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991.
Suzanna G.M. Frints Friederike Hennig Roberto Colombo Sebastien Jacquemont Paulien Terhal Holly H. Zimmerman David Hunt Bryce A. Mendelsohn Ulrike Kordaß Richard Webster Margje Sinnema Omar Abdul‐Rahman Vanessa Suckow Alberto Fernndez‐Jan Kees van Roozendaal Servi J.C. Stevens Merryn V.E. Macville Salwan Al‐Nasiry Koen van Gassen Norbert Utzig Suzanne M. Koudijs Lesley McGregor Saskia M. Maas Diana Baralle Abhijit Dixit Peter Wieacker Marcus Lee Arthur S. Lee Elizabeth C. Engle Gunnar Houge Gyri A. Gradek Andrew G.L. Douglas Cheryl Longman Shelagh Joss Danita Velasco Raoul C. Hennekam Hiromi Hirata Vera M. Kalscheuer 《Human mutation》2019,40(12):2270-2285
Pathogenic variants in the X‐linked gene ZC4H2, which encodes a zinc‐finger protein, cause an infrequently described syndromic form of arthrogryposis multiplex congenita (AMC) with central and peripheral nervous system involvement. We present genetic and detailed phenotypic information on 23 newly identified families and simplex cases that include 19 affected females from 18 families and 14 affected males from nine families. Of note, the 15 females with deleterious de novo ZC4H2 variants presented with phenotypes ranging from mild to severe, and their clinical features overlapped with those seen in affected males. By contrast, of the nine carrier females with inherited ZC4H2 missense variants that were deleterious in affected male relatives, four were symptomatic. We also compared clinical phenotypes with previously published cases of both sexes and provide an overview on 48 males and 57 females from 42 families. The spectrum of ZC4H2 defects comprises novel and recurrent mostly inherited missense variants in affected males, and de novo splicing, frameshift, nonsense, and partial ZC4H2 deletions in affected females. Pathogenicity of two newly identified missense variants was further supported by studies in zebrafish. We propose ZC4H2 as a good candidate for early genetic testing of males and females with a clinical suspicion of fetal hypo‐/akinesia and/or (neurogenic) AMC. 相似文献
992.
AsmaGul Naz Muhammad Ali Muhammad Assad Aslam Abrar Ul Haq Khan Hamid Manzoor Rehana Iqbal Muhammad Ahmed Shehzad Shahbaz Ahmad Zubair Shaheen Sumaira Rasul 《Annals of human genetics》2019,83(6):426-433
Tuberculosis (TB) is a global issue as one‐third of the population worldwide is considered to be infected. TB has become a critical public health problem as a result of increasing drug resistance, which poses a challenge to current control strategies. Similar to environmental factors, genetic makeup of the host equally contributes to disease onset. We performed genotypic analysis to examine the relationship between IFNG and TB onset and drug resistance in a Pakistani population comprising 689 subjects. Notable differences were observed in the IFNG polymorphism (+874T/A) between the case and control groups. The frequency of the wild‐type genotype (TT) in the controls (43.2%) was significantly higher than in the cases (25.3%) (odds ratio [OR] = 0.77, p < 0.0001), while the mutant genotype frequency (AA) (38.57%) in the cases was significantly higher than in the controls (22.6%) (OR = 1.46, p < 0.0001). The heterozygous genotype frequency (TA) did not significantly differ between the control and case groups. Compared with the controls, the variant allele (A) was approximately twice as frequent in the cases. Females and older people have a higher chance of disease development. Finally, the IFNG (+874T/A) polymorphism was not associated with drug sensitivity or resistance. However, a genotypic polymorphism of IFNG (+874T/A) was significantly associated with susceptibility to TB, and the T allele conferred protection against TB. Additional studies involving larger cohorts are needed to further explore this relationship between genetics and disease vulnerability. 相似文献
993.
Suchandan Sikder Georgina Price Md Abdul Alim Anil Gautam Robert Scott Simpson Catherine Margaret Rush 《Autoimmunity》2019,52(2):78-87
Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are autoimmune mediated diseases triggered by group A streptococcal (GAS) infections. Molecular mimicry between GAS M-proteins and host tissue proteins has been proposed as the mechanism that initiates autoreactive immune responses in ARF/RHD. However, the individual role of antibodies and T-cells specific for GAS M-proteins in the pathogenesis of autoimmune carditis remains under-explored. The current study investigated the role of antibodies and T-cells in the development of carditis in the Lewis rat autoimmune valvultis (RAV) model by transferring serum and/or splenic T-cells from rats previously injected with GAS recombinant M5 protein. Here we report that serum antibodies alone and serum plus in vitro expanded rM5-specific T-cells from hyperimmune rats were capable of transferring carditis to naïve syngeneic animals. Moreover, the rats that received combined serum and T-cells developed more severe carditis. Recipient rats developed mitral valvulitis and myocarditis and showed prolongation of P-R intervals in electrocardiography. GAS M5 protein-specific IgG reactivity and T-cell recall response were also demonstrated in recipient rats indicating long-term persistence of antibodies and T-cells following transfer. The results suggest that both anti-GAS M5 antibodies and T-cells have differential propensity to induce autoimmune mediated carditis in syngeneic rats following transfer. The results highlight that antibodies and effector T-cells generated by GAS M protein injection can also independently home into cardiac tissue to cross-react with tissue proteins causing autoimmune mediated immunopathology. 相似文献
994.
Rashid Mohammed H. Stevenson Mark A. Vaughan Jane L. Saeed Muhammad A. Campbell Angus J. D. Beveridge Ian Jabbar Abdul 《Parasitology research》2019,118(3):901-911
Parasitology Research - We conducted a longitudinal survey on 13 alpaca farms in four climatic zones of Australia to understand the epidemiology of gastrointestinal nematodes (GINs) of alpacas. A... 相似文献
995.
Current Surgical Therapy for Bronchiectasis 总被引:5,自引:0,他引:5
Mahmoud Ashour Khaled Al-Kattan Mohamad A. Rafay Khalid F. Saja Waseem Hajjar Abdul Rahman Al-Fraye 《World journal of surgery》1999,23(11):1096-1104
The ideal classification system for bronchiectasis continues to be debated. As an alternative to the present morphologic
classification, a hemodynamic-based functional classification is proposed. This study examines the rationale for and outcome
of surgery based on this classification in patients with unilateral or bilateral bronchiectasis. Between July 1987 and January
1997 the morphologic and hemodynamic features in 85 bronchiectatic patients were examined: 18 with bilateral bronchiectasis
and 67 with unilateral disease. A policy of unilateral lung resection of the nonperfused bronchiectasis and preservation of
the perfused type was adopted in all patients. The mean age at operation was 29.4 ± 9.7 years (range 6–55 years) with a mean
follow-up period of 45.2 ± 21.0 months (range 2–120 months). Left-sided predominance of bronchiectasis was evident in this
series both in frequency and severity. In those with unilateral disease, bronchiectasis was left-sided in 49 (73.1%) patients
and right-sided in 18 (26.9%). The left lung was totally bronchiectatic in 11 (16.4%) patients and the right in 3 (4.4%).
Moreover, among the patients with bilateral bronchiectasis, 14 of 18 (77.7%) patients had the left lung more severely involved.
Based on the morphologic and hemodynamic features in the investigated patients, two types of bronchiectasis were recognized:
a perfused type with intact pulmonary artery flow and a nonperfused type with absent pulmonary artery flow. Lobectomy was
performed in 55 patients, basal segmentectomy and preservation of the apical segment in 16, and pneumonectomy in 14. There
was no mortality in this series. Altogether 63 patients (74.1%) achieved excellent results, 19 (22.4%) scored good results,
and 3 (3.5%) patients had not benefited from surgery at last follow-up. In the face of the general criticism of the traditional
morphologic classification, the proposed classification not only predicts whether the involved lung will have a measure of
respiratory function with regard to gas exchange but reflects the degree of severity of the disease process. Thus the question
of which side to resect and which to preserve is defined more precisely. This classification was found to be logical, physiologically
sound, and of proven benefit. 相似文献
996.
Contribution of Quorum Sensing to the Virulence of Pseudomonas aeruginosa in Burn Wound Infections 下载免费PDF全文
Kendra P. Rumbaugh John A. Griswold Barbara H. Iglewski Abdul N. Hamood 《Infection and immunity》1999,67(11):5854-5862
The Pseudomonas aeruginosa quorum-sensing systems, las and rhl, control the production of numerous virulence factors. In this study, we have used the burned-mouse model to examine the contribution of quorum-sensing systems to the pathogenesis of P. aeruginosa infections in burn wounds. Different quorum-sensing mutants of P. aeruginosa PAO1 that were defective in the lasR, lasI, or rhlI gene or both the lasI and rhlI genes were utilized. The following parameters of the P. aeruginosa infection were examined: (i) lethality to the burned mouse, (ii) dissemination of the P. aeruginosa strain within the body of the infected mouse (by determining the numbers of CFU of P. aeruginosa within the liver and spleen), and (iii) spread of the P. aeruginosa strain within the burned skin (by determining the numbers of CFU of P. aeruginosa at the inoculation site and at a site about 15 mm from the inoculation site [distant site]). In comparison with that of PAO1, the in vivo virulence of lasI, lasR, and rhlI mutants was significantly reduced. However, the most significant reduction in in vivo virulence was seen with the lasI rhlI mutant. The numbers of CFU that were recovered from the livers, spleens, and skin of mice infected with different mutants were significantly lower than those of PAO1. At 8 and 16 h post burn infection, comparable numbers of CFU of PAO1 and lasI and rhlI mutants were obtained from both the inoculation and distant sites of the burned skin of infected mice. In contrast, CFU of the lasR mutant and the lasI rhlI double mutant were recovered only from the inoculation site of infected mice at 8 and 16 h post burn infection. The ability of a plasmid carrying either the lasI or rhlI gene or the lasI and rhlI genes to complement the defect of the lasI rhlI double mutant was also examined. The presence of any of these plasmids within the lasI rhlI double mutant significantly enhanced its in vivo virulence, as well as its ability to spread within the burned skin. These results suggest that the quorum-sensing systems play an important role in the horizontal spread of P. aeruginosa within burned skin and in the dissemination of P. aeruginosa within the bodies of burned-and-infected mice and contributed to the overall virulence of P. aeruginosa in this animal model. 相似文献
997.
Risk factors for nutritional rickets among children in Kuwait 总被引:1,自引:0,他引:1
Abdul Majid Molla Mona H Badawi Suhad Al-Yaish Prem Sharma Randa Salah El-Salam 《Pediatrics international》2000,42(3):280-284
AIM: To assess the risk factors for nutritional rickets among children in Kuwait. METHODS: One hundred and three children with rickets and 102 control children matched for age and socioethnic characteristics were recruited over a 2 year period (January 1995 to January 1997) in Al-Adan Hospital in Kuwait. Diagnosis was made on clinical, radiologic and biochemical parameters. A specially designed questionnaire was administered by one of the investigators to both mothers of patients and mothers of control subjects to assess the role of social, nutritional and other related factors in the pathogenesis of nutritional rickets. Biochemical investigations included estimation of hemoglobin, serum calcium, serum phosphorus, serum alkaline phosphatase and serum 25-hydroxy vitamin D. RESULTS: The mean birthweights of rickets patients and control subjects were 3.20 +/- 0.46 and 3.19 +/- 0.45 kg, respectively. At the time of diagnosis, bodyweights of the patients and controls were 9.36 +/- 1.50 and 10.15 +/- 2.10 kg, respectively. Heights at the time of diagnosis were 73.58 and 77.24 cm for the patients and the controls, respectively. Mean hemoglobin, serum calcium and serum phosphate were significantly lower in the patients compared with the controls. Alkaline phosphatase was higher among the patients (P < 0.0001). The mean serum 25-hydroxy vitamin D level of the patients was 26.5 nmol/L, compared with 83.5 nmol/L in the controls. The mean age of starting semisolid feeds for the patients was 8.12 months, compared with 5.7 months in the controls. The nutritional quality of semisolid feeds was adequate among 71.6% of the controls as opposed to 13.6% of the patients. CONCLUSION: Nutritional rickets is a multifactorial condition. However, several factors seem to make important contributions. Among these, lack of exposure to sunlight, prolonged breast feeding without supplementation and inadequate weaning practices are important. Maternal education is important as it can influence all of the above factors. 相似文献
998.
Abdul Shakoor Pawan Kumar Gupta Yash Pal Singh Meena Kataria 《Basic & clinical pharmacology & toxicology》2000,87(6):258-260
We studied the effect of aluminum on lead‐induced nephropathy in male albino rats. Five groups of male albino rats were given either water only or lead acetate (125 mg/kg body weight) and/or aluminum chloride (50 mg/kg body weight or 100 mg/kg body weight) for a period of 90 days. Aluminum was found to prevent the lead‐induced increase in the relative organ (kidney) weight in a dose‐dependent manner. Aluminum also prevented lead‐induced increase in plasma creatinine levels of the treated animals. Estimation of lead concentration in kidneys of different treatment groups revealed that the net deposition of lead was lower in animals which were given both lead acetate and aluminum chloride simultaneously. The results showed that aluminum offers some protection against lead‐induced nephrotoxicity in a time‐ and dose‐dependent manner. 相似文献
999.
Ali Haider Mohammed MD Bassam Abdul Rasool Hassan PhD Abdulrasool M. Wayyes PhD Haydar F. Al-Tukmagi PhD Ali Blebil PhD Juman Dujaili PhD Muhammed Hassan Nasr PhD Maguy Saffouh El Hajj PhD Diana Malaeb PhD Sara Abu Alhija MD Elham Kateeb PhD Ahmad Amro PhD Dalal Al-Taweel PhD Muna Arif Al Juma PhD Omar Abdulwahid Al-Ani MD Sinan Subhi Farhan PhD Rula M. Darwish PhD Ahmed Talib Al-Zaabi MPharm 《Journal of Cosmetic Dermatology》2023,22(1):296-305