Search PubMed⌕ Search

Biomedical subjects

D A Gordon

Publications and source records attributed to D A Gordon.

At least 73 records · Page 4Linked to original sources
PubMed1987

Regulation of chicken apolipoprotein B: cloning, tissue distribution, and estrogen induction of mRNA.

Apolipoprotein (apo) B is a major protein component of plasma very low-density and low-density lipoproteins (VLDL and LDL, respectively) and serves as a recognition signal for the cellular binding and internalization of LDL by the apoB/E receptor. In contrast to the situation in mammals, avian apoB is also a component of specialized VLDL particles that are produced by the liver in response to estrogen. These particles transport cholesterol and triglyceride from the liver to the ovary for deposition in egg yolk. We report here the identification and characterization of cDNA clones for chicken apoB and their use in examining the tissue distribution and hormonal regulation of chicken apoB mRNA. The cDNA clones were identified by immunological screening of a phage lambda gt11 library constructed with hen liver mRNA and their identity was supported by sequence comparisons with mammalian apoB. The chicken apoB mRNA is approximately the same size as mammalian apoB mRNA (14 kb), and, as occurs in mammals, is present at high levels in liver and small intestine. Unlike mammals, the chicken apoB mRNA is also found at high levels in the kidney, consistent with previous protein biosynthetic studies. A DNA-excess solution-hybridization assay was used to quantitate apoB mRNA in these tissues and to examine its hormonal regulation. In control roosters the liver and kidney contained 65% and 10%, respectively, as much apoB mRNA as the small intestine. Within 24 h after estradiol administration, apoB mRNA was increased five- to seven-fold in liver but was unchanged in intestine and kidney. The increase in apoB mRNA content and the kinetics of induction parallel hepatic apoB synthesis, indicating that estrogen regulates apoB production through changes in the cellular abundance of apoB mRNA. The apoB mRNA increased rapidly following hormone treatment while the mRNA for another VLDL protein (apoII) showed a lag or slow phase of several hours before significant mRNA accumulation occurred. These data indicate that the liver can respond immediately to estrogen to increase apoB mRNA accumulation, while apoII mRNA accumulation appears to involve additional events or signals which occur slowly and are specific to this gene.

Amino Acid Sequence↗
PubMed1986

Uniformity of metabolic enzymes within individual motor units.

Individual muscle fibers of 10 motor units from the tibialis posterior muscle of cat were identified by glycogen depletion techniques, characterized for histochemical type, diameter, and intramuscular locations, and analyzed by quantitative biochemical methods. Four enzymes, representing different energy-yielding pathways, were quantitatively assayed in muscle fibers belonging to motor units selected from each of the three major physiological types. All four enzymes demonstrated identical activities among fibers within a motor unit, while showing up to 11-fold differences among fibers belonging to different motor units. Moreover, fibers within a single motor unit, but of substantially different diameters, were nevertheless homogeneous in specific enzyme activities.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1985

Renal subcapsular islet cell transplantation.

This study was directed towards improving islet cell allotransplantation (ICTx) by testing the renal subcapsular region (RSC) as an alternative site for graft placement. In addition, a simplified, non-collagenase method was assessed for preparation of the allograft from the donor pancreas. Five groups of pancreatectomized mongrel dogs were followed. Group I (n = 10) were not transplanted and survived 5.0 +/- 2.92 days (M +/- SD). Five of six animals in Group II (n = 6) which received an ICTx prepared without collagenase in the RSC survived until allograft removal by nephrectomy at greater than 90 days (P less than .0005). No immunosuppression was given to this group. Recipients in Group III (n = 11) were transplanted as in Group II, but were given minimal immunosuppression with azathioprine. They also demonstrated excellent graft function until removal of the graft by nephrectomy at between 3 weeks and greater than 90 days. Animals in Group IV (n = 6) received an intrasplenic (IS) ICTx prepared without collagenase and survived only 4.16 +/- 1.16 days. In Group V (n = 6) poor survival was also noted (7.66 +/- 4.58 days) after IS-ICTx of a collagenase prepared allograft. All animals in Group IV and V received minimal immunosuppression as in Group III. These results indicate the potential for utilization of the RSC as an alternative site for ICTx. In addition, the collagenase-free method was satisfactory for ICTx preparation.

Animals↗
PubMed1985

The frequency of malignant neoplasms in patients with polymyositis-dermatomyositis. A controlled study.

Seventy-one patients with polymyositis-dermatomyositis (PM/DM) admitted to the Wellesley Hospital Rheumatic Disease Unit (RDU) in Toronto between 1965 and 1980 were followed up to 1981. The frequencies of malignant neoplasms occurring prior to or concurrent with initial RDU admission were compared, using case-control methods, with age- and sex-matched control groups with a diagnosis of any non-PM/DM rheumatic disease (rheumatic disease controls) or osteoarthritis, fibrositis, or fracture (noninflammatory musculoskeletal controls). In a cohort analysis, the incidence of malignant neoplasm subsequent to initial RDU admission in patients with PM/DM was compared with the expected incidence in the Canadian population. Fifteen of 71 patients with PM/DM had an antecedent or concurrent cancer compared with four of 71 rheumatic disease controls and one of 71 noninflammatory musculoskeletal controls. Cohort analysis showed no increase in the number of subsequent malignant neoplasms in patients with PM/DM compared with the age- and sex-matched Canadian population.

Adolescent↗
PubMed1984

Alternative applications of cyclosporin A to improve kidney allograft survival.

This study applies cyclosporin A as a donor pretreatment prior to organ harvesting or as a graft pretreatment during preservation of canine kidney allografts by hypothermic pulsatile perfusion or hypothermic storage. All recipients except those in Group IX received minimal immunosuppression with azathioprine after transplantation (5 to 2.5 mg. per kg. per day). No significant differences in survival (X +/- SD) were observed between the 3 control groups which were either 1) flushed with untreated Ringer's lactate solution and immediately transplanted (Group I, no. = 8, 14 +/- 3.33 days), 2) preserved by hypothermic pulsatile perfusion for 24 hours (Group II, no. = 7, 12.0 +/- 8.92 days), or 3) hypothermically stored for 24 hours (Group III, no. = 7 13.1 +/- 11.6 days). A trend towards improved survival was seen in the 2 groups of animals that received kidneys that had been graft pretreated with cyclosporin A (12.5 mg.) during 24 hours preservation by either hypothermic pulsatile perfusion (Group IV, no. = 10, 17.4 +/- 13.32 days, p less than .25) or hypothermic storage (Group V, no. = 6, 8 +/- 12.75 days, p less than .25). Survival of recipients in Groups VI (no. = 6) and VII (no. = 9) who received kidneys whose donors had been pretreated with 25 and 50 mg. per kg. respectively was dependent on the dosage of cyclosporin A used. Donor pretreatment at 50 mg. per kg. was deleterious to kidney function (Group VI, 2.16 +/- 1.47 days, p less than 0.0005). Donor pretreatment with 25 mg. per kg. did not significantly improve survival over control groups (15.66 +/- 12.9 days). Recipients in Groups VIII (no. = 10) and IX (no. = 6) were transplanted with kidneys from cyclosporin A pretreated donors (15 mg. per kg.). These kidneys also received cyclosporin A graft pretreatment (10 mg.) during 24 hours of hypothermic storage. The only difference between Groups VIII and IX was that the animals in Group IX received minimal amounts of cyclosporin A (5 mg. per kg. per day) after transplantation. Combined donor and graft pretreatment yielded improved kidney allograft survival (Group VIII, 21.7 +/- 13.36 days, p greater than .10, Group IX, 20.83 +/- 14.2 days, p greater than .10). However, there was no significant difference observed as a result of the different immunosuppressive protocols used in Groups VIII and IX. These results indicate a trend towards improved renal allograft survival under certain conditions, after donor and graft pretreatment with cyclosporin A.

Animals↗
PubMed1984

Renal subcapsular islet cell transplantation.

Islet cell transplantation has been associated with ultimate graft rejection. This preliminary study investigates the use of the renal subcapsular region as a site for placement of canine islet cell allografts. A new noncollagenase mechanical technique was used for preparation of the allografts. Animals in group I (N = 6) died of hyperglycemia in 4.0 +/- 1.89 days (X +/- SD) after pancreatectomy without subsequent islet cell transplant. Normoglycemia and excellent survival (greater than 60 days) was obtained in pancreatectomized animals in group II (N = 6) and in group III (N = 6), who received an islet cell allograft to the renal subcapsular site. Group II recipients were given no immunosuppression, and animals in group III received minimal immunosuppression with azathioprine. Dependence on the islet cell allograft for maintenance of normoglycemia was confirmed in the majority of the recipients by nephrectomy, to remove the graft, with resulting hyperglycemia and death. One normoglycemic animal in group II died on day 6 from peritonitis. One recipient in group II was normoglycemic at greater than 1 mo after removal of the first graft by nephrectomy, followed by retransplantation of islet cells from a third-party donor. Two other recipients are being studied on a long-term basis, and have been normoglycemic for greater than 6 mo and greater than 4 mo after transplantation. These studies encourage further investigation in this area for application of islet cell transplantation in man, and elucidation of the possible mechanisms for prolongation of islet cell allograft survival at the renal subcapsular site.

Animals↗
PubMed1984

New avenues in the use of cyclosporine for transplantation. Graft and donor pretreatment.

Modification of graft immunogenicity using graft (GPTX) and donor pretreatment (DPTX) has been pursued in an attempt to modify allograft immunogenicity using various immunosuppressive agents. The murine skin allograft and canine renal allograft models were used to study the efficacy of Cyclosporine (Cy A) as a DPTX and GPTX prior to transplantation. Tail skin allografts from C3HHeN male mice were grafted to Balb/c female mouse recipients. Minimal immunosuppression was given to all skin graft recipients. Skin allograft were either GPTX with Cy A, DPTX with either Cy A, methylprednisolone (MP), or cyclophosphamide (CP), or Cy A GPTX and DPTX with the three drugs alone or in combination. Cy A GPTX alone of skin allografts did not significantly prolong survival. DPTX with Cy A significantly prolonged skin graft survival, however, CP or MP alone did not. The various combinations of MP, Cy A, and CP as DPTX and MP, Cy A, and CP DPTX used together with Cy A GPTX also significantly prolonged murine skin allograft survival. Kidney allografts used unrelated mongrel dogs as donors or recipients. Renal transplant experimental groups were either: Non-pretreated and immediately transplanted, nonpretreated and hypothermically stored (HS) for 24 hours in Collins (C-2) solution, GPTX with 12.5 mg Cy A during 24 hr. HS in C-2, DPTX with Cy A (25 mg/Kg), or Cy A DPTX (15 mg/kg) and GPTX during 24 hrs. HS in C-2. Cy A GPTX during HS was sometimes effective in prolonging kidney allograft survival greater than 30 days using only minimal immunosuppression with azathioprine. Cy A DPTX prolonged survival somewhat, but not significantly. Improved results were seen, however, when Cy A DPTX was used together with Cy A graft pretreatment. These results indicate the potential for the successful use of Cy A as a donor and/or graft pretreatment, however, further studies will be necessary to optimize the use of Cy A in these modalities.

Animals↗
PubMed1984

Neurologic complications associated with gold therapy for rheumatoid arthritis.

Neurologic complications of gold are rare and include peripheral neuropathy, a Guillain-Barré-type syndrome, cranial nerve palsies and encephalopathy. Three cases of cranial neuropathy complicating chrysotherapy for rheumatoid arthritis are described. One also had a sensorimotor neuropathy associated with segmental demyelination and axonal degeneration, and another developed an encephalopathy which, on contrast enhanced computed tomographic scanning, showed reversible cerebral and cerebellar white matter lesions. Early recognition and prompt withdrawal of chrysotherapy are the mainstay of management of this lesser known complication.

Adult↗
PubMed1984

Orthotopic liver transplantation. Various immunosuppressive regimens to improve survival.

New approaches to immunosuppression, including cyclosporin A (Cy A), are being utilized to improve liver transplantation survival results. Donor livers from unrelated dogs were orthotopically transplanted to recipient animals, and only recipients that survived 2 or more days were included in this study. Animals were divided into the following groups: Group 1 (n = 6) received minimal immunosuppression (azathioprine) after orthotopic liver transplantation, Group 2 (n = 7) liver allografts were pretreated with Cy A (50 mg/L) prior to transplantation, and recipients were given minimal immunosuppression as in Group 1, Group 3 (n = 6) animals received azathioprine and methylprednisolone after transplantation, and Group 4 (n = 6) liver allograft recipients were given Cy A and methylprednisolone for 30 days followed by azathioprine. The improved survival seen in Groups 2, 3, and 4 in comparison with Group 1 (minimally immunosuppressed controls) indicates that graft pretreatment with Cy A or prophylactic Cy A administration (30 days), in conjunction with minimal immunosuppression, can prolong canine liver allograft survival as well as more standard regimens (Group 3). Therefore, it is possible that the use of steroids could be reduced or eliminated in hepatic transplantation with the application Cy A.

Animals↗
PubMed1984

Transplantation of islet cells.

In an effort to improve the viability of canine pancreatic islet cell allografts after cryopreservation, Cy A was used for graft pretreatment and as a general immunosuppressant on graft recipients who had previously undergone pancreatectomy. Using this combination in conjunction with cryopreservation, islet cell allografts exhibited good viability and long term function after freezing to minus 196 degrees C. These results might encourage the further use of this technique for transplantation.

Animals↗
PubMed1983

Application of cryopreservation techniques to islet cell allotransplantation.

This study continues our investigations in the area of canine islet cell cryopreservation. Islet cell allografts were frozen using a simple method to -196 degrees C with rapid freezing rates and dimethyl sulfoxide as the cryoprotectant. Good in vitro viability was observed using trypan blue dye exclusion. After intrasplenic transplantation, grafts which did not reject were able to maintain normoglycemia for periods of greater than 60 days. The use of either Cy A as an immunosuppressant or ALG as a graft pretreatment contributed to prolongation of allograft survival in these long-term surviving recipients. These results encourage further studies in this area for potential future clinical application of this technique to human pancreas.

Animals↗
PubMed1983

Graft pretreatment with cyclosporin A. Long-term study including four trials in one and a half years.

Four trials were conducted to establish whether Cyclosporin A (Cy A) could be used as a graft pretreatment to prolong the graft function and animal survival of kidneys transplanted into bilaterally nephrectomized mongrel dogs. The first nonrandomized trial analyzed various parameters such as concentration, flush temperatures, effect of reflushing, and the need for subsequent minimal immunosuppression. By analyzing data from the ten groups in this trial, we established that 50 mg/l Cy A could be flushed successfully at either 4 C or 25 C without nephrotoxic effects. This concentration was found to prolong graft function and animal survival in some animals greater than 100 days. Reflushing the kidney after primary graft pretreatment with Cy A did not entirely remove the immunosuppressive effect of the drug as significant prolongation of survival also was observed in this group. In addition, minimal immunosuppression with azathioprine was necessary to observe a delay in the onset of rejection and prolongation of animal survival when Cy A was used for graft pretreatment. Trials 2 and 4 compared the efficacy of the original batch that was obtained later. The effects observed in Trial 1 and reproduced in Trial 3, which were randomized and double blinded using the original batch, were not seen in either Trials 2 or 4. This may have been related to the amount of time that the Cy A was dissolved in ethanol prior to its use or the batch of Cy A utilized. These preliminary results indicate that Cy A, when used for graft pretreatment under certain conditions, can delay the onset of rejection and prolong animal survival of transplanted renal allograft recipients.

Animals↗