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PubMed1993

Role of the kidney in the expression of low molecular weight factors with growth factor activity.

Small molecules of peptidic nature, called low molecular weight growth factors (LMW-GF < 1000 Da) are present in normal human serum ultrafiltrate. They enhance the somatomedin activity as measured by the incorporation of 35SO4 into chick embryo cartilages. On the basis of this in vitro test, LMW-GF activities were measured in serum ultrafiltrates of hemodialyzed patients and renal transplant recipients during the post-transplantation follow-up. LMW-GF activity was always zero in patients with chronic renal failure. It was checked that these results were not due to the presence of low molecular weight somatomedin inhibitors or to the increased sulfate concentration. After successful renal transplantation, the LMW-GF activity of patients ultrafiltrates returned to normal at the same time or before the improvement of renal function. In case of post-transplant complications, a decrease in LMW-GF activity accompanied or even occurred prior to impairment of renal function. In functioning graft, LMW-GF activity reappears rapidly, whereas its normalization is delayed in case of tubular nephropathy or episode of acute rejection. It was suggested that the kidney is involved in LMW-GF molecules production or processing. It could be speculated that LMW-GF activity might be a prognostic factor in renal transplantation.

Adult↗
PubMed1969

Carcinogen-induced tumors of the thymus. IV. Humoral influences of normal thymus and functional thymomas and influence of posthymectomy period on restoration.

A progressive decrease of the restoring effectivity of syngeneic or allogeneic thymus and functional thymoma grafts was observed when the treatment of neonatally thymectomized mice was delayed. Early treatment (5-20 days postthymectomy) was effective, while the number of restored animals was markedly decreased after late treatment (30-50 days postthymectomy). Similar results were obtained with subcutaneous or intraperitoneal thymus grafts and with thymus grafts within cell-impenetrable diffusion chambers. After the onset of the postthymectomy-wasting syndrome the only successful treatment was the implantation of multiple thymus grafts. On the other hand, single thymus grafts, thymoma grafts, or thymus or thymoma within diffusion chambers were ineffective. When spleen cells from 5-day old or 45-day old neonatally thymectomized animals were given in association with thymoma grafts, only the cells derived from the 5-day old thymectomized mice proved effective in restoring wasted thymectomized hosts. These results suggest that a population of cells sensitive to the action of the thymus decreases progressively with time in the absence of thymic function.

Age Factors↗
PubMed1987

Pathology of the thymus after allogeneic bone marrow transplantation in man. A histologic immunohistochemical study of 36 patients.

A major hypothesis to explain the immunodeficiency associated with bone marrow transplantation states that thymic epithelial damage due to graft-versus-host disease (GVHD) abrogates or delays the recovery of normal immunologic function. This study evaluated the thymus glands of 36 human bone marrow transplant recipients dying between 4 and 1742 days after transplant using histology, histochemistry, and immunohistology. The observations lead to a model of thymic damage by irradiation, chemotherapy, and GVHD in which early injury by all three of these agents results in profound thymic atrophy followed by long-delayed restitution. Patients undergoing total body irradiation showed more severe damage to thymic cortical and medullary epithelium than did patients undergoing chemotherapy alone as preparation for transplantation. Patients with GVHD showed additional damage in the form of individual thymic epithelial cell death and showed HLA-DR surface protein expression on thymic epithelium during GVHD. Longer-term survivors showed a profoundly delayed restitution of normal thymic epithelium and delayed evidence of restored lymphopoiesis. A few patients dying late after transplant showed evidence of reconstitution of normal thymic structure or nodules of lymphopoiesis in focal areas of epithelial-cell reconstitution. Evidence of such lymphopoiesis was seen at times ranging between 90 and 1742 days after grafting. The data are consistent with a model of long-standing thymic damage caused by GVHD which is reversible after the development of tolerance.

Adolescent↗
PubMed1993

[Levels of beta-2-microglobulin (B2MG) in blood serum of patients during the early phase after kidney transplantation].

In uremic subjects serum B2MG levels was significantly higher than in normals. In kidney transplant patients (KTP) serum B2MG levels was 3-4 times higher than in normals. Elevated serum B2MG levels in KTP seems to depend not only on the kind of immunosuppressive therapy but also on other factors. In the present study we aimed to asses serum B2MG levels immediately after KT. B2MG were assessed in 25 uremic patients at the early phase after KT and in 12 controls (patients immediately after cholecystectomy). All uremic patients were divided on two groups: group I-patients with immediately graft function after transplantation (12 patients) and group II--patients with acute failure of the transplanted kidney (13 patients). In all examined subjects immediately before and 1, 2, 3, 4, 5, 10, 15, 20, 25, and 30 days after transplantation serum B2MG levels were assessed using RIA methods. In group I we observed gradually decline of B2MG concentrations parallel with creatinine after KT while in group II normalization of B2MG and creatinine levels were delayed (approximate 10 days). The significant positive correlation was found between plasma B2MG and creatinine levels in all examined patients. We concluded: 1. In all examined groups the tendency to normalization of B2MG levels after KT was observed. 2. Acute failure transplanted kidney delayed normalization of B2MG concentrations. 3. Normalization of B2MG levels was preferentially dependent on the graft function.

Adult↗
PubMedDate not supplied

Delay in manifestations of aging by grafting NGF cultured chromaffin cells in adulthood.

Dopamine agonists or grafts compensate impaired motor functions in aged rats. However, there is no evidence showing whether grafting in adulthood retard aging manifestations. Motor performance of 13-month-old rats was tested on 2 meter-long wooden beams which had a 15 degree inclination and whose thickness varied from 3, 6, 12, 18, to 24 mm. Rats at 14 months were randomly assigned to 3 groups: sham graft (Group 1); intrastriatal graft of chromaffin cells cultured with NGF (Group 2); intrastriatal graft of chromaffin cells (Group 3). Motor performance was tested at monthly intervals up until rats were 26 months old. Two more groups were included: 26-month-old naive rats (Group 4); and 3- to 5-month-old naive rats (Group 5) both evaluated only once. At 26 months, the basal activity of ventral mesencephalic dopaminergic neurons was recorded. Results showed in Group 2 delay of motor detriments seen in aged rats, maintenance of basal firing rates of nigral cells compared to those of younger rats, and greater survival of substantia nigra cells. It is suggested that NGF cultured chromaffin cells produce a delay of motor detriments in aged rats, as a result of inducing survival and firing rates of nigral cells comparable to those seen in young rats.

Age Factors↗
PubMed1979

Delayed hyperacute rejection in recipients of kidney transplants from HLA identical sibling donors.

Delayed hyperacute rejection, with its characteristic clinical course and histopathologic findings, occurred within one month after transplantation in five recipients of kidney transplants from HLA-A, B and D identical sibling donors. In all cases, unidirectional mixed lymphocyte cultures and immunologic studies to detect cytotoxic antibodies in the recipients against their respective donors, before kidney transplantation and after transplant nephrectomy, were unresponsive or negative. Onset of delayed hyperacute rejection was preceded by bacteremia in two of these patients. Two of these received second kidney transplants, three to six months later, from HLA-A, B and D identical sibling donors again. Although both have had an episode of acute rejection in the early postoperative period, the grafts have maintained excellent function for 21 and 25 months, respectively. Irreversible forms of transplant rejection, such as delayed hyperacute rejection, do occur even in recipients of kidney transplants from HLA-A, B and D identical sibling pairs, indicating that genetic determinants other than HLA-A, B and D loci, and perhaps other nongenetic immune mechanisms, play an important role in the ultimate results of kidney transplantation.

Adult↗
PubMed1990

Vascular thymus transplantation in rats. Technique, morphology, and function.

A new method of thymus transplantation is introduced, in which the graft is directly connected with the recipient's vascular system. This procedure was used both in euthymic rats and congenitally athymic nude rats. At all tested intervals after transplantation thymus grafts hardly differed from the recipient's own thymus in immunohistology and lymphocyte yield. In athymic nude rats, T cell-dependent immunity, tested by mitogen- and alloantigen-induced T cell responses, as well as by antibody production and delayed-type hypersensitivity after ovalbumin administration, showed that vascular thymus grafts could generate T cell functions to euthymic control levels. We conclude that the technique of vascular thymus transplantation represents a valuable tool, either in fundamental research on thymus function, or for the purpose of immune (re)constitution.

Animals↗
PubMedDate not supplied

Effects of local delayed hypersensitivity on the small intestine.

There are many T and B cells in the small intestinal mucosa and local T cell immunity could have a role both in protective immunity and as a cause of disease (i.e. hypersensitivity). This latter aspect has been investigated by using several animal models to assess the effects of local delayed hypersensitivity on the structure and function of the small intestine. Heterotopically transplanted grafts of fetal small intestine in mice (isografts and allografts) have been examined by conventional histology, scanning and transmission electron microscopy, by making direct measurements of villi, crypts, and lymphoid cell infiltrate, and by counting the number of mitoses per crypt. This cell-mediated immune reaction causes lymphocyte infiltration which is most marked in the lamina propria, hyperplasia of the crypts of Lieberkühn, increased cell loss with villous atrophy and a flat surface, but the individual enterocytes appear fairly normal. Graft-versus-host disease cause exactly the same changes in structure and in cell kinetics as does rejection. However, crypt hyperplasia has been found to precede villous atrophy by several days. Preliminary experiments on local contact hypersensitivity suggest that intraluminal injection of oxazolone in the gut of sensitized mice also produces villous atrophy and crypt hyperplasia. It is postulated that these effects are likely to be produced via lymphokines: by an 'enteropathic' factor which damages the lamina propria and basement membrane, and a factor which is mitogenic for crypt stem cells. In mice infected with Giardia lamblia, crypt hyperplasia and lymphocyte infiltration of the epithelium are present and there is accelerated epithelial cell turnover. In rats infected with Nippostrongylus brasiliensis, the flat mucosa has been shown to be due to the thymus-dependent immune response and not directly to the damage produced by the parasite itself. A common factor in the variety of conditions associated with villous atrophy and crypt hyperplasia may well be a local cell-mediated immune reaction to food, microbial, parasite or other antigens which causes changes in enterocyte turnover rate and malabsorption.

Animals↗
PubMed1991

Influence of time from donor death to graft harvest on conduit function of cryopreserved aortic allografts in lambs.

We examined the influence of time from donor death to graft harvest on conduit function of aortic allografts in the thoracic aortic position in 18 lambs (mean weight, 11.4 kg). Five grafts were harvested immediately after donor death (fresh), seven at 24 hours, and six at 48 hours following cadaver storage at 4 degrees C. All grafts were treated with antibiotics and were stored by cryopreservation. All animals were catheterized postoperatively and at 3, 6, 9, and 12 months. One animal in the 24-hour group developed an allograft aneurysm, and another one died from a ruptured allograft; one graft in the fresh group occluded by nine months. No animal, however, in the 48-hour group either developed an aneurysm or occluded. There was in fact minimal change in graft diameter over time (p greater than 0.05), while the native aorta grew appropriately (greater than 50%, p less than 0.01). Forty-eight hour delay from donor death to graft harvest did not have significant effect on conduit function. This information may expand the donor pool for allografts.

Animals↗
PubMed2002

Avoiding ischemia in latissimus dorsi muscle grafts: electrical prestimulation versus vascular delay.

BACKGROUND: Surgical mobilization of the latissimus dorsi muscle produces regional ischemic damage that may compromise its function in clinical applications such as cardiomyoplasty. We compared the effectiveness of two procedures designed to maintain blood flow throughout the mobilized muscle. METHODS: Adult pigs were assigned to two experimental groups: an electrically prestimulated group (n = 10) and a vascular delay group (n = 10). In the prestimulated group the left latissimus dorsi muscle was activated in situ at 2 Hz for 24 h/d. In the vascular delay group, the intercostal perforating arteries to the left latissimus dorsi muscle were divided. Two weeks later, hyperemic blood flow was measured by means of fluorescent microspheres immediately before and after mobilizing the latissimus dorsi muscle and again after recovery for a further 2 days. RESULTS: In the prestimulated group, blood flow was not significantly depressed in any region of the muscle immediately after mobilization, and blood flow increased significantly in proximal (p = 0.01), middle (p = 0.02), and distal (p = 0.007) regions following recovery. In muscles subjected to vascular delay the proximal and middle regions showed no significant changes in blood flow after mobilization or recovery, but flow in the distal region was 50% lower after mobilization (p = 0.003), and it remained significantly depressed even after recovery (p = 0.008). CONCLUSIONS: Prestimulation was significantly more effective than vascular delay in preserving distal blood flow. Because it is also less invasive and initiates metabolic transformation before mobilization, this technique should allow cardiac assistance to be introduced at an earlier postoperative stage without compromising the viability of the grafted muscle.

Animals↗
PubMed1992

Modified extravesical ureteral reimplantation in pediatric renal transplantation: 5 years of experience.

Numerous surgical procedures have been described to reimplant the ureter into the bladder during renal transplantation. Since November 1985 we have used a modified extravesical technique in 19 children. At the time of transplantation patient age ranged from 2 to 17 years (average age 10 years). Of these patients only 2 received a cadaveric kidney. Postoperative followup ranged from 4 to 54 months (average 32 months). No immediate or delayed urological complications were noted, and all but 1 graft has continued to function. This procedure is not only expeditious and safe but it also eliminates a long cystostomy suture line and requires a short ureteral length. Urinary leakage and ureteral obstruction, 2 of the most common urological complications, have not been observed in our patients. Although further experience and longer followup are required, this technique has become our procedure of choice for ureteral reimplantation in children undergoing renal transplantation.

Adolescent↗
PubMed1991

A multivariate approach to the treatment of peripheral nerve transection injury: the role of electromagnetic field therapy.

A multivariate approach to the treatment of peripheral nerve transection injury has been used in a rat model. A pilot study (48 animals, 8 groups) examined variables associated with the method and timing of surgical repair, the arrest of wallerian degeneration, and the role of pulsing electromagnetic field therapy (PEMF) in functional recovery. A second phase (90 animals, 6 groups) then studied the timing and duration of pulsing electromagnetic field therapy as the only variable in larger groups of animals. The pilot study revealed that a vein-graft conduit did not improve functional recovery compared with standard epineurial repair. Additionally, delayed repair compared favorably with immediate repair. The use of chlorpromazine to inhibit the toxic effects of calcium influx appeared to enhance early functional recovery, and the combination of delayed nerve repair and pulsing electromagnetic field therapy seemed to consistently improve function. The second phase of the study has demonstrated (for the first time) statistical improvement in ambulation in animals treated with delayed surgical repair and prolonged pulsing electromagnetic field therapy. We postulate that future treatment of nerve transection injuries will involve a combined treatment regimen consisting of the immediate arrest of wallerian degeneration, delayed surgery, and pulsing electromagnetic field therapy.

Analysis of Variance↗
PubMed2002

Bronchiolitis obliterans: the Achilles heel of lung transplantation.

Operative mortality in lung transplantation in many centers has decreased to less than 10%. Despite this improvement in early survival, delayed graft failure related to chronic graft rejection continues to limit the survival and function of lung transplant recipients. Chronic lung transplant rejection Bronchiolitis obliterans (BO) is an inflammatory process that leads to fibrous scarring of the terminal and respiratory bronchioles and subsequent total occlusion of the airways. The histological changes are manifest by a progressive obstructive ventilatory defect on spirometric testing. Histologic diagnosis of BO is difficult due to sampling. The term BO syndrome has been developed to allow clinical diagnosis using spirometric criteria. BO is an alloimmune phenomenon, aggravated by airway ischemia, and infection but predicted by frequent and severe acute vascular rejection. It is characterized by increased expression of TGF beta and other cytokines on airway epithelial cells, increased expression of class II antigens in the airways, lymphocytic bronchiolitis, and bronchial epithelial cell proliferation mediated by numerous cytokines. Airway neutrophilia, and activation of neutrophilis with release of their granules into the airway is a precursor of progressive BO. Loss of normal protective mechanisms--leukocyte antiproteases--against this oxidative insult may be an integral part of disease progression. To date treatment of BOS is infrequently successful. Better understanding of the pathophysiology, and earlier recognition of BO may result in improved long term patient and graft survival and function.

Bronchi↗
PubMed1988

Dipyridamole preserved platelets and reduced blood loss after cardiopulmonary bypass.

Cardiopulmonary bypass activates and depletes platelets, which may contribute to postoperative bleeding. In addition, activated platelets may be deposited in the coronary vasculature after ischemia and cardioplegia, which may delay recovery of cardiac function and metabolism and may contribute to early bypass graft occlusion. The antiplatelet agent dipyridamole reduces platelet activation and depletion and may decrease postoperative bleeding and transfusion requirements. A prospective randomized trial was conducted in 58 patients undergoing elective coronary bypass operations to compare the effects of oral (19 patients) and intravenous (21 patients) dipyridamole to the results obtained in a control group (18 patients) who received no dipyridamole. Preoperative oral administration of dipyridamole resulted in lower plasma drug concentrations in the early postoperative period than perioperative intravenous administration (p = 0.0001 by analysis of variance). Postoperative arterial platelet counts were highest in the patients receiving intravenous dipyridamole, intermediate in those receiving oral dipyridamole, and lowest in the control group (p = 0.03 by analysis of variance). Postoperative blood loss and blood product transfusions were significantly reduced with both oral and intravenous dipyridamole (p = 0.04 by analysis of variance). Dipyridamole preserved platelets and reduced postoperative bleeding. Intravenous dipyridamole resulted in higher platelet counts than oral dipyridamole and may be required to reduce postoperative bleeding in high-risk patients.

Administration, Oral↗
PubMed1978

Treatment of chronic granulocytic leukemia by chemotherapy, total body irradiation and allogeneic bone marrow transplantation.

Fourteen patients with chronic granulocytic leukemia received bone marrow grafts from HLA identical siblings. Ten patients were in blast crisis prior to grafting, three were in an accelerated phase of their disease, and one was aplastic secondary to chemotherapy. Prior to transplant all patients were conditioned with chemotherapy including cyclophosphamide plus 1,000 rad of total body irradiation. Ten patients achieved engraftment while four died 1 to 26 days after marrow infusion without functioning grafts. Two patients received a second infusion of donor marrow because of delayed engraftment. Neither marrow cell dose nor presence of myelofibrosis correlated with successful engraftment. Three out of ten engrafted patients developed graft-versus-host disease. Interstitial pneumonia occurred in seven patients. The immediate cause of death was bacterial septicemia in six patients. All evidence of leukemia disappeared in nine out of ten evaluable patients. The median survival was 43 days. One patient had a complete remission of 16 months duration.

Adolescent↗
PubMed1997

Reconstruction of the immune system after unrelated or partially matched T-cell-depleted bone marrow transplantation in children: functional analyses of lymphocytes and correlation with immunophenotypic recovery following transplantation.

Reconstitution of the immune system following T-cell-depleted bone marrow transplantation (BMT) in children has yet to be fully elucidated. Thus, we prospectively studied the recovery of immune function in 64 children who underwent T-lymphocyte-depleted marrow transplants using either matched family member donors or matched unrelated donors. We measured in vitro posttransplantation proliferative responses to phytohemagglutinin (PHA), concanavalin A, pokeweed mitogen, and Candida albicans antigen and assessed unidirectional allogeneic mixed-lymphocyte culture (MLC) responses at various times. A total of 129 healthy individuals served as normal controls for these assays. Responses to T-cell mitogens normalized within 12 months posttransplantation, while MLC responses normalized by 9 months. The presence of graft-versus-host disease (grade II or greater) and cytomegalovirus infection was associated with delays in immune function recovery. Importantly, immune function recovery correlated temporally with a rise in peripheral lymphocyte count. In contrast, the CD4/CD8 ratio was not predictive of immune recovery. Knowledge of immune function recovery may guide clinicians in devising strategies to minimize the risk of infection post-BMT.

Adolescent↗
PubMed1997

Early and delayed repair of orbitozygomatic complex fractures.

PURPOSE: The goal of this study was to review experience with early and delayed repair of orbitozygomatic complex fractures and develop guidelines for repair based on timing and extent of injury. PATIENTS AND METHODS: Records of patients with orbitozygomatic complex fractures over a 10-year period were reviewed for cause of injury, signs and symptoms, length of time from injury to repair, and method of repair. Results were evaluated by office examination and telephone interviews at least 6 months to 10 years after surgery. RESULTS: Seventy-eight patients who had undergone 81 surgical procedures were analyzed. The series consisted of 49 primary repairs (1 to 22 days postinjury), 10 delayed repairs using osteotomies at 21 days to 5 months postinjury, and 22 delayed repairs requiring onlay bone grafting from 4 months to 16 years postinjury. Forty patients (43 procedures) were available for follow-up. Early surgical intervention dramatically improved esthetic and functional outcomes, whereas late repair was less satisfactory. Hypoesthesia was not improved by surgery. Osteotomy and onlay grafting techniques were necessary for delayed treatment. CONCLUSION: Orbitozygomatic fractures can be repaired up to 21 days postinjury using primary reduction and fixation techniques. Osteotomies are required after 21 days and can be used successfully up to 4 months postinjury. After 4 months, successful repair requires onlay bone grafting.

Adolescent↗
PubMed1997

Mechanism of concordant corneal xenograft rejection in mice: synergistic effects of anti-leukocyte function-associated antigen-1 monoclonal antibody and FK506.

BACKGROUND: The mechanisms of corneal xenogeneic immunoreaction, as well as the potential role of immunosuppressive therapy in the suppression of corneal xenograft rejection, have not been thoroughly explored. METHODS: BALB/c mice who received orthotopic corneal transplants (Lewis rats donors) were administered intraperitoneally anti-leukocyte function associated antigen-1 (LFA-1) monoclonal antibody (mAb) or FK506 (3 mg/kg/day) or both of these immunosuppressants during a 12-day postoperative period. Histological (hematoxylin-eosin stain) and immunohistochemical evaluations of enucleated eyes were performed. Humoral immune response and delayed-type hypersensitivity (ear-swelling assay) were evaluated. RESULTS: The mean (+/-SD) graft survival time in the untreated control, FK506-treated, anti-LFA-1 mAb-treated, and combined-treatment groups was 5.8+/-0.8, 9.4+/-4.0, 8.7+/-5.0, and 67.7+/-16.4 days, respectively. In the untreated control group, mouse IgG, IgM, and C3 were expressed on the rat corneal grafts during the early postoperative phase. Flow cytometry studies revealed high titers of xenoreactive IgG and IgM antibodies. T helper 1 cytokines were expressed on xenografted corneal beds, and delayed-type hypersensitivity was induced. However, local expression of IgM, C3 and T helper 1 cytokines, serum antibodies of IgG and IgM, and delayed-type hypersensitivity were suppressed in the anti-LFA-1 mAb- plus FK506-treated group. CONCLUSIONS: Both humoral and cell-mediated immune reaction play an important role in the initial rejection in rat-to-mouse corneal xenotransplantation. The treatment with anti-LFA-1 mAb in combination with FK506 synergistically suppresses concordant corneal xenogeneic reaction.

Animals↗