Altered EphA5 mRNA expression in rat brain with a single methamphetamine treatment

Methamphetamine is a potent and indirect dopaminergic agonist which can cause chronic brain dysfunctions including drug abuse, drug dependence and drug-induced psychosis. Methamphetamine is known to trigger molecular mechanisms involved in associative learning and memory, and thereby alter patterns of synaptic connectivity. The persistent risk of relapse in methamphetamine abuse, dependence and psychosis may be caused by such alterations in synaptic connectivity. EphA5 receptors constitute large families of tyrosine kinase receptor and are expressed almost exclusively in the nervous system, especially in the limbic structures. Recent studies suggest EphA5 to be important in the topographic projection, development, and plasticity of limbic structures, and to be involved in dopaminergic neurotransmission. We used in situ hybridization to examine whether methamphetamine alters EphA5 mRNA expression in the brains of adult male Wister rats. EphA5 mRNA was widely distributed in the medial frontal cortex, cingulate cortex, piriform cortex, hippocampus, habenular nucleus and amygdala. Compared to baseline expression at 0 h, EphA5 mRNA was significantly decreased (by 20%) in the medial frontal cortex at 24 h, significantly increased (by 30%) in the amygdala at 9 and 24 h, significantly but transiently decreased (by 30%) in the habenular nucleus at 1 h after a single injection of methamphetamine. Methamphetamine did not change EphA5 mRNA expression in the cingulate cortex, piriform cortex or hippocampus. Our results that methamphetamine altered EphA5 mRNA expression in rat brain suggest methamphetamine could affect patterns of synaptic connectivity, which might be responsible for methamphetamine-induced chronic brain dysfunctions.     

慢性不完全性睡眠剥夺对幼鼠学习记忆的影响

目的：探讨慢性不完全性睡眠剥夺对幼鼠学习记忆能力的影响及其可能机制。方法：建立慢性不完全性睡眠剥夺动物模型，并测定其空间学习记忆能力，同时对幼鼠大脑前额皮质及海马神经元性一氧化氮合酶(nNOS)的表达进行分析。结果：睡眠剥夺组幼鼠完成预定任务所需的时间及发生错误的次数均超过正常对照组。睡眠剥夺组的nNOS在前额皮质区域阳性、强阳性表达面积及在海马区域强阳性表达面积均大于正常对照组。结论：慢性不完全性睡眠剥夺会影响幼鼠的学习记忆能力，而前额皮质及海马中nNOS表达水平的下降可能是慢性不完全性睡眠剥夺影响未成熟脑学习记忆能力的机制之一。     

Glomerular matrix proteins in nodular glomerulosclerosis in association with light chain deposition disease and diabetes mellitus

The diagnosis of light chain deposition nephropathy is based on the immunohistochemical demonstration of monoclonal light chain deposits within connective tissue matrix and on the presence at the ultrastructural level of electron-dense granular deposits along glomerular and tubular basement membranes. A nodular glomerulopathy characterized by amorphous periodic acid-Schiff-positive and argyrophilic widened mesangium and nodules is described in three patients with light chain deposition nephropathy. Light microscopic examination did not allow discrimination between the glomerular changes found in these specimens and the nodular glomerulosclerosis described in four patients with well-documented diabetes mellitus. Electron microscopic examination revealed microtubular fibrils 10 to 12 nm thick in mesangial areas in both groups. Such microfibrils could be glycoproteins. Immunofluorescence localization of matrix proteins, by staining with affinity-purified antibodies to types I, III, IV, and V (A, B) collagens, fibronectin, laminin, and heparan sulfate-containing proteoglycans, showed similar distributions in the two conditions. The mechanism of this abnormal accumulation of mesangial and glomerular basement membrane matrix proteins in two different conditions remains unknown.     

Skin test suppression by antihistamines and the development of subsensitivity

The suppression of skin test reactivity by single doses of six antihistamines was measured before and after a period of daily antihistamine ingestion in 18 subjects. Single doses of hydroxyzine, 50 mg; chlorpheniramine, 16 mg; and promethazine, 50 mg; induced significant suppression of skin test reactivity at 2 hr, whereas the suppression produced by tripelennamine, 100 mg; diphenhydramine, 50 mg; and cyproheptadine, 16 mg; did not differ significantly from that produced by placebo. After 3 wk of treatment with hydroxyzine, 75 mg per day, the suppressive effect of hydroxyzine as well as the five clinically unrelated antihistamines was significantly reduced. Although the response to chlorpheniramine was also reduced after chronic treatment with chlorpheniramine, 24 mg per day, the difference was not statistically significant. We conclude that antihistamines in the doses used differ greatly in their suppressive effect on skin test reactivity. The antihistamine producing the most skin test suppression, hydroxyzine, when it was taken daily for 3 wk, caused the development of partial tolerance not only to its own effect but to those of clinically unrelated antihistamines.     

Ecotropic and dualtropic mink cell focus-inducing murine leukemia viruses can induce a wide spectrum of H-2 controlled lymphoma types

Neonatal infection of C57BL and BALB/c mice by cloned ecotropic and dualtropic mink cell focus-inducing (MCF) murine leukemia viruses (MuLV) induces a wide spectrum of different lymphomas of T, B, and non-T/non-B cell types. Oncogenic dualtropic MCF viruses and poorly oncogenic ecotropic MuLV act synergistically in lymphomagenesis. Within one mouse strain virus-induced T-cell lymphomas arise earlier than B-cell lymphomas after neonatal inoculation of a single-cloned MuLV. The host genetic constitution, notably the H-2 complex has a marked influence on lymphoma type. This H-2 influence can be explained by an H-2-linked difference in penetration of the thymus early in life by oncogenic thymotropic MuLV, which in turn is correlated with, but not necessarily due to the magnitude of the anti-MuLV antibody response.     

Gustatory stimulus control and reversal learning in rats

Behavioral indices of taste discrimination have been used to study gustatory physiology and psychophysics though they are often biased by taste and position preferences and offer limited stimulus control. In the present experiment five rats were trained to discriminate distilled water from 0.9% NaCl using a discretetrials go-no go procedure. When two rats were further trained on a series of 0.1% saccharin/NaCl discrimination reversals, correct responding occurred more rapidly following saccharin presentations independent of its stimulus property (S^D or S^Δ). The results are discussed in the context of experimental methods and the usefulness of the present technique for studies of gustatory physiology.     

Karyotyping chromosomes by electron microscopy. Condensation-inhibition of G bands in human and Chinese hamster chromosomes by a BrdU-Hoechst 33258 treatment

A BrdU-Hoechst 33258 treatment of living cells, which selectively induced condensation-inhibition of G-band chromatin in human and Chinese hamster chromosomes, is presented. As a consequence mitotic chromosomes showed high resolution R-banding patterns when examined by light and electron microscopy. Besides each whole chromosome identification, this procedure also permitted the electron microscopic study of specific structures, such as satellites, secondary constrictions, telomeres, centromeres, as well as G and R bands, some of them not visible by light microscopy. We have also observed that the chromatin of G and R bands behave as blocks of chromatin condensation and that G-band chromatin develops condensation along G₂. Under the BrdU-Hoechst 33258 treatment, chromatin fibers seem to invert their spontaneous pattern of condensation within the chromosomes.     

The development of goal-directed reaching in infants II. Learning to produce task-adequate patterns of joint torque

 Nine young infants were followed longitudinally from 4 to 15 months of age. They performed multijoint reaching movements to a stationary target presented at shoulder height. Time-position data of the hand, shoulder, and elbow were collected using an optoelectronic measurement system. In addition, we recorded electromyographic activity (EMG) from arm extensors and flexors. This paper documents how control problems of proximal torque generation may account for the segmented hand paths seen during early reaching. Our analysis revealed the following results: first, muscular impulse (integral of torque) increased significantly between the ages of 20 (reaching onset) and 64 weeks. That is, as infants got older they produced higher levels of mean muscular flexor torque during reaching. Data were normalized by body weight and movement time, so differences are not explained by anthropometric changes or systematic variations in movement time. Second, while adults produced solely flexor muscle torque to accomplish the task, infants generated flexor and extensor muscle torque at shoulder and elbow throughout a reach. At reaching onset more than half of the trials revealed this latter kinetic profile. Its frequency declined systematically as infants got older. Third, we examined the pattern of muscle coordination in those trials that exhibited elbow extensor muscle torque. We found that during elbow extension coactivation of flexor and extensor muscles was the predominant pattern in 67% of the trials. This pattern was notably absent in comparable adult reaching movements. Fourth, fluctuations in force generation, as measured by the rate of change of total torque (NET) and muscular torque (MUS), were more frequent in early reaching (20–28 weeks) than in the older cohort (52–64 weeks), indicating that muscular torque production became increasingly smoother and task-efficient. Our data demonstrate that young infants have problems in generating smooth profiles of proximal joint torques. One possible reason for this imprecision in infant force control is their inexperience in predicting the magnitude and direction of external forces. That infants learned to consider external forces is documented by their increasing reliance on these forces when performing voluntary elbow extensions. The patterns of muscle coordination underlying active elbow extensions were basically the same as during the prereaching phase, indicating that the formation of functional synergies is based on a basal repertoire of innervation patterns already observable in very early, spontaneous movements. Received: 5 January 1996 / Accepted: 19 August 1996     

Early coping experience and later aversive conditioning in cats

Kittens were given differential early experience in order to compare an objective coping behavior with the result of an inescapable aversive experience. Separate groups of kittens were treated in a shock motivated runway task at either 4 or 12 weeks of age, by allowing one member of a weight matched sibling pair to acquire an escape behavior, while the other member was confined; a third subject served as a handled control. Escape behavior was significantly different for 4 and 12 week old subjects, since the older kittens reached a running asymptote within the first few shock trials. At 6 months of age, the subjects were tested for effects of differential early treatment; heart rate, respiration rate and amplitude, and somatic activity were measured during classical conditioning. While all groups gave evidence of acquisition in one or more response measures, only a potentiated heart rate response in 4 week kittens could be related to early experience. Heart rate did not differentiate escaping kittens from confined ones. Rather, heart rate was related to early treatment with shock, perhaps reflecting an increased tendency to react with a passive defensive response.     

Ejaculatory incompetence: a theoretical formulation and case illustration

Three theoretical formulations of ejaculatory incompetence have been proposed in the literature. They include: (1) aversive conditioned inhibition of the ejaculatory reflex, (2) an "autosexual" orientation associated with discrepant levels in the cognitive and physiological dimensions of sexual arousal, and (3) a discriminative learning model. These three models are discussed in relation to their theoretical and therapeutic implications. Clinical data supporting the discriminative view is presented.