Correlation between post-heparin lipase and phospholipase activities in human plasma

The hypothesis that a single lipolytic enzyme in post-heparin plasma effects the hydrolysis of both triglyceride and phospholipid was tested. After intravenous heparin, activity in plasma with the two substrate classes appeared and disappeared in parallel. The activities were not separable by the fractionation methods of zone electrophoresis, gel filtration, anion-exchange, ultracentrifugation, or by combinations of these techniques. The degree of purification of the two activities with the use ofn-butanol was similar. Lipolytic activity appeared to be associated with a large high density molecular aggregate. However, the concept of a single post-heparin enzyme does not explain all the observations since the ratio of activity with triglyceride substrate to activity with phospholipid substrate decreased markedly in some subjects after increased amounts of intravenous heparin. Presented in part at the AOCS Meeting, Washington, D.C., April 1968.     

Interaction of omeprazole with enteric-coated salicylate tablets

OBJECTIVE: Enteric-coated tablets are designed to resist gastric fluids and to disrupt and dissolve in the alkaline medium of the small intestine. Main objective of the present study was to investigate whether the increase in gastric pH due to omeprazole treatment alters the release rate of a drug from enteric-coated formulation. To this end, we have compared the single dose pharmacokinetics of a single-unit enteric-coated salicylate to that of uncoated acetylsalicylic acid tablets in the presence and absence of omeprazole treatment. METHODS: Study was carried out according to 4 x 4 Latin square design. Eight healthy subjects received either uncoated acetylsalicylic acid tablets or single-unit enteric-coated sodium salicylate tablets alone or following 4 days of treatment with single-dose 20 mg omeprazole, and blood samples were collected for 24 hours. Serum salicylate levels were determined by the modified spectrophotometric method of Brodie et al. [1994]. RESULTS: Salicylate was absorbed rapidly from uncoated tablets but absorption of salicylate from enteric-coated tablets was delayed, as expected. According to our results, omeprazole treatment did not influence the bioavailability from uncoated acetylsalicylic acid tablets but the absorption rate of salicylate from enteric-coated tablets was increased significantly. CONCLUSION: Findings of the present study demonstrate that omeprazole treatment significantly increases the rate of absorption of single-unit enteric-coated medication. Enhanced rate of absorption is most probably due to an early disruption of enteric coating and the intragastric release of the drug secondary to an omeprazole-mediated increase in gastric pH. The results of the present study also corroborate previous findings which have demonstrated highly variable absorption of enteric-coated single units.     

The unpredicted high affinities of a large number of naturally occurring tachykinins for chimeric NK1/NK3 receptors suggest a role for an inhibitory domain in determining receptor specificity

Three chimeric receptors were constructed by exchanging exon sequences between human NK1 and NK3 receptor genes. The resulting chimeric receptors not only retained high affinities for their natural ligands substance P and neurokinin B but also exhibited surprisingly high affinities for other naturally occurring tachykinins including neurokinin A, neuropeptide K, neuropeptide gamma, eledoisin, kassinin, physalaemin, and phyllomedusin. In contrast, these chimeric receptors displayed a wide range of variability in their affinities for non-naturally occurring ligands including selective agonists and antagonists of NK1, NK2, and NK3 receptors. Since the only common feature among these naturally occurring neurokinin peptides is the conserved C-terminal sequences, our data suggest that these conserved sequences must play the major role in conferring high affinity binding to the chimeric receptors. To explain the apparently "improved" affinities of these naturally occurring ligands for the chimeric receptors as compared with their affinities for the parent NK1 and NK3 receptors, we are proposing that certain inhibitory domains that are present in the NK1 and/or NK3 receptors are compromised in these chimeric receptors. Upon disruption of these inhibitory domains during the formation of chimeras, the naturally occurring ligands can interact more favorably with chimeric receptors through their conserved C-terminal sequences. Based on this hypothesis, the binding affinities of natural tachykinin ligands may be largely determined by their conserved C-terminal sequences, whereas receptor selectivities of these ligands are influenced more by the presence or absence of inhibitory domains rather than specific binding domains on their target receptors.     

Characterization of plantar verrucae among individuals with human immunodeficiency virus

Plantar verrucae, caused by human papillomavirus (HPV), are commonly found in patients who have tested positive for the antibodies to human immunodeficiency virus (HIV). A better understanding of the characteristics of plantar verrucae in HIV+ patients in needed. A pilot study was conducted concentrating on three characteristics--the size, the number, and the clinical type--of verrucae present in this population. These parameters were studied in HIV+ and HIV- populations, and they were evaluated in relation to the CD4 levels of HIV+ individuals. The HIV+ individuals presented with plantar verrucae that were larger and more numerous than those found in HIV- individuals. The HIV+ population presented with all three clinical types of plantar verrucae and had significantly more mosaic-type warts than did HIV- individuals. The three characteristics did not correlate with CD4 cell counts, suggesting that the severity and extent of HPV infection do not depend on the level of immunosuppression of the HIV+ patient.     

Measurement updating using the U-D factorization

The discrete linear filtering problem is treated by factoring the filter error covariance matrix as P = UDU^T. Efficient and stable measurement updating recursions are developed for the unit upper triangular factor, U, and the diagonal factor, D. This paper treats only the parameter estimation problem; effects of mapping, inclusion of process noise and other aspects of filtering are treated in separate publications. The algorithm is simple and, except for the fact that square roots are not involved, can be likened to square root filtering. Like the square root filter our algorithm guarantees nonnegativity of the computed covariance matrix. As is the case with the Kalman filter, our algorithm is well suited for use in real time. Attributes of our factorization update include: efficient one point at a time processing that requires little more computation than does the optimal but numerically unstable conventional Kalman measurement update algorithm; stability that compares with the square root filter and the variable dimension flexibility that is enjoyed by the square root information filter. These properties are the subject of this paper.     

Hyperbranched PbS and PbSe nanowires and the effect of hydrogen gas on their synthesis

We report a chemical vapor deposition (CVD) synthesis of hyperbranched single-crystal nanowires of both PbS and PbSe using PbCl2 and S/Se as precursors under hydrogen flow. Multiple generations of nanowires grow perpendicularly from the previous generation of nanowires in an epitaxial fashion to produce dense clusters of a complex nanowire network structure. The flow rate and duration of the hydrogen co-flow in the argon carrier gas during the CVD reactions are found to have a significant effect on the morphology of the PbS/PbSe grown, from hyperbranched nanowires to micrometer-sized cubes. No intentional catalyst was employed for the nanowire synthesis, but it is suggested that elemental lead that has been reduced from the vapor by the hydrogen might serve as a vapor-liquid-solid (VLS) catalyst for the anisotropic growth of PbS/PbSe. The nanowires were also investigated with Raman spectroscopy. These PbS and PbSe nanostructures can have applications in photovoltaics because multiple exciton generation has been demonstrated in nanocrystals of both materials.     

Numerical comparison of kalman filter algorithms: Orbit determination case study

Numerical characteristics of various Kalman filter algorithms are illustrated with a realistic orbit determination study. The case study of this paper highlights the numerical deficiencies of the conventional and stabilized Kalman algorithms. Computational errors associated with these algorithms are found to be so large as to obscure important mismodeling effects and thus cause misleading estimates of filter accuracy. The positive result of this study is that the U-D covariance factorization algorithm has excellent numerical properties and is computationally efficient, having CPU costs that differ negligibly from the conventional Kalman costs. Accuracies of the U-D filter using single precision arithmetic consistently match the double precision reference results. Numerical stability of the U-D filter is further demonstrated by its insensitivity to variations in the a priori statistics.     

Allogeneic-blood stem-cell collection following mobilization with low-dose granulocyte colony-stimulating factor

PURPOSE: The optimal dose of granulocyte colony-stimulating factor (G-CSF) for mobilization of allogeneic-blood stem cells (AlloBSC) has yet to be determined. As part of a prospective trial, 41 related human leukocyte antigen (HLA)-matched donors had blood cells mobilized with G-CSF at 5 micrograms/kg/d by subcutaneous administration. The purpose of this trial was to monitor adverse effects during G-CSF administration and stem-cell collection, to determine the optimal timing for stem-cell collection, and to determine the cellular composition of stem-cell products following G-CSF administration. PATIENTS AND METHODS: The median donor age was 42 years. Apheresis began on day 4 of G-CSF administration. At least three daily 12-L apheresis collections were performed on each donor. A minimum of 1.0 x 10(6) CD34+ cells/kg (recipient weight) and 8.0 x 10(8) mononuclear cells/kg were collected from each donor. All collections were cryopreserved in 5% dimethyl sulfoxide and 6% hydroxyethyl starch. RESULTS: Toxicities associated with G-CSF administration and the apheresis process included myalgias/arthralgias (83%), headache (44%), fever (27%), and chills (22%). The median baseline platelet count of 242 x 10(4)/ mL decreased to 221, 155, and 119 x 10(6)/mL on days 4, 5, and 6 of G-CSF administration, respectively. Median numbers of CD34+ cells in collections 1, 2, and 3 were 1.99, 2.52, and 3.13 x 10(6)/kg, respectively. The percentage and total number of CD4+, CD8+, and CD56+/CD3- cells remained relatively constant during the three collections. Median total numbers of cells were as follows: CD34+, 7.73 x 10(6)/kg; and lymphocytes, 6.93 x 10(8)/kg. CONCLUSION: Relatively low doses of G-CSF can mobilize sufficient numbers of AlloBSC safely and efficiently.     

Unique association of a rapidly growing right atrial myxoma in a child with double-outlet right ventricle

We have undertaken an analysis of semen from HIV infected men with regard to sperm counts and motility, non-spermatozoal cells, and viral nucleic acid. Regression analysis showed that sperm concentration and motility were positively associated with blood CD4 cell count. By contrast, non-spermatozoal cell concentration (round cells) was inversely related to CD4 count. Extracellular HIV RNA was detected in the majority of semen samples and proviral DNA in a minority. Percoll gradient washing of 12 semen samples yielded six samples containing adequate sperm concentration for analysis. This washing procedure reduced prewash extracellular RNA to below detectable limits in all cases; proviral DNA present in two of the six prewash samples was also reduced to below detectable limits after washing. We conclude that semen washing before artificial insemination may reduce the risk of HIV transmission from an infected man to an uninfected woman. However, further evidence from prospective analyses of such an approach is required.