Advantages of donor-specific blood transfusion in the rat via the portal vein for renal transplantation.

It is well known that blood transfusion can promote immune unresponsiveness to a renal allograft in both animals and humans. The present study examined the differences between either portal venous (PV) or intravenous (IV) donor-specific transfusion (DST) alone on the survival of rat renal allografts without other immunosuppression. Seven days before LEW (RT1(1)) renal transplantation, recipient WKA rats (RT1u) were inoculated with graded doses (1.0 to 0.0001 mL) of LEW whole blood through either the portal vein or the tail vein. A dose of 0.001 mL whole blood PV resulted in significantly greater prolongation of renal allograft survival than occurred with IV preimmunization (38.5 +/- 10.6 days v 12.5 +/- 2.7 days). Although recipient survival was not significantly different for the two routes for a lower dose (0.1 mL) of whole blood preimmunization 7 days before transplantation, azotemia and rejection were prevented when the PV route, but not the IV route, was used. However, when 0.1 mL of whole blood was administered 5 days before transplantation, survival was prolonged only in animals preimmunized by the PV route (54.7 +/- 14.0 days v 14.3 +/- 4.0 days). In the stronger reciprocal combination of WKA to LEW, there was an advantage of PV with 0.1 mL whole blood, but not with 1 mL. These results indicate that the beneficial effects of DST on renal allograft survival can be obtained when a smaller volume of blood is given via the PV rather than the IV route and a shorter interval elapses between preimmunization and transplantation.

Melanocyte chemotactic factor produced by skin metastases of a breast carcinoma.

A 65-year-old woman underwent right modified radical mastectomy for a malignant lesion which had developed just below the right nipple. Two years after the operation, skin lesions composed of dark brown to black, pigmented, papular lesions developed in the precordia. A biopsy revealed this to be a cutaneous metastasis of the previous breast carcinoma. However numerous pigment blockade melanocytes were also found in the tumor nests, located in and/or beneath the epidermis. Although a black-colored breast carcinoma has been reported, the presence of pigment blockade melanocytes was not determined. Culture of the tumor nest recovered a population of melanocytes as well as the carcinoma cells. Boyden chamber analysis revealed the presence of a chemotactic factor for melanocytes in the culture medium. This seems to be the first documentation of melanocyte incorporation in breast carcinoma tissue.

Effectiveness of a long intestinal tube in a one-stage operation for obstructing carcinoma of the left colon.

Five consecutive patients with obstructing carcinoma of the left colon were successfully managed by long intestinal tube decompression. The tube was introduced pernasal into the duodenum on the day of admission. The tube advanced spontaneously into the ascending colon with marked abdominal decompression within several days. Thereafter, preoperative colonic irrigation through this tube was performed. In three of five patients, segmental colectomy was accomplished without intraoperative cleansing. In two patients, fecal residue was removed by intraoperative colonic irrigation using the long tube. Proximal colostomy was avoided in all patients. This treatment protocol enabled: 1) both preoperative and intraoperative colonic irrigation and cleansing; 2) elective surgery instead of emergency; 3) safe one-stage operation with secure colonic anastomosis; and 4) segmental resection rather than subtotal resection of the colon.

Local chemotherapy for rectal polyposis: intraluminal administration of 5-fluorouracil for postoperative control of adenomas in the retained rectum in familial polyposis.

We administered the anticancer drug 5-fluorouracil locally to treat rectal adenomas in four patients with familial adenomatous polyposis who had undergone total colectomy and ileorectal anastomosis. The drug was administered either in suppository form or in high concentration as a rectal enema. One patient was treated successfully with 5-fluorouracil suppositories without any side effects, but the suppository regimen had to be stopped in three other patients because of severe rectal urgency. However, one of these patients was treated effectively with rectal administration of a high-dose 5-fluorouracil solution. Adenomas near the anastomotic site or dentate line were difficult to treat. Although severe urgency was seen in most patients, we think that the intraluminal administration of anticancer agents may prove effective in treating polyposis of the rectum retained after colectomy in familial polyposis. It deserves further study.

An aseptic method to loosen tight, relaxing sutures.

Relaxing sutures are placed to prevent wound dehiscence. These sutures sometimes become too tight, and local pain or edema ensues. An aseptic loosening of the relaxing sutures was devised and healing of the wound was accelerated.

A case of anomalous origin of the right coronary artery from the pulmonary trunk: imaging of abnormal flow by Doppler color flow mapping.

An asymptomatic 48-year-old woman was admitted to our hospital for evaluation of a precordial continuous murmur. The chest radiograph showed a normal cardiac silhouette. The resting electrocardiogram showed incomplete right bundle branch block. A multistage, graded treadmill exercise test did not affect the ST-T segment. A thallium-201 myocardial perfusion scan with a multistage ergometer exercise test showed no distinct perfusion defect. A two-dimensional echocardiogram disclosed a dilated left coronary artery arising from the left sinus of Valsalva, and a dilated right coronary artery crossing the aorta anteriorly to the pulmonary trunk. Real-time two-dimensional Doppler echocardiography of the same region showed an abnormal jet coming from the right coronary artery into the pulmonary trunk during diastole. A continuous wave Doppler flow study in the pulmonary trunk revealed a high-speed, disturbed flow which began in mid-systole, and continued during diastole. These findings were compatible with anomalous origin of the right coronary artery from the pulmonary trunk. An aortogram confirmed the diagnosis.

Adenomyoepithelioma of the breast. A case report with an immunohistochemical study.

We treated a 62-year-old woman with adenomyoepithelioma of the breast, an extremely rare tumor, which showed a bicellular pattern of ductal and myoepithelial elements bearing some histologic resemblance to pleomorphic adenoma of the salivary gland. The tumor was made up of cells positive for actin and S-100 protein, and some positive for epithelial membrane antigen (EMA). Thus, this tumor showed biphasic differentiation towards myoepithelial cells and to duct epithelial cells. Compared with findings in related tumors reported in the literature, the myoepithelial cells in the present tumor were less frequently spindle-shaped and had abundant eosinophilic or clear cytoplasm. A simple mastectomy was done and at the time of writing 20 months later there has been no recurrence. Adjuvant chemotherapy was not prescribed.

Swallowing-induced paroxysmal supraventricular tachycardia.

A 54-year-old man had palpitations on swallowing without any esophageal or heart disease. Electrophysiological findings, including an A wave in the high right atrial leads appearing prior to the A wave on His bundle electrogram, revealed that the arrhythmia was paroxysmal supraventricular tachycardia originating in an ectopic focus of the atrium with intraventricular aberration. Treatment with verapamil, 120 mg/day, reduced his symptoms in spite of an insignificant decrease in the arrhythmia observed with Holter dynamic electrocardiography.

The effect of cyclosporin-A, low-temperature culture, and anti-Ia antibodies on prevention of rejection of rat islet allografts.

The effect of cyclosporin-A, low-temperature culture, and anti-Ia antibodies on prevention of rejection of rat islet allografts was determined. Wistar-Furth islets were isolated by the collagenase technique and transplanted via the portal vein into diabetic Lewis recipients. Cyclosporin-A (30 mg/kg) injected at 0, 1, and 2 days after transplantation produced a significant prolongation of survival of the islet allografts (MST greater than 35.7 +/- 7.0 days) when hand-picked donor islets were used, whereas only a modest prolongation of survival (14.0 +/- 1.6 days) was obtained using donor islets removed directly from Ficoll gradients. This difference in survival was apparently due to the large number of lymphoid, antigen-presenting cells that were present in the islet fraction removed directly from the Ficoll gradients. Treatment of donor, hand-picked islets with a mixture of cross-reactive anti-Ia antibodies and complement without cyclosporin-A therapy did not prolong the survival of islet allografts (MST, 6.5 +/- 0.4 days versus 7.0 +/- 0.5 days in controls). In contrast, treatment of the donor islets with the mixture of anti-Ia antibodies and complement in conjunction with the 3-day course of cyclosporin-A therapy produced an 83% survival of the islet allografts at 60 days after transplantation. In vitro culture of hand-picked donor islets at 24 degrees C for 7 days and the 3-day course of cyclosporin-A therapy produced a 100% survival of the allografts at 60 days after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Characteristics of xenograft rejection. I. Augmented cytotoxicity of peritoneal T cells after intraperitoneal injection of booster antigen and/or proteose peptone.

Cytotoxic activity was detected by the 51 CR-release test in peritoneal exudate (PE) cells of mice immunized with rat lymphocytes 5 days previously, but not in their spleen or lymph node cells. This activity appeared to be exerted by cytotoxic T cells, which had the same characteristics as those for allogeneic systems in respect to antigen specificity and time course. An intraperitoneal booster with rat lymphocytes 2 days before the assay effectively enhanced the cytotoxic activity of PE cells. When mice were immunized with rat lymphocytes subcutaneously or intravenously, cytotoxic activity was scarcely detected in PE cells. However, significant activity was detected in PE cells when the immunized mice were injected intraperitoneally with proteose peptone 2 days before the assay.

Characteristics of xenograft. II. Cytostatic effector mechanism for xenograft rejection.

Cytolytic activity was detected by the 51 Cr-release test with Concanavalin A (Con A)-stimulated rat lymphocytes, when peritoneal exudate (PE) cells were obtained from mice immunized by intraperitoneal injection of rat lymphocytes. Such PE cells did not exert cytolytic activity on rat tumor cells. When mice were immunized with mitomycin C-treated rat tumor cells, their PE cells exerted low or negligible degrees of cytolytic activity on both types of target cells. When cytostatic activity was assayed by inhibition of the incorporation of 125 IUDR into rat tumor cells, the activity was detected in the whole PE cells of mice immunized with rat lymphocytes or tumor cells but not in their spleen or glass-nonadherent PE cells. Mouse tumor cells were also sensitive to the cytostatic activity of such a cell population. Normal AKR PE cells became cytostatic to rat tumor cells, when they were exposed to the supernatants prepared from the culture containing immune PE cells and antigens. The supernatants alone did not exert cytostatic activity.

Various immune reactions in hamsters after immunization with murine tumour cells and their roles in rejection.

Hamsters immunized with a murine tumour via the cheek pouch showed accelerated rejection following rechallenge with the same kind of tumour cells. Regional lymph node cells exhibited a suppressive effect on tumour growth in in vivo neutralization tests although cytotoxicity was not detected in such a population by 51Cr-release tests. Cytotoxicity became detectable using glass-nonadherent peritoneal exudate in cells in the 51Cr-release test, when the peritoneal cavity was used for primary immunization or rechallenge. These results suggested that lymphocytes acquired cytotoxic capacity at the site of xenograft rejection after close contact with target cells. Capacities to elicit delayed footpad reaction and to suppress tumour growth at rechallenge developed in hamsters exposed to 600 rad before immunization. Their capacity to produce cytotoxic antibody was abolished completely by such irradiation.

Relationships among differentiated T-cell subpopulations. V. T-cell dependent mechanism of xenograft rejection and its radioresistant nature.

Rat tumours grew progressively in nu/nu mice but not in nu/+ mice, normal AKR mice or sublethally irradiated AKR mice after subcutaneous inoculation. Suppression of tumour growth appeared to depend on radioresistant cytotoxic T cells which were detected in in vivo neutralization tests (Winn's test) with spleen cells of mice immunized with rat lymphocytes or tumour cells 5 days previously. Radioresistant cytotoxic activity was detected by 51Cr-release test in glass-non-adherent peritoneal exudate cells 5 days after intraperitoneal immunization with rat lymphocytes. These results suggested that immune lymphocytes might differentiate to mature cytotoxic cells at the site of direct graft rejection.

Relationships among differentiated T-cell subpopulations. IV. Preferential induction of delayed footpad reaction to xenografts and its radioresistant nature.

Immune response in mice to xenogeneic cells was characterized by positive delayed footpad reaction and negative macrophage migration inhibition. Mice immunized with allogeneic cells exhibited negative delayed footpad reaction and positive macrophage migration inhibition. Cytotoxic T lymphocytes were detected only in mice immunized with allogeneic tumour cells. Delayed footpad reaction against xenogeneic cells was radioresistant and the immune lymphocytes responsible for such a reaction were presumed to have some relation to xenograft rejection.