The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission

Factors involved in the stability of trinucleotide repeats during transmission were studied in 139 families in which a full mutation, premutation or intermediate allele at either FRAXA or FRAXE was segregating. The transmission of alleles at FRAXA, FRAXE and four microsatellite loci were recorded for all individuals. Instability within the minimal and common ranges (0-40 repeats for FRAXA, 0-30 repeats for FRAXE) was extremely rare; only one example was observed, an increased in size at FRAXA from 29 to 39 repeats. Four FRAXA and three FRAXE alleles in the intermediate range (41-60) repeats for FRAXA, 31-60 for FRAXE) were unstably transmitted. Instability was more frequent for FRAXA intermediate alleles that had a tract of pure CGG greater than 37 although instability only occurred in two of 13 such transmissions: the changes observed were limited to only one or two repeats. Premutation FRAXA alleles over 100 repeats expanded to a full mutation during female transmission in 100% of cases, in agreement with other published series. There was no clear correlation between haplotype and probability of expansion of FRAXA premutations. Instability at FRAXA or FRAXE was more often observed in conjunction with a second instability at an independent locus suggesting genomic instability as a possible mechanism by which at least some FRAXA and FRAXE mutations arise.      

Evidence for superantigenic activity during murine malaria infection

TCR V beta usage was examined in C57BL/6 mice infected with Plasmodium yoelii. In addition to a polyclonal T cell activation, already described, a superantigenic-like activity was observed during the acute infection. This superantigenic activity induces a preferential deletion without prior expansion of CD4+ and CD8+ T cells bearing the TCR V beta 9 segment. The superantigen could be released by the parasite at different stages of its development since the deletion of V beta 9+ T cells was observed in blood and lymph nodes of mice infected either with sporozoites or with erythrocytic stages. Injection of sporozoite or parasitized erythrocytes to newborn mice led to a deletion and anergy of peripheral V beta 9+ T cells, without affecting thymic T cell populations. These observations suggest that the superantigen is released at very low concentrations during parasite development. The role of such parasite superantigenic activity in infectivity can be underlined by the observation that congenic BALB.D2 Mis1a mice lacking V beta 9 T cells are more susceptible to infection by P. yoelii.      

Microduplication of Xp11.23p11.3 with effects on cognition,behavior, and craniofacial development

El‐Hattab AW, Bournat J, Eng PA, Wu JBS, Walker BA, Stankiewicz P, Cheung SW, Brown CW. Microduplication of Xp11.23p11.3 with effects on cognition, behavior, and craniofacial development. We report an ～1.3 Mb tandem duplication at Xp11.23p11.3 in an 11‐year‐old boy with pleasant personality, hyperactivity, learning and visual‐spatial difficulties, relative microcephaly, long face, stellate iris pattern, and periorbital fullness. This clinical presentation is milder and distinct from that of patients with partially overlapping Xp11.22p11.23 duplications which have been described in males and females with intellectual disability, language delay, autistic behaviors, and seizures. The duplicated region harbors three known X‐linked mental retardation genes: FTSJ1, ZNF81, and SYN1. Quantitative polymerase chain reaction from whole blood total RNA showed increased expression of three genes located in the duplicated region: EBP, WDR13, and ZNF81. Thus, over‐expression of genes in the interval may contribute to the observed phenotype. Many of the features seen in this patient are present in individuals with Williams‐Beuren syndrome (WBS). Interestingly, the SYN1 gene within the duplicated interval, as well as the STX1A gene, within the WBS critical region, co‐localize to presynaptic active zones, and play important roles in neurotransmitter release.     

Antibiogram and plasmid profiling of carbapenemase and extended spectrum Beta-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae in Abeokuta,South western,Nigeria

Background

The increased reports of ESBL dissemination from various centres in south western, Nigeria and the recent emergence of carbapenem resistant bacteria prompted the conception of this study.

Objectives

To demonstrate the relationship between high molecular weight plasmids and the expression of antibiotic multi-resistance including ESBL and carbapenemase.

Methods

We investigated 97 isolates of selected organisms consisting of 67 E. coli and 30 Klebseilla spp for the presence of plasmids expressing ESBL including carbapenem-hydrolysing enzymes. Beta-lactamase was determined using acidometric method, while ESBL and carbapenemase activity was determined using the double-disk diffusion test as well as the Modified Hodge test (MHT). Plasmid profiles of ESBL and carbapenemase positive isolates were determined according to standard protocols.

Results

An ESBL prevalence rate of 21.6% and carbapenem- resistance rate of 9.3% was recorded. Antibiotic susceptibility profile of ESBL isolates showed 100.0% resistance against Amoxicillin, Cotrimoxazole and Erythromycin. Moderate susceptibility was recorded against the Quinolone class of antibiotics; Meropenem remained the most active antibiotic against ESBL isolates with 62.5% against E. coli and 60% against K. pneumoniae. The plasmid profiles of our study isolates ranged from 11.8kbp to 35.5kbp.

Conclusion

Due to the relationship between high molecular weight plasmids and multi-drug resistance, we hereby recommend regular molecular surveillance of this form in our study setting.     

Intriguing issues of EGFR targeting in head and neck cancer

We have read the recent comprehensive review by Cruz et al.[1] regarding the targeting of receptor tyrosine kinases andtheir therapeutic perspectives in head and neck squamous cellcarcinomas (HNSCC). The major focus of this report was epidermalgrowth factor receptor (EGFR) biology and targeting. However,we feel     

Atrial natriuretic peptide in the diagnosis of patent ductus arteriosus

The aim of this study was to measure plasma atrial natriuretic peptide in preterm infants with a patent ductus arteriosus before and after closure with indomethacin. Atrial natriuretic peptide was measured in 28 preterm infants with clinical and echocardiographic evidence of a patent ductus arteriosus and in eight preterm infants who did not develop clinical evidence of a patent ductus arteriosus. Plasma concentration of atrial natriuretic peptide was measured by radioimmunoassay. In 18 infants the patent ductus arteriosus closed after one course of indomethacin; atrial natriuretic peptide levels decreased from median 1240 pg/ml (range 201-5483 pg/ml) to 266 pg/ml (range 62-1108 pg/ml). In four infants the patent ductus arteriosus closed after two courses of indomethacin and two infants had surgical ligation after indomethacin treatment failed. The patent ductus arteriosus closed spontaneously in four infants (atrial natriuretic peptide median level 152 pg/ml, range 61-495 pg/ml). In the eight infants without patent ductus arteriosus, atrial natriuretic peptide level was median 224 pg/ml (range 38-876 pg/ml). Measurement of plasma atrial natriuretic peptide concentration has a role in predicting when indomethacin treatment is indicated.     

Illicit drug use,cigarette smoking and alcohol drinking behaviour among a sample of high school adolescents in the Pietersburg area of the Northern Province,South Africa

AIM: The aim of this study was to investigate the prevalence of illicit drug use, cigarette smoking and alcohol drinking behaviour among a sample of high-school adolescents in the Pietersburg area (Central Region) of the Northern Province, South Africa. PARTICIPANTS: Participants in this study were 435 secondary-school adolescent students around the Pietersburg area (Central Region), in the Northern Province. Two hundred and forty-three (56%) participants were female and 192 (44%) were male. They were aged between 15 and 19 years, with the mean age of 17.25 years (S.D.=1.34). Their educational level ranged between standards 7 and 10 (Grades 9-12). INSTRUMENTS: Participants' demographic variables were determined by use of a questionnaire which covered participants personal characteristics such as age and gender, as well as educational level. Illicit drug use, cigarette smoking, and alcohol drinking behaviour were also measured using the questionnaire. RESULTS: Findings of this study indicate the prevalence rate of 19.8% for illicit drug use, 10.6% for cigarette smoking and 39.1% for alcohol consumption among the participants. Both drug use, cigarette smoking and alcohol consumption are associated more with males than with females. The majority of the drug users and cigarette smokers indicated that they do so when they are bored, tired or stressed up, or at parties; and most of those who drink alcohol indicated that they do so at parties, weekends, or any other time. The mean age for first drug use is 14.9 years (S.D.=1.77); 14.54 years (S.D.=1.80) for first cigarette smoking and 15.33 years (S.D.=1.91) for first alcohol consumption. Among those who drink alcohol, 24.1% and 14.1% experience unplanned drunkenness and irritability, respectively. Unplanned drunkenness is associated with males, while unplanned irritability (after drinking alcohol) is not associated with any gender. CONCLUSION: Mental health workers and the law-enforcement agencies should take note of the above findings while planning preventive and therapeutic strategies for the reduction of drug use, cigarette smoking and alcohol use and abuse among adolescents in the area.     

Prospective,randomized evaluation of a cuffed expanded polytetrafluoroethylene graft for hemodialysis vascular access

BACKGROUND: A cuffed expanded polytetrafluoroethylene (ePTFE) hemodialysis graft was developed to address the problem of recurrent stenosis at the graft-vein anastomosis. The purpose of this study was to compare graft patency and blood flow rates of cuffed and noncuffed (standard) ePTFE grafts placed for hemodialysis access. METHODS: Forty-eight patients were prospectively randomized and followed for up to 24 months after placement of a cuffed or standard ePTFE graft for hemodialysis access. Study end points included time to graft failure and blood flow rates on hemodialysis. RESULTS: Risk factors for graft failure were similar in both groups. However, the overall incidence of graft failure was significantly lower in the cuffed ePTFE graft group (P =.039). Graft patency rates in the cuffed versus standard groups were 64% versus 32% at 12 months (P =.037) and 58% versus 21% at 24 months (P =.0213). No cuffed ePTFE graft failed as a result of venous outflow stenosis. Average graft flow rates were similar when first measured 3 months postoperatively (845 mL/min, cuffed vs 715 mL/min, standard; P =.51) but declined more rapidly in the standard group (12 months, 623 vs 253 mL/min [P =.037]; 24 months, 531 vs 121 mL/min [P =.012]). CONCLUSIONS: The cuffed ePTFE graft was associated with increased blood flow rates during hemodialysis and improved graft patency compared with a standard ePTFE graft. Our results suggest a beneficial effect of the cuffed venous geometry for hemodialysis vascular access.