Search PubMed⌕ Search

Biomedical subjects

D H Adams

Publications and source records attributed to D H Adams.

At least 55 records · Page 3Linked to original sources
PubMed2000

Cardiac xenotransplantation: clinical experience and future direction.

The shortage of human organs has focused research on finding an animal source of replacement organs. The immunological barriers to xenotransplantation are now more clearly defined, allowing retrospective interpretation of past clinical experience in humans. Due to physiological compatibilities as well as ethical and infectious considerations, pigs have now emerged as the most likely source of future xenografts. The introduction of transgenic pigs expressing human complement regulatory proteins and new immunosuppressive regimens have shown early promise in the laboratory, although further advancements are needed to advance to clinical trials. Additional clarification of infectious risks and patient strategies are remaining obstacles to application in the clinical arena.

Animals↗
PubMed2000

Heterotopic heart transplantation: experimental development and clinical experience.

Heterotopic heart transplantation was initially developed in the laboratory for experimental transplantation. While it was more widely utilized in the pre-cyclosporine era to provide adjunct circulatory support in combination with the native heart, associated complications as well as improved long-term graft survival have now established orthotopic transplantation as the procedure of choice. Heterotopic heart transplantation is currently reserved for highly selected patients. The technique is only performed at selected transplantation centers, and indications include significant donor recipient size mismatch or irreversible recipient pulmonary hypertension. The foreseeable introduction of clinical porcine xenotransplantation may lead to renewed interest in the technique of heterotopic heart transplantation as a bridge to potential native heart recovery or allotransplantation in selected patients.

Adolescent↗
PubMed2000

Partial upper re-sternotomy for aortic valve replacement or re-replacement after previous cardiac surgery.

OBJECTIVE: We developed techniques for 'inverted T' partial upper re-sternotomy for aortic valve replacement (AVR) or re-replacement (AVreR) after previous cardiac surgery. We previously reported on decreased blood loss, transfusion requirements and total operative duration when compared to conventional full re-sternotomy. This report updates our series, one of the few to document a substantial benefit from a 'minimally-invasive' approach, refines a number of technical aspects of this new approach and reports follow-up. METHODS: Between November 1996 and December 1999, we performed 34 AVRs or AVreRs after previous cardiac surgery by use of an 'inverted T' partial upper re-sternotomy. There were 25 (74%) men. Median ejection fraction was 54%, range 15-80%. Median age was 72, range 38-93. All were New York Heart Association functional class (NYHA) functional class II or III. Twenty-one (62%) had previous coronary artery bypass grafts (CABG) while 14 (41%) had previous valve surgery. Follow-up was 100% complete for a total of 593 patient months (median 19 months). RESULTS: Twenty-three (66%) underwent AVR of the native aortic valve while 11 (33%) underwent AVreR of a prosthetic aortic valve. There were no intraoperative or valve-related complications, and no conversion to full re-sternotomy was necessary. There were two (5.9%) operative deaths from an arrhythmia on postoperative day 4 and a large stroke during surgery, respectively. Twenty-four (75%) patients were free of major complications. There was no need for reoperation for bleeding and patients required a median of two units of packed red blood cells. Complications included new atrial fibrillation (n=3, 9%), pacemaker implantation (n=3, 9%) and deep sternal wound infection (n=2, 6%). Median lengths of stay in the intensive care unit (ICU) and in the hospital were 1 and 7 days, respectively. There was one (3%) late deep sternal wound infection and 2/32 (6%) late deaths due to congestive heart failure at 22 months and myocardial infarction at 23 months, respectively. CONCLUSIONS: Partial upper re-sternotomy presents a safe and effective alternative approach to AVR and AVreR after previous cardiac surgery, and is associated with low morbidity and mortality.

Adult↗
PubMed2000

Monitoring pig-to-primate cardiac xenografts with live Internet images of recipients and xenograft telemetric signals: histologic and immunohistochemical correlations.

BACKGROUND: Monitoring pig-to-primate cardiac xenografts is often difficult in awake and uncooperative primates. We investigated the possibility of monitoring xenotransplantation through Internet broadcasting of (1) continuous video images of transplant recipients and (2) xenograft telemetric signals detected by an implanted device. The telemetric readings were later compared with histology and immunohistochemistry for signs of rejection. METHODS: Heterotopic baboon-to-baboon (n = 2) and transgenic pig (human complement regulatory proteins CD59/DAF, n = 3; MCP, n = 1)-to-baboon transplants were performed with serial biopsies for hematoxylin-and-eosin staining and immunohistochemical detection of immunoglobulin M (IgM) and complement membrane attack complex (MAC) deposition. Baboon recipients were continuously monitored with a QuickCamPro digital camera, whereas grafts were monitored with a Data Science International implantable telemetric system. Video images and telemetric signals were broadcast over the Internet through a laptop computer. RESULTS: Baboon allografts remained healthy until explant on Day 14, whereas pig xenografts were rejected on Day 5, 6, 7, and 11. Telemetry of allografts and xenografts documented regular rhythm with an average heart rate of 80 to 120, but xenografts developed bradycardia and widened/dampened QRS complexes 24 to 48 hours before graft loss. Continuous video monitoring of recipient activities was vital in differentiating between graft arrhythmias and telemetric artifacts. Allograft biopsies showed little cellular infiltrate, whereas xenograft biopsies showed increasing IgM and MAC deposition, with extensive thrombi and myocardial damage 24 hours before cessation of cardiac activities. CONCLUSIONS: Combined video surveillance of recipient activities and graft telemetric signals is a useful method to continuously monitor abdominal cardiac grafts in large, uncooperative, awake primates. QRS-complex widening associated with progressive bradycardia correlated with histologic and immunohistochemical evidence of xenograft rejection.

Animals↗
PubMed2000

Cocaine and methamphetamine differentially affect opioid peptide mRNA expression in the striatum.

In general, administration of methamphetamine and cocaine alters preprodynorphin and preproenkephalin mRNA levels in striatum. However, no study has directly compared the effects of these stimulants on opioid peptides in striatum. This study used in situ hybridization to compare directly the effects of cocaine and methamphetamine on preprodynorphin and preproenkephalin mRNAs in distinct striatal regions. Male Sprague-Dawley rats received a single administration of 15 mg/kg methamphetamine or 30 mg/kg cocaine and were killed 30 min or 3 h later. Methamphetamine and cocaine differentially affected preprodynorphin mRNA in striatum after 3 h. Densitometric analysis of film autoradiograms revealed that cocaine, but not methamphetamine, significantly increased preprodynorphin. This effect was seen throughout rostral striatum and dorsally in caudal striatum. However, specific analysis of "patches" in which preprodynorphin expression is high revealed a significantly greater effect of methamphetamine versus cocaine. In contrast, both cocaine and methamphetamine had similar effects on preproenkephalin mRNA, decreasing levels after 30 min in rostral striatum and in the core of nucleus accumbens. These data suggest that methamphetamine and cocaine have distinct postsynaptic consequences on striatal neurons.

Animals↗
PubMed2000

Circulating soluble vascular adhesion protein 1 accounts for the increased serum monoamine oxidase activity in chronic liver disease.

BACKGROUND & AIMS: Vascular adhesion protein 1 (VAP-1) is an endothelial glycoprotein that supports adhesion of lymphocytes to hepatic endothelium and has sequence homology with semicarbazide-sensitive amine oxidases (SSAOs). We investigated whether soluble VAP-1 (sVAP-1) displays SSAO activity and thereby accounts for increased monoamine oxidase activity in the serum of patients with liver diseases. METHODS: sVAP-1 concentration and SSAO activity were measured in peripheral, hepatic, and portal blood and in bile from patients with liver disease and in peripheral blood of control subjects, using enzyme-linked immunosorbent assay and enzymatic assays. RESULTS: sVAP-1 concentration (mean [+/-SE], 143. 67 [34.97-92.67] ng/mL) and SSAO activity (18.8 [12.0-24.6] nmol. mL(-1). h(-1)) were significantly increased in chronic liver diseases compared with healthy controls (87.1 [53.5-127] ng/mL [P<0.001] and 10.7 [6.5-12.7] nmol. mL(-1) x h(-1) [P<0.05]) but not in massive necrosis caused by paracetamol poisoning (109 [80.3-140] ng/mL and 8.9 [5.7-12.3] nmol. mL(-1) x h(-1)). sVAP-1 correlated with serum transaminase and bilirubin but not with creatinine. In 5 paired samples, sVAP-1 concentration was higher in hepatic (median, 113 [range, 53-122]) than in portal vein (102 [42-109]; 2P<0.05), and was not detected in bile. There was a highly significant correlation between serum sVAP-1 and SSAO activity in normal subjects, patients with acute liver failure, and those with chronic liver disease (r = 0.895; P<0.001). When serum was depleted of sVAP-1 by immunoaffinity chromatography, SSAO activity was eliminated. CONCLUSIONS: sVAP-1 levels are increased in chronic liver disease, and sVAP-1 is likely derived from the liver. Serum sVAP-1 displays SSAO activity and accounts for most of the monoamine oxidase activity in human serum.

Amine Oxidase (Copper-Containing)↗
PubMed2000

Fresh porcine cardiac valves are not rejected in primates.

OBJECTIVE: Transplanted porcine hearts are hyperacutely rejected by human immunoglobulin M antibodies against a porcine vascular endothelial molecule, galactose alpha-1,3-galactose, with ensuing human complement activation and membrane attack complex deposition. It is unclear, however, whether porcine valve endothelium triggers a similar immune response. We sought to investigate whether fresh porcine valves implanted into primates are rejected. METHODS: Wild-type porcine hearts before (n = 6) and after (n = 3) heterotopic transplantation into baboons underwent sectioning and were examined by hematoxylin and eosin staining and immunohistochemistry for galactose alpha-1,3-galactose, primate immunoglobulin M, and membrane attack complex. RESULTS: Examination of untransplanted porcine hearts showed that although cardiac microvascular endothelium strongly expressed the galactose alpha-1, 3-galactose antigen, galactose alpha-1,3-galactose was not detected on the endothelium of porcine aortic and pulmonary valves. Porcine hearts transplanted into baboon recipients were hyperacutely rejected 60 to 80 minutes after implantation. Despite dramatic tissue damage associated with extensive immunoglobulin M and membrane attack complex binding on the microvascular endothelium, the aortic and pulmonary valves were entirely spared. Valves remained morphologically intact at explant and showed no signs of immunoglobulin M- and membrane attack complex-mediated damage. CONCLUSIONS: The absence of galactose alpha-1,3-galactose expression may protect unfixed porcine valves from xenograft rejection in primates. Further investigation of viable porcine valves appears warranted.

Animals↗
PubMed2000

CD40 induces apoptosis in carcinoma cells through activation of cytotoxic ligands of the tumor necrosis factor superfamily.

CD40, a tumor necrosis factor (TNF) receptor (TNFR) family member, conveys signals regulating diverse cellular responses, ranging from proliferation and differentiation to growth suppression and cell death. The ability of CD40 to mediate apoptosis in carcinoma cells is intriguing given the fact that the CD40 cytoplasmic C terminus lacks a death domain homology with the cytotoxic members of the TNFR superfamily, such as Fas, TNFR1, and TNF-related apoptosis-inducing ligand (TRAIL) receptors. In this study, we have probed the mechanism by which CD40 transduces death signals. Using a trimeric recombinant soluble CD40 ligand to activate CD40, we have found that this phenomenon critically depends on the membrane proximal domain (amino acids 216 to 239) but not the TNFR-associated factor-interacting PXQXT motif in the CD40 cytoplasmic tail. CD40-mediated cytotoxicity is blocked by caspase inhibitors, such as zVAD-fmk and crmA, and involves activation of caspase 8 and caspase 3. Interestingly, CD40 ligation was found to induce functional Fas ligand, TRAIL (Apo-2L) and TNF in apoptosis-susceptible carcinoma cells and to up-regulate expression of Fas. These findings identify a novel proapoptotic mechanism which is induced by CD40 in carcinoma cells and depends on the endogenous production of cytotoxic cytokines and autocrine or paracrine induction of cell death.

Amino Acid Motifs↗
PubMed2000

Lack of ABH-antigen expression on human cardiac valves.

BACKGROUND AND AIM OF THE STUDY: Seeding of heart valve prostheses with human umbilical vein endothelial cells (HUVEC) and human saphenous vein endothelial cells (HSVEC) has been applied to create a viable valve surface and improve valve performance. HUVEC and HSVEC are well characterized and have been used as a model of endothelial antigenicity, but antigenicity of the valve endothelium is less well characterized. To clarify this issue, we studied the expression of blood group antigens by human valvular endothelium, HSVEC and HUVEC. METHODS: Human aortic and mitral valves and myocardial tissue were freshly harvested from explanted hearts of patients undergoing heart transplantation (blood group A, n = 4; group O, n = 4) or valve replacement (blood group B, n = 4). After fixation in Carnoy's or formalin solution, paraffin sections were stained with anti-A (blood group A), anti-B (blood group B), and anti-H (blood group O) antibodies. Human umbilical cords were freshly harvested postpartum, and human saphenous veins were obtained from patients undergoing coronary bypass grafting (each blood group, n = 2) and similarly fixed and stained to detect ABO antigens. The preservation of endothelium was confirmed by staining with anti-CD 31 monoclonal antibody. All sections were examined by light microscopy. RESULTS: CD 31 staining demonstrated vascular and valve endothelial preservation. Human umbilical cords, saphenous vein and myocardium showed strongly expressed A, B and H blood group antigens on vascular endothelium. However, no A, B and H antigens were detected on the valvular endothelium. CONCLUSIONS: Valve endothelial cells appear to be a class of specialized endothelial cells that does not express the ABO antigens. Due to the strong expression of A, B and H antigens by HUVEC and HSVEC blood group cross-matching should be considered for non-autologous endothelialization of valve prostheses.

ABO Blood-Group System↗
PubMed1999

Chemokine and chemokine receptor interactions provide a mechanism for selective T cell recruitment to specific liver compartments within hepatitis C-infected liver.

The role played by chemokines in regulating the selective recruitment of lymphocytes to different tissue compartments in disease is poorly characterized. In hepatitis C infection, inflammation confined to portal areas is associated with a less aggressive course, whereas T cell infiltration of the liver parenchyma is associated with progressive liver injury and cirrhosis. We propose a mechanism to explain how lymphocytes are recruited to hepatic lobules during bursts of necroinflammatory activity in chronic hepatitis C infection. We report here that lymphocytes infiltrating hepatitis C-infected liver express high levels of the chemokine receptors CCR5 and CXCR3. However, whereas the CCR5 ligands macrophage inflammatory protein-1alpha and -1beta were largely confined to vessels within portal tracts, the CXCR3 ligands IFN-inducible protein-10 and monokine-induced by IFN-gamma were selectively up-regulated on sinusoidal endothelium. In vitro, human hepatic sinusoidal endothelial cells secreted IFN-inducible protein-10 and monokine-induced by IFN-gamma in response to stimulation with IFN-gamma in combination with either IL-1 or TNF-alpha. This suggests that intrahepatic Th1 cytokines drive the increased expression of IFN-inducible protein-10 and monokine-induced by IFN-gamma and thereby promote the continuing recruitment of CXCR3-expressing T cells into the hepatic lobule in chronic hepatitis C infection.

Cell Movement↗
PubMed1999

Minimally invasive direct access for repair of atrial septal defect in adults.

This report documents our early experience with minimally invasive direct-access surgical repair of atrial septal defect (ASD) in adults. We have developed minimally invasive techniques for direct-access ASD repair in adults while maintaining the efficacy of the open operative procedure. Between June 1996 and September 1998, 59 consecutive patients underwent repair of ASD, 34 (58%) of whom underwent minimally invasive direct-access surgical closure of ASD through a right parasternal, submammary, or upper hemisternotomy incision. Twenty-three (68%) were secundum type ASD, 5 (15%) were sinus venosus types, 2 (6%) were primum types, and 4 (122%) were patent foramen ovales. Twenty-six (77%) were women (mean age 39 +/- 15 years, range 18 to 79). The mean pulmonary-to-systemic shunt ratio (Qp/Qs) was 2.3 +/- 0.6 (n = 15). There were no operative or late deaths. Follow-up was 100% complete. Four patients (12%) developed major complications. All were alive and well at the time of follow-up and there was 1 late arrhythmia (atrial fibrillation). In all but 1 patient, New York Heart Association functional class was improved or unchanged (1.47 +/- 0.51 vs 1.06 +/- 0.25, p = 0.0001). These results indicate that minimally invasive direct-access repair of ASD in adults is safe and effective, and is broadly applicable to the entire spectrum of defects.

Adult↗
PubMed1999

CD40 activation induces apoptosis in cultured human hepatocytes via induction of cell surface fas ligand expression and amplifies fas-mediated hepatocyte death during allograft rejection.

We propose that a novel mechanism of hepatocyte apoptosis, involving a cooperative interaction between CD40 and Fas, is involved in the hepatocyte loss of chronic liver allograft rejection. We detected increased hepatocyte expression of Fas, Fas ligand (FasL), and CD40 associated with dropout of centrilobular (acinar zone 3) hepatocytes in chronic allograft rejection. Expression of CD40 ligand (CD40L) was also increased but was largely restricted to CD68(+) macrophages. A functional role for CD40 and Fas in hepatocyte apoptosis was demonstrated in vitro using primary human hepatocytes and the HepG2 cell line in both of which apoptosis was induced, not only by cross-linking Fas directly but also via CD40 activation. Our data suggest that CD40 activation induces apoptosis via Fas because (a) ligation of CD40 upregulated hepatocyte FasL expression, and (b) apoptosis induced via activation of CD40 was prevented by a neutralizing monoclonal antibody to FasL. Thus, CD40 engagement triggers apoptosis of human hepatocytes and might amplify Fas-dependent hepatocyte apoptosis in chronic rejection and other inflammatory liver diseases in which Fas-mediated apoptosis is involved.

Antibodies, Monoclonal↗
PubMed1999

Expression and function of CXC and CC chemokines in human malignant liver tumors: a role for human monokine induced by gamma-interferon in lymphocyte recruitment to hepatocellular carcinoma.

Chemotactic cytokines (chemokines) play an important role in the recruitment of lymphocytes to tissue by regulating cellular adhesion and transendothelial migration. This study examined the expression and function of CXC (human monokine induced by gamma-interferon [HuMig], interleukin-8 [IL-8], and interferon-inducible protein-10 [IP-10]) and CC (macrophage inflammatory protein-1alpha [MIP-1alpha], MIP-1beta, regulated upon activation normal T lymphocyte expressed and secreted (RANTES), and macrophage chemoattractant protein-1 [MCP-1]) chemokines and their respective receptors on lymphocytes infiltrating human liver tumors. Chemokine and chemokine receptor expression was assessed by immunohistochemistry, flow cytometry, in situ hybridization and ribonuclease (RNAse) protection assays and function by in vitro chemotaxis of tumor-derived lymphocytes to purified chemokines and to HepG2 tumor cell culture supernatants. Tumor-derived lymphocytes showed strong chemotactic responses to both CC and CXC chemokines in vitro and expressed high levels of CXCR3 (HuMig and IP-10 receptor) and CCR5 (RANTES, MIP-1alpha, and MIP-1beta receptor). Expansion of tumor-derived lymphocytes in recombinant IL-2 increased expression of CXCR3. The corresponding chemokines were detected on vascular endothelium (HuMig, IL-8, MIP-1alpha, and MIP-1beta) and sinusoidal endothelium (HuMig, MIP-1alpha, MIP-1beta) in hepatocellular carcinoma. In vitro, HepG2 cells secreted functional chemotactic factors for tumor-derived lymphocytes that could be inhibited using anti-CCR5 or anti-CXCR3 monoclonal antibodies (MoAbs). Thus, lymphocytes infiltrating human liver tumors express receptors for and respond to both CXC and CC chemokines. The relevant chemokine ligands are expressed in hepatocellular carcinoma (HCC), particularly HuMig, which was strongly expressed by tumor endothelium, suggesting that they play a role in lymphocyte recruitment to these tumors in vivo. The ability of HepG2 cells to secrete lymphocyte chemotactic factors in vitro suggests that the tumor contributes to lymphocyte recruitment in vivo.

Aged↗