A tumor-associated antigen isolated from human breast adenocarcinoma.
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Biomedical subjects
Publications and source records attributed to H F Fitzpatrick.
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The shortage of cadaver kidneys for transplantation persists in most regions of the United States. Because so many patients have preformed antibodies against prospective donors, identification of appropriate donor-recipient pairs is proving difficult in spite of computerized interregional sharing. To avoid wasting valuable human organs, we have shared 11 kidneys between Italy, the Soviet Union, West Germany and the USA, 10 of which resulted in successful transplants. Such sharing guarantees better utilization of kidneys bilaterally and aids in transplanting cytotoxic patients by increasing the total number of kidneys available.
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Levels of circulating T lymphocytes sensitized to human lung tumor--associated antigens (LTA) were determined by the antigen-stimulated active rosette-forming T cell (AgARFC) assay. These levels were correlated with detection, pathological tumor stage, and postassay survival of patients with lung carcinoma. Peripheral blood lymphocytes (PBLs), from patients found to have lung cancer, were incubated with LTA and produced increased AgARFC compared to PBLs incubated without LTA. Significant levels of LTA-sensitive T cells were found in preoperative PBLs of 80% of patients with Stage I disease (8/10, p < 0.0005), 60% of those with Stage II disease (3/5, p < 0.025), and 46% of those with Stage III primary lung cancer (12/26, p < 0.01), compared with 11% of patients with either benign lung lesions (2/12) or lung metastases (0/6) of nonpulmonary malignant tumors (by chi square analysis). Postoperative survival correlated significantly with preoperative levels of LTA-sensitive T cells by AgARFC assay within Stage I lung cancer (r = 0.807, p < 0.0005). Stage I + II (r = 0.689, p < 0.001), and Stage III (r = 0.657, p < 0.001, not treated with chemotherapy). Preoperative PBL from patients with Stage I + II lung cancer were more frequently sensitized to LTA in the AgARFC assay than from patients with nonpulmonary carcinomas (0/22) or cigarette smokers (1/7) without pulmonary lesions (p < 0.0005). These findings demonstrate a high rate of detection of early, resectable lung carcinomas by preoperative AgARFC assay of PBL sensitized to LTA, and a significant correlation of LTA-sensitive T cell levels with tumor stage and patient survival. The AgARFC assay may be of prognostic as well as diagnostic value in the evaluation of patients with lung carcinoma.
Fifty cadaveric transplants were reviewed to determine whether graft failure was related to the method of preservation. Twenty-eight transplants were preserved by a combination of cold storage and perfusion with cryoprecipitated plasma. Twenty-two transplants were preserved by continuous perfusion with Plasmanate. The perfusate of 14 plasma-perfused kidneys contained 1.0 g of methyl prednisolone, whereas the Plasmanate contained only 100 mg hydrocortisone. Fourteen plasma-perfused kidneys functioned immediately (Group I), and 14 showed delayed function. Seventeen of 22 Plasmanate kidneys (Group III) functioned immediately. Of the Group I kidneys, 13 of 14 functioned for three to eight months, and eight (57%) are still functioning after two years vs. only three of 14 (21%) in Group II. Eleven of the 14 long-term surviving grafts were pretreated with methyl prednisolone. Only nine of the Plasmanate kidneys (39%) lasted more than three months; five (22%) survived more than 12 months. None of the Plasmanate-perfused kidneys that failed to function immediately lasted three months. It is concluded that immediate restoration of renal function after transplantation is a favorable sign for long-term graft survival. The addition of methyl prednisolone to the perfusate may enhance the survival of kidney allografts.
Levels of circulating T lymphocytes sensitized to breast tumour associated antigens (BTA) were correlated with pathological tumour stage or benign histopathology in preoperative studies of 180 patients by the antigen-stimulated active rosette-forming T cell (AgARFC) assay. Incubation of lymphocytes with allogeneic BTA extracts produced increased AgARFC compared with incubation without BTA. Significant levels of BTA-sensitive T cells were found in 78 per cent of breast cancer patients compared with 23 per cent of patients with benign disease (P less than 0.0005, by X2). Over 93 per cent of stage I cancer patients responded to BTA, compared with 69 per cent of stage II patients (P less than 0.025) and 59 per cent of stages III-IV patients (P less than 0.005). Twenty-nine per cent of 42 patients with fibrocystic disease were positive to BTA in contrast to 8 per cent of 25 patients with fibroadenomas. This was a 3.6-fold higher incidence of BTA-sensitive T cells associated with fibrocystic disease than with fibroadenomas, which was in agreement with the increased breast cancer risk rate associated with fibrocystic disease. These findings suggest that the AgARFC assay may detect early malignant change in fibrocystic disease. The AgARFC assay was found to reliably detect early invasive carcinoma.
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A case is presented in which successful repair of a superior vena cava gunshot wound was followed by death due to peritonitis. A mild case of endometritis progressed to generalized peritonitis after the patient's immune defenses were compromised by massive transfusion of banked blood. Clinicopathologic correlation is provided.
The antigen-stimulated active rosette-forming T-cell (AgARFC) assay was adapted for the preoperative study of 21 consecutive kidney transplants (17 cadaver donors and four living related donors; five retransplants). Recipient peripheral blood lymphocytes were incubated for 15 minutes with donor histocompatibility antigens preparaed by sonication of donor peripheral blood or splenic lymphocytes. Recipient presensitization to donor antigens was expressed as the difference between active rosette formation in the presence (%AgARFC) and in the absence (%ARFC) of donor antigens. This antigen-induced difference is rosette formation (%AgARFC - %ARFC) for all patients ranged from - 7.0% to 24.2%. Of those patients with pretransplant sensitization greater than 6.3% (group I: mean, 13.2 +/- 3.0; n = 7), 71% had severe acute rejection requiring dialysis within the first 2 weeks of transplantation. In contrast, none of the patients with pretransplant values below 6.3% (group II: mean, -0.8 +/- 1.0; n = 14) had rejection requiring dialysis within the first 2 weeks. Group I patients had 43% graft survival at 1 month and 14% survival at 2 months, whereas group II had 86% graft survival at 1 month and 71% at 2 months. The AgARFC assay provided a rapid means of measuring recipient T-cell presensitization to donor alloantigens, which was correlated with the accelerated rejection of renal allografts.
The kinetics of circulating antigen sensitive T-cells were studied in Hartley strain guinea pig recipients of Shorthair strain first- and second-set skin allografts. Peripheral blood donor antigen sensitive T-cells (AST) were quantitated by the antigen-stimulated active rosette-forming T-cell (AgARFC) assay by incubating lymphocytes in the presence and in the absence of soluble transplantation antigens. The number of circulating AST/cu mm rose to maximum levels (1,165 +/- 272 SEM) by day 3 and fell sharply before first-set graft rejection (453 +/- 117 SEM) on day 7 after transplant. In contrast, there were no detectable antigen-sensitive cells when lymphocytes from both recipient and control guinea pigs were stimulated with soluble recipient-strain antigen. Significant numbers (212 +/- 159 SEM) of circulating AST remained through day 68 after first-set grafts. Following placement of sencon-set allografts on day 73, the AST disappeared from the circulation for 2.5 days and then rose to peak levels (825 +/- 167 SEM) in circulating AST (579 +/- 327 SEM) preceded rejection of second-set skin allografts. When control guinea pigs were immunized with a single dose of soluble donor antigens, a progressive increase in circulating AST (579 +/- 327 SEM) was found through day 17 after sensitization without the fall associated with graft rejection. The antigen-stimulated, rosette-forming T-cell assay may prove useful in the detection of cellular presensitization and in the monitoring of graft rejection in clinical transplantation.
Forty-eight esophagastric resections performed for cancer of the esophagus and cardia resulted in a five-year survival rate of four per cent. An operative mortality rate of 23%, comparable to that reported by others, diminishes the value of esophagogastrectomy even for palliation. Nutritional depletion, commonly found in these patients, contributes significantly to the unacceptably high mortality. A review of the recent literature indicates that the routine use of preoperative hyperalimentation and prophylactic antibiotics can significantly reduce morbidity in these high-risk patients and thereby result in better palliation.
This is the first report that analyzes the time required for a general surgeon to master the technique of anastomosis of arteries with diameters of 1.25 and 1.5 mm. Probes of 0.25 mm gradation were used to calibrate the lumens of the arteries and the anastomoses. The Zeiss microscope was used at 25 magnifications to repair a transverse division of the abdominal aorta of a 120 gram rat. Fifteen hours were required for the surgeon (S.H.) to become accustomed to the use of the equipment. Then a series of 40 rats were operated upon and kept alive from 1 to 6 weeks. Patency rate was 100% (40 of 40). No anastomosis was less than 1.25 mm in diameter. After the initial practice period of 15 hours, quality of anastomosis was unchanged, but time required to perform it diminished from 45 minutes to 15 minutes during the course of 40 procedures that occupied 35 laboratory hours.
A group of 22 patients with bleeding esophageal varices were treated by creating mesocaval "H" shunts using autogenous veins as the "H" graft. The right external iliac vein was selected as the graft because of its appropriate size in diameter and length, its strength and elasticity. Details in operative technique are outlined. The age of our patients ranged from 24 to 75 years (average age 49), 19 patients had preoperative endoscopy, 10 patients received intraarterial pitressin drip to control hemorrhage, and surgery was done within 10 days of admission in 18 patients. There were two postoperative deaths (both patients Childs Class C), and very few postoperative problems. Right leg edema was a temporary and minimal problem. Encephalopathy was a major problem in only three patients, all of whom had poor hepatic reserve preoperatively. There has been no recurrent variceal bleeding in any of these patients. Our previous experimental data in dogs indicated that the long term patency of these shunts could be assured.
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1. Glucocorticoids have been empirically employed during perfusion preservation of transplantable organs. 2. Use of corticosteroids in organ preservation is based on their pharmocologic binding of released lysosomal enzymes, as membrane stabilizers, peripheral vasodilators, and inhibitors of the inflammatory response. 3. The incidence post-transplant of ATN in cadaveric kidney preservation by pulsa-tile perfusion has been reduced from 57% to 18% when the donor was protected with large doses of M-P. 4. There is sufficient clinical and laboratory evidence to substantiate the use of large doses of M-P given to the prospective donor as a protective agent against ischemic injury in organ recovery.
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