NK cell proliferation and inflammation

Considerable progress has been made in recent years in understanding the biology of NK cells. NK cells are no longer 'null cells', but express an array of functionally important molecules with which they mediate and regulate their cytolytic activity and the cytokines they secrete. Activation and proliferation of NK cells in influenced by cytokines produced by activated monocytes (IL-15, IL-12, IL-10) and activated T cells (IL-2). This paper reviews the phenotype and effector functions of NK cells, their tissue distribution, and evidence that NK cells proliferate in vivo as part of productive or pathologic consequences of immunity.     

Sulfation of parabens and tyrosylpeptides by bacterial arylsulfate sulfotransferases

Arylsulfate sulfotransferase purified from Eubacterium A-44 has higher specific activity than the enzymes from Klebsiella K-36 and Haemophilus K-12. Propylparaben and butylparaben were good substrates among several parabens. The antibacterial activity of parabens was reduced by the sulfation of the phenolic hydroxy group. Tyrosine-containing peptides, kyotorphin, enkephalin and cholecystokinin non-sulfate, were effective as acceptor substrates by A-44, K-36 and K-12 sulfotransferases.     

Nonlinear circuit analysis using the method of harmonic balance—A review of the art. Part I. Introductory concepts

The harmonic balance method is a technique for the numerical solution of nonlinear analog circuits operating in a periodic, or quasi-periodic, steady-state regime. The method can be used to efficiently derive the continuous-wave response of numerous nonlinear microwave components including amplifiers, mixers, and oscillators. Its efficiency derives from imposing a predetermined steady-state form for the circuit response onto the nonlinear equations representing the network, and solving for the set of unknown coefficients in the response equation. Its attractiveness for nonlinear microwave applications results from its speed and ability to simply represent the dispersive, distributed elements that are common at high frequencies. The last decade has seen the development and application of harmonic balance techniques to model analog circuits, particularly microwave circuits. The first part of this paper reviews the fundamental achievements made during this time. The second part covers the extension of the method to quasi-periodic regimes, optimization analysis, and practical application. A critical assessment of the various types of harmonic balance techniques is given. The different sampling and Fourier transform methods are compared, and numerical speed and precision results are given enabling a quantitative analysis of the merits of the major variants of the harmonic balance technique. Examples of designs which have been modeled using the harmonic balance technique and built both in hybrid and MMIC form are presented.     

Noninvasive evaluation of the lower extremity arterial tree and graft surveillance

The application of duplex ultrasonography in the evaluation of lower extremity arterial occlusive disease and in graft surveillance has enhanced significantly the vascular surgeon's diagnostic armamentarium. With continued refinements in gray scale image resolution, color flow, and spectral analysis, color duplex ultrasonography eventually will replace angiographic evaluation in carefully selected patients as the primary pre-interventional testing modality.     

Amifostine (WR-2721) shortens the engraftment period of 4-hydroperoxycyclophosphamide-purged bone marrow in breast cancer patients receiving high-dose chemotherapy with autologous bone marrow support

4-Hydroperoxycyclophosphamide (4-HC), a commonly used marrow-purging agent, is active against many tumors, but is also toxic to normal marrow progenitors. Amifostine (WR-2721) is a sulfhydryl compound with chemoprotectant activity. Preclinical studies using suspensions of bone marrow and breast cancer cells demonstrated that ex vivo treatment with amifostine followed by 4-HC resulted in protection of marrow progenitors, with no compromise in the antitumor effect of 4-HC. This fact stimulated the development of a clinical trial. Bone marrow was harvested from 15 poor-prognosis breast cancer patients and randomly assigned to ex vivo treatment with amifostine followed by 4-HC (amifostine + 4-HC), or treatment with 4-HC alone. High-dose chemotherapy was then administered followed by infusion of the purged autologous bone marrow support (ABMS). Leukocyte engraftment, defined as a white blood cell count > or = 1 x 10(9)/L, was achieved in an average of 26 days for patients whose marrow was purged with amifostine + 4-HC versus 36 days for patients whose marrow was purged with 4-HC alone (P = .032). The average number of platelet transfusions (12 v 29; P = .017) and days of antibiotic therapy (28 v 40; P = .012) were significantly less for patients whose marrow was exposed to amifostine + 4-HC, compared with 4-HC alone. Unpurged backup marrow fractions were infused into three patients whose marrow was purged with 4-HC alone, because of inadequate marrow recovery. None of the patients who received amifostine + 4-HC-purged marrow required a backup marrow fraction. Complete remissions were achieved in 83% of patients with measurable disease, with no difference between the two cohorts. Forty-three percent of patients remained alive and progression-free at a mean of 13 months posttransplant. There was no significant difference in the rate or pattern of relapse for patients whose marrow was purged with amifostine + 4-HC compared with those whose marrow was purged with 4-HC alone. Ex vivo treatment of marrow with amifostine significantly shortens the time to marrow recovery, thereby reducing the risk of myelosuppressive complications in breast cancer patients receiving high-dose chemotherapy and 4-HC-purged ABMS. Since supportive care requirements are also significantly decreased, amifostine may reduce the cost of such therapy.     

Stress analysis of a cantilevered fixed partial denture with normal and reduced bone support

A two-dimensional finite element model was constructed to analyze the simulated mechanical behavior of a cantilevered fixed partial denture. The variations of the models were made by altering the degree of bone support, the number of splinted abutments, and the length of the pontics. High stress concentrations were observed around the connectors of the fixed prosthesis and the tooth closest to the cantilever. Reduced bone support increased the deflection and stress concentrations. There was reduction in displacement and stress concentration when the teeth were splinted together. To improve the prognosis of the fixed partial denture cantilever, the number of abutments should be increased and the number of pontics decreased.     

Structures of sialylated oligosaccharides of human erythropoietin expressed in recombinant BHK-21 cells

The native structures of the Asn-linked oligosaccharides and the O-glycans at Ser126 of human erythropoietin expressed from recombinant BHK cells have been elucidated. Enzymatically released N-glycans were studied by methylation analyses, fast-atom-bombardment mass spectrometry as well as one- and two-dimensional 1H-NMR spectrometry at 600 MHz. Many (82.7%) were found to be tetraantennary N-acetyllactosamine-type (22.8% with one, 3.6% with two and 0.4% with three N-acetyllactosamine repeats) being tetrasialylated (41%), trisialylated (29.6%) and disialylated (12.2%). A few (9.7%; 4.1% 2,4-branched, 5.6%, 2,6-branched) of the chains were triantennary (5.4% trisialyl, 4.3% disialyl) and 4.6% were of the disialyl diantennary type. Almost all of the innermost GlcNAc residues were alpha 1-6 fucosylated and NeuAc was exclusively alpha 2-3 linked to Gal beta 1-4GlcNAc-R; 60% of the protein was found to be O-glycosylated at Ser126; structures were monosialylated (70%) or disialylated (30%) forms of the Gal beta 1-3GalNAc core type. Glycosylation patterns at individual Asn-Xaa-Thr/Ser sites were determined by analytical high-pH anion-exchange chromatography with pulsed amperometric detection. Only tetraantennary chains with 0-3 N-acetyllactosamine repeats were detected at Asn38 and Asn83, while almost all of the di- and triantennary oligosaccharides were attached to Asn24. Batch analysis of different preparations of recombinant erythropoietin revealed the high reproducibility of the production procedure. Structures containing terminal GalNAc-GlcNAc were detected in small amounts in a few batches.     

Border crossing for hospital care and its implications for the use of statewide data

A major concern of researchers using state data sets for population-based analyses and market share studies in the health care sector is the potential bias caused by 'border crossing'--patients receiving care out of state. By using the Health Care Financing Administration (HCFA) discharge abstract files for 1987 and 1988, we found that 'border crossing' is not a serious problem for the two large states we examined. Only 4.4% of New York patients and 2.15% of California patients received care out of state. At the county and zip code level, 'border crossing' is more frequent but tends to be concentrated in areas adjacent to other states. Even excluding all zips with more than 10% of patients crossing the 'border' results in a small loss of patients (2.2% for New York and 1.0% for California).