Qualitative and Quantitative Evaluation of Indirect Immuno-fluorescent H-2 Stain on Tissue Sections

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65483/1/j.1399-0039.1979.tb00826.x.pd

Hybrid immune response to parental liver tissue grafts

Parental-to-F 1 -hybrid liver tissue grafts in like-sex donor-recipient combinations survive indefinitely, although several F 1 recipients demonstrate an immunological response to the parental graft. Female F 1 recipients, particularly those carrying the H-2 b haplotype, respond vigorously to male parental liver grafts. However F 1 female responses to male parental liver tissue grafts differ substantively from the responses of parental females to syngeneic male grafts. C3H male liver grafts are rejected vigorously by F 1 females as long as the F 1 carries the H-2 b haplotype. These findings support previous reports of strong immunological responses to C3H H-Y antigen in female F 1 and C3H.SW animals, a response which is absent in C3H females. Female F 1 hybrids carrying the H-2 b haplotype do not reject grafts of B10 or B6 male liver as rapidly as do B10 or B6 parental females. This reduced F 1 response may be related to the formation of hybrid antigens and consequent alteration of the anti-H-Y response. Alternatively, cells that specifically suppress the anti-H-Y response may be present in F 1 hybrids. Factors responsible for suppression appear to be controlled by non-MHC antigens, at least in (OH x B6 or B10) F 1 hybrids.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46740/1/251_2004_Article_BF00696870.pd

Tissue graft rejection in mice

The influence of H-2 subregions on graft survival in a liver slice-tokidney bed grafting system has been investigated. H-2K -region and H-2IA -region donor-recipient differences, either individually or in concert, cause acute graft rejection. H-2D -region donor-recipient differences cause chronic immunological reaction as evaluated by histological criteria. Grafts across this barrier may ultimately be rejected or may survive indefinitely. Several possible explanations for the variation in survival are proposed. The remaining known H-2 regions ( IB, IC, S , and G ) all appear to cause immunological reactivity in a recipient animal which differs from the liver tissue donor at any of these regions. However, only an IC -region difference may ultimately cause complete graft destruction following an extended chronic immunological course. Grafts across background histocompatibility barriers of several genetic types show rejection patterns equivalent to those seen across K and IA barriers. These patterns are unchanged, whether or not the donor and recipient are congenic for H-2 alleles. Different H-2 allelic donor-recipient differences do, however, show different times of survival, indicating variation in strength or number of donor antigens or differences in recipient immune response.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46752/1/251_2005_Article_BF01575670.pd

Tissue graft rejection in mice

A tissue slice-to-kidney bed grafting system is used to study the mechanism of specific tissue rejection (in this case, rejection of liver tissue) over a series of histocompatibility barriers other than the H-2 barrier. Using the method described, it is possible to obtain a pattern or time-course picture of the immunological process, rather than a mean survival time. It is clear from histological observations of these patterns that, although there are considerable differences in numbers of liver grafts which survive for long period's across the several histocompatibility barriers studied, some grafts in almost every case survive the immunological challenge elicited by the genetic barriers. Grafts of liver tissue are therefore similar, but not identical, in survival patterns to grafts of tumor, ovary, and skin. These studies also indicate that immunological mechanisms controlling rejection of tissue over H barriers other than H-2 differ from those controlling rejection over the major histocompatibility barrier in the mouse.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46754/1/251_2005_Article_BF01563948.pd

H-2 and Background influences on tissue grafts across the H-Y barrier

Male liver was grafted to kidney beds in syngeneic female mice. Relative influences of H-2 haplotype, genetic background or interaction of H-2 haplotype with genetic background on anti-H-Y response were evaluated using 27 inbred strains carrying eight H-2 haplotypes of independent origin and three naturally occurring recombinants. Females of H-2 b haplotype acutely rejected the male graft as is reported for other tissue graft systems. An H-2 haplotype influence was found for all haplotypes studied, with a greater variation of immunologic response revealed by histological analysis of liver grafts than is demonstrated by skin grafts. Strains carrying H-2 k , H-2 j and H-2 p haplotypes expressed the greatest range of immunological variability with responses ranging from graft proliferation to graft rejection. Strains carrying the H-2 d haplotype had the most consistent responses with little reaction to the graft. The strong immune response by SJL/J ( H-2 s ) female mice to the H-Y antigen is not typical of other H-2 s strains, but is compatible with the reported hyperresponsiveness of this strain to alloantigens.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46755/1/251_2005_Article_BF01570432.pd

The distribution of la antigens of the H-2 complex on lymph node cells by immunoferritin labelling

The distribution of Ia antigens on the surfaces of lymph node lymphocytes of several mouse strains was investigated using indirect immunoferritin labeling and electron microscopy. The immunoferritin labeling results agreed with results of cytotoxic tests in strain distribution of reactivity, proportion of cells showing label, and cell populations reacting. Capping was induced by increased incubation temperature but conditions for Ia antigen mobilization varied somewhat between the two anti-Ia antisera employed. Uncapped specimens generally showed a denser, more evenly distributed antigen coating than is the case for H-2 antigens labeled by the same indirect immunoferritin method.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22111/1/0000538.pd

Tissue MicroRNA profiles as diagnostic and prognostic biomarkers in patients with resectable pancreatic ductal adenocarcinoma and periampullary cancers

BACKGROUND: The aim of this study was to validate previously described diagnostic and prognostic microRNA expression profiles in tissue samples from patients with pancreatic cancer and other periampullary cancers. METHODS: Expression of 46 selected microRNAs was studied in formalin-fixed paraffin-embedded tissue from patients with resected pancreatic ductal adenocarcinoma (n = 165), ampullary cancer (n=59), duodenal cancer (n = 6), distal common bile duct cancer (n = 21), and gastric cancer (n = 20); chronic pancreatitis (n = 39); and normal pancreas (n = 35). The microRNAs were analyzed by PCR using the Fluidigm platform. RESULTS: Twenty-two microRNAs were significantly differently expressed in patients with pancreatic cancer when compared to healthy controls and chronic pancreatitis patients; 17 miRNAs were upregulated (miR-21-5p, −23a-3p, −31-5p, −34c-5p, −93-3p, −135b-3p, −155-5p, −186-5p, −196b-5p, −203, −205-5p, −210, −222-3p, −451, −492, −614, and miR-622) and 5 were downregulated (miR-122-5p, −130b-3p, −216b, −217, and miR-375). MicroRNAs were grouped into diagnostic indices of varying complexity. Ten microRNAs associated with prognosis were identified (let-7 g, miR-29a-5p, −34a-5p, −125a-3p, −146a-5p, −187, −205-5p, −212-3p, −222-5p, and miR-450b-5p). Prognostic indices based on differences in expression of 2 different microRNAs were constructed for pancreatic and ampullary cancer combined and separately (30, 5, and 21 indices). CONCLUSION: The study confirms that pancreatic cancer tissue has a microRNA expression profile that is different from that of other periampullary cancers, chronic pancreatitis, and normal pancreas. We identified prognostic microRNAs and microRNA indices that were associated with shorter overall survival in patients with radically resected pancreatic cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40364-017-0087-6) contains supplementary material, which is available to authorized users

Accelerated autoimmune disease and lymphoreticular neoplasms in F1 hybrid PN/NZB and NZB/PN mice

This report describes the first studies of inheritance of autoimmunity in inbred Palmerston North (PN) mice, a model of systemic lupus erythematosus (SLE). Mating of PN mice with the nonautoimmune DBA/2 strain produced evidence that PN disease had a recessive mode of inheritance. When PN mice were crossed with autoimmune NZB mice, female offspring from both crosses developed anti-DNA antibodies and died prematurely with vasculitis, renal disease, and lymphomas. In contrast, reciprocal hybrid males had different patterns of mortality; PN/NZB males from the PN female x NZB male mating had moderately prolonged life spans, whereas NZB/PN males from the opposite cross (NZB female x PN male) had prolonged survival to the mean age of 104 weeks. To determine if testicular hormones were solely responsible for increased longevity in hybrid males, PN/NZB and NZB/PN mice were castrated at 2 weeks of age and compared to sham-operated littermate controls. Prepubertal castration did not influence longevity in PN/NZB males, but loss of gonadal hormones significantly reduced life spans in reciprocal NZB/PN males. Female hybrids were not affected by oophorectomy. Because castration changed disease expression only in male hybrids from the NZB female x PN male cross, it was concluded that parentage influenced sensitivity to the protective effects of male hormones. Although surgical sterilization had disparate effects on males, castrated PN/NZB and NZB/PN males consistently outlived oophorectomized females. The lack of clear-cut reversal of disease in males subjected to early castration suggested that nonhormonal, possibly genetic, factors contributed to longevity in both groups of male hybrids.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26206/1/0000286.pd

Studies on the heterogeneity of human serum Lp lipoproteins and on the occurrence of double Lp lipoprotein variants

Lp lipoproteins have been prepared by a mild method from the serum of a large number of individuals. Approximately 25% of the individuals tested showed the presence of a double Lp peak in analytical ultracentrifuge diagrams. These double peaks were designated Lp(a)-1 and Lp(a)-2 to distinguish them from the single Lp(a) peak. The mean viscosity-corrected sedimentation coefficient, S 1.004, 20 C and density of the single Lp(a) peak were 15.8±1.8 s ( n =32) and 1.076±0.01 g/ml, of the Lp(a)-1 peak were 13.5±1.1 s ( n =14) and 1.064±0.007 g/ml, and of the Lp(a)-2 peak were 16.8±1.7 s ( n =14) and 1.074±0.009 g/ml. Absorption tests using a double and single Lp preparation showed that both Lp peaks in the double variants possess Lp(a) specificity. Evidence is lacking as yet for individual specificities for either Lp(a)-1 or Lp(a)-2. Interand intra-individual heterogeneity among Lp lipoproteins is discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44186/1/10528_2004_Article_BF00485737.pd

Immunogenetic control of the response of female mice to male tissue grafts

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46736/1/251_2005_Article_BF01561664.pd