Passively transferable protection against Schistosoma japonicum induced in the mouse by multiple vaccination with attenuated larvae: the development of immunity, antibody isotype responses and antigen recognition

Vaccination of mice with attenuated S. japonicum cercariae induces protection against secondary infection which can be transferred to naive mice with serum (VMS). The presence of antibody does not per se impart protection as serum from mice carrying non-attenuated infections (CIS), contains high levels of specific antibody, but confers no protection. Here we describe the increased protection transferred (20 to 68%) with increased number of vaccinations (one to five) given to the donors, and its decline with time after the final vaccination. We also describe the development of IgM, IgA, IgE, total IgG and IgG subclass responses in VMS, giving different levels of protection and CIS, directed against sodium periodate-sensitive and -resistant epitopes in ‘skin-stage’, ‘lung-stage’and ‘liver-stage’schistosomula, adult worms and eggs. In addition, antibody affinity maturation, development of S. japonicum species-specific responses, and vaccination-specific responses were examined. No response developed in parallel with serum-mediated immunity, suggesting immunity may be due to responses against individual antigens. Preliminary examination of antigens recognized in Western blot showed that two schistosomal membrane antigens, of 13 and 40 kDa, were recognized by VMS from mice vaccinated five times (68% protection), but not by twice vaccinated VMS (27% protection). Neither antigen was recognized by non-protective CIS.     

Antibody isotype responses to the Schistosoma mansoni schistosomulum in the CBA/N mouse induced by different stages of the parasite life cycle

Summary During infection with Schistosoma mansoni the extent and nature of immune reactions against schistosomula may be influenced by responses to cross-reactive antigens in eggs or adult worms, and there is now extensive evidence for cross-reactivity between the different stages of the parasite life cycle. In this study IgM and IgG subclass antibodies produced in (CBA/N × Balb/c) Fl male and female mice were measured over a period of time following exposure to a chronic infection, to unisexual male cercariae or to irradiated larvae. Antibody levels were also measured following immunization with antigen preparations derived from adult worms, schistosomula or eggs. (CBA/N × Balb/c) Fl male mice exhibit an X-linked immune deficiency which results in an inability to respond to T-independent (TI) type 2 polysaccharides. Isotype levels were measured by ELISA to detergent-soluble schistosomulum antigen. Results showed that antigens on the different stages of the parasite life cycle have a qualitative influence on the antibody response to the larval surface, and that T-independent type 2 polysaccharides, particularly abundant in egg. exhibit antigen-directed isotype restriction in the form of IgM and IgG3 antibodies.     

Intramedullary Spinal Cord Metastases: A Clinical and Pathological Study of Nine Cases

The clinical and pathological findings In nine cases of intramedullaryspinal cord metastases are reported and are compared with thoseof previous studies. Intramedullary metastases are more commonthan is generally believed and the incidence is probably increasingwith the more prolonged survival of cancer patients. A widespectrum of symptoms and signs may be produced, frequently withattendant diagnostic difficulties. Most patients present withmyelopathy as the first manifestation of cancer or of its recurrence.Symptoms may be present for several months, with few clinicalsigns, despite distortion and destruction of much of the spinalcord by tumour. The extent of metastatic disease remains limitedin a significant proportion of patients. No neurological symptomsor signs differentiate intramedullary metastases clearly fromthe more common extradural deposits. However, the diagnosisshould be considered when myelopathy evolves more slowly, whereplain radiographic evidence of adjacent vertebral disease Isabsent, and particularly when myelography is normal. Early diagnosisand aggressive medical treatment may provide for a more favourableoutcome. ^* Currently Fellow in Neuropathology, The National Hospitalsfor Nervous Diseases, Queens Square, London.     

Non-convulsive Status Epilepticus: A Prospective Study in an Adult General Hospital

A prospective study of non-convulsive status epilepticus wasundertaken in order to evaluate the occurrence and characteristicsof this condition in adults. The diagnosis was established in22 of 113 patients (19 per cent) presenting with status epilepticusover a 23-month period. Non-convulsive status was most prevalentin the over 60 age group. Its two subgroups, absence status(18 cases) and complex partial status (four cases) were bothmanifest clinically by a prolonged alteration of consciousnessof variable extent. Absence status presented de novo (six cases) or against a backgroundof epilepsy (12 cases), often with a long seizure-free intervalbefore presentation. Precipitating factors included infection,inadequate anticonvulsant medication and benzodiazepine withdrawal.The clouding of consciousness was usually characterised by confusion,disorientation and partial responsiveness. Myoclonic or clonicmovements of the eyes, face or jaw were evident in all but twopatients. Automatisms, including ambulatory behaviour (threecases) were less common. Serious psychiatric disorders precededthe status in seven cases, and contributed to the difficultyin diagnosis. Complex partial status was associated with underlyingcerebrovascular disease in three of four cases, and is characterisedby a more severe and variable clouding of consciousness, lessfrequent facial clonic movements, episodic adversive head andeye movements, and a more gradual recovery after treament.     

INOBVIOUS STROKE: A CAUSE OF DELIRIUM AND DEMENTIA

Six hundred and sixty-one patients with stroke, confirmed by CT scan or at autopsy, were reviewed in order to evaluate the frequency of presentation with altered mental state. Nineteen patients (3%) had presented with delirium, an organic delusional state, the acute onset of dementia, or mania, mimicking psychiatric illness. All had focal cerebrovascular lesions which were usually, but not invariably, right sided. None had a previous history of cognitive impairment, psychiatric disease, drug abuse, or alcohol excess. Neurological signs were absent or mild and transient, and therefore easily missed. Post-mortem examinations in four patients showed localised cerebral infarctions with no evidence of multiple lesions, Alzheimer's disease, or metabolic encephalopathies. The possible causative factors are discussed and the evidence of asymmetrical cerebral representation of emotion, and for a relationship with epilepsy, is reviewed.     

ITAM receptor‐mediated generation of reactive oxygen species in human platelets occurs via Syk‐dependent and Syk‐independent pathways

Background: Ligation of the platelet‐specific collagen receptor, GPVI/FcRγ, causes rapid, transient disulfide‐dependent homodimerization, and the production of intracellular reactive oxygen species (ROS) generated by the NADPH oxidase, linked to GPVI via TRAF4. Objectives: The aim of this study was to evaluate the role of early signaling events in ROS generation following engagement of either GPVI/FcRγ or a second immunoreceptor tyrosine‐based activation motif (ITAM)‐containing receptor on platelets, FcγRIIa. Methods and Results: Using an H₂DCF‐DA‐based flow cytometric assay to measure intracellular ROS, we show that treatment of platelets with either the GPVI agonists, collagen‐related peptide (CRP) or convulxin (Cvx), or the FcγRIIa agonist 14A2, increased intraplatelet ROS; other platelet agonists such as ADP and TRAP did not. Basal ROS in platelet‐rich plasma from 14 healthy donors displayed little inter‐individual variability. CRP, Cvx or 14A2 induced an initial burst of ROS within 2 min followed by additional ROS reaching a plateau after 15–20 min. The Syk inhibitor BAY61‐3606, which blocks ITAM‐dependent signaling, had no effect on the initial ROS burst, but completely inhibited the second phase. Conclusions: Together, these results show for the first time that ROS generation downstream of GPVI or FcγRIIa consists of two distinct phases: an initial Syk‐independent burst followed by additional Syk‐dependent generation.     

Anticipatory anxiety in children visiting the dentist: lack of effect of preparatory information

Aim.  This study sought to explore whether viewing a leaflet explaining the benefits of dental treatment would have a significant impact on children's anticipatory anxiety.
Method.  Fifty children aged 8–12, attending the paediatric dental clinic of King's College Hospital, London, took part in this triple-masked, randomized control study. The participants were randomly allocated to one of two groups and either shown an intervention leaflet containing child-friendly dental information (the experimental group) or a leaflet with child-friendly information on the benefits of healthy eating (the control group). Using the Facial Image Scale, anxiety was measured when the children arrived for their dental appointment, once before reading the leaflet and again after reading the leaflet.
Results.  There was no statistically significant effect of the experimental leaflet on self-reported anxiety levels in this study, although anxiety levels did drop slightly in both groups after reading a leaflet.
Conclusions.  Providing paediatric patients with preparatory information about what to expect from a visit to the dentist had no effect on anticipatory anxiety in comparison to reading a leaflet about healthy eating. We speculate that reading, or cognitive processing, may have some beneficial effect. Future work should investigate this possibility.     

The isolation of a 22 kDa band after SDS-PAGE of Schistosoma mansoni adult worms and its use to demonstrate that IgE responses against the antigen(s) it contains are associated with human resistance to reinfection

In schistosomiasis endemic areas, intensities of reinfection after treatment are greater amongst young children than amongst adults, and high levels of parasite-specific IgE are associated with resistance to reinfection in an age-dependent manner. Previously we have reported that, in Western blots, a 22 kDa band was recognized by human IgE and that the incidence and intensity of S. mansoni reinfection were significantly lower amongst individuals who had IgE against this band, compared with those who did not (Dunne et al. 1992). Here we report the isolation of a 22 kDa SDS-PAGE band, its incorporation into ELISA and the demonstration that levels of human anti-22 kDa IgE had a significant negative correlation with intensities of subsequent reinfection. Rabbit anti-22 kDa band serum recognized the outer tegument, gut tegument, and the collecting ducts and flame cells of adult worms. The 22 kDa band antigen(s) was also present in 'lung'- and 'post-lung' schistosomula stages of S. mansoni , and in S. haematobium , S. bovis and S. japonicum adult worms. Metabolic labelling of schistosomula and worms demonstrated the in vitro synthesis and release of 22 kDa antigens.