Primary testicular and paratesticular tumors of childhood

Testicular and paratesticular neoplasms are uncommon tumors of childhood. Consequently, the experience gained with regard to their optimal management is limited in any given children's cancer centre. Here we review the classification, diagnosis, and staging of testicular and paratesticular neoplasms and subsequently discuss the more frequently occurring ones: germ cell tumors, gonadal stromal tumors, gonadoblastoma, tumors of the supporting tissue, lymphomas and leukemias, tumor-like lesions, secondary tumors, and tumors of the adnexa.     

The role of PET-FDG in questionable diagnosis of relapse in the presence of radionecrosis of brain tumors

INTRODUCTION: Although CT and MR are sensitive techniques for the detection of cerebral tumours, both have limitations in distinguishing between tumour relapse (TR) and post-treatment radionecrosis (RN). PATIENTS AND METHODS: In this study we have determined the usefulness of metabolic imaging with PET-FDG in such situations. We assessed 70 patients with CNS tumours (22 low grade astrocytomas, 25 high grade astrocytomas, 3 oligodendrogliomas, 13 metastatic tumours and 7 other tumours. All had been treated with radiotherapy and other treatments such as radiosurgery, chemotherapy or different types of surgery, and presented clinical pictures which made it necessary to decide the differential diagnosis of relapse or radionecrosis. RESULTS: In the PET-FDG study visual and semiquantitative analysis was done by SUV (Standardized Update Value). Confirmation of the findings was obtained in 44 cases (24 TR and 20 RN). MR was doubtful or inconclusive in most cases, whilst with PET correct diagnosis was made in all cases. CONCLUSIONS: Metabolic imaging with PET-FGD is better than anatomostructural imaging techniques for differential diagnosis between tumour relapse and radionecrosis in CNS tumours which have been treated. Prospective studies are necessary for evaluation of SUV as a factor for prognosis of survival.     

Identification of sorting determinants in the C-terminal cytoplasmic tails of the gamma-aminobutyric acid transporters GAT-2 and GAT-3

In order to perform their physiologic functions, polarized epithelial cells must target ion transport proteins to the appropriate domains of their plasma membranes. Molecular signals responsible for polarized sorting have been identified for several membrane proteins which span the bilayer once. Most ion transport proteins are polytopic, however, and little is known of the signals responsible for the targeting of this class of polypeptides. Members of the gamma-aminobutyric acid (GABA) transporter family are polytopic membrane proteins found endogenously in both epithelial cells and neurons. We have identified narrowly defined sequences which are required for the proper accumulation of two members of this transporter family in Madin-Darby canine kidney cells. The highly homologous GABA transporter isoforms, GAT-2 and GAT-3, localize to the basolateral and apical surfaces, respectively, when expressed stably in Madin-Darby canine kidney cells. We have generated deletion constructs and chimeric transporters composed of complimentary portions of GAT-2 and GAT-3. We find that information which directs their differential sorting is present in the C-terminal cytoplasmic tails of these two polypeptides. A sequence of 22 amino acids at the C terminus of GAT-2 is required for the transporter's basolateral distribution and is capable of directing GAT-3 to the basolateral surface when appended to the C terminus of this normally apical polypeptide. The deletion of 32 amino acids from the C terminus of GAT-3 causes this transporter to become mislocalized to both surfaces. Moreover, removal of the final three amino acids of GAT-3 (THF) similarly disrupts its apical sorting. The GAT-3 C-terminal sequence resembles motifs which interact with PDZ domains, raising the possibility that the steady state distribution of GAT-3 at the apical plasmalemmal surface requires a protein-protein interaction mediated by its extreme C-terminal cytoplasmic tail. These data provide the first characterization of a protein-based signal required for the apical distribution of a membrane protein.     

Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction

Opioid drugs play important roles in the clinical management of pain, as well as in the development and treatment of drug abuse. The mu opioid receptor is the primary site of action for the most commonly used opioids, including morphine, heroin, fentanyl, and methadone. By sequencing DNA from 113 former heroin addicts in methadone maintenance and 39 individuals with no history of drug or alcohol abuse or dependence, we have identified five different single-nucleotide polymorphisms (SNPs) in the coding region of the mu opioid receptor gene. The most prevalent SNP is a nucleotide substitution at position 118 (A118G), predicting an amino acid change at a putative N-glycosylation site. This SNP displays an allelic frequency of approximately 10% in our study population. Significant differences in allele distribution were observed among ethnic groups studied. The variant receptor resulting from the A118G SNP did not show altered binding affinities for most opioid peptides and alkaloids tested. However, the A118G variant receptor binds beta-endorphin, an endogenous opioid that activates the mu opioid receptor, approximately three times more tightly than the most common allelic form of the receptor. Furthermore, beta-endorphin is approximately three times more potent at the A118G variant receptor than at the most common allelic form in agonist-induced activation of G protein-coupled potassium channels. These results show that SNPs in the mu opioid receptor gene can alter binding and signal transduction in the resulting receptor and may have implications for normal physiology, therapeutics, and vulnerability to develop or protection from diverse diseases including the addictive diseases.     

Variability of clinical and pressure-flow study variables after 6 months of watchful waiting in patients with lower urinary tract symptoms and benign prostatic enlargement

PURPOSE: We quantified the physiological variability of clinical and pressure-flow study variables in patients with symptomatic benign prostatic enlargement. MATERIALS AND METHODS: Symptom scores were measured, and advanced urodynamic studies with pressure-flow analysis were performed in 178 patients before and 6 months after a period a watchful waiting. RESULTS: Patients without bladder outlet obstruction experienced significant symptomatic improvement. Symptoms in patients with obvious bladder outlet obstruction did not improve significantly. The reproducibility of mean pressure-flow variables was evident. However, there was an important intra-individual variability. Patients with obvious bladder outlet obstruction showed a significant decreases in detrusor pressure at maximal flow of 14cm. water, a significant decrease in the urethral resistance factor of 7 cm. water and a significant decrease of 1 obstruction class on the linear passive urethral resistance relation nomogram, indicating less severe bladder outlet obstruction. CONCLUSIONS: Mean differences among therapy groups must be regarded critically, especially when the difference are slight and possibly within physiological variability.     

Concurrent right diaphragmatic hernia and esophageal atresia

The occurrence of a coexisting congenital diaphragmatic hernia (CDH) and esophageal atresia (EA) with distal tracheoesophageal fistula is extremely rare and is considered highly lethal. Only 19 cases of CDH with EA have been reported in the world literature to date. This is a very challenging clinical problem, and the neonate is likely to deteriorate rapidly. Such a case is reported with a successful outcome, probably the first survivor with a right CDH and EA. Management guidelines for such a case are discussed.     

The role of glycoproteins gC, gE, gI, and gG in the induction of cell-mediated immune responses to bovine herpesvirus 1

Mutant viruses with deletions in genes encoding non-essential glycoproteins are considered as promising bovine herpesvirus 1 (BHV1) vaccine candidates. The present study compared the influence of various gene deletions (gC, gE, gI, gG) on the induction of cell-mediated immune responses against the virus. The highest BHV1 specific lymphoproliferative response was observed in the group of calves inoculated with the gC- mutant. However, in all groups of inoculated calves, limiting dilution analysis showed marked individual variability in the number of BHV1 specific T lymphocytes that were stimulated. The same animals were then challenged with wild-type BHV1. In these animals, limiting dilution analysis did not reveal gE, gI nor gG as a major T lymphocyte antigen. However, further analysis suggested the T cell antigenicity of gE in a low number of BHV1 hyperimmunized calves. Stimulation of MHC unrestricted cytotoxicity was also evaluated after inoculation with the various deletion mutants. Cytotoxicity in gC- inoculated calves was as high as in BHV1 inoculated calves. In conclusion, among the BHV1 deletion mutants that were tested, the gC- mutant stimulated the best cell-mediated immune responses.