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At least 847 records · Page 47Linked to original sources
PubMed2005

Interferon-beta1b for multiple sclerosis.

Interferon-beta1b (Betaseron/Betaferon) was the first approved therapy for relapsing-remitting multiple sclerosis. The US Food and Drug Administration has expanded the indication to include relapsing forms of multiple sclerosis which encompasses secondary-progressive multiple sclerosis if relapses are present. In one scientifically sound head-to-head comparison (Independent Comparison of Interferon trial), interferon-beta1b was shown to be clinically superior to low-dose interferon-beta1a (Avonex). Current studies are underway to compare it with a double dosage of interferon-beta1b [corrected] as well as glatiramer acetate. Neutralizing antibodies are more likely to occur with interferon-beta1b, but their clinical significance has shown conflicting and confusing results making the utility of measuring neutralizing antibodies uncertain. Up to 12 years of follow-up data suggest that the drug remains effective on T2 magnetic resonance imaging burden of disease in those who stay on therapy. Initially, the major problem with interferon-beta1b was a lack of tolerability due to high incidents of skin reactions and influenza-like side effects. Patient adherence has improved dramatically with the introduction of autoinjectors and protocol changes including initial dose escalation, prophylactic ibuprofen or acetaminophen, evening administration of drug and an attentive nurse support system. Interferon-beta1b remains a first-line treatment for relapsing-remitting multiple sclerosis and relapsing forms of secondary-progressive multiple sclerosis based on robust efficacy data and a long-term safety profile.

Adjuvants, Immunologic↗
PubMed2006

Osteopontin: a potential biomarker for successful bee venom immunotherapy and a potential molecule for inhibiting IgE-mediated allergic responses.

Venom immunotherapy (VIT) is proven to be curative for insect allergy, but the mechanisms and the biomarkers associated with clinical efficacy remain elusive. We report herein the discovery of a leading candidate biomarker, osteopontin (OPN), for VIT. From cDNA microarray and clustering analyses, an increased expression of OPN was found in patients who completed 5-6 years of VIT and discontinued therapy for 3-6 years as compared with the untreated group. A significantly higher level of serum OPN was found in the completed treatment group as compared with the untreated group. Following VIT, kinetically increased levels of OPN associated with reduced venom specific IgE levels were noted in subjects with large local allergic reactions to venom. These findings together with the fact that OPN is involved in Th1-associated immune response strongly suggest a role of OPN as a functional biomarker for VIT.

Bee Venoms↗
PubMedDate not supplied

[Inflammatory demyelinating chronic polyneuropathy: a contribution to the characterization of the disease].

INTRODUCTION AND OBJECTIVE: The chronic inflammatory demyelinating polyneuropathy (CIDP) is a controversial sickness. No doubt it is still a diagnosis without a strict nosologic delimitation until we acquire a greater knowledge about the underlying mechanisms, or whether a specific marker is found. We evaluated its clinical and laboratory findings, to contribute to its characterization in our environment. PATIENTS AND METHODS: We reviewed the records of 37 patients diagnosed with CIDP between 1986 and 1997. They were grouped in as to sex, age, beginning age (BA), evolution time, race, clinical form, symptoms, signs and evolutive profile. We analyzed the cytochemic and immunologic studies of cerebrospinal fluid (CSF) as well as sural nerve biopsy. RESULTS AND CONCLUSIONS: We demonstrated a predominance of BA between the fifth and sixth decades, and the presentation of a mixed polyradiculoneuropathy with motor predominance and a chronic progressive evolution. It was positively correlated with protein concentration levels in CSF, elevated in the 73.5% of the patients. There was an increase in the permeability of the blood brain barrier (BBB) in 50.8%, IgG intrathecal synthesis in 5.08 and oligoclonal bands in 8.8%. We found lost of myelin sheats in 90.6% of sural nerves and onion-bulbs formation in 60.5%, which demonstrated the high sensitivity of this study to confirm the diagnosis of demyelinating process as essential substrate in the illness.

Adolescent↗
PubMed2000

Decreased natural killer cell responses and altered interleukin-6 and interleukin-10 production in alcoholism: an interaction between alcohol dependence and African-American ethnicity.

BACKGROUND: Epidemiological data indicate that among alcoholics African-American men have higher rates of infections compared with white alcoholics. Alcohol is thought to reduce natural killer (NK) cell responses and to alter cellular immunity by changing the relative balance of Th1 versus Th2 cytokine response profiles. However, translation of these basic immunological observations into the clinical setting is limited, and what clinical data are available are contradictory, in part, because of heterogeneity within the alcoholic patient population. Whether ethnic characteristics contribute to variation in the immunological effects of alcohol is not known. METHODS: This study compared NK activity, interleukin (IL)-2-stimulated NK activity, and concanavalin A-stimulated peripheral blood mononuclear cell production of Th1 (IL-12 and IL-2), Th2 (IL-10), and proinflammatory (IL-6) cytokines in 31 hospitalized chronic alcoholic patients and 31 age-matched controls who were stratified on the basis of ethnicity. RESULTS: NK-cell responses were significantly different across the four groups, and African-American alcoholics showed the lowest levels of NK activity (F = 9.5;p < 0.001) and IL-2-stimulated NK activity (F = 2.9; p < 0.05). Compared with the other three groups, African-American alcoholics also showed lower levels of IL-6 (F = 7.2;p < 0.01) and higher levels of IL-10 (F = 4.9;p < 0.05). Stimulated production of IL-2 and IL-12 were similar in the four groups. Regression analyses showed that alcohol dependence and ethnicity predicted NK activity, whereas the interaction between alcohol dependence and ethnicity predicted levels of IL-6 and IL-10. CONCLUSIONS: In summary, the immunological effects of alcohol dependence are modified by ethnicity status, consistent with the increased health risks found in African-American alcoholics.

Adult↗
PubMed1985

Isoprinosine and Imuthiol, two potentially active compounds in patients with AIDS-related complex symptoms.

Isoprinosine and Imuthiol are immunomodulators with a unique effect on T-cells. The possibility of using them in treating patients with acquired immunodeficiency syndrome related complex (ARC) was initially examined regarding their in vitro effects on peripheral blood mononuclear cells. In six ARC patients Isoprinosine (100 micrograms/ml) and Imuthiol (10 pg/ml) induced in vitro an early chromatin activation as measured by nuclear refringency test and potentiated phytohemagglutinin (5 micrograms/ml) in the same 20-min assay in the absence of fetal calf serum. In all patients an early phytohemagglutinin induced chromatin dispersion was observed with a dose related response before interleukin 2 production can occur. Isoprinosine and Imuthiol increased significantly both the percentage and the absolute number of T4+ cells when peripheral blood mononuclear cells were incubated for 4 days in RPMI supplemented with 10% fetal calf serum. No changes in T8+ cells were noted. Three homosexual ARC patients were then treated p.o. with Imuthiol (5-10 mg/kg/week) for 4 to 6 months. Without any deleterious effect a clinical improvement (in terms of adenopathy and opportunistic infection regression) and restoration of the response to recall antigens were observed in all three patients. One patient with less than 500 T4+ lymphocytes/mm3 exhibited a complete restoration of OKT profiles. In such patients clinical and immunological effects of Isoprinosine have already been reported by others. Altogether these preliminary results indicate that more data should be obtained on the effects of these two agents in ARC patients.

Acquired Immunodeficiency Syndrome↗
PubMed1982

Isolation and characterization of two molecular variants of myosin heavy chain from rabbit ventricle. Change in their content during normal growth and after treatment with thyroid hormone.

We have prepared monoclonal antibodies specific for cardiac myosin heavy chain. These antibodies were used for the separation and characterization of the molecular variants of myosin heavy chain present in the rabbit heart. Two molecular forms of myosin heavy chain, HC alpha and HC beta, were isolated from the euthyroid rabbit heart by affinity chromatography. Their reactivity with our antibodies indicated that the primary structures of HC alpha and HC beta differ in at least four and share at least two antigenic determinants. Differences in the primary structure of HC alpha and HC beta were confirmed by analysis of the peptides produced by limited chymotryptic digestion of the two heavy chains. Thirteen peptide differences were consistently found. The HC alpha and HC beta variants are shown by immunologic analysis and in chymotryptic peptide profiles to be identical with the predominant forms of myosin heavy chain synthesized in the hearts of hyperthyroid and adult euthyroid rabbits, respectively. During development and maturation of the euthyroid rabbit heart, HC alpha comprises approximately 50% of the ventricular myosin between birth and 4 weeks of age; it diminishes to 20-30% by 8 weeks and to 10-20% by 12 weeks of age. Cardiac myosin from a 1-year-old rabbit is composed almost entirely of HC beta. Cardiac myosin from embryonic animals at 20 days gestation contained 20% HC alpha. These results show that HC alpha occurs normally in the euthyroid rabbit heart and that the relative proportions of HC alpha and HC beta depend on both the developmental stage and the thyroid state of the animal.

Aging↗
PubMed1983

Newer avenues in the monitoring of antithrombotic therapy: the role of automation.

In the future, we may find that antithrombotic therapy provides its major effects other than by Factors Xa and IIa inhibition, in which case a panel of assays may be of clinical use to determine how a given patient is responding to therapy. All methods discussed previously for direct factor assays, global tests, or specific factor inhibition can be modified for synthetic substrates. With instruments such as the IL Multistat III centrifugal analyzer, which has detection capabilities for visible light, fluorescence and light scatter, it will be possible to panel profile synthetic substrate-based assays, immunologic assays (for example, platelet release products or circulating complexes of enzyme-inhibitor, such as thrombin-AT III) and possibly platelet aggregations/luminescence in one rotor. The field of coagulation is rapidly expanding in the development of newer tests to measure newly discovered proteins (protein C), development of new drugs and therapeutic regimens, and incorporating immunologic and enzymologic technologies and clinical chemistry standardization and quality control practices. Throughout this period of growth, automation has been in the forefront and is playing an ever-increasing role in every old and new aspect of coagulation evaluation. We are aware of the advantages that accompany any automated device over manual techniques, so there should be much hope and expectation for the new hemostasis and thrombosis laboratory.

Administration, Oral↗
PubMed1994

Bronchoalveolar lavage findings in a young adult with idiopathic pulmonary haemosiderosis and coeliac disease.

Idiopathic pulmonary haemosiderosis is a rare disease of unknown autoimmune aetiology, mainly affecting children and adolescents. A variety of coexisting autoimmune diseases have been described, including coeliac disease. We describe the case of a man, aged 19 yrs, presenting with a one year history of recurrent haemoptysis. Gluten and gliadin antibodies were positive, and the jejunal biopsy revealed villous atrophy consistent with the diagnosis of coeliac disease. Bronchoalveolar lavage fluid analysis showed a mean haemosiderin score (Golde index) of 240, and a local suppressor/cytotoxic profile on immunocytology. Both clinical and immunological improvement was obtained after a month of gluten-free diet. These immunological findings provide new insight into the pathogenesis of this disease.

Adult↗
PubMed1997

Extended-spectrum beta-lactamases: an actual problem of hospital microbiology (a review).

Although there is a variety of mechanisms of bacterial resistance to beta-lactam antibiotics, the most important one is production of beta-lactamases inactivating penicillins and cephalosporins. The classification of beta-lactamases is based on biochemical, enzymological (i.e. molecular structure, inhibitory property, substrate-profile, relative rate of hydrolysis) and immunological characters. Extended-spectrum beta-lactamases (ESBLs) can be derived from TEM or SHV enzymes. These enzymes have now been sequenced and it has been found that relatively few point mutations have occurred in the gene of the TEM and SHV type enzymes. These point mutations clustered in five areas of the gene. The amino acid mutations can alter the conformation, the active site and change the hydrance of beta-lactamase-cephalosporin binding capacity. So the enzyme is able to bind and hydrolyse the third generation cephalosporins. Successive mutation interacted radically increasing the binding capacity of enzymes and confer resistance to newer cephalosporins. The use of these drugs provides a strong selective pressure to develop these mutations. Sporadic nosocomial outbreaks due to strains producing an ESBL led to an epidemic problem in some hospitals resulting in a concurrent dissemination of genes, plasmids or strains. Clinical epidemiological importance and role of ESBLs and emergence of multiply resistance of bacteria of nosocomial importance are discussed in this brief.

Aminohydrolases↗
PubMed2002

Immune profiles of patients with chronic idiopathic urticaria.

BACKGROUND: The immunologic characterization of chronic idiopathic urticaria (CIU) is still incomplete. In particular, it is not known if positivity to the intradermal autologous serum skin test (ASST) identifies an immunologic subset of CIU patients. METHODS: Nineteen CIU patients and 15 healthy controls were enrolled in the study. A diagnostic flowchart was designed to select CIU patients, who were then analyzed by ASST. Cytokine and chemokine production and the expression of adhesion molecules was measured in patients and controls. RESULTS: In CIU patients compared to controls, it was found that (1) TNF-alpha, IL-10, MIP-1alpha and RANTES production was augmented and IL-2 and INF-gamma reduced, and (2) CD44, CD11a and CD62L expression on CD4 and CD8 cells was augmented. Additionally, TNF-alpha and chemokine production was significantly increased in CIU patients with a negative ASST (p-; n = 10) compared to patients with a positive response to the test. CONCLUSIONS: The presence of an inflammatory process in CIU patients is suggested by the findings that the production of both TNF-alpha and chemokines as well as the expression of adhesion molecules is increased in these patients. Similarly to what is seen in rheumatoid arthritis, augmented IL-10 production might be secondary to the attempt to hamper the inflammatory milieu. Immune profiles are particularly altered in CIU p- patients, in whom a more aggressive therapeutic strategy might be considered.

Adult↗
PubMed1995

Behçet's disease in India: a clinical, immunological, immunogenetic and outcome study.

The clinical and laboratory profile of 58 consecutive patients satisfying the ISG 1990 criteria for the diagnosis of Behçet's disease was analysed. It appears that Behçet's disease in India is predominantly 'mucocutaneous' and 'arthritic'; 'ocular' and 'neuro' Behçet's being uncommon. In comparison to published literature, the onset of disease in this part of the world is significantly delayed. The pathergy test is rarely positive. There is no significant difference in clinical presentation and laboratory investigations between children and adults with this disease; also, no sex difference was observed. A combination of oral steroids and colchicine gives good relief in most cases. Preliminary observations seem to reflect no definite association of any known class I antigen to disease in this part of the world. A detailed study on immunogenetics is underway.

Adult↗
PubMed1998

[The protein profile of the cervical mucus: cyclic and ovulatory values].

Immunological and biochemical analysis on cervical mucus requested application of micromethods on sindle small specimens. The following micro-methods in agar gel are applied: immunoelectrophoresis--the normal cervical mucus developed by antiserum against total human serum is presented with 5 precipitin lines: prealbumin, albumin, a1-antitrypsin, transferrin and IgG. The single immunodiffusion technique in agar gel (Mancini et al., 1964) is suitable method to assess these proteins. The same diffusion method is applied for enzyme assessment with special importance like a-amilase and muraminidase (lysozyme). The assessment of these proteins shows pre-ovulatory decrease and post-ovulatory remarkable increase. These changes are not simply due to the increased water content of the cervical mucus during the fertile period but reflects estrogen effect on cervical secretions.

Cervix Mucus↗
PubMed1997

Immunological reactivity of Vibrio anguillarum sero-subgroups O2a and O2b, and comparison of their lipopolysaccharide profiles.

One hundred and twenty-nine Vibrio anguillarum serogroup O2 strains were compared by slide agglutination and Western blotting for their lipopolysaccharide (LPS) structure. The strains showed six different LPS profiles, four different reaction patterns in Western blotting, and four different kinds of reaction in slide agglutination, when both unabsorbed and absorbed anti-O2a and anti-O2b sera were used. All in all, nine different groups were detected when the combination of these three methods was applied. The two serological methods gave corresponding results for almost all strains (96%). Most of these strains (84%) belonged to sero-subgroup O2a, while 12% of the strains belonged to sero-subgroup O2b. The remaining six strains had varying reactions in the used serological methods; therefore, their sero-subgroups could not be determined. These results suggest the existence of additional sero-subgroups within serogroup O2.

Immune Sera↗
PubMed1994

Insulin-like growth factor-binding proteins in the human fetus: tissue-specific protein secretion, immunologic characterization, and gene expression.

OBJECTIVES: The objectives of this study were to investigate the profile of insulin-like growth factor-binding proteins secreted by human fetal tissues and their immunologic identification and tissue-specific gene expression. STUDY DESIGN: Explants of midgestational fetal tissues from seven fetuses were cultured with and without cycloheximide. Conditioned media were examined for insulin-like growth factor-binding proteins by Western ligand blot analysis, and insulin-like growth factor-binding proteins were identified by immunoprecipitation. Gene expression was analyzed by Northern analysis. RESULTS: Fetal liver and kidney explants secreted insulin-like growth factor-binding protein-1 to insulin-like growth factor-binding protein-4, with insulin-like growth factor-binding protein-1 being the most prominent in liver. Fetal lung secreted insulin-like growth factor-binding protein-2 and insulin-like growth factor-binding protein-4 and lesser amounts of insulin-like growth factor-binding protein-3, whereas white matter explants secreted exclusively insulin-like growth factor-binding protein-2 and insulin-like growth factor-binding protein-4. Cycloheximide inhibited secretion of binding proteins, suggesting de novo synthesis. Northern blot analyses were consistent with the protein studies. CONCLUSION: These data demonstrate that insulin-like growth factor-binding protein secretion by fetal tissues is tissue specific.

Blotting, Northern↗
PubMed1977

Biologically active luteinizing hormone (LH) in plasma: II. Comparison with immunologically active LH levels throughout the human menstrual cycle.

The levels of biologically active luteinizing hormone were determined by an in vitro bioassay method in plasma samples collected daily over a complete menstrual cycle from 12 menstruating women. These cycles were normal according to a number of criteria, including daily plasma levels of oestradiol, 17-hydroxyprogesterone and progesterone. Immunoreactive LH was estimated in the same 12 cycles by a radio-immunoassay (RIA) procedure (HCG-RIA) using an HCG antiserum and iodinated HCG. The 2nd IRP of HMG was selected as standard although significant deviations from parallelism were found with 7 out of the 12 plasma pools studied. The use of the 1st IRP of human pituitary gonadotrophins (FSH and LH (ICSH)) for bioassay (herafter HPG-1st IRP) as standard in this system resulted invariably in invalid assays, due to lack of parallelism. Immunoreactive LH was also measured in 8 of the 12 cycles by a RIA procedure (HLA-RIA) using a human LH antiserum and iodinated human LH of pituitary origin. Results are expressed in terms of the HPG-1st IRP. The plasma levels of biologically and immunologically active LH were qualitatively similar throughout the menstrual cycle. However, the LH levels measured by the bioassay invariably exceeded those estimated by the RIA procedures. The biological to immunological (B/I) ratio over the entire menstrual cycle (312 comparisons) was 5.5 with 95% confidence limits at 5.2 and 5.8 when the HCG-RIA system was employed. Using the HLH-RIA system (208 comparisons), the corresponding ratio was 6.4 (6.0:6.9). When regression lines were calculated using the bioassay results as the independent variable and the RIA results as the dependent variable, the 95% confidence limits of the regression lines did not include the origin. Furthermore,, in keeping with the high B/I ratios, the slopes of the two regression lines and their conficence limits differed markedly from unity. It is concluded that although qualitatively similar profiles were observed between the biological and immunological activities throughtout the menstrual cycle, two aspects require further attention. Firstly, the elevated B/I ratios together with the behaviour of the dose-effect lines obtained with different standards in the various RIA systems suggest that presently available reference standard preparations of pituitary and/or urinary origin are not suitable for the assay of LH in human plasms. Secondly, from the regression analyses of the biological and immunological activities it is infered that the RIA methods detect immunological activity which is not associated with biological activity. If so, the validity of these RIA procedures for specifically measuring low levels of biologically active LH in plasma may be in question.

Adult↗
PubMed2006

Memory T and memory B cells share a transcriptional program of self-renewal with long-term hematopoietic stem cells.

The only cells of the hematopoietic system that undergo self-renewal for the lifetime of the organism are long-term hematopoietic stem cells and memory T and B cells. To determine whether there is a shared transcriptional program among these self-renewing populations, we first compared the gene-expression profiles of naïve, effector and memory CD8(+) T cells with those of long-term hematopoietic stem cells, short-term hematopoietic stem cells, and lineage-committed progenitors. Transcripts augmented in memory CD8(+) T cells relative to naïve and effector T cells were selectively enriched in long-term hematopoietic stem cells and were progressively lost in their short-term and lineage-committed counterparts. Furthermore, transcripts selectively decreased in memory CD8(+) T cells were selectively down-regulated in long-term hematopoietic stem cells and progressively increased with differentiation. To confirm that this pattern was a general property of immunologic memory, we turned to independently generated gene expression profiles of memory, naïve, germinal center, and plasma B cells. Once again, memory-enriched and -depleted transcripts were also appropriately augmented and diminished in long-term hematopoietic stem cells, and their expression correlated with progressive loss of self-renewal function. Thus, there appears to be a common signature of both up- and down-regulated transcripts shared between memory T cells, memory B cells, and long-term hematopoietic stem cells. This signature was not consistently enriched in neural or embryonic stem cell populations and, therefore, appears to be restricted to the hematopoeitic system. These observations provide evidence that the shared phenotype of self-renewal in the hematopoietic system is linked at the molecular level.

B-Lymphocytes↗
PubMed1996

Abnormal cytokine profiles in patients with idiopathic dilated cardiomyopathy and their asymptomatic relatives.

OBJECTIVES: Immunological abnormalities in idiopathic dilated cardiomyopathy (DCM) include an increase in soluble interleukin (IL)-2 receptor, disease specific cardiac autoantibodies, an HLA-DR4 association, and familial aggregation of disease; however, cytokine profiles have not been defined. Serum concentrations of IL-2, IL-4, IL-10, and IL-12 were measured in patients with DCM (WHO criteria), relatives with asymptomatic left ventricular enlargement (LVE), patients with ischaemic heart failure (IHD), and healthy controls. DESIGN: Serum from 20 individuals from each of the four groups was assayed for cytokine concentrations by a commercial enzyme linked immunosorbent assay. RESULTS: IL-2 concentrations were abnormally increased in DCM patients and relatives with LVE. Concentrations of IL-10 were increased in DCM patients. Concentrations of IL-4 and IL-12 were not increased in any of the groups. CONCLUSION: These abnormalities may reflect defective/inappropriate T cell function in patients with DCM and in their relatives with LVE.

Adolescent↗
PubMed1997

Use of type I and type IV hypersensitivity responses to define the immunopharmacological profile of drugs.

Administration of antigen suspended in incomplete Freund's adjuvant supplemented with either heat-killed Mycobacterium tuberculosis (complete Freund's adjuvant, CFA) or Bordetella pertussis toxin sensitizes animals so that subsequent antigen challenge leads to delayed-type (DTH) or immediate type hypersensitivity (ITH) responses, named type IV and type I, respectively. Appropriate timing of administration of drugs with respect to immunization or antigen challenge allowed to detect predominantly immunosuppressive, antiinflammatory or antianaphylactic activities. Among the reference drugs tested, only cyclosporin A (CsA) and dexamethasone (Dex) markedly inhibited DTH reaction, due to their immunosuppressive and antiinflammatory activities, respectively, whereas leflunomide and indomethacin resulted less potent. On the other hand, only dexchlorpheniramine, a histamine-receptor antagonist, afforded significant protection against anaphylactic shock, a form of ITH. Two new chemical entities were studied according to this protocol: ITF 1697, a chemically stabilized C-reactive protein-derived tetrapeptide, and ITF 2018, a leflunomide analogue. Data obtained with these new compounds showed that ITF 1697 has antianaphylactic activity, while ITF 2018 is endowed, mainly, with antiinflammatory activity. These results show that, through appropriate timing of administration, established in vivo models of immunologically mediated disease states allow an accurate profiling of the effects of pharmacologically active molecules and the detection of unsuspected activities for new drugs.

Animals↗