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T P Gordon

Publications and source records attributed to T P Gordon.

At least 37 records · Page 2Linked to original sources
PubMed2000

Anti-calreticulin segregates anti-Ro sera in systemic lupus erythematosus: anti-calreticulin is present in sera with anti-Ro alone but not in anti-Ro sera with anti-La or anti-ribonucleoprotein.

OBJECTIVE: To examine a well characterized group of patients with systemic lupus erythematosus (SLE) for anti-calreticulin. METHODS: The sera of 77 patients with SLE were studied by immunodiffusion, solid phase immunoassay, and immunoblot for antibodies against ribonucleoprotein (RNP) autoantigens and calreticulin. RESULTS: Thirty-five had anti-calreticulin and 40 had anti-60 kDa Ro. There was no association of anti-60 kDa Ro and anti-calreticulin. However, among anti-60 kDa Ro positive sera that also contained either anti-La or anti-RNP, none of 18 had anti-calreticulin. All the remaining sera with anti-60 kDa Ro had anti-calreticulin and anti-52 kDa Ro. CONCLUSION: Anti-60 kDa Ro patients with SLE can be divided into those with anti-60 kDa Ro and either anti-La or anti-RNP or those with anti-60 kDa Ro, anti-52 kDa Ro, and anti-calreticulin.

Autoantigens↗
PubMed2000

Antibodies to AB blood group antigens mimic anti-salivary duct autoantibodies in patients with limited sicca symptoms.

OBJECTIVE: We evaluated the clinical relevance and pathogenic significance of anti-salivary duct autoantibodies (ASDA) in Sjögren's syndrome (SS) and rheumatoid arthritis (RA) by examining (1) their frequency in healthy controls, patients with sicca symptoms, and patients with various autoimmune and infective disorders; (2) their localization by confocal microscopy; and (3) their tissue distribution and cross reactivity with blood group antigens. METHODS: Indirect immunofluorescence (IF) was performed on commercial cryostat sections of monkey parotid salivary gland. Sections were examined by fluorescence and confocal laser scanning microscopy. Sera giving positive staining on the ducts were tested by IF on a range of monkey tissues and salivary glands from several mammalian species. Blocking experiments were performed with human erythrocytes of different ABO blood groups and AB antigens. RESULTS: We identified 2 distinct ductal staining patterns. The first resembled ASDA described in earlier studies and showed patchy bright staining of the apical (luminal) surfaces of the ducts and staining of apical cytoplasmic vesicles. The other was only observed with anti-mitochondrial antibody positive sera and stained the mitochondrial-rich ductal epithelium in a distinctive punctate pattern. Antibodies staining the apical surface of ducts were detected rarely in patients with antiRo/La autoantibody-positive primary SS (1/76) and RA (1/36) and were found in only 1115 with RA and secondary SS. ASDA were detected in sera from 13/51 (25.5%) of patients referred to our clinic with limited sicca symptoms who were anti-Ro/La antibody-negative and had no typical clinical or laboratory features of classical primary SS. The apical ductal staining pattern was not observed with sera from 63 healthy controls without sicca symptoms or in patients with autoimmune and infective disorders. Twelve of the 13 patients whose sera gave ASDA-like staining were blood group O and one group A. Ductal staining was abolished in all sera after absorption with blood group AB erythrocytes or AB antigen. In 5 patients ductal staining was removed by absorption with B erythrocytes but not with A erythrocytes; in the remainder ductal reactivity was abolished by both A and B erythrocytes. CONCLUSION: ASDA seem to occur rarely in patients with primary SS and RA. However, isotype-switched IgG AB blood group antibodies cross react with primate salivary ducts and may produce false positive ASDA staining. Detection of ASDA may be of value in identifying a subset of patients who present with mild sicca symptoms without other autoimmune features.

ABO Blood-Group System↗
PubMed1999

Induction of autoimmunity by multivalent immunodominant and subdominant T cell determinants of La (SS-B).

We investigated the consequences of altering the form and valence of defined autodeterminants on the initiation and spreading of experimentally induced La/Ro autoimmunity. Anti-La and Ro (SS-A) Ab responses were monitored following immunization of healthy mice with defined immunodominant and subdominant T cell determinants of the La (SS-B) autoantigen synthesized as either monomeric or multiple antigenic (MAP) peptides. Abs to mouse La (mLa) developed faster and were of higher titer in mice immunized with the subdominant mLa25-44 MAP compared with mice immunized with the 25-44 monomer. Rapid intermolecular spreading of the autoimmune response to 60-kDa Ro was observed in AKR/J mice immunized with mLa25-44 MAP, but not in mice immunized repeatedly with monomeric peptide. A/J mice immunized and boosted with the known tolerogenic mLa287-301 determinant delivered as monomeric peptide failed to develop Abs to either intact mLa or mLa287-301 peptide. However, immunization with the multivalent mLa287-301 peptide led to the rapid production of high titer mLa autoantibodies associated with a proliferative T cell response to the mLa287-301 peptide. The data suggested that the enhanced immunogenicity of MAPs was not due to augmented Ag presentation or T cell stimulation. However, MAP-, but not monomer peptide-, containing immune complexes were potent substrates for Ab-dependent fixation of complement. These results demonstrate that the form of Ag responsible for inducing autoimmunity can profoundly influence the nature and magnitude of the immune response. Thus, molecular mimicry of tolerogenic and nontolerogenic self determinants might trigger autoimmunity under conditions of altered valence.

Amino Acid Sequence↗
PubMed1999

Molecular chaperones are targets of autoimmunity in Ro(SS-A) immune mice.

We have used a murine model of experimental anti-Ro(SS-A) autoimmunity to dissect additional intermolecular interactions between the 52-kD Ro (Ro52) and 60-kD Ro (Ro60) autoantigens and molecular chaperones. Immune responses to members of the heat shock protein hsp70 and hsp90 families were measured by immunoblotting and ELISA in sera from mice immunized and boosted with purified recombinant Ro52, Ro60 and La (SS-B). All Ro52 and Ro60 immune sera immunoblotted the inducible glucose-regulated protein grp78 and hsp70 species but not constitutive hsc70 or hsp90. The kinetics of antibody production and reciprocal affinity purification experiments indicated that the grp78 and hsp70 responses were cross-reactive but distinct from immune responses to the primary Ro52 and Ro60 immunogens and the endoplasmic reticulum (ER)-resident chaperone calreticulin. No responses to molecular chaperones were detected in the La-immunized mice. Control immunizations indicated that the recruited grp78 and hsp70 responses were specific for the Ro proteins and not due to immunization with denatured protein. The rapid spreading of immunity to the inducible grp78 and hsp70 in Ro52- and Ro60-immunized mice suggests that these components may co-localize and physically associate under certain physiological conditions which may promote autoimmunization. The potential importance of the ER-resident chaperones grp78 and calreticulin is further supported by their co-localization with Ro in small apoptotic membrane blebs and the finding of a novel putative grp78 binding motif in the carboxyl-terminal region of Ro52.

Animals↗
PubMed1999

Cerebral white matter lesions in primary Sjögren's syndrome: a controlled study.

OBJECTIVE: To determine the prevalence of neurological and magnetic resonance imaging (MRI) abnormalities in a well defined population of unselected patients with primary Sjögren's syndrome (SS) and age and sex matched healthy patients. METHODS: Thirty patients with SS and 29 age and sex matched controls were examined by a neurologist and subsequently underwent MRI scanning with a 1.0 Tesla Siemens Impact MR scanner. Scans were graded by a neuroradiologist blinded to the clinical status of each subject. The number and location of white matter lesions > 3 mm in long axis (to exclude non-specific perivascular changes) were recorded for each subject. RESULTS: There was a significant increase in lesions detected by MRI in SS patients versus controls (p = 0.02) including deep white matter lesions (p = 0.03) and subcortical white matter lesions (p = 0.02). The presence of white matter lesions did not correlate with serum IgG or rheumatoid factor levels, or with presence of anticardiolipin antibodies. No subjects had symptoms or signs of serious neurological disease including multiple sclerosis, and corpus callosal lesions commonly seen in multiple sclerosis were notably absent in this study. CONCLUSION: Cerebral white matter lesions detected by MRI are more frequent in patients with primary SS than control subjects, yet do not appear to be associated with significant clinical manifestations. Although the pathological nature of these lesions is yet to be defined, their presence should not be over-interpreted.

Adult↗
PubMed1998

Determinant spreading: lessons from animal models and human disease.

Spreading of the immune response is a common theme in organ-specific and systemic autoimmune diseases. We evaluated whether some of the mixed antinuclear antibody patterns characteristic of systemic autoimmunity might be the result of determinant spreading from a single initiating event. Immunisation of healthy mice with individual protein components of the La/Ro ribonucleoprotein (RNP) targeted in systemic lupus erythematosus and primary Sjögren's syndrome induced autoantibodies recognising Ro60 (SS-A), Ro52 (SS-A) and La (SS-B) and in some cases the molecular chaperones calreticulin and Grp78. The endogenous antigen(s) driving determinant spreading might be derived from physiological apoptosis which could explain the involvement of some chaperone proteins in the autoimmune response. Diversified anti-La/Ro antibody responses were initiated by challenge with a single subdominant T epitope of La even though some self epitopes of La were efficiently tolerised. The pattern of autoantibody responses in primary Sjögren's syndrome was strongly influenced by HLA class II phenotype which we speculate controls activation of T cells recognising defined peptides from the La/Ro RNP. In this way, HLA class II alleles may be critical in influencing initiation and spreading of systemic autoimmune reactions. Molecular mimicry of such determinants by exogenous agents might readily initiate spreading of an autoimmune response in genetically susceptible hosts.

Amino Acid Sequence↗
PubMed1998

Spreading of the immune response from 52 kDaRo and 60 kDaRo to calreticulin in experimental autoimmunity.

Calreticulin (CR) is widely recognized as a new human autoantigen but there are conflicting data concerning its relationship with the Ro(SS-A) ribonucleoprotein (RNP). Recent evidence suggests that CR binds to 52 kDaRo (Ro52) by a protein/protein interaction and binds to hY RNA and rubella virus RNA. Other studies have shown that initiation of immunity to either Ro52 or 60 kDaRo (Ro60) can lead to reciprocal spreading of autoimmunity to Ro60 or Ro52, respectively, and induce anti-La autoantibodies in some strains of mice. These findings support a physical association of these polypeptides in Ro/La complexes. To test the hypothesis that CR is physically associated with Ro52 and/or Ro60 we examined the sera of Ro52-, Ro60- and La-immunized mice for intermolecular spreading to CR. Immune sera from BALB/c and C3H/HeJ mice immunized with recombinant 6xHis-mouse Ro52, 6xHis-human Ro60 or 6xHis-human La were tested for reactivity by ELISA and immunoblotting with a full-length human CR protein expressed as a soluble maltose binding protein fusion protein (CR-MBP). Five of the six Ro52-immunized C3H/HeJ mice sera and all six Ro60-immunized C3H/HeJ mice sera reacted with the CR-MBP (but not a MBP control) on ELISA. In the BALB/c group, the responder rate was lower with one in six of the Ro52-immunized and one in five of the Ro60-immunized mice spreading to CR. In contrast, none of the BALB/c or C3H/HeJ mice which was immunized with La showed evidence of a recruited anti-CR antibody response. Immunoblotting of the different recombinant proteins with immune sera from the C3H/HeJ mice confirmed the specificity of the initial and recruited antibody responses. The spreading of immunity from Ro52 and Ro60 to CR in Ro-immunized mice suggests that a subpopulation of CR or CR-like molecules must associate under certain circumstances with Ro52 and Ro60 polypeptides in vivo, possibly as Ro/CR complexes concentrated in surface membrane blebs of apoptotic cells. The lack of spreading to CR in La-immunized mice suggests that CR may be associated with a subpopulation of Ro particles from which La has already dissociated.

Animals↗
PubMed1996

Hierarchical self-tolerance to T cell determinants within the ubiquitous nuclear self-antigen La (SS-B) permits induction of systemic autoimmunity in normal mice.

Systemic autoimmune diseases are frequently associated with clustering of high titer autoantibody responses towards nuclear self-antigens. Little is known, however, about the extent of immune tolerance to the target nuclear antigens or the events leading to the complex autoantibody responses that are characteristic of systemic autoimmunity. To address these issues, we have examined the mouse immune response to La autoantigen (mLa) and the homologous human La antigen (hLa), which are components of the La(SS-B)/Ro(SS-A) ribonucleoprotein (RNP) complex targeted in systemic lupus erythematosus and primary Sjögren's syndrome. The findings reveal the presence of hierarchical T cell tolerance involving multiple autodeterminants within the La autoantigen expressed by normal H-2k and H-2a mice. At one end of this spectrum, there was no detectable T or B cell autoimmunity observed in mice that were immunized with the immunodominant mLa287-301 determinant, which differed by a single residue in its core sequence from the homologous but highly immunogenic human La288-302 determinant. Interestingly, the mLa287-301 peptide acted as an altered peptide ligand that specifically antagonized the activation of an hLa288-302-specific T cell hybridoma. In contrast to the tolerogenic mLa287-301 determinant, a range of autoimmune potential was identified among poorly tolerizing, subdominant self-peptides present within mouse La autoantigen. Notably, immunization of normal mice with the autologous subdominant La25-44 and La106-129 determinants resulted in limited or no detectable autoantibody response. In contrast, immunization with the subdominant mouse La13-30 determinant induced a proliferative T cell response associated with the appearance of specific autoantibodies recognizing multiple intrastructural (La) and intermolecular components (Ro) of the murine La/Ro RNP. The findings suggest how diversified autoimmunity might follow initiation of immunity to simple peptide mimics of poorly tolerogenic determinants that are present within ubiquitous self-antigens.

Amino Acid Sequence↗
PubMed1996

The immune response to 52-kDa Ro and 60-kDa Ro is linked in experimental autoimmunity.

Clustering of autoantibody specificities is a consistent finding in patients with systemic autoimmune diseases. Patients with Sjögren's syndrome frequently have autoantibodies to La, 60-kDa Ro(SS-A) protein (Ro60), and 52-kDa Ro(SS-A) protein (Ro52). In the case of anti-Ro60 and anti-La, there is evidence that these specificities occur together because of the physical association of the Ro60 and La proteins that form a ribonucleoprotein particle (RNP). Thus, the autoantibody response may spread from a single epitope to involve new epitopes located within other components of the RNP. The physical association of Ro52 with the Ro/La RNP has remained controversial, implying that Abs to Ro52 are not a consequence of intermolecular spreading and may be triggered independently of the anti-Ro60 response. To examine this relationship of the immune response to Ro52 and Ro60, mice were immunized with recombinant Ro52, Ro60, or La, and examined for autoantibody production. Immunization with Ro52 resulted in rapid, high titer Ab production to Ro52, followed 7 to 14 days later by lower titer autoantibody production to Ro60. Immunization with Ro60 led to anti-Ro60, which was also followed 7 to 14 days later by a lower titer anti-Ro52 response. Cross-reactivity of affinity-purified Abs from immune mouse sera was not observed. These observations suggest that the autoimmune responses to Ro60 and Ro52 are linked intrinsically, despite previous evidence suggesting they are not associated in vivo. The mechanism of linkage remains unclear, but the data are most consistent with some physical association of Ro52 and Ro60 allowing autoimmunization, presumably as a result of normal cell turnover or specific injury in vivo.

Animals↗
PubMed1996

Nonprecipitating anti-La(SS-B) autoantibodies in primary Sjögren's syndrome.

Anti-La(SS-B) precipitin-negative sera show a restricted epitope recognition and can be easily overlooked in routine laboratory testing. We have therefore determined the prevalence of nonprecipitating anti-La(SS-B) antibodies in patients with primary Sjögren's syndrome and studied their clinical and immunological associations. Clinical details were obtained from 68 patients with primary Sjögren's syndrome, and serum samples were examined by enzyme-linked immunosorbent assay using purified recombinant La, 60-kDa Ro, and 52-kDa Ro proteins and by counterimmunoelectrophoresis. Thirteen patients (19%) were identified with anti-La antibodies which were nonprecipitating. These patients had similar clinical findings to other groups of patients with Sjogren's syndrome, but had significantly lower rheumatoid factor and serum IgG levels than patients with anti-La precipitins. None of the patients with nonprecipitating anti-La antibodies had previously contained anti-La precipitins in their sera. Furthermore, they tended to have lower levels of antibodies directed against denatured 60-kDa Ro (but not 52-kDa Ro) compared with anti-La precipitin-positive patients. Patients with Sjögren's syndrome associated with nonprecipitating anti-La antibodies represent a stable serological and clinical subset in which there appears to be limited diversification of the autoimmune response to the Ro60 and La proteins of the Ro/La ribonucleoprotein.

Antibodies, Antinuclear↗
PubMed1996

Structural differences between the human and mouse 52-kD Ro autoantigens associated with poorly conserved autoantibody activity across species.

Anti-nuclear autoantibodies found in human autoimmune diseases frequently cross-react with homologous autoantigens in distant species, supporting the notion that autoantibodies target conserved functional domains. However, the 52-kD Ro(SS-A) protein is an exception, in that human autoantibodies are not known to recognize any equivalent antigen in the cells of rodents and other non-primate species. To understand this lack of cross-reactivity we have isolated cDNAs encoding the mouse 52-kD Ro molecule. The cDNA encoding mouse 52-kD Ro revealed an open reading frame of 470 amino acids, with 70% sequence identity to the human 52-kD Ro antigen. The putative leucine-zipper and zinc-finger motifs present in human Ro52 were conserved in the mouse protein. Recombinant mouse 52-kD Ro protein reacted with human autoantibodies by ELISA and immunoblot, but with approximately 10-fold lower reactivity than recombinant human 52-kD Ro protein under the same conditions. Detection of both human and mouse 52-kD Ro by immunoblot was dependent on antigen concentration which was limiting in the cell equivalents generally used in immunoblot assays. Differential chaotropic disruption of antibody binding suggested a lower avidity of human autoantibody binding to the mouse 52-kD Ro protein compared with the human antigen. Thus the poor reactivity of native mouse 52-kD Ro with human autoantibodies is associated with species divergence diffusely distributed throughout the primary structure of the 52-kD Ro molecule.

Amino Acid Sequence↗
PubMed1996

Rapid and sensitive detection of anti-Ro (SS-A) antibodies by indirect immunofluorescence of 60kDa Ro HEp-2 transfectants.

Anti-Ro (SS-A) antibodies are important diagnostic markers for primary Sjögren's syndrome and systemic lupus erythematosus, but their detection by indirect immunofluorescence (IF) in the diagnostic laboratory is hindered by the low cellular abundance of 60kDa Ro protein (Ro60). The approach we used to overcome this problem was to transfect and over-express the Ro60 gene into HEp-2 cells. In this study we have used a mixture of Ro60 transfectants and untransfected HEp-2 cells (HEp-Ro60) as a substrate for IF-antinuclear antibody (ANA) testing in a hospital laboratory. Screening of 240 routine serum specimens identified 14 Ro transfectant-positive sera which were confirmed by counterimmunoelectrophoresis (CIE); 3 of these sera were ANA-negative on untransfected cells and regular HEp-2. A comparison of HEp-Ro60 and regular HEp-2 showed strong concordance of the different ANA patterns between the 2 substrates. No increase in background staining was observed on the Ro transfectants when reacted with normal human sera. A comparison between HEp-Ro60 and CIE for 53 sera from patients with primary Sjögren's syndrome showed that HEp-Ro60 were a sensitive and specific substrate for detection of anti-Ro antibodies. Masking of positive Ro transfectants was observed rarely in sera containing multiple ANA specificities, but the Ro60 staining on these transfectants were unmasked at higher serum dilutions. We conclude that HEp-Ro60 are a suitable substrate for IF-ANA in the routine laboratory and that they have the additional advantage over regular HEp-2 slides of being able to detect anti-Ro in ANA-negative sera. HEp-RO60 are also a valuable confirmatory test for sera giving equivocal precipitin reactions or ELISA results.

Adult↗
PubMed1995

Cytoplasmic accumulation of the 52 kDa Ro/SS-A nuclear autoantigen in transfected cell lines.

The 60 kDa Ro/SS-A (Ro60) autoantigen is thought to reside predominantly in the nucleus; however, the intracellular localization of 52 kDa Ro/SS-A (Ro52) in normal cells is controversial, probably due to its low abundance. Therefore, we studied the intracellular expression and localization of the human Ro52 following transfection of a human Ro52 cDNA into cultured cell lines. Immunofluorescence staining of human (HEp-2) and mouse (LTA-5) cell transfectants with affinity-purified anti-Ro52 antibodies revealed that Ro52 antigen was most abundant in the cytoplasm and present to a lesser extent in the nucleus. This relative localization was supported by a preponderance of the Ro52 antigen in the cytoplasmic rather than nuclear fraction of enucleated cell lines detected by immunoblotting. In contrast to the Ro52 autoantigen, Ro60 and La autoantigens were mainly expressed in the nucleus of transfected cells under similar circumstances, indicating distinct localization of the intracellular pools of these autoantigens. The findings indicate that the Ro52 autoantigen lacks intrinsic signals required for nuclear localization and suggest that a significant pool of this autoantigen resides in the cytoplasm. Ro52 may therefore rely upon an association with other molecules for any specific nuclear transport.

Animals↗
PubMed1994

Transfection and overexpression of the human 60-kDa Ro/SS-A autoantigen in HEp-2 cells.

A full-length cDNA encoding human 60-kDa Ro/SS-A protein was transfected into and overexpressed in the human cell line HEp-2, with the aim of developing an improved reagent for indirect immunofluorescence (IF) detection of anti-Ro autoantibodies. Stable transfectants were analyzed by IF using a panel of 20 precipitin-positive anti-Ro human sera. Transfectants showed bright finely speckled nuclear and nucleolar staining. No surface membrane expression was detected despite marked overexpression of 60-kDa Ro. All human anti-Ro sera reacted with the transfectants with titers ranging from 1:320 to 1:40,960. The same sera tested on untransfected cells showed titers from negative (3 sera) to 1:160. These transfectants dramatically increase the sensitivity of IF testing (mean increase in titer of 41-fold) and allow detection of specific anti-Ro antibodies in samples negative or equivocal on untransfected cells. The staining patterns of antisera of other important specificities remained unaltered. In a study of sera from 22 patients with systemic lupus erythematosus, anti-60-kDa Ro autoantibodies were detected in all sera when tested on 60-kDa Ro-transfected HEp-2 cells; however, in 12 of 22 sera autoantibodies were undetectable by recombinant 60-kDa Ro ELISA. The 60-kDa Ro transfectants are a simple and sensitive method for detection of anti-Ro antibodies in patients with systemic rheumatic diseases.

Autoantibodies↗
PubMed1994

Effect of a preferred companion in modulating stress in adult female rhesus monkeys.

Using a counterbalanced design, seven adult female rhesus monkeys were removed from their social group and housed in a novel environment both alone and with a companion chosen on the basis of quantitative affiliative behaviors. Blood samples (n = 2) were collected from all study animals before the exposure to the novel environment, then at 2, 24, and 96 h thereafter for cortisol and immunological analyses. During both conditions, subjects showed evidence of stress as indicated by elevated cortisol concentrations and decreases in absolute numbers of lymphocyte subsets. There was no significant interaction between condition (alone vs. companion) and time in cortisol percent change and further planned post hoc analyses showed no significant between-condition differences for any of the postseparation time points. Similarly, no significant interaction was found between conditions and time for the absolute number of CD4+CD8-T cells, CD8+CD4- T cells, or CD20+CD2- B cells. However, planned post hoc comparisons showed that subjects in the companion condition exhibited a significantly smaller percent change from baseline than in the alone condition at the 24 h and 96 h sample periods in absolute numbers of CD4+CD8- and CD8+CD4- T cells. Results showed that adult female rhesus monkeys exhibited a profound stress response when removed from their social group to a novel environment and that recovery time of T cell subsets was significantly enhanced by the presence of a preferred companion.

Animals↗
PubMed1994

Removal of a trauma-inflicting alpha matriline from a group of rhesus macaques to control severe wounding.

Wounding in an 83-member group of rhesus macaques (Macaca mulatta) housed at the Yerkes Regional Primate Research Center Field Station became excessive to the point that intervention was deemed necessary. When observations indicated that three females from the group's alpha matriline were principally responsible for the wounding, the matriline (N = 7) was removed from the group. This study was conducted to document an atypical pattern of wounding in this group and to evaluate the effectiveness of removal as a procedure for controlling injuries. The aggression rates of 21 adult subjects and the wounds of all group members were recorded before and after the removal procedure and compared with those in a similar-sized group. Removing the alpha matriline did not alter aggression rates in the group or the rank order among the remaining matrilines. Aggression rates in the experimental group were also not significantly different from those in the comparison group before or after the removal. With the alpha matriline present, wounding levels in the group were significantly higher than those in the comparison group. After removal of the matriline, the frequency of wounds decreased significantly to levels similar to those of the comparison group. The pattern of excess wounding attributed to the extracted alpha females was idiosyncratic, involving removal of large patches of skin from the hindquarters of adult females or removal of the distal portion of the fingers, toes, or tail from juveniles.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗