传染病研究40年（1955～1995年）

本文综述本校传染病学教研室１９５５～１９９５年间所取得的科研成果。内容包括１０余种传染病与寄生虫病的临床和基础研究，其中以华支睾吸虫病、恙虫病等有广东特色的传染病以及伤寒、痢疾、病毒性肝炎等影响人民健康最普遍的传染病为重点。反映了建国以来各个时期本教研室对防治这些传染病所作的贡献。所取得的成果，相当一部分通过多年来的验证，已获得广大传染病工作者所认同或列为常规，部分已获得部委级奖励。现在重温这些成果，可能起承前启后的意义。     

Topical treatment with aqueous solutions of rofleponide palmitate and budesonide in a pollen-season model of allergic rhinitis

BACKGROUND: Rofleponide palmitate is an esterified glucocorticosteroid pro-drug with a promising pre-clinical profile designed to deliver topical airway treatment for allergic rhinitis and asthma in a novel manner. Thus, the rofleponide palmitate pro-drug is designed to provide topical exposure of the mucosa to the inactive lipophilic drug, which would be locally metabolized to the more hydrophilic and readily cleared drug rofleponide. OBJECTIVE: To examine whether rofleponide palmitate affects nasal symptoms and peak inspiratory flow (PIF) in a pollen-season model of allergic rhinitis and to compare any such effects with those of another glucocorticosteroid (i.e., budesonide). METHODS: During the pollen-free season, 40 patients with strictly seasonal allergic rhinitis received topical nasal spray treatment with an aqueous solution of rofleponide palmitate 400 microg and an aqueous solution of budesonide 128 microg once daily for 10 days in a double-blind, placebo-controlled, and crossover study. After 3 days of drug treatment, individualized allergen challenges were given once daily for 7 days while the treatment continued. The washout periods between each of the challenge series were 2 weeks. Nasal symptoms and PIF were recorded in the morning and evening, as well as 10 and 20 min after each allergen challenge. The mean recordings obtained during the last 3 days of the allergen-challenge series, when symptoms were established and when the treatment had lasted for 8-10 days, were used in the analysis. RESULTS: Both active treatments reduced nasal symptoms and improved nasal PIF compared with placebo (P<0.01-0.001). There was no overall difference in efficacy between rofleponide palmitate 400 microg and budesonide 128 microg. CONCLUSIONS: Topical treatment with aqueous solutions of rofleponide palmitate attenuates nasal symptoms and improves nasal PIF in allergic rhinitis. The overall efficacy of 400 microg of rofleponide palmitate is similar to that of 128 microg of budesonide in the pollen-season model used in this study.     

Neurokinin A with K channel blockade potentiates contraction to electrical stimulation in human bronchus

This study investigated the effects of neurokinin A (NKA) on cholinergic neural responses in human bronchus. NKA (0.1 nM) did not alter the contractile response to submaximal electrical field stimulation. However, K⁺ channel blockade with 4-aminopyridine (4-AP) (0.1 mM) potentiated the response to electrical field stimulation (to 182 ± 25% of control, n = 4, P < 0.05) and subsequent addition of NKA in the presence of 4-AP produced further potentiation (to 123 ± 6% of the response to 4-AP n = 4, P < 0.05). Neither 4-AP (0.01 or 0.1 mM) nor NKA in the presence of 4-AP potentiated the actions of exogenous acetylcholine but in these experiments 4-AP itself produced a marked direct contractile response. Thus NKA in the presence of K⁺ channel blockade potentiates cholinergic neural response in human bronchus and this occurs at a prejunctional site.     

The usefulness of detailed information to patients with contact allergy

To find out if patients with contact allergy are helped by computerized information lists, a retrospective study was carried out on 58 patients with contact allergy to lanolin, traced through our local database DALUK. All were sent a questionnaire about their usage of the information list, clearance of their eczema, their education and other details. Clearance of the patient's eczema was found to correlate with use of the information list. It was also found that the effectiveness of the information depended on factors such as education, family circumstances, ethnic background and, most of all, how and where the information list was used.     

Substance P induces inositol 1,4,5-trisphosphate and intracellular free calcium increase in cultured normal human epidermal keratinocytes

Abstract Substance P is a neuropeptide which is present in peripheral C nerve endings and released from them. Free nerve endings of C nerve are present in human epidermis. The effects of substance P on the transmembrane signaling system of pig epidermal sheets were previously reported. In these studies, a small amount of cells other than keratinocytes contaminated the epidermal sheets and the species difference from human was also noticed. Therefore we investigated the effects of substance P on cultured normal human epidermal keratinocytes. Alteration of intracellular free calcium (Ca²⁺) in single living keratinocytes was studied using an inverted fluorescence microscope and Ca²⁺ -sensitive dye, Fura 2-AM. Treatment of normal human epidermal kertinocytes with substance P resulted in an increase in inositol 1,4,5-trisphosphate and in intracellular Ca²⁺. Substance P inhibited DNA synthesis of the keratinocytes in a dose-dependent manner. These results are consistent with the view that substance P stimulates phosphatidylinositol-4,5-bisphosphate hydrolysis of human keratinocytes, resulting in inositol 1,4,5-trisphosphate-Ca²⁺ signal.     

A Neuromagnetic Study of the Functional Organization of the Sensorimotor Cortex

Movement-related neuromagnetic fields from eight healthy human subjects were investigated in a Bereitschaftspotential paradigm. The three conditions studied were right-sided mouth, index finger and foot movement. The neuromagnetic field patterns corresponding to the motor field and the movement-evoked field I were analysed using a moving dipole model. For both components a somatotopic organization was found: the estimated dipole locations for the mouth were more lateral and those for the foot more medial than the estimated dipole positions for the index finger movement. With regard to possible clinical applications, e.g. non-invasive mapping of the sensorimotor cortex and studies of plasticity of the motor function, the present results suggest that the investigation of movement-evoked field I for the index finger condition is most likely to yield further results.     

Human brain atlas: For high-resolution functional and anatomical mapping

We present the new computerized Human Brain Atlas (HBA) for anatomical and functional mapping studies of the human brain. The HBA is based on many high-resolution magnetic resonance images of normal subjects and provides continuous updating of the mean shape and position of anatomical structures of the human brain. The structures are transformable by linear and nonlinear global and local transformations applied anywhere in 3-D pictures to fit the anatomical structures of individual brains, which, by reformatting, are transformed into a high-resolution standard anatomical format. The power of the HBA to reduce anatomical variations was evaluated on a randomized selection of anatomical landmarks in brains of 27 young normal male volunteers who were different from those on whom the standard brain was selected. The HBA, even when based only on standard brain surface and central structures, reduced interindividual anatomical variance to the level of the variance in structure position between the right and left hemisphere in individual brains. © 1994 Wiley-Liss, Inc.     

Allergen activates peripheral blood eosinophil nuclear factor-κB to generate granulocyte macrophage-colony stimulating factor, tumour necrosis factor-α and interleukin-8

BACKGROUND: Allergic inflammation is characterized by the influx and activation of eosinophils. Cytokines generated by both resident and infiltrating cells are responsible for the initiation and maintenance of this pathogenesis. This study focuses on allergen-induced activation of eosinophil NF-kappaB and generation of granulocyte macrophage-colony stimulating factor (GM-CSF), TNF-alpha, and IL-8. METHODS: Peripheral blood eosinophils were enriched to >99.9% by Percoll gradient sedimentation and negative magnetic affinity chromatography. NF-kappaB activation by 10 microg/mL house dust mite (HDM) extract was demonstrated immunocytochemically using a monoclonal antibody against the active form of NF-kappaB (NF-kappaBa). The authenticity of NF-kappaB was confirmed by Western blot. Cytokine production was assessed both by immuno-staining of eosinophils and by assay of cytokines in the cell supernatant. RESULTS: Activation of peripheral blood eosinophils from atopic, but not non-atopic, donors induced activation of NF-kappaB, which peaked at 4 h and was accompanied by a decline in IkappaB-alpha. The activation of authentic NF-kappaB was confirmed in gel shift assays. Supershift assays showed p65 to be the major subunit of eosinophil NF-kappaB. Immunofluorescent confocal microscopy demonstrated localization of NF-kappaBa to the nucleus. Following activation, cytokine immunoreactivity was seen in a fraction of the eosinophils and cytokines were released into the supernatant. The NF-kappaB inhibitors, calpain inhibitor 1 (10 microm), pentoxifylline (0.5 mm), pyrrolidine dithiocarbamate (PDTC, 10 microm) or gliotoxin (1 pg/mL) reduced the generation of GM-CSF, TNF-alpha and IL-8 in parallel with their inhibition of NF-kappaB. CONCLUSIONS: HDM allergen activates human eosinophil NF-kappaB leading to the production of the cytokines GM-CSF, TNF-alpha and IL-8. We speculate that a role for eosinophil NF-kappaB-dependent cytokines is to act as an autocrine loop augmenting the survival of eosinophils in vivo.