Cortical GABAergic regulation of dopaminergic responses to psychological stress in the rat dorsolateral striatum

The present study was undertaken to examine the possible involvement of cortical gamma-aminobutyric acid (GABA) neuronal mechanisms in the regional differences of dopamine (DA) response to psychological stress: contextual fear conditioning (CFC) in the rat prefrontal cortex (PFC) and dorsolateral striatum (DLS). Rats that received five footshocks (shock intensity, 0.5 mA; shock duration, 2 sec) were subjected to CFC and dynamic changes in DA and GABA in both PFC and DLS were examined using dual-probe microdialysis. Extracellular levels of DA in the PFC were enhanced during exposure to CFC, whereas the levels in the DLS were not affected by this stimulus. Extracellular levels of GABA in the PFC, but not in the DLS, were markedly enhanced by CFC. Freezing behavior observed during exposure to CFC was attenuated by the GABA(A) receptor antagonist bicuculline (10(-3) M), which was perfused into the PFC. Intracortical application of bicuculline (10(-3) M) furthermore caused sustained increases in DA levels in the DLS by CFC. These data suggest that cortical GABA(A) receptors contribute to modulation of DA release in the DLS in response to CFC. Thus, the GABAergic neuronal system in the PFC appears to play a key role in the regional differences of the DAergic response to psychological stress.     

Subcellular localization of glucose transporter 4 in the hypothalamic arcuate nucleus of ob/ob mice under basal conditions

Glucose transporter (GLUT) 4 plays an important role in insulin-induced glucose uptake in skeletal muscle and white adipose tissue. Although GLUT4 is abundant in the hypothalamus as well as in these peripheral tissues, little is known about the role of GLUT4 in the hypothalamus. In this study, we examined the subcellular localization of GLUT4 and the activation of insulin signaling pathways in the hypothalamic arcuate nucleus of ob/ob mice under basal conditions. The expression of GLUT4 in the arcuate nucleus of ob/ob mice was higher than that in lean mice. Interestingly, GLUT4 on the plasma membrane increased significantly in neurons of the arcuate nucleus of ob/ob mice when compared to that in lean mice. Because serum insulin levels of ob/ob mice were very high, we hypothesized that insulin strongly stimulates GLUT4 translocation in the arcuate nucleus of ob/ob mice. Unexpectedly, tyrosine phosphorylation of IR and insulin receptor substrate-1 (IRS-1) was faint in the hypothalamus of lean and ob/ob mice. In addition, phosphorylation of IRS-1 at Ser307 in the hypothalamus of ob/ob mice was higher when compared to that in lean mice, suggesting that insulin signaling is impaired by phosphorylation of IRS-1 at Ser307 in the hypothalamus of ob/ob mice. However, serine phosphorylation of Akt in the arcuate nucleus of ob/ob mice increased significantly when compared to that in lean mice. Furthermore, the expression of brain-derived neurotrophic factor, an activator of PI3K-Akt pathway in neurons, increased significantly in the ventromedial hypothalamus of ob/ob mice. We discuss the possibility of novel pathways which induce the translocation of GLUT4 in the arcuate nucleus of ob/ob mice.     

Herpetic lumbosacral radiculoneuropathy in patients with human immunodeficiency virus infection

We report 4 cases of human immunodeficiency virus infection associated with lumbosacral radicular dysfunction and urinary retention. Three of these cases had the so-called Elsberg syndrome in that their symptoms were associated with genital herpes. In 1 case, different herpes simplex virus types were isolated from the cerebrospinal fluid and genital swabs. Lumbosacral radiculoneuropathy with urinary retention caused by herpes viruses can develop not only with an initial genital herpes infection, but also due to reactivation of a latent herpes virus.     

Pigment epithelium-derived factor induces the production of chemokines by rat microglia

Many studies have shown that pigment epithelium-derived factor (PEDF) has neurotrophic effects on retinal cells and hippocampal, spinal cord, and cerebellar granule cell neurons, but much less work has examined the effects of PEDF on glia. In this study, we show that PEDF changes microglial morphology within 1 h of exposure, to a more deactivated form, while having no effect on the expression of such activation markers as OX-42 and ED-1. In contrast, urea activates acid phosphatase, and PEDF blocks that activation. PEDF also activates NFkappaB, accompanied by the induction of mRNAs and proteins for the chemokines macrophage inflammatory protein-1alpha (MIP-1alpha, MIP-2, and MIP-3alpha. All the chemokines stimulate acid phosphatase activity, and high doses of MIP-2 and MIP-3alpha), alter the morphology of the microglia at 1 h after treatment. These results suggest that the use of PEDF for clinical treatments, such as for retinal neovascularization, brain injury, or ischemia, should be undertaken with caution because of the possibility of induction of inflammation caused by microglial or other immune cell migration in response to the chemokines induced by PEDF.     

Dysmenorrhea: evaluation with cine-mode-display MR imaging--initial experience

PURPOSE: To prospectively evaluate uterine contractility during menstruation and its relation to primary dysmenorrhea by using magnetic resonance (MR) imaging with cine mode display. MATERIALS AND METHODS: The university ethics committee approved the study protocol, and all subjects gave written informed consent. Nineteen healthy women were examined during menstrual cycle days 1-3 by using a 1.5-T-magnet unit. Sixty serial half-Fourier rapid acquisition with relaxation enhancement MR images of the uterus were obtained every 3 seconds for 3 minutes and displayed in cine mode. MR images were analyzed in terms of thickness of the inner low-signal-intensity myometrial layer, presence of endometrial distortion, and uterine peristalsis detectability. Pain was assessed by using a four-point scale. For 56 MR imaging cases, the association between MR imaging findings and pain degree was examined with Spearman correlation and Mann-Whitney tests. MR imaging findings in the dysmenorrheic and eumenorrheic subject groups were compared by using Mann-Whitney and chi(2) tests. The area of the uterine myometrium in both groups was calculated for quantitative assessment of uterine contraction and was compared between the groups by using the Student t test. RESULTS: MR imaging findings revealed marked changes during cycle days 1-3. Thickness of the inner low-signal-intensity myometrial layer and endometrial distortion were significantly associated with pain degree (P < .001), while uterine peristalsis was undetectable when pain was severe or moderate. The area of the uterine myometrium significantly decreased during cycle days 1-3 in the dysmenorrheic group, as compared with that in the eumenorrheic group (P = .010). CONCLUSION: MR imaging features of the uterus on cycle days 1-3 correlated with pain degree. Cine-mode-display MR imaging is a potential tool for evaluating dysmenorrhea.     

Optical mapping of neural responses and their gamma-aminobutyric acid-ergic inhibitory effects in the auditory brainstem of early postnatal mice

gamma-Aminobutyric acid (GABA)ergic neurons play important tropic and modulatory roles in the auditory pathway, especially in the early stage between postnatal Days 0 and 5. The effects of GABA and GABAa receptor antagonist were observed in this experimental study. Numerous histological and electrophysiological studies have been performed on the contribution of GABA to the auditory pathway; however, the spatio-temporal patterns of excitatory propagation and the relationships between GABA receptor and excitatory propagation have yet to be reported. Using an optical recording technique and a voltage-sensitive dye, the spatio-temporal patterns of excitatory propagation were observed in the auditory brainstem slices of early postnatal mice. A bath containing 50 microM GABA was applied, which largely inhibited the excitatory activities along the vestibulocochlear pathway. Bicuculline methiodide (BMI), a competitive antagonist against GABAa receptor, partially reversed the effects of GABA on the optical signals. Bath application of BMI alone helped to facilitate the depolarization course and its effect was apparent as an enlargement of the depolarized region from the cochlear nucleus and vestibular nucleus to some adjacent brainstem nuclei, as well as enhancing the amplitude of changes in the optical signals. The experimental results seem to suggest that GABAa receptors are widely distributed in an early postnatal auditory brainstem. GABA exhibited a greater modulating effect in the adjacent brainstem nuclei, which are involved in complex information processes, than that observed in the modulating primary auditory pathway. In the present experiment, significant GABAergic contributions to the optical recordings in the auditory brainstem were observed.     

ATP-induced hexameric ring structure of the cyanobacterial circadian clock protein KaiC

BACKGROUND: KaiA, KaiB and KaiC are cyanobacterial circadian clock proteins. KaiC contains two ATP/GTP-binding Walker's motif As, and mutations in these regions affect the clock oscillations. RESULTS: ATP induced the hexamerization of KaiC. The Km value for the ATP for the hexamerization was 1.9 micro m. Triphosphate nucleotides bound to the two Walker's motif As, and their binding functioned cooperatively for the hexamerization. An unhydrolysable substrate, 5'-adenylylimidodiphosphate (AMPPNP), also induced the hexamerization, indicating that nucleotide binding, but not its hydrolysis, is essential for the hexamerization. Mutations in each of the two Walker's motif As that affect the clock phenotype increased the Km value for ATP and inhibited the hexamerization. Thus, the KaiC hexamerization seems to be necessary for its clock function. The KaiC hexamer has the shape of a hexagonal pot with a diameter and height of approximately 100 A and with a relatively large cavity (73 A deep and 18-34 A wide) inside. This pot-shaped structure suggests that KaiC functions in a similar manner to F1-ATPase, helicase or ATP-dependent protease/chaperon, all of which have dynamic activities inside the central cavity of their hexameric rings. CONCLUSION: ATP-induced KaiC hexamerization is necessary for the clock function of KaiC.     

Epidemic nosocomial keratoconjunctivitis caused by adenovirus type 4

PURPOSE: To evaluate the clinical features of nosocomial epidemic keratoconjunctivitis(EKC) occurring in the ophthalmology ward of Sapporo Medical University Hospital and to devise preventive measures for it. MATERIALS AND METHODS: We studied the symptoms and clinical course of 2 patients who had EKC and 16 patients who had EKC caused by nosocomial infections in our hospital. We attempted to detect adenovirus antigen and viral DNA from conjunctival swabs and also to isolate the virus. RESULTS: The clinical symptoms of EKC were conjunctival hyperemia in 18 patients(100%), conjunctival follicles in 11 patients (61.1%), discharge in 8 patients(44.4%), superficial punctate keratopathy in 7 patients(38.9%), swelling of the eyelids in 3 patients(16.7%), and fever in 3 patients(16.7%). 72% were positive for Adeno-check. Adenovirus type 4 was isolated from the conjunctival swabs. We considered that the route of hospital infection was infection from the doctor's hands, from eye drops, and from contact lenses. We disclosed that nosocomical EKC had occurred in our hospital. The hospital infection was eliminated by closing the ophthalmology ward and sterilizing instruments and washing hands. CONCLUSIONS: The delay of proper measures increased the risk of nosocomical infection. We recognized the importance of careful observation of patients and immediate preventive efforts in nosocomical infection.     

Propofol was useful for intractable convulsion in a patient with tetanus: a case report

An 82-year-old woman with severe tetanus was admitted to our ICU. Anti-convulsive treatment was started by continuous intravenous administration of midazolam followed by thiamylal. On day 15, thiamylal became insufficient to manage the spastic convulsion without frequent intravenous administration of other sedative and muscle relaxants. On day 16, intravenous infusion of propofol was started at the rate of 1 mg.kg-1.h-1. Propofol was more effective than thiamylal to treat convulsion and to stabilize the sympathetic nerve activity. Propofol was also effective to achieve the better general condition in which enteral nutrition could be started. In this case, propofol was apparently more suitable than thiamylal to manage a patient with tetanic convulsion.