An essential receptor for adeno-associated virus infection.

Adeno-associated virus (AAV) vectors are currently the leading candidates for virus-based gene therapies because of their broad tissue tropism, non-pathogenic nature and low immunogenicity. They have been successfully used in clinical trials to treat hereditary diseases such as haemophilia B (ref. 2), and have been approved for treatment of lipoprotein lipase deficiency in Europe. Considerable efforts have been made to engineer AAV variants with novel and biomedically valuable cell tropisms to allow efficacious systemic administration, yet basic aspects of AAV cellular entry are still poorly understood. In particular, the protein receptor(s) required for AAV entry after cell attachment remains unknown. Here we use an unbiased genetic screen to identify proteins essential for AAV serotype 2 (AAV2) infection in a haploid human cell line. The most significantly enriched gene of the screen encodes a previously uncharacterized type I transmembrane protein, KIAA0319L (denoted hereafter as AAV receptor (AAVR)). We characterize AAVR as a protein capable of rapid endocytosis from the plasma membrane and trafficking to the trans-Golgi network. We show that AAVR directly binds to AAV2 particles, and that anti-AAVR antibodies efficiently block AAV2 infection. Moreover, genetic ablation of AAVR renders a wide range of mammalian cell types highly resistant to AAV2 infection. Notably, AAVR serves as a critical host factor for all tested AAV serotypes. The importance of AAVR for in vivo gene delivery is further highlighted by the robust resistance of Aavr(-/-) (also known as Au040320(-/-) and Kiaa0319l(-/-)) mice to AAV infection. Collectively, our data indicate that AAVR is a universal receptor involved in AAV infection.

Hydration during intense exercise training.

Hydration status has profound effects on both physical and mental performance, and sports performance is thus critically affected. Both overhydration and underhydration - if sufficiently severe - will impair performance and pose a risk to health. Athletes may begin exercise in a hypohydrated state as a result of incomplete recovery from water loss induced in order to achieve a specific body mass target or due to incomplete recovery from a previous competition or training session. Dehydration will also develop in endurance exercise where fluid intake does not match water loss. The focus has generally been on training rather than on competition, but sweat loss and fluid replacement in training may have important implications. Hypohydration may impair training quality and may also increase stress levels. It is unclear whether this will have negative effects (reduced training quality, impaired immunity) or whether it will promote a greater adaptive response. Hypohydration and the consequent hyperthermia, however, can enhance the effectiveness of a heat acclimation program, resulting in improved endurance performance in warm and temperate environments. Drinking in training may be important in enhancing tolerance of the gut when athletes plan to drink in competition. The distribution of water between body water compartments may also be important in the initiation and promotion of cellular adaptations to the training stimulus.

Gestational diabetes: postpartum glucose tolerance testing.

OBJECTIVE: Our purpose was to determine the incidence of and evaluate risk factors for postpartum glucose intolerance among predominantly black gestational diabetic women. STUDY DESIGN: One hundred forty-five gestational diabetics underwent a standard 2-hour glucose tolerance test in the early puerperium according to the criteria of the National Diabetes Data Group. RESULTS: Fourteen patients (10%) were diabetic and eight (5%) showed impaired glucose tolerance. Maternal age, race, or obesity did not predict abnormal postpartum glucose tolerance testing. The requirement of insulin for glucose control during gestation and gestational age at diagnosis were significantly associated with abnormal postpartum glucose tolerance (p < 0.0001 and p = 0.012, respectively). Multivariate analysis showed that only a requirement for insulin for glucose control was significant (p < 0.001). CONCLUSION: Pregnancies complicated by gestational diabetes are at increased risk of glucose intolerance during the early postpartum period. Abnormal glucose tolerance occurs predominantly among those patients requiring insulin therapy during gestation or those diagnosed before 24 weeks' gestation.

Ureteral injury during elective pregnancy termination. A case report.

This case is the sixth reported one of ureteral injury following elective pregnancy termination. It reemphasizes that the anatomic relationship of the ureter to the lower genital tract can predispose to surgical injury.

Positive serum screening for fetal Down syndrome does not predict adverse pregnancy outcome in absence of fetal aneuploidy.

OBJECTIVE: The purpose of this study was to determine whether false-positive maternal serum screening for fetal Down syndrome is predictive of poor pregnancy outcome. METHODS: The pregnancy outcomes of 99 women having positive serum screening for fetal Down syndrome (study group)--based upon maternal serum alpha-fetoprotein (MSAFP), unconjugated estriol (uE3), hCG, and maternal age--were compared to the outcomes of matched control patients having negative serum screening results (control group). The outcome indices analyzed were fetal death, intrauterine growth retardation (IUGR), preeclampsia, and fetal anomalies. RESULTS: Between the study group and the control group, there were no statistically significant differences in pregnancy outcome with respect to fetal death, IUGR, preeclampsia, or fetal anomalies. CONCLUSIONS: Our findings demonstrate no apparent increase in the adverse perinatal outcomes analyzed in women having unexplained positive serum screening for fetal Down syndrome. Although further investigation is needed, these results provide no evidence to support increased antepartum surveillance in such patients.

Urinary dipstick protein: a poor predictor of absent or severe proteinuria.

OBJECTIVE: Our purpose was to compare urinary protein dipstick values with standard 24-hour urinary protein excretion in women with hypertension in pregnancy. STUDY DESIGN: Urinary protein dipstick determinations and concurrent 24-hour urinary protein excretion measurements were compared by review of 300 urine samples obtained from women with hypertension in pregnancy. RESULTS: One hundred twenty-three samples had negative to trace protein on dipstick on two occasions at least 6 hours apart. Eight-one (66%) of these patients had significant proteinuria (> or = 300 mg per 24 hours). Seventy-six samples revealed 3+ to 4+ protein on dipstick in at least two samples. Of these, 27 (36%) had heavy proteinuria (> or = 5 gm per 24 hours), and 42 (55%) had nephrotic range proteinuria of > or = 3.5 gm per 24 hours. One hundred one patients had urine dipstick values of 1+ to 2+, of whom 89 (88%) had significant proteinuria. CONCLUSION: Urinary protein dipstick values > or = 1+ have a positive predictive value of 92% (162/177) for predicting > or = 300 mg per 24 hours. In contrast, a dipstick of negative to trace should not be used to rule out significant proteinuria because its negative predictive value is only 34% (42/123) in hypertensive patients. Moreover, urine dipstick values of 3+ to 4+ should not be used to diagnose severe preeclampsia because their positive predictive value is only 36% (27/76).

Adhesion formation associated with the use of absorbable staples in comparison to other types of peritoneal injury.

Adhesion formation was assessed after inducing peritoneal injury with absorbable staples, absorbable suture, surgical excision or thermal injury. In addition, adhesion formation was assessed in the presence of Hyskon. Absorbable staples were associated with increased adhesion formation when compared to the other methods of injury. Hyskon appears to significantly reduce the formation of peritoneal adhesions at sites of peritoneal suturing, excision, and thermal injury, but did not reduce adhesion formation in the area of stapling.

A histologic evaluation of peritoneal injury and repair: implications for adhesion formation.

A study of peritoneal healing after specific types of peritoneal injury was conducted in rabbits. Histologic specimens were examined at four, eight, 12, 24, and 48 hours, and at five, seven, and 14 days postperitoneal injury. Comparison of types of injury and attempts at peritoneal repair revealed differences in healing mechanisms. Histologic evidence of rapid reperitonealization was associated with those types of repair that involved minimal tissue necrosis and absence of foreign body reaction.

Cytological events associated with in vitro aged and fertilized rabbit eggs.

The morphogenetic events associated with rabbit eggs aged in vitro for 12 to 50 hours prior to mixing with sperm have been examined by light and electron microscopy. After 12 hours in culture, morphological alterations of the meiotic spindle and the cortex of unfertilized eggs were evident. By 24 to 50 hours in culture, unfertilized eggs contained subnuclei, structures which formed when individual and/or groups of meiotic chromosomes dispersed and becmae invested by a double-laminated structure reminiscent of a nuclear envelope. Although most eggs obtained 11.5 to 12 hours after induced ovulation and in vitro fertilized displayed morphogenetic patterns similar to those described for in vivo fertilized ova, some (10%) contained three pronuclei. Many eggs obtained 13 to 15 hours after induced ovulation and subsequently mixed with sperm in vitro appeared to undergo processes of fertilization typical of in vivo fertilized eggs, however, approximately 30% contained subnuclei in association with the male pronucleus. Few eggs (15%) aged 12 hours prior to in vitro fertilization displayed patterns of pronuclear development and association typical of fertilized unaged ova. Subnuclei developed in many of the fertilized ova. Supernumerary sperm nuclei, which did not develop into male pronuclei, were observed in some zygotes. Cleavage of eggs aged 12 hours prior to fertilization was abnormal or retarded. After 24 hours in culture approximately 16% of the eggs fertilized. Seventy percent of the fertilized eggs failed to support the development of a male or female pronucleus.