Non-surgical treatment of abdominal aortic aneurysms

Percutaneous placement of an endovascular stent, with and without coils, in the treatment of large AAA in animal models is feasible, safe and effective. The covered stent sealed off AAA immediately after stent placement, however, it interrupted blood flow into arteries in the area covered by the stent. The uncovered stent prevented further expansion of the aneurysm and also significantly decreased the incidence of rupture. The long-term patency of branch arteries by the uncovered stent supported the possibility of safely using this approach in humans. Furthermore, either covered stent or uncovered stent with additional coils have the potential for treatment of acute aneurysm rupture or leaking. Most importantly, the aneurysm lumen in our model was gradually replaced by collagen after stent placement which further reduces the risk of aneurysm rupture: and this healing process was enhanced by the addition of coils. If proven safe and effective for humans as well, this technique has the potential for substantially reducing the morbidity and mortality associated with AAA.     

Flow cytometric analysis of basophil numbers in chronic urticaria: basopenia is related to serum histamine releasing activity

BACKGROUND: Peripheral blood basophils are reduced in some chronic urticaria patients when counted with granule stains. Approximately 30% of patients with severe chronic urticaria have functional autoantibodies which release histamine from healthy donor basophils in vitro but the relationship between basophil numbers in vivo and serum histamine releasing activity has not been studied. OBJECTIVE: To determine the relationship between basophil numbers and serum basophil histamine releasing activity and to assess whether basophils are present, but undetectable, in peripheral blood with granule stains by using a new flow cytometric method based on surface immunophenotype. METHODS: Basophils were counted manually by a chamber method using a granule stain and by flow cytometry using dual staining with anti-IgE and anti-Fc epsilonRI in 25 chronic idiopathic urticaria patients and 25 healthy controls. Serum histamine releasing activity was assessed on healthy donor basophils in vitro and by the weal response to autologous serum skin testing in vivo (patients only). RESULTS: Basophils were significantly reduced in chronic urticaria by manual counting and flow cytometry. A subgroup of seven patients with in vitro histamine releasing activity showed a marked reduction or absence of basophils by both methods. There were no obvious distinguishing clinical characteristics between these patients and the others; six of them showed positive autologous serum skin-test responses. On comparing the two methods, the manual basophil counts were generally lower than flow cytometric counts. Agreement over the full range of values was not strong and therefore counts obtained by the two methods are not directly interchangeable. CONCLUSION: Basopenia in chronic idiopathic urticaria is associated with serum basophil histamine releasing activity in a subgroup of patients. The lack of granule and surface immunophenotype staining suggests a reduction in numbers rather than an inability to detect circulating degranulated cells by conventional counting methods.     

Fluorometric determination of acid phosphatase in cooked, boneless, nonbreaded broiler breast and thigh meat

This method is applicable for determining activity of acid phosphatase (ACP), a heat-labile enzyme, in cooked, boneless, nonbreaded broiler marinated (83.65% meat) and nonmarinated (100% meat) breast and thigh and in a 50:50 blend of breast and thigh meat. The assay uses a self-indicating substrate that, when acted upon by ACP, loses a phosphate radical and becomes a highly fluorescent compound. Cooked meat is added to deionized distilled water in a 1:3 ratio, blended with a hand-held homogenizer, and then centrifuged at 2500 relative centrifugal force for 5 min. ACP activity in the filtrate is measured after shaking on a Vortex mixer 75 microL of the extract with a pH 5.00 acetate buffer containing a nonfluorescent aromatic monophosphoric ester substrate. The rate of fluorophore formation is monitored during a 3 min incubation period (38 degrees C) in a fluorometer, and ACP enzyme activity (mU/kg sample) is calculated. Three laboratories analyzed 6 cooked poultry products (marinated and nonmarinated breast, thigh, and 50:50 breast/thigh blend). Five cooking temperatures were used to generate different ACP activity levels, which were replicated twice with duplicate samples and duplicate sample tests representing 720 data points. Log10 ACP activity (mU/kg sample) performance repeatability and reproducibility standard deviations (sr and sR) and relative standard deviations (RSDr and RSDR) over 5 cooking treatments for 6 products were as follows: marinated breast: sr = 0.02, sR = 0.08, RSDr = 0.60%, RSDR = 2.12%; nonmarinated breast: sr = 0.02, sR = 0.04, RSDr = 0.66%, RSDR = 1.29%; marinated thigh: sr = 0.01, = 0.01, RSDr = 0.37%, RSDR = 0.37%; nonmarinated thigh: sr = 0.02, sR = 0.05, RSDr = 0.53%, RSDR = 1.43%; marinated 50:50 breast/thigh blend: sr = 0.01, sR = 0.05, RSDr = 0.36%, RSDR = 1.31%; nonmarinated 50:50 breast/thigh blend: sr = 0.01, sR = 0.04, RSDr = 0.32%, RSDR = 1.12%.     

Urolithiasis in dogs. II: Breed prevalence, and interrelations of breed, sex, age, and mineral composition

OBJECTIVE: To analyze selected breed-related data for canine urinary calculi. SAMPLE POPULATION: 11,000 specimens: 5,781 from female dogs, 5,215 from males, and 4 from dogs of unrecorded sex. PROCEDURE: Information was compiled for all canine urinary calculi submitted between July 1981 and January 1994. Results for a mixed-breed group and 26 of the most common breeds of stone-forming dogs were analyzed. Interrelations of breed, sex, and age of affected dogs and mineral composition of the specimens were determined. RESULTS: Prevalence of 5 specific mineral types was significantly correlated between the sexes of 27 common breed groups: struvite, calcium phosphate (apatite), calcium oxalate, brushite, and urate. Struvite-containing calculi were seen in high proportions in both sexes of 7 breeds, and in low proportions in both sexes of 7 other breeds. Male and female Lhasa Apsos, Cairn Terriers, and 5 other breeds had high proportions of oxalate-containing calculi; values in males were substantially higher. Low numbers of oxalate-containing calculi were seen in both sexes of 7 breeds; Dalmatians had the lowest numbers. Males and females of 6 breeds had high numbers of urate-containing calculi, Dalmatians and English Bulldogs had the highest numbers. Low amounts of urate were found in calculi from males and females of 6 breeds, Samoyeds had the lowest numbers. Highest proportions of cystine-containing calculi were seen in male Dachshunds, English Bulldogs, and Chihuahuas. Males of 8 breeds had no specimens that contained cystine; only 2 such specimens were obtained from females. CONCLUSIONS: Prevalence of uroliths differs among breed, age, and sex of affected dogs. CLINICAL RELEVANCE: Breed, sex, and age of dogs; mineral types of calculi in males versus females; and their anatomic location within the tract are important considerations for clinicians when evaluating risk in dogs with urolithiasis and in identifying areas that need further in-depth applied or clinical investigation, or both.     

Comparison of acceleration subjects to other populations: spinal anomaly distribution

Prior studies demonstrate an inconsistent relationship between occupational inorganic lead exposure and simple reaction time (SRT) performance. In this study, we administered a computerized SRT test to 78 currently employed lead smelter workers and then investigated the relationship between different measures of blood lead and components of SRT performance. The measures of blood lead included current blood lead (PbB) and mathematically derived blood lead fractions from the environment (PbB-env) and from bone (PbB-bn). Measures of SRT performance, obtained from 44 trials with interstimulus intervals (ISIs) ranging from 1 to 10 seconds, included median SRT (SRT-md), mean SRT for ISIs between 1 and 5 seconds (SRT-1-5), and mean SRT for ISIs between 6 and 10 seconds (SRT-6-10). Multiple regression analysis after adjustment for age and education revealed a curvilinear relationship between PbB and SRT-md. As PbB increased from 0 to 30 micrograms dl-1, SRT-md decreased, and only with PbB levels above 30 micrograms dl-1 did SRT-md increase. PbB terms accounted for 13.7% of the variance in this SRT measure (P < 0.01). The longer ISI variable, SRT-6-10, was found to be more strongly related to PbB, to have lesser variability across ISIs, and to be unrelated to age. Additional multiple regression analysis to examine the relationship between components of SRT and the PbB fractions, PbB-env and PbB-bn, showed only PbB-env to account for significant variance in SRT-md, (14.4%, P < 0.01), SRT-1-5 (9.7%, P < 0.03), and SRT-1-6 (15%, P < 0.01). We conclude that the relationship between PbB and SRT is U-shaped, that the SRT measure SRT-6-10 has properties that make it the preferred measure of SRT performance in future studies, and finally that only PbB-env, and not PbB-bn, is related to components of SRT.     

Purification of the lysosomal sialic acid transporter. Functional characteristics of a monocarboxylate transporter

Sialic acid and glucuronic acid are monocarboxylated monosaccharides, which are normally present in sugar side chains of glycoproteins, glycolipids, and glycosaminoglycans. After degradation of these compounds in lysosomes, the free monosaccharides are released from the lysosome by a specific membrane transport system. This transport system is deficient in the human hereditary lysosomal sialic acid storage diseases (Salla disease and infantile sialic acid storage disease, OMIM 269920). The lysosomal sialic acid transporter from rat liver has now been purified to apparent homogeneity in a reconstitutively active form by a combination of hydroxyapatite, lectin, and ion exchange chromatography. A 57-kDa protein correlated with transport activity. The transporter recognized structurally different types of acidic monosaccharides, like sialic acid, glucuronic acid, and iduronic acid. Transport of glucuronic acid was inhibited by a number of aliphatic monocarboxylates (i.e. lactate, pyruvate, and valproate), substituted monocarboxylates, and several dicarboxylates. cis-Inhibition, trans-stimulation, and competitive inhibition experiments with radiolabeled glucuronic acid as well as radiolabeled L-lactate demonstrated that L-lactate is transported by the lysosomal sialic acid transporter. L-Lactate transport was proton gradient-dependent, saturable with a Km of 0.4 mM, and mediated by a single mechanism. These data show striking biochemical and structural similarities of the lysosomal sialic acid transporter with the known monocarboxylate transporters of the plasma membrane (MCT1, MCT2, MCT3, and Mev).     

Muscle contraction as a Markov process. I: Energetics of the process

Force generation during muscle contraction can be understood in terms of cyclical length changes in segments of actin thin filaments moving through the three-dimensional lattice of myosin thick filaments. Recent anomalies discovered in connection with analysis of myosin step sizes in in vitro motility assays and with skinned fibres can be rationalized by assuming that ATP hydrolysis on actin accompanies these length changes. The paradoxically rapid regeneration of tension in quick release experiments, as well as classical energetic relationships, such as Hill's force-velocity curve, the Fenn effect, and the unexplained enthalpy of shortening, can be given mutually self-consistent explanations with this model. When muscle is viewed as a Markov process, the vectorial process of chemomechanical transduction can be understood in terms of lattice dependent transitions, wherein the phosphate release steps of the myosin and actin ATPases depend only on occurrence of allosteric changes in neighbouring molecules. Tropomyosin has a central role in coordinating the steady progression of these cooperative transitions along actin filaments and in gearing up the system in response to higher imposed loads.     

Split-receptors in the tachykinin neurokinin-1 system--mutational analysis of intracellular loop 3

Several membrane proteins have been functionally expressed from non-covalently coupled, contiguous segments especially with the split-site located between natural domains. Experiments using such 'split-proteins' were here performed in the tachykinin neurokinin-1 (NK1) receptor with co-expression of contiguous segments with split-sites positioned in various intracellular and extracellular loops. The construct where the split-site was located in intracellular loop 3 gave a reasonable expression level of substance-P-binding sites, i.e. 12% of wild-type expression. Of the other split-receptors tested, only the one with the split-site located just outside transmembrane (TM) segment-V gave any detectable substance P binding, which however only was 1% of the wild-type expression level. The construct with the split-site located in intracellular loop 3 bound all of the tested peptide agonists and non-peptide antagonists with normal affinity and was able to stimulate inositol phosphate turnover with a normal EC50 for substance P and an Emax according to the expression level. When intracellular loop 3 was either extended with 112 amino acid residues derived from the muscarine M2 receptor or, when major parts of the loop were deleted in the non-split NK1 receptor, the affinity for neither substance P nor for the prototype nonpeptide antagonist, CP96,345 was affected, yet an increase in EC50 for substance P was observed. Also in the split-receptor, most of intracellular loop 3 could be substituted or even deleted without affecting ligand affinity, although a decreased expression level was observed in constructs having major deletions. It is concluded, that the NK1 receptor is preferentially reconstituted by co-expression of a putative A-domain including TM-I-V and a B-domain including TM-VI and -VII. It is suggested that a number of rhodopsin-like 7TM receptors may function as two-domain structures based on the finding that a network of short loops has been highly conserved within each of the putative domains and, that these domains are separated by a relatively long and in respect of length poorly conserved loop, i.e. intracellular loop 3.     

A computerised adaptometer

The hippocampal EEG power spectra of rabbits were analyzed to clarify the relationship between the theta-wave and emotionality. The relative power of T2 (6.0-7.9 Hz)/T1 (4.0-5.9 Hz) represented the index of theta-wave change. Emotional excitement (produced with novelty stress or methamphetamine) or suppression (produced with restraint stress or reserpine) increased or decreased T2/T1 ratios within around +/- 1 Hz changes. Furthermore, the imaging patterns of the peak feature make possible detailed characterization of emotional states. These results suggest that the hippocampus finely adjusts the theta-wave on a +/- 1 Hz level, with a fine balance of voltage, in response to the emotional activity.     

Superior temporal gyrus and the course of early schizophrenia: progressive, static, or reversible?

Accumulating evidence suggests alterations in brain structure, especially in the prefrontal and temporal cortex, in schizophrenia. Previous studies examining the progression of brain structural alterations in schizophrenia have led to conflicting results. Morphometric studies of the superior temporal gyrus (STG) volumes were conducted in a series of neuroleptic-naive first-episode schizophrenic patients, non-schizophrenic first-episode psychotic patients, and matched healthy controls. Three-dimensional MRI scans were carried out in these subjects before and after one year of treatment. Volume reductions were seen at baseline in the left superior temporal gyrus (adjusted for intracranial volume) in both of the patient groups. Pretreatment illness duration was inversely related to the volume of the left superior temporal gyrus; this relation was confined to males. One-year follow-up MRI investigations in a smaller subset of patients suggested that the STG volume reductions may be reversible. No significant changes were noted in the STG volumes in matched healthy controls who were also scanned at baseline as well as at one-year follow-up. These findings have implications for understanding the nature of the neuropathological processes in early schizophrenia, as well as the potential impact of early treatment.