Differential effects of dopamine agonists on evoked dopamine release from slices of striatum and nucleus accumbens in rats

The effects of dopamine receptor agonists on electrically evoked dopamine release from slices of nucleus accumbens were compared with the effects on release from striatal slices in rats. Apomorphine, which has equal potency at the dopamine D₂ and D₃ receptors, reduced the evoked dopamine release from both regions to the same extent (ED₅₀, 0.42 μM for nucleus accumbens; ED₅₀, 0.46 μM for striatum). Quinpirole of 7-[³H]hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OHDPAT), which are much more potent at the D₃ receptor than at the D₂ receptor, reduced the evoked dopamine release from the nucleus accumbens (ED₅₀, 0.12 μM for quinpirole; 0.02 μM for 7-OHDPAT) much more than the release from the striatum (ED₅₀, 1.6 μM for quinpirole; 0.55 μM for 7-OHDPAT). These results suggest that the contribution of D₃ receptors in nucleus accumbens to regulate dopamine release from dopamine nerve terminals is much greater than that in striatum.     

4-Aminopyridine and l-cis-diltiazem block the cGMP-activated K channels closed by light in the molluscan extra-ocular photoreceptors

The cGMP-activated K⁺ channels closed by light lead to the depolarizing photocurrent of photoreceptors in the Onchidium ganglion. Whole-cell current records showed that external application of 100–200 μM 4-aminopyridine or 200–400 μM l-cis-diltiazem completely blocked the macroscopic photocurrent at any depolarizing and hyperpolarizing potentials. Single-channel current recordings suggested that both 4-aminopyridine and l-cis-diltiazem act to block the cGMP-activated K⁺ channels in their open state from inside the cell.     

Fast inhibitory postsynaptic potentials and responses to inhibitory amino acids of sympathetic preganglionic neurons in the adult cat.

Intracellular recordings were obtained from sympathetic preganglionic neurons (SPNs) of the intermediolateral nucleus (IML) in slices of upper thoracic spinal cord of the anesthetized cat. A total of 44 neurons was studied. Single shock stimulation of an area of white matter dorsolateral to the IML, close to the recording electrode (< 0.5 mm), evoked fast IPSPs with rise time of 3.8 ms and 1/2 decay time of 14.7 ms (n = 12). In 17 other cells only fast EPSPs were recorded but, after suppression of the EPSPs by the excitatory amino acid receptor antagonists CNQX (20 microM) and APV (100-250 microM), fast IPSPs were unmasked. The IPSP reversed polarity at -63 mV (-67 mV in the presence of CNQX and APV). The reversal potential shifted to a less negative value when the extracellular chloride concentration was reduced. The IPSP was reversibly abolished by the GABAA receptor antagonist bicuculline in 32% of the cells, by the glycine receptor antagonist strychnine in 47% of the cells and by the combination of the two in 21% of the cells. The IPSP was abolished by TTX (0.5 microM), had constant latency and showed no failures during high frequency stimulation. The IPSP presumably resulted from the excitation of inhibitory axons and/or inhibitory neuron somata with monosynaptic connections to the SPN. Glycine and GABA (1-3 mM) produced hyperpolarization associated with decreased membrane resistance. Sixty-nine percent of cells responded to both agonists, 19% to glycine only and 12% to GABA only. The GABAB agonist baclofen (5 microM) had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)     

An Autopsied Case of Interferon Encephalopathy

Abstract: A 78-year-old male with renal carcinoma was treated with a high dose infusion of interferon-alpha (IFN-alpha) for eight months. The patient had evidence of organlc brain syndrome such 88 : dysfunction of memory, slowing of behavior, and development of mental confusion that appeared eight months after the treatment. MRI at the time of mental confusion revealed difise white matter lesions. Neuropathologic findings were compatible to Binswanger's disease and Senile Dementia of Alzheimer Type (SDAT), Preexisting neurologic abnormalities including intracerebral arteriosclerosis and cerebral atrophy may increase susceptibility to unacceptably severe IFN neurotoxicity.     

Reduction in the incidence of MRSA with use of alcohol-based hand rub solutions and gloves

Methicillin-resistant Staphylococcus aureus (MRSA) is highly contagious. It is spread by direct contact with MRSA-infected people or objects. Healthcare workers' hands are the most common vehicle for the transmission of healthcare-associated pathogens from patient to patient and within the healthcare environment. The present study aimed to investigate the correlation between the incidence of MRSA among Staphylococcus aureus recovered from clinical culture and the use of alcohol-based hand rub solutions or gloves and antimicrobial use density (AUD). All data were examined every 6 months between January 2005 and June 2008. The increasing use of alcohol-based hand rub solutions was correlated with a decreasing incidence of recovery of MRSA from clinical cultures (r(2) = 0.58). A statistically significant (P < 0.05) correlation (r(2) = 0.68) was observed between glove use and the incidence of MRSA. On the other hand, we did not find any correlation between the AUD of each antibiotic group and the incidence of MRSA. Thus, we suggest that it is important to use not only alcohol-based hand rubs, but also gloves, because MRSA is transmitted from patient to patient by the hands of healthcare workers.     

Lectin affinity electrophoresis in a yolk sac tumour in the vagina with yolk sac tumour-type glycoform of alpha fetoprotein.

AIMS: To investigate a potential diagnostic use of alpha fetoprotein (alpha FP) isoform analysis by lectin affinity electrophoresis to distinguish between endodermal sinus tumours arising in the vagina in infants from those at other sites. METHODS: alpha FP in the serum of a patient with a vaginal endodermal sinus tumour was analysed for its isoforms by lectin affinity electrophoresis. The isoforms were compared with that of cord serum, sera of hepatoid adenocarcinoma of the uterus, and endodermal sinus tumour of the ovary. RESULTS: The isoforms of alpha FP obtained by lectin affinity electrophoresis in the serum of the patient with vaginal endodermal sinus tumour differed from the isoforms of alpha FP in the cord serum of normal neonates, and sera of patients with hepatoid adenocarcinoma of the uterus or endodermal sinus tumour of the ovary. CONCLUSIONS: Endodermal sinus tumour arising in the vagina could be distinguished from that in the ovary by the lectin affinity electrophoresis, and a potential diagnostic use of alpha FP isoform analysis by the lectin affinity electrophoresis for the detection of the endodermal sinus tumour in infants was demonstrated.     

Laboratory Surveillance for Prospective Plasmid-Mediated AmpC β-Lactamases in the Kinki Region of Japan

Extended-spectrum β-lactamases, plasmid-mediated AmpC β-lactamases (PABLs), and plasmid-mediated metallo-β-lactamases confer resistance to many β-lactams. In Japan, although several reports exist on the prevalence of extended-spectrum β-lactamases and metallo-β-lactamases, the prevalence and characteristics of PABLs remain unknown. To investigate the production of PABLs, a total of 22,869 strains of 4 enterobacterial species, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, and Proteus mirabilis, were collected during six 6-month periods from 17 clinical laboratories in the Kinki region of Japan. PABLs were detected in 29 (0.13%) of 22,869 isolates by the 3-dimensional test, PCR analysis, and DNA sequencing analysis. PABL-positive isolates were detected among isolates from 13 laboratories. Seventeen of 13,995 (0.12%) E. coli isolates, 8 of 5,970 (0.13%) K. pneumoniae isolates, 3 of 1,722 (0.17%) K. oxytoca isolates, and 1 of 1,182 (0.08%) P. mirabilis isolates were positive for PABLs. Of these 29 PABL-positive strains, 20 (69.0%), 6 (20.7%), 2 (6.9%), and 1 (3.4%) carried the genes for CMY-2, DHA-1, CMY-8, and MOX-1 PABLs, respectively. Pattern analysis of randomly amplified polymorphic DNA and pulsed-field gel electrophoretic analysis revealed that the prevalence of CMY-2-producing E. coli strains was not due to epidemic strains and that 3 DHA-1-producing K. pneumoniae strains were identical, suggesting their clonal relatedness. In conclusion, the DHA-1 PABLs were predominantly present in K. pneumoniae strains, but CMY-2 PABLs were predominantly present in E. coli strains. The present findings will provide significant information to assist in preventing the emergence and further spread of PABL-producing bacteria.β-Lactamase production is the most important factor for β-lactam resistance in Gram-negative rods (16). Plasmid-mediated β-lactamases, such as extended-spectrum β-lactamases (ESBLs), plasmid-mediated AmpC β-lactamases (PABLs), and plasmid-mediated metallo-β-lactamases (MBLs), hydrolyze broad-spectrum β-lactams. Detection of these plasmid-mediated β-lactamase-producing isolates is important for epidemiological studies and hospital infection control, because plasmid-mediated genes can spread to other organisms.The Study of Bacterial Resistance in the Kinki Region of Japan (SBRK) Antimicrobial Surveillance Program was established in 1997 to monitor the predominant pathogens and antimicrobial resistance patterns of nosocomial and community-acquired infections via a broad network of clinical laboratories differing in geographic location and size. Our previously reported survey data from the Kinki region of Japan revealed the prevalence of ESBLs and plasmid-mediated MBLs (21, 30); however, the epidemiology of PABLs remains unknown. For this reason, a laboratory-based surveillance study was conducted to determine the presence and prevalence of PABLs among members of the family Enterobacteriaceae.PABL CMY-1 was first found in a Klebsiella pneumoniae isolate in South Korea in 1989 (4, 5). Since then, additional organisms producing PABLs have been reported worldwide (25). PABLs are a heterogeneous group of enzymes that originated from the chromosomal genes of Enterobacter spp. (ACT-1/MIR-1 type), Citrobacter freundii (CMY/LAT type), Morganella morganii (DHA type), Hafnia alvei (ACC-1), and Aeromonas spp. (CMY/MOX type and FOX type). The most prevalent and most widely distributed PABLs are the CMY/LAT-type enzymes (25). In addition to these enzyme types, DHA-type enzymes have been identified in Taiwan (31) and China (15). In Korea (14, 26), DHA-, CMY/MOX-, and ACT-1/MIR-1-type enzymes have also been identified, while in the United States (1, 17), in addition to the types mentioned above, DHA-, ACT-1/MIR-1-, and FOX-type enzymes have been identified. To date, in Japan, MOX-1 (11), CMY-9 (9, 28), CMY-19 (28), CFE-1 (19), CMY-2 (18), and DHA-1 (18) have been found in clinical isolates. Muratani et al. (18) reported PABL producers among cephem-resistant K. pneumoniae isolates, but this report did not indicate the rate of occurrence of PABLs.For the present study, we collected 22,869 isolates from 17 clinical laboratories in the Kinki region of Japan, and we assessed the prevalence and types of PABL-positive bacteria.     

Bergmann glia expression of polyglutamine-expanded ataxin-7 produces neurodegeneration by impairing glutamate transport

Non-neuronal cells may be pivotal in neurodegenerative disease, but the mechanistic basis of this effect remains ill-defined. In the polyglutamine disease spinocerebellar ataxia type 7 (SCA7), Purkinje cells undergo non-cell-autonomous degeneration in transgenic mice. We considered the possibility that glial dysfunction leads to Purkinje cell degeneration, and generated mice that express ataxin-7 in Bergmann glia of the cerebellum with the Gfa2 promoter. Bergmann glia-specific expression of mutant ataxin-7 was sufficient to produce ataxia and neurodegeneration. Expression of the Bergmann glia-specific glutamate transporter GLAST was reduced in Gfa2-SCA7 mice and was associated with impaired glutamate transport in cultured Bergmann glia, cerebellar slices and cerebellar synaptosomes. Ultrastructural analysis of Purkinje cells revealed findings of dark cell degeneration consistent with excitotoxic injury. Our studies indicate that impairment of glutamate transport secondary to glial dysfunction contributes to SCA7 neurodegeneration, and suggest a similar role for glial dysfunction in other polyglutamine diseases and SCAs.     

Fabrication of micropored elastomeric film-covered stents and acute-phase performances

To prevent thrombus formation in the acute phase and restenosis in the subacute to chronic phase after stenting of atherosclerotic arteries, we developed a covered stent with a micropored elastomeric film, the blood-contacting surface of which was coated with a photocured gelatin layer immobilized with heparin. Segmented polyurethane (SPU) film (30 microm in wall thickness) as a cover material was multiply micropored by excimer laser-directed microprocessing (pore diameter, 30 microm; interpore distance, 125 microm). An aqueous mixed solution of benzophenone-derivatized gelatin and heparin was coated on the micropored SPU film. Upon ultraviolet light irradiation, a thin layer of a gelatin gel immobilized with heparin was formed and simultaneously fixed on the SPU film. The fully covered stents were assembled by wrapping a balloon-expandable stent with gelatin/heparin gel-layered SPU film and subsequently suturing and then gluing. To assess the validity of this covered stent in vivo, "half-covered" stents, in which half at the distal side was covered with the gel-layered SPU film, was implanted in rabbit common carotid arteries (about 3 mm in diameter). After 3 months of implantation, all the half-covered stents (n = 7) were patent. Regardless of the covered or noncovered region of the stents, the entire luminal surface of the stents was fully endothelialized and a thin neointimal tissue was formed. The potential advantages of a covered stent as designed above are discussed.     

Galectin-9 suppresses the generation of Th17, promotes the induction of regulatory T cells, and regulates experimental autoimmune arthritis

The effects of galectin-9 on a mouse collagen-induced arthritis (CIA) model were assessed to clarify whether galectin-9 suppresses CIA by regulating T cell immune responses. Galectin-9 suppressed CIA in a dose-dependent manner, and such suppression was observed even when treatment was started on 7 days after the booster, indicating its preventive and therapeutic effects. Galectin-9 induced the decreased levels of pro-inflammatory cytokines, IL-17, IL-12, and IFNgamma in the joint. Galectin-9 induced the decreased number of CD4(+) TIM-3(+) T cells in peripheral blood. Galectin-9-deficient mice became susceptible to CIA may be by increased number of CD4(+) TIM-3(+) T cells and decreased number of Treg cells. We further found that galectin-9 induces differentiation of naive T cells to Treg cells, and it suppresses differentiation to Th17 cells in vitro. The present results suggested that galectin-9 ameliorates CIA by suppressing the generation of Th17, promoting the induction of regulatory T cells.