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D Hanes

Publications and source records attributed to D Hanes.

15 recordsLinked to original sources
PubMed1996

Metabolism of amyloid proteins.

Metabolic processing of amyloid precursor proteins is an important factor in the genesis of practically all forms of amyloidosis. Of the three major forms of systemic amyloidosis, reactive amyloid (amyloid A protein; AA) formation shows the most consistent role of partial proteolysis of serum amyloid A (SAA) to AA proteins which form fibrils. Immunoglobulin amyloidosis is also usually associated with C-terminal degradation of the fibril precursor light chain protein. Although it is commonly thought that transthyretin amyloidosis is associated with fibril formation from the tetrameric circulating plasma transthyretin, chemical analyses of transthyretin fibril deposits show significant fragmentation of the fibril protein constituents. In addition, it has been documented that proteolytic fragments are the fibril subunit proteins in gelsolin, cystatin C. Alzheimer's beta-amyloid precursor protein and apolipoprotein AI (apoAI) amyloidoses. Notable exceptions to the role of proteolysis in amyloid fibril formation would appear to be the lysozyme and beta 2-microglobulin amyloidoses. Few studies have examined the metabolism of amyloid-forming proteins. Perhaps the best data are on apoAI, which show decreased plasma residence time for the amyloidogenic Gly26Arg apoAI (1.8 d vs. normal 4.5 d). Similarly, preliminary data show increased clearance of Val30Met transthyretin when compared with the wild-type protein (18 h vs. 26 h). Also, biosynthetically 35S-labelled SAA proteins reconstituted with HDL show increased plasma clearance of murine SAA2, the amyloid fibril subunit protein, when compared with murine SAA1. Few data are available on metabolism of amyloid immunoglobulin light chain proteins, but it has been shown that radiolabelled Bence-Jones proteins are cleared very rapidly from the circulation. A better understanding of the metabolism of precursor proteins in each of the amyloid deposition diseases will give insight into the mechanisms of fibril formation and pathogenesis of amyloidosis.

Alzheimer Disease↗
PubMed1994

EKGenius: a computer-interactive electrophysiology learning tool.

EKGenius is a computer-interactive learning environment in electrocardiography for the cardiovascular specialist including those who design and evaluate monitoring equipment. It provides a comprehensive review and assessment in electrocardiographic principles, 12-lead EKG interpretation, and arrhythmia detection. The program combines a simulated examination, tutorial lessons, and practice quizzes. An authoring system facilitates implementation of an a database of 250 questions and 100 lessons. The program provides the user with his/her score at the end of the exam, and the user has the option to review incorrect responses with the associated lessons. In the quiz mode, 10 questions are selected from the bank in the category selected by the user. Immediate feedback is provided with each response, and the user has the option of receiving a hint or reviewing an associated lesson. A mode is also available to view the tutorial lessons independently.

Computer-Assisted Instruction↗
PubMed1986

Dissection of the early steps in the porphobilinogen synthase catalyzed reaction. Requirements for Schiff's base formation.

The porphobilinogen (PBG) synthase catalyzed reaction requires both Zn(II) and reducing equivalents for the production of PBG from two molecules of 5-aminolevulinic acid (ALA). An early step in the reaction is the production of a Schiff's base between PBG synthase and one ALA molecule. Because both substrate molecules are chemically identical, there had been no evidence of enzyme-catalyzed partial reactions of ALA under conditions where PBG is not formed. In this study, NaBH4 was used to trap the Schiff's base formed between substrate ALA and active holo-PBG synthase, inactive apo-PBG synthase, and inactive methylmethanethiosulfonate-modified apo-PBG synthase. ALA-dependent NaBH4 inactivation of these enzyme forms was quantified at 50-62, 94-97, and 93-96% inactivation, respectively. [4-14C]ALA was used to determine the stoichiometry of Schiff's base trapping which was 2.3, 3.5-4.0, and 3.4 per octamer for holoenzyme, apoenzyme, and methylmethanethiosulfonate-modified apoenzyme, respectively. These results are consistent with four active sites per octamer or half-of-the-sites reactivity. We conclude that the production of the Schiff's base formed between one ALA molecule and the enzyme requires neither Zn(II) nor reduced enzyme sulfhydryl groups. Furthermore, the possible number of kinetic schemes for formation of the quaternary complex of enzyme, Zn(II), and two ALA moieties, one as the Schiff's base, has been reduced from 12 to 3. This is the first demonstration of a partial reaction catalyzed by PBG synthase with the natural substrate ALA under conditions which do not support PBG formation. Thus, we have opened the way toward investigating the partial reactions which may precede Zn(II) participation in the PBG synthase reaction.

Aminolevulinic Acid↗
PubMed1981

Pretreatment with donor-specific blood transfusions in related recipients with high MLC.

Pretreatment with deliberate DST has not resulted in hyperacute or irreversible rejection in patients receiving kidneys after negative donor-specific crossmatches, but has afforded immunologically disparate related recipients enhanced opportunity at successful transplantation. Additionally, with a post-transplant course paralleling that of HLA-identical siblings, high-dose immunosuppressive therapy for rejection has been spared in many recipients. Transplantation, however, proved unsuccessful in a patient receiving a kidney from his positive B-warm crossmatch blood donor in a protocol departure. This case experience and subsequent antibody studies have reconfirmed our initially established criterion of not proceeding with transplantation against a persistently positive B-warm donor-specific crossmatch. By pursuing the initially established DST protocol, it appears that a potentially unsuccessful living related transplant can be avoided, while the transplants actually performed have enhanced prospects of success. The nature of the various immunologic responses in this patient population remain to be more clearly defined.

Antibody Formation↗
PubMed1980

Deliberate donor-specific blood transfusions prior to living related renal transplantation. A new approach.

In order to select MLC incompatible one-haplotype related donor-recipient pairs that would achieve better graft survival and in an effort to alter the recipient immune response, 45 patients received three fresh blood transfuions from their prospective kidney donors. Recipient sensitization was evaluated by cross-match testing weekly sera obtained during and after the blood transfusions against donor T- and B-lymphocytes at 5 C (cold) and 37 C (warm). Thirteen (29%) of the 45 potential related recipients developed a positive warm T-cell cross-match or a persistent warm B-cell cross-match to their blood donor and related transplantation was not performed. Thirty-two (71%) patients had an appropriate negative cross-match to their blood donor. Thirty of these patients subsequently received kidneys from their blood donor. Ninety-seven per cent of the kidneys are functioning from one to 25 months with a single graft failure due to a patient discontinuing immunosuppressive medication. In addition to the excellent graft survival there was an unusually low incidence of rejection episodes in the recipients of kidneys from their blood donor so that the posttransplant course paralleled that of HLA-identical siblings. This approach may have future application with two-haplotype mismatched donor-recipient pairs, both related and unrelated.

Adult↗