Abnormal XY interchange between a novel isolated protein kinase gene, PRKY, and its homologue, PRKX, accounts for one third of all (Y+)XX males and (Y-)XY females

XX males and XY females have a sex reversal disorder which can be caused by an abnormal interchange between the X and the Y chromosomes. We have isolated and characterized a novel gene on the Y chromosome, PRKY. This gene is highly homologous to a previously isolated gene from Xp22.3, PRKX, and represents a member of the cAMP-dependent serine threonine protein kinase gene family. Abnormal interchange can occur anywhere on Xp/Yp proximal to SRY. We can show that abnormal interchange happens particularly frequently between PRKX and PRKY. In a collection of 26 XX males and four XY females, between 27 and 35% of the interchanges take place between PRK homologues but at different sites within the gene. PRKY and PRKX are located far from the pseudoautosomal region where XY exchange normally takes place. The unprecedented high sequence identity and identical orientation of PRKY to its homologous partner on the X chromosome, PRKX, explains the high frequency of abnormal pairing and subsequent ectopic recombination, leading to XX males and XY females and to the highest rate of recombination outside the pseudoautosomal region.      

Targeted replacement of normal and mutant CFTR sequences in human airway epithelial cells using DNA fragments

Recent studies have reported that mutant genomic cystic fibrosis (CF) transmembrane conductance regulator ( CFTR ) sequences can be corrected in transformed CF airway epithelial cell lines by targeted replacement with small fragments of DNA with wild-type sequence. To determine if the observed genotype modification following small fragment homologous replacement (SFHR) was limited to transformed CF cell lines, further studies were carried out in both transformed and non-transformed primary normal airway epithelial cells. The endogenous genotype of these normal cell lines was modified following liposome or dendrimer transfection using DNA fragments with DeltaF508 CFTR sequence (488 nt, complementary single strands) designed to also contain a unique restriction enzyme cleavage site (Xho I). Replacement at the appropriate genomic locus by exogenous DeltaF508 CFTR DNA and its expression as mRNA was demonstrated by PCR amplification of genomic DNA and mRNA-derived cDNA as well as Xho I digestion of the PCR products. These studies show that SFHR occurs in both transformed and non- transformed primary human airway epithelial cells and indicate that single base substitution (the silent mutation giving rise to the Xho I site) and deletion or insertion of at least three consecutive bases can be achieved in both normal and CF epithelial cells. Furthermore, these studies reiterate the potential of SFHR as a strategy for a number of gene targeting applications, such as site-specific mutagenesis, development of transgenic animals, development of isogenic cell lines and for gene therapy.      

Mothers' reports of infant crying and soothing in a multicultural population

OBJECTIVES: To investigate the prevalence of infant crying and maternal soothing techniques in relation to ethnic origin and other sociodemographic variables. DESIGN: A questionnaire survey among mothers of 2-3 month old infants registered at six child health clinics in Amsterdam, the Netherlands. SUBJECTS: A questionnaire on sociodemographic characteristics and crying behaviour was completed for 1826 of 2180 (84%) infants invited with their parents to visit the child health clinics. A questionnaire on soothing techniques was also filled out at home for 1142 (63%) of these infants. RESULTS: Overall prevalences of "crying for three or more hours/24 hour day" "crying a lot", and "difficult to comfort" were 7.6%, 14.0%, and 10.3%, respectively. Problematic infant crying was reported by 20.3% of the mothers. Of these infants, only 14% met all three inclusion criteria. Problematic crying occurred less frequently among girls, second and later born children, Surinamese infants, and breast fed infants. Many mothers used soothing techniques that could affect their infant's health negatively. Shaking, slapping, and putting the baby to sleep in a prone position were more common among non-Dutch (especially Turkish) mothers than among Dutch mothers. Poorly educated mothers slapped their baby more often than highly educated mothers. CONCLUSIONS: Mothers' reports of infant crying and soothing varied sociodemographically. Much harm may be prevented by counselling parents (especially immigrants) on how and how not to respond to infant crying. Health education should start before the child's birth, because certain soothing techniques could be fatal, even when practised for the first time.     

Back pain and leg complaints that revealed non–small cell carcinoma: a case study

Objective

The purpose of this case study is to describe the clinical presentation of a patient with a chief complaint of low back and leg pain with no prior diagnosis of lung cancer.

Clinical Features

A 48-year-old man with a history of back pain presented to a chiropractic office with a complaint of low back and left leg pain.

Intervention and Outcome

Abnormal examination and radiographic findings were discovered. The patient was immediately referred to the pulmonologist for co-management. Through the use of advanced imaging and biopsy, stage 4 lung cancer was diagnosed.

Conclusion

Low back pain recurrence in an established patient should constitute a reevaluation of the problem. The cause cannot be assumed to be musculoskeletal in origin even though this may have been the case with the initial complaint. Metastatic disease should be considered with any type of recurrent low back pain.     

Human subject rear passenger symptom response to frontal car-to-car low-speed crash tests

Objective

The purpose of this study was to determine whether healthy adult volunteers report symptoms following exposure to low-speed frontal crashes at low velocities.

Methods

Nineteen medically screened, healthy, informed, and willing volunteers (17 men, 2 women; mean age, 37 years) were exposed to low-speed frontal crashes. All volunteers were seated in the rear seat position of the bullet vehicle. Closing velocities ranged from 4.1 to 8.3 mph (mean, 6.7 mph). For the bullet vehicle, the delta V ranged from 1.4 to 3.9 mph with a mean of 2.8 mph.

Results

Eighty-eight percent of volunteers attributed symptoms of discomfort to their crash exposure. All reported symptoms were transient, and none required medical treatment. The mean duration was 1 day.

Conclusions

Even at relatively low speeds, there is no lower threshold below which it can be reasonably assumed that healthy and prepared volunteer rear seat passengers will not sustain some level of minor injury in a frontal collision. Although the reported mean delta V for injured persons in real-world frontal crashes has been reported to be as high as 8.1 mph, this does not offer any insight into the minimum threshold for such injuries among all at-risk vehicle occupants.     

Going the Extra Mile: Beyond Health Teaching to Political Involvement

TOPIC. Addressing community health problems through political involvement. PURPOSE AND SOURCES OF INFORMATION. This article describes how a group of RN–BSN students completing an assigned community‐assessment and health‐teaching project in a small, rural, southern county exceeded course requirements to address a significant community health problem. Specifically, after documenting a high rate of dental caries among local children and consulting with state officials and other experts, these students involved themselves in local politics in an effort to persuade county officials to implement community water fluoridation. CONCLUSIONS. These RN–BSN students successfully demonstrated their ability to move beyond a focus on individuals to embrace the concept of community as client. In the process, they honed their skills in advocacy, communication, and political involvement, and achieved all of their BSN program's objectives.     

Neutrophil transfusions: kinetics and functions of neutrophils mobilized with granulocyte-colony-stimulating factor and dexamethasone

BACKGROUND: The collection of adequate numbers of neutrophils (polymorphonuclear leukocytes, PMNs) from normal donors has long hampered the development of neutrophil transfusion therapy. The stimulation of donors with granulocyte-colony-stimulating factor (G- CSF) plus dexamethasone is a promising way of improving PMN collections. STUDY DESIGN AND METHODS: Sixteen normal subjects received G-CSF (600 micrograms subcutaneously) and dexamethasone (8 mg by mouth) 12 hours before leukapheresis. Measurements included PMN morphology, immunophenotype analysis, chemiluminescence, bactericidal activity, in vivo kinetics, and adverse effects. RESULTS: A mean of 77.4 +/− 6.4 × 10(9) PMNs was collected with each leukapheresis; 14 percent were bands. PMNs had increased surface expression of CD11b, CD18, CD14, CD32, and CD64. Bactericidal capacity against Staphylococcus aureus was normal. Inducible respiratory burst was maintained, although the responses to some agonists were diminished. Returned leukapheresis cells labeled with 3H-diisopropylfluorophosphate had a modestly decreased percentage of recovery and circulated with a prolonged half- life. Migration of these cells to skin chambers was approximately equal to that of the subjects' own blood PMNs. Adverse effects included transient bone pain, headache, hunger, and insomnia. CONCLUSIONS: Precollection treatment of leukapheresis donors with G-CSF plus dexamethasone is an effective way to enhance the collection of PMNs with normal or near-normal functional properties for PMN transfusion therapy.