摘要:

The Use of Laboratory Animals in Biomedical and Behavioral Research, the report of the National Academy of Sciences-National Research Council (NAS-NRC) has now been released. 1 was on the committee that authored the report and fully concur with it as far as it went. It is no mean task to agree on reasonable and comprehensible standards for the humane treatment of animals in research. Nonetheless, in my view, there is something missing: the committee slighted what I believe is the most important practical aspect of the issue of“animal rights”—the political dimension. Biomedical research is now under serious political attack from a variety of organizations and individuals who, for ideological reasons, desire to stop or drastically reduce the use of animals in experimentation, and they are willing to use virtually any tactics to achieve this goal. They rarely state this aim, or pursue it directly, perhaps because this would lead to an open discussion of all the benefits and costs involved in biomedical research. Rather, the activists concentrate on a series of restrictive measures, seemingly less radical, each of which makes the use of animals more expensive and more burdensome—chipping away bit by bit at our ability to afford animal research.

ISSN:0894-1939    

DOI:10.3109/08941938909057426

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

A tremendous technological advance occurred in 1975 when a method was developed to fuse two cells producing a“hybridoma”which secretes a single clone of antibody, having one immunoglobulin (Ig) class, one structure, one affinity, and one specificity for an antigenic determinant. Because monoclonal antibodies are more precise reagents than conventional antisera they open new doors to diagnosis und therapy of disease, and they are useful tools in research. The pathologist uses monoclonals in immunocyto-chemistry to determine tumor type; the surgeon uses monoclonals for immunosupression in renal transplantation; the immunologist uses monoclonals to decipher cellular and humoral inteructions that could not be appreciated with polyclonal reagents. This review outlines the background of monoclonal antibodies und some of their clinically important uses, both in vitro and in vivo. We also project into the future and describe chimeric antibodies and their possible uses.

ISSN:0894-1939    

DOI:10.3109/08941938909057427

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

ISSN:0894-1939    

DOI:10.3109/08941938909057428

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

The biodistribution and kinetics of 7 monoclonal antibodies (MAb) with known reactivity against CX-I tumor were examined over 21 days using a hand-held gamma-detecting probe (Neoprobe system). Twenty-eight irnmuno-deprived (athymic) nude mice implanted with human colon adenocarcinoma CX-1 xenografts were injected intraperitoneally with 50µCi of125I-labeled antibodies (4 mice/antibody). Of the 7 monoclonal antibodies, 4 were anti-CEA (MA, MB, MC, and MD), 2 were anti-TAG 72 (B72.3 NCI and B72.3 fermented) and one was anti-colorectal cancer (17-1A). Daily probe counts were recorded in duplicate over the tumor site and the contralateral nontumor site (background), and tumor-to-background (Tu/Bkg) ratios were calculated. Animals were sacrificed on day 21, and blood, heart, liver, spleen, lungs, kidneys, intestine, muscle, and the tumor were removed for gamma well counting. All antibodies identified the tumor as early as 24 h postinjection and speciJic tumor localization improved over time. Patterns of prolonged tumor binding varied considerably from one antibody to another, although all but one (MB) showed continuously increasing TulBkg ratios. These data indicate progressive clearance of the antibodies from the background tissue and a persistence of labeled MAb activity in tumor resulting in improved tumor localizution with increasing postinjection time.

ISSN:0894-1939    

DOI:10.3109/08941938909057429

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

Graft versus host disease (GVHD) may be abrogated and host survival prolonged by in vitro depletion of T lymphocytes from bone marrow (BM) prior to allotransplantation. Using a mouse anti-rat pan T-lymphocyte monoclonal antibody (0×19) bound to monosized, magnetic, polymer beads, T lymphocytes were removed in vitro from normal bone marrow. The removal of the T lymphocytes was confirmed by flow cytometry. Injection of the T-lymphocyte-depleted bone marrow into fully allogeneic rats prevents the induction of GVHD and prolongs host survival.A highly efficient technique of T-lymphocyte depletion using rat bone marrow is described. It involves the binding of OX-19, a MoAb directed against all rat thy-mocytes and mature peripheral T lymphocytes, to monosized, magnetic polymer spheres. Magnetic separation of T lymphocytes after mixing the allogeneic bone marrow with the bead/OX-19 complex provides for a simple, rapid depletion of T lymphocytes from the bone marrow. In vitro studies using flow cytometry and the prevention of GVHD in a fully allogeneic rat bone marrow model have been used to demonstrate the effectiveness of the depletion procedure.

ISSN:0894-1939    

DOI:10.3109/08941938909057430

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

The area postrema (AP) is being widely studied to delineate its role in such varied functions as blood pressure regulation, conditioned taste aversion, water and energy balance, and radiation-induced emesis. This paper describes the preoperative preparation, surgical procedure, and postoperative care of cats kept long-term in which the AP was lesioned by electrocautery. A dorsal midline approach under gas anesthesia allowed access to selectively lesion the AP. Cats fully regained consciousness the same day and many became homeostutic within 24-48 h. Results of experiments using this model demonstrate the usefulness and effectiveness of the technique for model preparation.

ISSN:0894-1939    

DOI:10.3109/08941938909057431

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

This document is not meant to be a regulatory statement but rather to be utilized as a guideline for research institutions who are trying to adhere to the training regulations detailed by various governmental agencies. It is our hope that institutions and individuals will take a proactive stance in requiring adequate training and experience for persons performing experimental surgery on laboratory animals. Only by adherence to voluntary standards that ensure humane care and use of laboratory animals in research can we expect to avoid more stringent laws and regulations. More importantly, by adhering to these voluntary standards the quality of animal research can be improved, which should result in more effective and efficient use of our resources.

ISSN:0894-1939    

DOI:10.3109/08941938909057432

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

Currently two pumps are used for cardiopulmonary bypass, the roller pump and the centrifugal or vortex pump. Both are steady-flow pumps. The procedure of cardiopulmonary bypass possesses a finite morbidity and mortality. The degree to which steady flow is responsible for this morbidity and mortality remains to be clarified, but investigators have established the fact that a physiologic degree of pulsatile flow must be achieved before its beneficial results, such as normal systemic resistance and absence of lactate production, can be demonstrated. Availability of a satisfactory pulsatile pump for cardiopulmonary bypass has been a problem in the past but the pump presented here may satisfy this need. It produces physiologic pulsatility with rate dependent ejection time equal to or less than that of humans (413µs minus 1.7 times heart rate), and it is preload-responsive, varying its pumping rate and output with filling pressure. The pump is externally valved to minimize hemolysis, which has been demonstrated in two laboratory studies to be significantly less than with the roller pump. It produces pulsatile flow through membrane oxygenators. The pump is thought to have potential for several clinical applications in addition to (I) pulsatile-flow cardiopulmonary bypass, including (2) left, right, or combined transthoracic QRS synchronized ventricular assist, (3) femoral vein to femoral artery QRS synchronized left ventricular assist, (4) adult or infant ECMO, (5) pulsatile flow hemodialysis. In the latter, spallation and embolization of hemodialysis tubing particles should not be a problem as has proved to be the case with the present hemodialysis Pump.

ISSN:0894-1939    

DOI:10.3109/08941938909057433

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

A portable heart-lung preservation system was developed to enable distant organ procurement. In 8 dogs, a functioning heart-lung system was isolated, cannulated in situ, removed en bloc, and placed into a Plasmalyte-filled, temperature-controlled (15-38°C) chamber. The perfusion circuit consisted of an adjustable-height, autologous-blood reservoir. The heart ejected through the aortic cannula with venous return (VR) into the superior vena cava. Respiration was maintained with a positive pressure ventilator. Intramyocardial tissue pressure (IMP), tissue pH, right atrial (RAP), aortic pressure (AOP), and cardiac output (CO) were monitored. Autoperfusion at normothermia and CO of 50 mL/min/kg resulted in early (3 h) deterioration of pulmonary function with progressive interstitial lung edema. Pulmonary dysfunction always preceded changes in regional myocardial contractile viability (peak IMP and d(IMP)/dt) and global function (CO, AOP). When tissue pH was regulated ectothermically (as in cold-blooded animals) (ΔpH/°C = -0.015) the heart maintained a stable pumping mode (>6 h) at myocardial temperatures of 17-28°C, pH = 7.70-7.55, and heart rate of 25-50 bpm, respectively. The results indicate that a viable (>6 h) autoperfused, working heart-lung system can be achieved by reducing the circulating blood flow to 30-50% of normal CO. More significantly, ectothermic alpha-stat modulation of perfusate pH and pCO2allows a substantial reduction in organ temperature and metabolic demand without endangering induction of fibrillation and ultimate allograft failure.

ISSN:0894-1939    

DOI:10.3109/08941938909057434

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

In this study kidneys were harvested from bred-for-research cats weighing 4 to 5 kg. General principles of donor bilateral nephrectomy en bloc with aorta, vena cava, renal vessels, and ureters were followed. After the harvest the grafts were placed in lactated Ringer slush. A cuff was prepared on the renal vein over a 10 French plastic tube. The aorta was divided and left in connection with the renal artery at each side. Twenty female checkered Flemish giant rabbits weighing 4.0-6.0 kg served as recipients. After pre-medication with 40 mg/kg of ketamine, anesthesia was maintained with repeated doses (every 10-15 min) of a 0.1-mL mixture of 5 parts ketamine and I part acepromazine diluted 50% in a normal saline. Arterial pressure, CVP, blood gases, and temperature were monitored. Through a limited midline incision a native left nephrectomy was performed. The venous anastomosis was performed with a cuff technique without clamping the vena cava (which causes severe hemodynamic instability); the anastomotic time was 2-3 min. The arterial anastomosis was performed with an end-to-side aorta-to-aorta anastomosis; the anastomotic time was 5 to 7 min. There were no episodes of venous or arterial thrombosis. The donor procedure took approximately 40 min, and the backtable preparation of the graft an additional 45 to 60 min. Preparation of the recipient for the anastomosis took 15 min and the anastomotic time (warm ischemia) was 13±5 min. In this model suitable for xeno-graft research the duration of the surgery in the recipient has been greatly reduced because of(1) the previous backtable preparation of the graft, und (2) the cuff technique used for venous anastomosis. The present anesthesia regimen and careful hemodynamic monitoring were also important in the success of this model.

ISSN:0894-1939    

DOI:10.3109/08941938909057435

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor