Assessment of fetal behavior and general movements by four-dimensional sonography

The aim of this paper was to review the clinical applications of four-dimensional ultrasonography in the assessment of fetal behavior. With the use of a computerized database, articles on three-dimensional ultrasonography were reviewed. Several applications of dynamic three-dimensional ultrasonography have been reported, including imaging of fetal movements, facial expression and fetal hand movements. The importance of the assessment of fetal behavior by four-dimensional sonography is stressed. Four-dimensional sonography seems to be a useful imaging tool for clinical problem solving in perinatology, especially in observing the development of the central nervous system in utero.     

Rapid diagnosis of glucocorticoid suppressible hyperaldosteronism in infants and adolescents

Glucocorticoid suppressible hyperaldosteronism (GSH) is an uncommon form of dominantly inherited hypertension. Presentation with hypertension and complications such as stroke in early life are well recognised. The use of a simple genetic test carried out on blood or placenta facilitates the detection of infants and children with GSH before the development of hypertension, allowing prompt treatment of hypertension if it occurs, and an opportunity to study the effects of growth and environmental influences on the progression of the condition.     

Patellofemoral joint: kinematic MR imaging to assess tracking abnormalities

The patellofemoral joint was imaged with magnetic resonance (MR) in the axial plane while the knee was positioned from 0 degrees to 32 degrees of flexion (nine positions). These multiple sequential images obtained within the early phases of flexion of the knee were viewed in a "cine-loop" format, producing a kinematic study that clearly demonstrated the relationship of the patella to the trochlear groove. Four healthy subjects and one patient with known bilateral subluxing patellae were studied. The preliminary results suggest that kinematic MR imaging of the patellofemoral joint is potentially useful for the evaluation of patellar tracking abnormalities.     

Some properties of marrow derived adherent cells in tissue culture

It has previously been shown that monolayer cultures derived adherent cells (MDAC), apparently consisting of fibroblasts, macrophages, epithelioid cells, and fat cells, can support long-term stem cell proliferation in vitro. In the present study, the hematopoietic support capability of murine MDAC monolayers was confirmed and the cultured cells further characterized with respect to the following properties: esterase I activity, complement (C3) receptors, IgG (Fc) receptors, colony stimulating activity (csa) production, and collagen synthesis. The cultures were also examined immunohistochemically to localize fibronectin, laminin, and collagen synthesis and to identify the collagen subtypes synthesized. MDAC morphology was as described in previous studies, although fat cells were few in number. It was found that MDAC included some cells with esterase I activity and C3 receptors. Fc receptors were not, however, detected, nor did the cultures produce csa, indicating that mononuclear phagocytes were not present. MDAC synthesized collagen types I and III and also fibronectin. Staining for epithelial basement membrane proteins (collagen types IV and V and laminin) was negative. The results indicate that the vast majority of these cultured MDAC were fibroblasts.     

Expanding the mutational spectrum of LZTR1 in schwannomatosis

Schwannomatosis is characterized by the development of multiple non-vestibular, non-intradermal schwannomas. Constitutional inactivating variants in two genes, SMARCB1 and, very recently, LZTR1, have been reported. We performed exome sequencing of 13 schwannomatosis patients from 11 families without SMARCB1 deleterious variants. We identified four individuals with heterozygous loss-of-function variants in LZTR1. Sequencing of the germline of 60 additional patients identified 18 additional heterozygous variants in LZTR1. We identified LZTR1 variants in 43% and 30% of familial (three of the seven families) and sporadic patients, respectively. In addition, we tested LZTR1 protein immunostaining in 22 tumors from nine unrelated patients with and without LZTR1 deleterious variants. Tumors from individuals with LZTR1 variants lost the protein expression in at least a subset of tumor cells, consistent with a tumor suppressor mechanism. In conclusion, our study demonstrates that molecular analysis of LZTR1 may contribute to the molecular characterization of schwannomatosis patients, in addition to NF2 mutational analysis and the detection of chromosome 22 losses in tumor tissue. It will be especially useful in differentiating schwannomatosis from mosaic Neurofibromatosis type 2 (NF2). However, the role of LZTR1 in the pathogenesis of schwannomatosis needs further elucidation.     

Suppression of apoptosis in hematopoietic factor-dependent progenitor cell lines by expression of the FAC gene

Fanconi anemia (FA) is a genetically heterogeneous, inherited blood disorder characterized by bone marrow failure, congenital malformations, and a predisposition to leukemias. Because FA cells are hypersensitive to DNA cross-linking agents and have chromosomal instability, FA has been viewed as a disorder of DNA repair. However, the exact cellular defect in FA cells has not been identified. Sequence analysis of the gene defective in group C patients (FAC) has shown no significant homologies to other known genes. The FAC protein has been localized to the cytoplasm, indicating that FAC may either play an indirect role in DNA repair or is involved in a different cellular pathway. Recent evidence has indicated that FA cells may be predisposed to apoptosis, especially after treatment with DNA cross-linking agents. The demonstration that genes can suppress apoptosis has been accomplished by overexpression of such genes in growth factor-dependent cell lines that die by apoptosis after factor withdrawal. Using retroviral-mediated gene transfer, we present evidence that expression of FAC in the hematopoietic factor-dependent progenitor cell lines 32D and MO7e can suppress apoptosis induced by growth factor withdrawal. Flow cytometry and morphologic analysis of propidium iodide stained cells showed significantly lower levels of apoptosis in FAC-retroviral transduced cells after growth factor deprivation. Expression of FAC in both cell lines promoted increased viability rather than proliferation, which is consistent with other apoptosis-inhibiting genes such as Bcl- 2. These findings imply that FAC may act as a mediator of an apoptotic pathway initiated by growth factor withdrawal. Furthermore, the congenital malformations and hematologic abnormalities characterizing FA may be related to an increased predisposition of FA progenitor cells to undergo apoptosis, particularly in the absence of extracellular signals.