ISSN:0041-1337    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Platelet activating factor (PAF, 1-alkyl-2(R)-acetylglycero-3-phosphorylcholine) is a phospholipid that is released by a variety of cells. The similarity between the pathophysiological effects of PAF and posttransplant pulmonary dysfunction led to an evaluation of a PAF antagonist as an adjunct to lung preservation. The ginkgolide B, BN 52021, was selected as the PAF antagonist to be studied because of the large data base available on this compound.BN 52021 was given to the donor and recipient (10 mg/kg i.v.) prior to harvest and transplantation and was included in 1 L of preservation solution (10 mg/kg) used for flushing the pulmonary artery and for storage. Left single-lung transplantation was performed following a 22-hr preservation period at 10°C. Arterial oxygen tension (pO2), pulmonary vascular resistance (PVR), alveolar arterial oxygen difference (A-aDO2), and dynamic lung compliance (DLC) were recorded for 6 hours following ligation of the native pulmonary artery. At the end of 6 hr pO2was 243.5±61.5 vs. 71.7±10.2 mmHg (P<0.02) for the controls. A-aDO2was less in the BN 52021 groups: 431.8±58.3 vs. 606.0±9.8 mmHg in the control groups (P<0.001), and PVR was significantly less in the BN 52021 group: 346±70.8 vs. 663±64.3 dynes/sec/cm−5(P<0.035).We conclude that PAF antagonists like BN 52021 may be useful adjuncts for lung preservation. The effects of BN 52021 are easily explained by PAF antagonist activity in ischemic and reperfusion-induced pulmonary dysfunction. However this study does not exclude that BN 52021 may have direct effects.

ISSN:0041-1337    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Previous experiments xenografting human fetal pancreas into athymic mice made diabetic with streptozotocin have demonstrated that normoglycemia can be achieved 1–3 months after implantation, but that the blood glucose levels obtained were significantly lower than those of control mice (1). These lower levels could be due either to genetic regulation by the grafted human beta cell—human neonatal blood glucose levels are lower than those of athymic mice—or to excess release of insulin from the increasing number of beta cells in the implant. In order to address the latter possibility, human fetal pancreas was grafted beneath the renal capsule of athymic mice, the pancreas of which was intact, and they and their ungrafted litter mates monitored during their life span—71±17 weeks after surgery for the 4 successfully grafted mice. The random blood glucose level in all mice was the same initially and remained so until a significant lowering 20 weeks later—2.0±0.2 vs. 3.4±0.4; this difference was maintained thereafter. Data obtained from the oral glucose tolerance tests conducted at 8 weekly intervals paralleled these results. Human C-peptide was detectable in blood by 26 weeks, with a rise demonstrable during the

ISSN:0041-1337    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

A limited collagenase digestion was used to prepare human fetal pancreatic (HFP) proislets that maintained in vitro and in vivo functional viability. Digestion times, collagenase concentrations, and culture conditions were optimized by assessing insulin release in response to low glucose (3.3 mM), high glucose (16.7 mM), and high glucose plus theophylline (10 mM). A stimulation index (ng insulin release in low glucose/ng insulin in high glucose plus theophylline) and insulin production (ng insulin/mg tissue) were used to determine functional viability. A media change 24 hr after digestion resulted in a marked increase in mean stimulation index (6.18± 1.2 vs. 3.12±0.9). IGF-1 was found to enrich β-cell viability as demonstrated by insulin-specific immunoperoxidase staining and insulin release in response to HGT (36.3±7.7 ng/mg tissue vs. 18.1±5.2 ng/mg tissue). Immunohistologic staining of proislets suggested selective enrichment of β cells. Diabetic BALB/c/nu/nu transplanted with proislets cultured in the presence of IGF-1 (100 ng/ml) returned to normoglycemia in 6.7±3.1 weeks (range 4–11) versus 12.0±4.0 (range 10–15) in controls. Oral glucose tolerance test demonstrated in vivo serum glucose control equivalent to nondiabetic control mice. These findings suggest that HFP proislet preparation and culture with endocrine growth factors, specifically IGF-1, may provide a source of tissue with enriched β-cell activity that may have decreased immunogenic load and is more suitable for clinical transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We have investigated the effects of recombinant human granulocyte colony-stimulating factor (rG-CSF) on hemopoietic reconstitution after bone marrow transplantation (BMT) following lethal irradiation in mice. Mice received a daily administration of 10 μg/kg rG-CSF or control vehicle one through 21 days after BMT. Spleen colony-forming units (CFU-S), granulocyte-macrophage colony-forming units (CFU-GM), megakaryocyte colony-forming units (CFU-Meg), and erythroid burst-forming units (BFU-E) increased in both bone marrow and spleen of the rG-CSF-treated mice as compared with the control. This increase was evident during the administration period. In spite of the increase in the progenitor cells in bone marrow and spleen, only a recovery of neutrophils was accelerated in peripheral blood. Thus rG-CSF accelerated granulopoietic recovery in the BMT mice, with an enhanced recovery of the stem cells and the progenitors for erythrocytes and megakaryocytes. These results indicate the potential clinical usefulness of rG-CSF in the treatment of patients undergoing BMT.

ISSN:0041-1337    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The gracilis musculocutaneous flap was developed as an allograft model to study acute rejection and immunosuppression in the cat. Twelve adult cats received a MLC incompatible flap. Six of the cats received cyclosporine oral solution and prednisolone (0.5 mg/kg/24hr) for 100 days and six cats were not treated. Trough whole-blood levels of cyclosporine in the treatment group were maintained at approximately 750 ng/ml for 70 days, then 500 ng/ml for the remaining 30 days. Three flaps failed due to technical problems; 5 flaps were studied in the treatment group and 4 in the untreated group. All 5 flaps in the treatment group survived the 100 day treatment period and were rejected 30±26 days following cessation of treatment. Prior to discontinuation of treatment, with the exception of one cat, inflammatory changes associated with rejection were not observed in biopsy specimen. The flaps in the untreated group survived 13±1.5 days. Histopathologic examination of the flaps revealed little difference in the appearance of acute rejection and rejection after cessation of therapy. The most prominent lesion was a vasculitis with extensive perivascular lymphohistocytic inflammation. The lymphoid infiltrates consisted predominantly of T cells of both major classes (CD4 and CD8). Full-thickness epidermal necrosis and subsequent bacterial invasion followed vascular compromise.

ISSN:0041-1337    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We have demonstrated that the sinusoidal lining cell injury sustained by rat liver allografts during hypothermic storage is a critical determinant of graft viability. The present study was designed to examine the effect of donor nutritional status on hepatic microcirculation and graft function. Rat livers from four nutritional groups (group I, fasted; group II, fed; group III, intraperitoneal glucose; and group IV, fed plus intraperitoneal glucose) were excised and stored for 24 hr in Marshall's isotonic citrate solution. Then the livers were perfused under anoxic conditions with trypan blue. The percentage of nonviable SLC in each group was 26.7±8.1, 24.9±7.9, 17.6±6.9, and 5.9±1.9 in groups I, II, III, and IV respectively; i.e., there was a significant improvement in SLC viability with nutritional repletion in group IV. Electron microscopy was performed on livers from groups I and IV following 30-hr preservation in University of Wisconsin solution and after 16-hr preservation in Marshall's isotonic citrate solution. Biopsies were taken at the end of storage and after 1 hr of reperfusion at 37°C. At the end of preservation group IV livers contained glycogen and had much more normal liver ultrastructure than group I livers. After reperfusion there was partial recovery of normal SLC morphology in both groups and depletion of glycogen in group IV. Liver function was studied on the isolated perfused rat liver system at 37°C following 30-hr storage in UW solution. Transaminase release into the perfusate was significantly lower in nutritionally repleted livers than in livers from fasted animals. A significant reduction in perfusate platelet count occurred only in livers from fasted animals. The results show that nutritional repletion can reduce the injury of cold preservation to both hepatocytes and endothelial cells and improve liver function in the postpreservation period.

ISSN:0041-1337    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The long-term kidney function (KF) in the three categories of diabetic type 1 pancreas (P) transplant recipients (simultaneous P and kidney [SPK]; P after K [PAK]; PTx alone [PTA]) was studied sequentially over a 2-year period in 62 patients who received a bladder-drained allograft that functioned for at least 1 year. Fifty-three (85%) patients were analyzed at 1 month, 42 (68%) at 1 year, and 16 (26%) at 2 years posttrans-plant. Comparison of KF was made within each recipient category and between categories. In addition, the KF in the SPK and PAK patients was compared to a matched group of diabetic type 1 recipients of KTx alone (functioning at least 1 year). In the SPK group, KF was stable over time: the mean ±SD serum creatinine (mg/dl) was 1.5±0.5 at 1 month, 1.8±1.0 at 1 year, and 1.7±0.5 at 2 years. In the PAK category, the pre-PTx serum creatinine value was 1.4±0.5, and then remained stable after the PTx (1.3±0.2 at 1 month, 1.3±0.4 at 1 year, and 1.2±0.4 at 2 years). In the recipients of a PTA, the values at 1 month (1.1±0.4), 1 year (1.4±0.5), and 2 years (1.3±0.5) were significantly higher (P≤0.03) than the pre-PTx value (0.9±0.2); and results at 1 month and 2 years were lower than those at 1 year, a significant difference compared to the 1-month value (P=0.01). Comparisons between the categories of PTx recipients demonstrated that the pre-PTx value in the PTA group (0.9±0.2) was significantly lower (P=0.01) than in the PAK group (1.4±0.5). At 1 month the serum creatinine value in the PTA category (1.1±0.4) was significantly lower (P=0.02) than in the SPK category (1.5±0.5), but thereafter (1 and 2 years) the difference was not significant (P>0.1). KF in recipients of KTx alone was similar at each post-Tx time point when compared to the SPK and PAK categories. We concluded that a PTx can be performed in diabetics without a detrimental effect on a simultaneously or a previously transplanted kidney and that a statistically significant, albeit minimal to moderate, initial but not progressive deterioration in native KF occurs in recipients of a PTx alone.

ISSN:0041-1337    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

This study examined the safety and pharmacokinetic profile of a potentially therapeutic and fully human anti-CMV monoclonal antibody (SDZ MSL-109) in a phase I dose escalation trial in patients receiving allogeneic bone marrow transplants. Fifteen adult marrow transplant patients, twelve with chronic myelogenous leukemia and three with acute nonlymphocytic leukemia, in cohorts of five patients each, were administered monoclonal antibody intravenously at doses of 50, 250, and 500 μg/kg at approximately three-week intervals for six months. Administration of the monoclonal antibody was associated with minimal side effects and no dose-related toxicity. Antibody elimination curves in all dose groups were consistent with a two-compartment model with an alpha half-life at the low, middle, and high dose groups of 1.03, 0.82, and 0.79 days, and a beta half life of 13.9, 14.0, and 16.5 days, respectively. The volume of distribution decreased with repetitive dosing to approximate the plasma volume in each patient and the pharmacokinetic profile was comparable to that of human IgG. There was no host antiidiotypic or antiallotypic antibody formation, indicating that MSL-109 was not immunogenic. Further studies are warranted to assess the potential efficacy of human monoclonal anti-CMV antibodies in the prophylaxis and treatment of CMV disease in marrow transplant recipients and other patients with immunodeficiency disorders.

ISSN:0041-1337    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We have analyzed factors associated with acute graft-versus-host disease following allogeneic bone marrow transplantation in 469 patients with histocompatible sibling donors between 1979 and 1987. Overall, 46±5% (95% confidence interval) developed clinical grade II-IV acute GVHD following transplantation. In univariate analysis, patient or donor age ≥18 years was significantly associated with increased GVHD risks (≥18, 63± 6% grade II-IV GVHD vs. <18,27±6%, P<.0001), without incremental risk in older adults. Univariate analysis showed that donor:recipient sex match and female: female transplants were associated with less-frequent GVHD. More frequent GVHD was associated with chronic myelogenous leukemia, cytomegalovirus seropositivity, and prior donor alloimmunity (pregnancy or transfusion). Additionally, the allele HLA-A26 was associated with increased risk of GVHD (72%, P=.005) while HLA-DR3 was associated with less GVHD (31%, P=.03). Stepwise multivariate analysis confirmed the increased GVHD risks associated with older recipient age, HLA-A26 and donor:recipient gender (not female: female) and the protective effect of HLA-DR3. Similar results were found using the different analytic technique of recursive partition analysis, which identified within the adult population the lowest GVHD risk in female recipients with nonalloimmunized female donors (20%), while other gender combinations had 68% acute GVHD, regardless of donor alloimmunity. In children (<18 years), lower GVHD risk accompanied donor:recipient sex-matched (18%) versus mismatched (33%) BMT. Clinical trials undertaken to lessen the hazards of GVHD must be designed with appropriate attention to these reproducibly identified clinical variables associated with different GVHD risks.

ISSN:0041-1337    

出版商:OVID    

年代:1991

数据来源: OVID