A rare polymorphism affects a mitogen-activated protein kinase site in synapsin III: possible relationship to schizophrenia.

BACKGROUND: Synapsin III plays a role in neuronal plasticity and maps to chromosome 22q12-13, a region suggested to be linked to schizophrenia. To determine if synapsin III plays a role in this disease, we searched for polymorphisms in this gene in patients with schizophrenia and controls. METHODS: The synapsin III gene was initially sequenced from 10 individuals with schizophrenia to identify polymorphisms. Association analysis was then performed using 118 individuals with schizophrenia and 330 population controls. Synapsin III expression was studied by immunoblot analyses, and phosphorylation sites were mapped by sequencing trypsin-digested synapsin III fragments phosphorylated with phosphorus-32. RESULTS: A rare, missense polymorphism, S470N, was identified in the synapsin III gene and appeared more frequently in individuals with schizophrenia than in controls (p =.0048). The site affected by the polymorphism, Ser470, was determined to be a substrate for mitogen-activated protein kinase, a downstream effector of neurotrophin action. Phosphorylation at Ser470 was increased during neonatal development and in response to neurotrophin-3 in cultured hippocampal neurons. CONCLUSIONS: Our observations suggest an association of a rare polymorphism in synapsin III with schizophrenia, but further studies will be required to clarify its role in this disease.     

PRKCG mutation (SCA-14) causing a Ramsay Hunt phenotype.

Progressive myoclonic ataxia, also referred to as Ramsay Hunt syndrome, is characterized by a combination of myoclonus and cerebellar ataxia, infrequently accompanied by tonic-clonic seizures. Its differential diagnosis overlaps with progressive myoclonic epilepsy, a syndrome with myoclonus, tonic-clonic seizures, progressive ataxia and dementia. In patients with progressive myoclonic epilepsy, specific diseases can frequently be recognized, but the diagnostic yield in progressive myoclonic ataxia is much lower. We describe a patient who presented with multifocal myoclonus in his thirties and who later developed cerebellar ataxia and focal dystonia. His father was similarly affected. Genetic studies revealed a mutation in the protein kinase C gamma (PRKCG) gene, known to cause spinocerebellar ataxia type 14 (SCA-14). This case illustrates that both myoclonus and dystonia are part of the clinical spectrum in SCA-14 and that myoclonus can even be the presenting symptom. We suggest that SCA-14 should be considered in the differential diagnosis of progressive myoclonic ataxia.     

多发伤患者外周血降钙素原及C反应蛋白的动态变化及意义

目的探讨多发伤患者外周血降钙素原(procalcitonin,PCT)与C反应蛋白(C reac- tive protein,CRP)的动态变化及其临床意义。方法将96例多发伤患者按照ISS、输血量的多少、有无MODS、感染、脓毒血症及预后情况进行分类,分别检测不同类别患者外周血PCT、CRP浓度。结果与对照组相比,多发伤患者PCT和CRP均明显升高,其峰值分别出现在伤后2 d (PCT),5,7 d(CRP)。发生MODS、感染及脓毒血症时,PCT和CRP均明显升高。此外,PCT还与患者ISS评分、预后和输血量具有相关性。结论联合检测PCT、CRP有助于多发伤患者伤情的诊治及预后判断,其中PCT较CRP更具有敏感性。     

Pharmacokinetics of orally administered hexobarbital in plasma and saliva of healthy subjects

Hexobarbital (HB) concentrations were determined in plasma and saliva of 8 healthy subjects, following oral administration of 500 mg HB-Na. Mean plasma half-lives were 3.2 +/- 0.1 h, and salivary half-lives 3.3 +/- 0.2 h. Mean plasma clearance was 22.9 +/- 2.3 1 h-1. There was a linear relationship between HB concentrations in saliva and plasma (r = 0.92). Mean salivary levels were 34 per cent of plasma levels. Salivary pH was constant throughout the experiment, 7.06 +/- 0.09. There was an inconsistent tendency of the saliva over plasma ratios to increase as a function of time. The percentage of protein binding calculated from saliva over plasma ratios was in reasonable agreement with in vitro data of equilibrium dialysis, 64.1 +/- 2.6 per cent and 65.9 +/- 0.8 per cent, respectively. The experiment was repeated in 4 subjects, and considerable intraindividual differences were shown to exist in saliva over plasma ratio, half-lives, and protein binding. It was concluded that HB elimination half-lives can relatively accurately be determined from salivary concentrations. Oral plasma clearance can only be estimated if the individual saliva over plasma ratios are known; this would require the taking of at least one blood sample during the experiment. When employing HB as a model substrate for drug metabolizing enzyme activity in vivo, the determination of its pharmacokinetic parameters, particularly oral plasma clearance as a reflection of cytochrome P-450 activity, cannot be achieved by taking saliva samples only.     

降纤酶对ACI患者血清sCRP的影响及改善神经缺损的作用

目的:探讨降纤酶对急性脑梗死(ACI)患者血清超敏C反应蛋白(sCRP)水平的影响及其在改善神经功能缺损方面的作用。方法:46例ACI患者随机分为2组,对照组23例,静脉滴注曲克芦丁注射液,0.6g/d;治疗组23例,入院后立即给予降纤酶10IU溶入250ml生理盐水静脉滴注,1~1.5h滴完,第3、5天各给予降纤酶5IU,其他用药同对照组;应用免疫比浊法检测2组治疗前及治疗后第7天、14天的血清sCRP水平变化,并对神经功能缺损进行评分。结果:2组sCRP水平在治疗后第7天最高,随后逐渐降低。治疗组治疗前血清sCRP水平和治疗前、第7天的神经功能缺损总分与对照组比较差异无统计学意义(P>0.05),治疗组治疗后第7天、14天sCRP水平分别为(7.73±2.16)、(2.92±2.24)mg/L,对照组分别为(10.18±3.16)、(4.66±2.42)mg/L,治疗组明显低于对照组(P<0.05~0.01);第14天治疗组神经功能缺损总分为(10.68±4.08)分,明显低于对照组[(16.81±4.86)分](P<0.01)。结论:降纤酶能明显降低ACI患者血清sCRP水平,有利于减轻炎症反应,改善神经功能缺损程度。     

Plasma protein binding of furosemide in the elderly

Summary The protein binding of furosemide was investigated in plasma from 22 old and 11 young subjects by equilibrium dialysis. The unbound fraction of furosemide was 3.16% in plasma from the elderly and 1.71% in plasma from the young. A significant correlation was found between the unbound fraction of furosemide and the plasma concentration of albumin. The average number of binding sites was 3.8 (elderly) and 2.7 (young) 10^–6 mol/g albumin. The average association constant (K) was 4.3 (elderly) and 4.2 (young) 10⁵ M^–1. By increasing the concentration of furosemide up to 200 µg/ml buffer the unbound fraction of the drug rose to 5.2% (elderly) and 3.5% (young).     

Neurogenous hyperplasia leading to appendiceal obliteration: an immunohistochemical study of 237 cases

A series of 237 appendices was studied immunohistochemically for neurogenous hyperplasia. This was observed in 195 cases. It was possible to trace a continuum from appendices with intact lumens, featuring intramucosal neurogenous hyperplasia often with co-existent submucosal and muscular nerve growth, to obliterated specimens whose axial portions were composed of varying proportions of nerve tangles and fibrous tissue. Predominantly fibrotic specimens were considered as end-stages of this process. Stromal, argyrophilic cells lying amidst the nerve elements were prominent in the early, non-obliterated cases; their number decreased in the obliterated nerve rich specimens and such cells became inapparent in the late fibrotic stage. Repeated minimal subclinical attacks of inflammation are thought to trigger this lesion.     

Light microscopy of GTP-binding protein (Go) immunoreactivity within the retina of different vertebrates

To examine species differences in the distribution pattern of guanosine triphosphate (GTP)-binding protein (Go) within the vertebrate retina, paraffin-embedded retinae from a number of vertebrate species, including the goldfish, frog, turtle, chicken, monkey, and human, were immunohistochemically stained with affinity-purified antibody against the alpha-subunit of Go. Go-immunoreactive products were found to be located in the neuropil, but not in the cell bodies of neurons, in the retina of all these species. However, some species differences were observed. In the frog, monkey and human, the inner plexiform layer (IPL) was homogeneously stained with this antibody, but in the goldfish, turtle and chicken, the IPL was heterogeneously stained. In the frog, chicken, turtle and human, the outer plexiform layer (OPL) was densely stained with this antibody, but in the goldfish and monkey, the OPL was rather faintly immunoreactive to the antibody. In the goldfish, monkey and human, the outer nuclear layer (ONL) was not immunoreactive to the Go-antibody, whereas in the frog, turtle and chicken, the ONL was immunoreactive to it. The implications of these species differences in Go localization in the vertebrate retina are discussed.     

Coronavirus induced primary demyelination: indications for the involvement of a humoral immune response

Coronavirus MHV-JHM infection of rodents can result in demyelinating encephalomyelitis. We analysed histological changes induced by coronavirus MHV-JHM infection in Lewis rats. Besides an acute disease (AE), chronic panencephalitis (CPE) and subacute demyelinating encephalomyelitis (SDE) were induced. These disease types were differentiated by the incubation period, the localization of lesions, the type of tissue damage and distribution of virus antigen. In AE and CPE, virus antigen was detected in neurons, astrocytes and oligodendrocytes, whereas in SDE neurons lacked virus antigen. Viral nucleocapsid protein (N) was present in the cytoplasm and the spike protein (S) was displayed on the surface of infected neural cells. However, expression of S protein relative to N protein was severely impaired in SDE lesions. Quantitative analysis of infiltrating inflammatory cells revealed that the number of macrophages and T cells were similar in lesions of AE, CPE and SDE. In contrast to that, SDE lesions contained a significantly higher number of IgG + B cells and plasma cells. In addition active demyelinating SDE lesions displayed an enhanced IgG content and deposits of complement C9. These results indicate that virus induced primary demyelination could be a consequence of antibody mediated cytotoxicity. Furthermore, a reduction in the number of cells producing spike protein in the chronic forms of the disease indicates down-regulation of this protein, possibly mediated by anti-S antibodies.     

Competitive dissociation of encephalitogenic complexes between antigen presenting cells and myelin basic protein

Splenic T cells from myelin basic protein (MBP)-immunised Lewis rats were activated to transfer experimental autoimmune encephalomyelitis (EAE) by co-culture with MBP-pulsed lymphoid dendritic cells (DC). MBP-pulsed DC could be kept for at least 24 h at 37 degrees C in antigen-free medium without affecting their ability subsequently to activate encephalitogenic T cells. However, MBP-pulsed DC were rendered much less stimulatory after a 6 h, but not 2 h, secondary incubation with ovalbumin. Thus, although encephalitogenic complexes between MBP and DC appear very stable in the absence of competing antigens, in their presence, antigen exchange can take place over a period of a few hours; this has positive implications for therapy of EAE by antigen competition.