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Biomedical subjects

D Taube

Publications and source records attributed to D Taube.

At least 73 records · Page 4Linked to original sources

Improved staining of proteins in polyacrylamide gels including isoelectric focusing gels with clear background at nanogram sensitivity using Coomassie Brilliant Blue G-250 and R-250.

An improved procedure for staining of proteins following separation in polyacrylamide gels is described which utilizes the colloidal properties of Coomassie Brilliant Blue G-250 and R-250. The new method is based on addition of 20% v/v methanol and higher concentrations of ammonium sulfate to the staining solution previously described. The method combines the advantage of much shorter staining time with high sensitivity, a clear background not requiring destaining, stepwise staining, and stable fixation after staining. The method has been applied to staining of polyacrylamide gels after sodium dodecyl sulfate-electrophoresis and isoelectric focusing in carrier ampholyte-generated pH gradients.

Acrylic Resins↗

Non-insulin-dependent diabetes and renal replacement therapy.

Reports of renal replacement therapy in diabetes usually refer to patients with insulin-dependent diabetes mellitus (IDDM) only, and little is known about renal failure in non-insulin-dependent diabetics (NIDDM). A high proportion, 46/141 (32%), of the diabetics treated at our unit since 1974 had NIDDM. They were older at treatment (56 +/- 9 years, mean +/- SD) compared to the IDDM patients (39 +/- 10 years, p less than 0.001), and had a shorter duration of diabetes (13 +/- 8 years versus 23 +/- 8 years, p less than 0.001). Asians and Afro-Caribbeans accounted for 48% of the NIDDM patients (22/46) compared to only 7% of those having IDDM (6/95, p less than 0.0001). Non-diabetic renal disease accounted for the renal failure in 32% (15/46) of the NIDDM patients but only in 10.5% (10/95) of the IDDMs (p less than 0.001). Despite these differences the prevalence of other diabetic complications (retinopathy, neuropathy, and cardiovascular disease) was similar. Patient survival after transplantation was poorer in NIDDM than IDDM (23% and 57%, respectively, at 2 years). Survival on dialysis was equally poor in NIDDM and IDDM. Thus, NIDDM patients treated for renal failure are more commonly non-European and more often have non-diabetic renal disease. Yet other diabetic complications occur to the same extent in both IDDM and NIDDM patients with diabetic nephropathy.

Adult↗

Effect of vitamin E on the production of collagen, DNA and fibronectin in keratocytes in vitro.

Vitamin E (DL-alpha-tocopherol acetate) can inhibit collagen production in rabbit corneal keratocytes in vitro when incubated in the absence of serum. Cell growth is not appreciably affected but fibronectin synthesis is increased after exposure to vitamin E (DL-alpha-tocopherol and DL-alpha-tocopherol acetate) in the absence of serum. These findings may be important in understanding how vitamin E is advocated as both an inhibitor of scar formation and as an aid to healing.

Animals↗

Platelet intermediate filaments: detection of a vimentinlike protein in human and bovine platelets.

Human and bovine platelets contain a 58,000-dalton vimentinlike protein that cross-reacts with antivimentin antibody. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blots indicate that this protein is present in whole platelet lysates and triton insoluble cytoskeletons. Transmission electron microscopy of platelets reveals an isotropic network of individual intermediate filaments distributed throughout the platelets. High salt, triton extracted, glutaraldehyde and tannic acid fixed platelets reveal 10-nm filaments that can be seen to form a peripheral ring, as well as an isotropic network in the body of the cells. Indirect immunofluorescence of resting and spread platelets demonstrates a circumferential staining pattern close to the cell membrane, with additional fibrillar staining throughout the platelets. Our data suggest that the 58,000-dalton vimentinlike protein may be associated with the microtubule coil and the plasma membrane, and may thus help to maintain the resting platelet's discoid shape.

Animals↗

Needle biopsy evaluation of class II major histocompatibility complex antigen expression for the differential diagnosis of cyclosporine nephrotoxicity from kidney graft rejection.

Twenty needle biopsies from 14 patients were taken at times of renal dysfunction, and frozen sections were stained for class I and class II major histocompatibility complex (MHC) antigen expression using the immunoperoxidase technique and monomorphic mouse monoclonal antibodies. Eight of the 9 biopsies taken during periods of dysfunction attributed to cyclosporine toxicity had normal levels of class II expression. In contrast, 9 of the 10 biopsies taken during episodes of rejection had easily recognized increases in class II expression. In the one case where no definite clinical diagnosis was possible, no class II induction was present. Class I levels were less definitive but tended to be markedly raised in the cases of rejection, and only mildly raised in the cases of nephrotoxicity. Biopsy results can be available within 1 1/2-2 hr. The test is therefore likely to be of value in the correct diagnosis of the cause of renal dysfunction and thereby improve the management of cyclosporine-treated renal transplant patients.

Antibodies, Monoclonal↗

Clinical and immunological evolution of oligoanuric anti-GBM nephritis treated by haemodialysis.

Eight patients with oligoanuric anti-glomerular-basement-membrane (GBM), antibody-mediated glomerulonephritis without lung haemorrhage who were not treated with plasma exchange therapy were reviewed. All had severe crescentic nephritis and required dialysis. Circulating anti-GBM antibodies disappeared gradually and spontaneously in all patients. The autoantibodies became undetectable in five patients after an average of 11 months. No patient recovered renal function. Two patients have been successfully transplanted and anti-GBM nephritis has not recurred. One of these needed a pre-transplant course of plasma exchange and immunosuppression to reduce a slightly raised anti-GBM antibody titre. Of five patients who remain on dialysis, only two cannot be transplanted due to the persistence of circulating autoantibodies. One patient died from causes unrelated to renal disease. Oligoanuric patients with anti-GBM nephritis who need dialysis rarely benefit from aggressive therapy unless lung haemorrhage is present.

Acute Disease↗

Adriamycin analogues. Preparation and biological evaluation of some N-(trifluoroacetyl)-14-O-[(N-acetylamino)acyl]adriamycin derivatives.

In connection with structure-activity studies related to the novel DNA-nonbinding adriamycin analogues N-(trifluoroacetyl)adriamycin 14-valerate (AD 32) and N-(trifluoroacetyl)adriamycin 14-O-hemiadipate (AD 143), we have now prepared a series of N-(trifluoroacetyl)adriamycin derivatives with N-acylamino acid esters at the 14-carbinol position. Target compounds were made by reaction of N-(trifluoroacetyl)-14-iododaunorubicin with the sodium salts of N-acylamino acids generally in dimethylformamide-ethylene glycol solvent. Products were evaluated for in vitro growth-inhibitory activity and, to a limited extent, in vivo antitumor activity in the murine P388 leukemia system. ID50 values for the target compounds vs. cultured CCRF-CEM cells were generally in the same range as those for the above-mentioned DNA nonbinding adriamycin analogues. Of the four compounds tested for in vivo activity, although none was as effective as N-(trifluoroacetyl)adriamycin 14-valerate, all showed significant activity in the P388 assay system, with three of the compounds, at the doses used, being essentially equiactive with an optimal dose of adriamycin. Studies on the rate of esterase-mediated deacylation of the products, in a defined system containing unfractionated mouse serum as the source of enzyme, showed no relationship between the in vitro and in vivo activities of these compounds and the relative ease at which the side-chain ester substituents were hydrolyzed.

Animals↗

Tc-99m DTPA scans in renal allograft rejection and cyclosporine nephrotoxicity.

Renal allograft dysfunction arising from rejection or cyclosporine (CsA) nephrotoxicity can currently only be distinguished reliably by allograft biopsy. We have assessed Technetium (Tc)-99m diethylamine pentacetic acid (DTPA) scanning in 30 CsA-treated patients with allograft dysfunction. Scintigrams were performed during 20 biopsy-proved episodes of rejection and during 14 episodes of CsA nephrotoxicity. These results were compared with the scintigrams of 15 allografts showing stable function. Quantitative indices expressing allograft perfusion (flow index) and function (uptake index) derived from the DTPA scintigrams showed no significant differences between the groups of patients with rejection, CsA nephrotoxicity, or stable or improving function. Similarly, the flow and uptake indices of individual allografts obtained during periods of stable or improving function and then during episodes of dysfunction due to rejection or CsA nephrotoxicity did not significantly change. We conclude that Tc-99m DTPA scintigrams are of limited value in the management of allograft dysfunction in patients immunosuppressed with CsA.

Cyclosporins↗

Human renal allograft and peripheral blood T lymphocyte subpopulations during the onset and treatment of rejection.

In order to study the changes in T lymphocyte subpopulations in both allografts and peripheral blood of patients following renal transplantation, we have examined 72 fine needle allograft aspirates and 56 peripheral blood samples from 24 patients during the first month following transplantation. The patients were studied before, during and after rejection episodes. Monoclonal antibodies directed against T helper (TH) and T cytotoxic/suppressor (TCS) cells were used to identify lymphocyte subpopulations in the allograft aspirates and peripheral blood. The ratio of TH:TCS cells in both the allograft aspirates and peripheral blood decreased significantly (p less than 0.01) during the three days before rejection became clinically manifest. During rejection, the aspirate TH:TCS ratios, but not the peripheral blood TH:TCS ratios, remained depressed. Following successful treatment for rejection, the aspirate TH:TCS ratios returned to levels found in non-rejecting allografts. However, in the allografts which were lost as a result of rejection or had persistent rejection despite treatment, the aspirate TH:TCS ratios, but not peripheral blood TH:TCS ratios, remained significantly low (p less than 0.01) when compared with the successfully treated allografts. Our study indicates that TH:TCS ratios, particularly in allograft aspirates, may be of value in predicting the onset and outcome of renal allograft rejection.

Adolescent↗