Rational design of hypoallergens applied to the major cat allergen Fel d 1

BACKGROUND: Allergen-specific immunotherapy is the only treatment for allergic disease providing long-lasting symptom relief. Currently, it is mainly based on the use of crude allergen extracts. The treatment may be improved by the use of genetically engineered allergens, hypoallergens, aiming at a more effective and safer therapy. OBJECTIVE: The aim of this study was to provide a rational design of hypoallergen candidates for immunotherapy by using structural information and knowledge of B and T cell epitopes of an allergen. METHODS: The three-dimensional structure of the major cat allergen Fel d 1 was systematically altered by duplication of selected T cell epitopes and disruption of disulphide bonds. Seven Fel d 1 derivatives were generated and screened for allergenic reactivity in comparison with recombinant Fel d 1 in competition-ELISA. The allergenicity was further evaluated in basophil activation experiments and T cell reactivity was assessed in a lymphoproliferation assay. RESULTS: Three out of seven Fel d 1 derivatives, with two duplicated T cell epitopes and one or two disulphide bonds disrupted, were carefully evaluated. The three derivatives displayed a strong reduction in allergenicity with 400-900 times lower IgE-binding capacity than recombinant Fel d 1. In addition, they induced a lower degree of basophil activation and similar or stronger T cell proliferation than recombinant Fel d 1. CONCLUSION: By a rational approach, we have constructed three Fel d 1 hypoallergens with reduced IgE-binding capacities and retained T cell reactivities. This strategy may be applied to any well-characterized allergen to improve immunotherapy for allergic patients.     

Multiple sclerosis with higher cerebral dysfunction: a case report

Higher cerebral dysfunctions such as aphasia, apraxia and agnosia have seldom been reported in multiple sclerosis (MS). 12 year-old right-handed boy felt unsteadiness of the body and headache for several days. Two months later, he had the same episode and complained of visual disturbance, and weakness and sensory disturbance on the face and the extremities. Additionally, he showed amnestic aphasia, acalculia, ideomotor apraxia, finger agnosia and right-left disorientation. Cerebrospinal fluid examinations revealed increases IgG, myelin basic protein and neuron specific enolase (11%, 25 ng/ml and 28.8 ng/ml, respectively). X-ray CT scan and MRI-CT examinations revealed sclerotic lesions on the left parietal white matter and the right mid-brain. The diagnosis was made as MS. He was treated with m-PSL (methyl-prednisolone) pulse therapy for three weeks and consecutively treated with PSL for four weeks. He recovered gradually, but visual disturbance and facial palsy remained. After seven months MRI-CT showed a high signal intensity on the left parietal white matter in spite of the disappearance of the lesion on X-ray CT scan. We suggest that these higher cerebral dysfunctions may result from the lesion of the left parietal white matter which produces a disconnection between each cortical area.     

The Voluntary Euthanasia (Legalization) Bill (1936) revisited.

In view of the continuing debate on euthanasia, the restrictions and safeguards which were introduced into the Voluntary Euthanasia (Legislation) Bill 1936 are discussed. Proposals for a new Terminal Care and Euthanasia Bill are suggested, based on some of the principles of the Mental Health Act 1983.     

Pedaling automatism in atypical West syndrome: a case report]

A seven-month-old girl with atypical West syndrome with pedaling automatism was reported. She started to have early infantile epileptic encephalopathy with suppression-burst (EIEE) at age 14 days followed by infantile spasms at 3 months of age. She began to have spasms with automatism at 4 month, mainly consisting of pedaling movements of both feet associated with tonic spasms of upper extremities and writhing of trunk. Ictal EEG showed irregular slow waves with occasional spikes predominantly over the right hemisphere mixed with artifacts. Interictal EEG during sleep showed suppression-burst patterns. Cerebral atrophy and microcephaly were revealed on brain CT, immature myelination on MRI and decreased blood flow in the frontal, temporal, and parietal lobes on the right on PET scan. Pedaling automatism is rare in infancy and its clinical significance was discussed in relation to West syndrome and complex partial seizures.     

Three-dimensional human pattern visual evoked potentials. II. Multiple sclerosis patients.

Pattern visual evoked potentials were obtained from 46 patients with definite relapsing/remitting multiple sclerosis, using both a conventional 5-channel occipital array and a 3-D recording technique consisting of three bipolar derivations approximating the three dimensions of space. These three orthogonal wave forms were displayed as a 3-D Lissajous trajectory for each subject. Two of the 15 patients with completely normal conventional pattern VEPs had abnormalities of the orientation of the B-C curvilinear segment of the 3-D pattern VEPs. Delays in the first major occipital positive component (P100) were evident using both techniques; the correlation between P100 latency and the latency of the corresponding trajectory apex was r = 0.99 (P less than 0.01). Post-chiasmal MRI abnormalities were associated with 3-D VEP orientation abnormalities. Three-dimensional pattern VEPs are moderately more sensitive than conventional pattern VEPs at detecting dysfunction posterior to the optic chiasm in demyelinating disease and do not require the use of eccentric fixation to do so.     

Unusual case of Klüver-Bucy syndrome in a Chinese boy.

Following an encephalopathic illness, a 13-year-old Chinese boy had a partial form of Klüver-Bucy syndrome with emotional disturbance, recent memory loss, hypersexuality, and polyphagia. Other unusual features included narcolepsy, polydipsia, and polyuria. Virologic studies failed to incriminate the etiologic agent, including herpes simplex virus. Brain biopsy of the frontal lobe demonstrated Alzheimer type II astrocytosis.