Comparative Study of the Effect of ACE-Inhibitors and Other Antihypertensive Agents on Proteinuria in Diabetic Patients

Several studies during the past 15 years have shown that antihypertensive therapy with different types of drugs can reduce microalbuminuria or clinical proteinuria and retard the progression toward end-stage renal failure. However, some authors reported disparate renal protective effects of different antihypertensive drugs in diabetic animals and humans. In an attempt to resolve the controversy surrounding this possibility, previously we reported a meta-analysis of published studies in diabetics with microalbuminuria or overt proteinuria treated with conventional agents, angiotensin-converting enzyme (ACE) inhibitors, or calcium antagonists (Ca2+ antagonists). Here we present an updated meta-analysis of published studies in diabetics with microalbuminuria or clinical proteinuria (UProt), treated during ≥ 4 weeks with ACE inhibitors, Ca2+ antagonists, or conventional therapy (diuretic and/or β-blocker). Despite similar blood pressure (BP) reductions, UProt tended to decrease more on ACE inhibitors (on average -45%) than on conventional therapy (on average -23%) or Ca2+ antagonists other than nifedipine (on average -35%); in contrast, UProt tended to increase slightly on nifedipine (on average 5%, P 5% and the slope was steeper (4% UProt change per percent BP change) than on ACE inhibitors. On Ca2+ antagonists other than nifedipine, UProt was unchanged at zero BP change, and the regression line for the relationship between changes in UProt (r = 0.55, P < .05) was in an intermediate position between ACE inhibitors and conventional treatment. Seventy reports also contained data on glomerular filtration rate (GFR). On ACE inhibitors, GFR was on average unchanged, but tended to increase slighty with progressive BP reduction (r = -0.55, P < .0001). On conventional therapy or Ca2+.antagonists, variations in GFR were unrelated to changes in BP. As ACE inhibitors exert a specific antiproteinuric effect even without a change in systemic BP, they are superior to other agents in treating microalbuminuria or overt proteinuria in initially normotensive or mildly hypertensive diabetic patients. On the other hand, when systemic BP can be lowered by 20%, as it is desirable in severely hypertensive patients, ACE inhibitors, conventional therapy, and several Ca2+ antagonists all have a distinct antiproteinuric action. In contrast, as the example of nifedipine illustrates, drug-specific intrarenal effects may antagonize a BP-dependent antiproteinuric action and even counteract the effect of lowering systemic pressure. It is of note that ACE inhibitors may, in addition to their antiproteinuric effect, exert a drug-specific beneficial influence on GFR. Am J Hypertens 1994;7:84S-92

Leveraging range joins for the computation of overlap joins

Joins are essential and potentially expensive operations in database management systems. When data is associated with time periods, joins commonly include predicates that require pairs of argument tuples to overlap in order to qualify for the result. Our goal is to enable built-in systems support for such joins. In particular, we present an approach where overlap joins are formulated as unions of range joins, which are more general purpose joins compared to overlap joins, i.e., are useful in their own right, and are supported well by B+-trees. The approach is sufficiently flexible that it also supports joins with additional equality predicates, as well as open, closed, and half-open time periods over discrete and continuous domains, thus offering both generality and simplicity, which is important in a system setting. We provide both a stand-alone solution that performs on par with the state-of-the-art and a DBMS embedded solution that is able to exploit standard indexing and clearly outperforms existing DBMS solutions that depend on specialized indexing techniques. We offer both analytical and empirical evaluations of the proposals. The empirical study includes comparisons with pertinent existing proposals and offers detailed insight into the performance characteristics of the proposals

Leveraging range joins for the computation of overlap joins

Joins are essential and potentially expensive operations in database management systems. When data is associated with time periods, joins commonly include predicates that require pairs of argument tuples to overlap in order to qualify for the result. Our goal is to enable built-in systems support for such joins. In particular, we present an approach where overlap joins are formulated as unions of range joins, which are more general purpose joins compared to overlap joins, i.e., are useful in their own right, and are supported well by B+-trees. The approach is sufficiently flexible that it also supports joins with additional equality predicates, as well as open, closed, and half-open time periods over discrete and continuous domains, thus offering both generality and simplicity, which is important in a system setting. We provide both a stand-alone solution that performs on par with the state-of-the-art and a DBMS embedded solution that is able to exploit standard indexing and clearly outperforms existing DBMS solutions that depend on specialized indexing techniques. We offer both analytical and empirical evaluations of the proposals. The empirical study includes comparisons with pertinent existing proposals and offers detailed insight into the performance characteristics of the proposals

Versioned relations: Support for conditional schema changes and schema versioning

We introduce the versioned relational data model, which allows a user to apply conditional schema changes to a populated database without breaking applications compiled against an existing schema, and without loss of existing data. Our model is based on keeping a history of conditional schema changes, and converting tuples on demand to fit the correct schema in any schema version. We provide a concrete defnition of schema versioning: The ability to specify an operator on any schema version, such that the tuples in the result are unaffected by schema versions created after the specified schema version. Finally, we show that our model supports schema versioning

\u3csup\u3e1\u3c/sup\u3eH, \u3csup\u3e15\u3c/sup\u3eN, \u3csup\u3e13\u3c/sup\u3eC and \u3csup\u3e13\u3c/sup\u3eCO Assignments and Secondary Structure Determination of Basic Fibroblast Growth Factor Using 3D Heteronuclear NMR Spectroscopy

The assignments of the 1H, 15N, 13CO, and 13C resonances of recombinant human basic fibroblast growth factor (FGF-2), a protein comprising 154 residues and with a molecular mass of 17.2 kDa, is presented based on a series of three-dimensional triple-resonance heteronuclear NMR experiments. These studies employ uniformly labeled 15N- and 15N-/13C-labeled FGF-2 with an isotope incorporation \u3e95% for the protein expressed in E. coli. The sequence-specific backbone assignments were based primarily on the interresidue correlation of Cα, Cβ, and Hα to the backbone amide 1H and 15N of the next residue in the CBCA(CO)NH and HBHA(CO)NH experiments and the intraresidue cor-relation of Cα, Cβ, and Hα to the backbone amide 1H and 15N in the CBCANH and HNHA experi-ments. In addition, Cα and Cβ chemical shift assignments were used to determine amino acid types. Sequential assignments were verified from carbonyl correlations observed in the HNCO and HCACO experiments and Cα correlations from the HNCA experiment. Aliphatic side-chain spin sys-tems were assigned primarily from H(CCO)NH and C(CO)NH experiments that correlate all the aliphatic 1H and 13C resonances of a given residue with the amide resonance of the next residue. Additional side-chain assignments were made from HCCH-COSY and HCCH-TOCSY experiments. The secondary structure of FGF-2 is based on NOE data involving the NH, Hα, and Hβ protons as well as 3JHNHα coupling constants, amide exchange, and 13Cα and 13Cβ secondary chemical shifts. It is shown that FGF-2 consists of 11 well-defined antiparallel β-sheets (residues 30–34, 39–44, 48–53, 62–67, 71–76, 81–85, 91–94, 103–108, 113–118, 123–125, and 148–152) and a helix-like structure (residues 131–136), which are connected primarily by tight turns. This structure differs from the refined X-ray crystal structures of FGF-2, where residues 131–136 were defined as β-strand XI. The discovery of the helix-like region in the primary heparin-binding site (residues 128–138) instead of the β-strand conformation described in the X-ray structures may have important implications in understanding the nature of heparin–FGF-2 interactions. In addition, two distinct conformations exist in solution for the N-terminal residues 9–28. This is consistent with the X-ray structures of FGF-2, where the first 17–19 residues were ill defined

Isolation and characterization of epidermal growth factor from human milk

AbstractEpidermal growth factor (EGF) has been purified from human milk. The purification was monitored with a human placental membrane radioreceptor assay using murine salivary epidermal growth factor I (mEGF I) as a competitive ligand and was achieved exclusively by the use of reverse-phase liquid chromatography (RPLC). The sequential use of preparative, semipreparative and analytical RPLC on an octylsilica support with solvent systems of different solute selectivity such as pyridine formate, triethylammonnium phosphate or perfluorocarbonic acids in the presence of n-propanol or acetonitrile allowed purification to homogeneity with 5 consecutive runs. The molecular mass, amino acid composition and NH2-terminal sequence of human EGF were determined. Gas-phase microsequencing of residues 1-17 revealed the following sequence: Asn -Ser-Asp-Ser-Glu-X-Pro-Leu-Ser-His-Asp-Gly-Tyr-X-Leu-X-Asp which is identical with the NH2-terminof urogastrone from human urine. The purified polypeptide competes with mEGF for the placental membrane receptor with a ki, of 1 ng. Furthermore, it stimulates the anchorage-dependent as well as -independent proliferation of human and rat indicator cells with half-maximal stimulation at 1 and 2.5 ngml, respectively. Although human epidermal growth factor has been unequivocally identified in human milk and - for the first time - shown to be identical with urogastrone from human urine, the high-resolution techniques employed have also revealed the presence of EGF-related molecules which await further characterization. It is possible that EGF and the EGF-related growth factors possess important regulatory functions in normal growth of the human breast during pregnancy and lactation as well as in abnormal growth during mammary tumor formation and progression