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ID PMID Title PublicationDate abstract
8880213 Two spatially distant epitopes of human lactoferrin. 1996 Aug Lactoferrin (LF) is an iron binding protein, which may represent a target for antineutrophil cytoplasmic antibodies (ANCA) in patients affected by rheumatoid arthritis, ulcerative colitis, and primary sclerosing cholangitis. Here we describe the production and characterization of two new monoclonal antibodies (MAbs) against human LF. These MAbs (AGM 10.14, an IgG1, and AGM 2.29, an IgG2b) recognize spatially distant epitopes of LF as assessed by cross-blocking experiments. We also demonstrated by indirect immunofluorescence that both MAbs react with ethanol-fixed neutrophil granulocytes showing a perinuclear staining pattern. AGM 2.29 and AGM 10.14 have been utilized as capture and labeled tracer antibody, respectively, in a double determinant immunoassay (DDIA) to measure soluble LF. The results obtained show that this DDIA allows us to quantify even low concentrations of LF, the maximal range of the assay sensitivity being between 12 and 780 ng/ml. Therefore, AGM 10.14 and AGM 2.29 may represent useful reagents for studying the role of autoantibodies to LF as well as for measuring soluble LF, which is a reliable secretory marker of neutrophil activation.
8809571 [Study on the specificity of a monoclonal antibody against recombinant envelope proteins o 1996 Jul Human endogenous retroviruses (HERVs) and its related sequences have been known to occupy about 1% on human genome, and the expression of messenger RNA has been demonstrated by many investigators including our laboratory. However, only few papers have been indicated they are translated in proteins. Either physiological roles in man or pathogenic roles in diseases are still unknown at present. In this study, to investigate the protein expression of one copy type HERV, ERV3 and its pathogenicity, a recombinant protein to ERV3 env region was produced using E. coli expression system, and a monoclonal antibody to the recombinant protein was prepared. The monoclonal antibody evidenced the translation of ERV3, and 170 and 180 kilodaltons of proteins were detected in normal placentas and adrenal glands by Western blot. Natural antibodies to the products of ERV3 env region with high reactivities were detected in sera from some patients with systemic lupus erythematosus (SLE) compared with normal population and patients with rheumatoid arthritis (RA). The result suggests that ERV3 products may play as one of autoantigens in patients with SLE. The recombinant protein and monoclonal antibody described here may be useful to study the role of ERV3 in vivo and the etiologic relation of HERVs to autoimmune diseases.
8621114 Capsaicin in hot chili pepper: carcinogen, co-carcinogen or anticarcinogen? 1996 Mar Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is a major pungent ingredient of the Capsicum fruits such as hot green and red peppers. Besides its use as a food additive in various spicy cuisines, capsaicin is currently utilized for therapeutic purposes to treat various peripheral painful conditions such as rheumatoid arthritis and diabetic neuropathy. Considering consumption of capsaicin as a food additive and its current medicinal application in humans, correct evaluation and precise assessment of any harmful effects of this compound are essential from the public health standpoint. Numerous investigations have been conducted to determine the potential mutagenic and carcinogenic activity of capsaicin and chili pepper, but results are discordant. This review briefly examines findings in the literature of studies testing mutagenicity and tumorigenicity of capsaicin and presents a possible mechanistic basis for the dual effects exerted by the compound.
8845587 Anorexia in older persons: epidemiology and optimal treatment. 1996 Feb Anorexia and weight loss are common findings in older persons. Over a life-time, normal persons decrease their food intake to counterbalance the decrease in physical activity and resting metabolic rate that occurs with aging. This physiological anorexia of aging increases the propensity to develop pathological anorexia and weight loss when an older person develops either a medical or psychological illness. The physiological anorexia of aging is due to a decreased opioid (dynorphin) feeding drive and an increase in the satiating effect of the gastrointestinal hormone, cholecystokinin. Nitric oxide deficiency may play a role in the early satiation commonly seen in older persons. A variety of social, psychological and medical conditions can lead to pathological anorexia. Depression is the most common cause of weight loss and anorexia in older persons. A number of conditions such as cancer and rheumatoid arthritis produce their anorectic and wasting effects by releasing cytokines. An idiopathic pathological senile anorexia has been characterised which also appears to be a cytokine-dependent syndrome. Early screening for malnutrition is a cornerstone of the management of anorexia; the Mini Nutritional Assessment is a well validated screening tool available for this purpose. Aggressive use of caloric supplements, enteral tube feeding and peripheral parenteral nutrition all have a role in the early management of anorexia. Numerous drugs (growth hormone, megestrol, cyproheptadine, tetrahydrocannabinol, anabolic steroids, prokinetic agents and antidepressants) have been utilised to treat the anorexia of aging with varying success.
7567836 [Superantigens and their implication in autoimmune diseases]. 1995 Sep 2 Superantigens, unlike conventional antigens, are capable of stimulating cell growth and differentiation of a large proportion of T cells (10 -40%). There are two types of superantigens: endogenous retroviral superantigens (described only in mice) and bacterial superantigens. Bacterial superantigens are heat-resistant enterotoxins responsible for Staphylococcus food poisoning or toxic shock syndromes. T lymphocyte proliferation is associated with production of large quantities of cytokines, including interleukin-1, 2, 4, 6 and tumour necrosis factor which induce the symptoms observed in toxic syndromes. These superantigens form trimolecular complexes with the beta chains on the outer peptide pouch of class II HLA molecules and with certain families of V beta chains of the T-cell receptors on CD4 and CD8 lymphocytes. Unlike conventional antigens, superantigens do not have to be processed in small-sized peptides before presentation to T-cell receptors by the class II HLA molecules. The late consequences of T-cell activation by superantigens are either a deletion of the T-lymphocytes carrying V beta chains in families specific for a superantigen, or an anergy. The oligoclonal characteristic of T-lymphoid populations infiltrating the central nervous system, the synovial membrane or the salivary glands suggests that superantigens are implicated in the pathogenesis of certain autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and Sjögren's syndrome. Certain Staphylococcus superantigens could be the cause of Kawasaki's syndrome.
7871382 Iron requirements of human lymphocytes: relative contributions of intra- and extra-cellula 1995 Mar A supply of iron is of vital importance if lymphocyte proliferation is to proceed successfully and two major sources of iron are available, intracellular stores and serum transferrin. We have investigated the relative importance to the human T lymphocyte of these two sources of iron by depleting them of intracellular iron with the chelator desferrioxamine and by culturing them in medium completely depleted of transferrin iron. The chelator decreased mitogen-stimulated proliferation of human peripheral blood T cells, in a dose-dependent manner, in the absence of extracellular transferrin-iron. By culturing the cells in iron-depleted medium, we found that normal lymphocytes proliferated, to a degree, in the absence of extracellular transferrin-iron. We also observed that transferrin receptor mRNA expression was sustained in mitogen-stimulated, iron-deprived lymphocytes, compared with untreated cells suggesting that up-regulation of transferrin receptor may occur in these cells through stabilization of the mRNA. We propose that intra- and extra-cellular iron may contribute to early and late activation processes and that a low level of intracellular iron in lymphocytes, chronically activated in the iron-deficient environment associated with chronic inflammatory diseases such as rheumatoid arthritis, may be a factor in the abnormal cell-mediated immunity associated with such diseases.
7748624 Metabolic basis for high paracetamol dosage without hepatic injury: a case study. 1995 Jan 1. Studies of paracetamol metabolism were performed in a 58-year-old female with rheumatoid arthritis who had consumed 15-20 g paracetamol daily for 5 years without developing liver damage and data were compared with results in seven normal volunteers. 2. After a test dose of 2 g paracetamol, the formation of paracetamol sulphate and glucuronide conjugates detected in plasma from the patient was delayed by around 2 h relative to values in normal volunteers and the proportion of sulphate conjugates excreted in urine was 1.5 to 2 times those in normal volunteers (52% vs 26-35% of dose, respectively). The fractional metabolite clearance of paracetamol to glutathione-derived conjugates (0.28 ml min-1 kg-1) in our patient was > 30% lower than in normal females. 3. A combination of slow paracetamol absorption, enhanced detoxication of paracetamol (by sulphation) and reduced metabolism to potentially cytotoxic metabolites may have reduced the risk of liver damage in this patient. The latter may have reflected pharmacogenetic deficiencies in cytochrome P450 isoenzymes persisting despite chronic alcohol consumption (40-60 g per day) or resulted from inhibition of paracetamol activation by concomitant ingestion of aminophylline.
7597323 [Current status of human cytomegalovirus disease]. 1995 Human cytomegalovirus (HCMV) can establish lifelong persistence after primary infection with reactivation occurring as a result of immunosuppression. There is much evidence that molecular interactions between the immune system and the HCMV are responsible for immune escape. HCMV in many cells especially in mononuclear blood cells during latency are frequently the source of transmission and spreading and results in a variety of disorders. In this review some data about acute infection in immunocompetent host (mononucleosis, hepatitis), about intrauterine HCMV infection, about infection and endogenous reinfection in bone marrow and solid organ transplant recipients (pneumonitis) and about HCMV disease in AIDS patients (encephalitis, neuropathy, retinitis, colitis) are investigated. Moreover, HCMV associated vasculitis is described in patients with myocarditis, rheumatoid arthritis or polyradiculopathy. HCMV could play an important role in atherosclerosis. Several types of human malignancy have been linked to HCMV and it has been shown that HCMV ie genes upregulate expression of cellular oncogenes. The diagnosis of HCMV infection is carried out by viremia in cell culture using immediate early antigen staining, by antigenaemia which appears to be an early quantitative and predictive tool, by HCMV DNA detection using hybridization and PCR, and by IgM and IgG antibody evaluation. Two antiviral drugs are used for treatment: ganciclovir and phosphonoformic acid; few resistant clinical isolates have been reported. Specific gammaglobulin activity is discussed. HCMV vaccine is not available.
7957236 Signal-transduction therapy. A novel approach to disease management. 1994 Nov 15 In the past decade it has become apparent that many diseases result from aberrations in signaling pathways. These include proliferative diseases such as cancers, atherosclerosis and psoriasis and inflammatory conditions such as sepsis, rheumatoid arthritis and tissue rejection. These findings refocused the research of the medical community to seek new modalities for disease management which essentially consist of designing drugs which intercept cell signaling. In this review, the emerging success in using tyrosine kinase blockers and other signal interceptors, such as protein kinase C blockers, Ras blockers, Ca2+ signaling inhibitors and estrogen antagonists which inhibit growth of cancer cells in vitro and in vivo, will be discussed. These signal interceptors, especially tyrosine-kinase blockers, are also able to block inflammatory responses and the proliferation of vascular smooth muscle cells and psoriatic keratinocytes. The utility of signal interceptors in analyzing signal-transduction pathways is also discussed.
7884629 Slow release of chloroquine phosphate from multiple taste-masked W/O/W multiple emulsions. 1994 Nov The efficacy and safety of chloroquine as an antimalarial has contributed to the survival of millions in the past 50 years. Chloroquine is widely available, cheap, well tolerated and orally well absorbed. Therefore, it remains an important antimalarial drug. However, on oral administration, particularly to children, the unpleasant taste is a problem. This could be avoided by 'taste-masked and controlled release' formulations such as multiple emulsions. Although Plasmodium falciparum has developed resistance to many antimalarial drugs, including chloroquine, resistance may be attributed, among other factors, to subclinical dosage of chloroquine from administered pharmaceutical forms. This could also be relevant in the treatment of rheumatoid arthritis. Multiple W/O/W emulsions of chloroquine phosphate were prepared. Assessment of emulsion stability showed no significant change in the system. Prolonged storage (four months) of the emulsion resulted in negligible loss of chloroquine phosphate. The results suggest, therefore, that chloroquine phosphate releases due to diffusion of the drug from the internal globules and not as a consequence of instability of the W/O/W emulsion. These characteristics are in accordance with the requirements for controlled release pharmaceuticals. Stability of multiple emulsions could have resulted from interfacial polymerization or complexion between molecules. Release assessments showed faster rates for W/O/W emulsions which had smaller internal aqueous globules and, therefore, an increased interfacial area. Furthermore, transport of high-diffusion coefficient micelles could have given a greater solute flux in these systems.
7988077 Importance of Lp(a) lipoprotein and HLA genotypes in atherosclerosis and diabetes. 1994 Jul Lp(a) lipoprotein [Lp(a)] was found in previous studies to be independently associated with early atherosclerosis and its sequelae. Lp(a) in vitro bound to glucosaminoglycans and was easily aggregated at physiological Ca2+ concentration, and small Lp(a) aggregates were phagocytosed by macrophages. Lp(a) was also found to be related to carbohydrate metabolism, and increased Lp(a) levels have been described in diabetic patients with clinical complications and were recently found in rheumatoid arthritis patients. In this study of nondiabetic male patients with documented CAD before 50 years of age and controls, a significant correlation was found between Lp(a) and IGF-1 levels. HLA class II DR13 (DR6) was more frequent and DR15 (DR2) was less frequent in patients than in controls. The calculated relative risk for CAD was 4.0 for DR17 (DR3), but the difference was not significant. These differences seem to be related to high Lp(a) levels. It is suggested that phagocytosis of preferably Lp(a) aggregates can induce an immunological tissue response that may contribute in the pathogenesis of Lp(a)-associated diseases and may be more prominent in combination with some inherited HLA class II haplotypes. Probably due to sex hormone effects, the association may be most pronounced in young males and in older females.
8011173 The action of hypochlorous acid on polymeric components of cartilage. 1994 Mar The action of sodium hypochlorite on N-acetylglucosamine, N-acetylgalactosamine, chondroitinsulfate and hyaluronic acid was studied by 1H-nuclear magnetic resonance (1H-NMR) in order to model some aspects of degradation processes caused by neutrophils on carbohydrate polymers of cartilage in rheumatoid arthritis. N-Acetyl side groups of carbohydrate monomers and chondroitinsulfate yield a resonance at 2.01-2.04 ppm in proton NMR-spectra. This resonance is observed in hyaluronic acid solutions only after a prolonged incubation to yield shorter polymeric chains. Sodium hypochlorite causes a continuous decrease of the line for N-acetyl groups. Two new resonances appear in the 1H-NMR spectra. An intermediate product, assumed as a chlorinated product of N-acetyl side chains, shows a chemical shift of about 2.35 ppm. This intermediate is hydrolyzed to a carbohydrate ring and acetate (1.90 ppm). Sodium hypochlorite acts in all systems investigated mainly on N-acetyl groups. Only small effects on the carbohydrate ring were found under our experimental conditions.
7660963 Analysis of the genotypes for aldehyde dehydrogenase 2 in Japanese patients with primary g 1994 Alcoholic ingestion is one of the major factors for increasing serum uric acid levels. Genotypes of aldehyde dehydrogenase 2 (ALDH2, E.C.1.2.1.3), which regulates the sensitivity of an individual to ethanol, were determined in Japanese patients with gout and control subjects by allele specific oligonucleotide hybridization using PCR amplified gene. The most common allele ALDH2*1 codes for normal ALDH2 activity, while the less common allele ALDH2*2 codes for a lower enzyme activity. The frequency of homozygotes of ALDH2*2 was significantly lower in patients with gout than those with rheumatoid arthritis or a normal population. Plasma and urinary hypoxanthine levels were strikingly increased after ethanol drinking in homozygotes for ALDH2*1 but not in heterozygotes for ALDH2*1/ALDH2*2, indicated extensive purine nucleotide degradation in homozygote for ALDH2*1. These data indicated that alcohol ingestion may not be the requisite factor but is deeply involved in the pathogenesis of gout and hyperuricemia.
9312341 [Evaluation of the hypophyseal-hypothalamo-adrenal axis in patients undergoing chronic cor 1993 Sep A cortisol curve was practiced on 32 healthy persons with an average age of 38.7 years, being the morning amount at 8 o'clock of 10 mg/100 ml o higher. Later we practiced the same study in 42 patients with an average age of 41.4 years, that were under a corticosteroid therapy higher than 10 mg per day of prednisone during more than three months of an uninterrupted prescription and said treatment was stopped 48 previous hours to the study. We found that 27 of them (64.2%) had lowe morning amount of cortisol to those of the control group, and the patients with rheumatoid arthritis being the lowest. It is concluded that the type of systemic disease could be another factor in the suppression of the axis H-H-A of patients under a higher dosis than 10 mg of prednisone and a durability longer than three continuous months.
8411652 [Multiple myeloma presenting with amyloid arthropathy]. 1993 Aug Amyloid arthropathy rarely occurs in patients with multiple myeloma (MM) or primary amyloidosis (PA). Amyloid infiltration in and about the joints may be so extensive as to simulate the findings of rheumatoid arthritis. Some cases have been reported in which the articular manifestations were present for many months prior to the diagnosis of amyloid arthropathy. The delay of the diagnosis can result in the development of a fatal complication of MM or PA, which is not always unavoidable. We have encountered an unusual case of MM which the articular manifestations were present prior to the diagnosis of MM. A 59-year-old woman had a four-month history of hypesthesia in the median-nerve distribution of both hands and polyarthralgia. Far advanced renal insufficiency was evident, but its etiology was not determined. The patient was maintained on hemodialysis. The shoulders, wrists, hips and finger joints were symmetrically involved with articular swelling. All of these joints showed the avid uptake of Tc-99m (V) DMSA. The serum and urine immunoelectrophoresis demonstrated the presence of IgG-lambda type M-component and lambda type Bence Jones proteins, respectively. The bone marrow findings and bone roentgenograms supported the diagnosis of MM. Biopsy specimens from the synovial membrane revealed amyloid deposition. Her condition was much improved with melphalan and prednisolone.
8371004 [Diseases associated with cytokine dysregulation]. 1993 Aug Communication between cells is essential for a wide variety of biological functions. One way cells interact in immune and hemopoietic systems is through soluble mediators called interleukins or cytokines. Many cytokines and their receptors have been identified and characterized at the molecular level. These studies have observed that most cytokines function in a pleiotropic and redundant manner. Receptor studies have shown that many cytokine receptors consist of two polypeptide chains, a ligand-binding receptor, and a nonbinding signal transducer. This arrangement may explain the pleiotropic and redundant effects of cytokines. For example, leukemia inhibitory factor (LIF) and IL-6 share many biological activities including platelet production, and the receptors of these cytokines utilize gp130 as a common signal transducer. IL-6 is multifunctional and produces both favorable and unfavorable effects on human health. Dysregulation of IL-6 expression is linked to the occurrence of cancer and autoimmune diseases, such as multiple myeloma, Castleman's disease, mesangial proliferative glomerulonephritis, and rheumatoid arthritis. Studies in transgenic mice in which the IL-6 gene was overexpressed have confirmed these pathogenic actions of IL-6. The pathogenesis of these diseases and therapies to treat them are discussed here based on insights derived from cytokine research.
8275826 [Antibodies to Klebsiella pneumoniae in ankylosing spondylitis]. 1993 Jul This study was performed to evaluate the involvement of Klebsiella pneumoniae (Kp) in ankylosing spondylitis. Serum IgA, IgG and IgM antibodies to Kp were measured with ELISA in 60 patients with ankylosing spondylitis (AS), 28 patients with rheumatoid arthritis (RA) and 45 healthy individuals. A marked elevation of IgA antibody to Kp was detected in the sera of patients with AS, compared to that in patients with RA (P < 0.02) and healthy controls (P < 0.001). The positive rate of antibodies to Kp was 55% in patients with active AS, significantly higher than that in patients with inactive AS (16.7%, P < 0.01), patients with RA (17.8%, P < 0.05) and healthy controls (4.4%, P < 0.001). Stool culture for Kp was carried out in 15 of the 60 patients with AS simultaneously, 3 (20%) of them were positive. Our results are in line with the previously published findings suggesting that Kp may play a role in the pathogenesis of AS.
8476255 Interleukin-2 receptor-directed therapies: antibody-or cytokine-based targeting molecules. 1993 With the exception of certain hematologic malignancies, the high affinity interleukin-2 (IL-2) receptor is only transiently expressed during the brief antigen-triggered proliferative burst of lymphocytes. Hence, we wondered whether administration of anti-IL-2 receptor (IL-2R) monoclonal antibody (mAb) or chimeric IL-2 toxins would provide a utilitarian way to achieve immunosuppression aimed directly at activated lymphocytes, or whether this approach could be used to treat IL-2R+ leukemia/lymphoma. Studies in preclinical autoimmune and transplant models indicate that this approach can be effective. The results of open, uncontrolled studies provide preliminary evidence that a chimeric IL-2 toxin is well tolerated at doses that may induce improvement in patients with IL-2R+ leukemia/lymphoma, as well as in patients with refractory rheumatoid arthritis or new-onset diabetes mellitus.
1578486 Novel anthraquinone inhibitors of human leukocyte elastase and cathepsin G. 1992 May 1 A large series of variously substituted anthraquinones has been synthesized and assayed for inhibitory capacity against human leukocyte elastase (HLE) and cathepsin G (CatG), two serine proteinases implicated in diseases characterized by the abnormal degradation of connective tissue, such as pulmonary emphysema and rheumatoid arthritis. It was found that 2-alkyl-1,8-dihydroxyanthraquinone analogues are competitive inhibitors of HLE with IC50 values ranging from 4 to 10 microM, and also inhibit CatG with IC50 values ranging from 25 to 55 microM. Consequently, analogues containing the 2-alkyl-1-hydroxy-8-methoxyanthraquinone substitution pattern inhibit HLE to the same magnitude as for the compounds above, but show very little inhibition of CatG. Anthraquinones containing long, hydrophobic n-butyl carbonate moieties in the 1- and 8-positions in conjunction with a third hydrophobic substituent in the 2- or 3-position are highly selective for HLE, with Ki values in the range of 10(-7) M. All of the inhibitors described are completely reversible, with no evidence of acyl-enzyme formation detected.
1375648 Effect of topical capsaicin in the therapy of painful osteoarthritis of the hands. 1992 Apr Topical capsaicin 0.075% was evaluated for the treatment of the painful joints of rheumatoid arthritis (RA) and osteoarthritis (OA) in a 4 week double blind, placebo controlled randomized trial. Twenty-one patients were selected, all of whom had either RA (n = 7) or OA (n = 14) with painful involvement of the hands. Assessments of pain (visual analog scale), functional capacity, morning stiffness, grip strength, joint swelling and tenderness (dolorimeter) were performed before randomization. Treatment was applied to each painful hand joint 4 times daily with reassessment at 1, 2 and 4 weeks after entry. One subject did not complete the study. Capsaicin reduced tenderness (p less than 0.02) and pain (p less than 0.02) associated with OA, but not RA as compared with placebo. A local burning sensation was the only adverse effect noted. These findings suggest that topical capsaicin is a safe and potentially useful drug for the treatment of painful OA of the hands.