Nonsteroidal anti-inflammatory drugs and severe psychiatric side effects

In the systemic mucopolysaccharidoses (MPS) in animals, corneal clouding resulted from storage of glycosaminoglycans (GAG) in stromal keratocytes. The corneal epithelium was normal (MPS VI and VII) or minimally affected (MPS I), and stromal edema was not a feature even though the corneal endothelium demonstrated variable pathology. The MPS I (cat) cornea showed endothelial cells with large numbers of secondary lysosomal inclusions that were vacuolated or had a granular matrix. The endothelium was uniformly affected, but was not markedly hypertrophied. In contrast, the MPS VI (cat) cornea showed no endothelial cell disease. The MPS VII (dog) cornea had the most significant and dramatic endothelial pathology. The cells were massively hypertrophied and contained large numbers of vacuolated lysosomal inclusions. Regardless of the severity of the morphologic disease, the endothelial cells in these animal models functioned normally in maintaining the relative dehydration of the cornea. The corneal clouding was the result of storage in stromal keratocytes rather than corneal edema from endothelial dysfunction.     

Immunization of Aotus monkeys with recombinant Plasmodium falciparum hybrid proteins does not reproducibly result in protection from malaria infection

Plasmodium falciparum antigens SERP, HRPII, MSAI, and 41-3 have shown promise as vaccine components. This study aimed at reproducing and extending previous results using three hybrid molecules. Antibody responses were reproduced in Aotus monkeys, but solid protection from a P. falciparum blood-stage challenge that showed an unintendedly enhanced pathogenicity was not observed.     

Circulating iodide concentrations during and after pregnancy

Early, indirect studies suggested that an important aspect of thyroid economy during pregnancy was a decline in plasma or serum inorganic iodide (PII) concentrations, but there is little information concerning circulating iodide concentrations as assessed by direct measurement. The present study was undertaken to determine the relationship between gestation and serum iodide concentrations as assessed by direct measurement of PII. PII concentrations, urinary iodide levels, and other parameters of thyroid economy were measured during the first, second, and third trimesters and after delivery in 16 women. Mean serum T4 concentrations were significantly higher in all 3 trimesters than those after delivery. Serum free T4 index concentrations were significantly higher in the first trimester than during later periods of gestation or after delivery, but serum TSH concentrations were not depressed in the first trimester. Serum thyroglobulin concentrations were similar during pregnancy and after delivery. There was wide variability in PII and urinary iodide concentrations during and after pregnancy, but there was no trend for PII concentrations to be depressed during pregnancy. Pregnancy, at least in iodine-sufficient regions, does not have an important influence on circulating concentrations of iodide.     

Endothelial cell VE-cadherin functions as a receptor for the beta15-42 sequence of fibrin

The contact of fibrin with the apical surface of human umbilical vein endothelial cells (HUVEC) can induce capillary tube formation via the interaction of fibrin beta15-42 with a putative cell receptor (Chalupowicz, D. G., Chowdhury, Z. A., Bach, T. L., Barsigian, C., and Martinez, J. (1995) J. Cell Biol. 130, 207-215). To characterize this interaction, we studied the binding of the thrombin-cleaved N-terminal disulfide knot of fibrin (NDSK II), a dimeric fragment with exposed beta15-42, to HUVEC in three separate assay systems. Time-course binding of 125I-NDSK II to HUVEC monolayers or suspensions revealed that binding was specific at 50-60%, as determined by the addition of unlabeled NDSK II. Specific binding of 125I-NDSK II to HUVEC was 70% reversible by dilution or by competition, and was found to be divalent cation-independent. Binding plateaued after 10 min at a saturation of 15-20 nM. Scatchard analysis using the LIGAND computer program defined a single population of receptors with a KD of 7.7 +/- 1.6 nM and approximately 21,000 +/- 7000 binding sites/cell. N-terminal disulfide knot derivatives in which beta15-42 was absent (NDSK 325) or unexposed (NDSK, NDSK I) did not show specific binding. Specific binding of 125I-NDSK II could not be inhibited by RGDS or by antibodies to the alphavbeta3 or beta1 integrins, PECAM-1, ICAM-1, or N-cadherin. In contrast, a synthetic beta15-42/ovalbumin conjugate inhibited total 125I-NDSK II binding by 47 +/- 19% (corresponding to 95% of specific 125I-NDSK II bound) and a monoclonal antibody to vascular endothelial cadherin (VE-cadherin) inhibited binding by 35 +/- 8% (corresponding to 70% of specific 125I-NDSK II bound). Another assay was based on the capture of cadherins from HUVEC lysates by a polyclonal pan-cadherin antibody immobilized on plastic dishes. Binding of NDSK II to the captured cadherins was 89 +/- 5% specific, while specific binding of NDSK 325 and NDSK was negligible. An immortalized line of human adipose-derived microvascular endothelial cells, which express N-cadherin but not VE-cadherin, demonstrated no specific binding of NDSK II by the capture assay. These data define a novel interaction of fibrin with VE-cadherin, which is mediated by the fibrin N-terminal beta15-42 sequence, and may contribute to the mechanism through which fibrin induces angiogenesis.     

Antenatally detected urinary tract abnormalities: changing incidence and management

Contribution of two cases of renal adenocarcinoma in pediatric patients. Comments on the most updated and relevant aspects of epidemiology, clinical manifestations, diagnosis, treatment, prognosis and follow-up. Comparison to nephroblastoma and renal adenocarcinoma of the adult.     

The activity of the high-affinity K+ uptake system Kdp sensitizes cells of Escherichia coli to methylglyoxal

Expression of the Kdp system sensitizes cells to methylglyoxal (MG) whether this electrophile is added externally or is synthesized endogenously. The basis of this enhanced sensitivity is the maintenance of a higher cytoplasmic pH (pHi) in cells expressing Kdp. In such cells, MG elicits rapid cytoplasmic acidification via KefB and KefC, but the steady-state pHi attained is still too high to confer protection Lowering pHi further by incubation with acetate increases the sensitivity of cells to MG.     

Apoptosis of neutrophils

Cercarial behavior patterns were examined in 4 species of frog lung flukes (Haematoloechus spp.). Cercariae of Haematoloechus complexus, Haematoloechus medioplexus, Haematoloechus longiplexus, and Haematoloechus varioplexus were exposed to 3 species of experimental arthropods and an inanimate control. The number of cercariae attached to an experimental host at 5 min postexposure was recorded. Haematoloechus longiplexus and H. complexus cercariae attached to experimental hosts at higher rates than cercariae of H. medioplexus and H. varioplexus. Cercariae of H. longiplexus attached to experimental hosts in approximately the same numbers as H. complexus, but H. longiplexus penetrated only damselfly naiads, and only at the base of the zygopteran caudal gills. Cercariae of H. complexus, a second intermediate host generalist, were able to penetrate and enter several arthropod species at the intersegmental membranes. Haematoloechus medioplexus and H. varioplexus are restricted to development in dragonfly naiads and cercariae rarely attached to and never penetrated experimental hosts. These behavioral patterns dictate the range of hosts suitable for metacercarial development of H. complexus, H. longiplexus, H. medioplexus, and H. varioplexus. The evolution of disparate patterns of behavior among the cercariae of these 4 congeners has directly affected subsequent patterns of transmission to the definitive host.     

Head-related transfer functions of the barn owl: measurement and neural responses

Sounds arriving at the eardrum are filtered by the external ear and associated structures in a frequency and direction specific manner. When convolved with the appropriate filters and presented to human listeners through headphones, broadband noises can be precisely localized to the corresponding position outside of the head (reviewed in Blauert, 1997). Such a 'virtual auditory space' can be a potentially powerful tool for neurophysiological and behavioral work in other species as well. We are developing a virtual auditory space for the barn owl, Tyto alba, a highly successful auditory predator that has become a well-established model for hearing research. We recorded catalogues of head-related transfer functions (HRTFs) from the frontal hemisphere of 12 barn owls and compared virtual and free sound fields acoustically and by their evoked neuronal responses. The inner ca. 1 cm of the ear canal was found to contribute little to the directionality of the HRTFs. HRTFs were recorded by inserting probetube microphones to within about 1 or 2 mm of the eardrum. We recorded HRTFs at frequencies between 2 and 11 kHz, which includes the frequencies most useful to the owl for sound localization (3-9 kHz; Konishi, 1973). Spectra of virtual sounds were within +/- 1 dB of amplitude and +/- 10 degrees of phase of the spectra of free field sounds measured near to the eardrum. The spatial pattern of responses obtained from neurons in the inferior colliculus were almost indistinguishable in response to virtual and to free field stimulation.