Tissue specific expression of FMR-1 provides evidence for a functional role in fragile X syndrome

Prostaglandin E2 levels in isolated rat islets were increased from 64 +/- 11 pg/30 islets when incubated in medium containing 2 mM glucose to 115 +/- 9 pg/30 islets in medium containing 20 mM glucose. In contrast, glyceraldehyde (10 mM) reduced prostaglandin E2 levels to 29 +/- 6 pg/30 islets. Inhibition of glucose metabolism by mannoheptulose (10 mM) abolished the stimulatory effect of glucose on prostaglandin E2 levels and inhibited glucose-induced insulin release. The cyclooxygenase inhibitor, flurbiprofen (20 microM), did not affect insulin release caused by glucose or glyceraldehyde. In the presence of 1 mg/ml bovine serum albumin, insulin secretion induced by 20 mM glucose (6.9 +/- 1.1% of islet insulin content) was reduced by the lipoxygenase inhibitor BW755 C (20 microM) to 3.1 +/- 0.6%, and by the phospholipase A2 inhibitor, p-bromophenacyl bromide (10 microM), to 2.1 +/- 0.8%. In the absence of bovine serum albumin the inhibitory action of BW755 C and p-bromophenacyl bromide on glucose-induced insulin release was significantly more pronounced. These drugs whether in the presence or absence of bovine serum albumin, did not affect glyceraldehyde-stimulated insulin secretion. Glyceraldehyde (10 mM), potentiated glucose-induced insulin release in the presence of 2-8 mM glucose, but not for 10-20 mM glucose. Although the phospholipase A2 activator, melittin, initiated insulin release in the presence of 2 mM glucose and enhanced 10 mM glyceraldehyde-stimulated insulin secretion it had no effect on 20 mM glucose-induced insulin release. These two stimulatory effects of melittin on insulin release were totally abolished by p-bromophenacyl bromide.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy of surgical treatment in traumatic central cord syndrome

BACKGROUND: Controversy surrounds the treatment of traumatic central cord syndrome (TCCS), as there are strong advocates for nonsurgical treatment for most patients. However, conservative treatment has been shown to yield a longer period of discomfort from pain and weakness in certain cases. METHODS: In a retrospective review of 114 patients presenting with acute or chronic TCCS from 1988-94, four different age groups were separately observed under different treatments. Motor and sensory recovery were assessed. RESULTS: Better results were achieved in younger patients, with or without radiographic abnormalities, and in patients with clinically correlated encroaching cord lesions who received early surgical decompression. CONCLUSIONS: Surgical intervention for TCCS must be addressed with careful clinical and radiographic survey. Removal of offending lesions in the subacute period results in significant motor and sensory improvement in short-term and long-term follow-up.     

Generation of high-frequency oscillations in local circuits of rat somatosensory cortex cultures

1. Rhythmic cortical activity was investigated with intracellular recordings in cortex-striatum-mesencephalon organotypic cultures grown for 42 +/- 3 (SE) days in vitro. 2. Electrical stimulation of supragranular layers induced a self-sustained high-frequency oscillation (HFO) in pyramidal neurons and interneurons. 3. The HFO started 197 +/- 39 ms after stimulation and had a mean duration of 1.0 +/- 0.2 s and an initial frequency of 38 +/- 2 Hz. A decrease in frequency at a rate of 11.5 +/- 2.7 Hz/s started on average 547 +/- 109 ms after the onset of the HFO. 4. During the HFO, local interneurons and pyramidal neurons synchronized their activities. The synaptic origin of the HFO was confirmed by its reversal potential at -57 +/- 4 mV. 5. These results suggest that a self-maintained HFO can be induced in local cortical circuits by excitation of supragranular layers. This HFO would facilitate synchronization between distant cortical and thalamic regions.     

Multifocal primary neuroblastoma

The purpose of this study is to present three patients with multifocal primary neuroblastoma, to review the literature, and describe the radiographic findings. SUBJECTS AND METHODS: Three children with multifocal neuroblastoma have been identified. The case histories and imaging findings in these patients are reviewed. RESULTS: Two children had synchronous and one child had metachronous multifocal primary neuroblastoma. The primary tumors were both in the abdomen in one patient, both in the chest in another patient, and in the chest and abdomen in the third patient. Evidence for multifocal origin of these tumors, rather than metastatic spread, is presented. CONCLUSION: Multifocal primary neuroblastomas can occur. The tumors maybe synchronous or metachronous. Awareness of this disorder may prevent errors in diagnosis and staging. Although not identified in our patients there is a strong familial incidence of neuroblastomas in those patients with multifocal tumors.     

Modern electronic and chemical thermometers used in the axilla are inaccurate

Rectal and axillary temperatures were measured simultaneously in 83 children using three different thermometer devices providing 166 pairs of results. In the first series consisting of 22 febrile children (44 measurements) and 20 afebrile children (40 measurements), the rectal mercury measurement was compared to an axillary mercury and axillary Tempa-DOT thermometer. The axillary mercury had sensitivity of 14/22 (64%) and specificity of 20/20 (100%) while the Tempa-DOT had sensitivity of 15/22 (68%) and specificity of 19/20 (95%). In the second series comprising 21 febrile children (42 measurements) and 20 afebrile children (40 measurements) the axillary mercury had sensitivity of 11/21 (52%) and specificity of 20/20 (100%) while the electronic thermometer had sensitivity of 10/21 (48%) and specificity of 20/20 (100%). Regardless of the thermometer used, the axilla is a poor alternative to rectal measurements in the diagnosis of fever. CONCLUSION: Mercury-free thermometers, when used in the axilla are as poor alternatives to rectal measurements as mercury-in-glass thermometers.     

Structure of very early protein folding intermediates: new insights through a variant of hydrogen exchange labelling

BACKGROUND: Hydrogen exchange labelling has been a key method in characterizing the structure of transient folding intermediates. In studies of several proteins, however, there has been clear spectroscopic evidence for partial folding of some kind at very early times, before any protection from exchange was measurable. These results, presumably a consequence of limited stability of specific backbone interactions, have made it difficult to assess the extent of native-like folding in the very early intermediates. We have used a variant of the labelling method to investigate marginally stable structures formed within the first few milliseconds of refolding of two such proteins, hen lysozyme and ubiquitin. RESULTS: In lysozyme, population of a subset of native-like secondary structures on this timescale is revealed, thus reconciling the exchange behaviour with circular dichroism measurements and confirming the significance of the rapidly formed embryonic structure as a foundation for the subsequent folding pathway. In the case of ubiquitin, by contrast, no significantly protective structure was detectable, suggesting that here secondary structural elements can be populated only marginally ahead of the major cooperative folding event; this was also supported by stopped-flow circular dichroism measurements. CONCLUSIONS: The hydrogen exchange approach can be extended to probe the formation of native-like structure formed in very early folding intermediates, even when the stability of specific interactions is marginal. In the case of lysozyme, this has provided a new window on an early stage of organization of the alpha-helical domain.     

Crystal structures of Escherichia coli and Salmonella typhimurium 3-isopropylmalate dehydrogenase and comparison with their thermophilic counterpart from Thermus thermophilus

The basis of protein stability has been investigated by the structural comparison of themophilic enzymes with their mesophilic counterparts. A number of characteristics have been found that can contribute to the stabilization of thermophilic proteins, but no one is uniquely capable of imparting thermostability. The crystal structure of 3-isopropylmalate dehydrogenase (IPMDH) from the mesophiles Escherichia coli and Salmonella typhimurium have been determined by the method of molecular replacement using the known structure of the homologous Thermus thermophilus enzyme. The structure of the E. coli enzyme was refined at a resolution of 2.1 A to an R-factor of 17.3%, that of the S. typhimurium enzyme at 1.7 A resolution to an R-factor of 19.8%. The three structures were compared to elucidate the basis of the higher thermostability of the T. thermophilus enzyme. A mutant that created a cavity in the hydrophobic core of the thermophilic enzyme was designed to investigate the importance of packing density for thermostability. The structure of this mutant was analyzed. The main stabilizing features in the thermophilic enzyme are an increased number of salt bridges, additional hydrogen bonds, a proportionately larger and more hydrophobic subunit interface, shortened N and C termini and a larger number of proline residues. The mutation in the hydrophobic core of T. thermophilus IPMDH resulted in a cavity of 32 A3, but no significant effect on the activity and thermostability of the mutant was observed.