从病人外周血单个核细胞中检测HHV－6：分离培养和基因扩增

收集婴幼儿急疹及淋巴系统增生性疾病患者外周血单个核细胞进行体外培养,从７例婴幼儿急疹及２例淋巴系统增生性疾病患者中分离出一种病毒,此病毒能在ＰＨＡ激活的人脐血单个核细胞中传代生长,产生典型ＣＰＥ：形成气球样巨细胞。电镜下观察,感染细胞中可见直径１８０ｎｍ左右,有包膜,疱疹样病毒颗粒;血清学试验证明分离株与ＨＳＶ－１,２、ＨＣＭＶ、及ＥＢＶ无抗原交叉,而与ＨＨＶ－６ＧＳ株间存在抗原一致性;多聚酶链反应表明该分离株ＨＨＶ－６特异性ＤＮＡ阳性;综合以上结果,初步认为该分离株为ＨＨＶ－６。同时还用ｐＣＲ法对所收集的标本直接检测ＨＨＶ－６特异性ＤＮＡ。ＰＣＲ法与病毒分离法相比较,前者ＨＨＶ－６检出率为８８．８％（１６／１８）．后者为３８．９％（７／１８）。     

Electron microscopic study of a herpes-type virus isolated from an infant with exanthem subitum

Human lymphocytes and MT4 cells infected with a virus isolated from a patient with exanthem subitum were examined by transmission and scanning electron microscopy. The most striking characteristic of the ultrastructure of this herpes-type virus was that nucleocapsids located outside the nucleus were each coated distinctly with a tegument of moderate electron density. Tubular structures formed due to some mistakes in the viral assembly were also detected in the nucleus. Morphological differentiation of this virus from the other human herpesvirus was discussed. From these observations it was concluded that this virus has the same ultrastructural characteristics as HBLV (HHV-6).     

Comparison of the Complete DNA Sequences of Human Herpesvirus 6 Variants A and B

Human herpesvirus 6 (HHV-6), which belongs to the betaherpesvirus subfamily and infects mainly T cells in vitro, causes acute and latent infections. Two variants of HHV-6 have been distinguished on the basis of differences in several properties. We have determined the complete DNA sequence of HHV-6 variant B (HHV-6B) strain HST, the causative agent of exanthem subitum, and compared the sequence with that of variant A strain U1102. A total of 115 potential open reading frames (ORFs) were identified within the 161,573-bp contiguous sequence of the entire HHV-6 genome, including some genes with remarkable differences in amino acid identity. All genes with <70% identity between the two variants were found to contain deleted regions when ORFs that could not be expressed were excluded from the comparison. Except in the case of U47, these differences were found in immediate-early/regulatory genes, DR2, DR7, U86/90, U89/90, and U95, which may represent characteristic differences of variants A and B. Also, we have successfully typed 14 different strains belonging to variant A or B by PCR using variant-specific primers; the results suggest that the remarkable differences observed were conserved evolutionarily as variant-specific divergence.     

Human herpesvirus-6 and human herpesvirus-7 (HHV-6, HHV-7)

human herpesvirus 6 (HHV-6) is the major causative agent of exanthem subitum which is one of popular diseases in infant, and establishes latent infections in adults of more than 90%. Recently, the encephalitis caused by reactivated- HHV-6 has been shown in patients after transplantation. In addition, the relationship HHV-6 and drug-induced hypersensitivity syndrome has also been reported. human herpesvirus 7 (HHV-7) was isolated from the stimulated-peripheral blood lymphocytes of a healthy individual, and also causes exanthema subitum. Both viruses are related viruses which belong to betaherpesvirus subfamily, and replicate and produce progeny viruses in T cells.     

Molecular biology and clinical associations of Roseoloviruses human herpesvirus 6 and human herpesvirus 7

Human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) are members of the Roseolovirus genus within the Betaherpesvirinae subfamily. HHV-6 and HHV-7 primary infection occurs in early childhood and causes short febrile diseases, sometimes associated with cutaneous rash (exanthem subitum). Both HHV-6 and HHV-7 are highly prevalent in the healthy population, establish latency in macrophages and T-lymphocytes, are frequently shed in saliva of healthy donors, and the pathogenic potential of reactivated virus ranges from asymptomatic infection to severe diseases in transplant recipients. These features have contributed to the notion that HHV-6 and HHV-7 are more or less "harmless" viruses. Consequently, the medical and scientific interest originally prompted by their discovery has been gradually waning. The aim of this review is to provide a short update of the current knowledge on these viruses, and to suggest that the medical importance of Roseoloviruses should not be understimated.     

Primary immunisation and febrile convulsions in Oxford 1972-5.

A three-year study of febrile convulsions in Oxford with comprehensive notification from general practice and hospitals showed a 3% risk for all children of suffering at least one febrile convulsion by the age of 5 years. Children were most at risk between 6 and 27 months, and febrile convulsions were most likely to be prolonged in children aged 9-15 months. The association between febrile convulsions and primary immunisations in the preceding 28 days was compared in case and control children, matched for age and sex. Results suggested that such association was a chance relationship with age. If association was direct, the febrile convulsion rates per 1000 immunisation doses were estimated as follows: diphtheria, pertussis, tetanus--0-09 per 1000; poliomyelitis--0-6 per 1000; and measles--0-9 per 1000. Hence if any of these vaccines had a secific causal relationship with febrile convulsions, these rates would probably have been much higher.     

Predominant CD4 T-lymphocyte tropism of human herpesvirus 6-related virus.

Human herpesvirus 6 (HHV-6)-related virus was isolated from CD4+ CD8- and CD3+ CD4+ mature T lymphocytes but could not be isolated from CD4- CD8+, CD4- CD8-, and CD3- T cells in the peripheral blood of exanthem subitum patients. HHV-6-related virus predominantly infected CD4+ CD8+, CD4+ CD8-, and CD3+ CD4+ cells with mature phenotypes and rarely infected CD4- CD8+ cells from cord blood mononuclear cells, which suggested predominant CD4 mature T-lymphocyte tropism of HHV-6-related virus.     

Intracranial Aspergillosis in an Immunocompetent Young Woman

Intracranial aspergillosis (ICA) is very rare in the immunocompetent individuals, usually misdiagnosed as a tumor or an abscess. A high index of clinical suspicion is required in patients who present with focal neurological deficits, headache, or seizures. We report the case of a 25-year-old immunocompetent female, who presented with a 15-month history of headache, seizures, left-sided proptosis and ophthalmoplegia, and right hemiparesis. Recovery from the symptoms and decrease in the lesion size seen on the radiological assessment were achieved through two decompressive craniotomies followed by prolonged combined systemic antifungal therapies. Although the initial neuroimaging suggested a mitotic pathology, the surgical sample confirmed ICA. Now the patient is on single antifungal therapy (Tab. voriconazole, 200 mg twice daily) and doing her daily activities, but with a reduced intelligent quotient. We report a challenging case of ICA where multiple courses of combined antifungal therapies and repeat surgeries paved the way for a good prognosis.     

Effect of Isonicotinic Acid Hydrazide on Extracellular Amino Acids and Convulsions in the Rat: Reversal of Neurochemical and Behavioural Deficits by Sodium Valproate

Abstract: We have studied the effect of isonicotinic acid hydrazide (INH), a convulsant agent, on the extracellular levels of amino acids in the hippocampus, and the effect of sodium valproate (VPA) administration in INH-treated rats. INH (250 mg/kg) caused a rapid and sustained decrease in basal levels of GABA, and during this period convulsions of increasing severity were observed. Basal levels of glutamine, taurine, aspartate, and glutamate were unchanged by INH. When VPA was coadministered with INH, basal GABA levels were increased and no convulsions were observed. When transmitter release was evoked using 100 m M K⁺, the increase in dialysate GABA observed in INH-treated animals was less than that seen in controls and convulsions increased in frequency. K⁺-evoked release of glutamate and aspartate tended to be higher following INH treatment, and in the case of aspartate, this increase was significant. VPA reversed the changes in evoked release of glutamate and aspartate, and release of GABA was considerably greater than that seen in control or INH-treated rats. No drug effect on evoked changes in taurine or glutamine level was seen. These are the first data to show decreased extracellular GABA in conjunction with convulsions in freely moving animals in vivo.     

IgM neutralizing antibody responses to human herpesvirus-6 in patients with exanthem subitum or organ transplantation.

The assay for detecting IgM neutralizing (NT) antibody activity to human herpesvirus-6 (HHV-6) was developed by using pretreatment of blood sample with staphylococcal protein A. The activity was mostly present in IgM fractions of serum but not in IgA fractions separated by ultracentrifugation. The assay was used for seroepidemiological studies for HHV-6 infection. In primary HHV-6 infection, IgM NT antibodies appeared 5 to 7 days after onset of exanthem subitum, reached maximum titers at 2 to 3 weeks, and tended to decline to undetectable levels after 2 months. In contrast, reactivation of HHV-6 observed in organ transplants showed somewhat greater degree of IgM NT antibody responses that persisted for 2 to 3 months and became undetectable 5 to 6 months after transplantation. The level and persistence of NT antibody titers measured by the conventional method was generally greater than those of the IgM titers. The prevalence of the IgM NT antibodies was examined in healthy individuals. The antibody was first detected at 4 to 7 months of age (5%), reached maximum level at 8 to 11 months (40%), and was detectable by 4 to 6 years (17%). A few (4 to 5%) of adolescents and adults were positive for the antibody.     

Catecholamines in the rat brain during hypoglycemic convulsions and coma

The purpose of the study was to investigate the relation between the catecholamines: noradrenaline and dopamine in the rat brain on one hand and hypoglycemic convulsions and coma on the other. Concentrations of noradrenaline in the hypothalamus, brain stem and cerebral cortex were decreased during hypoglycemic convulsions and were lower during coma than those during convulsions. Dopamine concentration in the striatum was decreased during convulsions and coma. It was shown that the decrease in concentration of catecholamines was a result of hypoglycemia but not of insulin action itself. Clonidine- alpha 2 agonist accelerated occurrence and prolonged duration of hypoglycemic convulsions. Haloperidol-dopamine receptor blocker had no effect on the time of occurrence or duration of convulsions and coma. The results indicate that noradrenaline may exert an inhibitory influence on hypoglycemic convulsions. No evidence has been provided to support involvement of dopamine in the control of hypoglycemic convulsions and coma.     

Reversible Hypomagnesaemia-Induced Subacute Cerebellar Syndrome

Magnesium is the second most abundant intracellular cation and is a fundamental cofactor in a multitude of cellular enzymatic reactions. Magnesium deficiency causes diverse clinical features predominantly due to cardio- and neurotoxicity. We describe a case of severe hypomagnesaemia associated with intermittent downbeat nystagmus, cerebellar ataxia, generalised convulsions and a supraventricular tachycardia. On MRI imaging, a transient lesion of the cerebellar nodulus was observed, which has not, to our knowledge, been previously described in isolated hypomagnesaemia.     

Rash Associated with Coxsackie A9 Infection

Coxsackie A9 virus was identified by the authors during the fall of 1965 in Montreal in six children with fever and exanthem. Three of the six children were siblings. The exanthem was centrally distributed as described by Lerner et al. and consisted of discrete maculopapules 3 to 4 mm. in diameter. The viral agent was recovered and identified in tissue culture in five cases, while in the sixth Coxsackie type-A lesions were produced in suckling mice. Serological confirmation was obtained in two patients from whom sera were available. In contrast, no exanthem was observed in three older patients with a diagnosis of aseptic meningitis associated with Coxsackie A9 virus. In only one of 16 patients with Coxsackie B virus infection was an exanthem observed during the same period.The true incidence of Coxsackie A9-associated exanthems is difficult to determine because of the benign nature of the disease.     

Infection of primary human fetal astrocytes by human herpesvirus 6.

Human herpesvirus 6 (HHV-6) is a lymphotropic betaherpesvirus which productively infects human CD4+ T cells and monocytes. HHV-6 is the etiologic agent for exanthem subitum (roseola), and it is well-known that central nervous system complications occur frequently during the course of HHV-6-associated disease. In addition, HHV-6 has been associated with encephalitis or encephalopathy. However, very little is known about its tropism for neural cells. There are reports that HHV-6 may infect some glial cell lines, but whether it can infect any primary neural cells is not known. Our studies show that both HHV-6A (GS) and HHV-6B (Z-29) can infect highly purified primary fetal astrocytes in vitro. Infected cells showed cytopathic effects, forming giant syncytia. In dual immunofluorescence assays, the infected cells were detected by antibodies against the HHV-6 p41 nuclear antigen and glial fibrillary acidic protein, indicating that the infected cells are indeed astrocytes. PCR and Northern (RNA) blot analyses also confirmed that the astrocytes are infected by HHV-6. The progeny virus did not alter its host range and could reinfect T cells as well as primary astrocytes. These findings suggest that infection of primary human astrocytes may play a role in the neuropathogenesis of HHV-6.     

Occurrence of brain calcifications,iron deposits,and tonic-clonic convulsions following experimental infections with Candida albicans

Summary During the prolonged presence ofCandida albicans in the spleen of Wistar rats, two cases of calcium deposits in the brain were observed. In one case there was one big calcium deposit at some distance from the cortex. In this case, thickening in a limited area of the leptomeninges was found. The animal had generalized tonicclonic convulsions which lead to death. In the second case, calcium deposits formed two separate agglomerations in the posterior part of the thalamus. Serial sections made at six micron intervals showed the presence of calcium deposits to a depth of forty-eight microns. At twenty-four microns other calcium deposits were observed in the thalamus symmetrically located to those described above.Small iron deposits were found in the anterior part of the thalamus and other iron deposits were found in the temporal lobe of the brain. They were arranged in a straight line along the capillary vessels and most of them were seen in the macrophages in the vicinity of the vessels.Since calcium deposits in the brain occurred in the same experimental conditions as reported cases of calcinosis, it is probable that the same mechanism is involved in all these pathological calcium deposits.This work was supported by a Damon Runyon Memorial Fund Grant Nr. 720.     

Retrospective study of concussive convulsions in elite Australian rules and rugby league footballers: phenomenology,aetiology, and outcome.

OBJECTIVES: To study the ictal phenomenology, aetiology, and outcome of convulsions occurring within seconds of impact in violent collision sport. DESIGN: Retrospective identification of convulsions associated with concussive brain injury from case records from medical officers of football clubs over a 15 year period. SUBJECTS: Elite Australian rules and rugby league footballers. MAIN OUTCOME MEASURES: Neuroimaging studies, electroencephalography, neuropsychological test data, and statistics on performance in matches to determine presence of structural or functional brain injury. Clinical follow up and electroencephalography for evidence of epilepsy. RESULTS: Twenty two cases of concussive convulsions were identified with four events documented on television videotape. Convulsions began within 2 seconds of impact and comprised an initial period of tonic stiffening followed by myoclonic jerks of all limbs lasting up to 150 seconds. Some asymmetry in the convulsive manifestations was common, and recovery of consciousness was rapid. No structural or permanent brain injury was present on clinical assessment, neuropsychological testing, or neuroimaging studies. All players returned to elite competition within two weeks of the incident. Epilepsy did not develop in any player over a mean (range) follow up of 3.5 (1-13) years. CONCLUSIONS: These concussive or impact convulsions are probably a non-epileptic phenomenon, somewhat akin to convulsive syncope. The mechanism may be a transient traumatic functional decerebration. In concussive convulsions the outcome is universally good, antiepileptic treatment is not indicated, and prolonged absence from sport is unwarranted.     

Altered response to GABAergic agents following electro and chemo convulsions in mice.

Effects of GABAergic agents and that of electroconvulsive shock (ECS) treatment were studied on bicuculline and picrotoxin (PTX)-induced convulsions in mice. Neither acute nor chronic ECS had any significant effect on bicuculline-induced convulsions, whereas the latency for PTX-induced convulsions was delayed by both acute and chronic ECS. Baclofen treatment delayed significantly the latency for PTX-induced convulsions in animals which were subjected to both acute and chronic ECS, whereas in bicuculline-induced convulsions, it shortened the latency of convulsions 24 hr after acute ECS. Progabide delayed the bicuculline-induced convulsions except in the case of 24 hr after acute ECS and PTX-induced convulsions except in the case of animals treated chronically with ECS. Fengabine showed no significant effect on bicuculline-induced convulsions. However, on PTX-induced convulsions, the latency was delayed in animals not subjected to ECS and in those subjected to chronic ECS. The possible explanations for the alterations in the effect of GABAergic agents following electro and chemo convulsions are (i) differences in the nature of antagonism by bicuculline and PTX, (ii) alterations in receptor sensitivity or number, and (iii) alterations in the levels of endogenous neurotransmitters, the latter two resulting as a result of acute or chronic ECS.     

Lower cranial nerve motor function in unilateral vascular lesions of the cerebral hemisphere.

Motor function subserved by cranial nerves V, VII, X, XI, and XII was assessed in 100 patients with hemiparesis due to a unilateral vascular lesion of the cerebral hemisphere. Several of the findings were not described clearly in many of the standard textbooks of neurology. Weakness of sternomastoid when present was always contralateral to the hemiparesis. This emphasises the principle that the cerebral hemisphere controls movement of the body parts in or towards the contralateral half of the body rather than simply the contralateral muscle groups. An apparent exception to this was seen, however, in the small group of patients who had unilateral weakness of the tongue. In those patients deviation of the tongue was towards the hemiparetic side--that is, the cerebral hemisphere controlled the contralateral half of the tongue and hence protrusion towards the ipsilateral side. Mild dysarthria was common with both right and left sided hemiparesis.     

Renal functions following hyperbaric oxygen toxicity in conscious rats

The after-effects of renal function were studied in rats exposed to hyperbaric oxygen (HBO) at either 4.8 ATA for 60 min or 6.8 ATA until the onset of convulsions. Only the rats which suffered from HBO convulsions were found to have alterations in renal function. It was observed that 4 hr after convulsions, there was a decrease in urinary excretion of urea and creatinine, which resulted in an elevation of blood urea nitrogen (BUN) and creatinine. Clearances of inulin and p-aminohippuric acid showed a decrease in the glomerular filtration rate and effective renal blood flow 4 hr after HBO convulsions. These parameters nearly returned to normal in 24 hr after convulsions. The renal handling of a large volume of infused saline was also retarded 4 hr after HBO convulsions, but by the end of 24 hr after HBO convulsions, it was much improved. Therefore, it was concluded that the renal function was altered after HBO convulsions, but nearly recovered in 24 hr.     

The effect of multiple audiogenic seizures upon the sleep organization in rats

The organization of sleep during and after frequentative convulsions, consisting of 2, 3, or 5 comparatively rare seizures (following one another with a 90-minute interval) or of 3, 5 or 9 comparatively frequent seizures (following one another with a 45-minute interval) of generalized tonic-clonic character in Krushinskii-Molodkina strain rats with inherited predisposition to audiogenic convulsions, was studied. In frequentative convulsions with rare seizures, between separate seizures, passive wakefulness (75.2 +/- 4.6% time) prevailed under low (24.8 +/- 4.3%) slow-wave sleep and full absence of fast-wave sleep. In rats under frequentative convulsions with frequent seizures, in interictal period, only passive wakefulness was observed under reduction of slow-wave sleep and fast-wave sleep, i.e. total sleep deprivation. Minimal latensy of first episodes of the slow-wave sleep after frequentative convulsions was 59.9 +/- 10.8, and of fast-wave sleep: 158.2 +/- 13.4 min. First episodes of slow-wave sleep and fast-wave sleep had normal structure, though they were lesser and shorter than in control experiments. In spite of long-lasting (up to 7 hrs) absence of slow-wave sleep during seizure and prolonged (8.5 hrs) reduction of fast-wave sleep with no subsequent compensatory increase, these conditions occurred in the wakefulness-sleep cycle during 12-hour reconstruction after convulsions. The reconstruction period after frequentative convulsions was characterized by increase in general share of wakefulness and reduction of total slow-wave and fast-wave sleep as compared with control data. Paroxysmal status seems to disorganize work of the brain somnogenic structures. The function of systems responsible for slow-wave sleep are affected to a lesser extent, but disorganization of the system responsible for fast-wave sleep is more significant and associated with mechanisms of starting the phase of sleep in the first place.