a major cause of cancer death among elderly men in America, Europe, and Japan. However, the molecular mechanism of carcinogenesis is not yet well characterized. Frequent loss of heterozygosity (LOH) on chromosome 10q was reported in prostate cancer, and a candidate tumor suppressor gene, PTEN, was isolated on chromosome band 10q23.3. To investigate the genetic alterations of PTEN, we examined 45 primary prostate cancer specimens. LOH at the PTEN locus was observed in two (11.1%) of 18 tumors. However, no mutations were observed in any of the primary prostate cancers. These data suggest that mutation of the PTEN gene does not play a major role in prostate carcinogenesis of Japanese patients. Received: February 6, 1998 / Accepted: July, 3, 1998     

Two dinucleotide repeat polymorphisms at the D8S1442 and D8S1443 loci

Two polymorphic dinucleotide (CA) repeat clones were isolated from cosmids, cCI8-1121 and cCI8-1199, mapped to chromosome 8p11.2-p12.     

Modulation of neuronal activities by iontophoretically applied catecholamines and acetylcholine in the primate motor cortex during a visual reaction-time task

Single neuronal activities in the primate motor cortex were modulated by iontophoretically applied acetylcholine (ACh), noradrenaline (NA) or dopamine (DA) while monkeys were performing a visual reaction-time. task. ACh caused general increases of the discharge activities of both the background baseline and the task-related activity peaks, whereas NA caused decreases mainly of the baseline. DA caused activity increases in half of the tested neurons, and decreases in 25% of the neurons. NA modulated the firing rate to enhance the signal-to-noise ratio of the related activities. ACh and DA, by contrast, subserved to enhance the synaptic transmission in the motor cortex.     

ULTRASTRUCTURAL ASPECTS OF THE ROLE OF THE MEDIA-SMOOTH MUSCLE CELLS IN ARTERIOSCLEROSIS OF MAN AND ANIMALS

In various arterial lesions including atherosclerotic lesions, the main morphological change involves smooth muscle cells. The potential sensitivity is different among the arterial smooth muscle cells, venous smooth muscle cells and smooth muscle cells of other organs. The modified smooth muscle cells characterized by the increase of rough endoplasmic reticula are considered to express their latent ability to synthesize collagen fibers, elastic fibers and other ground substances.
The foam cells noted in atherosclerosis and fatty streak consist of lipid accumulated smooth muscle cells and hematogenous macrophages. Lipid metabolism and synthesis in the latter differ from those in the former. The ratio of the two kinds of foam cells in atheroma or fatty streak varies by the stage of the lesion.
It is possible to suppose that there exists a factor which would selectively attack the media smooth muscle cells of small arteries or arterioles. This is observed electron microscopically as focal cytoplasmic necrosis (cytoplasmolysis) of smooth muscle cells and plays an important role in the histogenesis of fibrinoid necrosis.
In case of experimental periarteritis nodosa the early stage begins with cytoplasmolysis of smooth muscle cells and marked increase of rough endoplasmic reticula in adjacent smooth muscle cells.     

Role of KCNQ1 in the cell swelling-induced enhancement of the slowly activating delayed rectifier K(+) current

Cell swelling enhances a slowly activating delayed rectifier K(+) current (I(Ks)) in cardiac cells. This investigation was undertaken to determine which of the two structural units reconstituting the I(Ks) channel, KCNQ1 (KvLQT1) and KCNE1 (minK/IsK), plays a key role in the cell swelling-induced I(Ks) enhancement and to dissect a possible involvement of tyrosine phosphorylation therein. KCNQ1 was transiently expressed alone or together with KCNE1 in a heterologous mammalian cell line. Two distinct whole-cell membrane currents were separately observed during the exposure of transfected cells to various degrees of hyposmotic solutions. A hyposmotic challenge (0.7 times control osmolarity) resulted in about a twofold increase not only in the heteromeric KCNQ1/KCNE1, but also in the homomeric KCNQ1 channel currents. There was no significant difference in the incremental ratio of current amplitude in response to hyposmotic stress between the two KCNQ1-related currents, and the cells expressing the heteromeric channels swelled less than those with the homomeric channels or without the exogenous ones. The cell swelling-induced I(Ks) enhancement was not affected by a protein tyrosine kinase (PTK) inhibitor, by genistein (50 microM), or by an inhibitor of phosphotyrosine phosphatase (PTP), orthovanadate (500 microM), or a nonhydrolyzable ATP analogue, AMP-PNP (5 mM). Taken together, it is very likely that KCNQ1 might primarily participate in the I(Ks) enhancement by osmotic cell swelling. The obligatory dependence of the I(Ks) augmentation on PTK activity remained to be demonstrated, at least, in this expression system.     

The effectors of killer activity induced by interferon-alpha and gamma in peripheral blood mononuclear cells

The nature of effectors of interferon (IFN)-alpha or IFN-gamma-induced killer cell activity remains unclear. The aim of this study was to examine killer cell activity induced by IFN-alpha alone, IFN-gamma alone or a combination of both in patients with renal cell carcinoma (RCC) and to determine the phenotypic patterns of these effectors. The study group included 14 patients (12 men and 2 women, median age 64 years, range 36-77) with confirmed RCC. Peripheral blood mononuclear cells (PBMC) from RCC patients or normal volunteers were cultured with IFN-alpha alone, IFN-gamma alone or a combination of both. Cytotoxic activity was assayed against ACHN cells. Subpopulations of effector cells in IFN-induced killer cell activity were characterized by cell sorting. The most effective type of IFN and the optimal concentration of IFN necessary to induce the maximal killer cell activity varied among RCC patients. The killer activity induced by a combination of IFN-alpha and IFN-gamma was significantly greater than that induced by IFN-alpha or IFN-gamma alone. The greatly increased killer activity induced by IFN-alpha and IFN-gamma was seen in the subpopulations CD3(-) CD16(+), CD3(-) CD56(+) and subpopulation CD3(+)CD4(-), CD3(-)CD16(+), CD3(-)CD56(+), CD57(+)CD16(-), respectively. An optimal type of IFN and optimal concentration of IFN seem to increase the effective rate of treatment of RCC. In addition, the role of IFN-alpha seems to be different from that of IFN-gamma in host defense against RCC. A combination treatment with IFN-alpha and IFN-gamma seems to be suitable to increase the effective rate if we could reduce the side effects of IFNs.