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Biomedical subjects

D Kaplan

Publications and source records attributed to D Kaplan.

231 records · Page 13Linked to original sources

Long-term maintenance therapy with azathioprine in systemic lupus erythematosus.

One hundred ten patients with systemic lupus erythematosus (SLE) were classified into two groups, patients with central nervous system (CNS) or severe renal disease (usually associated with a poor prognosis) and patients without these manifestations, to define criteria for azathioprine therapy. Fifty-four of 68 patients with a poor prognosis received azathioprine. Azathioprine-treated patients showed improved long-term survival (72% vs 29%, P less than .005) and fewer hospitalizations (0.24/patient-years vs 0.89/patient-years, P less than .001). Azathioprine therapy in 19 of 42 patients with a good prognosis was associated with fewer hospitalizations (.02/patient-years vs .17/patient-years, P less than .05), but no decrease in maintenace prednisone requirement. Progression from a good to a poor prognosis was less frequent (1 of 20 vs 11 of 34, P = less than .05) among azathioprine-treated patients. Toxicity of azathioprine was minimal. Azathioprine therapy is indicated in patients with CNS or severe renal disease, and in patients whose prognosis was good with frequent hospitalizations or a maintenance prednisone requirement greater than 15 mg/day.

Adolescent↗

Computer analysis of factors influencing frequency of infection in systemic lupus erythematosus.

Data from a prospective study of the clinical course in 223 patients with systemic lupus erythematosus followed for 655 patient-years were analyzed by computer to determine the influence on frequency of infection of 1) corticosteroid dose; 2) azathioprine; 3) active disease, measured by new disease exacerbations, elevated ESR, hypocomplementemia, active urinary sediment, and proteinuria; 4) uremia; and 5) leukopenia. The frequency of all infections, and of bacterial and opportunistic infections specifically, increased progressively with increasing steroid dose. Azathioprine use, independent of steroid dose, did not account for an increased risk of bacterial, opportunistic, or nonspecific viral infections. Leukopenia did not predispose to infection, except possibly when associated with azathioprine-induced bone marrow suppression. Active renal disease, especially when manifested by abnormal urine sediment, was associated with an increase in infection frequency.

Azathioprine↗

Comparative analysis of macromolecules in mollusc shells.

1. Proteins and polysaccharides were isolated from the shells of molluscs; blue mussel, Mytilus edulis, chambered nautilus, Nautilus pompilius, and red abalone, Haliotus rufescens. 2. N-acetyl glucosamine was detected in nautilus but not mussel or abalone. 3. Amino acid analysis of protein fractions was completed for the three molluscs and purified proteins from the mussel were partially sequenced. 4. Calcium binding studies were carried out with some of the protein fractions.

Acetylglucosamine↗

Designing recombinant spider silk proteins to control assembly.

The consensus repeat sequence found in the dragline silk from the spider, Nephila clavipes, was redesigned to incorporate a redox trigger flanking the beta-sheet forming polyalanine sequences. The methionine redox trigger, in the oxidized state, was incorporated to prevent the formation of the beta sheets, while in the reduced state would not result in sterical limitations to beta sheet formation. A synthetic gene incorporating the trigger was constructed, cloned and then expressed in Escherichia coli. The purified protein, about 25 kDa, contained the expected amino acid composition and migration behavior on SDS-PAGE. The recombinant protein was analyzed by X-ray diffraction, TEM, electron diffraction and circular dichroism in both oxidized and reduced states. Based on the results, the incorporation of a redox trigger appears to be a powerful experimental strategy to explore the self-assembly of fibrous proteins such as silks.

Amino Acid Sequence↗

Bombyx mori silk fibroin liquid crystallinity and crystallization at aqueous fibroin-organic solvent interfaces.

A banded morphology has been observed for Bombyx mori silk fibroin films obtained from an aqueous hexane interface; the period of the banding is approximately 1 microm. Morphology and diffraction from different regions of the banded structure suggest that it is a free surface formed by a cholesteric liquid crystal. Truncated hexagonal lamellar crystallites of B. mori silk fibroin have been observed in films formed in the surface excess layer of fibroin at the interface between aqueous fibroin and hexane or chloroform. Based on initial crystallographic evidence, a three-fold helical conformation has been ascribed to the fibroin chains within the crystals. The chain conformation and crystalline habit appear to be similar to the silk III structure previously observed at the air-water interface (Valluzzi R, Gido SP. Biopolymers 1997;42:705-717; Valluzzi R, Gido S, Zhang W, Muller W, Kaplan D. Macromolecules 1996;29:8606-8614) but the crystalline packing is different. Diffraction data obtained for the crystallites are similar to diffraction behavior for a collagen-like model peptide. Diffraction patterns obtained from crystallized regions of the banded morphology can be indexed using the same unit cell as the hexagonal lamellar crystallites. Surfactancy of fibroin and subsequent aggregation and mesophase formation may help to explain the liquid crystallinity reported for silk, which is long suspected to play a role in the biological silk spinning process (Valluzzi R, Gido SP. Biopolymers 1997;42:705-717; Willcox, P. J.; Gido, SP, Muller W, Kaplan DL. Macromolecules 1996:29:5106-5110; Magoshi J, Magoshi Y, Nakamura S. In: Kaplan D, Adams W, Farmer B, Viney C, editors, Mechanism of Fiber Formation of Silkworm. Washington, DC: American Chemical Society 1994:292-310; Magoshi J, Magoshi Y, Nakamura S. J Appl Polym Sci Appl Polym Symp 1985;41:187-204; Magoshi J, Magoshi Y, Nakamura S. Polym Commun 1985;26:309.).

Animals↗

A comparison of the composition of silk proteins produced by spiders and insects.

Proteins that are highly expressed and composed of amino acids that are costly to synthesize are likely to place a greater drain on an organism's energy resources than proteins that are composed of ingested amino acids or ones that are metabolically simple to produce. Silks are highly expressed proteins produced by all spiders and many insects. We compared the metabolic costs of silks spun by arthropods by calculating the amount of ATP required to produce their component amino acids. Although a definitive conclusion requires detailed information on the dietary pools of amino acids available to arthropods, on the basis of the central metabolic pathways, silks spun by herbivorous, Lepidoptera larvae require significantly less ATP to synthesize than the dragline silks spun by predatory spiders. While not enough data are available to draw a statistically based conclusion, comparison of homologous silks across ancestral and derived taxa of the Araneoidea seems to suggest an evolutionary trend towards reduced silk costs. However, comparison of the synthetic costs of dragline silks across all araneomorph spiders suggests a complicated evolutionary pattern that cannot be attributed to phylogenetic position alone. We propose that the diverse silk-producing systems of the araneoid spiders (including three types of protein glues and three types of silk fibroin), evolved through intra-organ competition and that taxon-specific differences in the composition of silks drawn from homologous glands may reflect limited or fluctuating amino acid availability. The different functional properties of spider silks may be a secondary result of selection acting on different polypeptide templates.

Amino Acids↗

Differential density of normal renal parenchyma on nonenhanced CT: a new observation.

PURPOSE: Nonenhanced CT scans through the kidneys commonly show a difference in radiopacity between the inner peripelvic portion of the renal parenchyma and the more peripheral regions of the renal parenchyma. This normal observation has not been described. METHOD: We reviewed 50 nonenhanced CT scans. Renal parenchyma was evaluated by both visual inspection and density measurements of inner and outer aspects of the kidneys in 38 and visual inspection only in 12. A narrower window was used to better show density differences (100 W, 35 L). We recorded the indication for the CT, history, and recent blood chemistries. RESULTS: The inner parenchyma was of greater radiopacity than the outer parenchyma in 35 of 50 cases by visual inspection and in all densitometry cases (38 of 38). There was no correlation with clinical history or blood chemistry. CONCLUSION: A difference in density between the inner and outer portions of the renal parenchyma is very common and will often be seen if one looks for it. We have not shown an etiology for this difference, and indeed, it may be physiological. One must be aware of this finding to avoid mistaking it for pathology.

Aged↗