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Rats fed diets containing different amounts of polyunsaturated fatty acids either of the n-3 or n-6 type, received cultured, syngeneic mammary tumor (BN472) cells intravenously. Animals were sacrificed 2 weeks after tumor inoculation, and the number of pulmonary tumor foci was counted. No significant differences in the number of metastatic foci were observed between the dietary groups. Prostaglandin measurements in the supernatant of tumor cells cultured in vitro showed that the tumor cells could produce thromboxane A2. Many investigators connected this tumor synthesis capacity with tumor metastatic activity. Yet in our study, diets rich in menhaden oil, with the known capacity to inhibit thromboxane synthesis, could not control tumor metastasis in this particular tumor model.

The effect of partially purified rat interferon ( RIFN ) was evaluated in CC531 colon tumor-bearing rats. Tumor CC531 is a DMH-induced, transplantable adenocarcinoma exhibiting weak immunogenicity. When small tumor fragments were implanted under the renal capsule, daily treatment with RIFN for 5 days led to a highly significant (p less than 0.001) inhibition of tumor growth, measured 7 days after implantation. Cyclic treatment with RIFN (10(5) units/kg/day, for 7 days in weeks 2, 4, 6 and 8) significantly retarded the development of artificial lung metastases, induced by intravenous (i.v.) injection of 5 X 10(5) colon tumor cells. The median survival time was 177 days in the RIFN group as compared to 116 days in the control group. Three of eight animals treated with RIFN showed no sign of lung metastases when they were killed 250 days after tumor cell injection. The same cyclic RIFN treatment which was effective in the lung metastases model had no influence on the growth of liver metastases evoked by the intraportal injection of 5 X 10(5) tumor cells. Laparotomy performed at days 30 and 50 after inoculation revealed equal numbers of liver metastases in the RIFN -treated group and the control group. The mean survival times obtained in the two groups were 96 +/- 20 days and 108 +/- 14 days, respectively (0.05 less than p less than 0.10). The results indicate that (1) there is no inherent resistance of this solid tumor to RIFN therapy and (2) the effect of RIFN treatment is determined by the site of tumor development. The finding that the liver can provide a protective environment against tumor immunity may have important clinical implications.

In an investigation of the pathogenesis of acute necrotizing pancreatitis (ANP) the plasma levels of TXB2, 6-keto-PGF1 alpha, and PGE2 were measured in rats. After induction of ANP by injection of 5% sodium taurocholate into the pancreatic duct, a marked increase in TXB2 levels and a slight increase in 6-keto-PGF 1 alpha levels were found. PGE2 levels decreased. Mortality was 100% within 30 h. Pretreatment with chloroquine, a phospholipase A2 inhibitor, led to a inhibition of TXB2 production, whereas 6-keto-PGF1 alpha and PGE2 levels showed a surprising slight elevation in the first 6 h. Pretreatment with chloroquine decreased mortality by 30%. Pretreatment with FPL 55712, a leukotriene synthesis blocker, caused an increase in TXB2 and PGE2 levels, whereas the formation of 6-keto-PGF1 alpha remained unaltered. Two out of nine animals survived after pretreatment with FPL 55712. The results of the present study indicate that arachidonate end products are involved in ANP. The significance of the high TXB2 levels, decreased PGE2 levels, and only slightly elevated 6-keto-PGF1 alpha levels during ANP requires further investigation. The thromboxane A2 to prostacyclin ratio may be important.

The relevance of matching for the serologically defined (SD) and lymphocyte-defined (LD) antigens of the major histocompatibility complex (MHC) for renal allograft survival was evaluated in a dog model. Kidney recipients were treated with a standard regimen of immunosuppressive drugs (azathioprine, 2 mg/kg body wt, and prednisolone, 1 mg/kg body wt, daily i.v.) after transplantation. In seven of the eight SD- and LD-identical beagle littermate donor-recipient pairs (DRPs), and in all seven SD- and LD-identical beagle nonlittermate DRPs, kidney function remained normal for the period of 150 days during which immunosuppressants were given. Of the 8 beagle littermate DRPs differing in one haplotype and all 25 unrelated mismatched mongrel DRPs, kidney function deteriorated during immunosuppressive therapy, and most of the recipients died eventually from graft rejection. Thus, it seems that, in moderately immunosuppressive dogs, non-DLA incompatibilities rarely, if ever, cause rejection, whereas DLA incompatibilities almost always do so. The data differ from those obtained in a previous study in nonimmunosuppressed dogs, in which non-DLA incompatibilities seemed to be as strong as DLA incompatibilities in this respect. Differences in minor histocompatibility antigens can apparently be overcome more easily by immunosuppressive drug therapy than differences in major histocompatibility antigens. After the gradual complete withdrawal of immunosuppression, 11 of the 15 matched littermate and nonlittermate DRPs survived for another 150 days or more, implying that some kind of unresponsiveness was induced in those dogs.

The role of the spleen in the manifestation of the transfusion phenomenon was studied in beagle dogs. Beagles were transfused 3 times with 100 ml blood from different mismatched mongrel dogs, at 4, 3, and 2 weeks before mongrel kidney transplantation or splenectomy. Seven transfused dogs were splenectomized 1 week before transplantation, 9 transfused animals were not splenectomized, and a group of 9 kidney allografted controls was neither transfused nor splenectomized. All recipients were given postoperative immunosuppression, which consisted of azathioprine and prednisolone. As with earlier demonstrations it was found that 3 pretransplant blood transfusions in the nonsplenectomized group led to a significant prolongation of kidney graft survival. All transfused animals survived for more than 3 weeks, a period in which more than 50% of the kidneys in the control group were rejected. Four out of 9 transfused dogs became long-term survivors. In the transfused-splenectomized group, 70% of the recipients rejected their kidney acutely within 3 weeks, and only one animal became a long-term survivor. The absence of a transfusion effect in most of the splenectomized dogs suggests that, under the experimental conditions employed, the spleen plays a crucial role for the induction and manifestation of the transfusion phenomenon.

To study the biological characteristics of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in rats, 20 Sprague Dawley female rats received a single oral dose of 5 mg of this carcinogen. During the 35-week observation time 78 primary tumors were removed. While in most cases the primary tumor could be removed completely, 7 out of 20 animals eventually had to be sacrificed for inoperable local recurrence of the primary tumor. Notwithstanding, the long period of time given for tumor metastases to develop (mean time between tumor removal and termination was 18.5 weeks), tumor spread either to lungs or regional lymph nodes could not be established. This relatively benign behavior of the tumor was in contrast with the morphological characteristics of the tumor, which uniformly showed the features of adenocarcinomas. The difference in biological behavior between DMBA-induced mammary tumors in rats and malignant mammary tumors in humans suggests that as a model this system is of limited value for investigations of mechanisms of malignant behavior of human tumors.

Significant prolongation of survival of nonrelated DLA-mismatched renal allografts has been obtained in beagle recipients receiving three blood transfusions from nonrelated donors prior to kidney transplantation and immunosuppression after transplantation. Nontransfused DLA-identical or DLA 1 haplotype-different littermates of the transfused dogs were used as controls. Lymphocytotoxic antibodies were formed after the blood transfusions. A quantitative immune reactivity score correlated with graft survival. Low scores prior to transplantation were found in five transfused dogs that did not reject their allografts. High scores prior to transplantation were found in four animals rejecting their graft and in one dog that survived after an abortive rejection episode. The great similarities between the results obtained in this animal model and the observations made in human transplant patients indicate that this model can be utilized for a further analysis of the possibilities of blood transfusions in protecting subsequent renal allografts from immunological rejection.

In a previous study, significant differences in the growth rate of a transplantable mammary adenocarcinoma were observed between rats receiving a diet rich in saturated fatty acids (lard, diet A), and rats on a diet in which the saturated fat was partly replaced by polyunsaturated fatty acid of the omega-3 type (Menhaden oil, diet B). In the present investigation, it was our aim to study tumor growth in rats on diet A and B, as well as in rats that had, at tumor inoculation, a change of diets, from diet A to diet B. Tumor growth of rats receiving diet A throughout the whole experiment was the same as in those rats that had a conversion of diets. The data shows that the observed inhibiting effect of diet B on tumor growth could not be obtained when this diet was given exclusively after tumor inoculation.

Discriminant analysis was used to interpret the results of the secretin-cholecystokinin (CCK) test in the diagnosis of chronic pancreatitis. An allocation rule based on the use of two test variables--mean chymotrypsin concentration and peak bicarbonate output--was constructed to distinguish between 63 patients with chronic pancreatitis and 68 patients without organic disease. These latter patients had signs and symptoms similar to those of the patients with chronic pancreatitis and were used as controls. The allocation rule was applied to a larger set of individuals, including 105 patients with various other diseases. The sensitivity of the test was 83%, and the specificity was 89%. With a prevalence of chronic pancreatitis of 27% in this set of individuals, the positive predictive value was 73%, the negative predictive value was 93%, and the accuracy rate 87%. This diagnostic performance of the secretin-CCK test gives the test a meaningful place in the examination of patients suspected of having chronic pancreatitis.

The Third International Workshop on Canine Immunogenetics involved 80 potentially DLA-D homozygous typing cells obtained from dogs of various breeds and submitted from five laboratories in Europe and the United States. Mutual reactivity of all cells was studied in mixed leukocyte cultures, and stabilized relative responses were used for analysis. Intralaboratory and interlaboratory comparisons of results suggest that a stabilized relative response of 30% represents an acceptable parameter for "typing responses" indicating phenotypic DLA-D identity of stimulator and responder cells. Using this criterion, 10 clusters of homozygous typing cells were defined and accepted on an international level, and they were assigned the specificities Dw1 to Dw10. At least six additional (provisional) specificities were recognized that were well characterized within individual laboratories but require additional testing before workshop specificities can be assigned. These data show that DLA-D typing is feasible and represents a useful tool in the genetic analysis of the canine major histocompatibility complex. Much work is needed to confirm the present results in family studies, to determine gene frequencies, and to analyze at a molecular level the antigens responsible for mixed leukocyte culture reactivity.

The findings from endoscopic retrograde pancreatography (ERP) and secretin-CCK test data were compared in 69 patients: 36 with chronic pancreatitis, 9 with possible chronic pancreatitis, and 24 without chronic pancreatic disease. The ERP findings were also compared with the histologic changes in pancreatic tissue in 18 patients who underwent pancreatic surgery for chronic pancreatitis. ERP films were reviewed according to the criteria proposed by Kasugai et coll. (8) with special attention paid to the side branches. Secretin-CCK test data were interpreted using the discriminant analysis. A good correlation between bicarbonate and chymotrypsin output and ductular changes at ERP was found. The results of ERP and the secretin-CCK test were compatible in 86 per cent of the patients. The relationship between ERP findings and histologic changes was not straightforward. It was concluded that ERP and the secretin-CCK test are complementary in the diagnosis of chronic pancreatitis. ERP does not necessarily represent the histology in chronic pancreatitis.

A single transfusion of 200 ml of donor blood 14 days before renal transplantation in prospectively DL-A tissue typed beagle littermates appeared to have an effect on graft survival. Seventeen per cent of the recipients did respond to the transfusion with formation of lymphocytotoxic and haemagglutinating antibodies. These "responder dogs" rejected kidney grafts in an accelerated way, compared with the "nonresponders" and with the nontreated control dogs. Responsiveness appeared to occur in pairs of littermates, which suggests that responding potency is genetically determined. There was histological evidence of acute arteritis in the renal grafts of responders, whereas cell-mediated rejection was noted in nonresponders.

For suppression of primary tumor growth and metastatic spread, aspirin and theophylline, either alone or combined, were given daily to inbred female BN rats after sc implantation of a syngeneic nonimmunogenic tumor. Treatment with 200 mg aspirin/kg (body wt) resulted in a statistically significant regression of tumor growth as well as of the number of metastases in the lungs. Aspirin given in a lower dose (20 mg/kg) did not show significant difference from the vehicle group. Theophylline (75 mg/kg) significantly increased primary tumor growth as well as lung metastases. Inhibition of in vitro platelet aggregation, determined in whole blood taken from non-tumor-bearing animals treated with the same therapeutic regimen, was most pronounced in those groups in which tumor growth and spread were significantly retarded. However, this positive correlation between inhibition of tumor spread and platelet aggregation was not associated with a favorable balance of prostacyclin and thromboxane A2 in these animals.

Therapy with high dose recombinant alpha 2 interferon (IFN-α 2) produces a depression in natural killer cell cytotoxicity

The relationships between immune reactivity after blood transfusions, subsequent kidney allograft survival, and donor selection were studied in dogs. Animals with a high as well as low serological immune reactivity toward antigens contained in blood transfusion were observed. Genetic control of this reactivity or a linkage of this property to DLA, sex, or red blood cell markers inheritance was not apparent in the four beagle families studied. The two recipients with the lowest immune reactivity scores were also found to be the longest survivors after a DLA-mismatched kidney graft. Seven other recipients with higher scores rejected their DLA-mismatched kidneys as rapidly as did untransfused animals. Kidney graft survival was decreased in some recipients of DLA-identical kidneys (n = 5), presumably through sensitization for minor histocompatibility antigens. A normal or an increased survival time of DLA-identical kidneys was found in the remaining animals (n = 6). The majority of these recipients appeared to have a higher than average reactivity in two-stage microcytotoxicity testing. This might have been attributable to the presence of enhancing antibodies. Further studies in preclinical animal models are needed to define the optimal transfusion policy for human patients awaiting a kidney graft.

Three cases of disputed paternity in dogs are reported. An identification or exclusion of a sire was possible in all families with the help of genetic markers. Attention is drawn to the lack of communication between dog-breeders, veterinarians and medico-biological research workers all of whom would benefit from an intensified co-operation in the field of dog genetics.

Recently, the demonstration of serum agglutinins to Eubacterium and Peptostreptococcus strains has been found to be useful as a diagnostic test for Crohn's disease. Therefore, conditions determining the occurrence of these antibodies were studied in patients with Crohn's disease and ulcerative colitis. Localization of Crohn's disease in the colon, the presence of fistulae and serum levels of immunoglobulins were found to be contributory determinants for the occurrence of the agglutinins.

It has been shown previously that, at least in dogs, a vascularized pancreatic allograft with ligation of the pancreatic duct can maintain normal beta-cell function for at least 5 years. In this study common organ preservation techniques, as used in human cadaveric kidney transplantation, were applied to canine pancreatic allografts to determine the influence of 24-hour preservation on beta-cell function, graft survival and histological appearances. Three groups of dogs were compared: group A consisted of 9 dogs with fresh grafts; group B consisted of 5 dogs who received grafts preserved for 24 hours by pulsatile hypothermic cryoprecipitated plasma perfusion; and group C was composed of 5 animals who received grafts that had been flushed with Collins' solution followed by hypothermic storage for 24 hours. It appeared that both preservation methods were equally effective and that preservation did not alter either the graft's function or its histological appearance. No significant differences after transplantation were observed in the endocrine function tests of the three groups when compared with the preoperative values; neither was there a significant difference in the mean graft survival time between the groups.

Pancreas transplantation was studied in the dog using a total duct ligated pancreas as allograft. In a group of 10 mongrel dogs the effects of longterm (6–36 months) total duct ligation on the endocrine pancreas function were studied by means of repeated intravenous glucose tolerance tests (iv-GTT). One year after total duct ligation the mean glucose assimilation coefficient (k-value) was 75%, the median insulin peak value (IPV) 63% and "total" insulin secretion in the first thirty minutes (TIS) 58 % of the pre-operative values. These levels were maintained up to three years after duct ligation. The total duct ligated pancreas was then used as an allograft in 28 beagles in order to study the influence of DL-A (dog leucocyte-antigens) matching on the survival time of the graft. DL-A identity compared to one or two haplotype diference gave a fourfold increase in median survival time from 9 to 40 days. In a second group of 14 beagles with one haplotype difference the effect of immunosuppressive therapy was studied. The methods used (antilymphocyte serum and a combination of prednisone and azathioprine) increased the median survival time to the level seen in DL-A identity. In conclusion the total duct ligated pancreas can be used as an insulin secreting allograft, providing rejection can be suppressed adequately.

Previous studies have shown that lung metastases from a non-immunogenic sarcoma (LS175) in BN (homozygous for RT1n) rats were stimulated by blood transfusions. Enhanced growth was also observed after abdominal surgery combined with allogeneic blood transfusions while syngeneic blood transfusions had no effect. These experimental findings have been confirmed in retrospective clinical studies. The allogeneic blood transfusion effect may be avoided in cancer patients by autologous blood transfusions although this implies blood donation before surgery. The aim of the present study was to investigate the effect of blood loss before surgery on formation (‘take’) of lung colonies, and on the outgrowth of established metastases in the BN rat model. These aspects of tumour behaviour were also investigated in rats undergoing surgery, or receiving blood transfusion, or both, after blood loss. The results indicate that blood loss has a profound stimulating effect on the growth of established metastases, but not on the ‘take’ of tumour cells. This stimulating effect was also present when blood loss was combined with surgery, while previously surgery alone was found to have no effect. Allogeneic and syngeneic transfusions in combination with blood loss both had a strong stimulating effect on growth of established lung metastases. The results indicate that blood loss may be an important factor in determining the outcome of metastatic growth.

The effect of pretransplant blood transfusion (PBT) and histocompatibility matching on kidney allograft survival was studied in immunosuppressed dogs. PBT was found to be beneficial for related and unrelated mismatched kidney grafts. In contrast, after withdrawal of the immunosuppressants, transfused recipients of related and unrelated matched grafts rejected the kidney significantly more often than non-transfused dogs. Crossimmunisation for minor histocompatibility antigens may be responsible for this adverse effect, but could not be demonstrated in vitro by serology or mixed lymphocyte reactions. The possible deleterious effect of PBT in this model argues against the routine use of pretransplant blood transfusions in man.

Growth of BN175, a malignant fibrosarcoma, was correlated with high plasma TXB 2 and PGE 2 levels. This statistically significant increase was first detected 17 days after inoculation of the tumor, at which time the tumors were 20 mms in diameter. A further increase in tumor size was associated with still higher PGE 2 and TXB 2 values. At the same time, progressive alterations in platelet function, as measured by ADP-induced platelet aggregation, were observed.6-keto-PGF 1α levels remained normal throughout the whole experiment. It was concluded that tumor growth was associated with changes in PG synthesis and platelet function, although it remains unclear whether these changes were caused by some host immunological response towards the tumor or were predominantly the result of tumor PG-synthesis.

A simple and reliable method for the calibration of stenoses in intestinal Crohn's disease, using a marble, is presented. With this procedure, unnecessary resection or stenoplasty can be avoided and adequate passage of intestinal contents throughout the whole length of the small intestine is secured.

Aspirin (group I, 20 mg/kg, 0.5 hour preoperatively, ip, xylocaine (group II, topical administration of 1 ml of a 2% solution), and ZK 36,374 (Iloprost) either pre- or per- or postoperatively (group III, 10 micrograms/kg 0.5 hour peroperatively iv; group IV, topical administration of 1 ml of a solution containing 25 micrograms/ml peroperatively; and group V, 10 micrograms/kg 0.5 hour postoperatively iv) were given to groups of BN female rats in order to improve the patency rate of small artery (less than 0.5 mm) anastomoses. The rats in group VI received saline peroperatively by topical application, this group served as a control. The patency was established by means of arteriography and macroscopical examination. Neither aspirin nor xylocaine improved the number of successful anastomoses. However, Iloprost administered topically, while performing the anastomosis, substantially improved the patency rate when compared with group VI, the control group. In the control group only five out of 21 animals showed patent anastomoses, whereas in group IV (Iloprost, topical administration) seven out of ten operations were successful. The results suggest that Iloprost applied locally could be helpful in clinical microsurgery for elective operations as well as in replantation surgery.

The effects of small circulating blood volume alterations on the SNP dosage required to maintain the mean arterial pressure at 70 mm Hg were studied in 6 anesthetized dogs; (A) normovolemia, (B) hypovolemia by arterial bleeding 7 ml/kg, and (C) hypervolemia by infusing 7 ml/kg whole blood. The animals became extremely SNP sensitive during hypovolemia and resistant during hypervolemia (SNP dosage A: 25.8, B: 14.7, C: 70.0 microgram/kg/min); these changes were accompanied by significant changes in cardiac output (A: 193, B: 142, C: 249 ml/kg/min). The intravenous administration of SNP with the aim of inducing hypotension generally causes a balanced pre- and afterload reduction. This balance is rather delicate and easily disturbed by small intravascular fluid changes leading to cardiac output and thus to SNP sensitivity changes. Slowly developing tachyphylaxis can be explained on the basis of such intercompartimental fluid shifts and a case of SNP tachyphylaxis reported in literature is discussed on the basis of overinfusion. SNP tachyphylaxis or resistance might be treated by preload reducing measures like phlebotomy or the administration of nitroglycerin.

The findings from endoscopic retrograde pancreatography (ERP) and secretin-CCK test data were compared in 69 patients: 36 with chronic pancreatitis, 9 with possible chronic pancreatitis, and 24 without chronic pancreatic disease. The ERP findings were also compared with the histologic changes in pancreatic tissue in 18 patients who underwent pancreatic surgery for chronic pancreatitis. ERP films were reviewed according to the criteria proposed by Kasugai et coll. with special attention paid to the side branches. Secretin-CCK test data were interpreted using the discriminant analysis. A good correlation between bicarbonate and chymotrypsin output and ductular changes at ERP was found. The results of ERP and the secretin-CCK test were compatible in 86 per cent of the patients. The relationship between ERP findings and histologic changes was not straightforward. It was concluded that ERP and the secretin-CCK test are complementary in the diagnosis of chronic pancreatitis. ERP does not necessarily represent the histology in chronic pancreatitis.

A continent ileostomy for patients with ulcerative colitis or polyposis coli is one of the alternatives to a conventional ileostomy. Construction of the continent ileostomy is a complex operation that can be followed by multiple, serious, and rather intractable surgical complications. In a small series of ten patients, a temporary diversion loop ileostomy was used to promote uncomplicated healing. The lack of any immediate surgical postoperative complications supports our point of view that, at least in centers with little experience of continent ileostomy, a two-stage procedure is preferable to a one-stage procedure.

The influence of subregions of the canine major histocompatibility complex (MHC) on renal allograft survival is assessed in recipients without immunosuppressive therapy. Results in six beagle littermate donor-recipient pairs in which the donor or recipient had a recombination in the MHC are compatible with the concept of a predominant role for the subregion containing the major mixed lymphocyte reaction (MLR) locus in determining allograft survival. Results in unrelated mongrel dogs indicate that compatibility for MLR induces a longer kidney allograft survival than compatibility for the serologically defined (SD) antigens. However, the effect of combined matching for MLR and SD antigens in unrelated donor-recipient pairs is slight in comparison to the effect of MLR and/or SD matching in littermate-related dogs. This indicates that other important histocompatibility systems probably exist in this species.

Diets high (17.7 cal%) and low (3.3 cal%) in linoleic acid were given to groups of Brown Norway female rats before and after inoculation of syngeneic tumor models with different characteristics, with regard to tumor spread, malignancy, immunogenicity, growth rate, rat strain, and histopathological features. Despite the differences in characteristics, in most tumor models, tumor growth was identical in both experimental groups. However, in 2 tumor models, an adrenal cortical carcinoma and a myeloid leukemia, differences in growth were noted. In rats given the diet low in linoleic acid, growth of the cortical carcinoma was significantly increased, whereas the opposite effect was seen in rats with myeloid leukemia.

Over 25 percent of recipients of HLA-identical bone marrow cells die from graft-versus-host disease (GvHD) (6) and, despite maximal immunosuppression, approximately 25 percent of HLA-identical kidneys are rejected within 5 years (1,18). Recently, it has been suggested that GvHD in HLA-identical sibling donor recipient pairs is influenced by minor histocompatibility differences controlled by the sex chromosomes (7,25). However, ethical and practical limitations in the treatment of human patients prevent the proper control of many variables. A better understanding of minor histocompatibility systems is needed to increase survival in humans after transplantation.

High linoleic acid (C18:2) (group I; 17.7 cal%) and low C18:2 (group II; 3.3 cal%) diets were given to groups of inbred Brown Norway virgin female rats (100 animals/group), during their whole life-span. A total of 140 tumors were found in group I and 123 tumors in group II; the median survival times of the 2 groups were 124.2 and 118.5 weeks, respectively. Total spontaneous tumor incidence and median survival times were not significantly different. However, significant differences were found in the incidences of some specific tumors: The numbers of reticuloendothelial tumors and adrenocortical carcinomas were significantly higher in the group of animals receiving the low-C18:2 diet. A high incidence of tumor multiplicity, however, resulted in a significantly greater number of mammary tumors in the high-C18:2 diet group.

The influence of passive and active immunization on kidney allograft survival was tested in littermate beagles differing in one and two DL-A haplotypes. Immunization by treatment of recipients with hyperimmune antidonor serum (ADS) prolonged graft survival only in a few donor-recipient combinations differing in one DL-A haplotype. All ADS batches that were tested in MLC reaction did block this reaction, but no correlation with its in vivo activities was found. Hyperimmunization of recipients with donor lymphoid cells before grafting caused a second-set rejection, whereas one injection with donor blood did so only in 14%, with antibody production and accelerated rejection. A short course of horse antidog lymphocyte serum (HADLS) prolonged kidney graft survival. The addition of intravenously given donor bone-marrow cells to this protocol did not lead to a further increase in graft survival.

Constipation is an age-old and worldwide problem. In ancient times the Chinese technique for handling the problem of constipation consisted of massaging the abdomen with wooden rollers (Figure 1).

BN/Bi inbred female rats fed diets containing different amounts of polyunsaturated fatty acids, either of the omega-3 or omega-6 type, each received an implant of a syngeneic mammary adenocarcinoma. When the diameter of the tumors reached 20 mm, they were surgically removed; 2 weeks thereafter the animals were sacrificed and lung metastases were counted. Cellular immune response was determined before tumor inoculation; certain prostaglandin values in plasma and platelet aggregation were measured before and after tumor inoculation. Plasma prostaglandin E2 and thromboxane B2 values were significantly decreased in those rats fed a diet containing menhaden oil. 6-Keto-prostaglandin F1 alpha, cellular immune response, and platelet function were not significantly different in either one of the diet groups. Tumor growth in the groups of rats receiving the omega-3 fatty acids in their diet was significantly inhibited in comparison with that in the rats receiving the omega-6 fatty acids. However, the number of metastases was not significantly altered.

10 patients with disseminated colorectal cancer were treated either chronically or cyclically with human recombinant leukocyte A interferon (IFl-rA) for 3 months. During this period, leukocyte adherence inhibition (LAI), natural killer (NK) cell activity, concanavalin A-induced gamma-interferon production capacity (GIPCA) and phytohemagglutinin response were sequentially monitored. In both chronically and cyclically treated patients, IFl-rA therapy led to a 'short-lived' augmentation of NK cell activity. In the chronically treated patients, there was a further depression in the NK cell activity during the course of therapy. The outcome of LAI remained unaltered irrespective of the mode of IFl-rA therapy. There was an inverse correlation between GIPCA and phytohemagglutinin response.

As a way to induce mild chronic stress, light-dark (L-D)-shift stress was applied to inbred BN virgin female rats during their whole life-span (group I, 100 animals); the incidences of spontaneous tumor and nontumor processes were recorded. A group of rats (group II, 100 animals) exposed to a standard lighting system served as the control group. Total tumors of 128 in group I and of 154 in group II were found in 74 and 86 animals, respectively. Neither were these differences nor was the pattern of spontaneous tumors statistically significant. Although in earlier studies L-D-shift stress had proved to be effective, especially with regard to its capacity to induce a substantial decrease in cellular immune response, apparently such alterations did not unfavorably affect longevity of BN female rats. Although as a side issue of this study, a strong predisposition for tumor incidence appeared to exist, in particular for the incidence of Langerhans' islet tumors, in fat animals at weaning.

In a dog model, both transfusion of leucocytes and of erythrocytes induced lymphocytotoxic antibodies. The results, obtained in DLA identical littermate and DLA nonidentical nonrelated beagle recipient pairs, suggest a correlation between DLA-type and lymphocytotoxic immune response. Two weeks after the last of three transfusions from different blood donors, kidneys from unrelated DLA-mismatched donrs were transplanted to the beagle recipients. A standard postoperative immunosuppressive regimen was given. No correlation between erythrocyte or leucocyte induced immune response was observed, but both erythrocyte as well as leucocyte transfusions significantly prolonged renal allograft survival as compared with nontransfused controls.

Total pharyngolaryngo-oesophagectomy is performed for carcinoma of the cervical oesophagus, the piriform sinuses and the postcricoid region. A safe effective way of reconstructing the cervical oesophagus is of the utmost importance in these patients. Use of a revascularized intestinal segment for this purpose is described. Twenty-one patients who underwent reconstruction of the cervical oesophagus with an ileal autograft were studied, with a follow-up period of one to .58 months. The low postoperative mortality and morbidity, quick resumption of oral intake, short hospitalization and good functional results obtained with this method yield benefits for these patients.

Recent data stress the importance of matching donor and recipient of an organ graft for both the serologically defined (SD) and lymphocyte-defined (LD) determinants. To allow experimental evaluation of the effect of these SD and LD structures in a noninbred experimental animal, mixed leukocyte culture tests were performed between SD identical and nonidentical dogs to clarify the LD system in these animals. The results of these experiments can be summarized as follows: (a) In the dog there is a LD locus distinct from the known SD loci, which in all probability is localized outside the first (SD-1) series locus on the chromosome. (b) The crossing-over frequency between the SD and LD loci on the chromosome is low. (c) Studies in SD identical unrelated dogs and random unrelated dogs show an apparent high linkage disequilibrium between SD and LD loci. (d) The LD system in dogs is polymorphic.

A total of 20 patients with advanced colorectal cancer received recombinant leukocyte interferon-alpha A (rIFN alpha A) either chronically (group I: twice a week up to 20 X 10(6) IU/m2 i.m.) or cyclically (group II: 1-4 periods of 8 consecutive days up to 20 X 10(6) IU/m2 i.m. daily at 20-days intervals) over a period of 12 weeks. There was 1 partial response, 1 mixed response and 1 patient with stable disease, whilst 17 patients had progressive disease. Median survival was 15.5 months. Survival was significantly shorter when the extent of hepatic disease was greater than 25% (P = 0.05), extrahepatic disease was extensive (P less than 0.005), alkaline phosphatase level was greater than 2 X normal (P less than 0.02), or performance status was less than 100% (P less than 0.001). Toxicity consisting mainly of fever, fatigue, anorexia and weight loss was serious in group I and minimal in group II. Administration of rIFN alpha A led to a "short lived" augmentation of natural killer (NK) cell activity. In the cyclically treated group this was a recurrent phenomenon whereas a marked lasting depression of NK cell activity was seen in chronically treated patients. Interferon-gamma production capacity was significantly stimulated during rIFN alpha A therapy. The differences in toxicity and immunostimulatory effects between the two schedules may be of importance in the design of further studies.