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.     

Large scale identification of genes involved in cell surface biosynthesis and architecture in Saccharomyces cerevisiae

The sequenced yeast genome offers a unique resource for the analysis of eukaryotic cell function and enables genome-wide screens for genes involved in cellular processes. We have identified genes involved in cell surface assembly by screening transposon-mutagenized cells for altered sensitivity to calcofluor white, followed by supplementary screens to further characterize mutant phenotypes. The mutated genes were directly retrieved from genomic DNA and then matched uniquely to a gene in the yeast genome database. Eighty-two genes with apparent perturbation of the cell surface were identified, with mutations in 65 of them displaying at least one further cell surface phenotype in addition to their modified sensitivity to calcofluor. Fifty of these genes were previously known, 17 encoded proteins whose function could be anticipated through sequence homology or previously recognized phenotypes and 15 genes had no previously known phenotype.     

Introduction to the AFDC program. Aid to Families with Dependent Children

The NADYA Group, integrated in the Spanish Society of Parenteral and Enteral Nutrition (SENPE), and made up of professionals dedicated to Artificial Nutrition, and specifically, to Artificial Nutrition in the home, annually undertakes the task of collecting data on diagnosis, type of support, follow up characteristics, complications, and quality of life, of patients included in programs of at home artificial nutrition in Spain. In the Annual Register corresponding to 1994, 17 hospitality groups have participated, providing 369 patients with Home Enteral Nutrition, and 30 with Home Parenteral Nutrition. Home Enteral Nutrition is mainly applied in patients with neoplasias (36%) or neurological alterations (35%). The most commonly used access route in the nasogastric tube, although there is an observed increase in the application of Percutaneous Gastrostomies (21%) in relation to previous data of the Spanish population. There is an observed complications index of 0.07 episodes/patient-year, a mortality of 30% (neoplasias) and 20% (neurological alterations), and low rehabilitation indexes in this group. In Home Parenteral Nutrition, post-radiation enteritis, neoplasias, and mesenteric ischemia, are the main diagnostic groups. The majority of the patients have a tunneled tube (63%), with 37% using an implanted tube. With an index of hospitalizations of 0.83 hospitalizations/ patient-year, catheter septicemia justifies the majority of the re-hospitalizations derived from nutritional treatment (0.56 hospitalizations/patient-year), note the mortality of 37%. There are complete rehabilitations, continuing the previously normal activity in 80% of the cases.     

A novel role for murine IL-4 in vivo: induction of MUC5AC gene expression and mucin hypersecretion

Mucus hypersecretion and plugging of lower respiratory tract airways contributes to the morbidity and mortality associated with asthma. Interleukin (IL)-4 plays a putative role in some forms of asthma. Thus, transgenic mice that overexpress murine IL-4 selectively within the lung were used to study the effect of IL-4 on mucus glycoprotein gene expression and mucin release. Histologic examination of lung sections from IL-4 mice revealed that nonciliated epithelial cells from conducting airways were hypertrophic, due at least in part to the accumulation of mucus glycoprotein. The cytoplasm of these cells stained positively for glycoproteins using mucicarmine, alcian blue (AB), and periodic acid-Schiff (PAS). Ciliated cells were also enlarged but did not show any mucin-specific staining. Inclusion granules typically found in nonciliated (Clara) cells of control mice were absent in the IL-4 transgenic mice. Northern blot analysis of total RNA from lung tissue revealed that the expression of the MUC5AC, but not MUC2, mucin gene was distinctly upgraded in IL-4 transgenic mice compared to transgene-negative controls. In addition, a 5- to 10-fold increase in AB- and PAS-positive material was found in lavage fluid from IL-4 overexpressing mice compared to transgene-negative controls. Thus, the overexpression of IL-4 locally within the lung enhances mucus glycoprotein synthesis by altering gene expression, results in the accumulation of mucus glycoprotein in nonciliated epithelial cells, and induces the release of mucus into the airway lumen. We therefore hypothesize that the overproduction of mucus seen in some patients with asthma may be a direct result of the action of IL-4 within the inflamed lung.     

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.     

Recombinant proteins in newly developed foods: identification of allergenic activity

A number of agricultural crops are being modified for various purposes using recombinant DNA technology. Since transferred genes may code for proteins that are ordinarily not present, there is concern about the potential allergenicity of these new varieties. The safety evaluation of transgenic foods is relatively easy when the allergenicity of the gene source is known. Recombinant allergens in genetically engineered or altered foods can be identified using traditional immunological assays such as RAST or ELISA inhibition or immunoblotting procedures. Our recent studies of two corn proteins (10 kD and HSZ) used to alter grain amino acid composition and of transgenic soybeans with an altered fatty acid profile are examples of this approach. Both 10 kD and HSZ did not bind IgE antibodies from sera of corn-reactive subjects by immunoblotting. Studies of wild-type and transgenic soybeans with high oleic acidic content by RAST inhibition and immunoblotting with pooled sera of soy-allergic individuals demonstrated no difference in the allergen content of both extracts. In contrast to these studies, a recent investigation by Nordlee et al. (1996) of transgenic soybeans which expressed a methionine/cysteine-rich protein from Brazil nuts identified this protein as a major Brazil nut allergen. These studies indicate that, when the gene source is from a known allergen or if the recipient contains allergens, it is possible to determine whether the allergen content of the transgenic line is altered relative to the nontransgenic varieties.     

Couvelaire uterus

Uteroplacental apoplexy is a rare but nonfatal complication of severe forms of placental abruption. It occurs when vascular damage within the placenta causes hemorrhaging that progresses to and infiltrates the wall of the uterus. It is a syndrome that can only be diagnosed by direct visualization or biopsy (or both). For this reason, its occurrence is perhaps underreported and underestimated in the literature. The subject of this report is a 24-year-old pregnant woman who had a placental abruption an in whom classic uteroplacental apoplexy was diagnosed at the time of her cesarean section.