Immunochemical characterization of multiple forms of cytochrome P-450 in rabbit nasal microsomes and evidence for tissue-specific expression of P-450s NMa and NMb

Two unique forms of cytochrome P-450 (P-450), designated NMa and NMb, were recently isolated in this laboratory from nasal microsomes of rabbits. In the present study, polyclonal antibodies to the purified nasal cytochromes were prepared. Immunochemical analysis with specific rabbit anti-NMa and sheep anti-NMb antibodies indicated that P-450 isozymes identical to or having a high structural homology with NMa are present in both olfactory and respiratory mucosa, as well as in liver, but NMb was detected only in the olfactory mucosa. Neither form was detected in other tissues examined, including brain, esophageal mucosa, heart, intestinal mucosa, kidney, and lung. The specific occurrence of NMb in the olfactory mucosa was further substantiated by the detection and specific inhibition by anti-NMb of the formation of unique NMb-dependent metabolites of testosterone in olfactory microsomes but not in microsomes from liver or respiratory mucosa. Similar experiments with antibodies to previously purified rabbit hepatic P-450 isozymes indicated that not all of the hepatic cytochromes are expressed in the nasal tissues. Thus, P-450 isozymes structurally homologous to hepatic forms 2, 3a, and 4, but not 3b and 6, were found in the olfactory mucosa. On the other hand, only form 2 was detected in the respiratory mucosa. Immunoquantitation experiments revealed that NMa and NMb are the major P-450 forms in olfactory microsomes, whereas NMa and P-450 form 2 (or its homolog) constitute the major portion of the respiratory nasal microsomal P-450. The level of NMa in the liver is relatively low, accounting for less than 3% of total microsomal P-450 in this tissue. In addition, evidence is provided that NMa is the major catalyst in the dealkylation of two nasal carcinogens, hexamethylphosphoramide and phenacetin, in both olfactory and respiratory nasal microsomes.     

Reflex Cardiorespiratory Effects of Nociceptive Oesophageal Distension in the Decerebrate Rat

It is well established that painful distension of hollow viscera such as the oesophagus can evoke a reflex tachycardia and pressor response; however, the nature of the oesophageal afferent pathway(s) remains controversial. This study investigated the afferent arc which mediates these reflex cardiovascular changes in the decerebrate rat. In addition, the effect of oesophageal distension on the respiratory activity of the costal diaphragm was studied. Focal distension of the oesophagus (volume of 0.3 ml applied for 10 s) just above the diaphragmatic hiatus evoked a reproducible pressor response and tachycardia in the decerebrate rat. Respiration was transiently inhibited at the beginning of oesophageal distension and prior to the rise in blood pressure. Neuromuscular blockade with the nicotinic acetylcholine receptor blocker alpha-bungarotoxin (140 microg bolus) had no effect on the magnitude of the cardiovascular response. Therefore the efferent supply to the striated muscle of the rat oesophagus was not essential in mediating this reflex. Signal averaging of the mean blood pressure response showed that neither selective ablation of oesophageal spinal afferents nor bilateral vagotomy altered the early trajectory of the pressure response. Bilateral vagotomy reduced the peak magnitude of the response to sustained oesophageal distension. In contrast, selective removal of spinal afferents had no effect on the response. Ablation of both neural pathways was essential to abolish the reflex cardiovascular and respiratory responses. It can be concluded that both vagal and spinal afferent pathways are utilised in the reflex cardiorespiratory response to painful oesophageal distension. Although ablation of one neural pathway had no effect on the response it was still implicated in the reflex, since ablation of both pathways was necessary to prevent the cardiorespiratory changes. This study emphasises the need for caution when inferences are made concerning single selective ablations of multiply innervated organs.     

Specific sensitization to common allergens and pulmonary function in the European Community Respiratory Health Survey

BACKGROUND: The role of atopy in the evolution to chronic obstructive disease remains controversial. AIM: We aimed to assess the association between individual sensitization to common allergens and lung function. METHOD: We analysed data from 12,687 subjects aged 20 to 44 years, from 34 centres in 15 countries participating in the European Community Respiratory Health Survey (ECRHS). Participants performed a blood test, lung function test, methacholine challenge, and answered an administered questionnaire. The relationships between specific IgE, FEV1 and FEV1/FVC ratio were assessed for each study centre stratified by sex, followed by random effects meta-analysis. RESULTS: Asthmatics sensitized to house dust mite had a lower FEV1 (-119 mL in women and -112 mL in men) and FEV1/FVC ratio (-1.95%, and -2.48%) than asthmatics without sensitization. Asthmatics sensitized to cat had a lower FEV1 (statistically significant for women only) and a lower FEV1/FVC ratio. Asthmatic women sensitized to grass had a lower FEV1 and a lower ratio, and those sensitized to Cladosporium had a lower FEV1. A weak association was found with sensitization to cat and to Cladosporium among non-asthmatic women, which disappeared after adjusting for BHR. CONCLUSION: We conclude that atopy was related to a lower lung function, which was only apparent among asthmatics. This relationship was explained by specific sensitization to cat and to house dust mite, the latter being homogeneous across areas.     

TRH、EGF及地塞米松促进未成熟胎肺组织分化及表面活性物质合成的研究

目的 比较TRH、EGF与地塞米松对未成熟胎肺形态发育及表面活性物质水平的影响。方法 在兔妊娠第22－24d或第24－26d分别用TRH、EGF或地塞米松母体静脉注射治病，通过光镜、图像分析及电镜等技术观察胎肺的形态结构，并检测胎肺的磷脂水平。结果 光镜下，TRH、EGF与地塞米松治疗组第25d及27d胎肺肺泡腔、肺泡间隔发育均明显好于对照组；EGF、TRH与地塞米松治疗组第27d胎肺的肺泡腔与肺泡间隔的面积比无明显差异。但EGF和TRH治疗组第25d胎肺的肺泡腔与肺泡间隔之比明显小于地塞米松治疗组。电镜下，三个治疗组第27d胎肺内含有板层体的Ⅱ型上皮细胞数量明显多于对照组，但各治疗组及对照组第25d的胎肺Ⅱ型上皮细胞胞浆内几乎未见明显板层体，相反胞浆内糖原含量却非常丰富。此外，三个治疗组27d胎肺的磷脂水平均明显高于对照组。结论 EGF、TRH及地塞米松在兔妊娠第24－26d母体治疗均能促进胎肺的形态发育和表面活性物质的合成，三种治疗方法对胎肺的影响程序无明显不同；在妊娠第22－24d治疗，地塞米松对胎肺形态结构的促进作用较EGF和TRH更明显，但三者对Ⅱ型上皮细胞分化及表面活性物质的合成均无明显影响。