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At least 325 records · Page 18Linked to original sources
PubMed2026

Structural and functional gastrointestinal abnormalities in ACTA2 R179H mice modeling multisystemic smooth muscle dysfunction syndrome.

Multisystemic smooth muscle dysfunction syndrome (MSMDS) is a rare disorder caused by ACTA2 mutations, including the R179H variant, which alters actin filament stability and dynamics and smooth muscle contractility. Cardiovascular complications dominate its clinical presentation, but gastrointestinal (GI) dysfunction significantly affects quality of life. To investigate the structural, functional, and cellular basis of gut dysmotility in MSMDS, we reviewed clinical data from 24 patients with MSMDS and studied the ACTA2 R179H mouse model. Patients exhibited severe gut dysmotility, with 75% requiring medication for chronic constipation. ACTA2 mutant mice displayed cecal and colonic dilatation, reduced intestinal length, and disrupted colonic migrating motor complexes. Delayed whole-gut transit and impaired contractile responses to electrical and pharmacological stimulation were observed. Transcriptomic analysis revealed significant actin cytoskeleton-related gene changes in smooth muscle cells, and immune profiling identified increased lymphocytic infiltration. Despite functional abnormalities, there were no obvious changes in the enteric nervous system. These findings establish ACTA2 mice as a robust model for studying GI pathology in MSMDS, elucidating the role of smooth muscle dysfunction in gut dysmotility. This model provides a foundation for developing targeted therapies aimed at restoring intestinal motility by directly addressing actin cytoskeletal disruptions in smooth muscle cells.

Animals↗
PubMed2005

Balance of IL-10 and interferon-gamma plasma levels in human visceral leishmaniasis: implications in the pathogenesis.

BACKGROUND: Leishmaniasis remains a serious public health problem in several parts of the developing world. Effective prophylactic measurements are hampered by imprecise comprehension of different aspects of the disease, including its immunoregulation. A better comprehension of immunoregulation in human VL may be useful both for designing and evaluating immunoprophylaxis. METHODS: To explore immunoregulatory mechanisms, 20 visceral leishmaniasis (VL) patients were evaluated during active disease and at different periods up to one year after treatment determining their plasma cytokine levels, clinical parameters (palpable spleen and liver) and antibody levels. RESULTS: Elevated plasma levels of IFN-gamma and of IL-12 p40 were observed during active disease, significantly decreasing after treatment whereas in vitro Leishmania antigen-stimulated IFN-gamma production by PBMC exhibited an inverse pattern being low during disease and increasing steadily thereafter. Absence of IFN-gamma activity is a hallmark of VL. The main candidate for blunting IFN-gamma activity is IL-10, a cytokine highly elevated in plasma with sharp decrease after treatment. Activity of IL-10 is inferred by high levels of anti-Leishmania specific IgG1 and IgG3. TGF-beta had elevated total, but not of active, levels lessening the likelihood of being the IFN-gamma counterpart. Spleen or liver size presented a steady decrease but return to normal values at only 120 days after treatment. Anti-Leishmania IgG (total and subclasses) levels and DTH or Leishmania-stimulated lymphocyte proliferation conversion to positive also present a slow decrease after treatment. IL-6 plasma levels were elevated in only a few patients. CONCLUSION: Taken together our results suggest that IFN-gamma and IL-10 are the molecules most likely involved in determining fate of disease. After treatment, there is a long delay before the immune profile returns to normal what precludes using plasma cytokine levels as criteria of cure as simpler clinical evaluations, as a palpable spleen or liver, can be used.

Adolescent↗
PubMed2003

Dendritic cell-based vaccination in solid cancer.

PURPOSE: Dendritic cell (DC)-based immunotherapy is rapidly emerging as a viable tool in cancer treatment. This approach has been used mostly in patients in the presence of defined tumor antigens such as melanoma. In this study, cancer patients with advanced disease that lacks defined tumor antigens were vaccinated with tumor lysate-pulsed DCs. PATIENTS AND METHODS: Twenty patients (pancreatic, hepatocellular, cholangiocellular, and medullary thyroid carcinoma) with stage IV disease were enrolled in the study. In 3-week intervals, freshly isolated autologous CD14 magnetic bead-selected monocytes were cultured in granulocyte-macrophage colony-stimulating factor and interleukin-4 to obtain immature DCs. These cells were pulsed with autologous tumor lysate and matured with tumor necrosis factor alpha. Mature DCs were applied into a groin lymph node, under ultrasound guidance. Adjuvant interleukin-2 (20,000 U/kg) was given subcutaneously daily, for 12 days, after each vaccination. Toxicity, tumor marker profile, immune response, and clinical response were determined. RESULTS: Vaccination was well tolerated. No physical signs of autoimmunity were detected. DC vaccination induced delayed-type hypersensitivity reactivity in 18 patients. Tumor marker responses were observed in eight patients. In addition, in three patients the generation of interferon gamma-positive T cells was induced during the vaccination. Objective changes in measurable lesions or tumor markers were evident in seven of 20 assessed patients. None of the patients was found to meet the criteria for partial or complete responses. CONCLUSION: These data indicate that vaccination with autologous tumor-pulsed DCs generated from peripheral blood is safe and can induce tumor-specific cellular cytotoxicity. Clinical responses are achievable, even in patients with advanced disease.

Adult↗
PubMed2006

Increased adverse drug reactions to antimicrobials and anticonvulsants in patients with HIV infection.

OBJECTIVE: To review the incidence, signs, symptoms, and mechanisms of adverse drug reactions (ADRs) to sulfonamides, anticonvulsants, and antimycobacterial medications among people with HIV. DATA SOURCES: Searches of MEDLINE/PubMed (1980-November 2005) and National Library of Medicine Meeting Abstracts (1989-November 2005), as well as hand searches of journals and abstracts, were conducted to identify primary literature. Reference lists were reviewed to identify additional relevant reports. STUDY SELECTION AND DATA EXTRACTION: Relevant articles and abstracts, particularly of in vitro experiments and clinical studies, were compiled and reviewed. DATA SYNTHESIS: ADRs, especially in HIV-infected patients, are a cause for concern. Sulfonamides, anticonvulsants, and antimycobacterial drugs are commonly used to prevent and treat complications of HIV, including seizures and opportunistic infections. Patients with HIV have a much greater rate of ADRs to these drug classes, including severe and life-threatening hypersensitivity reactions. Several mechanisms of these ADRs have been postulated. Sulfamethoxazole and anticonvulsant hypersensitivity may involve the increased formation and decreased detoxification of reactive metabolites. The mechanisms for the marked increase in hypersensitivity ADRs to antimycobacterial drugs may be related to an altered immune profile in patients infected with both tuberculosis and HIV. CONCLUSIONS: ADRs to antimicrobial and anticonvulsant therapy cause markedly increased morbidity and mortality in HIV-positive patients. Further research involving the interaction between HIV and the increased ADRs to these drugs is required.

Anti-Infective Agents↗
PubMed2025

Mycobacterium tuberculosis complex Lineage 1: A neglected cause of tuberculosis.

The Mycobacterium tuberculosis complex (MTBC) phylogenetic lineages 1-4 (L1-L4) are the main causes of human tuberculosis (TB). Until now, most of the focus in the TB field has been on MTBC L2 and L4, as these two lineages are geographically widespread and have been repeatedly associated with multidrug resistance. By comparison, MTBC L1 has received little attention, partially because of its restricted geographical range that mainly includes low- to middle-income countries in South and Southeast Asia, and East Africa. However, recent estimates indicate that MTBC L1 is in fact the most common cause of human TB in terms of absolute numbers of TB patients, particularly among several high TB burden countries. As more L1 strains are being sampled in L1-endemic countries, the high genetic diversity of this geographically restricted MTBC lineage is slowly uncovered. This discovery has also impacted L1 nomenclature, which has been modified as new distinct L1 clades were identified. In parallel to the genomic discoveries ushered by progress in whole genome sequencing, clinical researchers have also studied several phenotypes that better describe L1 TB disease. L1 strains have been shown to have increased vulnerability to oxidative stress, which was associated with decreased virulence in animal and in vitro models. L1 infection also shows possible association with extrapulmonary TB and asymptomatic TB. However, despite belonging to the same lineage, L1 strains display phenotypic diversity that can be attributed to high within-lineage genetic diversity and possibly the interaction of different L1 genotypes with different human host genotypes. Among the clinical phenotypes that show heterogeneity are bacterial factors, immune profiles, and clinical virulence. The traditional view regarding the reduced transmissibility in L1 is now being challenged by new data indicating that L1 may be as transmissible as L2 or L4. Lastly, although historically referred to as being negatively associated with drug resistance, there is indication that the contribution of L1 to TB drug resistance is significant and that it may evolve drug resistance in ways distinct from those of other MTBC lineages.

Mycobacterium tuberculosis↗
PubMed2003

Hepatitis A and considerations regarding the cost-effectiveness of vaccination programs.

Hepatitis A vaccines have demonstrated a high degree of immunogenicity and an excellent safety profile. Immunization of certain populations and patient subgroups is recommended according to specific epidemiological and clinical factors, such as a greater likelihood of acquisition of infection or concerns regarding the risk of development of fulminant hepatitis and death. Therefore, the economic implications of routine and/or targeted vaccination programs in the general population and high-risk individuals have been examined. In this manuscript, the available data from the literature regarding the cost-effectiveness of hepatitis vaccination programs in healthy individuals and in those with chronic liver disease are reviewed.

Cost-Benefit Analysis↗
PubMed1986

Rapidly progressive periodontitis. Report of a case.

A nineteen year old white female was referred for an evaluation of severe, rapidly progressive periodontitis. Although the patient was physically healthy and did not demonstrate any remarkable abnormalities in routine laboratory tests or upon physical examination, a detailed immune profile elucidated abnormal findings. Additionally, the patient demonstrated a poor healing response after tooth removal and a continued loss of bone following insertion of dentures.

Adult↗
PubMed2003

Alteration in thyroid after formaldehyde (HCHO) treatment in rats.

Formaldehyde (HCHO) exposure in industry causes health impairment, especially immune profile. Male albino rats when exposed to HCHO at 5, 10, 15 mg/kg day for 30 days showed decrease in thyroid weight in 10, 15 mg/kg/day HCHO fed group with commensurate follicular regression (epithelial cells), decreased triiodothyronine (T3), thyroxin (T4) deficiency and enhanced thyroid stimulating hormone (TSH). Repeated chemical stimulation might have increased thyroid activity of the follicles and rapidly deteriorated the capacity for synthesis of thyroxin hormone and thus becomes atrophied. The chronic action of HCHO on thyroid may be due to a block at the source of thyroid hormone (s).

Animals↗
PubMed1994

Human Th1 and Th2 cells: functional properties, regulation of development and role in autoimmunity.

Evidence has accumulated suggesting the existence in humans of polarized T helper (Th) cell subsets, coded as Th1 and Th2, with defined cytokine secretion profiles. Immune responses to intracellular bacteria and viruses result in the preferential development of the Th1 cell subset. Th1 cells express cytolytic activity against antigen-presenting cells and provide helper function for IgM, IgG and IgA synthesis only at low T/B cell ratios. In contrast, Th2 cells develop in response to allergens or helminth antigens, provide help for all immunoglobulin classes, including IgE, and lack cytolytic potential. The cytokine milieu in the microenvironment plays a fundamental role in determining the functional phenotype of the subsequent antigen-specific Th1 or Th2 responses. In recent years it has become clear that Th1 and Th2 cells play different roles not only in protection against exogenous offending agents, but also immunopathology. Th2 cells are involved in immunopathology induced by helminths and are responsible for the initiation and maintenance of allergic disorders. Th1 cells seem to be involved in contact dermatitis, acute allograft rejection and organ-specific autoimmunity, such as thyroid autoimmune disorders, diabetes mellitus or multiple sclerosis, whereas less polarized patterns of Th cells are detectable in target organs of patients with rheumatoid arthritis. Sjogren's syndrome or systemic lupus erythematosus.

Autoimmunity↗
PubMed2003

Induction of autoantigen-specific Th2 and Tr1 regulatory T cells and modulation of autoimmune diabetes.

Autoantigen-based immunotherapy can modulate autoimmune diabetes, perhaps due to the activation of Ag-specific regulatory T cells. Studies of these regulatory T cells should help us understand their roles in diabetes and aid in designing a more effective immunotherapy. We have used class II MHC tetramers to isolate Ag-specific T cells from nonobese diabetic (NOD) mice and BALB/c mice treated with glutamic acid decarboxylase 65 peptides (p206 and p221). Based on their cytokine secretion profiles, immunization of NOD mice with the same peptide induced different T cell subsets than in BALB/c mice. Treatment of NOD mice induced not only Th2 cells but also IFN-gamma/IL-10-secreting T regulatory type 1 (Tr1) cells. Adoptive transfer experiments showed that isolated tetramer(+) T cells specific for p206 or p221 could inhibit diabetes development. These cells were able to suppress the in vitro proliferation of other NOD mouse T cells without cell-cell contact. They performed their regulatory functions probably by secreting cytokines, and Abs against these cytokines could block their suppressive effect. Interestingly, the presence of both anti-IL-10 and anti-IFN-gamma could enhance the target cell proliferation, suggesting that Tr1 cells play an important role. Further in vivo experiments showed that the tetramer(+) T cells could block diabetogenic T cell migration into lymph nodes. Therefore, treatment of NOD mice with autoantigen could induce Th2 and Tr1 regulatory cells that can suppress the function and/or block the migration of other T cells, including diabetogenic T cells, and inhibit diabetes development.

Adoptive Transfer↗
PubMed2005

Regulatory T cells and cytokines in malignant pleural effusions secondary to mesothelioma and carcinoma.

Immunotherapy against a variety of malignancies, including pleural-based malignancies, has shown promise in animal models and early human clinical trials, but successful efforts will need to address immunosuppressive factors of the tumor and host, particularly certain cytokines and CD4(+) CD25(+) regulatory T cells (Treg). Here, we evaluated the cellular and cytokine components of malignant pleural effusions from 44 patients with previously diagnosed mesothelioma, non-small cell lung cancer (NSCLC), or breast cancer and found significant differences in the immune profile of pleural effusions secondary to mesothelioma vs. carcinoma. Although a high prevalence of functionally suppressive CD4(+) CD25(+) T cells was found in carcinomatous pleural effusions, mesothelioma pleural effusions contained significantly fewer CD4(+) CD25(+) T cells. Activated CD8(+) T cells in pleural fluid were significantly more prevalent in mesothelioma than carcinoma. However, there is clear patient-to-patient variability and occasional mesothelioma patients with high percentages of CD4(+) CD25(+) pleural effusion T cells and low percentages of CD8(+) CD25(+) pleural effusion T cells can be identified. Mesothelioma pleural effusions contained the highest concentrations of the immunosuppressive cytokine transforming growth factor (TGF)-beta. Thus, the contribution of cellular and cytokine components of immunosuppression associated with malignant pleural effusions varies by tumor histology and by the individual patient. These results have implications for the development of immunotherapy directed to the malignant pleural space, and suggest the need to tailor immunotherapy to overcome immunosuppressive mechanisms in tumor environments.

Breast Neoplasms↗
PubMed1978

[Arterial hypertension in pregnancy: current concepts].

Although the term hypertension in pregnancy is a simple and uncontroversial one, it unfortunately encompasses some ill defined clinical conditions as well as pre-eclampsia. The prime cause of pre-eclampsia is utero-placental ischaemia. Such utero-placental ischaemia is responsible for the hypothetical secretion of a vasopressor agent and for intravascular coagulation. An immunological cause should also be suspected: a study of the immune profile of the kidney has shown that the glomerular capillaries contain immunoglobulins G and M as well as the C3 fraction of complement. Renal biopsies carried out three months after delivery have shown deposits of C3 in the arteriolar walls. During normal pregnancy, there exists a state of stable equilibrium of hormonal, haemodynamic, haematological and immunological factors. It seems that all components of this equilibrium are disturbed in cases of hypertension in pregnancy.

Adolescent↗
PubMed2000

Hypocomplementemic urticarial vasculitis and lower cranial nerve palsies.

A 55 years post menopausal lady presented with puffiness of face, and a pruritic urticarial rash over face and upper trunk of one week duration with accompanying dysphagia. Clinical examination revealed an urticarial rash over face and upper trunk, two small ulcers over floor of mouth and evidence of bilateral VIII, IX and Xth cranial nerve palsies. Hypocomplementemia, negative immune profile and evidence of vasculitis on skin biopsy suggested a diagnosis of hypocomplementemic urticarial vasculitis. The patient responded to a course of steroids.

Complement C3↗
PubMed2001

Relevance of the rates of PCNA, Ki-67 and p53 expression according to the epithelial compartment in cervical lesions.

In order to assess further biological evidence for similarities among the "diagnostic classes" of cervical lesions, which are now a matter of international discussion in the search for a uniform classification, the purpose of this study was to characterize the immunoexpression of cell proliferation markers (proliferating cell nuclear antigen, PCNA and Ki-67) and protein p53. Each marker was individually quantified in basal, intermediate, and superficial epithelial compartments presenting chronic cervicitis (CC) accompanied by the cytopathic effects of infection by human papillomavirus (CCHPV) or not (CC), as well as in cervical intraepithelial neoplasia (CIN) grades I, II, and III. A total of 100 patients were evaluated and the positive nuclei were counted separately, including all extensions of the available epithelium. The percentage of PCNA- and Ki-67-positive cells increased with increasing grade of the cervical lesions, although PCNA immunoreactivity was always greater than the immunoreactivity observed with Ki-67 antigen. The immunoexpression of p53 protein was found to be weak, with no remarkable behavior in any specific "diagnostic class". The differences in cell proliferation markers found herein further emphasize the progressive loss of epithelial layer organization in the course of the development of preneoplastic changes in cervical squamous epithelium. Furthermore, difficulties in morphologically distinguishing "borderline lesions" persist when cell cycle markers are studied, further supporting the suggestion to consider the lesions of CCHPV and CIN I together as only one diagnostic class. Conversely, the different immune profile found between CIN II and III further supports the validity of the subdivision of CIN into three groups.

Biomarkers, Tumor↗
PubMed1984

Immunodiagnosis of bacterial meningitis.

The quest for the search of rapid, cheap, easy to perform and highly sensitive and specific tests has resulted into the introduction and application of various new tests for the diagnosis of bacterial meningitis. Most of these tests are based on immunological principles, viz. counter-immunoelectrophoresis, latex agglutination test, co-agglutination, radio-immunoassay, haemagglutination inhibition as well as study of immune profile of cerebrospinal fluid. Apart from these certain non-immunological tests viz. Limulus amoebecyte lysate test, gas liquid chromatography, nitroblue tetrazolium dye reduction test have also been evaluated to make the laboratory diagnosis of this important clinical entity rapid and more reliable. These tests have been discussed and their current status presented.

Counterimmunoelectrophoresis↗
PubMed1992

Issues related to dust aerosols in the magnesite industry. I. Chamber exposure.

The present paper is an overview of the experimental research into the effects of flue magnesite dust in the magnesite industry in which the raw material (magnesite) is processed into refractory magnesite clinker. The issues related to dust are divided into two problem areas: a) dust aerosol arising in the process of ore mining and consisting largely of magnesite (MgCO3) and b) dust aerosol originating during ore baking in rotatory furnaces and made up mostly of MgO. Thus, larger groups of people become exposed to these aerosols as a result of solid particles escaping into the atmosphere than in the case of occupational exposure. Experimental research carried out on laboratory animals after chamber exposure provided findings on the deposition, retention and elimination of magnesite dust, on impaired balance between magnesium and calcium leading to damage of biological membranes, on how the immune profile or reproduction and embryogenesis is impacted as well as on the possible interaction with sodium salicylate as a result of an impaired acid base balance. These findings are followed up by evidence produced in the course of biological monitoring (Part II).

Animals↗
PubMed1976

[Mixed organ culture as new possibility for study of cellular immune phenomena according to Krebs].

A method for the detection of cellular tumor-versus-host relations is described, which consist in cultivating human tumor material together with autologous lymphocytes in one organ system and in determinating tumor and lymphocyte DNA synthesis separately before and after mixed organ culture. Advantages and disadvantages of this method are discussed. 58 human tumors were investigated (40 mammary, 13 gastric, 5 bronchial cancers). 37 tumors showed a sufficient in vitro growth. In about 50% of the mixed organ cultures, there was an increase in lymphocyte DNA synthesis compared to the controls. On the other hand, only in 9 cases a decrease in the tumor DNS synthesis could be observed under the influence of autologous lymphocytes. The investigations emphasize the individuality of the tumor-versus-host relations and lead to the consequence of a routine determination of the immune profile by a spectrum of several methods in tumor patients as a prognostic and therapeutic aid.

Breast Neoplasms↗
PubMed2004

Thyroid autoantibodies in autoimmune diseases.

Abnormalities in the thyroid function and thyroid autoantibodies have been frequently described in patients with autoimmune diseases but seldom in antiphospholipid syndrome patients. In order to determine the prevalence of thyroid function and autoimmune abnormalities, we compared serum thyrotropin (TSH, serum free thyroxine (T4) levels, thyroid antithyroglobulin (TgAb) and antithyroperoxidase (TPOAb) levels of 25 patients with systemic sclerosis, 25 patients with rheumatoid arthritis and 13 patients with antiphospholipid syndrome to a control group of 113 healthy individuals. Evaluation included a thorough clinical examination with particular attention to thyroid disease and a serologic immune profile including rheumatoid factor, antinuclear and anticardiolipin antibody measurements. Subclinical hypothyroidism (4.2<TSH<10 mU/L) was diagnosed in five patients (8%), and subclinical hyperthyroidism (undetectable<TSH<0.34 mU/L) in four patients (6%). Anti-thyroglobulin (TgAb) and/or anti-thyroperoxidase (tPOAb) antibodies were present in 21/63 (33%) of our patients: 13/25 (52%) of the systemic sclerosis cases, 8/25 (32%) of the rheumatoid arthritis patients, but 0 (0/13) of the antiphospholipid syndrome patients. In conclusion, our data confirm a high prevalence of silent autoimmune thyroid diseases in association with systemic sclerosis and rheumatoid arthritis (p<0.02), but not with antiphospholipid syndrome. Elevated antibody titres may reflect an epiphenomenon of the underlying autoimmune disorders and play an additive role in the development of the euthyroid sick syndrome in these patients, but our data suggest that the antiphospholipid syndrome presents a different pattern of response. Subclinical thyroid diseases should be considered when evaluating patients with autoimmune diseases.

Adult↗