Buffalo Research Articles

Wax D of Mycobacterium tuberculosis induced osteomyelitis accompanied by reactive bone formation in Buffalo rats.

A suspension of heat-killed Mycobacterium tuberculosis in liquid paraffin has been reported to induce foot swelling accompanied by new bone formation in Buffalo (BUF) rats, which are low responders to the induction of adjuvant arthritis. In the present study, we found that wax D, a mycobacterial cell wall peptidoglycan fragment-arabinogalactan-mycolic acid complex, was an effective component of this bacterium for the induction of osteomyelitis accompanied by reactive bone formation in BUF rats. Chronic inflammation was produced in BUF rats by a single subcutaneous injection of wax D suspended in liquid paraffin. Other Mycobacterium species and Gordona bronchialis were also capable of inducing this reaction. Other bacterial cells including the acid-fast bacteria Nocardia and Rhodococcus, purified cell walls and peptidoglycans from Lactobacillus plantarum, wax C, cord factor, arabinogalactan and mycolic acid prepared from M. tuberculosis were inactive in this respect. In addition, when wax D was administered as a water-in-oil emulsion (Freund's type adjuvant), bone formation scarcely occurred in BUF rats. In Fisher (F344) and Wistar rats, both of which are responder strains to adjuvant arthritis, wax D in liquid paraffin did not induce bone formation.

Genetic determinant and environmental carcinogens

2-Amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) is the most abundant mutagenic heterocyclic amine (HCA) present in cooked foods. PhIP induces colon cancer in male Fischer 344 (F344) rats, and its role in human colon carcinogenesis has been suspected. To study the ecogenetics in PhIP colon carcinogenesis, rat system using aberrant crypt focus (ACF) formation as a phenotypic marker was applied. Among Buffalo (BUF), Brown Norway (BN), F344 and ACI/N (ACI) strains of rats, F344 rats produced a lower level of PhIP-DNA adducts than other three strains, and the number of ACFs/rat was highest in BUF, intermediate in BN and F344 and lowest in ACI. Thus there was no correlation between adduct levels and number of ACF induced by PhIP. F1 progenies of BUF and ACI developed ACF at a similar level to that of F344, and F1 progenies of F344 and ACI developed ACF at a similar level to that of F344. Thus it was indicated that susceptibility of F344 to the ACF induction was autosomally dominant over ACI rats. The results also suggest that BUF rats have at least two genes, one is autosomally recessive against ACI rats and one is autosomally dominant similar to that F344 has. A total of 170 progeny of ACI backcross of F344/ACI F 1 were examined for number of ACFs and 65 progeny were phenotyped as F344 and 60 were ACI. Using these 125 rats, chromosomal mapping is being performed using markers of simple sequence length polymorphism (SSLP) and representational difference analysis (RDA). By mapping the gene, we will be able to identify humans who might belong to high risk group in general population, and cancer can be prevented more efficiently by attaining early diagnosis.

In vitro analysis of gadolinium chloride abrogation of the systemic tolerance induced by portal venous administration of ultraviolet B-irradiated donor cells.

Normally, a Buffalo (BUF) recipient (RT1b) rejects a heterotopically transplanted Lewis (LEW) heart (RT1l) drained into the portal vein (PV) within 14 days. However, the addition of PV administration of 25x10(6) ultraviolet B (UVB)-treated LEW spleen cells (SC) to BUF recipients 7 days before cardiac transplantation results in 70% long-term allograft survival. In this study, we used gadolinium chloride (GdCl3) (7 mg/kg/day) to selectively block the phagocytosis of recipient hepatic Kupffer cells before PV injection of UVB-treated donor SC to examine the mechanism of tolerance induction, as measured by in vitro analysis of mixed lymphocyte culture (MLC), T cell cytotoxicity, T helper cell precursors (pTH), and cytotoxic T cell precursors (pCTL) by limiting dilution analysis. A BUF recipient that received untreated or gamma-irradiated LEW SC intraportally reacted to in vitro stimulation by LEW alloantigen with increased MLC proliferation, T cell cytotoxicity, pTH and pCTL frequencies, and interleukin-2 production. In contrast, SC from BUF that received UVB-treated LEW SC were hyporesponsive on MLC stimulation by donor LEW alloantigen and exhibited markedly reduced cytotoxicity, pTH and pCTL frequency, and interleukin-2 production. However, normal in vitro responsiveness resulted with stimulation by third-party Brown-Norway (RT1n) SC, thus indicating that the systemic hyporesponsiveness was specific for the UVB donor alloantigen given PV. On the other hand, GdCl3 given by intravenous injection daily for 3 days before PV alloantigen blocked the induction of in vitro hyporesponsiveness. Therefore, prevention of alloantigen sequestration by GdCl3 inhibition of hepatic Kupffer cell phagocytosis was pivotal in preventing the development of portal venous tolerance.

IN VITRO ANALYSIS OF T CELL-MEDIATED CYTOTOXICITY DISPLAYED BY RAT HEART ALLOGRAFT RECIPIENTS RENDERED UNRESPONSIVE BY TOTAL-LYMPHOID IRRADIATION AND EXTRACTED DONOR ANTIGEN

The addition of 3M KCl-extracted donor antigen (HAg) to immunosuppressive therapy with 16 Gy total lymphoid irradiation produces a significantly higher fraction of Wistar-Furth (WFu) recipients displaying indefinite survival of heterotopic buffalo (BUF) heart allografts, namely 80 versus 20%. The experiments presented herein analyzed the direct activity as well as estimated the potential precursor numbers at 1 and 3 months in treated recipients. At 1 month post-TLI/HAg therapy, recipients showed reduced proliferative responses in mixed lymphocyte reactions (MLR) in a specific pattern toward donor but not third-party stimulators. Both TLI/Graft and TLI/HAg/Graft groups showed a higher frequency of BUF antigen-directed T-cytotoxic cells (fTc) than TLI-treated, but nontransplanted, WFu hosts. In addition, the TLI/HAg group alone displayed alloantigen-specific suppressor cells that suppressed the MLR proliferative responses of normal spleen T cells against donor, but not third-party, alloantigens. At 3 months postirradition, both TLI/Graft and TLI/HAg/Graft groups displayed variable MLR proliferative responses toward donor and third-party alloantigens. Whereas nontransplanted, TLI-treated WFu rats recovered their fTc to normal levels at 3 months, the TLI and TLI/HAg treated recipients bearing functional heart allografts demonstrated significantly decreased splenic fTc. These results show that reduced numbers of cytotoxic cell precursors may afford more reliable indices of prolonged heart allograft survival than MLR responses. The observations suggest that TLI/HAg transplant hosts display both reduced cytotoxic precursors and activated suppressor elements.

A comparative study of photic injury in four inbred strains of albino rats

The effects of light damage were studied in four inbred strains of albino rats, Fischer (F344), Lewis (L), Wistar (W), and Buffalo (BUF). Thirty-five-day-old rats (3 from each strain) were kept in cyclic light for two weeks, after which they were exposed to constant fluorescent light (180-190 foot-candles, 490-580 nm) for 24 hours. The rats were sacrificed 6 days after exposure. Photic injury to the exposed eyes was evaluated morphometrically by measuring the mean outer nuclear layer (ONL) thickness and qualitatively by light microscopy. Statistical analysis of the quantitative data revealed that the Lewis and Buffalo strains were more severely affected than the Wistar and Fischer strains. The effects of injury were more severe in the superior and temporal quadrants. Taking both quantitative and qualitative assessment into consideration, it appeared that, among the strains studied, the rats from the Lewis strain were most sensitive to photic damage. These findings support previous findings of differential light sensitivity and further suggest that similar variability occurs among inbred strains with type 1 light damage.

39] Autoimmune orchitis and thyroiditis

Publisher Summary This chapter discusses both an experimentally induced and a spontaneous model of organ-specific auto-immune disease. The first model of organ-specific auto-immune disease has the advantage of being induced by a single surgical operation, vasectomy, without the need of any adjuvant. The findings in vasectomized rabbits resemble those of the experimental auto-immune orchitis obtained in rabbits by immunization with testicular antigens in antigens in CFA (CFA). The second model described is the spontaneous auto-immune thyroiditis of Buffalo (BUF) rats. One of the major advantages of this model is its occurrence in animals of an inbred strain. There are very few models of organ-specific auto-immune disease that arise spontaneously (i.e., without experimental manipulations) in inbred animals. Second, BUF rat thyroiditis is similar to the condition observed in humans because of its predilection for older females and the presence of circulating autoantibodies to thyroglobulin.

Induction of autoantibodies to thyroglobulin by anti-idiotypic antibodies.

We report on the induction of autoantibodies to thyroglobulin (Tg) and idiotype-positive molecules (Id') in naive BALB/c mice and Buffalo (BUF) rats after immunization with affinity-purified rabbit anti-Id antibodies directed against the Id of a mouse monoclonal antibody ( mAb62 ) specific for a hormone-containing epitope of Tg. Autoantibodies to Tg were produced in about one-half of anti-Id immunized mice, whereas Id' was detected in all but one mouse. Autoantibodies to Tg and Id' were not produced in control mice similarly immunized with non-anti-Id Ig. To clarify the relationship between molecules with Tg-binding activity and those referred to as Id', Tg-specific monoclonal antibodies were generated from an anti-Id-immunized mouse. By competitive inhibition experiments, we could determine that they were idiotypically very similar to the monoclonal antibody ( mAb62 ) at the origin of the immunologic cascade. Thus, autoantibodies induced by anti-idiotypic immunization alone are likely to be of the Ab1' type. Similarly, autoantibody to Tg and Id' molecules were induced in young normal rats of the autoimmune-prone BUF strain. Together, these results suggest that antibodies to Id directed against autoantigens are sufficient per se to activate self-reactivity.

A potential synergistic effect of donor antigenic extracts and cyclosporine on the prolongation of rat renal allografts.

Administration of five daily doses of 15 mg/kg Cyclosporine on the day before, the day of, and three days after, renal transplantation prolonged the survival of Buffalo (BUF) renal allografts in Wistar-Furth recipients from a mean survival time (MST) of 7.9 +/- 0.74 to 25.5 +/- 1.2 days. The immunologic effects of this brief cyclosporine course were assessed using spleen cells harvested five days after transplantation. Cyclosporine abrogated both the direct lymphocyte-mediated cytolysis of donor 51Cr-labelled BUF targets, and the early, three-day enhanced proliferation, and it stimulated lympholysis of labelled donor cells markedly after restimulation in vitro with BUF lymphocytes. Therefore, cyclosporine disrupts the maturation of both proliferative and cytotoxic precursors of the alloimmune response. A potentially synergistic effect of soluble donor antigen with cyclosporine was postulated, because 3 M KCl extracts are capable of directly stimulating both suppressor T cells and helper T cells. Because the activity of T helper cells appeared in these experiments to be dampened by cyclosporine, antigen stimulation of suppressor cells could lead to unresponsiveness. On the day prior to transplantation, 5 mg of a 3 M KCl extract of BUF spleen (Ag) was administered intravenously in addition to the cyclosporine regimen. Although there was no difference in the overall survival of grafts in the Ag-cyclosporine group and the cyclosporine only group, the Ag-cyclosporine regimen did prolong graft survival significantly in the subset of animals with grafts functioning more than 35 days (Ag-cyclosporine MST = 109.5, cyclosporine alone MST = 54 days). Therefore, it may be possible to exploit the selective properties of cyclosporine and of soluble antigen treatments to achieve unresponsiveness without the hazards of continued administration of immunosuppressive agents.

Anti-idiotypic immunity and autoimmunity: II. Idiotypic determinants of autoantibodies and lymphocytes in spontaneous and experimentally induced autoimmune thyroiditis

In a previous report, it was demonstrated that heterologous anti-idiotypic antibodies to autoantibodies against rat thyroglobulin (ART) were capable of inhibiting the in vitro binding between ART and rat thyroglobulin. It has also been shown that repeated injections of antiidiotypic antibodies into Buffalo (BUF) rats with spontaneous autoimmune thyroiditis were followed by a significant decrease in the levels of circulating ART. In this report, cross-reacting idiotypic determinants, detectable by rabbit anti-idiotypic antibodies to ART, are shown to also be present on ART from rats with experimentally induced autoimmune thyroiditis. In addition, antibodies to rat thyroglobulin from animals of various strains and species are shown to also express idiotypes cross-reacting with those of spontaneous ART of BUF rats. Finally, it is reported that idiotypic determinants similar to those of circulating ART are present on spleen lymphocytes from rats with autoimmune thyroiditis.

An Interview with Ishmael Reed

Ishmael Reed was born on February 22, 1938, in Chattanooga, Tennessee, but grew up in a working-class neighborhood of Buf falo, New York. A novelist, poet, essayist, and playwright, Reed is known for his sharp-tongued, pugilistic satire in which he takes on the hypocrisies of American society. He has particularly focused on this nation's treatment of African Americans, along with its choices in presidents. Critics have praised the jazz sensibility of Reed's work, his verve, and his experimentation with both language and theme. Reed's novels include The Free-Lance Pallbearers (1967); Mumbo Jumbo (1972); The Last Days of Louisiana Red (1974); The Terrible Twos (1982); and The Terrible Threes (1989). His New and Collected Poems was published in 1988. His essay collection, Writin' is Fightin', was also published in 1988. He has received a National Endowment for the Arts Fellowship in creative writing and a Guggenheim Memo rial Foundation award for fiction. His work has been nominated for both the National Book Award and the Pulitzer Prize. Reed has taught at a number of universities, including Harvard, the Univer sity of Washington, State University of New York at Buffalo, and Yale, and for many years he has been a lecturer at the University of Califomia at Berkeley.

Genetics of natural resistance to thermal injury.

The possible influence of genetic factors in conditioning the host's natural resistance to the lethal effects of severe thermal injury has been studied in 908 rats of comparable age and weight, originating from two outbred, eight inbred, and two congenic strains of animals of defined genetic background. Each animal was exposed to a standard, full-thickness, 40% body surface area skin burn by controlled contact with a heated metal plate. The 21-day postburn mortality was 100% in 217 Fisher (F-344) and 97 ACI male and female rats. The mortality was reduced to 49-63% in an intermediate group of 84 Lewis, 98 Wistar, 48 Sprague-Dawley, 96 Wistar-Furth (WF), and 48 Osborne-Mendel (OM) male rats; 48 female OM rats had a mortality of 86% at 21 days after injury. The same injury produced a mortality in 4% in 90 Buffalo (BUF) and 22% in 41 Brown-Norwegian (BN) males, while females of the same strains exhibited a 21-day mortality of 23% and 54%, respectively. Further studies of the effects of similar injury in two congenic strains of rats derived from some of the inbred lines of animals listed above yielded a 21-day mortality of 50% in 18 BN.1B(BUF) and 20% in 15 BN.1U(WF) male rats, and 65% and 36%, respectively, in females of the same lines. These data point to the importance of genetic factors as a key determinant of host resistance or susceptibility to the effects of severe thermal injury. The segregation of responses to thermal injury in inbred rats into susceptible, intermediate, and resistant groups on the basis of strain origin indicates that such natural resistance may be a quantitative trait. One of the genetic components affecting host resistance is sex-linked. The existence of genetically controlled variations in natural resistance to trauma may be an important determinant of survival and may be a source of guidelines for the triage and clinical care of injured patients. It may also be an important selective factor in evolution.

Anti-idiotypic immunity and autoimmunity. I. In vitro and in vivo effects of anti-idiotypic antibodies to spontaneously occurring autoantibodies to rat thyroglobulin.

The effects of anti-receptor (anti-idiotypic) immunity on autoimmune responses have been investigated in Buffalo (BUF) rats with autoimmune thyroiditis. As compared to other animal models of autoimmune disease, BUF rat thyroiditis has the following advantages: it occurs in an inbred strain, arises spontaneously (i.e. without the experimental administration of autoantigens and adjuvants) and is characterized by production of autoantibodies to only one autoantigen, thyroglobulin. Finally, its pathogenesis is mediated by autoantibodies to rat thyroglobulin, and therefore this model is particularly suitable to study the effects of anti-idiotypic reactions on those autoimmune disorders whose damage is caused by humoral immunity. The experiments reported in the present study show that first, heterologous anti-idiotypic antibodies to autoantibodies against rat thyroglobulin have been produced and characterized. It has then been demonstrated that such anti-idiotypic antibodies are capable of inhibiting the in vitro binding between thyroglobulin and thyroglobulin autoantibodies obtained from BUF rats. It has also been shown that repeated injections of anti-idiotypic antibodies into sublethally X-irradiated BUF rats with autoimmune thyroiditis were followed by a significant change in the levels of circulating autoantibodies to rat thyroglobulin. These results provide evidence that in spite of the complexity of autoantigens and the heterogeneity of autoimmune responses, established autoimmune diseases may be controlled by sequential immunosuppression and anti-idiotypic immunity.

Strong and weak immune responses across the same major histocompatibility barrier in rats

Inbred rat strains, Fischer 344 (F-344) and Lewis (LEW), share the serologicalAg-Bl allele and react very weakly in mixed lymphocyte culture (MLC). Despite this apparent identity atAg-B, these strains differ markedly in their immune responses to anAg-B disparate third strain Marshall 520 (M-520) (Ag-B6). F-344 recipients allowed M-520 heart grafts an extended survival, whereas LEW recipients rejected them rapidly. F-344 and M-520 showed a weak response in MLC in contrast to a strong response for LEW and M-520. F-344 produced antisera in response to injection of M-520 cells that had a relatively high antibody titer but low cytotoxic activity. F-344 responded to another strain, Buffalo (BUF) (alsoAg-B6), in a similar fashion. F-344 apparently can produce a strong allogeneic response, as it was able to rapidly reject heart grafts from (LEW x Brown-Norway) F(1) donors (LBN) (Ag-B 1/3). The low response of F-344 to M-520 probably was not due to shared antigens between the two strains because M-520 heart grafts underwent rapid rejection in LEW hosts highly tolerant to F-344. To explain the contrasting response of F-344 and LEW to theAg-B6 disparity, we propose that it is controlled by an immune-response gene(s); that F-344 has a low-responding allele and LEW has a high-responding allele. The data do not reveal a location for this proposed gene. The high-responding allele appears to be dominant, as M-520 hearts were rejected rapidly by (F-344 x LEW) F(1) recipients.

RENAL TRANSPLANTATION BETWEEN HISTOINCOMPATIBLE RATS

SUMMARY Renal transplantation between two inbred strains of rats which differed strongly at a major histocompatibility locus was performed without immunosupperssive treatment. Eleven percent of 55 allografted animals in the Buffalo (BUF) ➝ Lewis (LEW) combination were alive 180 days after transplantaion. Allografted animals of the BUF ➝ LEW and LEW ➝ BUF strain combinations which died less than 50 days post-transplant demonstrated differing patterns of post-transplant renal function and survival times. When lymphocytes from allografted animals surviving more than 180 days were mixed with lymphocytes from normal animals of the donor strain, marked proliferative activity occurred, demonstrating the immunocompetency of the long lived allografted animals. Prolonged allograft survival may not be attributable 10 tolerance

The Professional-Standards Movement in Teaching-Its Origin, Purpose, and Future

The Journal reproduces here the text of an address presented at the concluding session of the Palo Alto Conference, June 30, 1951. As America was emerging from World War II, Mr. McDonald conceived the idea of an official agency of the pro fession of education to lead the teachers of the nation to true professional status. After organizing the Chautauqua Confer ence in 1946 and authoring the resolu tion which was adopted unanimously by the NEA Representative Assembly at Buf falo establishing the National Commis sion on Teacher Education and Profes sional Standards, Mr. McDonald served as Executive Secretary of the Commission from the date of its establishment until July, 1951. At the time this address was presented he had submitted his resigna tion to accept the presidency of the Bowl ing Green State University in Ohio. It is thus as the originator, architect, and dur ing its formative years director of the dynamic program of the National Com mission that Mr. McDonald speaks to the profession through this printed version of his address.