白色念珠菌的耐药性和随机扩增DNA多态性分型研究

采用Etest药敏试验方法检测 30株临床分离白色念珠菌对 5种抗真菌药物的敏感性 ,并用随机扩增DNA多态性 (RAPD)分型方法对这些菌株进行基因分型。结果发现有两株对氟康唑耐药 ,且它们的RAPD带型有着高度相似性 ,提示RAPD带型可能与耐氟康唑基因有关。     

Tumor Necrosis Factor Gene Polymorphism in Chronic Sinusitis

Objectives It is likely that genetic factors play a role in the etiology of chronic sinusitis, and airway inflammation is an important pathological feature in chronic sinusitis. We hypothesized that individuals with greater inflammatory responses may be more likely to acquire the disease. Polymorphisms of the tumor necrosis factor (TNF) genes have been described, and certain inflammatory diseases are reportedly associated with certain alleles of TNF genes. The purpose of this study is to examine whether there is an association between some alleles of TNF genes and chronic sinusitis. Study Design Thirty‐eight Japanese patients with intractable chronic sinusitis were selected on the basis of the following criteria: 1) persistent mucous or mucopurulent nasal discharge and/or postnasal dripping for longer than 3 years and 2) opacification in bilateral maxillary sinuses and ethmoid cells on plain radiographic films. Methods Both tumor necrosis factor‐α (TNF‐α) and tumor necrosis factor‐β (TNF‐β) gene polymorphisms were analyzed by polymerase chain reaction (PCR) with restriction fragment length polymorphisms in these patients and 35 healthy control subjects. Results A significantly higher frequency (P < .05) of TNFB*2 allele of TNF‐β gene polymorphism was observed in patients with chronic sinusitis (74%) compared with control subjects (56%). There was no association between alleles of TNF‐α and chronic sinusitis. Conclusion We concluded that TNF‐β gene polymorphism may form a component of the genetic predisposition to chronic sinusitis in Japanese patients.     

妊高征患者与ACE基因缺失多态性研究

目的：探讨血管紧张素转换酶（ＡＣＥ）基因的缺失多态性与妊高征的关系。方法：对５２例妊高征患者（观察组）及１００例正常产妇,应用聚合酶链反应技术检测ＡＣＥ基因的缺失／插入多态性。结果：观察组的缺失型纯合子（ＤＤ型）ＡＣＥ基因占６５％,高于对照组的１６％;观察组的缺失型（Ｄ型）ＡＣＥ等位基因出现频率为７５％,亦高于对照组的３３％（Ｐ〈０．０１）。结论：妊高征的发病与ＡＣＥ基因的缺失多态性有关。     

POLYMORPHISM OF ANGIOTENSIN-CONVERTING ENZYME GENE AND GENETIC SUSCEPTIBILITY TO ASTHMA WITH FAMILIAL AGGREGATION

Objective. Angiotensin-converting enzyme (ACE) plays a key role in the metabolism of angiotensin Ⅱ (AT Ⅱ) and inactivation of bradykinins and tachykinins, which are potent bronchialconstrictors and mediators of inflammation asthma, and ACE is heavily expressed in the lungs. An insertion-deletion (D/I) polymorphism of ACE gene has been shown to be associated with levels of ACE. We investigate whether the polymorphism of ACE gene is associated with asthma and bronchial responsiveness.Methods. A case-control study was carried out in 50 asthmatics, 7 families with at least 2 asthmatic individuals, and 50 healthy subjects. The insertion/deletion (I/D) polymorphism of ACE gene was amplified by polymerase chain reaction (PCR). Methacholine brocho-provocation and pulmonary function tests were performed in all asthmatics. Results. There was an higher gene frequency of DD genotype of ACE gene in asthmatic subjects and families individuals compared with healthy subjects (46%, 53% vs 16%, P＜0.05; odd ratio 4.98). Anhigher prevalence of DD genotype of ACE was in patients with bronchial hyperresposiveness (BHR) (67%vs 33%, P＜0.05; odd ratio 3.8). Accordingly, the mean values of FEV1% and FEV1/FVC were higher in asthmatics carrying non-DD alleles than patients with DD genotype (73.78% vs 56.56%, P＜0.05; 79.19% vs 69.29%, P＜0.05, respectively).Conclusion. These results suggested that DD allele of ACE genotype was significantly involved in genetic susceptibility to asthma. DD genotype of ACE might be a risk factor for the degree of airway obstruction, it could also be implicated in pathogenesis of bronchial hyperresponsiveness.     

单链构象多态性分析技术检测结核杆菌利福平耐药基因

目的：研究本地区临床分离结核杆菌ｒｐｏＢ基因突变与利福平（ＲＦＰ）耐药性的关系。方法：对３６株ＲＦＰ敏感株和４４株ＲＦＰ耐药株ｒｐｏＢ基因的３２８ｂｐ的ＰＣＲ扩增产物进行单链构象多态性（Ｓｉｎｇｌｅ－ｓｔｒａｎｄ ｃｏｍｆｏｒｍａｔｉｏｎｐｏｌｙｍｏｒｐｈｉｓｍ,ＳＳＣＰ）分析。结果：３６株ＲＦＰ敏感株的ＳＳＣＰ带谱均与参考株Ｈ３７Ｒｖ相同,４４株ＲＦＰ耐药株中,２５株高度ＲＦＰ耐药株和１１株低度ＲＦＰ耐药株的ＳＳＣＰ带谱与Ｈ３７Ｒｖ带谱有差异;另８株低度ＲＦＰ耐药株的ＳＳＣＰ带谱与Ｈ３７Ｒｖ带谱相同。结论：ＳＳＣＰ分析可检测出ｒｐｏＢ基因突变,该基因突变与本地区临床分离结核杆菌对ＲＦＰ耐药有关。     

Adverse childhood experiences and the development of Down syndrome regression disorder

Down syndrome regression disorder (DSRD) is a clinical symptom cluster of acute or subacute neurocognitive regression in otherwise health persons with Down syndrome. The objective of this study was to evaluate if adverse childhood experiences (ACEs) were more prevalent in children with DSRD than those with DS alone. A survey-based, cohort-based study was performed. Caregivers of individuals with DSRD with onset of symptoms between age 10 and 30 years and DS alone were administered the ACEs questionnaire via an online REDCap survey. A total of 159 responses were collected after excluding incomplete surveys and those not meeting criteria for DSRD. Individuals with DSRD were not more likely to experience ACEs (p = 0.18, 95% confidence interval [CI]: 0.43–1.17). In those with ACEs prior to the onset of symptoms, the median time prior was 7 months (interquartile range: 5–10). Individuals with DSRD were more likely to report three or more ACEs (52, 33%) compared to those with DS alone (39, 22%) (p = 0.02, 95% CI: 1.08–2.87). Exposure to ACEs were not predictive of response to particular therapeutic interventions although those with multiple ACEs 3 months prior to the onset of symptoms was associated with lower response rates to benzodiazepines and immunotherapy (p = 0.02, 95% CI: −3.64–−1.13). This study provides preliminary data that individuals with DSRD experience ACEs at a similar rate to individuals with only DS alone, although three or more ACEs, often preceding the onset of symptoms, was more prevalent in individuals with DSRD.     

OACE inhibition does not interfere with acute extrarenal or renal potassium disposal in chronic renal failure

The influence of angiotensin converting enzyme (ACE) inhibition on acute extrarenal and renal potassium elimination in stable chronic renal failure has been examined in 10 male patients median age 44 y; mean CL_CR 42 ml·min^–1·1.73 m^–2. In a double blind, placebo-controlled cross-over study, K⁺ 0.3 or 0.4 mmol·kg^–1 body weight was infused IV on two occasions while the patients also received an infusion either of placebo or 0.5 mg of the ACE inhibitor perindoprilat in random order. Plasma K⁺ levels and urinary K⁺ excretion were measured at regular intervals. During the study patients adhered to an isocaloric diet providing a standardised daily intake of potassium and sodium (50 mmol K⁺ and 40 mmol Na⁺).The median rise in plasma K⁺ was not significantly different after placebo ( K 0.66 mmol·1^–1) compared with to the infusion of perindoprilat ( K 0.66 mmol·1^–1). The median baseline urinary K⁺ excretion rate was 6.5 mmol·3 h^–1 before the placebo infusion and 5.9 mmol·3 h^–1 before infusion of perindoprilat. During the potassium load, the urinary excretion rate rose to 16.1 mmol·3 h^–1 (after placebo) and 15.1 mmol·3 h^–1 after perindoprilat in the first 3 h, and it returned almost to the baseline value within the next 3 h (5.6 mmol·3 h^–1 after placebo and 5.7 mmol·3 h^–1 after perindoprilat); the differences were not statistically significant.With perindoprilat a decrease in mean arterial blood pressure and ACE activity, an increase in renin plasma activity and a decrease in aldosterone concentrations were observed compared to the placebo infusion. There was no significant differences plasma in adrenaline or insulin levels after either infusion.Thus, ACE inhibition did not interfere either with the extrarenal or the renal disposal of an acute potassium load in patients with chronic renal failure.     

Thalidomide-induced neuropathy and genetic differences in drug metabolism

A pharmacogenetic predisposition to thalidomide-induced neuropathy has been investigated. Differences of drug metabolism were examined in 16 patients with severe orogenital ulceration, who were treated with thalidomide (200 mg/day) for 0.3–5.0 years. Eight had evidence of early peripheral neuropathy according to nerve conduction studies. Rates of C-hydroxylation, N-acetylation, and conjugation reactions with sulphate, glucuronide and glycine, were tested with the probe compounds debrisoquine, sulphadimidine, paracetamol and aspirin, respectively. Urinary drug metabolites were analysed by high pressure liquid chromatography. Results were compared with 16 healthy age- and sex-matched volunteers.Of the patients 6.25% and 13.3% of the controls had a poor Debrisoquine Hydroxylator Ratio (DMR); none of the patients with neuropathy had a poor DMR as compared to 12.5% without neuropathy. Of the patients 40.0% and 35.7% of the controls were slow acetylators; 28.6% with neuropathy were slow acetylators as opposed to 50% without neuropathy. Similarly, there were no significant differences in rates of conjugation between groups. All unaffected patients were active smokers, whereas only two of those with neuropathy smoked. Cumulative dose or duration of therapy were unrelated to risk of neuropathy.In conclusion, changes of nerve conductivity are a frequent and unpredictable adverse effect of thalidomide (200 mg/day), although smoking may have a protective action against their development. Nerve conduction studies are required before and during treatment, irrespective of the prescribed dose.     

急性白血病患者MGMT基因突变的研究

目的研究甲基鸟嘌呤－脱氧核糖核酸－甲基转移酶（ＭＧＭＴ）基因突变与急性白血病发病的关系。方法应用聚合酶链反应－单链构象多态性（ＰＣＲ－ＳＳＣＰ）技术对６２例急性白血病中ＭＧＭＴ基因进行了突变分析。结果ＭＧＭＴ基因突变在急性白血病中为１４．５％。结论急性白血病中存在ＭＧＭＴ基因突变,其在急性白血病的发生与发展中起到一定作用。