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PubMed2006

Anti-chromatin (anti-nucleosome) antibodies.

Chromatin is the native complex of histones and DNA found in the cell nucleus of eukaryotes. The fundamental subunit of chromatin is the nucleosome, which is composed of a core particle in which 146 bp of helical DNA are wrapped around an octamer made up of two H2A-H2B dimers that surround an H3-H4 tetramer. The prevalence of anti-chromatin (nucleosome) antibodies in systemic lupus erythematosus (SLE) varies from 50% to 90%, being similar to that of the classical positive LE cell. The presence of these antibodies can be used, in conjunction with clinical findings and other laboratory tests, to help in the diagnosis of SLE and drug induced lupus. The presence of anti-chromatin antibodies has also been linked to glomerulonephritis in SLE patients.

Animals↗
PubMed2000

Frequent expression of sialyl Le(a) in human esophageal squamous cell carcinoma.

Sialyl Le(a) antigen (CA19-9), a member of a family of high molecular weight glycoproteins, was originally described as a gastrointestinal- and pancreatic-specific tumor marker. Recent studies have demonstrated that sialyl Le(a) is a ligand for E-selectin and may play an important role in tumor metastasis. However, expression patterns of sialyl Le(a) have not yet been established in human esophageal carcinomas. In this study, we examined sialyl Le(a) expression and its histopathological localization in human esophageal squamous cell carcinoma. Sialyl Le(a) immunoreactivity was detected in 28 (51.9%) of the 54 esophageal squamous cell carcinomas, regardless of the depth of tumor invasion, vascular invasion or lymph nodal status. In 13 cases (29.5%), significant sialyl Le(a) expression was detected not only in the intramucosal carcinoma components, but also in the invasive carcinoma components. These observation suggested that sialyl Le(a) expression is associated with early-stage cancer progression.

CA-19-9 Antigen↗
PubMed1977

Ultrastructural appearance and morphogenesis of renal glomerular hematoxylin bodies.

The fine morphology of hematoxylin bodies--structures which, by light microscopy, are considered to be pathognomonic for systemic lupus erythematosus--is described in renal glomeruli. These bodies are highly pleomorphic and are predominantly of cellular origin. The nuclear components, which are responsible for the characteristic tinctorial properties, appear as aggregates of clumped chromatin and/or irregular masses of finely granular, moderately dense, lobulated material, generally enveloped by membranes. The cytoplasmic components consist of a multitude of vesicles, vacuoles, degenerating granules, and glycogen. Hematoxylin bodies are usually contained within the bounderies of mesangial cells. A transition from circulating leukocytes to typical hematoxylin bodies could be demonstrated. It is suggested that the changes in leukocytes which culminate in hematoxylin bodies are intiated by the action of antinuclear antibodies and also possibly by the ingestion of immune complexes. This proposed appearance and morphogenesis of hematoxylin bodies is in general agreement with a few previously published investigations on these structures and also with the in vitro counterpart, the lupus erythematosus (LE) cell.

Antibodies, Antinuclear↗
PubMed1997

Intracellular association between UDP-glucose:glycoprotein glucosyltransferase and an incompletely folded variant of alpha1-antitrypsin.

Genetic variants of human alpha1-antitrypsin unable to fold into the native structural conformation are poorly secreted from hepatocytes. The molecular chaperone calnexin coimmunoprecipitates with secretion-incompetent variant null(Hong Kong) retained in stably transfected mouse hepatoma cells (Le, A., Steiner, J. L., Ferrell, G. A., Shaker, J. F., and Sifers, R. N. (1994) J. Biol. Chem. 269, 7514-7519). Mobilization of intracellular Ca2+ stores with metabolic poisons diminished interaction with calnexin and coincided with coimmuoprecipitation of a 150-kDa protein (p150). Mobilization of endoplasmic reticulum lumenal Ca2+ with thapsigargin, an inhibitor of the microsomal Ca2+ATPase, gave a similar result. Coimmunoprecipitation of p150 was specifically disrupted in response to incubation of the cell lysate with exogenous CaCl2. Finally, in ECL Western blotting, p150 was recognized by polyclonal antiserum against UDP-glucose:glycoprotein glucosyltransferase that likely functions in glycoprotein folding and quality control (Sousa, M. C., Ferrero-Garcia, M. A., and Parodi, A. J. (1992) Biochemistry 31, 97-105). The data are consistent with a model in which perturbation of endoplasmic reticulum Ca2+ results in a stable physical association between unfolded human alpha1-antitrypsin and UDP-glucose:glycoprotein glucosyltransferase.

Animals↗
PubMed2000

Induction of apoptosis by arsenic trioxide and hydroxy camptothecin in gastriccancer cells in vitro.

AIM:To study the effects of arsenic trioxide and HCPT on dif ferent degrees of differentiated gastric cancer cells (SGC-7901, MKN-45, MKN-28) with respect to both cytotoxicity and induction of apoptosis in vitro.METHODS:The cytotoxicity of As(2)O(3) and HCPT on gastric cancer cells was det ermined by MTT assay.Morphologic changes of apoptosis of gastric cancer cells were observed by light microscopy and transmission electron microscopy.Apoptosis and cell cycle changes of gastric cancer cells induced by HCPT and As(2)O(3) we re investigated by TUNEL method and flow cytometry.RESULTS:As(2)O(3) and HCPT had remarkable cytotoxic effects on different degrees of differentiated gastric cancer cells. The IC(50) of As(2)O(3) on well differentiated gastric cancer cell MKN-28, moderately differentiated gastric cancer cell SGC-7901, and poorly differentiated gastric cancer cell MKN-28 were 8.91 &mgr;mol/L, 10.57 &mgr;mol/L, and 11.65&mgr;mol/L, respectively. The IC(50) of HCP T on MKN-28, SGC-7901, and MKN-45 were 9.35 mg/L, 10.21 mg/L,and 12.63 mg/L respectively after 48 h treatment. After 12 h of exposure to both drugs, gastric cancer cells exhibited morphologic features of apoptosis, includ ing cell shrinkage,nuclear condensation, and formation of apoptotic bodies. A ty pical subdiploid peak before G(0)/G(1) phase was observed by flow cytometry. The apoptotic rates of SGC-7901, MKN-45, and MKN-28 were 13.84%, 22.52%, and 9.68%, respectively after48 h exposure to 10&mgr;mol/L As(2)O(3). The apoptotic ra tes of SGC-7901, MKN-45, and MKN-28 were 21.88%, 12.35%, and 30.26%, resp ectively after 48 h exposure to 10 mg/L HCPT. The apoptotic indice were 7%-15% a s assessed by TUNEL method. The effect of As(2)O(3) on SGC-7901 showed remarkab le cell cycle specificity, which induced cell death in G(1) phase, and blocked G(2)/M phase.HCPT also showed a remarkable cell cycle specificity, by inducing cell death and apoptosis in G(1) phase and arrest of proliferation at Sphase.CONCLUSION:As(2)O(3) and HCPT exhibit significant cytotoxicity on gastric canc er cells by induction of apoptosis. As(2)O(3) and HCPT might have a promising pr ospect in the treatment of gastric cancer, which needs to be further studied.

Journal Article↗
PubMed2000

Is there any association between Peyronie's disease and serum collagen markers?

Several theories regarding the pathogenesis of Peyronie's disease have been investigated under many clinical conditions. We have investigated the association of Peyronie's disease with the most common markers of collagen disease. Several serum markers of collagen disease (mucoproteins, C-reactive protein, antinuclear antibody, rheumatoid factor, lupus erythematosus cells, proteinograms) of 30 patients with Peyronie's disease were compared with those obtained from 30 patients, matched for age, with other urological conditions unrelated to the penis. Mucoproteins were altered in 66.7% of patients of the Peyronie's disease group and in 46.7% of the control patients (P>0.05). C-reactive protein was altered in 23.3% of the Peyronie's disease patients and in 13.3% of the control patients (P>0.05). Antinuclear antibody (ANA) was reactive in 16.7% of the tested group and in 6.7% of the control group (P>0.05). The rheumatoid factor was elevated in 6.7% of the patients from both groups (P>0.05). LE cells were normal in all the patients in our study. No statistical significance between the two groups was found in the protein electrophoresis test. Only the Waaler-Rose test (rheumatoid hemagglutination test) was statistically significant in our study (P<0.05). We have not found any significant association between the serum markers of collagen diseases in patients with Peyronie's disease, except the rheumatoid hemagglutination test (Waaler-Rose).

Adult↗
PubMed1984

Potential for endotoxin-activated Kupffer's cells to induce microvascular thrombosis.

The potential contribution of Kupffer's cells, le, hepatic macrophages (HM phi s) to the diffuse microvascular thrombosis seen during septicemia was evaluated by measuring the ability of a homogeneous population of explanted HM psi s to express procoagulant activity (PCA). Addition of as little as 100 ng/mL of endotoxin stimulated a 30-fold increase over control values of PCA within eight hours. This PCA was membrane associated and functioned externally to the macrophage. Sensitivity to heat (56 degrees C) and diisopropyl fluorophosphate differentiated this PCA from typical tissue thromboplastin activity. The increase in PCA was blocked by pretreatment with warfarin sodium (a phytonadione blocker) and could be restored by addition of phytonadione. These studies showed that endotoxin induces in HM psi s a significant increase in PCA, functioning like coagulation factor VII. These results support a role for Kupffer's cells in the initiation of microvascular thrombosis in endotoxemia.

Animals↗
PubMedDate not supplied

[Seronegative systemic lupus erythematosus (author's transl)].

Seronegative systemic lupus erythematosus is defined as a SLE devoided of antinuclear factors as well as of LE cells when at least 4 out of the 14 ARA criteria are present. We describe herein two case reports and review previous literature concerning this topic. This kind of SLE is characterized by a high incidence of Raynaud's disease, photosensitivity, oral ulcerations, alopecia and perhaps less frequent kidney and central nervous system involvement. The hypotheses about the absence of ANF are discussed. The awareness of such a SLE ("devoided of ANF rather than" seronegative") is to be kept in mind from a chemical, therapeutic and pathophysiologic point of view.

Adult↗
PubMed1975

Hydralazine-induced lupus erythematosus-like syndrome.

A reversible syndrome resembling systemic lupus erythematosus and induced by hydralazine hydrochloride therapy is a well-recognized phenomenon in adults but does not seem to have been reported in children. A 9-year-old girl had fever, arthralgias, modest joint swelling, splenomegaly, antinuclear antibodies (ANAs), anitbodies against native and denatured DNA, and positive LE cell preparations after nine months of hydralazine hydrochloride therapy, 120 mg/day. Clinical findings returned to normal within four weeks of discontinuing the drug therapy, and serological abnormalities disappeared after 11 months. Like previously reported patients, the child is white and has a slow acetylation phenotype. It is not known whether children receiving hydralazine are as susceptible to this complication as adults. Periodic ANA determinations may be advisable for children receiving hydralazine, especially if they are white and have a slow acetylation phenotype.

Acetylation↗
PubMed1978

Multiple myeloma complicating the course of seronegative systemic lupus erythematosus.

A patient with a 20-year history of clinical systemic lupus erythematosus (SLE) who later developed multiple myeloma is described. SLE was diagnosed on the basis of a butterfly rash, photosensitivity, nondeforming arthritis, pleuropericarditis, and alopecia. However, the patient has never had LE cells, antinuclear antibody, or depressed complement. The patient was treated with intermittent courses of corticosteroids over a 20-year period with good results. Multiple myeloma, diagnosed by bone marrow biopsy, has responded favorably to therapy with L-phenylalanine mustard and prednisone.

Adrenal Cortex Hormones↗
PubMed1981

Hereditary deficiency of the third component of complement in two sisters with systemic lupus erythematosus-like symptoms.

We observed two sisters with lupus-like syndrome with homozygous C3 deficiencies. A 19-year-old woman and her 15-year-old sister developed malar rash, arthralgia, and photosensitivity, but antinuclear antibodies and LE cell preparations were negative. The older sister experienced recurrent bronchitis in her childhood, but the younger sister had no recurrent infections. Serum C3 was not detected immunochemically in either sister, and total complement activity and C3 hemolytic activity were extremely low.

Adolescent↗
PubMedDate not supplied

Hepatic injury associated with the use of nitrofurans: a clinicopathological study of 52 reported cases.

Fifty cases of nitrofurantoin-associated hepatic injury and two cases of nifurtoinol (hydroxymethylnitrofurantoin)-associated hepatic injury reported to the Netherlands Centre for Monitoring of Adverse Reactions to Drugs were analyzed in detail. In 38 cases, a causal relationship was considered likely [i.e., "highly probable" (n = 4), "probable" (n = 23) or "possible" (n = 11)]. In 25 cases, hepatic injury was of the acute type whereas 13 cases presented a chronic type of reaction. Both types were more common in the elderly. Eighty per cent of the acute reactions appeared within the first 6 weeks of treatment and were sometimes accompanied by fever (28%), rash (12%) and eosinophilia (16%). Biochemically, the pattern was mainly hepatocellular (32%), whereas mixed cholestatic-hepatocellular (4%) and cholestatic (4%) patterns were uncommon. Although mild to moderate liver enzyme elevations (60%) were common, these were primarily symptomatic. The reaction was fatal in one "acute" and one "chronic" case. In the chronic cases, nuclear (82%) and smooth muscle (73%) antibodies and LE cells (50%) were frequently present. HLA typing showed no increase of the HLA B8 or HLA DRw3 haplotype. HLA DR2 (56%) and HLA DRw6 (56%) were more frequent than in controls (both 29%), but this was not statistically significant. Histology showed mainly necrosis, varying from spotty to massive, in the acute cases and a pattern consistent with chronic active hepatitis in the chronic cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1989

Torticollis and blepharospasm in systemic lupus erythematosus.

A case of torticollis and blepharospasm as the major manifestation of neurological involvement in systemic lupus erythematosis (SLE) is presented. A 56-year-old woman presented with blepharospasm in February 1985 and with torticollis in April 1985. She was diagnosed as having SLE in 1966, on the basis of positive LE cells, when she presented with fever and joint pains. There was no evidence that she had ever been on major tranquilizers. An attempt has been made to correlate the level of antibody titres and exacerbation of these movements with response to steroids. The possibility of an association between blepharospasm, torticollis, and autoimmune disorders has recently been considered.

Blepharospasm↗
PubMed1987

Immunological abnormalities in a patient with lysinuric protein intolerance.

We report an 8-year-old girl with lysinuric protein intolerance and immunological abnormalities including impaired function of lymphocytes, the presence of LE cells, antinuclear antibodies, and hypergammaglobulinaemia. These abnormalities have not been reported before and may be due to an amino acid imbalance or protein malnutrition in cells or tissues. The coincidence of a pre-stage of systemic lupus erythematosus (SLE) and LPI is not excluded.

Amino Acid Metabolism, Inborn Errors↗
PubMed1981

Testing clinical criteria for systemic lupus erythematosus in other connective tissue disorders.

The American Rheumatism Association (ARA) clinical criteria have been tested in systemic lupus erythematosus (SLE), progressive systemic sclerosis, polyarteritis nodosa and polymyositis/dermatomyositis. Hospital admissions from a defined population over the same period were studied. Increased weighting of the scores for the features showing the greatest specificity is suggested. These features are discoid lupus, alopecia, photosensitivity, LE cells and/or antinuclear antibody (ANA) and oral ulcers. Inclusion of histological evidence increased the sensitivity of the SLE scores.

Adolescent↗
PubMed1996

Idiopathic portal hypertension associated with high serum titer of autoantibodies and liver dysfunction.

Idiopathic portal hypertension (IPH) is a condition marked by unexplained portal hypertension. Although a number of immunological abnormalities occur in patients with IPH, liver function is usually normal. We experienced an unusual case of IPH in a 49-year-old woman, who had pronounced splenomegaly. Laboratory data revealed pancytopenia, hypergammaglobulinemia, and liver dysfunction. Antinuclear antibodies were positive, with high titer at 1280 dilutions of sera. LE cell phenomena were also positive. Histological examination of biopsied liver showed only mild changes, but portal venous pressure was markedly elevated, at 38 cm H2O. This case was thus characterized by both a high serum titer of autoantibodies and liver dysfunction.

Autoantibodies↗
PubMed1987

Chronic active hepatitis with histological features of primary biliary cirrhosis.

A 51-year-old woman was evaluated because of Raynaud's phenomenon, Sjögren's syndrome, and general malaise. There was neither skin itching nor jaundice. Endoscopic retrograde cholangiopancreatography showed a normal extrahepatic as well as intrahepatic biliary tree. Serum GOT and GPT fluctuated with episodes of marked increases. The alkaline phosphatase was slightly increased and total cholesterol was normal. There were marked increases of IgG and IgM. AMA was positive at a titer of 1:320, which was measured by an indirect immunofluorescence method. PBC-specific AMA (anti-M2) was positive, but mixed-form AMA (anti-M4) negative. An LE-cell test, ASMA, ANA, and anti-DNA antibody were all positive on several repeated tests. A wedge liver biopsy tissue showed mixed features of PBC and CAH. A diagnosis of CAH was made on the basis of the clinical, serological, and morphologic findings. The patient responded well to prednisolone treatment with prominent improvement of her symptoms and liver function tests. Subsequently, AMA fell to undetectable levels by indirect immunofluorescence method.

Antibodies↗
PubMed1992

Immunopathogenesis of Takayasu arteritis.

Takayasu arteritis is a common cause of renovascular hypertension in India. Sensitization to infective agents, particularly mycobacterium tuberculosis or autoimmune disturbances have been incriminated in its pathogenesis. Twenty patients of Takayasu arteritis along with groups of normal individuals, patients of essential hypertension, autoimmune disorders, tuberculosis, and healthy tuberculin reactors were studied. Besides detailed immunological profiles including LE cell phenomenon, serum complement C3 levels, antibodies to single (SS) and double stranded (DS) DNA, rheumatoid factor, lymphocyte subsets, blast transformation to antigens including, phytohemagglutinin, PPD, pokeweed, and purified human aortal antigen (PHAA) were examined. Soluble protein from human aorta was fractionated into 9 peaks by DEASE-52 and Sephadex G-75 chromatography, and 25 micrograms of major protein fraction-II was used for blast transformation study. Blast transformation by PHAA was higher in Takayasu arteritis as compared to all other groups (P < 0.05). Blast transformation to PPD showed wide variation in all the groups, and was significantly higher only in tuberculin reactors as compared to controls. These observations support aortal sensitization to PHAA playing a role in pathogenesis of Takayasu arteritis and do not relate tuberculosis to Takayasu arteritis, at least immunologically. In addition, the ratio of CD-4 positive to CD-8 positive lymphocytes changing in favor of the former and the concomitant increase in B lymphocytes favor the presence of autoimmune disturbances in Takayasu arteritis.

Adolescent↗