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Biomedical subjects

M G Donovan

Publications and source records attributed to M G Donovan.

At least 19 recordsLinked to original sources
PubMed1994

Maxillary and mandibular reconstruction using calvarial bone grafts and Branemark implants: a preliminary report.

A review of 24 patients reconstructed with calvarial bone grafts and 93 Branemark implants (Nobelpharma, Chicago, IL) revealed an overall success rate of 91.4%. Two grafting techniques were used. A vertical grafting technique with delayed implant placement had an 86% success rate in 13 patients who had 50 implants placed. The average follow-up for this group was 31 months. A horizontal grafting technique with immediate implant placement had a success rate of 98%. This group included 13 patients who had 43 implants placed at the time of their bone grafting procedure. Two patients had a combination of grafting techniques. The average follow-up for this group was 18 months. A patient questionnaire revealed a high percentage and degree of satisfaction.

Adult↗
PubMed1994

Experimental evaluation of expanded polytetrafluoroethylene for reconstruction of orbital floor defects.

OBJECTIVE: This study evaluates the efficacy of a medical grade expanded polytetrafluoroethylene (e-PTFE) sheet for reconstruction of the orbital floor. MATERIALS AND METHODS: Orbital floor defects were created in 10 domestic sheep and reconstructed with the 1-mm thick e-PTFE sheet. The surgical sites were evaluated for the development of enophthalmos and biocompatibility at 2 weeks, and at 1-, 2-, 4-, and 6-months intervals. RESULTS: The results of this indicate that the e-PTFE material has excellent handling characteristics, provides stability to correct surgically created enophthalmos, and causes essentially no foreign body reaction. CONCLUSION: Expanded polytetrafluoroethylene proved to be an excellent alloplastic material for the repair of orbital floor defects in this experimental study.

Animals↗
PubMed1994

Transplant nephrectomy over 20 years: factors involved in associated morbidity and mortality.

Of 1,048 renal transplants performed between 1971 and 1990, transplant nephrectomy was performed in 86 (8.2%). Mean patient age was 33 years (range 3.8 to 66.5). Postoperative complications occurred in 60% of the patients, including wound infection in 20% and major hemorrhage in 4 patients. The external iliac artery was ligated in 4 patients. The incidence and severity of the complications were greater in patients with acute rejection. Four patients died: 1 of ischemic bowel and metastatic carcinoma, 1 of pulmonary embolism, and 2 of sepsis and disseminated intravascular coagulation. The nephrectomy rate increased significantly (p < 0.005) when cyclosporine A was initially introduced. Added care is necessary when new immunosuppressants are used. The majority of our failed transplants were left in situ without compromising overall patient well-being.

Adolescent↗
PubMed1994

Renal transplantation in patients with spina bifida.

OBJECTIVES: Renal transplantation in patients with spina bifida is not commonly performed, although these patients have a high incidence of end-stage renal disease. METHODS: Between February 1989 and December 1991, we performed 5 cadaveric renal transplants in 4 patients with spina bifida. There were 3 male patients and 1 female patient with a mean age of 22.5 years (range, 10 to 36 years). All patients had lumbar myelomeningoceles repaired shortly after birth. Three patients were wheelchair-bound due to their neurologic deficit. Prior to renal transplantation, management of neuropathic bladder dysfunction consisted of ileal conduit (1 patient), "clam" cystoplasty with clean intermittent self-catheterization (CISC; 1 patient), and CISC alone (2 patients). RESULTS: In this series, 1 patient died of fungal septicemia 6 weeks postoperatively. One patient underwent transplantation again following primary nonfunction of his original allograft. Serum creatinine levels were 56, 91, and 120 mmol/L, respectively, after 18 months' follow-up. CONCLUSIONS: This article demonstrates the feasibility of cadaveric renal transplantation in selected patients with end-stage renal failure and spina bifida. We currently recommend that these patients not be excluded from gaining the benefits of renal transplantation.

Adolescent↗
PubMed1993

Older donors and kidney transplantation.

Reluctance to use kidneys from older donors (> 50 years of age) is based on reports of inferior results. We reviewed our experience with 45 kidneys transplanted from older donors. Primary nonfunction, immediate graft function, and 1-, 2- and 3-year graft survival rates were similar to those obtained with kidneys transplanted from donors aged between 20 and 40 years. Renal function at 1 year (as measured by serum creatinine) was poorer in kidneys from older donors. No beneficial effect with respect to graft survival was noted with cyclosporin therapy compared to conventional immunosuppression; however, the numbers are small. We conclude that kidneys from older donors are a valuable source for transplantation.

Adult↗
PubMed1993

Autologous calvarial and iliac onlay bone grafts in miniature swine.

Calvarial bone has been reported to be superior to iliac bone for onlay bone grafting due to decreased resorption. This study evaluated the physical, histologic, and radiographic characteristics of calvarial and corticocancellous iliac onlay bone grafts in nine Pitman-Moore miniature swine at 2 weeks, and at 1-, 2-, 4-, 6-, 7-, 8-, 10-, and 12-month intervals. Compared with iliac grafts, the calvarial onlay grafts had more than a twofold greater radiographic density. Statistical analysis of the mature grafts using the standard of estimated means of the bone graft volumes revealed 85% retention of the calvarial grafts compared with 34% retention of the grafted iliac bone. There was no subjective difference in the rate or degree of revascularization between the two grafted materials.

Animals↗
PubMed1993

Combined transmandibular-zygomatic approach and infratemporal craniotomy for intracranial skull base tumors.

Large intracranial skull base tumors remain surgically treacherous lesions. The preauricular transzygomatic infratemporal approach to this area has rapidly gained popularity. This article presents modifications to this approach which improved visualization and access to the infratemporal fossa. The procedure increases visualization, minimizes brain retraction, and results in improved resection and outcome. Reconstruction is rapid and there are minimal functional and cosmetic deficits.

Bone Plates↗
PubMed1993

c-myc expression in renal carcinoma: correlation with clinical parameters.

There is evidence that c-myc is expressed in renal carcinomas and that it is associated with histological grade. This study reports on the clinical correlations of oncogene expression and clinical features of the disease. Tissue sections from 97 patients (95 primary and 12 secondary cancers) were immunostained with a c-myc oncoprotein antibody. The tumours were scored for extent and intensity of nuclear and cytoplasmic staining. Ninety patients were suitable for follow-up study. High levels of expression correlated significantly with increasing T category and nuclear grade, as well as with venous invasion. No correlation with nodal involvement, the presence of metastases, tumour architecture or cell type was found. The extent of nuclear staining was related to survival (although not to recurrence), but in a multivariate analysis did not provide independent prognostic information. It was concluded that semiquantitative assessment of levels of c-myc oncoprotein does not provide clinically useful prognostic information.

Adult↗
PubMed1993

Ploidy and prognosis in renal carcinoma.

The value of tumour ploidy status as a prognostic indicator in renal carcinoma is disputed. In this retrospective study the DNA content of 90 primary and 10 secondary renal cell carcinomas was measured using flow cytometry. Data on recurrence and survival were available in all cases. Tumours were staged according to the TNM system and histological grade was based on nuclear morphology. Formalin-fixed, paraffin-embedded material was processed using standard techniques. Multiple samples were examined in 19 cases. Of the primary tumours, 52 were diploid, 24 were aneuploid and 6 were tetraploid; 8 patients had uninterpretable histograms. Ploidy of the secondary tumours was similar to that of their respective primaries. Aneuploidy correlated with higher grade but not with TNM category and, although associated with an increased risk of death, did not provide independent prognostic information. Heterogeneity of ploidy was found in 6 of the 19 cases where more than 1 sample was assessed. It was concluded that tumour DNA content in renal carcinoma is weakly linked to outcome, is subject to sample error and does not provide accurate prognostic information as a single independent variable.

Adult↗
PubMed1992

A screening procedure for the intracellular expression of native proteins by Saccharomyces cerevisiae: discrimination of diphtheria toxin-resistant mutants.

A general method is described for screening Saccharomyces cerevisiae colonies for the intracellular expression of native proteins. Colonies are replicated onto nitrocellulose membranes and yeast cell walls are removed enzymatically. The resulting spheroplasts are rapidly lysed by placing chromatography paper soaked in hypotonic buffer on the membranes. Intracellular proteins released by spheroplast lysis are bound in situ to the nitrocellulose under non-denaturing conditions and potentially can be examined using enzymatic or immunologic methods. For example, in the present study colonies were screened for the presence of elongation factor 2 (EF-2) that can be [32P]ADP-ribosylated by diphtheria toxin and [32P]NAD+. Recognition by the toxin requires the presence in EF-2 of the unique post-translationally modified histidine derivative, diphthamide. The procedure described here reliably discriminates between wild-type yeast colonies and mutant colonies that do not synthesize diphthamide. In addition to facilitating the study of diphthamide biosynthesis in yeast, the more general application of this procedure will enable the screening of colonies with assays that require native proteins.

Collodion↗
PubMed1992

Artificial bladder replacement: a new design concept [see comment].

An effectively functioning artificial bladder would be useful after cystectomy because of the ease of insertion and the availability to all patients. In this report, we describe a new design concept based on negative pressure drainage of the kidneys and active voiding, and we present the results of testing this device. Although previous prosthetic bladders have had difficulties with renal failure from hydronephrosis, infection from retention of urine, and encrustation of the luminal surface, the current artificial complete bladder system addresses these problems.

Humans↗
PubMed1992

Image analysis in the determination of ploidy and prognosis in renal cell carcinoma.

The usefulness of ploidy determination by flow cytometry in renal cell carcinoma is disputed. An alternative technique for DNA quantitation, computerised static image analysis, has several advantages over flow methods. Tissue from 90 cases of primary renal cell carcinoma was analysed by image analysis. Cases were assigned a histological grade and staged and stratified by the TNM system. Fifty-two cases were diploid, 28 were aneuploid and 9 were tetraploid (1 was unanalyzable). Heterogeneity of ploidy was noted in 4 cases. The degree to which nuclear DNA content exceeded that of normal nuclei from the same block was also calculated (5C exceeding rate). Stage and grade provided independent prognostic information. Aneuploidy was associated with higher mortality but neither ploidy nor 5C exceeding rate were prognostic indicators. Image analysis is a useful and accurate method for ploidy determination and provides additional data on DNA quantitation but this information is not predictive of the clinical outcome.

Adult↗
PubMed1991

Saccharomyces cerevisiae elongation factor 2 is phosphorylated by an endogenous kinase.

Mammalian cells contain a Ca2+/calmodulin-dependent protein kinase that specifically phosphorylates and inactivates elongation factor 2 (EF-2) in response to hormones and other agents which increase intracellular Ca2+ concentrations. Therefore, it has been proposed that the rate of translation in mammals is regulated by EF-2 phosphorylation. In the present study, EF-2 purified from the yeast Saccharomyces cerevisiae is shown to be a substrate for the mammalian EF-2 kinase. Furthermore, evidence was obtained using two-dimensional gel electrophoresis and peptide mapping which suggests that yeast EF-2 is a substrate for an endogenous kinase which phosphorylates the same site as the mammalian EF-2 kinase. Based on these findings, we propose that in yeast as in higher eukaryotes, the protein synthesis elongation cycle is regulated by phosphorylation of EF-2.

Animals↗
PubMed1991

Purification and assay of cell-invasive form of calmodulin-sensitive adenylyl cyclase from Bordetella pertussis.

An invasive form of the CaM-sensitive adenylyl cyclase from Bordetella pertussis can be isolated from bacterial culture supernatants. This isolation is achieved through the use of QAE-Sephadex anion-exchange chromatography. It has been demonstrated that the addition of exogenous Ca2+ to the anion-exchange gradient buffers will affect elution from the column and will thereby affect the isolation of invasive adenylyl cyclase. This is probably due to a Ca2(+)-dependent interaction of the catalytic subunit with another component in the culture supernatant. Two peaks of adenylyl cyclase activity are obtained. The Pk1 adenylyl cyclase preparation is able to cause significant increases in intracellular cAMP levels in animal cells. This increase occurs rapidly and in a dose-dependent manner in both N1E-115 mouse neuroblastoma cells and human erythrocytes. The Pk2 adenylyl cyclase has catalytic activity but is not cell invasive. This material can serve, therefore, as a control to ensure that the cAMP which is measured is, indeed, intracellular. A second control is to add exogenous CaM to the Pk1 adenylyl cyclase preparation. The 45-kDa catalytic subunit-CaM complex is not cell invasive. Although the mechanism for membrane translocation of the adenylyl cyclase is unknown, there is evidence that the adenylyl cyclase enters animal cells by a mechanism distinct from receptor-mediated endocytosis. Calmodulin-sensitive adenylyl cyclase activity can be removed from preparations of the adenylyl cyclase that have been subjected to SDS-polyacrylamide gel electrophoresis. This property of the enzyme has enabled purification of the catalytic subunit to apparent homogeneity. The purified catalytic subunit from culture supernatants has a predicted molecular weight of 45,000. This polypeptide interacts directly with Ca2+ and this interaction may be important for its invasion into animal cells. Finally, the technique for purifying the catalytic subunit by SDS-polyacrylamide gel electrophoresis may prove useful in studying the interaction of the adenylyl cyclase with other components produced by the bacteria, as well as the interaction of the enzyme with eukaryotic target cells.

Adenosine Triphosphate↗
PubMed1991

Transplantation of kidneys from pediatric cadaver donors to adult recipients.

Pediatric donors (less than 12 years old) are a potentially important source of kidneys for adult recipients. Previous reports of decreased graft survival and increased complication rates have made surgeons wary of using such kidneys. In 64 kidneys from younger donors transplanted to adult recipients the delayed graft function rate (41 versus 42%), and 2 and 3-year graft survival rates (67 versus 72% and 61 versus 65%, respectively) were similar to those seen with kidneys from adult donors. Kidneys from donors 24 months old or less experienced an 80% rate of graft loss at 1 year. When these kidneys are excluded the 1-year graft survival rate was similar to kidneys from older and younger donors (70 versus 77%). Mean serum creatinine at 1 year was similar in both groups (155 +/- 21 versus 151 +/- 10). Pediatric kidneys except those obtained from donors 2 years old or less are suitable for adult recipients. However, kidneys from very young donors may be more appropriate to pediatric recipients.

Adult↗
PubMed1991

A model of human small intestinal absorptive cells. 1. Transport barrier.

The Caco-2 cell culture model of human small intestinal absorptive cells was used to investigate transepithelial transport. Transport of permeability markers such as mannitol demonstrated that Caco-2 monolayers became less permeable with increasing age in culture. Cells were routinely used for transport studies between day 18 and day 32. A transport index was determined for each compound by calculating the ratio of transport of the molecules under investigation to transport of an internal standard such as the permeability marker mannitol. Comparison of transport rates at 4 and 37 degrees C was a simple approach for differentiating primary transport mechanisms (passive paracellular, passive transcellular, or transporter-mediated) but must be coupled with additional experimental manipulations for definitive determination of transport pathways. Compounds predicted to undergo predominantly paracellular transport (mannitol, FITC, PEG-900, and PEG-4000), transporter-mediated transcellular transport (glucose, biotin, spermidine, or alanine), or lipophilic transcellular transport (alprenolol, propranolol, clonidine, or diazepam) showed differential effects of temperature on rates of transport as well as the transport index.

Biological Transport↗
PubMed1990

Secretion of the Bordetella pertussis adenylate cyclase from Escherichia coli containing the hemolysin operon.

The extracellular calmodulin-sensitive adenylate cyclase produced by Bordetella pertussis is synthesized as a 215-kDa precursor. This polypeptide is transported to the outer membrane of the bacteria where it is proteolytically processed to a 45-kDa catalytic subunit which is released into the culture supernatant [Masure, H.R., & Storm, D.R. (1989) biochemistry 28, 438-442]. The gene encoding this enzyme, cyaA, is part of the cya operon that also includes the genes cyaB, cyaD, and cyaE. A comparison of the predicted amino acid sequences encoded by cyaA, cyaB, and cyaD with the amino acid sequences encoded by hlyA, hlyB, and hlyD genes from the hemolysin (hly) operon from Escherichia coli shows a large degree of sequence similarity [Glaser, P., Sakamoto, H., Bellalou, J., Ullmann, A., & Danchin, A. (1988) EMBO J. 7, 3997-4004]. Complementation studies have shown that HlyB and HlyD are responsible for the secretion of HlyA (hemolysin) from E. coli. The signal sequence responsible for secretion of hemolysin has been shown to reside in its C-terminal 27 amino acids. Similarly, CyaB, CyaD, and CyaE are required for the secretion of CyaA from Bordetella pertussis. We placed the cyaA gene and a truncated cyaA gene that lacks the nucleotides that code for a putative C-terminal secretory signal sequence under the control of the lac promoter in the plasmid pUC-19. These plasmids were transformed into strains of E. coli which contained the hly operon. The truncated cyaA gene product, lacking the putative signal sequence, was not secreted but accumulated inside the cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗