Liposomal amikacin: improved treatment of Mycobacterium avium complex infection in the beige mouse model

1. Binding of D,L-(E)-2-amino-4-[3H]-propyl-5-phosphono-3-pentenoic acid ([3H]-CGP 39653), a high affinity, selective antagonist at the glutamate site of the N-methyl-D-aspartate (NMDA) receptor, was investigated in rat brain by means of receptor binding and quantitative autoradiography techniques. 2. [3H]-CGP 39653 interacted with striatal and cerebellar membranes in a saturable manner and to a single binding site, with KD values of 15.5 nM and 10.0 nM and receptor binding densities (Bmax values) of 3.1 and 0.5 pmol mg-1 protein, respectively. These KD values were not significantly different from that previously reported in the cerebral cortex (10.7 nM). 3. Displacement analyses of [3H]-CGP 39653 in striatum and cerebellum, performed with L-glutamic acid, 3-((+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) and glycine showed a pharmacological profile similar to that reported in the cerebral cortex. L-Glutamic acid and CPP produced complete displacement of specific binding with Ki values not significantly different from the cerebral cortex. Glycine inhibited [3H]CGP 39653 binding with shallow, biphasic curves, characterized by a high and a low affinity component. Furthermore, glycine discriminated between these regions (P < 0.005, one-way ANOVA), since the apparent Ki of the high affinity component of the glycine inhibition curve (KiH) was significantly lower (Fisher's protected LSD) in the striatum than the cortex (33 nM and 104 nM, respectively). 4. Regional binding of [3H]-CGP 39653 to horizontal sections of rat brain revealed a heterogeneous distribution of binding sites, similar to that reported for other radiolabelled antagonists at the NMDA site (D-2-[3H]-amino-5-phosphonopentanoic acid ([3H]-D-AP5) and [3H]-CPP). High values of binding were detected in the hippocampal formation, cerebral cortex and thalamus, with low levels in striatum and cerebellum. 5. [3H]-CGP 39653 binding was inhibited by increasing concentrations of L-glutamic acid, CPP and glycine. L-Glutamic acid and CPP completely displaced specific binding in all regions tested, with similar IC50 values throughout. Similarly, glycine was able to inhibit the binding in all areas considered: 10 microM and 1 mM glycine reduced the binding to 80% and 65% of control (average between areas) respectively. The percentage of specific [3H]-CGP 39653 binding inhibited by 1 mM glycine varied among regions (P < 0.05, two-ways ANOVA). Multiple comparison, performed by Fisher's protected LSD method, showed that the inhibition was lower in striatum (72% of control), with respect to cortex (66% of control) and hippocampal formation (58% of control). 6. The inhibitory action of 10 microM glycine was reversed by 100 microM 7-chloro-kynurenic acid (7-CKA), a competitive antagonist of the glycine site of the NMDA receptor channel complex, in all areas tested. Moreover, reversal by 7-CKA was not the same in all regions (P < 0.05, two-ways ANOVA). In fact, in the presence of 10 microM glycine and 100 microM 7-KCA, specific [3H]-CGP 39653 binding in the striatum was 131% of control, which was significantly greater (Fisher's protected LSD) than binding in the hippocampus and the thalamus (104% and 112% of control, respectively). 7. These results demonstrate that [3H]-CGP 39653 binding can be inhibited by glycine in rat brain regions containing NMDA receptors; moreover, they suggest the existence of regionally distinct NMDA receptor subtypes with a different allosteric mechanism of [3H]-CGP 39653 binding modulation through the associated glycine site.     

Induction of complement-sensitivity in Leishmania amazonensis metacyclic promastigotes by protease treatment but not by specific antibodies

Acute appendicitis, particularly pelvic, may cause a suppurative process that spontaneously drains to the bladder and an appendicovesical fistula may result. The pelvic appendix and the bladder may occasionally become fused in an inflammatory and necrotic focus, directly creating a fistula. A case of vesicointestinal fistula secondary to appendiceal pelvic peritonitis is described and the cases reported in the literature are reviewed.     

Members of the G protein-coupled receptor kinase family that phosphorylate the beta2-adrenergic receptor facilitate sequestration

We recently reported that a beta2-adrenergic receptor (beta2AR) mutant, Y326A, defective in its ability to sequester in response to agonist stimulation was a poor substrate for G protein-coupled receptor kinase (GRK)-mediated phosphorylation; however, its ability to be phosphorylated and sequestered could be restored by overexpressing GRK2 [Ferguson et al. (1995) J. Biol. Chem. 270, 24782]. In the present report, we tested the ability of each of the known GRKs (GRK1-6) to phosphorylate and rescue the sequestration of the Y326A mutant in HEK-293 cells. We demonstrate that in addition to GRK2, GRK3-6 can phosphorylate the Y326A mutant and rescue its sequestration; however, GRK1 was totally ineffective in rescuing either the phosphorylation or the sequestration of the mutant receptor. We found that the agonist-dependent rescue of Y326A mutant phosphorylation by GRK2, -3, and -5 was associated with the agonist-dependent rescue of sequestration. In contrast, overexpression of GRK4 and -6 led mainly to agonist-independent phosphorylation of the Y326A mutant accompanied by increased basal receptor sequestration. Our results demonstrate that phosphorylation per se, but not the interaction with a specific GRK, is required to facilitate beta2AR sequestration.     

Feeding behaviour in chickens given diets containing medium chain triglyceride

This article discusses the importance of cultural sensitivity in providing nursing services to Native Americans. This necessitates general information about cultural universals that transcend specific tribes as well as cultural-specific knowledge. Cultural sensitivity also requires an understanding of the centuries-long oppression of Native Americans and their cultures by the dominant society.     

Temperature-dependent Raman investigation of rolled up InGaAs/GaAs microtubes

Large arrays of multifunctional rolled-up semiconductors can be mass-produced with precisely controlled size and composition, making them of great technological interest for micro- and nano-scale device fabrication. The microtube behavior at different temperatures is a key factor towards further engineering their functionality, as well as for characterizing strain, defects, and temperature-dependent properties of the structures. For this purpose, we probe optical phonons of GaAs/InGaAs rolled-up microtubes using Raman spectroscopy on defect-rich (faulty) and defect-free microtubes. The microtubes are fabricated by selectively etching an AlAs sacrificial layer in order to release the strained InGaAs/GaAs bilayer, all grown by molecular beam epitaxy. Pristine microtubes show homogeneity of the GaAs and InGaAs peak positions and intensities along the tube, which indicates a defect-free rolling up process, while for a cone-like microtube, a downward shift of the GaAs LO phonon peak along the cone is observed. Formation of other type of defects, including partially unfolded microtubes, can also be related to a high Raman intensity of the TO phonon in GaAs. We argue that the appearance of the TO phonon mode is a consequence of further relaxation of the selection rules due to the defects on the tubes, which makes this phonon useful for failure detection/prediction in such rolled up systems. In order to systematically characterize the temperature stability of the rolled up microtubes, Raman spectra were acquired as a function of sample temperature up to 300°C. The reversibility of the changes in the Raman spectra of the tubes within this temperature range is demonstrated.     

Tuberculosis meningitis in Hong Kong: experience in a regional hospital

Tuberculous meningitis (TBM) remains common in Hong Kong. From January 1996 to June 1997, 11 adult patients with TBM presented to Queen Mary Hospital, a regional hospital in Hong Kong. The annual incidence of TBM was estimated at 1.8 per 100,000 population. Nine patients were local Chinese, and only one patient had the acquired immune-deficiency syndrome (AIDS). In contrast to the classical presentation as a chronic indolent disease, our patients presented acutely: the mean duration from onset of symptoms to presentation was 4.8 days (range 0-10). The most common presenting symptoms were headache (64%), fever (46%), or both (36%), with focal deficits occurring in 64% of patients. Cerebrospinal fluid (CSF) culture and polymerase chain reaction (PCR) were positive in 30% and 29% of cases. Mean CSF cell count, protein and glucose levels were 340 x 10(6)/L, 267 mg/dL, and 2.3 mmol/L, respectively. Extra-neural tuberculosis occurred in 46% of cases. All patients survived and responded to treatment. Drug-induced hepatotoxicity was common; 64% of patients developed biochemical hepatitis.     

Antibody response against a Leishmania donovani amastigote-stage-specific protein in patients with visceral leishmaniasis

Shoots of higher plants grow upward in response to gravity. To elucidate the molecular mechanism of this response, we have isolated shoot gravitropism (sgr) mutants in Arabidopsis thaliana. In this report, we describe three novel mutants, sgr4-1, sgr5-1 and sgr6-1 whose inflorescence stems showed abnormal gravitropic responses as previously reported for sgr1, sgr2 and sgr3. These new sgr mutations were recessive and occurred at three independent genetic loci. The sgr4-1 mutant showed severe defect in gravitropism of both inflorescence stem and hypocotyl but were normal in root gravitropism as were sgr1 and sgr2. The sgr5-1 and sgr6-1 mutants showed reduced gravitropism only in inflorescence stems but normal in both hypocotyls and roots as sgr3. These results support the hypothesis that some mechanisms of gravitropism are genetically different in these three organs in A. thaliana. In addition, these mutants showed normal phototropic responses, suggesting that SGR4, SGR5 and SGR6 genes are specifically involved in gravity perception and/or gravity signal transduction for the shoot gravitropic response.     

Improvement of the cement mantle of the acetabular component with bone cement spacers. A retrospective analysis of 200 cemented cups

A discontinuous or thin cement mantle of a socket is associated with increased polyethylene wear and cement fractures. In a retrospective radiological analysis we examined the quality of the cement mantle in cups without (group I = 100 Charnley-Mueller cups) and with (group II = 100 Contemporary cups, Howmedica) bone cement spacers. Under-filling (0-2 mm) and over-filling (> 8 mm) of the cement mantle were noted and classified. Statistics show significantly less under-filling of the cement mantle in group II than in group I (P = 0.001), in particular when comparing separate cup regions (thirds: P < 0.001). Furthermore, there is no significant difference in the frequency of overfilling with cement between groups I and II (P = 0.108). To sum up, utilization of an acetabular component with performed bone cement spacers considerably improves the quality of the cement mantle without additional cost.     

An interstate outbreak of tick-borne relapsing fever among vacationers at a Rocky Mountain cabin

Clinical observation suggests that deformities of the foot and ankle are common in children with cerebral palsy. Two hundred children with cerebral palsy attending the Central Remedial Clinic were examined and photographed. The children had no previous surgical intervention and were between 1.5 and 19 years of age. Deformities were assessed and related to the type of cerebral palsy and mobility status.     

PHAS/4E-BPs as regulators of mRNA translation and cell proliferation

Insulin and growth factors elicit rapid increases in protein synthesis by stimulating mRNA translation. PHAS/4E-BPs, a recently discovered family of elF4E-binding, proteins, appear to play a key role in this process, as well as in the control of cell proliferation.