Biomedical subjects
Publications and source records attributed to J Kanter.
We analyzed the function and outcome of 16 kidney transplants performed in our hospital from non-heart-beating donors who were harvested at other hospitals. The cold ischemia times were longer and the delayed graft function rates higher. However, graft function was no different from that of kidneys from heart-beating donors. This experience has encouraged us to use this type of donor to reduce the transplant waiting list.
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A randomized clinical trial was conducted to evaluate whether Dialectical Behavior Therapy (DBT), an effective cognitive-behavioral treatment for suicidal individuals with borderline personality disorder (BPD), would also be effective for drug-dependent women with BPD when compared with treatment-as-usual (TAU) in the community. Subjects were randomly assigned to either DBT or TAU for a year of treatment. Subjects were assessed at 4, 8, and 12 months, and at a 16-month follow-up. Subjects assigned to DBT had significantly greater reductions in drug abuse measured both by structured interviews and urinalyses throughout the treatment year and at follow-up than did subjects assigned to TAU. DBT also maintained subjects in treatment better than did TAU, and subjects assigned to DBT had significantly greater gains in global and social adjustment at follow-up than did those assigned to TAU. DBT has been shown to be more effective than treatment-as-usual in treating drug abuse in this study, providing more support for DBT as an effective treatment for severely dysfunctional BPD patients across a range of presenting problems.
Fasciculin, a selective peptidic inhibitor of acetylcholinesterase, is a member of the three-fingered peptide toxin superfamily isolated from snake venoms. The availability of a crystal structure of a fasciculin 2 (Fas2)-acetylcholinesterase complex affords an opportunity to examine in detail the interaction of this toxin with its target site. To this end, we constructed a synthetic fasciculin gene with an appropriate leader peptide for expression and secretion from mammalian cells. Recombinant wild-type Fas2, expressed and amplified in Chinese hamster ovary cells, was purified to homogeneity and found to be identical in composition and biological activities to the venom-derived toxin. Sixteen mutations at positions where the crystal structure of the complex indicates a significant interfacial contact point or determinant of conformation were generated. Two mutants of loop I, T8A/T9A and R11Q, ten mutants of the longest loop II, R24T, K25L, R27W, R28D, H29D, DeltaPro30, P31R, K32G, M33A, and V34A/L35A, and two mutants of loop III, D45K and K51S, were expressed transiently in human embryonic kidney cells. Inhibitory potencies of the Fas2 mutants toward mouse AChE were established, based on titration of the mutants with a polyclonal anti-Fas2 serum. The Arg27, Pro30, and Pro31 mutants each lost two or more orders of magnitude in Fas2 activity, suggesting that this subset of three residues, at the tip of loop II, dominates the loop conformation and interaction of Fas2 with the enzyme. The Arg24, Lys32, and Met33 mutants lost about one order of magnitude, suggesting that these residues make moderate contributions to the strength of the complex, whereas the Lys25, Arg28, Val34-Leu35, Asp45, and Lys51 mutants appeared as active as Fas2. The Thr8-Thr9, Arg11, and His29 mutants showed greater ratios of inhibitory activity to immunochemical titer than Fas2. This may reflect immunodominant determinants in these regions or intramolecular rearrangements in conformation that enhance the interaction. Of the many Fas2 residues that lie at the interface with acetylcholinesterase, only a few appear to provide substantial energetic contributions to the high affinity of the complex.
A soluble, monomeric form of acetylcholinesterase from mouse (mAChE), truncated at its carboxyl-terminal end, was generated from a cDNA encoding the glycophospholipid-linked form of the mouse enzyme by insertion of an early stop codon at position 549. Insertion of the cDNA behind a cytomegalovirus promoter and selection by aminoglycoside resistance in transfected HEK cells yielded clones secreting large quantities of mAChE into the medium. The enzyme sediments as a soluble monomer at 4.8 S. High levels of expression coupled with a one-step purification by affinity chromatography have allowed us to undertake a crystallographic study of the fasciculin-mAChE complex. Complexes of two distinct fasciculins, Fas1-mAChE and Fas2-mAChE, were formed prior to the crystallization and were characterized thoroughly. Single hexagonal crystals, up to 0.6 mm x 0.5 mm x 0.5 mm, grew spontaneously from ammonium sulfate solutions buffered in the pH 7.0 range. They were found by electrophoretic migration to consist entirely of the complex and diffracted to 2.8 A resolution. Analysis of initial X-ray data collected on Fas2-mAChE crystals identified the space group as P6(1)22 or P6(5)22 with unit cell dimensions a = b = 75.5 A, c = 556 A, giving a Vm value of 3.1 A3/Da (or 60% of solvent), consistent with a single molecule of Fas2-AChE complex (72 kDa) per asymmetric unit. The complex Fas1-mAChE crystallizes in the same space group with identical cell dimensions.
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We have evaluated potential molecular mechanisms by which a group of synthetic lymphokine-like molecules, the 7,8-disubstituted guanine ribonucleosides, acts on second messenger pathways to augment the responses of murine B lymphocytes. Despite its extensive structural homology with GTP, 7-methyl-8-oxoguanosine (7-Me-8-oGuo), a prototypical disubstituted nucleoside, does not inhibit the binding of guanosine 5'-3-O-(thio)triphosphate either to purified G-proteins, or to G-proteins in situ in the plasma membrane. In contrast to anti-IgM antibodies, 7-Me-8-oGuo fails to induce elevation of intracellular free calcium in B lymphocytes. It does not elicit enhanced production of inositol phosphates in either unfractionated or large, cycling B cells (the cells on which it acts preferentially). It is unable to modify the cellular distribution or activity of protein kinase C, whereas phorbol 12-myristate 13-acetate, anti-IgD antibodies, and lipopolysaccharide do activate protein kinase C. Inhibitors of protein kinase C activity diminish stimulation of mRNA transcription by anti-IgD antibodies and lipopolysaccharide but not by 7-Me-8-oGuo. These data demonstrate that 7-Me-8-oGuo either uses a pathway distinct from that mediated by G-proteins, intracellular free calcium, inositol phosphates, and protein kinase C, or else bypasses the early events of this pathway, activating the cell at a point beyond their involvement. In either event, these nucleosides represent the only class of activator to date that is capable of driving B cell proliferation and differentiation without involvement of protein kinase C.
The burgeoning field of case management for long-term psychiatric patients has been handicapped by a lack of conceptual models that delineate the diverse activities of case managers. Based on the actual practice of case management, the author outlines a model of clinical case management that moves beyond the view of the case manager as a systems coordinator, service broker, or supportive companion. Using a contemporary biopsychosocial model of mental illness, the clinical case management model integrates the clinical acumen, personal involvement, and environmental interventions needed to address the overall maintenance of the patient's physical and social environment. Clinical case management involves 13 distinct activities, including engagement of the patient, assessment, planning, linkage with resources, consultation with families, collaboration with psychiatrists, patient psychoeducation, and crisis intervention.
Research on expressed emotion in the families of schizophrenic patients has seemed to offer a new perspective on environmental factors that cause relapse in schizophrenia. A review of the literature, however, reveals that while expressed emotion may predict relapse, there is no evidence that it causes relapse. Nor does the evidence support the continued linkage of the three components of expressed emotion--criticism, hostility, and emotional overinvolvement--in a single global variable. The authors also question the clinical significance of expressed emotion ratings and believe that treatment strategies based on them tend to blame relatives for the patient's continuing difficulties. They suggest that clinicians assess family responses in the context of the patient's behavior and life situation before helping families develop more effectual coping strategies.
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This study was designed to measure percentage of weight loss during simulated toothbrushing of five different composite resins. The surface roughness of each composite resin was also measured after each year of simulated toothbrushing for a period of 5 years. The following conclusions were reached: 1. Despite the loss of toothbrush efficiency, all composite resins tested tended to have a decreasing wear rate with the increasing time of toothbrushing. 2. Profile (with a soft filler) and Isopast (with a microsized filler) showed the greatest resistance to abrasion and retained the smoothest surface. 3. Prestige, which demonstrated the greatest percent weight loss, also has a soft barium filler. Loss of the filler as an alkaline reaction in water due to soluble barium compounds may cause the binder to release filler particles prematurely.
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