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F Sanfilippo

Publications and source records attributed to F Sanfilippo.

At least 145 records · Page 8Linked to original sources

Humoral immunity to heterotopic corneal allografts in the rat.

Despite indications that humoral immune responses may be involved in corneal allograft rejection, few definitive reports of such responses exist, and the antigens responsible for evoking and targeting these responses remain unknown. We report the development of donor-specific humoral immunity in PVG (RT1c) rats given fully allogeneic ACI (RT1a) corneal grafts heterotopically. PVG anti-ACI cornea serum lysed ACI, but not PVG, target cells in complement-dependent cytotoxic assays. Target cells from PVG.1A or PVG.R1 congenic rats, which respectively share the entire rat major histocompatibility complex (MHC) region (i.e., RT1) or only class I MHC antigens (RT1.A region) with ACI (on PVG backgrounds) were also lysed by this serum. Lysis of PVG.1A targets was significantly more extensive than lysis of PVG.R1 cells, indicating that both RT1.A and non-RT1.A antigens act as targets for cell lysis. Levels of PVG.1A and ACI target lysis were equivalent, suggesting that minor transplantation antigens were not significantly involved in this humoral response.

Animals↗

Cellular immunity to heterotopic corneal allografts in the rat.

Although the immune nature of corneal allograft rejection has been recognized for over thirty years, the specific mechanisms involved in such reactions remain obscure. We investigated the cellular immune responses of PVG (RT1c) rats that were grafted with fully allogeneic ACI (RT1a) skin, ACI cornea, or PVG cornea to the chest wall or given sham grafts. Cell-mediated lymphocytotoxicity (CML) was tested at 10 days posttransplant by placing recipient spleen cells in culture with irradiated ACI stimulator cells, and six days later measuring specific lysis of 51Cr-labeled target lymphoblasts at several effector-to-target ratios. Effector cells from animals receiving allogeneic skin or cornea grafts lysed targets from the donor (ACI) strain at levels significantly (P less than 0.01) above those obtained using effectors from control (sham grafted or syngeneic corneal graft recipient) animals. Significant lysis was also seen using target cells from PVG.1A (RT1a) or PVG.R1 (RT1r1) congenic rats, which differ from recipients only at the RT1 complex and the RT1.A (class I antigen) region, respectively. Stimulator cells from PVG.1A and PVG.R1 animals also permitted detection of specific responses in secondary CML, but syngeneic PVG stimulators did not, indicating that in vitro restimulation of effector cells can be met by using stimulator cells bearing only allogeneic class I major histocompatibility complex (MHC) antigens. These results indicate that corneal allografts evoke specific cellular immune responses in the rat, and that class I MHC antigens act as effective targets for these responses.

Animals↗

Use of SEOPF regional crossmatch trays to share kidneys for sensitized patients. Local experience of three centers.

Regional organ procurement (ROP) crossmatch trays are used by members of the South-Eastern Organ Procurement Foundation (SEOPF) to facilitate sharing of cadaver kidneys for highly sensitized patients. ROP trays carry a single representative serum sample from over 900 patients with panel reactive antibody (PRA) levels of greater than or equal to 60%. Trays are centrally prepared periodically and distributed to member laboratories where they are used for preliminary crossmatching against locally obtained donors. Crossmatching results are used in conjunction with the SEOPF computer match program for sharing of kidneys. Proficiency testing studies by the 40-member laboratories show a greater than 90% concordance rate on results with these highly and broadly reactive sera. Data were available from 3 centers on 74 kidneys shared between SEOPF-member institutions on the basis of a remote, preliminary, negative ROP tray crossmatch. Of these, 44 (59%) crossmatched negative locally with the same and other sera, and were thus considered acceptable to be transplanted to the intended highly sensitized patients. Sixteen (22%) donors had a positive crossmatch locally, but with sera other than that present on the ROP tray used for screening. In 14 cases (19%) the same serum as on the ROP tray gave a positive crossmatch. The majority of ROP tray inconsistencies appeared to be due to use of more sensitive crossmatching techniques at the recipient center. Of the 27 patients transplanted at these 3 centers with kidneys received on the basis of ROP tray results, none experienced hyperacute or early irreversible rejection and actual graft survival at 6-48 months is 74%. These studies indicate that regional sharing of patient sera by the existing network of histocompatibility testing laboratories is an effective and reliable mechanism to identify crossmatch-negative donors for highly sensitized patients.

ABO Blood-Group System↗

Renal allograft cell infiltrates associated with irreversible rejection.

All 74 renal transplant biopsies performed between 11/78 and 8/84 at Duke University and Durham VA Medical Centers having cellular infiltrates that could be phenotyped by immunoperoxidase labeling were examined to identify histologic and immunopathologic features which correlated with rejection. Monoclonal antibodies identifying hematopoietic cells, T cells, T helper cells, T cytotoxic-suppressor cells, macrophages, and B cells were used, and each phenotype population was graded separately based on pattern of infiltration: cortical-diffuse (CD), perivascular (PV), and cortical-aggregate (CA). Histologic and immunofluorescent studies were used to evaluate acute (humoral) and cellular types of vascular and interstitial inflammation. By univariate analysis, patients having irreversible rejection within 10 weeks postbiopsy (n = 23) had significantly higher grades of both acute vascular (humoral) inflammation and TC-S cell infiltrates in a CD pattern as compared with those who had good graft function. Multivariate (Cox regression) analysis was also performed considering biopsy changes, therapy before and after biopsy, and intervals between transplant, rejection onset, and biopsy--as well as other factors potentially affecting the biopsy or graft outcome. Of nine cell phenotype-pattern combinations, only TC-S infiltrates in a CD pattern were associated with a significant (P less than 0.03) relative risk (RR) of subsequent failure from rejection (RR = 8.2). When those cases with significant acute (humoral) inflammation (n = 10) were excluded, the relative risk of TC-S-CD infiltrates increased to 46.4 (P less than 0.04). These findings indicate that the location, as well as the number and type of cell infiltrates are critical in evaluating cellular forms of rejection, and that the extent of diffuse, cortical TC-S infiltration on biopsy provides the greatest predictor of subsequent irreversible graft failure.

Acute Disease↗

The expression of HLA antigens by cells in the human cornea.

Although antigens of the human major histocompatibility complex, HLA, appear to be involved in the rejection of corneal allografts, the expression of these antigens by cells of the human cornea remains controversial. Using sensitive immunoperoxidase techniques, we readily demonstrated class I HLA antigens on corneal epithelial, stromal, and endothelial cells, regardless of donor age. Moreover, the expression of class I antigens by epithelium increased markedly from the central to the peripheral cornea. Finally, class II HLA antigens were found on cells scattered throughout both central and peripheral epithelium as well as the stroma. A cornea obtained from a donor of known HLA type expressed all expected and no unexpected polymorphic HLA determinants in the cornea, in a pattern similar to that seen for monomorphic HLA determinants.

Adult↗

Benefits of HLA-A and HLA-B matching on graft and patient outcome after cadaveric-donor renal transplantation.

Data collected prospectively on 3811 renal transplantations performed between June 1977 and July 1982 by the 42 member institutions of the South-Eastern Organ Procurement Foundation were analyzed to determine the influence of donor-recipient HLA-A and HLA-B matching on patient and graft outcome. Well-matched recipients were more likely to have received kidneys from outside their own centers, were more highly presensitized, included fewer blacks, and were more likely to have lost an earlier graft. Multivariate Cox regression analysis that included these and six other potential confounding variables revealed a significant association (P less than 0.001) between good HLA-A and B matching and increased graft survival. The difference in mean (+/- S.E.) actuarial graft survival between recipients worst matched and best matched for HLA-A and B antigens increased with time: 55 +/- 2 per cent as compared with 64 +/- 4 per cent at six months and 18 +/- 4 per cent as compared with 44 +/- 7 per cent at four years. Poor HLA matching of donor with recipient provided the greatest relative risk (2.16) of irreversible graft rejection of all the variables examined. Among patients with functioning grafts, well-matched recipients had lower serum creatinine levels and received significantly smaller amounts of glucocorticoids. Our findings indicate that good HLA-A and B matching is highly dependent on a system for sharing organs among institutions, and results in decreased graft rejection, better long-term graft function, and less need for post-transplantation immunosuppression.

Adult↗

The association of pretransplant native nephrectomy with decreased renal allograft rejection.

Analysis of 2808 first and 823 second or subsequent cadaveric renal allograft recipients transplanted between June 1977 and July 1982 as part of the Southeastern Organ Procurement Foundation (SEOPF) Prospective Study was performed to determine the influence of pretransplant bilateral native nephrectomy (BNN) on graft and patient outcome. A highly significant increase in overall graft survival was associated with BNN in first transplant recipients (P less than 0.003) but not in regrafted patients. However, no increased graft survival was seen in patients receiving BNN at the time of the transplant operation. Interestingly, the improvement in graft survival associated with BNN appeared to be the result of a significant decrease in the incidence of graft loss caused by rejection--and especially accelerated acute rejection (P less than 0.007). Comparing actuarial graft survival for first graft recipients that had BNN prior to transplantation (n = 434) with those who had no nephrectomy (n = 2240) showed differences of 62% +/- 3 vs. 52% +/- 1 and 46% +/- 3 vs. 38% +/- 2 at one and three years, respectively. Analysis of first graft survival stratified for other factors known to influence outcome showed that the beneficial influence of BNN was independent of transfusion status or the number of transfusions given, use of antilymphocyte serum, pretransplant splenectomy, HLA match, or time on dialysis. The most striking increase in graft survival associated with BNN was seen in patients with evidence of presensitization as manifested by a positive panel reactive antibody (PRA) and in patients having delayed function (ATN) posttransplantation. The beneficial association of BNN was also found to be independent of the primary cause of renal failure or the specific indication leading to nephrectomy. These results suggest that patients receiving native bilateral nephrectomy prior to transplantation have a reduced incidence of graft loss from rejection by some as yet unexplained mechanism.

Adult↗

The timing of pretransplant transfusions and renal allograft survival.

Analysis of over 3000 cadaveric renal allograft recipients transplanted between June 1977 and June 1982 as part of the South-Eastern Organ Procurement Foundation Prospective Study was performed to determine the influence of timing of blood transfusions (BT) on patient and graft survival. Four mutually exclusive BT groups were identified for 2480 first-transplant and 655 regrafted patients studied: group 1 (n = 348, 29, respectively) received no BT; group 2 (n = 256, 29, respectively) received perioperative BT only (i.e., at the time of, or within 10 days of transplant); group 3 (n = 972, 287, respectively) received preoperative BT only (i.e., 10 or more days pretransplant); group 4 (n = 904, 310, respectively) received both preoperative and perioperative BT. For first graft recipients, actuarial graft survival for group 2 was significantly greater (P less than 0.035) than group 1 (49% vs. 41% at one year; 35% vs. 25% at 4 years), but to a lesser degree than groups 3 or 4, which were equivalent (58% at one year and 38% at 4 years). For regrafted patients, actuarial graft survival was again significantly greater (P less than 0.03) for group 2 patients, as compared with group 1 (59% vs. 29% at one year), and group 3 and 4 patients were not significantly different from each other (45% and 48% at one year, respectively) or from group 2. Interestingly, for regrafted patients who were presensitized at the time of transplant, those in group 4 (n = 94) had significantly better graft survival than group 3 (n = 111) at all time points examined (54% vs. 47% at one year, 46% vs. 22% at 3 years). In all comparisons, increases in graft survival were associated with decreased graft loss resulting from rejection, and no significant differences in patient survival were seen between any of these groups. These findings indicate that: (1) perioperative transfusions alone may have benefit in decreasing allograft rejection; (2) perioperative transfusions provide no apparent risk for patients who have already received pretransplant transfusions; and, (3) sensitized regrafted patients who receive pretransplant transfusions may gain an additional benefit from perioperative transfusions.

Adult↗

The influence of pretransplant transfusions, using different blood products, on patient sensitization and renal allograft survival.

An analysis of data collected during the South Eastern Organ Procurement Foundation (SEOPF) Prospective Study from 1977-1982 was performed to identify the relative effects of different blood products on patient sensitization and graft survival in cadaveric donor renal transplant recipients. More than 2700 primary and 800 regrafted patients from 40 transplant centers were included in this study. A significant increase in actuarial graft survival was seen in primary recipients who had pretransplant transfusions with only frozen blood (P less than 0.003), washed blood (P less than 0.0005), packed blood (P less than 0.0001), or any combination of blood products (P less than 0.002) as compared with those who received no transfusions. No blood product was found to provide a significantly greater increase in graft survival than any other blood product. Likewise, regrafted patients had significant and equivalent increases in graft survival associated with each type of blood product examined. The increased graft survival associated with each blood product was the result of decreased graft rejection, and not apparently related to other differences among patients receiving different types of blood. Furthermore, the type of blood used in pretransplant transfusions did not significantly influence the degree of patient sensitization for first-graft recipients, although regrafted recipients who received packed blood or a combination of blood products showed a slightly greater degree of sensitization than those who received only frozen or washed blood. First-graft recipients given packed or mixed blood had a small, statistically insignificant increase of hepatitis B virus (HBV) antigenemia, compared with those receiving frozen, washed, or no blood. Regrafted patients given any type of transfusion had a 3-4-fold increased incidence of HBV antigenemia as compared with nontransfused patients, but this difference also was statistically not significant. These findings suggest that the benefits of increased graft survival and the risks of sensitization or HBV infection associated with pretransplant transfusions are not significantly affected by the type of blood used.

Adult↗

Autoantibodies to nuclear, cytoplasmic, and cytoskeletal antigens in renal allograft rejection.

Autoantibodies (AA) detected by indirect immunofluorescence on HEp-2 cells and lymphocyte panel reactive antibodies (PRA) were measured pretransplant and within 2 weeks after transplant nephrectomy in a group of 21 consecutive renal allograft recipients with irreversible graft rejection. No patient had clinical evidence or history of autoimmune disease. Although 43% of patients had AA and 29% had a positive PRA pretransplant, 90% had AA and 100% had a positive PRA post-transplant nephrectomy (P less than 0.0032, 0.00001, respectively). Analysis of AA detected following graft failure revealed that all were of IgG class, and more than half the patients had multiple patterns including speckled nuclear, cytoplasmic, perinuclear, mitotic spindle apparatus, and smooth muscle staining. Of 11 patients retested up to one year later, all showed a persistence of previously detected AA in both pattern and titer, although none of the patients had any other signs or symptoms of autoimmune disease. A control group of 21 transplant recipients with functioning grafts was similarly tested revealing that 35% had AA and 29% had positive PRA pretransplant, but only 14% had AA and 14% positive PRA posttransplant. The presence of post-transplant AA or PRA was not associated with antecedent delayed graft function (ATN), rejection episodes, treatment with antithymocyte globulin, the interval posttransplantation, or subsequent graft outcome. However, pretransplant AA and PRA in both groups were associated with prior graft loss, but not with other variables examined. These findings indicate that serologically detectable sensitization to lymphocyte (HLA) antigens and the presence of persistent, multiple autoantibodies to nuclear, cytoplasmic, and cytoskeletal antigens is a frequent occurrence following graft loss. Furthermore, the development of AA following graft rejection appears to be unrelated to the prior presence or subsequent development of clinical autoimmune disease.

Adolescent↗

Cadaver renal transplantation ignoring peak-reactive sera in patients with markedly decreasing pretransplant sensitization.

A review of more than 3000 cadaver donor renal allograft recipients transplanted between June 1977 and July 1982 as part of the South-Eastern Organ Procurement Foundation (SEOPF) Prospective Study was performed to identify patients who received a transplant following a significant decrease in pretransplant sensitization as measured by the percentage of panel-reactive antibody (PRA). Such patients were identified as having had a most reactive (historical peak sera) PRA level at least 40 percentage points higher than their last sample tested prior to transplant (current sera). Additional data were obtained on 157 of these patients, who also had no history of pretransplant immunosuppression and had a negative pretransplant crossmatch with current sera. Data included the dates of pretransplant sera samples, the specific techniques used for each serum sample that was crossmatched or screened for PRA, and the serological results. The population studied included 17 of 87 first-transplant recipients and 17 of 70 regrafted recipients whose pretransplant crossmatches with peak sera were positive or not done. These subgroups showed no decrease in graft or patient survival compared with cohorts (70/87 first-transplant recipients and 53/70 regrafted recipients) for whom peak sera crossmatching was performed with negative results. Additional stratification for the techniques used in crossmatching and screening, as well as the interval between peak and current PRA levels, showed no significant associations with eventual graft or patient outcome. These results suggest that crossmatch testing using peak sera may not be important in predicting eventual graft or patient outcome for patients with a marked decrease in PRA prior to transplantation and a negative crossmatch with current sera.

Adult↗

Influence of changes in pretransplant sensitization on patient and graft survival in cadaver renal transplantation.

Analysis of 2778 primary and 606 regrafted cadaveric donor renal allograft recipients transplanted between June 1977 and July 1982 as part of the South-Eastern Organ Procurement Foundation (SEOPF) Prospective Study was performed to determine the influence of changes in presensitization on graft and patient outcome. Four mutually exclusive groups of patients were identified based on the relative difference in the percentage of panel-reactive antibody (PRA) from highest ever (peak) to most recent (current) pretransplant levels as follows: group 1 (unsensitized): peak = current PRA = 0; group 2 (rising or stable PRA): (peak = current PRA) greater than 0; group 3 (small decrease): (peak - current PRA) = 1-40%;) and group 4 (large decrease): (peak - current PRA) greater than 40%. First-transplant recipients in group 4 had significantly higher mortality when compared with groups 1-3 (P less than 0.002). This decrease in patient survival was evident at 6 months (81% +/- 4 vs 91% +/- 1) and persisted to three years (68% +/- 8 vs 78% +/- 2), and it was associated with a significant (P less than 0.037) increase in death from infectious causes. This finding was even more striking when only transfused recipients were considered: at three years the difference in patient survival was 63% +/- 11 vs. 77% +/- 2. In addition, transfused patients with a decrease in pretransplant PRA of greater than 40% had significantly lower overall graft survival (P less than 0.02) and a higher incidence of irreversible graft rejection (50% +/- 8 vs 33% +/- 1 at two years). For regrafted recipients, there were no differences in patient survival among groups, but those in group 4 had significantly lower graft survival (P less than 0.0033) than groups 1-3. These findings suggest that a substantial decrease in PRA prior to transplant does not necessarily indicate a decrease in potential donor alloreactivity, and in first-graft recipients it may reflect an increased susceptibility to life-threatening infections following transplantation.

Adult↗

The effect of HLA-A, -B matching on cadaver renal allograft rejection comparing public and private specificities.

Data collected prospectively on 3811 cadaver renal transplants performed between June 1977 and July 1982 by the 42 member institutions of the South-Eastern Organ Procurement Foundation (SEOPF) were analyzed to determine whether donor-recipient compatibility based on public rather than private HLA-A,-B specificities influenced the beneficial effect of HLA matching on outcome. HLA compatibility was calculated considering match and mismatch based on common private or various public (crossreactive group, [CREG]) specificities. Donor-recipient compatibility using certain CREG assignments provided an equivalent means of stratifying graft outcome by the degree of HLA-A,-B match or mismatch, and other CREGs assignments did not. Multivariate Cox regression analysis of donor-recipient compatibility based on certain public antigens showed as high an association (P less than 10(-5) between good matching and decreased graft rejection as did matching for private antigens alone. Patient stratification by HLA match provided a stronger association with graft outcome than by HLA mismatch, irrespective of whether private or public antigens were considered. The likelihood of finding a better match was significantly increased using CREG assignments, and patients with at least one matched private antigen had equivalent or better graft survival when additional public antigens were matched. These findings indicate that with conventional immunosuppressive therapy: (1) matching of private or public HLA-A,-B antigens plays a highly significant role in decreasing renal allograft rejection; (2) matching based on certain public antigens can provide the same or a better association with outcome as private antigens; and (3) the association (crossreactivity) of various HLA specificities can be defined on a functional basis in terms of graft survival.

Cadaver↗

Rapid serologic diagnosis of serum sickness from antithymocyte globulin therapy using enzyme immunoassay.

Although the use of antithymocyte globulin/antilymphocyte serum (ATG/ALS) has been shown to be beneficial in treating renal allograft rejection, the incidence and nature of serum sickness reactions following such treatment have received limited attention. In the setting of rejection or infection, the diagnosis of serum sickness is often difficult on clinical grounds, and biopsy may be an undesirable means of obtaining documentation. A sensitive enzyme-linked immunosorbent assay (ELISA) was developed to detect antibodies against ATGAM (Upjohn) and was utilized in 35 patients treated for rejection with ATGAM following clinical unresponsiveness to bolus methylprednisolone therapy. Serum sickness was diagnosed clinically in 7 of these patients (20%) during or immediately following ATGAM therapy. Significant titers of anti-ATGAM antibody were found in these 7 cases, as well as 5 additional cases (14%). Upon retrospective review, the diagnosis of serum sickness was also made in each of these 5 additional cases based upon the immunopathologic detection of horse immunoglobulin deposits in vessels of tissue (lung or kidney) examined. In 2 other cases where serologic testing was negative, there was some clinical suggestion of serum sickness that could not be documented pathologically. ELISA for anti-ATGAM antibodies was negative in testing 46 control patients and pooled normal sera. In one case, retrospective testing of pre-ATGAM therapy serum samples showed significant antihorse antibodies. Despite a negative skin test prior to administration, this patient developed symptoms of serum sickness 15 days after the onset of ATGAM therapy. Extremely high titers of antibody were detected 5 days earlier (10 days posttherapy), and the presence of horse immunoglobulin immune complexes in the kidney was documented following graft loss that occurred within 4 weeks. These findings indicate (1) serologic testing for anti-ATGAM antibodies using a sensitive ELISA method provides a quick, inexpensive, noninvasive means for the presumptive diagnosis of serum sickness in complicated clinical situations, and (2) screening of patient sera prior to administration of ATGAM may be useful in avoiding potential serum sickness reactions.

Antibodies, Anti-Idiotypic↗

The detrimental effects of delayed graft function in cadaver donor renal transplantation.

Data collected prospectively on over 3800 cadaveric renal transplants performed between June 1977 and July 1982 by the 41 member institutions of the South-Eastern Organ Procurement Foundation were analyzed to determine the influence of delayed graft function (DGF) on patient and graft outcome. Approximately 35% of first graft recipients and 47% of regrafted patients were found to have DGF, as determined by the necessity for dialysis at one week posttransplant. First-graft recipients with DGF tended to include more black recipients, patients with higher peak levels of panel reactive antibody (PRA), less use of antilymphocyte serum (ALS) posttransplant, slightly longer organ preservation times and the more frequent use of organs by ice alone. Multivariate (Cox) regression analysis considering DGF simultaneously with ten other potentially confounding variables showed a highly significant association between DGF and overall graft loss from all causes (P less than 10(-5], irreversible graft rejection (P less than 0.001) as well as patient death (P = 0.012). The differences in graft survival between first graft recipients with DGF (n = 961) versus those without DGF (n = 1769) at one and four years posttransplant were 46% +/- 2 vs. 60% +/- 1 and 28% +/- 3 vs. 40% +/- 2, respectively. The detrimental effect of DGF was highly significant irrespective of the source of donor organs or the type of preservation used. For first transplant recipients who recovered good graft function by one month following DGF (n = 564), there was a significant decrease in eventual graft survival, as compared with patients who had graft function at one month but no prior history of DGF (n = 1407; P = 0.008). However, patients with history of DGF who had good graft function at six months (n = 361) showed no significant difference in longer-term graft survival when compared with similar patients with good graft function at six months but no history of DGF (n = 912). Interestingly, first transplant recipients with DGF were found to have significantly better graft survival if they had received bilateral native nephrectomy at least one month prior to transplantation. These results indicate that delayed graft function following cadaver donor renal transplantation provides a significant risk for eventual graft and patients survival that is principally manifested during the first six months posttransplant. In addition, patients who recover graft function following DGF appear to also remain at higher risk for early graft loss, while pretransplant bilateral native nephrectomy may afford some protection against the detrimental effects of DGF.

Female↗

Relationships among the histologic pattern, intensity, and phenotypes of T cells infiltrating renal allografts.

The evaluation of renal allograft rejection by routine histologic evaluation of transplant biopsy is often a diagnostic problem. Advances in monoclonal antibody and immunohistochemical technology have led to their application in characterizing the phenotype of peripheral blood lymphocytes in transplant recipients, as well as the infiltrating lymphocytes in renal biopsy specimens (both tissue and aspiration cytology samples). Recent reports suggest that the relative number of infiltrating T cells and the T cell phenotypic subset ratio may have some association with graft survival. However, most allograft biopsy studies have not examined the relationship of the intensity and phenotype of T cells to the histologic pattern of infiltration, while fine-needle aspiration cytology (FNAC) and peripheral blood analysis do not allow for this assessment. To examine the association of histologic pattern with the intensity and phenotype of T cell infiltrates, immunoperoxidase labeling of cells using monoclonal antibodies was evaluated in 66 renal allograft biopsies performed because of clinical suspicion of rejection. Our findings indicate that the ratio of T helper-inducer (Leu 3) cells to T suppressor-cytotoxic (Leu 2) cells is significantly lower in the pattern of diffuse renal cortex infiltration (cortical diffuse [CD] pattern) when compared with other histologic patterns (cortical aggregate or perivascular), regardless of the overall intensity of the T cell infiltrate. A significant difference in T cell phenotypes was also found among different histologic patterns as expressed by Leu 3/Leu 2 ratios and by the number of Leu 2 cells. An increase in the overall intensity of T cell infiltrate was not associated with significant changes in T cell phenotype seen in any pattern, but an increase in the intensity of the cortical diffuse T cell infiltrate was associated with a significant decrease in the Leu 3/Leu 2 ratio (P less than 0.04), which was due to an increase in the population of Leu 2 cells (P less than 0.002). Interestingly, increases in the intensity of either cortical aggregate or perivascular T cell infiltrates were associated with significant increases in both Leu 3 and Leu 2 cells, as well as a tendency towards higher Leu 3/Leu 2 ratios. These findings indicate that evaluation of T cell infiltrates by phenotype in renal allografts is dependent upon the pattern as well as the intensity of infiltrate.

Adolescent↗

The predictive value of 2,-4, dinitrochlorobenzene skin testing in patients with bilharzial bladder cancer.

A group of 40 patients with bilharzial bladder cancer underwent quantitative skin testing with dinitrochlorobenzene and purified protein derivative of tuberculin before radical surgery. Correlations were made between various clinical parameters, patient outcome, skin test results and pathologic changes in the resected bladder and draining lymph nodes. Striking associations between dinitrochlorobenzene responses and tumor stage, tumor recurrence and several specific parameters of lymph node stimulation were found, while no correlations were made with the pathologic grade, size or type of tumor, degree of schistosomal infestation or tumor bed inflammation. Purified protein derivative responses showed no correlation with any parameter examined. Patient outcome also showed a good correlation with tumor stage and draining lymph node reaction. These findings indicate that dinitrochlorobenzene skin testing as a presumptive test of cell-mediated immunity may represent a good predictor of clinical outcome in patients with bilharzial bladder cancer, and correlates well with draining lymph node stimulation.

Dinitrochlorobenzene↗