Nancy B. Genieser

Roles of uroplakins in plaque formation, umbrella cell enlargement, and urinary tract diseases.

The apical surface of mouse urothelium is covered by two-dimensional crystals (plaques) of uroplakin (UP) particles. To study uroplakin function, we ablated the mouse UPII gene. A comparison of the phenotypes of UPII- and UPIII-deficient mice yielded new insights into the mechanism of plaque formation and some fundamental features of urothelial differentiation. Although UPIII knockout yielded small plaques, UPII knockout abolished plaque formation, indicating that both uroplakin heterodimers (UPIa/II and UPIb/III or IIIb) are required for plaque assembly. Both knockouts had elevated UPIb gene expression, suggesting that this is a general response to defective plaque assembly. Both knockouts also had small superficial cells, suggesting that continued fusion of uroplakin-delivering vesicles with the apical surface may contribute to umbrella cell enlargement. Both knockouts experienced vesicoureteral reflux, hydronephrosis, renal dysfunction, and, in the offspring of some breeding pairs, renal failure and neonatal death. These results highlight the functional importance of uroplakins and establish uroplakin defects as a possible cause of major urinary tract anomalies and death.

Some physical parameters of young autistic children.

Abstract This paper provides information relevant to growth and development in a sample (N = 101) of young autistic children. Though birth weights of patients did not deviate from normative findings or from those of their own siblings, the distribution of heights between ages 2 and 7 years was significantly different from the normal population. Certain additional measures were available in a subgroup of patients: severity of illness and blood lead levels were negatively correlated with language DQ and IQ levels. A significant number had elevated T 3 and T 4 levels, and the latter were positively correlated with minor physical anomaly scores. These results are discussed as they relate to the concepts of biological age and hypothalamic dysfunction.

Interrupted aortic arch: diagnosis with gadolinium-enhanced 3D MRA.

PURPOSE Our goal was to describe the use of gadolinium-enhanced 3D MR angiography (MRA) in the diagnosis of interrupted aortic arch (IAA). METHOD A review of our MR data base from a 1 year period yielded three patients (1 day, 8 days, and 16 years old) with IAA. All were referred for evaluation of aortic arch abnormalities, only one of whom had suspected IAA. Patients were imaged at 1.5 T with a 3D spoiled gradient echo pulse sequence (TR/TE 3.8-8/1.3-2.7 ms) following the administration of intravenous gadolinium chelates. Surgical correlation was available in all cases. RESULTS In the patient with clinically suspected IAA, a previously unsuspected aberrant right subclavian artery was identified that was not seen on preoperative echocardiography. In another patient with a history of previous mediastinal surgery, IAA was diagnosed without concomitant cardiac anomalies, suggesting surgical ligation. In the remaining patient, IAA was detected as well as a patent truncus arteriosus. CONCLUSION Gadolinium-enhanced 3D MRA may provide for a rapid diagnosis of IAA that may not be possible with other noninvasive modalities. The rapid acquisition time enables unstable pediatric patients to spend minimal time in the MR suite.

Computed tomography of the pulmonary parenchyma. part 1: Distal air-space disease

Because of greatly enhanced contrast resolution and the advantages of cross-sectional visualization of lung anatomy, computed tomography (CT) has the potential to add significantly to the conceptualization of parenchymal lung disease. Although the value of CT has been well documented in the detection and characterization of lung nodules, the role of CT has been less clearly defined for other types of lung disease. This report describes the CT appearance of distal air-space disease. As demonstrated by the use of inflated and contrast-injected lungs obtained at autopsy, air-space disease is definable by the following: poorly marginated nodules ranging up to 1 cm in size; coalescence of nodules; air-bronchograms and air-alveolograms; ground-glass opacification; and distinct zonal patterns of distribution, including central and peripheral configurations. These patterns of air-space abnormalities are further refined by review of case material, including examples of air-space disease secondary to aspiration and primary intraalveolar disease, evaluated by the authors over a five-year period.

Hypertrophic Pulmonary Osteoarthropathy in Pulmonary Metastases

Hypertrophic pulmonary osteoarthropathy is most commonly encountered in association with bronchogenic carcinoma and tumors of the pleura. Its association with pulmonary metastases from extrathoracic neoplasms is rare, with only 44 documented cases in the literature. Three additional cases are reported. Nearly half of the reported cases have been sarcomas, mainly of bone and soft tissues; among the rest are tumors of the nasopharynx and uterus and cervix. It has recently been noted that symptoms can be dramatically relieved by intrathoracic or cervical vagotomy.

Monitoring of girls undergoing medical therapy for isosexual precocious puberty

We evaluated the use of sonography in monitoring the efficacy of suppressive therapy with a gonadotropin releasing hormone analogue in girls being treated for isosexual precocious puberty. Ten girls 5 to 9 years of age underwent serial sonography and hormonal stimulation tests on the same day. Sonographic trends of decreasing ovarian volume and uterine length indicated early suppression even when absolute values were above threshold. Changes in ovarian volume were the most sensitive predictor of pituitary‐gonadal suppression. Sonography is a sensitive and accurate method of monitoring medical therapy; ovarian volume and analysis of interval change are the most sensitive barometers of change.

Brain tumors in infants less than a year of age

A retrospective examination of brain tumors in infants less than a year of age was undertaken by reviewing their charts and CT scans. In contradistinction to brain tumors found in older children, most tumors were supratentorial in location. The most common histologic types included: astrocytoma, ganglioglioma and primative neuroectodermal tumors. Apart from their larger size at the time of presentation, these tumors were radiologically and pathologically similar to analogous tumors found in adults.

The syndrome of achalasia of the esophagus, ACTH insensitivity and alacrima

A 7-year-old male presented with a triple A syndrome, a tirad of ACTH insensitivity, achilasia and alacrima. His clinical course is followed and the literature reviewed.

Sonographic diagnosis of intramural duodenal hematoma.

Intramural duodenal hematoma, sometimes accompanied by retroperitoneal extension, is a frequent injury resulting from blunt abdominal trauma in childhood. In fact, it may be the first sign of child abuse identified in the young child. The typical appearance of this injury on upper gastrointestinal examination was described by Felson, 1 although its radiographic variability has been stressed more recently.2 We have encountered two cases of intramural duodenal hematoma diagnosed with sonography. In the appropriate clinical setting, this diagnosis may be made sonographically with specificity using state-of-the-art equipment and technique. Computerized tomography (CT} and barium meal (UGI} studies were done in these cases and the multimodality appearance of the injury is discussed.

Congenital pulmonary steal associated with Tetralogy of Fallot, right aortic arch and an isolated left carotid artery

In patients with Tetralogy of Fallot, collateral supply to the pulmonaryartery from systemic arterial sources is fequently encountered. However, collateral blood flow arising from the cerebral circulation has, to our knowledge, not been reported in this condition. We describe a patient with Tetralogy of Fallot in whom the left pulmonary artery filled directly via retrograde flow from the left carotid artery. Review of the literature in search of a similar case was unrevealing. A theoretical embryologic basis for this anomaly is discussed.