Renal vein renin analysis: Limitations of its use in predicting benefit from percutaneous angioplasty

Two hundred forty-four consecutive patients (mean age 61 years), including 123 who had technically valid renal vein renin (RVR) analysis and 121 without RVR data, underwent technically successful percutaneous renal artery angioplasty (PTRA). They were retrospectively examined to evaluate the utility of RVR analysis in identifying renal hypertension (RVH), predicting benefit from PTRA, and determining if the lack of knowledge of renin levels significantly affected clinical outcome after PTRA. Abnormal RVR values were associated with clinical benefit after PTRA in 62 of 93 patients (67% sensitivity, 20% specificity, 72% positive predictive value). Clinical improvement following PTRA occurred in 31 of 37 patients with normal pre-PTRA RVR values (16% negative predictive value). RVR analysis correctly identified 86 of 117 patients with renovascular hypertension (74% sensitivity, 16% negative predictive value). Improved blood pressure (BP) control occurred in 72% with abnormal RVR analysis and 66% of the 121 patients without RVR data (p>0.1). We conclude that the very low negative predictive value significantly limited the use of RVR analysis in this elderly (mean age 60 years) patient population with a high incidence of mild renal functional impairment (mean serum creatinine 1.4 mg/dl) and bilateral renal artery stenosis (38%). The lack of pre-PTRA renin data did not significantly affect clinical outcome. If RVR data were relied upon as the exclusive selection criterion in patients of this type, many would be prevented from having the benefit of cure or improvement by PTRA.     

Impaired spatial working and reference memory in segmental trisomy (Ts65Dn) mice

To evaluate the cognitive phenotype of the segmental trisomy 16 (Ts65Dn) mouse, a model of Down Syndrome (DS, trisomy 21), we assessed spatial working and reference memory using a 12-arm radial maze (RAM). Ts65Dn mice made a greater number of reference memory errors across trials compared to control mice. Both genotypes showed improvement across trials, although improvement was slower in Ts65Dn mice. Ts65Dn mice also made a greater number of working memory errors on the RAM, and in contrast to control mice, did not improve across trials, always performing at near-chance levels. These results provide evidence for both spatial working and reference memory deficits in Ts65Dn mice, characteristics of cognitive dysfunction.     

The effects of photoperiod on olfactory c-fos expression in prairie voles,Microtus ochrogaster

Reproduction stops among the majority of prairie voles (Microtus ochrogaster) during the winter. Short day lengths suppress male reproductive function dramatically in the laboratory, but photoperiod exerts only subtle effects on female reproductive function. Thus, the regulation of seasonal breeding in this species remains partially unspecified. In contrast to commonly studied rodents, female prairie voles do not undergo spontaneous estrous cycles; rather, they are induced into estrus by exposure to chemosignals expressed in conspecific male urine. In the present study, the hypothesis was tested that seasonal breeding among female prairie voles in the field reflects photoperiod-mediated changes in the responsiveness of the chemosensory system to male urine. Responsiveness was assessed by localizing the product of the c-fos immediate early gene with an immunocytochemical procedure. Female prairie voles were maintained in either long (LD 16:8) or short (LD 8:16) photoperiods from birth until adulthood, and exposed to either male urine or skim milk. Immunocytochemistry forfos protein revealed an increased number of immunoreactive cells within the accessory olfactory system of female prairie voles, including the accessory olfactory bulbs, granule cell layer, as well as the medial and cortical divisions of the amygdala 1 h after exposure to a single drop of urine as compared to individuals exposed to skim milk. The number of immunoreactivefos cells induced in females by conspecific male urine was also affected by photoperiod; short day females displayed fewer immunoreactivefos neurons in the accessory olfactory system as compared to long-day animal. Taken together, these results indicate that similar mechanisms underlie the responses of different rodent species to the chemosignals of conspecifics and that the pattern offos expression observed in the present study has functional significance for the regulation of reproduction in prairie voles.     

Two novel paradigms for the simultaneous assessment of conditioned taste aversion and food intake effects of anorexic agents

The conditioned taste aversion (CTA) is routinely used to assess the aversive consequences of anorexic agents, including potential pharmacological therapies for obesity. In a typical CTA paradigm, rats briefly sampling a novel tastant (e.g., saccharin) are acutely administered with toxin (e.g., lithium chloride, LiCl). After as few as one taste-toxin pairing, rats will reliably avoid the novel tastant. This paradigm is frequently used for the assessment of possible aversive consequences of drugs that are candidates for pharmacological therapies. The degree to which the drug supports development of a CTA is interpreted as an index of its aversive properties. Difficulties with previous work include the inability to assess affects on food intake and CTA simultaneously, particularly during chronic drug administration. We report here two novel CTA paradigms for the assessment of appetitive and aversive consequences of anorexic agents, simultaneously. In the first experiment, animals receive an intraoral infusion of a novel and highly palatable tastant immediately prior to administration of increasing doses of LiCl. In the second experiment, rats were implanted intraperitoneally with osmotic minipumps that chronically delivered a low dose of LiCl for 7 days. LiCl did not affect short or long term food intake in either experiment. However, LiCl did support the development of a CTA in both paradigms. These results suggest that both the appetitive and aversive consequences of anorexic agents can be assessed simultaneously during either acute or chronic drug administration.     

Prominent intrasinusoidal infiltration of the bone marrow by mantle cell lymphoma

Intrasinusoidal infiltration of bone marrow (BM) may accompany several malignant lymphoproliferative disorders. In small B-cell lymphomas, this pattern is considered specific for splenic marginal zone lymphoma (SMZL) when exclusive or prominent, although it may occur in other subtypes of non-Hodgkin's lymphomas (NHLs) as a minor feature. Here we report 2 cases of mantle cell lymphoma (MCL) with a prominent intrasinusoidal BM infiltration pattern. Both patients presented with massive splenomegaly and peripheral blood involvement characterized by markedly atypical lymphocytes, but no lymphadenopathy. The cytological features and the phenotype of the lymphoma cells were diagnostic of MCL. The malignant B cells showed coexpression of B-cell markers (CD20+ and CD79a+), CD5 antigen, and cyclin D1 by immunohistochemistry. We discuss the specificity of an intrasinusoidal growth pattern in the bone marrow, emphasizing the importance of using a broader immunohistochemical panel in the differential diagnosis of intrasinusoidal BM infiltration by NHL.     

Influence of Agonist, Shear Rate, and Perfusion Time on Nitric Oxide Inhibition of Platelet Deposition

Nitric oxide (NO) is a physiological species involved in inhibition of platelet adhesion and aggregation. A novel NO delivery device was utilized to quantitatively assess the effects of gaseous NO on platelet deposition to agonist-coated biomaterials in the presence of a platelet suspension. Platelet deposition was evaluated as a function of agonist (collagen, fibrinogen, or IgG), shear rate (250, 500, and 750 s^–1), and perfusion time (5, 7.5, and 15 min). The minimal aqueous surface NO concentrations and fluxes necessary for significant inhibition of platelet deposition were quantified. Platelet deposition was completely inhibited at a gaseous NO exposure of 0.1 ppm, irrespective of the platelet agonist, shear rate, and perfusion time. The corresponding aqueous surface NO concentration was 0.09 nM at 250 s^–1 as predicted by a validated model. Surface fluxes ranged between 0.3 and 0.6 femtomoles cm^–2 s^–1. The results of this study are useful for establishing generalized guidelines (i.e., NO flux requirements in the presence of agonists, shear rate, and perfusion time) for the design and development of suitable biomaterials incorporating NO to reduce platelet deposition. Further studies incorporating blood, rather than platelet suspensions, are required to provide a more complete assessment of the required NO flux necessary to inhibit platelet deposition. © 2000 Biomedical Engineering Society. PAC00: 8717-d, 8719Tt     

Effects of Lymphocyte Isolation and Timing of Processing on Detection of CD127 Expression on T Cells in Human Immunodeficiency Virus-Infected Patients

Decreases in the detection of CD127 expression on T cells of human immunodeficiency virus-infected patients by flow cytometry can occur by delayed processing or by peripheral blood mononuclear cell isolation and cryopreservation. These observations should be considered in the interpretation of functional studies and the planning of multicenter clinical trials.     

Uncovering novel inter- and intrachromosomal chromosome 1 aberrations in follicular lymphomas by using an innovative multicolor banding technique

Follicular lymphoma (FL) is characterized by t(14;18)(q32;q21), which is the initial genetic perturbation in this disease. Additional genetic mutations are required to generate a fully malignant phenotype. Secondary chromosomal alterations seen in FL include prominent involvement of chromosome 1 in the form of balanced or unbalanced translocations, insertions, deletions, and duplications involving both the p and q arms. We investigated a diagnostically well defined set of 55 t(14;18)-positive FL cases with complex karyotypes by means of multicolor karyotyping. Sixteen cases showed involvement of chromosome 1 and were analyzed in further detail by a novel multicolor banding technique for this chromosome. We defined three groups showing varying complexity of chromosome 1 alterations. The first group revealed simple translocations, such as t(1;2), t(1;6), t(1;8), and t(1;17), involving breakpoints on either the p or the q arm of chromosome 1. The second group showed more complex rearrangements with translocations, insertions, regional duplications, and involvement of more than one partner chromosome with either the p or the q arm of chromosome 1. The third group was defined by highly complex rearrangements involving translocations, regional duplications, amplifications, and intrachromosomal band relocations affecting the entire chromosome 1. All three groups shared interchromosomal rearrangements of chromosome 1 with chromosome 8, often involving the MYC protooncogene site, amplification involving region 1q21-q31, and deletion involving region 1p36. Thus, the use of sophisticated multicolor molecular cytogenetic assays in the investigation of malignant lymphoma allows precise characterization of chromosomal alterations and will provide a better understanding of their biology.