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H T Aretz

Publications and source records attributed to H T Aretz.

At least 19 recordsLinked to original sources
PubMed2004

Studies on the differentiation pathway and growth characteristics of epithelial culture cells of the human prostate.

We established explant primary cultures in order to study the growth and hormone responsiveness, and the differentiation process of prostatic epithelial cells. Cell outgrowth was achieved from explant tissue by using a new DU145-cell-conditioned medium and special plastic coverslips. To define the present model, proliferation assays were tested by [3H]thymidine assay and planimetric analysis. Cells were analyzed using immunocytochemistry, light, phase contrast and electron microscopy, polymerase chain reaction, telomerase ELISA and immunoassay (PSA). Morphology and electron microscopy revealed typical epithelial differentiation. Immunocytochemistry showed the content of basal and secretory epithelial cells, endocrine paracrine cells and a high level of proliferation. With increasing culture time, mature epithelial differentiation (PSA) increases and the initial increase of alpha-smooth muscle actin (alpha-SMA) decreases again. After further passaging, alpha-SMA expression is no longer detected and PSA expression decreases. Furthermore, epithelial cells showed both androgen responsiveness and androgen receptor expression. These findings show the presence of epithelial cells in a process of differentiation with endocrine paracrine cells and a high level of proliferation. This model may maintain the cellular and functional properties more closely related to the human prostate and may provide a valuable tool for studying stem cells and differentiation characteristics.

Cell Culture Techniques↗
PubMed2003

Evaluation of intracoronary stenting by intravascular optical coherence tomography.

BACKGROUND: Conventional contrast cineangiography and intravascular ultrasound (IVUS) provide a limited definition of vessel microstructure and are unable to evaluate dissection, tissue prolapse, and stent apposition on a size scale less than 100 micro m. OBJECTIVE: To evaluate the use of intravascular optical coherence tomography (OCT) to assess the coronary arteries in patients undergoing coronary stenting. METHODS: OCT was employed in patients having percutaneous coronary interventions. Images were obtained before initial balloon dilatation and following stent deployment, and were evaluated for vessel dissection, tissue prolapse, stent apposition, and stent asymmetry. IVUS images were obtained before OCT, using an automatic pull back device. RESULTS: 42 stents were imaged in 39 patients without complications. Dissection, prolapse, and incomplete stent apposition were observed more often with OCT than with IVUS. Vessel dissection was identified in eight stents by OCT and two by IVUS. Tissue prolapse was identified in 29 stents by OCT and 12 by IVUS; the extent of the prolapse (mean (SD)) was 242 (156) microm by OCT and 400 (100) microm by IVUS. Incomplete stent apposition was observed in seven stents by OCT and three by IVUS. Irregular strut separation was identified in 18 stents by both OCT and IVUS. CONCLUSIONS: Intracoronary OCT for monitoring stent deployment is feasible and provides superior contrast and resolution of arterial pathology than IVUS.

Adult↗
PubMed2001

Endothelial nitric oxide synthase limits left ventricular remodeling after myocardial infarction in mice.

Background- To investigate the role of endothelial nitric oxide synthase (NOS3) in left ventricular (LV) remodeling after myocardial infarction (MI), the impact of left anterior descending coronary artery ligation on LV size and function was compared in 2- to 4-month-old wild-type (WT) and NOS3-deficient mice (NOS3(-/-)). Methods and Results- Two days after MI, both strains of mice had a similar LV size, fractional shortening, and ejection fraction by echocardiography. Twenty-eight days after MI, both strains had dilated LVs with decreased fractional shortening and lower ejection fractions. Although the infarcted fraction of the LV was similar in both strains, LV end-diastolic internal diameter, end-diastolic volume, and mass were greater, but fractional shortening, ejection fraction, and the maximum rate of developed LV pressure (dP/dt(max)) were lower in NOS3(-/-) than in WT mice. Impairment of diastolic function, as measured by the time constant of isovolumic relaxation (tau) and the maximum rate of LV pressure decay (dP/dt(min)), was more marked in NOS3(-/-) than in WT mice. Mortality after MI was greater in NOS3(-/-) than in WT mice. Long-term administration of hydralazine normalized blood pressure in NOS3(-/-) mice, but it did not prevent the LV dilatation, impaired systolic and diastolic function, and increased LV mass that followed MI. In WT mice, capillary density and myocyte width in the nonischemic portion of the LV did not differ before and 28 days after MI, whereas in NOS3(-/-) mice, capillary density decreased and myocyte width increased after MI, whether or not hydralazine was administered. Conclusions- These results suggest that the presence of NOS3 limits LV dysfunction and remodeling in a murine model of MI by an afterload-independent mechanism, in part by decreasing myocyte hypertrophy in the remote myocardium.

Animals↗
PubMed2000

Mechanisms of tolerance induction and prevention of cardiac allograft vasculopathy in miniature swine: the effect of augmentation of donor antigen load.

OBJECTIVE: Cotransplantation of a donor kidney along with a heart allograft can induce tolerance to both organs and prevent cardiac allograft vasculopathy in miniature swine. To determine whether the tolerogenic effect of donor kidney cotransplantation was due to an effect specific to the kidney graft or to an increase in donor antigen load, we compared heart-kidney recipients with recipients receiving two class I disparate hearts or with recipients receiving donor peripheral mononuclear cells at the time of isolated heart transplantation. METHODS: Recipients of major histocompatibility complex class I disparate allografts received 12 days of cyclosporine (INN: cyclosporin; 10-13 mg/kg administered intravenously on days 0-11). Group 1 animals received a heart alone (n = 5). Group 2 animals received heart and kidney allografts (n = 4). Group 3 animals received two major histocompatibility complex-matched heart allografts (n = 4). Two double-heart recipients were thymectomized 21 days before transplantation. Group 4 animals received a heart allograft and an infusion of high-dose donor peripheral blood leukocytes (2.5 x 10(9) cells/kg, n = 2). RESULTS: Vasculopathy developed in group 1 recipients and the allografts were rejected within 55 days. Group 2 recipients accepted their heart and kidney allografts indefinitely without vasculopathy. Euthymic recipients from group 3 accepted their hearts long-term (>190 and >197 days), but vascular lesions developed. In thymectomized recipients from group 3, the hearts were rejected in 63 and 96 days with severe vasculopathy. Group 4 recipients demonstrated transient macrochimerism but their hearts were rejected within 47 and 63 days. CONCLUSIONS: The beneficial effects of donor kidney cotransplantation on cardiac allograft survival and prevention of cardiac allograft vasculopathy are likely to involve both an increase in donor antigen load and an effect specific to the kidney allograft.

Animals↗
PubMed2000

The impact of cocaine on the donor heart: a case report.

With a limited supply of donor hearts in the United States and a prevalent history of cocaine abuse among potential heart donors, the question of transplanting the hearts of cocaine users presents a dilemma to the surgeon. We report a patient who died of the acute right ventricular failure of a heart from a donor with a history of binge drinking and cocaine abuse and who had sustained traumatic brain death. The donor's serum was positive for cocaine prior to transplantation, and autopsy findings were consistent with cocaine cardiomyopathy. This case illustrates the importance of accurate donor history and toxicologic screen prior to heart transplantation and suggests that hearts of cocaine users should not be transplanted, especially in a setting of traumatic brain death.

Adult↗
PubMed2000

Regional myocardial perfusion after experimental subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The pathophysiology of cardiac injury after subarachnoid hemorrhage (SAH) remains controversial. Data from animal models suggest that catecholamine-mediated injury is the most likely cause of cardiac injury after SAH. However, researchers also have proposed myocardial ischemia to be the underlying cause, as a result of coronary artery disease, coronary artery spasm, or hypertension and tachycardia. To test the hypothesis that SAH-induced cardiac injury occurs in the absence of myocardial hypoperfusion, we developed an experimental canine model that reproduces the clinical and pathological cardiac lesions of SAH and defines the epicardial and microvascular coronary circulation. METHODS: Serial ECG, hemodynamic measurements, coronary angiography, regional myocardial blood flow measurements by radiolabeled microspheres, 2D echocardiography, and myocardial contrast echocardiography were performed in 9 dogs with experimental SAH and 5 controls. RESULTS: Regional wall motion abnormalities were identified in 8 of 9 SAH dogs and 1 of 5 controls (Fisher's Exact Test, P=0.02) but no evidence was seen of coronary artery disease or spasm by coronary angiography and of significant myocardial hypoperfusion by either regional myocardial blood flow or myocardial contrast echocardiography. CONCLUSIONS: In this experimental model of SAH, a unique form of regional left ventricular dysfunction occurs in the absence of myocardial hypoperfusion. Future studies are justified to determine the cause of cardiac injury after SAH.

Animals↗
PubMed2000

Porcine coronary imaging in vivo by optical coherence tomography.

OBJECTIVE: A high-resolution coronary artery imaging modality has the potential to address important diagnostic and management problems in cardiology. Optical coherence tomography (OCT) is a promising new optical imaging technique with a resolution of approximately 10 microm. The purpose of this study was to use a new OCT catheter to demonstrate the feasibility of performing OCT imaging of normal coronary arteries, intimal dissections, and deployed stents in vivo. METHODS AND RESULTS: Normal coronary arteries, intimal dissections, and stents were imaged in five swine with OCT and compared with intravascular ultrasound (IVUS). In the normal coronary arteries, visualization of all of the layers of the vessel wall was achieved with a saline flush, including the intima which was not identified by IVUS. Following dissection, detailed layered structures including intimal flaps, intimal defects, and disruption of the medial wall were visualized by OCT. IVUS failed to show clear evidence of intimal and medial disruption. Finally, the microanatomic relationships between stents and the vessel walls were clearly identified only by OCT. CONCLUSIONS: In this preliminary experiment, we have demonstrated that in vivo OCT imaging of normal coronary arteries, intimal dissections, and deployed stents is feasible, and allows identification of clinically relevant coronary artery morphology with high-resolution and contrast.

Animals↗
PubMed2000

The use of a novel tissue sealant as a hemostatic adjunct in cardiac surgery.

BACKGROUND: In spite of advances in the management of bleeding associated with cardiac surgery, hemorrhage remains a troublesome problem, particularly in complex cases and high risk patients. In minimally invasive cardiac surgery, limited exposure and tight quarters may make accurate suturing difficult, and increase the risk of surgical bleeding. A surgical sealant that effectively prevents suture line bleeding would be a valuable resource for cardiac surgeons and might help to facilitate minimal access cases. METHODS: We undertook acute canine studies with a new polyethylene glycol-based tissue sealant (FocalSeal, Focal, Inc., Lexington, MA) to determine its effectiveness in controlling bleeding from graduated needle punctures sites in the arteries of heparinized animals. For chronic canine studies, the sealant was applied to the suture line of a left internal mammary artery (LIMA) to left anterior descending (LAD) anastomoses. The anastomoses were then evaluated for patency and tissue reaction after a three-month recovery period. RESULTS: The sealant prevented bleeding from arterial puncture wounds up to 2.5 mm in diameter. Three months following the application of sealant to coronary anastomoses, no adverse tissue reaction was found on histologic examination. All anastomoses treated with the sealant remained patent. CONCLUSION: When applied as a hemostatic adjunct to sutures at a coronary anastomosis, the sealant appears to be an effective means of preventing bleeding without adverse tissue reaction or scarring.

Anastomosis, Surgical↗
PubMed1999

Immunolocalization of the keratinocyte growth factor in benign and neoplastic human prostate and its relation to androgen receptor.

BACKGROUND: Growth and development of the prostate are androgen-dependent. Keratinocyte growth factor (KGF), widely expressed by mesenchymal cells, is thought to act like an andromedin between stroma and epithelium of the prostate. Since KGF has recently emerged as an autocrine mediator in prostate cancer, we investigated the role KGF plays in the human prostate and its relationship to androgen receptor (AR). METHODS: Normal (n = 13), benign hyperplastic (n = 5), and neoplastic (n = 14) human prostate tissues as well as cultured epithelial and stromal cells were analyzed using polymerase chain reaction (PCR), Western blot analysis, and immunohistochemistry. RESULTS: Reverse transcriptase polymerase chain reaction and Western blotting showed KGF expression in stromal cultured cells of the normal prostate but not in epithelial cells. Using immunohistochemistry, KGF was found to be localized in fibroblasts and smooth muscle cells, independent of prostate disease. There was KGF expression in epithelial cells of BPH and prostate cancer. Human androgen receptor was uniformly expressed in the same secretory glandular cells that were positive for KGF in BPH and prostate cancer. CONCLUSIONS: Our results provide evidence that KGF is a stromal-derived mediator, recently shown to act in a paracrine manner in normal prostate but now detected in epithelial cells in prostate cancer and BPH. These findings support the hypothesis that KGF might act as an autocrine factor in prostate cancer and BPH.

Antibody Specificity↗
PubMed1999

The effect of thymectomy on tolerance induction and cardiac allograft vasculopathy in a miniature swine heart/kidney transplantation model.

BACKGROUND: We have previously demonstrated that MHC class I disparate hearts transplanted into miniature swine treated with a short course of cyclosporine developed florid cardiac allograft vasculopathy (CAV) and were rejected within 55 days. However, when a donor-specific kidney is cotransplanted with the heart allograft, recipients become tolerant to donor antigen and accept both allografts long-term without the development of CAV. In the present study, we have investigated the role of the host thymus in the induction of tolerance and prevention of CAV in heart/kidney recipients. METHODS: Total thymectomies were performed in six animals (postoperative day [POD]-21), which on day 0 received either an isolated MHC class I disparate heart allograft (n=3) or combined class I disparate heart and kidney allografts (n=3), followed in both cases by a 12-day course of cyclosporine (POD 0-11). Graft survival and the development of CAV in these thymectomized recipients were compared to the same parameters in non-thymectomized, cyclosporine-treated recipients bearing either class I disparate heart allografts (n=5) or heart and kidney allografts (n=4). RESULTS: In the group of animals bearing isolated class I disparate heart allografts, the thymectomized recipients rejected their allografts earlier (POD 8, 22, 27) than the non-thymectomized recipients (POD 33,35,45,47,55). The donor hearts in both the thymectomized and non-thymectomized animals developed florid CAV. In the group of animals bearing combined class I disparate heart and kidney allografts, the nonthymectomized recipients accepted both donor organs long term with no evidence of CAV. In contrast, none of the thymectomized heart/kidney recipients survived >100 days, and they all developed the intimal proliferation of CAV. CONCLUSION: Thymic-dependent mechanisms are necessary for the induction of acquired tolerance and prevention of CAV in porcine heart/kidney recipients.

Animals↗
PubMed1999

Thoracoabdominal aortic aneurysm in Cogan's syndrome.

Cogan's syndrome is an autoimmune disease of unknown etiology, clinically manifested as non-syphilitic interstitial keratitis and audiovestibular symptoms. Increasing evidence suggests that Cogan's may be a systemic vasculitis. In this report, we review the vascular manifestations of Cogan's syndrome and report two cases of thoracoabdominal aortic aneurysm in patients with this disorder.

Adolescent↗
PubMed1999

Characterization of a stromal cell model of the human benign and malignant prostate from explant culture.

PURPOSE: There is a lack of suitable in vitro models for the human prostate. To study stromal-epithelial interactions, we established stromal cells in cultures from benign and malignant prostate tissue that resemble more closely the in vivo conditions of the human prostate. MATERIALS AND METHODS: Stromal cells were obtained from explant primary culture, established in DU145 cell conditioned medium and maintained in RPMI-fetal bovine serum (FBS) supplemented with insulin, transferrin and selenium (ITS). Proliferation studies to compare different media were performed using a 3[H]thymidine assay. Stromal cells were characterized by immunocytochemistry using epithelial and mesenchymal markers. Morphology was evaluated by electron microscopy, light and phase-contrast microscopy. Androgen receptor (AR) mRNA expression was measured by polymerase-chain-reaction (PCR). The response to different concentrations of dihydrotestosterone (DHT) and the antihormones flutamide and hydroxyflutamide was tested by 3[H] thymidine assay. RESULTS: Microscopic evaluation revealed typical stromal morphology with elongated cell shapes, cilia, collagen and microfilaments. Immunocytochemical characterization revealed typical fibroblastic and smooth muscle differentiation. ITS supplemented in RPMI-FBS showed the best growth stimulation compared with other serum-free media (p <0.05) and became our basal medium. The presence of DU145 cell conditioned medium in this basal medium showed a significant increase in cell proliferation in stromal cells. Stromal cells maintained AR mRNA expression and significant DHT dose dependent growth stimulation in up to 10 passages. Both the antiandrogens flutamide and hydroxyflutamide counteracted the DHT effect (p <0.05). CONCLUSIONS: This stromal cell model maintains many cellular and functional properties of the human prostate, which may enable us to study growth factor modulation, drug and hormone metabolism in stromal-epithelial interaction with emphasis on the pathogenesis of BPH and prostate cancer.

Cell Division↗
PubMed1998

Creation of the "thymoheart" allograft: implantation of autologous thymus into the heart prior to procurement.

BACKGROUND: A state of tolerance may be more easily achieved if fully vascularized and functional donor thymus is transferred to the recipient at the time of whole organ transplantation. METHODS: A composite "thymoheart" allograft was created by implanting autologous thymus into a donor heart 60-90 days before organ procurement. Successful intracardiac engraftment of autologous thymus was documented by histology and by flow cytometric analysis. RESULTS: Histology of the thymic autografts at explantation revealed viable thymus with preservation of normal thymic architecture. Cells retrieved from thymic autografts 60 days after implantation exhibited the same MHC class I and class II staining profiles by flow cytometry as cells taken from the residual native thymus. CONCLUSION: We have created a novel composite organ that confers vascularized and functional donor thymus to heart allograft recipients at the time of transplantation without affecting cardiac function.

Animals↗
PubMed1995

Tracheal anastomosis with the diode laser and fibrin tissue adhesive: an in vitro and in vivo investigation.

Absorbable sutures have been advocated for tracheal anastomosis to reduce fibrosis and foreign body reaction leading to recurrent stenosis. Fibrin tissue adhesive (FTA) and diode laser welding with indocyanine green-dyed fibrinogen were evaluated in tracheal anastomosis to reduce the number of sutures and to improve healing. In vitro studies demonstrated strong anastomoses with a combination of laser welding and FTA with minimal tissue damage. In a controlled in vivo study, circumferential resections of canine tracheas were repaired with laser welding and FTA augmented with a few stay sutures. These anastomoses had less fibrosis and tissue damage than anastomoses in control animals repaired with sutures alone. This study supports investigation of laser welding and FTA in human beings for tracheal anastomosis and other procedures in which suturing may be difficult.

Anastomosis, Surgical↗
PubMed1994

Androgen receptor immunohistochemistry on paraffin-embedded tissue.

Androgen deprivation remains the primary therapy for patients with metastatic prostate cancer. Response to hormonal manipulation, however, has been quite variable. Androgen receptor (AR) expression has been used to predict clinical response to antiandrogenic treatment. However, methods of detection of AR expression have been limited to receptor biochemical assays in cytosolic or nuclear fractions of frozen tissue homogenates with obvious contamination problems by nonmalignant epithelial and stromal cells. As a result, studies correlating AR expression with response to hormonal therapy have been limited and controversial. More recently, immunohistochemical methods of analysis have become available, but only on frozen tissue. We describe a simple method to evaluate ARs on formalin-fixed, paraffin-embedded tissue sections using antigen retrieval methods. Primary, as well as metastatic, prostate carcinomas showed nuclear staining for ARs. Secretory cells stained uniformly in hyperplastic and normal prostatic glands. The majority of stromal cells had strong nuclear positivity. All other cancers tested (colon, breast, lung, skin, kidney) were negative. This immunohistochemical technique allows evaluation of prostate cancer AR status in routinely processed tissues. Thus, application of this technology to archival material should permit assessment of whether AR expression is predictive of response to endocrine therapy in advanced prostate cancer.

Adenocarcinoma↗
PubMed1993

In vitro decalcification of aortic valve leaflets with the Er:YSGG laser, Ho:YAG laser, and the Cavitron ultrasound surgical aspirator.

This study was designed to compare the efficacy of the erbium:yttrium-scandium-gallium-garnet (Er:YSGG) laser and the holmium:yttrium-aluminum-garnet (Ho:YAG) lasers in debriding calcium from freshly explanted aortic valve leaflets and to compare the Er:YSGG laser with the Cavitron ultrasonic surgical aspirator (CUSA). Aortic valve leaflets were freshly explanted from patients undergoing aortic valve replacement for aortic stenosis. Initially, 4 leaflets each were debrided with the Er:YSGG and the Ho:YAG lasers to attempt removal of calcium deposits while preserving the underlying integrity of the leaflets and minimizing thermal damage. The Er:YSGG laser was more effective in doing so with less thermal and photoacoustic damage when compared with the Ho:YAG laser. Twelve more leaflets each were then debrided with the Er:YSGG laser and the CUSA. The Er:YSGG laser again proved less injurious to the underlying leaflet. The CUSA-treated leaflets demonstrated shattering and disruption of adjacent tissue as well as collagen fiber exposure. These changes were not seen with the Er:YSGG laser. Because of these properties, the Er:YSGG laser merits further evaluation as a tool for aortic valvuloplasty procedures in selected patients with senescent calcific aortic stenosis.

Aortic Valve↗
PubMed1993

Metaiodobenzylguanidine: evaluation of its potential as a tracer for monitoring doxorubicin cardiomyopathy.

We evaluated alterations in cardiac adrenergic neuron activity and progression of left ventricular dysfunction in comparison with the severity of structural changes using a rat model of adriamycin cardiomyopathy. Rats were treated with adriamycin (2 mg/kg s.c. once a week) for 6, 7, 8 and 9 wk. Accumulation of 125I-metaiodobenzylguanidine (MIBG) 4 hr after intravenous administration was determined and left ventricular ejection fraction (LVEF) was calculated from gated blood-pool images. H & E and Masson-Trichrome stained specimens of the myocardium were examined by light microscopy. Histopathologic examination demonstrated dose-dependent myocyte damage, although there were no differences between the 8-wk and 9-wk groups. LVEF did not differ between controls and the 6-wk group (81.3% +/- 5.5% versus 82.1% +/- 4.8%, p = ns). LVEF began to decrease slightly in the 7-wk group (75.0% +/- 5.7%, p < 0.05) and showed a remarkable decrease in the 8-wk group (53.7% +/- 2.6%, p < 0.001). In the 9-wk group, LVEF diminished to 47.9% +/- 3.1% (p < 0.001), accompanied by massive pleural effusions and ascites. MIBG accumulation in the heart (%ID/heart) significantly and progressively diminished; 1.42% +/- 0.15% in the 6-wk group, 1.06% +/- 0.16% in the 7-wk group, 0.77% +/- 0.13% in the 8-wk group and 0.34% +/- 0.11% in the 9-wk group, respectively p < 0.001, compared to controls (1.99% +/- 0.30%). These results demonstrate that MIBG accumulation in the heart showed a greater and more linear dose-dependent decrease than LVEF. Furthermore, MIBG uptake was significantly reduced in the 6-wk group where only mild myocyte damage (isolated vacuolation or myofibrillar loss) was observed. Thus, MIBG may be a sensitive biochemical marker of adriamycin cardiomyopathy.

3-Iodobenzylguanidine↗