Partial duplication of 3q and distal deletion of 11q in a stillbirth with an omphalocele containing the liver, short limbs, and intrauterine growth retardation

We describe a female stillbirth with duplication of 3q21-->qter and deletion of 11q23-->qter resulting from an unbalanced segregation of a maternal t(3;11) reciprocal translocation. The proband had some of the clinical features consistent with those seen in patients with dup(3q) syndrome or distal del(11q) syndrome. Prenatal sonographic examination showed short limbs, intrauterine growth retardation, and an omphalocele containing the liver.     

Gastroesophageal reflux in infants and children

Gastrooesophageal reflux is a common clinical condition in infancy and childhood. Evaluation and treatment are indicated if it is associated with complications such as failure to thrive, oesophagitis or pulmonary symptoms. Depending on the clinical symptoms, investigations may include pH-monitoring, upper gastrointestinal series and endoscopy. Gastrooesophageal reflux may be treated by parental reassurance, dietary advice, positional treatment, prokinetic agents and acid secretion inhibitors. Surgery is rarely indicated.     

Crystal structure of human uroporphyrinogen decarboxylase

Uroporphyrinogen decarboxylase (URO-D) catalyzes the fifth step in the heme biosynthetic pathway, converting uroporphyrinogen to coproporphyrinogen by decarboxylating the four acetate side chains of the substrate. This activity is essential in all organisms, and subnormal activity of URO-D leads to the most common form of porphyria in humans, porphyria cutanea tarda (PCT). We have determined the crystal structure of recombinant human URO-D at 1.60 A resolution. The 40.8 kDa protein is comprised of a single domain containing a (beta/alpha)8-barrel with a deep active site cleft formed by loops at the C-terminal ends of the barrel strands. Many conserved residues cluster at this cleft, including the invariant side chains of Arg37, Arg41 and His339, which probably function in substrate binding, and Asp86, Tyr164 and Ser219, which may function in either binding or catalysis. URO-D is a dimer in solution (Kd = 0.1 microM), and this dimer also appears to be formed in the crystal. Assembly of the dimer juxtaposes the active site clefts of the monomers, suggesting a functionally important interaction between the catalytic centers.     

Homologous desensitization of the D1A dopamine receptor: efficacy in causing desensitization dissociates from both receptor occupancy and functional potency

The role of drug efficacy in agonist-induced desensitization was studied in C-6 glioma cells transfected with the monkey dopamine D1A (mD1A) receptor. Dopamine pretreatment for 2 hr produced greater than 80% loss of responsiveness in the stimulation of cAMP accumulation that was blocked by the D1 antagonist SCH23390. A series of full and partial D1 agonists from structurally dissimilar classes were then examined. Three full agonists (dihydrexidine, SKF82958, A77636) desensitized the receptor to the same extent as dopamine, whereas two other full agonists (dinapsoline and A68930) and all the partial agonists tested (SKF38393, pergolide and d-lysergic acid diethylamide tartrate) produced only partial desensitization (i.e., 50% that of dopamine). Whereas partial agonists (i.e., SKF38393, pergolide and d-lysergic acid diethylamide tartrate) caused no alteration in ligand-accessible mD1A receptors, four of the full agonists (dopamine, dihydrexidine, dinapsoline, A68930) caused a 30 to 40% reduction in receptor number. One full agonist, A77636, caused nearly an 80% decrease in receptor number, despite the fact that the degree of functional desensitization was similar to the other full agonists. The desensitization of the D1 receptor was homologous, not affecting beta-2 adrenergic receptors endogenous to C-6 cells. Neither incubation with cAMP analogs, nor inhibition of protein kinase A, affected dopamine-induced desensitization, suggesting a cAMP-independent mechanism in this cell line. Together, these data suggest that functional desensitization of the mD1A receptor expressed in C-6 glioma cells is a cAMP-independent mechanism, cannot be predicted reliably from agonist efficacy for stimulating adenylate cyclase and can occur in the absence of changes in receptor number.     

Kikuchi''s histiocytic necrotizing lymphadenitis associated with ruptured silicone breast implant

Mortality rates and injuries requiring medical treatment associated with sports and exercise are generally low. However, higher injury rates are reported for athletes and members of sports clubs. This study focuses on the sport- and exercise-related injury rate for various age and sex groups in the general population and how sport and exercise injury rates compare with those for other activities. The data presented are based on telephone interviews. Of the participants (N = 6,596), 335 (5.1%) reported having sustained an injury in the previous month; 46% of injuries among males and 14% of those among females were sport or exercise related. The data show a downward trend in sport- and exercise-related injury rates with increasing age. It is concluded that, as a proportion of all injuries sustained, the sport- and exercise-related injury rate is high, particularly among males. Possible future research on sport- and exercise-related injuries is discussed.     

Ultrasonographic detection of adrenal gland tumors in two ferrets

Hyperadrenocorticism is recognized as a common medical condition in middle- to old-aged ferrets. Because diagnosis of adrenocortical tumors in ferrets, using results of adrenocorticotropic hormone stimulation or dexamethasone suppression tests, is unreliable, ultrasonography was used as an alternative to laparotomy for the detection of tumors in 2 ferrets. The diagnosis was confirmed by surgical excision and histologic examination of the adrenal gland. In a typical manifestation of the condition, clinical signs in 1 ferret included vulvar swelling and serous to mucopurulent vaginal discharge, which resolved after the adrenalectomy.     

Changes in bone mass and bone biomarkers of cynomolgus monkeys during pregnancy and lactation

A substantial amount of calcium is transferred from the mother to the fetus and infant during pregnancy and lactation. Involvement of the skeleton in meeting this demand should be reflected in changes in bone mass and turnover. The purpose of the study was to determine the effects of pregnancy, lactation, and recovery on the skeleton in 43 young (prepeak bone mass) female monkeys. Whole body (WBBMC) and lumbar vertebrae 2-4 bone mineral content were determined by dual x-ray absorptiometry at baseline and 1, 4, and 10 months postpartum. Alkaline phosphatase, bone Gla protein, and urinary crosslinks were measured at baseline, during the third trimester, and 1, 4, and 10 months postpartum. Compared to nonpregnant, nonlactating monkeys, pregnant monkeys had similar rates of bone mass gain (nonpregnant, nonlactating WBBMC, 25+/-9 mg/day; pregnant WBBMC, 20+/-14 mg/day). Compared to pregnant monkeys, lactating females had increased bone turnover, as indicated by elevated bone biomarker levels (lactating alkaline phosphatase, 259+/-20 IU/L) and decreased bone mass (lactating WBBMC, -99+/-21 mg/day). Densitometry showed that bone mass gain in the lactating monkeys did not compensate for lactational loss by 10 months postpartum (WBBMC, 6.95+/-9 mg/day). This lack of recovery may have been due to the fact that serum estrogen concentrations were just beginning to return to baseline at 10 months postpartum. In conclusion, the cynomolgus monkey skeleton responds similarly to that of women during pregnancy and lactation. Recovery from lactational bone loss is not complete by 10 months postpartum.