Biomedical subjects

V McGrath

Publications and source records attributed to V McGrath.

4 recordsLinked to original sources

PubMed2005

Isolation and characterisation of a human monoclonal autoantibody to the islet cell autoantigen IA-2.

A hybridoma secreting a human monoclonal autoantibody to the islet cell autoantigen IA-2 was prepared from peripheral lymphocytes of a patient with type 1 diabetes and Graves' disease using EBV infection followed by fusion with a mouse/human hybrid cell line. The monoclonal antibody (M13) is an IgG1/kappa and in an immunofluorescence test M13 at 1 microg/mL showed islet cell antibody reactivity equivalent to 40 JDF units. M13 IgG bound (35)S-labelled IA-2 (26% at 100 microg/mL) and (125)I-labelled IA-2 (34% at 100 microg/mL) in an immunoprecipitation assay and reacted well with IA-2 in western blotting analysis. Amino acids 777-808 in the PTP domain of IA-2 were found to be important for M13 binding in an analysis using modified (35)S-labelled IA-2 proteins. M13 V region genes were from VH1-3, D3-22, JH4b, VKI DPK8/Vd+ and JK3 genes and showed a high replacement/silent mutation ratio for both the heavy (11.0) and the light (6.0) chain genes. Mouse monoclonal antibodies (mMAbs) reactive with at least three different epitopes within IA-2 aa 604-686 corresponding to the juxtamembrane domain were also obtained. F(ab')(2) or Fab from the mMAbs inhibited serum IA-2 autoantibody binding to IA-2 in 20/22 diabetic sera whereas M13 F(ab')(2) caused inhibition in only 6/22 sera. M13 is representative of some patient serum IA-2 autoantibodies and as such provides a useful tool to study autoimmune responses to IA-2.

Animals↗

PubMed1999

The interaction of TSH receptor autoantibodies with 125I-labelled TSH receptor.

Detergent-solubilized porcine TSH receptor (TSHR) has been labeled with 125I using a monoclonal antibody to the C-terminal domain of the receptor. The ability of sera containing TSHR autoantibody to immunoprecipitate the labeled receptor was then investigated. Sera negative for TSHR autoantibody (as judged by assays based on inhibition of labeled TSH binding to detergent-solubilized porcine TSHR) immunoprecipitated about 4% of the labeled receptor, whereas sera with high levels of receptor autoantibody immunoprecipitated more than 25% of the labeled receptor. The ability to immunoprecipitate labeled TSHR correlated well with ability of the sera to inhibit labeled TSH binding to the receptor (r = 0.92; n = 63), and this is consistent with TSHR autoantibodies in these samples being directed principally to a region of the receptor closely related to the TSH binding site. Preincubation of labeled TSHR with unlabeled TSH before reaction with test sera inhibited the immunoprecipitation reaction, providing further evidence for a close relationship between the TSHR autoantibody binding site(s) and the TSH binding site. This was the case whether the sera had TSH agonist (i.e., thyroid stimulating) or TSH antagonist (i.e., blocking) activities, thus, providing no clear evidence for different regions of the TSHR being involved in forming the binding site(s) for TSHR autoantibodies with stimulating and with blocking activities. The ability of TSHR autoantibodies to stimulate cyclic AMP production in isolated porcine thyroid cells was compared with their ability to immunoprecipitate labeled porcine TSHR. A significant correlation was observed (r = 0.58; n = 50; P < 0.001) and the correlation was improved when stimulation of cyclic AMP production was compared with inhibition of labeled TSH binding to porcine TSHR (r = 0.76). Overall, our results indicate that TSHR autoantibodies bind principally to a region on the TSHR closely related to the TSH binding site, and this seems to be the case whether the autoantibodies act as TSH agonists or antagonists.

Animals↗

PubMed1998

Rectal trauma: management based on anatomic distinctions.

Principles of rectal wound management, including routine diversion, injury repair, presacral drainage and distal washout, evolved from World War II and the Vietnam conflict and have been questioned in recent years. We believe significant confusion arises because of imprecise definition of injury location relative to retroperitoneal involvement. Our 5-year experience with penetrating rectal injuries at a Level I trauma center was analyzed. Injuries to the anterior and lateral surfaces of the upper two-thirds of the rectum were classified as intraperitoneal (IP, serosalized), and those of the posterior surface extraperitoneal (EP, no serosa); injuries to the lower one-third were EP. A total of 58 injuries were managed (92% gunshot wounds). Of these, 16 were IP, and 42 had some EP component. Ten patients underwent repair without diversion (6 IP, 4 EP); there were no leaks. Ten septic complications occurred in the remaining population: 2 necrotizing fasciitis, 5 abdominal abscess, and 3 presacral infections (PIs) (2 presacral abscesses and 1 wound tract infection). PI is the only complication that can be specifically associated with EP rectal injuries relative to management; as associated injury confounds interpretation of the other complications. The operative management in the 38 patients with diverted EP wounds with respect to presacral infection (PI) demonstrated the following: repair injury (n = 10), 0 PI versus no repair (n = 28), 3 PI (P = 0.55); washout (n = 33), 2 PI versus no washout (n = 5), 1 PI (P = 0.35); presacral drain (n = 30), 1 PI versus no drain (n = 8), 2 PI (P = 0.11). We conclude that most IP injuries can be managed with primary repair. EP wounds to the upper two-thirds of the rectum should usually be repaired. EP wounds to the lower one-third, which are explored and repaired, do not require drainage. EP wounds that are not explored should be managed with presacral drainage to minimize the incidence of presacral abscess.

Adolescent↗

PubMedDate not supplied

The importance of follow-up: why is it my responsibility?

Like poor communication, poor office management can create ill-will among patients and can actually contribute to negligence itself. It is imperative that every office have a system for tracking test results and referrals to ensure that patients do not "fall though the cracks". There are several types of effective tracking systems. But, the key to a good follow-up system is to use the system.

Appointments and Schedules↗