Catalytic subunit of DNA-dependent protein kinase: impact on lymphocyte development and tumorigenesis

The DNA-dependent protein kinase (DNA-PK) consists of a heterodimer DNA-binding complex, Ku70 and Ku80, and a large catalytic subunit, DNA-PKcs. To examine the role of DNA-PKcs in lymphocyte development, radiation sensitivity, and tumorigenesis, we disrupted the mouse DNA-PKcs by homologous recombination. DNA-PKcs-null mice exhibit neither growth retardation nor a high frequency of T cell lymphoma development, but show severe immunodeficiency and radiation hypersensitivity. In contrast to the Ku70-/- and Ku80-/- phenotype, DNA-PKcs-null mice are blocked for V(D)J coding but not for signal-end joint formation. Furthermore, inactivation of DNA-PKcs leads to hyperplasia and dysplasia of the intestinal mucosa and production of aberrant crypt foci, suggesting a novel role of DNA-PKcs in tumor suppression.     

Effects of maternal antibodies on protection and development of antibody responses to human rotavirus in gnotobiotic pigs

Although maternal antibodies can protect against infectious disease in infancy, they can also suppress active immune responses. The effects of circulating maternal antibodies, with and without colostrum and milk antibodies, on passive protection and active immunity to human rotavirus (HRV) were examined in gnotobiotic pigs. Pigs received intraperitoneal injections of high-titer serum (immune pigs [groups 1 and 2]) from immunized sows, low-titer serum from naturally infected sows (control pigs [groups 3 and 4]), or no serum (group 5). Immune or control colostrum and milk were added to the diet of groups 2 and 4, respectively. After inoculation (3 to 5 days of age) and challenge (postinoculation day [PID] 21) with virulent HRV, the effects of maternal antibodies on protection (from diarrhea and virus shedding), and on active antibody responses (measured by quantitation of antibody-secreting cells [ASC] in intestinal and systemic lymphoid tissues by ELISPOT) were evaluated. Groups 1 and 2 had significantly less diarrhea and virus shedding after inoculation but higher rates of diarrhea and virus shedding after challenge than did groups 3 and 5. Group 1 and 2 pigs had significantly fewer immunoglobulin A (IgA) ASC in intestinal tissues at PID 21 and at postchallenge day (PCD) 7 compared to group 5. Significantly fewer IgG ASC were present in the intestines of group 2 pigs at PID 21 and PCD 7 compared to group 5. There was a trend towards fewer ASC in intestinal tissues of group 2 than group 1, from PID 21 on, with significantly fewer IgA ASC at PCD 7. IgG ASC in the duodenum and mesenteric lymph nodes of group 3 and 4 pigs were significantly fewer than in group 5 at PCD 7. These decreases in ASC emphasize the role of passive antibodies in impairing induction of ASC rather than in merely suppressing the function of differentiated B cells. To be successful, vaccines intended for populations with high titers of maternal antibodies (infants in developing countries) may require higher titers of virus, multiple doses, or improved delivery systems, such as the use of microencapsulation or immune stimulating complexes, to overcome the suppressive effects of maternal antibodies.     

Paradoxical reactions in children associated with midazolam use during endoscopy

All 2,617 children who received midazolam and meperidine for a variety of endoscopic procedures were monitored for the development of adverse behavioral problems. Thirty-six (1.4%) of the children (ages 1-17 years) experienced a paradoxical behavioral reaction, which consisted of inconsolable crying, combativeness, disorientation, dysphoria, tachycardia, agitation, and restlessness. The reaction occurred at a mean of 17 minutes after the administration of midazolam. Following treatment with flumazenil, the reaction dissipated within a mean of 14 minutes. Three of the 36 patients underwent additional endoscopic procedures utilizing only meperidine. No similar reaction was observed in these patients. Awareness of the reaction and prompt administration of flumazenil decreased the duration of the reaction.     

Results of conventional and hysteroscopic surgery

Müllerian anomalies usually come to medical attention when they become problematic and require treatment. Most of these complications require surgical correction. The most commonly presenting anomaly is the double uterus which can be the source of recurrent abortion and preterm deliveries. The Strassman, Jones and Tompkins metroplasties have been shown to greatly improve the rate of successful deliveries in these patients. Hysteroscopic metroplasty, using either scissors, resectoscope or laser is now the recommended treatment for most septate uteri due to its relative simplicity, low morbidity and excellent reproductive outcome.     

Modern approach to the diagnosis of osteomyelitis in children

Osteomyelitis in childhood is common and causes serious morbidity. X-rays and bone scans are the primary tools of radiological investigation. Other imaging techniques, including ultrasound, computed tomography, magnetic resonance imaging and white cell scintigraphy have a valuable role in difficult cases.