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Biomedical subjects

T Wasfie

Publications and source records attributed to T Wasfie.

16 recordsLinked to original sources

UVB pretreatment of rat bone marrow allografts. Prevention of GVHD and induction of allochimerism and donor-specific unresponsiveness.

Ultraviolet B irradiation has been used to pretreat blood and islets to prevent subsequent graft rejection. In this study the optimal dose of UVB irradiation of bone marrow was determined in syngeneic recipients and was subsequently applied to in-vitro treatment of bone marrow allografts. UVB pretreatment of donor bone marrow inoculum led to complete prevention of GVHD in allogeneic rat recipients without major marrow or other toxicity. Long-standing recipients of allogeneic UVB-BM became stable adult chimeras. The recipients of allogeneic BM were populated by donor-type peripheral blood lymphocytes and did not reject host or donor-type heart grafts. The BM allograft recipients were immunocompetent as measured by their ability to normally reject third-party cardiac allografts. We suggest that the prevention of GVHD and induction of stable chimerism in adult recipients of allogeneic UVB-BM may be mediated by suppressor mechanisms.

Animals

Specific immunosuppression by local lymphoid irradiation using subcutaneous injection of palladium-109 labeled allogeneic lymphocytes.

We have previously shown that intravenously administered palladium-109 labeled lymphocytes (Pd-L) migrated specifically to peripheral lymphoid organs where they caused selective lymphoid irradiation resulting in significantly prolonged cardiac allograft survival. This study evaluates the biodistribution of subcutaneously injected allogeneic Pd-L and the capacity of such labeled cells carrying a large dose of irradiation at a local site to attract and subsequently delete alloreactive T lymphocytes. It was hypothesized that subcutaneously administered allogeneic lymphocytes labeled with a large dose of palladium-109 will attract and then kill by irradiation the host effector cells which might permit prolongation of donor-specific allograft via partial clonal deletion. The results showed that 80% (injected dose) of subcutaneously injected allogeneic Pd-L remained at the site of administration while 20% of injected dose/gram was localized in the ipsilateral popliteal lymph node. No significant radioactivity was found in the other lymphoid and nonlymphoid organs. Pd-L effectively deleted the donor-specific effector cells, as measured by specific unresponsiveness to donor lymphocytes in mixed lymphocyte reaction. Donor cardiac allograft survival, however, was not prolonged over that found in naive recipient controls, although it was significantly prolonged when compared to cardiac allograft survival in controls sensitized by identical injections of unmodified subcutaneous allogeneic lymphocytes (mean survival time +/- SD of 6.5 +/- 0.8 vs. 3.0 +/- 0.6 days). These results suggest that partial clonal deletion of specific alloreactive cells achieved by this approach alone is insufficient to induce unresponsiveness to allografts in vivo.

Animals

Production of antiidiotypic antibodies in the rat: in vitro characterization of specificity and correlation with in vivo specific suppression of cardiac allograft immune reaction across major histocompatibility complex.

We studied the effect of antiantidonor major histocompatibility complex antibodies (antiidiotypic antibodies) in vivo on ACI cardiac allograft survival in Lewis rats and correlated the results with in vitro mixed lymphocyte culture. Lewis anti-ACI hyperimmune sera (Ab1) were obtained from animals that have rejected successive ACI skin grafts. Purified immunoglobulin (Ig) G and IgM fractions were obtained from the sera. These putative "idiotypic antibodies" (IgG fractions) were used to immunize groups of five naive Lewis rats. Purified Ig (0.5 mg) was mixed with 0.5 ml incomplete Freund's adjuvant and injected intraperitoneally -15, -7, and -3 days before and at the time of ACI cardiac allografting. The median allograft survival time was 11.2 +/- 0.7 days in animals treated with Ab1 compared with 6.4 +/- 0.5 days in untreated control rats (p less than 0.001). Use of IgM with adjuvant did not prolong graft survival. Purified IgG obtained from sera collected before transplantation was tested for antiidiotypic antibodies with the complement-mediated cytotoxicity assay. For this, serial dilutions of the hyperimmune serum were tested for cytotoxicity against ACI lymphocyte in the presence of Ig from sera collected after immunization with Ab1. Blocking was demonstrated by sera and IgG obtained from Lewis rats that received anti-ACI IgG (Ab1) with adjuvant. The blocking activity of purified IgG (Ab2) was strain specific because it did not block the reaction of Lewis hyperimmune sera against third-party Wistar-Furth rats. Thoracic duct lymphocytes from immunized recipients showed no blastogenic responses when tested in in mixed lymphocyte culture for reactivities against splenocytes from ACI rats. The finding that Lewis rats treated with Ig from sera containing anti-ACI antibodies exhibit impaired anti-ACI T- and B-cell reactivity and prolong allograft survival suggests that pretreatment of recipients with idiotypic antibodies leads to development of antiidiotypic antibodies that modulate alloreactivity suppressing allograft rejection.

Animals

Humoral immunity in allograft rejection. The role of cytotoxic alloantibody in hyperacute rejection and enhancement of rat cardiac allografts.

The role of humoral immunity in graft rejection in the rat model remains controversial. Passive transfer of cytotoxic alloantibody (CAA) has resulted either in hyperacute rejection or in graft enhancement. This study examines the effect of transfer of CAA on cardiac allograft survival in three rat strain combinations that are fully mismatched at the major histocompatibility (MHC) loci. Strain-specific immune responsiveness in donor-recipient pairs varied from low (Lewis-to-ACI) to high (ACI-to-Lewis) as measured by mixed lymphocyte reactions. CAA was obtained from rats sensitized by three successive skin grafts at weekly intervals. Group 1 (high responder recipients), which consisted of Lewis rats presensitized to ACI and had a lymphocytotoxicity titer of 1:512 to 1:2048, rejected ACI cardiac allografts in 10.8 +/- 7.2 hr compared with 6.5 +/- 0.5 days in naive controls (p less than 0.001). Injection of 1 ml of high-titer CAA into naive Lewis rats immediately after ACI cardiac grafting led to hyperacute rejection of ACI hears in 2.1 +/- 0.8 hr while 1 ml of CAA followed by 2 ml of guinea pig complement (GPC) resulted in even faster rejection (mean survival time (MST) of 23.8 +/- 4.7 min). Injection of 2 ml GPC alone or in combination with 1 ml naive Lewis serum had no effect on graft survival. Multiple pretransplant injections of 1 ml of CAA on days -3, -2,-1, and 0 relative to transplantation resulted in significant prolongation of allograft survival (MST of 10.3 +/- 0.3 days; P less than 0.01). In group 2 (intermediate responder recipients), where Lewis rats were presensitized to WF strain and where cytotoxicity titer was 1:16 to 1:256, the recipients rejected WF hearts in 23.8 +/- 5.8 hr compared with 6.8 +/- 0.8 days in unsensitized control recipients (P less than 0.001). Injection of 1 ml of Lewis anti-WF CAA resulted in prolonged graft survival of 9.7 +/- 3.5 days, while injection of 1 ml of CAA followed by 2 ml of GPC caused hyperacute rejection in 104 +/- 61.7 min. Pretransplant injections of CAA on days -3, -2, -1, and 0 resulted in enhancement, with an MST of 16.3 +/- 1.3 days (P less than 0.001). In group 3 (low responder recipients), ACI presensitized to Lewis developed a cytotoxicity titer of 1:2 to 1:32 and rejected Lewis hearts in 5.3 +/- 0.4 days compared with 10.6 +/- 1.0 days in naive recipients.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Intraaortic balloon pumping for prolonged circulatory support.

Prolonged circulatory support with an intraaortic balloon pump (IABP) is controversial, in part because it has not been performed frequently enough to base treatment policy on adequate data. To help clarify this problem, 733 cases of consecutive patients who were supported by IABP between 1967 and 1982 were analyzed. Twenty-seven patients were supported for 20 days or more (range 20 to 71). Twelve (44%) had prior histories of chronic congestive heart failure. Complications were more frequent in prolonged-support patients than in those assisted for less than 20 days (vascular, 37% vs 15%, p = 0.001; infectious, 67% vs 25%, p = 0.0001; and bleeding, 26% vs 15%, p = 0.04, respectively). The survival rate of prolonged-support patients, however, was 63% (17 of 27), essentially the same as that of the controls (57%, p = 0.5). Of 17 prolonged-pumping patients discharged alive from the hospital, 9 died within 6 months but 8 survived greater than 2 years. Among congestive heart failure patients, none was a long-term survivor. Prolonged IABP support in congestive heart failure patients lacking surgically correctable lesions can extend life while arrangements for definitive therapy are made (transplant, permanent mechanical assistance). Where definitive therapy is unavailable, IABP may provide additional months of life.

Adult

Risks associated with intraaortic balloon pumping in patients with and without diabetes mellitus.

Between 1967 and 1982, intraaortic balloon pumping (IABP) was attempted in 733 patients. Of these, 132 were diabetic: 51 patients were managed with diet alone, 46 patients took oral hypoglycemic agents and 35 patients required insulin. Vascular complications associated with IABP occurred in 34% of the insulin-dependent diabetics, in 18% of other diabetics and in 14% of nondiabetic patients. Infectious complications were 37, 22 and 25%, respectively. Seventy-five diabetic patients (57%) were discharged alive from the hospital after balloon pumping, essentially the same proportion as among nondiabetic patients (58%). It is concluded that although diabetics incur a higher complication rate, IABP is not contraindicated.

Adult

Laryngeal carcinoma in black patients.

The majority of reports on laryngeal carcinoma are from institutions serving a mostly white population. This report is about laryngeal carcinoma in black patients at Harlem Hospital Center. In a retrospective analysis, 113 patients (male-female, 3.5:1) with carcinoma of the larynx were examined. Sixty-seven patients (59%) were between 50 and 60 years of age. There were two patients (2%) with carcinoma in situ, 15 (13%) in Stage I, 40 (35%) in Stage II, 39 (35%) in Stage III, and 15 (13%) in Stage IV. Of the 113 patients, 70 (62%) were treated surgically, Group I; 24 (21%) received radiotherapy only, Group 2; and 19 (17%) refused treatment or died before therapy initiation. For patients in Group 1, the 1-year survival rate was 68% (43 of 63), the 3-year survival rate was 38% (20 of 53), and the 5-year survival rate was 15% (7 of 47). For Group 2, the survival rate was 48% (11 of 23), 30% (7 of 23), and 14% (3 of 22), respectively. In this patient population, laryngeal carcinoma occurred at a younger age than other reported groups, had a higher incidence in females, and had a lower 1-, 3-, and 5-year survival rate.

Adult

Intraaortic balloon pumping 1967 through 1982: analysis of complications in 733 patients.

Between June 1967 and December 1982, 872 attempts at intraaortic balloon pumping (IABP) were made in 733 patients. Nearly 75% of the patients were men; the proportion of women has increased in recent years. The principal indication for IABP support initially was cardiogenic shock, but over the years, preoperative support, weaning from cardiopulmonary bypass and unstable angina have become the primary indications. Complications of IABP were classified and distributed by severity (minor: I [15%] and II [26%]; major: III [3%] and IV [1%]) and type ([vascular [22%], infectious [22%], and bleeding [7%]). Vascular complication rates were higher in women (32 vs 18%; p = 0.0001), in diabetic patients (32 vs 20%, p = 0.003), and in hypertensive patients (27 vs 20%, p = 0.02). These did not vary with the duration of IABP support (range of duration 0 to 76 days). The rate of infectious complications was related to location where IABP was performed (coronary care unit 26%, operating room 12%). The rate of fever and bacteremia increased significantly with duration of IABP support, but the rate of local wound infection did not. In conclusion, most IABP complications are minor, resolve after balloon removal, are related to vascular status of the patient and, with the exception of bacteremia, are independent of IABP duration.

Adolescent