Marked decrease of neuropeptide Y Y2 receptor binding sites in the hippocampus in murine prion disease

Using autoradiographic binding methodology with monoiodinated peptide YY together with the agonists neuropeptide Y (NPY) and NPY (13-36), as well as in situ hybridization with oligonucleotide probes complementary to the NPY Y2 receptor (Y2-R) mRNA, we have studied whether or not intracerebral prion inoculation affects Y2-Rs in male CD-1 mice. Monoiodinated peptide YY binding, mainly representing Y2-Rs, was down-regulated by 85% in the CA1 strata oriens and radiatum and by 50-65% in the CA3 stratum oriens 110-140 days postinoculation. In the CA3 stratum radiatum, where the mossy fibers from the dentate granule cells project, there was a significant decrease in PYY binding at 110-120 days. Y2-R mRNA, moderately expressed both in the CA1 and CA3 pyramidal cell layers and the granule cell layer in the dentate gyrus, showed a slight, but not significant, decrease in CA3 neurons 130 days postinoculation. The results indicate that the accumulation of the scrapie prion protein in the CA1-3 region strongly inhibits NPY binding at the Y2-Rs, which, however, is only marginally due to reduced Y2-R mRNA expression. The loss of the ability of NPY to bind to inhibitory Y2-Rs may cause dysfunction of hippocampal circuits and may contribute to the clinical symptoms in mouse scrapie.     

Endogenous glucose production following injury increases with age

To evaluate the influence of aging on the increase in endogenous glucose production that follows injury, we studied 22 fully resuscitated, clinically stable, previously healthy patients aged < or = 30 yr or > or = 60 yr admitted to hospital following injury, and 11 healthy volunteers in the same age groups. Endogenous glucose production was determined using a primed constant infusion of D-glucose-6,6-2d2. Urine cortisol and C-peptide were markedly higher in patients than volunteers (both P < 0.01), and urine C-peptide was lower in older than in younger patients (P < 0.05). Urine cortisol increased as a function of the interaction of age and Injury Severity Score (ISS) (r2 = 0.40, P < 0.001). Intracellular water was markedly lower and extracellular water greater in patients compared with volunteers (both P < 0.001), reflecting the loss of body cell mass and expansion of the extracellular space following injury. Endogenous glucose production (milligrams per minute per liter intracellular water) was best described as a function of ISS and age-ISS interaction (r2 = 0.35, all P < 0.05), and was increased 56% and 78% in younger and older patients, respectively, in comparison with the respective volunteer groups. Endogenous glucose production following injury increases in relation to the severity of injury and patient age. Greater cortisol elaboration and diminished insulin secretion in older patients may contribute to this age effect.     

Benign and malignant esophageal strictures: treatment with a polyurethane-covered retrievable expandable metallic stent

PURPOSE: To evaluate the clinical effectiveness of a polyurethane-covered, retrievable, self-expandable metallic stent and hook catheter in the treatment of esophageal strictures. MATERIALS AND METHODS: Stents were constructed of 0.4-mm stainless steel wire in a cylindric zig-zag configuration of six to nine bends. Four to eight stents were connected in tandem by dipping in a polyurethane solution. A nylon loop was hooked inside to each bend of the proximal portion of the stent and strung with a thread. Under fluoroscopic guidance, 22 stents were placed in 16 patients with a malignant stricture and five patients with a benign stricture. The stent was removed with a hook catheter 2 months after placement in patients with a benign stricture and when complications occurred in patients with a malignant stricture. All patients had dysphagia with ingestion of soft foods or liquids. RESULTS: Stent placement was technically successful and well tolerated in 20 patients. In one patient, the stent was misplaced but relocated successfully. After stent placement, all patients were able to ingest solid and/or soft foods without dysphagia. After stent removal, strictures showed improvement but recurred in two patients. CONCLUSION: Use of polyurethane-covered, retrievable expandable stents seems to be a feasible and effective method of treatment of benign and malignant esophageal strictures.     

Interactions of spatial frequency and unequal monocular contrasts in stereopsis

Increasing the contrast of just one eye's image degrades stereothresholds; this phenomenon is referred to as the stereo contrast paradox. In experiment one, this paradox was found to be absent in dynamic random-element stereograms; thresholds were simply limited by the lower of the two eyes' contrasts. In experiment two, in which narrowband Gabor targets were used, the paradox was found to be strongest at relatively low spatial frequencies (1 cycle deg-1). As spatial frequency was increased, the paradox gradually disappeared. At relatively high spatial frequencies (5 cycles deg-1), thresholds were generally limited by the lower of the two eyes' contrasts, as was found for the dynamic noise targets. These results demonstrate the interactions of spatial frequency and contrast in binocular image combination and yield clues as to the different roles which high and low spatial frequencies may play in stereopsis.     

Risk factors and outcome of human immunodeficiency virus-infected patients with sporadic multidrug-resistant tuberculosis in New York City

The discovery of neuroendocrine differentiation in hormone-refractory prostatic adenocarcinoma has opened a potentially new therapeutic approach in this group of patients with a poor prognosis and few effective therapy modalities. Based on previous findings of increased uptake of 11C-5-hydroxytryptophan (11C-5-HTP) in neuroendocrine tumours using the PET technique, this tracer was applied in the study of 10 patients with metastatic hormone-refractory prostatic adenocarcinoma. In three patients, the study was repeated after treatment. An increased uptake of 11C-5-HTP was observed in all investigated skeletal lesions, although the magnitude of the uptake was moderate. The difference between the standard uptake values (SUV) in normal bone and metastatic lesions was significant (p < 0.001). A kinetic analysis of the uptake of 11C-5-HTP demonstrates an increase during the first minutes followed by a wash-out and a stabilization of the tissue/blood ratio at about 2. The Patlak plots demonstrated a gradual increase in the transport rate during the first 20 to 30 min, after which a constant level was observed. The SUV varied between patients and between lesions over time and treatment. The uptake of 11C-5-HTP discriminates metastatic lesions from normal bone and may thus aid in the diagnosis and, potentially, in treatment monitoring of metastatic hormone-refractory prostatic adenocarcinoma. Uptake kinetics are characterized by a wash-out and cannot alone be used as proof of neuroendocrine differentiation in hormone-refractory prostatic adenocarcinoma.     

Oligoaniline intermediates in the aniline-peroxydisulfate system

Chemical oxidative polymerization of aniline using peroxydisulfate oxidant in aqueous pH 2.5–10.0 buffers yields electrically insulating brown powders that are believed to be mixtures of Michael-type adducts of benzoquinone monoimine and aniline at various stages of hydrolysis. A spectroscopically similar product is formed when solid 1,4-benzoquinone is added to an aqueous solution of aniline at room temperature in the absence of peroxydisulfate. This suggests that the peroxydisulfate oxidant in the aniline/S₂O₈^2? system provides a pathway for the formation of benzoquinone monoimine as an intermediate. Benzoquinone monoimine intermediate could be formed as a result of a Boyland–Sims rearrangement of aniline proceeding via the intermediacy of p-aminophenyl sulfate. Benzoquinone monoimine undergoes a series of conjugate 1,4-Michael-type addition/reoxidation/coupling steps with aniline or p-aminophenyl sulfate yielding the oligoaniline product. The precipitate that is isolated is also in the midst of two simultaneous pH dependent hydrolysis reactions: (i) hydrolysis of the imine groups to quinone, and (ii) hydrolysis of arylsulfates to phenols. The ratio of hydrolysis in each case was determined by the C/N ratio and sulfur elemental analysis values yielding analytical data that is consistent with experimentally determined values and also with our proposed reaction scheme. These findings offer a rationale for the high C/N ratios (>6.0) frequently observed in these systems while tracing the genesis of the residual sulfur in the product to unhydrolyzed arylsulfate. The oligoaniline product has previously been reported to have a novel poly-aza structure consisting of continuously linked –N–N–N– bonds, and alternately also reported to consist of phenazine-type linkages. This study is consistent with the latter and describes a pathway to phenazine coupling through a second and third stage hydrolysis of the arylsulfate and reoxidation with peroxydisulfate. There is no pathway for the formation of linear –N–N–N– linkages in the aniline/benzoquinone adduct and the striking similarity between its spectroscopic properties and the aniline/S₂O₈^2? adduct suggests that it is not a preferred pathway under these experimental conditions.