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Organ-specific support in multiple organ failure: pulmonary support.

The catastrophic pulmonary failure that complicates management of patients with multiple trauma or sepsis syndrome with shock is recognizable to nearly all experienced surgeons. However, the spectrum of injury is broad, the distribution of lung injury may be heterogeneous within a single patient, and many patients will not develop acute respiratory distress syndrome (ARDS) even after a major predisposing insult. The lung responds stereotypically to many disparate insults, so a better conceptual construct of ARDS may be to consider it as one component of the multiple organ dysfunction syndrome. Support of oxygen transport with positive pressure ventilation and high levels of positive end-expiratory pressure, long the mainstay of pulmonary support, has been criticized for its predilection to cause barotrauma. Newer modes of ventilation, such as pressure-controlled, inverse-ratio ventilation and permissive hypercapnia, are under investigation but have not yet been reported with scientific rigor. However, pulmonary support extends beyond the support of gas exchange. Fluid management requires close attention so that the circulation is supported but lung water accumulation is minimized. Nosocomial pneumonia greatly increases the mortality rate in ARDS, but is difficult to diagnose and must be sought aggressively. Until recently, pharmacologic therapy has held little promise, but inhalation of very low concentrations of nitric oxide appear to decrease pulmonary vascular pressures and intrapulmonary shunt. It remains unknown whether nitric oxide is effective therapy for the underlying injury, or is simply treatment for certain manifestations.

Acute Disease↗

Novel organ-specific circulating cardiac autoantibodies in dilated cardiomyopathy.

To determine whether organ-specific cardiac autoantibodies are present in dilated cardiomyopathy, indirect immunofluorescence on human heart and skeletal muscle was used to test sera from 200 normal subjects and from 65 patients with dilated cardiomyopathy, 41 with chronic heart failure due to myocardial infarction and 208 with other cardiac disease. Three immunofluorescence patterns were observed: diffuse cytoplasmic on cardiac tissue only (organ-specific), fine striational on cardiac and, to a lesser extent, skeletal muscle (cross-reactive 1) and broad striational on both cardiac and skeletal muscle (cross-reactive 2). Cardiac specificity of the cytoplasmic pattern was confirmed by absorption studies with homogenates of human atrium, skeletal muscle and rat liver. Organ-specific cardiac antibodies (IgG; titer range 1/10 to 1/80) were more frequent in patients with dilated cardiomyopathy (17 [26%] of 65) than in those with other cardiac disease (2 [1%] of 208, p less than 0.0001) or heart failure (0 [0%] of 41, p less than 0.001) or in normal subjects (7 [3.5%] of 200, p less than 0.0001). Organ-specific cardiac antibodies were more common in patients with dilated cardiomyopathy and in those with fewer symptoms (8 of 15 in New York Heart Association functional class I versus 9 of 50 in classes II to IV, p less than 0.01) and more recent (less than 2 years) onset of disease (9 of 19 versus 8 of 46, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Antithyroid antibodies and the association with non-organ-specific antibodies in recurrent pregnancy loss.

OBJECTIVES: The purpose of our study was to evaluate the incidence of antithyroid antibodies and non-organ-specific antibodies in women who have had three or more recurrent spontaneous abortions. STUDY DESIGN: Sera from 45 women for the presence of antithyroid antibodies to thyroglobulin and thyroid peroxide and for the non-organ-specific autoantibodies to 6 phospholipids, 5 histones, and 4 polynucleotides were analyzed. Sera from 100 apparently health blood donors served as controls. RESULTS: The test results of 14 (31%) of 45 study subjects were positive for one or both antithyroid antibodies compared with 19 (19%) of controls. Five (11%) of 45 patients had positive test results for one or more non-organ-specific antibodies, and 4 (8%) of 45 had positive test results for the lupus anticoagulant by either activated partial thromboplastin, tissue thromboplastin time, or both. Only 3 (21%) of 14 subjects whose test results were positive for thyroid antibodies also demonstrated non-organ-specific autoantibodies. COMMENTS: The incidence of antithyroid antibodies in women who have had recurrent abortions appears not to be significantly increased compared with a normal random control population. Antithyroid antibodies do occur, however, with significantly greater frequencies in women with recurrent spontaneous abortions than non-organ-specific autoantibodies (p = 0.02). Organ-specific and non-organ-specific autoantibodies may serve as independent markers of risk for repeated pregnancy loss in patient populations where pregnancy loss is associated with abnormal autoimmune function.

Abortion, Habitual↗

Idiopathic dilated cardiomyopathy: lack of association between circulating organ-specific cardiac antibodies and HLA-DR antigens.

Organ-specific cardiac antibodies are serological markers of autoimmunity in dilated cardiomyopathy (DCM). HLA-DR4 and possibly DR5 are immunogenetic markers of susceptibility in DCM, but it is not known whether they are associated with autoantibody production. We studied the frequency of HLA-DR antigens and the presence of organ-specific cardiac antibodies in 80 DCM Caucasian patients from Northern Italy. HLA-DR typing was performed by serology; 289 healthy blood donors from the same region were tested as controls. HLA-DR frequencies in DCM were also compared with VIII International Workshop control data for Italy. Cardiac antibodies were detected by indirect immunofluorescence on human heart. Skeletal muscle was used to identify cross-reacting antibodies. The prevalence of cardiac antibodies in DCM was: organ-specific 34% and skeletal muscle cross-reactive 30%. The previously reported positive association between DCM and HLA-DR4 was confirmed using either the controls from the same region (21.25% vs 10.73% p = 0.02, relative risk = 2.30) or from all of Italy (21.25% vs 12.3%, p = 0.03). HLA-DR5 frequency was slightly but not significantly higher in DCM than in controls from the same region (46.25% vs 31.49% p = 0.02, relative risk of 1.87, p corrected = NS) or from all of Italy (46.25% vs 35.8% p = NS). HLA-DR3 frequency was lower in DCM than in controls from the same region (12.50% vs 29.41% p = 0.003, relative risk of 0.36, p corrected = 0.03). This negative association was not confirmed using the control data from the whole of Italy (12.50% vs 16.5% p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Immunochemical characterization of the adenine nucleotide translocator. Organ specificity and conformation specificity.

Antibodies have been prepared against purified preparations of the heart and kidney nucleotide translocator in the 'c'-conformation. The results show organ-specific antigenic determinants on the translocator proteins isolated from heart, kidney and liver although a partial cross-reactivity between these three proteins was demonstrable. The organ specificity was observed both with the solubilized and with the membrane-bound translocator protein indicating organ-specific determinants on exposed regions of the carrier. An organ-specific inhibition of the nucleotide transport in heart mitochondria by the heart carboxyatractylate-protein antiserum leads to the conclusion that the organ specificity is at least partially conditioned by the binding site for the substrate and/or the closely linked gate of the carrier protein. Apart from the organ specificity the results also demonstrate a specificity of the antibodies for the translocational conformations of the carrier: the 'c'-conformation stabilized in the carboxyatractylate-protein complex and the 'm'-conformation present in the bongkrekate-protein complex. However, after denaturation of the carboxytraktylate-protein and bongkrekate-protein complexes the binding of the anti-(carboxyatractylate-protein) antiserum to both inhibitor-protein complexes was nearly identical. The conformation specificity was also expressed by the inhibition of the conformation transition from the 'c'- to the 'm'- state. This side-specific inhibition of the nucleotide transport and the identical binding activity of the carboxyatractylate-protein antiserum against the denatured carboxyatractylate-protein and bongkrekate-protein complexes suggested that the conformation-specific antigenic determinants are topographic surface regions which are determined by the chain folding.

Animals↗

Urinary organ specific neoantigen. A potentially diagnostic test for colorectal cancer.

Urinary organ-specific neoantigen from colorectal cancer patients has been used to make a monoclonal antibody, BAC 18.1. In this study we assessed the potential of this antibody for the diagnosis of colorectal cancer. We evaluated binding in both urine and effluent samples and compared it with effluent carcinoembryonic antigen standardized for both volume (nanograms per milliliter) and protein. Urinary organ-specific antigen as detected by BAC 18.1 was significantly greater in 29 cancer patients (A405: 0.717 +/- 0.500) vs 27 controls [0.121 +/- 0.273 (P < 0.05)]. Considerable overlap of binding of BAC 18.1 was observed in the colonic effluent of patients with CRC (N = 13), adenomas (N = 26), inflammatory bowel disease (N = 8), or having a normal colonoscopic examination (N = 24). CEA levels (nanograms per milliliter) were significantly elevated in the effluent samples of patients with a past history of colorectal cancer, as compared to that of normal individuals (P < 0.05). The presence of the M(r) 30,000 organ-specific neoantigen in colonic effluent was also demonstrated by western blot. Organ-specific neoantigen originates in the colon and is excreted into the urine, so the BAC 18.1 binding levels in the urine may be a diagnostic aid for CRC.

Adult↗

Organ-specific circulating heart autoantibodies in Chagas' cardiomyopathy: exploratory study.

Chagas' disease can evolve to a chronic phase with cardiomyopathy that may include autoimmune mechanisms, among others. Recently an organ-specific anti-heart muscle antibody was detected in idiopathic cardiomyopathy, using human heart muscle as antigen. We decide to standardize an indirect immunofluorescence assay using rat organs in order to evaluate frequency of organ-specific anti-heart antibodies in chagasic cardiomyopathy. We tested 18 patients with chagasic cardiomyopathy for serum organ-specific anti-heart muscle antibodies. Nine patients were positive for organ-specific anti-heart antibodies (positive in heart muscle but negative in tongue muscle) and one was positive for non-organ-specific anti-heart muscle antibodies (positive in both heart and tongue muscle). We conclude that organ-specific anti-heart muscle antibodies can be detected using rat organs as antigens. Organ-specific anti-heart muscle antibodies are present in patients with chagasic cardiomyopathy.

Adult↗

Organ-specific chemotactic factors present in lung extracellular matrix.

The preferential colonization of a distant organ by a circulating tumor cell (organ specific metastasis) may be regulated by chemotactic factors present within the extracellular matrix of the host organ. Organ-specific extracellular matrix was prepared from murine kidney and lung by high salt extraction and DNAase/RNAase digestion. A soluble protein fraction (S2) from each of the matricies was obtained by 4 M guanidine extraction and was tested for organ-specific chemotactic activity in a modified Boyden chamber. The lung colonizing B16-F10 and B16-BL6 tumor cell lines demonstrated organ-specific motility only toward the lung extract. The low metastasizing B16 parental line and liver colonizing B16-L4b line showed no preference for either lung or kidney. The lung activity resolves into five fractions by gel filtration chromatography, with the highest activity eluting at Mr approximately 71,000. Chemotactic factors present in lung extracellular matrix may regulate the preferential colonization of an organ by stimulating the migration of tumor cells in a specific manner. These factors may be released during the degradation of the extracellular matrix.

Cell Line↗

Organ-specific mucin antigens and gastrointestinal carcinogenesis.

Organ-specific mucin antigens detected by polyclonal antibodies were first used to characterize abnormal differentiation of gastrointestinal (GI) adenocarcinomas (1,2). These mucin tumour markers can thus be useful as criteria for evaluating the degree of gastric or intestinal differentiation of gastric carcinomas. In addition, some of these mucin antigens are expressed early during GI carcinogenesis where they are associated to premorphological abnormalities (3-5). Consequently, these markers are of importance for studying genetic changes occurring in precancerous mucosa, in which cancer cell transformation can occur. Finally, recent observations have pointed out a putative value of these mucin antigens for screening high risk populations for GI cancers. First of all, we shall define the words: mucin, mucin antigen (or epitopes) and organ-specificity before described abnormal antigen expression during GI carcinogenesis in the cancerous and in the precancerous mucosae and specially concerning their association with premorphological abnormalities.

Adenocarcinoma↗

Organ-specific cardiac antibodies: serological markers for systemic hypertension in autoimmune polyendocrinopathy.

Circulating organ-specific autoantibodies are serological markers of destruction or impairment of the relevant endocrine tissue cells and may be associated with abnormal hormone levels with or without clinical evidence of overt disease. We sought organ-specific cardiac antibodies in patients with autoimmune polyendocrinopathy because of increasing evidence that the heart has endocrine characteristics (secretion of atrial natriuretic peptide [ANP] and other peptide hormones). Serum samples from 166 patients with polyendocrinopathy, 80 with autoimmunity confined to one gland, and 200 healthy blood donors were tested for these antibodies by means of immunofluorescence on human heart. Skeletal muscle was used to identify cross-reacting antibodies. Organ-specific cardiac antibodies were detected in significantly more of the patients with autoimmune polyendocrinopathy (28 [17%]) than of those with autoimmunity confined to one gland (1 [1%]) or of normal subjects (7 [3.5%]; p = 0.0001). Among the patients with autoimmune polyendocrinopathy, the prevalence of systemic hypertension was higher in those with cardiac autoantibodies than in those without (5/28 [18%] vs 2/80 [3%]; p = 0.01); the same was true for a family history of hypertension (11 [42%] vs 5 [7%]; p = 0.0001). There were no significant differences in mean basal or stimulated ANP concentrations between patients with or without antibodies or between patients and controls. 5 of the 22 antibody-positive patients had ANP concentrations outside the normal range, but these disturbances were not associated with systemic hypertension or a family history of the disorder. Patients with autoimmune polyendocrinopathy can have organ-specific cardiac antibodies, which may represent novel serological markers for an autoimmune form of systemic hypertension in the absence of overt cardiac disease.

Adult↗

Organ specificity of metastatic tumor colonization is related to organ-selective growth properties of malignant cells.

In cancers such as malignant melanoma, tumor spread or metastasis occurs preferentially to certain organ sites. Mouse B16 melanoma cell sublines that have been selected sequentially in vivo for enhanced blood-borne colonization of lung, brain, or ovary were tested for their survival and growth stimulation in vitro by soluble factors released from suspensions of mouse lung, brain, liver, ovary or kidney tissues. In general, the growth rate of lung-colonizing B16 cells was stimulated by high concentrations of lung-tissue-derived factors significantly more than by factors from the other tissues, whereas the growth rate of ovary-colonizing B16 cells was stimulated by ovary or lung-tissue-derived factors significantly more than by factors from the other tissues. In contrast, the growth of brain-colonizing B16 cells was not stimulated by factors released from brain tissue. When it occurred, stimulation of B16 cell growth by factors released from mouse organ tissues was dose-dependent. Liver tissue factors, and at high concentrations kidney tissue factors, inhibited cell growth of the B16 sublines, an inhibition correlating with the low potential of B16 cells to colonize liver and kidney in vivo. In addition to preferential target-organ cell adhesion found previously with B16 sublines (Nicolson et al., 1985a), the present results suggest that metastasis to specific organ sites is also dependent on the survival and growth of B16 cells affected by soluble organ-derived factors.

Animals↗

Partial purification of organ-specific neoantigens from human colon and breast cancer by affinity chromatography with human tumour-specific gamma-globulin.

Organ-specific neoantigens (TA) shed from the tumours of patients with metastatic breast or colon cancer and which had filtered into the urine were partially purified by a combination of physicochemical methods and affinity chromatography. TA activity of the isolated materials was monitored by the blocking Tube LAI assay. Urinary protein was precipitated by 80% saturated ammonium sulphate. Albumin was removed by affinity chromatography with blue Sepharose CL-6B. Affinity columns of human IgG were prepared from sera of patients whose leucocytes were LAI+ to the breast- or colon-cancer extracts. The anti-breast-TA affinity column bound the TA in the urine of patients with metastatic breast cancer but not that of patients with metastatic colon cancer. The TA in urine of patients with metastatic colon cancer was bound by the anti-colon-TA affinity column. Analysis by SDS PAGE revealed that the isolates with and without TA activity were composed mostly of urinary protein which had bound nonspecifically to the human IgG affinity columns. With an affinity column of anti-NHS and Protein A, some of the contaminants were removed, to reveal SDD PAGE unique bands at about 38,000 and 12,000 mol. wt in the isolate with breast-TA activity. Rabbit antisera, raised to the material that had bound nonspecically to the anti-breast-TA affinity column, were used as an anti-nonspecific affinity column to remove the contaminants in the isolates from the affinity columns of anti-breast TA and anti-colon TA. After passage through the anti-nonspecific affinity column, the material that contained the putative breast or colon cancer TA revealed a unique band at about 38,000-40,000 mol. wt and residual fine bands at about 25,000-30,000 mol. wt. Both the control material and material with TA activity had similar bands at about 25,000 and 50,000 mol. wt. The specific activity of the putative colon or breast TAs, as measured by the blocking Tube LAI assay, was increased from about 30 to 5000-10,000 u/mg, a 125-400-fold enrichment.

Antigens, Neoplasm↗

Interleukin 2 suppression of a murine bladder cancer implanted into kidney, bladder and skin; its organ specificity.

Little is known about organ associated tumor response to systemic interleukin 2 (IL2) therapy. The effect of IL2 on bladder cancer growth in the skin and in the genitourinary tract was investigated. C3H mice were implanted with the syngeneic transitional cell carcinoma, MBT-2, intradermally (i.d.), beneath the left renal subcapsular area, and in one experiment, simultaneously in the bladder. IL2 (human recombinant form; Biogen Research Co) was given i.p. at 5000 U thrice daily for 5 consecutive days commencing on Day 3, or for 10 to 11 days commencing on Day 10 with some doses omitted at signs of toxicity. For comparison, mice bearing 3-d and 10-d tumors in the skin and subcapsular kidney were treated with chemotherapy (cisplatin, 6 mg./kg. X 3; mitomycin C, 3 mg./kg. X 3; cyclophosphamide, 75 mg./kg. X 1). IL2 therapy mediated growth suppression of 10-d tumors in the genitourinary organs and skin at a similar rate. In contrast to IL2, systemic chemotherapy mediated tumor suppression in an organ specific manner; renal subcapsular tumors responded to the chemotherapy, whereas i.d. tumors were insensitive. Three-day tumors (both i.d. and renal subcapsular tumor) responded relatively well to each treatment compared to 10-d tumors. These data suggest that in systemic immunotherapy with IL2, anatomic location of the tumor is less important for inducing an antitumor response than in chemotherapy.

Animals↗

Chromosome-specific organization of human alpha satellite DNA.

Restriction endonuclease analysis of human genomic DNA has previously revealed several prominent repeated DNA families defined by regularly spaced enzyme recognition sites. One of these families, termed alpha satellite DNA, was originally identified as tandemly repeated 340- or 680-base pair (bp) EcoRI fragments that hybridize to the centromeric regions of human chromosomes. We have investigated the molecular organization of alpha satellite DNA on individual human chromosomes by filter hybridization and in situ hybridization analysis of human DNA and DNA from rodent/human somatic cell hybrids, each containing only a single human chromosome. We used as probes a cloned 340-bp EcoRI alpha satellite fragment and a cloned alpha satellite-containing 2.0-kilobase pair (kbp) BamHI fragment from the pericentromeric region of the human X chromosome. In each somatic cell hybrid DNA, the two probes hybridized to a distinct subset of DNA fragments detected in total human genomic DNA. Thus, alpha satellite DNA on each of the human chromosomes examined--the X and Y chromosomes and autosomes 3, 4, and 21--is organized in a specific and limited number of molecular domains. The data indicate that subsets of alpha satellite DNA on individual chromosomes differ from one another, both with respect to restriction enzyme periodicities and with respect to their degree of sequence relatedness. The results suggest that some, and perhaps many, human chromosomes are characterized by a specific organization of alpha satellite DNA at their centromeres and that, under appropriate experimental conditions, cloned representatives of alpha satellite subfamilies may serve as a new class of chromosome-specific DNA markers.

Animals↗

Organ-specific autoantibodies with muscle weakness.

The motor unit includes the anterior horn cell, the motor axon and the muscle fibers it innervates, and the neuromuscular junction. Diseases of the motor unit usually present with weakness. Diagnosis of motor unit disorders involves the history, physical examination, electrophysiologic studies of nerve and muscle, and blood testing for creatine kinase, genetic disorders, and autoantibodies. Antibody testing is often useful for the identification of specific immune-mediated motor unit disorders. Identification of these disorders is important because they are often treatable. Antibodies with disease specificity include those directed against autoantigens with and without organ specificity. Several autoantibodies to non-organ-specific antigens are associated with subgroups of immune myopathies. Organ-specific autoantibodies in motor unit disorders with weakness occur in myasthenia gravis, especially with thymoma, a myopathy associated with Waldenstrom's macroglobulinemia, Lambert-Eaton myasthenic syndrome, and multifocal motor neuropathy.

Autoantibodies↗

All the adult stem cells, where do they all come from? An external source for organ-specific stem cell pools.

Stem cells can self-renew and maintain the ability to differentiate into mature lineages. Whereas the "stemness" of embryonic stem cells is not discussed, the primitiveness of a stem cell type within adult organisms is not well determined. Data presently available are either inconclusive or controversial regarding two main topics: maintenance or senescente of the adult stem cell pool; and pluripotentiality of the cells. While programmed senescence or apoptosis following uncorrected mutations represent no problem for mature cells, the maintenance of the stem cell pool itself must be assured. Two different mechanisms can be envisaged for that. In the first mechanism, which is generally accepted, stem cells originate during ontogeny along with the organ which they are responsible for, and remain there during all the lifespan of the organism. Several observations derived from recent reports allow the suggestion of a second mechanism. These observations include: organ-specific stem cells are senescent; adult stem cells circulate in the organism; stem cell niches are essential for the existence and function of stem cells; adult stem cells can present lineage markers; embryo-like, pluripotent stem cells are present in adult organisms, as shown by the development of teratomas, tumors composed of derivatives of the three germ layers; and the fact that the gonads may be a reservoir of embryo-like, pluripotent stem cells in adult organisms. The second mechanism for the maintenance of adult stem cells compartments implies a source external to the organ they belong, consisting of pluripotent, embryo-like cells of unrestricted life span, presenting efficient mechanisms for avoiding or correcting mutations and capable to circulate in the organism. According to this model, primitive stem cells exist in a specific organ in adult organisms. They undergo asymmetrical divisions, which originate one "true" stem cell and another one which enters the pool of adult stem cells, circulating through the entire organism. Upon signals liberated by organ-specific niches, this cell becomes activated to express lineage-specific genes, homes to that particular organ and repopulates its stem cell compartment, differentiating thus in what is seen as the organ-specific stem cell. The gonads are the natural candidates for homing the primitive stem cells in adult organisms. The model proposed in this work for the maintenance of organ-specific stem cell pools from an external source, represented by primitive, embryo-like germinal stem cells present in testes and ovaries, may contribute to the more complete understanding of this complex issue.

Adult↗

[Diagnostic imaging in polytrauma: comparison of radiation exposure from whole-body MSCT and conventional radiography with organ-specific CT].

PURPOSE: To compare the radiation dose of whole-body multislice CT (MSCT) and conventional radiography with organ-specific CT in polytrauma. MATERIALS AND METHODS: The whole-body MSCT encompassing brain, neck and midface, chest, abdomen and pelvis was performed on a Somatom Volume Zoom (Siemens). Conventional radiography consisted of chest and cervical, thoracic and lumbar spine in two views as well as pelvis (Polymat, Siemens). Three combinations of organ specific CT were chosen: CT examination of (1) head and cervical spine, (2) head, cervical spine and chest, (3) head, cervical spine and abdomen. The effective doses of whole-body MSCT and conventional radiography with organ-specific CT were calculated. RESULTS: Effective doses were 20 mSv for whole-body MSCT, 2 mSv for conventional x-ray, and 5 mSv for combination (1), 8 mSv for combination (2) and (3) 16 mSv for combination (3) of the organ-specific CT. The ratio of radiation dose between whole-body MSCT and radiography was 10 : 1. This ratio was reduced to 3 : 1, 2 : 1 and 1 : 1 when a combination of radiography and CT was performed. CONCLUSIONS: Whole-body MSCT in polytrauma compared to conventional radiography with organ-specific CT induces a threefold increased dose in unfavorable situations and no increased dose in favorable situations. Nevertheless, routine use of whole-body MSCT should be critically evaluated and should be adapted to the clinical benefit.

Humans↗

Spontaneous development of organ-specific autoimmune lesions in aged C57BL/6 mice.

We have shown that spontaneously occurring, organ-specific autoimmune lesions develop in aged C57BL/6 mice of both sexes, especially in 24-month-old senescent mice. The inflammatory lesions were found in the multiple organs such as salivary gland, kidney, pancreas, lung, and liver, associated with ageing process. Organ-specific autoimmune lesions first appeared in 6-month-old C57BL/6 mice, and were aggravated with advancing age. In contrast, significant inflammatory changes did not develop in the thyroid, stomach, testis, ovary, and prostate in aged C57BL/6 mice. The incidence and severity of organ-specific autoimmune lesions in this strain of non-autoimmune mice increase with advance of age. The most severely affected lesion was sialadenitis developed in the submandibular salivary gland of aged mice, and a significant difference between male and female mice was noted only in the salivary gland. The infiltrating cells within the lesions of multiple organs consisted mainly of Thy 1.2+ and L3T4+ cells. Autoantibodies were detected in the sera of the mice with each corresponding organ-specific autoimmune lesions.

Aging↗