摘要:

Organ transplantation has progressed rapidly during the last decades. Furthermore, tissue engineering has and will continue to enlarge the scope of organ grafting. Thus, severe skin wounds, as observed in large burn trauma patients, can now be permanently treated with cultured autologous epithelial sheets. However, the time required for autologous cell growth is a major limitation. We propose to alleviate this pitfall through a novel chimeric (allogeneic-syngeneic) epithelial cell culture technique. These chimeric epidermal grafts implanted in an animal model have been shown to allow the reappearance of a histologically normal epidermal coverage similar to simultaneously performed isografts. The regenerated epidermis contained only syngeneic keratinocytes. Thus, allogeneic cells were eliminated passively. This new culture technology could find multiple applications, notably in various skin disease therapies.

ISSN:0041-1337    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Using inbred mouse strains C3H/He and BALB/c and an anti-class I MHC monoclonal antibody, we examined the graftability of mixed cultures composed of syngeneic and allogeneic mouse keratinocytes. Keratinocytes from neonatal C3H/He (syngeneic donor) and BALB/c (allogeneic donor) mice were cultured for 7 days, both individually and at the inoculum ratio of 1:1, 1:3, or 1:15. The resulting sheets of keratinocytes were implanted subcutaneously into adult C3H/He mice and morphological evaluation was made on the 4th, 7th, and 14th days after grafting. The control cultures of 100% allogeneic keratinocytes were rejected, whereas epidermal reconstruction without typical signs of rejection took place in all grafts derived from the mixed cultures, including the 1:15 cultures. However, immunofluorescence staining showed that, within the grafts, the allogeneic keratinocytes were gradually replaced by syngeneic cells. Thus, these results suggested that graftable skin substitutes may be produced by co-culturing a small amount of autologous keratinocytes with allogeneic keratinocytes, which are readily available.

ISSN:0041-1337    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The hemodynamic alterations in hepatic microvasculature during acute rejection of rat liver allografts was studied using in vivo fluorescence microscopy. ACI rat livers were transplanted into Lewis (allograft) or ACI (isograft) recipients. Microscopy was performed on days 3 (n=7) and 6 (n=7) in allografts, and on day 6 (n=7) in isografts. Naive ACI livers (n=7) served as nontransplant controls. Changes in sinusoidal blood perfusion, microvascular structure, and leukocyte-endothelial interactions were observed and quantitated. Six days after transplantation, acinar perfusion was markedly impaired in allografts and was accompanied by a lower percentage of perfused sinusoids (59±8%, mean ± SEM, P<0.01) relative to isografts (89±3%) and nontransplant controls (100±0%). The hepatic cord width in allografts was significantly greater than in isografts or in nontransplant controls, indicating swelling of parenchymal and sinusoidal lining cells. Furthermore, the number of leukocytes adhering to the sinusoidal endothelium significantly increased in allografts. Adherence to postsinusoidal venules was more prominent in allograft livers (4025±1400/mm2of vascular endothelial surface) compared with that in isografts (574±77/mm2) and nontransplant controls (185±28/mm2). These microcirculatory alterations in allografts were significant even on day 3. The results show extensive abnormalities of the microcirculatory hemodynamics in rejecting liver allografts which were associated with increased leukocyte adherence to microvascular endothelium. Our findings may provide strategic information for the prevention and treatment of allograft rejection.

ISSN:0041-1337    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Pancreatic islets from BALB/c mice were transplanted to the kidney of syngeneic hosts. After 1–40 weeks, the grafts were removed, perifused in vitro, and extracted. Fresh islets were similarly examined. The graft insulin content fell by 70% in 1 week and remained low throughout the observation period. In contrast, rates of basal or glucose-stimulated insulin release were not much, if at all, decreased. In fresh islets and grafts removed after 3 or 28 weeks, 2 consecutive pulses of glucose stimulation, 20–25 min long and separated by 20 min at basal glucose concentration (2 or 2.8 mmol/L), elicited the same insulin secretory response. When 10 μmol/L acetylcholine and 10 μmol/L eserine were present during the second pulse, the glucose-stimulated insulin release from fresh islets was potentiated as much as 11-fold. This potentiation was reduced by one half during the first week of transplantation, and subsequently by 80–90%. It is concluded that vagal deprivation rapidly induces a state of persistent cholinergic refractoriness in transplanted β-cells, despite morphological signs of autonomic reinnervation of the grafts.

ISSN:0041-1337    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Vasoactive intestinal peptide (VIP) is a known pulmonary and bronchial vasodilator as well as an oxygen free radical scavenger. Since its effect as an additive to University of Wisconsin (UW) solution for lung preservation has been shown previously, the aim of this study was to determine the ability of VIP to improve lung preservation followed by reperfusion. Four groups of excised Sprague-Dawley rat lungs (n=24) were studied using an isolated blood perfused working lung model. The first 3 groups of lungs were flushed and stored in UW solution at 4°C for: (1) 4 hr, (2) 18 hr, and (3) 24 hr. Group 4 lungs were flushed with UW solution + VIP (1 μg/ml) and stored in UW solution + VIP (0.5 μg/ml) for 24 hr. After preservation, the lungs were reperfused to evaluate their functions for 2 hr or until lung failure occurred (arterial oxygen saturation less then 90% and/or appearance of bronchial fluid in the bronchial cannula). In the lungs stored in UW solution for 24 hr, failure occurred after 10 min of reperfusion and all functions were significantly altered. The addition of VIP to UW solution maintained the functional capacity of the lungs, recorded by lung resistance, lung compliance, elastic work, flow resistive work, shunt fraction, and blood oxygen tension. No statistical difference in these parameters other than shunt fraction was found when the VIP group was compared with the group preserved for 4 hr in UW solution. We conclude that lung preservation can be extended to 24 hr with the maintenance of lung functional capacity if VIP is added to UW solution.

ISSN:0041-1337    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Rat hearts were preserved for 18 hr under totally ischemic storage conditions at 0–1°C with the commercially supplied EuroCollins, Bretschneider's HTK, and University of Wisconsin (UW) preservation solutions compared with our new preservation solution, EuroFlush-glutathione solution, and a “refreshed” UW solution (UWG) with 3 mmol/L reduced glutathione added before use. Recovery of the organs was measured during 30 min of parabiotic reperfusion with whole blood of a host rat of the same inbred LEW strain, following an initial warm reflush for 5 min. Functional measurements were performed using a latex balloon in the left ventricle. The metabolic recovery was determined from the myocardium freezeclamped at the end of reperfusion. The left ventricular pressure (LVP) amplitude during pacing to a heart rate of 300/min, as well as +dp/dtmax, —dp/dtmax, isotonic stroke volume, coronary flow, ATP, and ECP values, recovered significantly better after storage in Euro-Flush-glutathione solution (LVP: 63% of controls on average) compared with when the commercially available solutions were used (EuroCollins: 20%, HTK: 42% of controls in LVP). Hearts preserved in UW solution ViaSpan did not recover during the reperfusion period, when unfiltered solution was used. Filtered ViaSpan resulted in LVP recoveries of 38% of controls, while addition of reduced glutathione immediately before use (UWG) improved the effectivity of this solution significantly (LVP 63% of controls). Similar improvements were found for all other functional and metabolic parameters. Thus, the effectivity of UW solution ViaSpan depends upon extraction of the typical particles by a filtering procedure. Effectivity can be improved by a refreshment procedure with reduced glutathione immediately before use.

ISSN:0041-1337    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

This prospective, randomized study investigates the effect of two immunosuppressive treatment regimens on quality of life after renal transplantation. At 3 months after transplantation, patients treated with cyclosporine (CsA) and prednisone (Pred) were allocated to either withdrawal of Pred (n=60) or to conversion of CsA to azathioprine (Aza) (Aza-Pred, n=60). Quality of life was evaluated just before randomization, and at 6 and 12 months after transplantation using the Sickness Impact Profile (SIP), the Affect Balance Scale (ABS), the Center for Epidemiological Studies Depression Scale (CES-D), measures of satisfaction with several domains of life experience, and a population-specific physical symptoms questionnaire. In both groups, the overall SIP score as well as the scores on its physical and psychosocial dimensions improved continuously after transplantation, reaching levels that are comparable to those found in the general population. The occurrence of acute or chronic rejection had a significantly negative effect on SIP and CES-D scores. Intention-to-treat analysis showed no differences between groups for scores on SIP, ABS, CES-D, and satisfaction measures. Exclusion of 41 patients who did not strictly adhere to their originally designated therapy showed a tendency for better psychosocial SIP scores in CsA patients (P=0.05), which mainly resulted from a difference on the category of social interaction (P=0.01). This difference occurred despite a similar rejection rate and worse renal function in CsA-treated patients. Shortly after steroid withdrawal, a high proportion of CsA patients complained of stiff or painful muscles (CsA: 74%, Aza-Pred: 36%; P=0.002). Our data indicate that if successfully completed, CsA monotherapy from 3 months after transplantation may lead to a higher degree of psychosocial well-being as compared with conversion from CsA-Pred to Aza-Pred. It seems likely that this advantage is related to the withdrawal of Pred.

ISSN:0041-1337    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Most patients with secondary hypertension due to renal disease or on maintenance hemodialysis have lost the physiologic fall of blood pressure during sleep. To test the notion that kidney transplantation normalizes the blood pressure profile, we monitored ambulatory blood pressure over 24 hr in 45 patients (29 males and 16 females) after successful renal transplantation.The longer the time after renal transplantation, the more marked was the decrease of blood pressure during sleep (r=0.38,P<0.01). This effect of time after renal transplantation on the fall of blood pressure during sleep was independent of the prevailing level of 24-hr ambulatory blood pressure. The prevalence of dippers (defined by a fall in mean blood pressure during sleep of 10% or more of the awake mean) increased from 27% in the early phase (< 7 months) to 73% in the late phase (≥ 1 year) after renal transplantation (P<0.01). Again, this effect was not attributable to the level of 24-hr ambulatory blood pressure and concomitant antihypertensive or immunosuppressive medication.We conclude that renal transplantation leads to a normalization of the circadian blood pressure profile with a marked decrease of blood pressure during sleep. As a consequence, the lower hemodynamic load imposed on the cardiovascular system may in turn lead to a reduction of cardiovascular morbidity and mortality.

ISSN:0041-1337    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The exact incidence of recurrence of membranous nephropathy (MN) after renal transplantation is not well documented because of the limited number of series involving a small number of patients. The aim of this study was to assess the incidence of MN recurrence in our population of renal transplant patients, to identify the risk factors associated with the recurrence, and to analyze the influence of the recurrence on graft and patient survival rates. The recurrence was defined as biopsy-proven MN on the renal graft in a patient whose original disease was MN. Among 1614 consecutive renal transplantations performed from January 1, 1980, to June 1, 1993, the incidence of recurrence was 26.3%, i.e., 5 recurrences out of 19 transplantations. We were unable to show pretransplant epidemiological, immunological, and therapeutic factors associated with recurrence. The HLA DR3 allele was present in 2 patients with recurrence (40%), compared with 3 patients without recurrence (21.4%). The early use of cyclosporine was not associated with a decreased prevalence of MN recurrence. Graft survival was not influenced by the recurrence. Three lymphomas were observed in the 19 transplanted patients with MN as causal nephropathy.

ISSN:0041-1337    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Chronic rejection of renal allografts is a major cause of late graft loss. However, time of onset, relation with acute early rejection episodes, and risk factors are largely unknown. We undertook a cohort study of 482 consecutive patients from a single center who received a cadaveric renal allograft between January 1983 and April 1991. During the first 3 months after transplantation, 76 (15.8%) patients developed vascular rejection and 115 (23.9%) developed interstitial rejection. One-year graft survival of patients without rejection, with interstitial rejection, and with vascular rejection was 87.8%, 87%, and 48.7%, respectively. Five-year graft survival was 73.5% for the group without rejection, 71.4% for patients with interstitial rejection, and 34.3% for patients with vascular rejection. The adjusted relative risk of graft loss was 4.92 (95% CI 3.25–7.43) for patients with vascular rejection and 1.27 (95% CI 0.80–2.02) for patients with interstitial rejection compared with patients without early rejection, taking the time dependency of the rejection events and prognostic factors into account.The incidence of vascular rejection was increased in patients with primary nonfunction (RR 1.69, 95% CI 1.01–2.84), with 1 HLA-DR mismatch (RR 2.38, 95% CI 1.44–3.93), with 2 HLA-DR mismatches (RR 3.24, 95% CI 1.25–8.42), with a prolonged cold ischemia time (RR 1.03, 95% CI 1.00–1.06 per hr), and with 1 or more previous transplantations (RR 1.76, 95% CI 1.01–3.07). Risk of developing vascular rejection was decreased in patients using CsA as compared with azathioprine (RR 0.41, 95% CI 0.24–0.67).Early vascular rejection, occurring within 3 months after transplantation, is the most important predicting variable of both early and late graft loss. Use of CsA, less HLA-DR mismatching, and a cold ischemiatime of short duration possibly prevent the development of vascular rejection.

ISSN:0041-1337    

出版商:OVID    

年代:1995

数据来源: OVID