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E Cantu

Publications and source records attributed to E Cantu.

16 recordsLinked to original sources
PubMed2006

Prolonged function of macrophage, von Willebrand factor-deficient porcine pulmonary xenografts.

Porcine von Willebrand factor (vWF) activates human and primate platelets. Having determined the importance of pulmonary intravascular macrophages (PIMs) in pulmonary xenotransplantation, we evaluated whether, in the absence of PIMs, vWF might play a role in pulmonary xenograft dysfunction. Utilizing a left single-lung transplant model, baboons depleted of anti-alphaGal antibodies received lungs from either vWF-deficient (n = 2); MCP-expressing (n = 5); MCP PIM-depleted (n = 5); or vWF-deficient PIM-depleted swine (n = 3). Two out of three of the PIM-depleted, pvWF deficient grafts survived longer than any previously reported pulmonary xenografts, including PIM-depleted xenografts expressing human complement regulatory proteins. Depletion of PIM's from vWF-deficient lungs, like depletion of PIM's from hMCP lungs, resulted in abrogation of the coagulopathy associated with pulmonary xenotransplantation. Thus, in terms of pulmonary graft survival, control of adverse reactions involving pvWF appears to be equally or even more important than is complement regulation using hMCP expression. However, based on the rapid failure of PIM-sufficient, pvWF-deficient pulmonary xenografts, pVWF-deficient pulmonary xenografts appear to be particularly sensitive to macrophage-mediated damage. These data provide initial evidence that vWF plays a role in the 'delayed' (24 h) dysfunction observed in pulmonary xenotransplantation using PIM depleted hMCP organs.

Animals↗
PubMed2005

Oral feeding with pig peripheral lymphocytes decreases the xenogeneic delayed type hypersensitivity reaction in galactosyltransferase knockout mice.

PURPOSE: Oral tolerance induction has shown promising results in experimental allotransplantation models but is not well investigated in xenotransplantation. We investigated the possibility to induce tolerance against pig peripheral lymphocytes (pPBL) in galactosyltransferase knockout mice (gal -/-), which produce antibodies against Galalpha1-3Gal. MATERIAL AND METHODS: Female (gal -/-) mice 6 to 8 weeks old weighing 35 to 40 g (n = 10) were fed orally every third day five times with 2 x 10(7) isolated, viable pPBL, or with phosphate-buffered saline (PBS) only (n = 7). They were then immunized subcutaneously on day 0 with a subcellular lysate from 4 x 10(7) isolated, viable pPBL. On day 13, 25 microL of a subcellular lysate corresponding to 1 x 10(7) isolated, viable pPBL was injected in the right dorsal foot pad, and the delayed type hypersensitivity (DTH) reaction was calculated after 24 hours by subtracting the swelling response from 25 microL PBS in the left footpad. Anti-Galalpha1-3Gal immunoglobulin IgG and IgM antibody titers were measured in the serum before oral feeding and at day 14. RESULTS: The DTH reaction of the pPBL fed mice was 0.07 +/- 0.05 mm vs 0.57 +/- 0.23 mm for the controls (P < .001). No significant differences in anti Gal alpha1-3 Gal IgG and IgM antibody titers were seen. CONCLUSIONS: This study demonstrates for the first time that oral delivery of pPBL can counteract the indirect T-cell reaction against xenogeneic subcellular antigens from pPBL. These observations warrant further investigation in immunologically modified mice and perhaps in primate models of xenotransplantation.

Administration, Oral↗
PubMed2000

Role of platelet-activating factor in functional alterations induced by xenoreactive antibodies in porcine endothelial cells.

BACKGROUND: Platelet-activating factor (PAF) is a phospholipid mediator of inflammation which has been implicated in rejection. The interaction of anti-alpha-galactosyl natural antibodies (anti-alpha gal Abs) with endothelial cells is the initial step for the development of xenograft rejection. In our study, we stimulated porcine aortic endothelial cells (PAEC) with anti-alpha gal IgG to investigate the synthesis of PAF from PAEC and its biological consequences. METHODS AND RESULTS: PAF was extracted and chromatographically purified from cultured PAEC stimulated with baboon anti-alpha gal Abs. The Abs induced a dose-dependent synthesis of PAF peaking after 30 min of incubation, and decreasing thereafter. Concomitant cell shape change, motility, and cytoskeleton redistribution were observed. These events were prevented by addition of a panel of PAF-receptor antagonists. An SV40 T-large antigen-immortalized PAEC line was engineered to express PAF acetyl-hydrolase (PAF-AH) cDNA, the major PAF-inactivating enzyme. These transfected cells exposed to anti-alpha gal Abs showed reduced cell contraction and motility compared with empty vector-transfected cells. Moreover, in PAEC stimulated with anti-alpha gal Abs, the synthesis of PAF promoted the adhesion of a monocytic cell line as shown by the inhibitory effect of PAF-receptor antagonists and of PAF-AH expression. Finally, studies on cell monolayer demonstrated an enhanced permeability 48 hr after exposure to anti-alpha gal Abs, and this increase was prevented by PAF-inactivation and by PAF-receptor blockade. CONCLUSIONS: These results demonstrate that on stimulation with anti-alpha gal Abs, PAEC synthetize PAF which can contribute to several vascular events involved in xenograft rejection.

Animals↗
PubMed2000

alpha-galactosyl epitopes on glycoproteins of porcine renal extracellular matrix.

BACKGROUND: The pig is the donor animal of choice for human xenotransplantation. In the most relevant pig-to-baboon model, pig organs transplanted into baboons are hyperacutely rejected by natural xenoantibodies, which mainly bind to alpha-galactosyl (alphaGal) epitopes expressed at the surface of endothelial cells. Recent advances in controlling hyperacute rejection have led to improved survival of these xenografts, and it is now important to identify alphaGal binding sites in other cells and tissues that may be subject to immunologic attack. To this end, we have studied whether alphaGal antibodies bind to glycated proteins of the extracellular matrix in the kidney and other organs most likely to be used for human xenotransplantation. METHODS: High-titer anti-alphaGal antibodies, similar to human natural xenoantibodies, were prepared in baboons, and their reactivity with components of pig extracellular matrix was tested by serology and immunohistology. RESULTS: The antibodies recognized epitopes of immobilized murine, bovine or porcine thyroglobulin, laminin, heparan sulfate proteoglycans, and fibronectin. In sections of pig tissue, the antibodies bound to endothelial and certain epithelial cells, as shown in previous studies, and also to mesenchymal cells, basement membranes, and extracellular matrices, in which they colocalized with matrix glycoproteins, especially laminin and heparan sulfate proteoglycans. CONCLUSIONS: These results suggest that when pig xenografts can be made to survive for prolonged periods, the reactivity of alphaGal antibody with matrix molecules can induce basement membrane and matrix lesions similar to those induced in laboratory animals by antilaminin and antiheparan sulfate proteoglycans antibodies.

Animals↗
PubMed1999

Interaction of baboon anti-alpha-galactosyl antibody with pig tissues.

As barriers to xenotransplantation are surmounted, such as suppression of hyperacute rejection allowing improved graft survival, it becomes important to define longer-term host-xenograft interactions. To this end we have prepared in baboons high titer anti-alpha-Galactosyl (alphaGal) and anti-porcine aortic endothelial cell antibodies, similar to human natural xenoantibodies and reactive with epitopes of thyroglobulin, laminin, and heparan sulfate proteoglycans. When injected into pigs with a protocol similar to that used in the rat to show the nephritogenic potential of heterologous anti-laminin and anti-heparan sulfate proteoglycan antibodies, baboon immunoglobulins bound first to renal vascular endothelium, and later to interstitial cells, especially fibroblasts and macrophages, and to antigens in basement membranes and extracellular matrix, where they colocalized with laminin- and heparan sulfate proteoglycan-antibodies, and with bound Griffonia simplicifolia B4. A similar binding was observed in other organs. The pigs did not develop an acute complement-dependent inflammation, but rather chronic lesions of the basement membranes and the extracellular matrix. Incubation of renal fibroblasts with baboon anti-alpha-Galactosyl antibodies resulted in increased synthesis of transforming growth factor-beta and collagen, suggesting a possible basis for the fibrotic response. The results demonstrate that in this experimental model a consequence of alphaGal antibody interaction with porcine tissues, is immunoreactivity with alphaGal on matrix molecules and interstitial cells, priming mechanisms leading to fibrosis resembling that in chronic allograft rejection. The possibility that similar lesions may develop in long-surviving pig xenografts is discussed.

Animals↗
PubMed1999

Salvage by volume reduction of chronic allograft rejection in emphysema.

BACKGROUND: We hypothesized that native lung volume reduction surgery (LVRS) would improve respiratory function in patients who had previously undergone single lung transplantation for emphysema and who were disabled by obliterative bronchiolitis. METHODS: Seven single lung transplant recipients who had advanced bronchiolitis obliterans syndrome (BOS grade 3b), absence of active infection, and suitable anatomy underwent native LVRS. Mean time from lung transplantation to LVRS was 39 +/- 17 months. RESULTS: Mean FEV1 rose from 684 +/- 164 ml before LVRS to 949 +/- 219 ml at 3 months after LVRS, an increment of 40% (p = .002). Mean 6-minute walk rose from 781 +/- 526 ft before LVRS to 887 +/- 539 ft at 3 months after LVRS (p = .031), and mean dyspnea index declined from 3.1 +/- 1.1 before LVRS to 1.6 +/- 0.5 at 3 months after LVRS (p = .010). Mean native lung volume declined from 2956 +/- 648 ml before LVRS to 2541 +/- 621 ml at 3 months after LVRS, but the change was not statistically significant (p = .12). Mean transplant lung volume was little changed before and after LVRS (2099 +/- 411 ml and 1931 +/- 607 ml, respectively, p = NS). There was also a trend toward increased ventilation and perfusion of the native lung and reduction in ventilation and perfusion of the transplant lung, but these changes did not achieve statistical significance. By six months after LVRS, three patients died (two as a consequence respiratory failure), and survivors began to show evidence of deteriorating spirometry. CONCLUSIONS: LVRS is capable of salvaging respiratory function in chronic allograft rejection in emphysema by reducing native lung hyperinflation. These benefits, however, appear to be limited in magnitude and duration by the severity of the underlying allograft dysfunction.

Aged↗
PubMed1999

Membranous glomerulonephritis induced in the pig by antibody to angiotensin-converting enzyme: considerations on its relevance to the pathogenesis of human idiopathic membranous glomerulonephritis.

In the course of studies on the humoral consequences of swine to primate xenotransplantation, the investigators induced formation of glomerular subepithelial immune deposits and tubular lesions in pigs injected with heterologous antibody to angiotensin-converting enzyme. This study describes the morphology of the lesions, discusses their mechanism, explains their relevance for understanding the pathogenesis of human idiopathic membranous glomerulonephritis, and proposes future directions for investigations.

Animals↗
PubMed1998

Preliminary experience with mycophenolate mofetil used after lung transplantation.

This study reports our preliminary experience with mycophenolate mofetil (MMF)-based immune suppression after lung transplantation. Thirteen patients (group 1) received MMF as primary therapy immediately after transplantation. Use of MMF was associated with a linearized rate of 0.85 episodes of acute rejection per 100 patient days during the first 3 months after transplantation, as compared with rates of 1.49 and 1.38, observed in two groups of historical control subjects (p = .094 and p = .053, respectively). Rejection rates after the first 3 months were not lower than in historical control subjects. Nine additional patients were switched from azathioprine to MMF because of recurrent episodes of high-grade acute rejection (group 2). In this group, the linearized rate of acute rejection episodes declined significantly (p = .004) after initiation of MMF therapy. These data suggest a potential role for MMF in reducing the rate of acute rejection episodes after lung transplantation.

Azathioprine↗
PubMed1987

A custom speech valve retainer for the laryngectomee.

A technique is presented for the fabrication of a custom silicone speech valve retainer that is easily fabricated, may be tinted to match the skin tone, is well tolerated, noninvasive, and functions well in patients who can generate sufficient air pressure to close the valve. This device can greatly improve the quality of life for laryngectomees by allowing hands-free, alaryngeal oral speech.

Colloids↗
PubMed1986

Customized valve housing.

Numerous remarkable advancements have been made in the area of voice prosthetics. A significant, persistent problem, however, has been the development of air leaks around the tracheostome housing. This problem is particularly apparent with patients having deeply recessed, irregular stomas. This paper describes a customized tracheostome valve housing that is fabricated to minimize or alleviate difficulties associated with maintenance of an airtight seal. Our experience with 12 patients revealed that they maintain adequate seals for 72 hours and enjoy the functional benefits provided by the customized housing.

Humans↗
PubMedDate not supplied

Current status of laryngectomee rehabilitation: I. Results of therapy.

Of 103 people with the clinical diagnosis of laryngeal cancer studied by the authors, 53 eventually were treated by total laryngectomy and, in some cases, radical neck dissection (43), preoperative radiation therapy (15), postoperative radiation therapy (29), and post-operative chemotherapy (7). All were entered into a comprehensive rehabilitation program. Six months following completion of their cancer therapy 47 were re-evaluated. Of these, 12 (26 per cent) used esophageal speech as the dominant mode of communication, 16 (34 per cent) the electrolarynx, and the remainder either wrote (16 [34 per cent]) or signed (3 [6 per cent]). Twenty-six (55 per cen) were considered to be successfully) rehabilitated overall and 21 (45 per cent) were not. These data indicate that the rehabilitative needs of today's laryngectomee are not being met successfully with traditional methods.

Adult↗
PubMedDate not supplied

Current status of laryngectomee rehabilitation: II. Causes of failure.

The study records of 47 laryngectomees were analyzed to determine the factors related to acquisition of failure to acquire esophageal speech and to successful or unsuccessful rehabilitation. The successful speakers wee able to phonate longer preoperatively, had less postoperative radiotherapy and dysphagia, took more speech instruction, and were more vigorous and tender-minded. Factors that correlated with successful rehabilitation were less postoperative radiotherapy, more vigor, greater imaginativeness, independence, and self-assuredness, and absence of denial.

Attitude to Health↗
PubMedDate not supplied

Current status of laryngectomee rehabilitation: III. understanding of esophageal speech.

To assess those aspects of esophageal speech that contribute to effective communication, a series of measures were applied to the esophageal speech of a prospectively studied group of recent laryngectomees (n = 20) six months following completion of their cancer therapy and to that of a second group (n = 27) studied retrospectively 6.6 years postoperatively. Ages of the two groups did not differ, but there were more whites and more males in the group studied retrospectively. The technical proficiency of the subjects studied prospectively was slightly but significantly less than that of those studied retrospectively. Measures of technical proficiency correlated well with other measures of quality of esophageal speech and were much easier to perform. The understandability of the esophageal speech of the group studied retrospectively was significantly superior. For both groups, understandability was enhanced significantly during audiovisual compared with audio-only presentations. Naive judges had great variability in understanding esophageal speech.

Esophagus↗
PubMedDate not supplied

Tracheoesophageal speech: predictors of success and social validity ratings.

PURPOSE: The purpose of this study was to examine long-term success rates and predictors of success for patients who had undergone either primary or secondary tracheoesophageal puncture. An additional aim was to compare judgments of communication effectiveness made by a speech-language pathologist with those made by the patient or significant other. PATIENTS AND METHODS: Thirty-six laryngectomees were initially rated on a 5-point functional communication scale. These ratings resulted in the formation of two distinct groups that were identified as "successful" and "unsuccessful." The groups were compared on the basis of age at time of surgery and 10 categorical variables that have been implicated in the success or failure of tracheoesophageal puncture surgery. RESULTS: Results indicated that nearly two thirds of the patients had successful communication at an average of approximately 4 years posttracheoesophageal puncture. For the 13 patients judged as "unsuccessful," reduced vision, limited arm/hand movement, and history of radiotherapy were found in significantly greater numbers. When communication profile ratings made by a speech-language pathologist were compared with those made by the patient or significant other (P/SO), approximately one-third varied by at least "1" scale value, with the vast majority resulting in comparatively higher ratings by the speech-language pathologist. CONCLUSION: The findings of this study are in general agreement with previously published success rates for tracheoesophageal puncture and attest to the long-term nature of these success rates in a majority of patients. Additional investigation is necessary to identify factors that may contribute to discrepancies between clinician expectations and those of the patient or significant other.

Female↗