A nonrandom interneuronal pattern in the developing frog spinal cord

In the developing spinal cord of the frog, Xenopus laevis, a population of interneurons assumes a pattern that represents a previously undescribed level of organization. Glyoxylic acid treatment and immunocytochemistry show that the neurons contain catecholamines and their synthetic enzyme, tyrosine hydroxylase. Cells are located within the ependymal layer of the floor plate region of the larval spinal cord. The cells have several processes including a long one that projects toward the brain without fasciculating with other labeled processes. In addition, the cytoplasm of the catecholaminergic cells extends into the central canal, showing that they are a population of cerebrospinal fluid-contacting neurons. The spatial domain of catecholaminergic neurons starts abruptly at the boundary between the hindbrain and spinal cord and continues to the tip of the tail. The neurons occupy two longitudinal columns within the sheet of floor plate cells, which includes cells that do not exhibit the catecholaminergic phenotype. Unlabeled cells are intercalated between catecholaminergic cells in each column, giving the labeled cells the appearance of being spaced along the length of the spinal cord. This general arrangement is evident at the time of hatching. Spatial analysis showed that the position of cells along a column is not random. The nonrandom behavior is due to cells being excluded from the area immediately surrounding other catecholaminergic cells. Further analysis showed that the cellular pattern lacks segmental or other periodic repeats. Ultimately, the location of a cell within a column depends upon the position of its closest catecholaminergic neighbor. © 1993 Wiley-Liss, Inc.     

The potential of topoisomerase I inhibitors in the treatment of CNS malignancies: report of a synergistic effect between topotecan and radiation

Summary Despite innovations in imaging, surgery, and radiation therapy, local failure remains the principle clinical problem in most CNS malignancies. To date, chemotherapy has not made a major impact in the treatment of most adult CNS tumors. The inroads made by chemotherapy in pediatric CNS malignancies suggest that novel drugs, or drug combinations, may improve therapy. Topoisomerase I (Topo I) inhibitors are a relatively new group of chemotherapy drugs with a novel mechanism of action. Drugs in this group currently undergoing clinical trials are the Camptothecin analogues Topotecan, CPT-11, and 9-aminocamptothecin. There is substantial preclinical and some clinical evidence to suggest that these drugs could be useful in the treatment of CNS malignancies. Preclinical studies with the water soluble Topo I inhibitor, Topotecan, demonstrate antineoplastic activity in a variety of CNS malignancies. In addition, Topotecan has good CNS penetration in primates, and recent preliminary phase I and II clinical trials of Topotecan in pediatric and adult CNS malignancies have been promising. In this paper, we describe the unique mechanism of action, antineoplastic activity, and radiosensitizing properties of Topo I inhibitors. We present the first report demonstrating potentiation of radiation lethality by Topotecan in a human glioma (1354) cell line. The dose enhancement ratio was 3.2 at 10% survival. Thus, there is evidence to suggest that Topo I inhibitors may be beneficial in the treatment of CNS neoplasms on the basis of their antineoplastic activity alone, as well as their radiosensitizing effects. Two clinical trials which utilize concurrent Topotecan and radiation in the treatment of pediatric and adult CNS malignancies are discussed.     

Helical CT of calcaneal fractures: technique and imaging features

 Since the degree of comminution, fracture alignment, and articular congruity of intra-articular calcaneal fractures are important determinants in surgical treatment and patient prognosis, we review helical computed tomographic (CT) technique and features for detecting and assessing the extent of acute calcaneal fractures. Helical CT can be used to classify these fractures and facilitate the surgeon’s understanding of the anatomy and position of the fracture components in all orthogonal planes independently of the patient’s condition, foot placement in the CT gantry, or other injuries.     

Selective cytotoxicity associated with in vitro exposure of fresh rat renal fragments and continuous cell lines to atractyloside

The consumption of plants containing the diterpenoid atractyloside (ATR) causes selective proximal tubule injury, renal failure and death in humans. We have compared the effects of ATR in freshly isolated renal proximal tubules and glomeruli from rat and also in cell lines: NRK, derived from the proximal tubules, and MDBK and MDCK more closely representing the distal nephron. The effects of ATR (10– 500?μM) on proximal tubules and glomeruli were assessed by changes in lipid peroxidation, de novo protein synthesis and the leakage of alkaline phosphatase (ALP), lactate dehydrogenase (LDH), glutamate dehydrogenase (GDH) and N-acetyl-β-D-glucosaminidase (NAG). The susceptibility of NRK, MDBK and MDCK cell lines to ATR was assessed by the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, measuring mitochondrial reduction. Enzyme leakage was the most sensitive of the markers of cell injury in fresh fragments and ranked LDH>GDH>ALP>NAG in proximal tubules. As little as 20?μM ATR caused significant enzyme leakage from proximal tubules, but there were no increases in enzyme leakage from glomeruli at concentrations ?500?μM ATR. De novo protein synthesis was only inhibited 50% at ATR concentration >5?mM in the proximal tubules, but there were no effects in glomeruli. Malondialdehyde production was significantly elevated at 1?mM ATR for proximal tubules, and 500?μM for glomeruli. NRK cells were sensitive to ATR (IC₅₀, 120?μM), but MDBK or MDCK cells were unaffected by?1?mM of this diterpenoid. Both freshly isolated fragments and continuous cell lines representing the proximal tubules are more sensitive to ATR than either glomeruli or cells representing the distal nephron. These data also show that protein synthesis is a less specific and sensitive measure of ATR cytotoxicity than enzyme leakage in fragments. MTT reduction to formazan was the most sensitive in the NRK cell line. The low levels of lipid peroxidation products in proximal tubular fragments or sensitive renal cell lines at toxic levels of ATR suggest that oxidative injury is not a key mechanism.     

Heterotopic microvascular epiphyseal plate transplantation: A new model using the rabbit metatarsal

The purpose of this study is to develop a new vascularized epiphyseal plate model in the New Zealand White rabbit using a metatarsal epiphyseal plate having limited longitudinal growth potential. Such a model could be utilized in various experiments aimed at manipulating epiphyseal plate growth. The viability of the harvested live subject grafts was demonstrated with continued epiphyseal uptake during Tc99-MDP radionuclide bone scanning. The currently described models used in epiphyseal transplant research all involve long bone epiphyseal plates with significantly greater growth potential than the new metatarsal model. This new model therefore fills a void in the field by allowing investigators to transplant a growth plate with limited growth potential into any heterotopic site and study the effects of various hormonal and physical influences upon epiphyseal plate growth performance. © 1995 Wiley-Liss, Inc.     

Changes in depression during and following pregnancy

Summary. .Rates of depression were studied in a sample of over 9000 women who were participants in the Avon Longitudinal Study of Pregnancy and Childhood. Assessments of depression were made at 18 and 32 weeks gestation, and at 8 and 32 weeks postpartum. Changes in depressive status across time were modelled using latent Markov modelling methods. This analysis showed that when classification errors were taken into account there was relatively high stability in diagnostic status during pregnancy and after pregnancy. However, the transition from late pregnancy to the early postnatal period showed evidence of increased instability and remission of depression. The net effects of this were that rates of depression tended to decline following childbirth. The implications of these results for a series of issues including measurement errors in depression reports and the prevalence of depression before and after childbirth are discussed.