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At least 1,333 records · Page 74Linked to original sources
PubMed2003

Dissemination of bacteria in multiple organs associated with apoptosis and macrophage activity in different stages of experimental sepsis.

BACKGROUND: Gram negative sepsis is reported to induce massive translocation of bacteria into tissues, which associates with decreased macrophage function and increased macrophage apoptosis. AIMS: The objective of this study was to detect the translocation of bacteria into different organs and to evaluate macrophage activity and the apoptosis of macrophages in the liver during different stages of sepsis and to correlate these parameters. MATERIAL: Wistar rats (n = 43) were inoculated intraperitoneally with an E. coli and divided into 5 groups, which were killed at different times. METHODS: Counts of translocated bacteria in tissues were evaluated by using morphological and bacteriological methods. Macrophage activity and apoptotic cells in the liver were studied by applying immunohistochemical methods. RESULTS: The counts of E. coli were the highest in the organs and blood 6 h after the onset of sepsis, being in correlation with the highest counts of apoptotic cells in the liver and the falling counts of activated macrophages. The counts of microbes show a new wave of elevation in tissues by 120th h. CONCLUSIONS: The massive penetration of bacteria, the depressed macrophage response in early sepsis following the increased rate of apoptotic macrophages, the different rate of bacterial multiplication in tissues and blood and the second wave of the multiplication of bacteria in tissues in late sepsis all refer to the significance of developing immune dysfunction.

Animals↗
PubMed2006

(A3) HIV Phenotypes, oral lesions, and management of HIV-related disease.

Workshop participants discussed: the role of HIV subtypes in disease; the treatment of oral candidiasis; the relationship between and among viral load, CD4+ counts, oral candidiasis and oral hairy leukoplakia, pigmentation; and the development of a reliable oral index to predict disease progression. Regarding HIV, the literature revealed that Type I (HIV-I), in particular group M, is involved in the majority (90%) of documented infections, and groups N and O to a lesser extent. Viral envelope diversity led to the subclassification of the virus into nine subtypes, or clades-A-D, F-H, J, and K-each dominating in different geographical areas. HIV-2, currently occurring mostly in West Africa, appears to be less virulent. No evidence could be produced of any direct impact of type, subtype, or clade on oral lesions, and participants believed that further research is not feasible. Oral candidiasis in patients from resource-poor countries should be prevented. When the condition does occur, it should be treated until all clinical symptoms disappear. Oral rinsing with an antimicrobial agent was suggested to prevent recurrence of the condition, to reduce cost, and to prevent the development of antifungal resistance. Lawsone methyl ether, isolated from a plant (Rhinacanthus nasutus leaves) in Thailand, is a cost-effective mouthrinse with potent antifungal activity. Evidence from a carefully designed prospective longitudinal study on a Mexican cohort of HIV/AIDS patients, not receiving anti-retroviral treatment, revealed that the onset of oral candidiasis and oral hairy leukoplakia was heralded by a sustained reduction of CD4+, with an associated sharp increase in viral load. Analysis of the data obtained from a large cohort of HIV/AIDS patients in India could not establish a systemic or local cause of oral melanin pigmentation. A possible explanation was a dysfunctional immune system that increased melanin production. However, longitudinal studies may contribute to a better understanding of this phenomenon. Finally, a development plan was presented that could provide a reliable prediction of disease progression. To be useful in developing countries, the index should be independent of costly blood counts and viral load.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Lack of changes in soluble interleukin-2 receptor serum levels during chemotherapy-induced lymphocyte damage.

The biological significance of soluble IL-2 receptors (sIL-2R) is still unknown; in particular, it is not yet clear whether their increase in the blood may reflect activation of immune cells, or whether it is related to an immune dysfunction. To investigate this problem, we evaluated serum levels of sIL-2R before and after administration of a highly lymphocytolitic chemotherapy (FEC: fluorouracil, epirubicin, cyclophosphamide) in a group of 6 patients with advanced breast cancer. SIL-2R were analyzed in relation to lymphocyte number. Absolute mean number of lymphocytes was significantly lower after than before chemotherapy. On the contrary, no significant difference was seen in sIL-2R mean levels, and no significant correlation was observed between changes in sIL-2R and in lymphocyte number following chemotherapy. These results would exclude that sIL-2R may simply be due to a passive release following lymphocytic damage.

Adult↗
PubMed1991

Presence of adenosine deaminase on the surface of mononuclear blood cells: immunochemical localization using light and electron microscopy.

Adenosine deaminase, which is essential for lymphoid differentiation and function, has previously been considered to be a cytosolic enzyme. In this report we demonstrate that it can be found associated with the plasma membrane of lymphocytes. By means of immunological techniques using both light and electron microscopy, adenosine deaminase was localized on the external side of the plasma membrane of normal lymphocytes and monocytes. Since the enzyme expression differed depending on the type of cell examined, new hypotheses about the mechanisms involving purine metabolism in immune dysfunctions or immunodeficiency syndromes may be considered.

Adenosine Deaminase↗
PubMed2001

Full hematopoietic engraftment after allogeneic bone marrow transplantation without cytoreduction in a child with severe combined immunodeficiency.

Bone marrow transplantation (BMT) for severe combined immunodeficiency (SCID) with human leukocyte antigen (HLA)-identical sibling donors but no pretransplantation cytoreduction results in T-lymphocyte engraftment and correction of immune dysfunction but not in full hematopoietic engraftment. A case of a 17-month-old girl with adenosine deaminase (ADA) deficiency SCID in whom full hematopoietic engraftment developed after BMT from her HLA-identical sister is reported. No myeloablative or immunosuppressive therapy or graft-versus-host disease (GVHD) prophylaxis was given. Mild acute and chronic GVHD developed, her B- and T-cell functions became reconstituted, and she is well almost 11 years after BMT. After BMT, repeated studies demonstrated: (1) Loss of a recipient-specific chromosomal marker in peripheral blood leukocytes (PBLs) and bone marrow, (2) conversion of recipient red blood cell antigens to donor type, (3) conversion of recipient T-cell, B-cell, and granulocyte lineages to donor origin by DNA analysis, and (4) increased ADA activity and metabolic correction in red blood cells and PBLs.

Adenosine Deaminase↗
PubMed2003

Genetic aspects of susceptibility to air pollution.

Inter-individual variation in human responses to air pollutants suggests that some subpopulations are at increased risk, and it is increasingly clear that genetic background is an important susceptibility factor. Genetically standardised animal models provide useful investigative tools. Linkage analyses using inbred mice identified chromosomal segments (quantitative trait loci (QTL)), with genes controlling susceptibility to the lung inflammatory (chromosome 17), injury (chromosome 11), and hyperpermeability (chromosome 4) responses to ozone (O3) exposure. An immune dysfunction response induced by exposure to sulphate-associated particles is linked to the identical chromosome 17 and 11 QTLs described for O3 susceptibility, thus similar genetic mechanisms may be controlling pulmonary responses to these pollutants. Candidate genes within the QTLs on chromosomes 4 and 17 include the toll-like receptor 4 and the pro-inflammatory cytokine, tumour necrosis factor-alpha, respectively. Functional analyses strongly support a role for these candidate genes in determining susceptibility to O3 and particulates. Because striking linkage homology exists between the human and mouse genomes, candidate susceptibility genes identified in the mouse are likely to aid research aimed at understanding human genetic factors that contribute to differential susceptibility. To date, no studies have examined the interaction between age and genetic background in the development of air pollution-induced lung disease. However, investigations have suggested an influence of age on genetic susceptibility to lung cancer and other diseases, which indicate that an interaction between age and genetic background may be important in air pollution disease pathogenesis.

Age Factors↗
PubMed1991

Interleukin-2 and lymphokine-activated killer cells in 15 children with advanced metastatic neuroblastoma.

A phase II trial using interleukin-2 (IL2) and lymphokine-activated killer (LAK) cells was carried out in an attempt to treat children with end-stage neuroblastoma. Fifteen patients (median age, 7 years) were enrolled in the study. Twelve were in relapse after massive chemotherapy and autologous bone marrow transplantation (ABMT), and three had a primary refractory disease after conventional chemotherapy. IL2 was administered as an 18 x 10(6) IU/m2/d continuous infusion. One course consisted of a double 5-day treatment period separated by a 6-day break. Cytapheresis to harvest LAK progenitor cells was performed during the rest period. After a 4-day in vitro culture, LAK cells were reinjected during the second cycle of therapy. A phenotypic and functional analysis of immunologic parameters was conducted along with the therapeutic protocol. Toxicity was significant with two toxic deaths (cardiotoxicity and respiratory distress). The reinfusion of large amounts of LAK cells was clearly involved in one case, but this particularly severe toxicity has to be related to the patient's status (ie, heavy pretreatment). No significant clinical response was seen. The immunologic monitoring showed phenotypic and functional modifications in these patients before initiation of treatment and an unexpected absence of evolution of these parameters during IL2 therapy. Although the origin of these immune dysfunctions is not clear, they could be involved in the failure of IL2 therapy. Future studies of IL2 therapy in neuroblastoma should be undertaken earlier in the course of the disease.

Antibodies, Monoclonal↗
PubMed1995

Extramedullary myeloid cell tumors in acute nonlymphocytic leukemia: a clinical review.

PURPOSE: To discuss the predisposing risk factor for all forms of extramedullary leukemia (EML) and to review the clinical features, prognostic significance, and treatment strategies for primary EML and leukemia cutis (LC)/granulocytic sarcomas (GS) in the setting of acute nonlymphocytic leukemia (ANLL). METHODS: A review of all reports published since 1965 related to all forms of extramedullary leukemia (LC, GS, gingival hypertrophy, and meningeal leukemia [ML]). RESULTS: Several factors, including chromosomal abnormalities [t(8;21), inv(16)], cell-surface markers (CD56, CD2, CD4, CD7), French-American-British (FAB) subtype (M2, M4, M5), blast differentiation and maturation, patient nutritional status, age, cellular immune dysfunction, high presenting leukocyte count, and decreased blast Auer rods, have been associated with a higher incidence of EML. Of 154 published cases of primary EML identified, 71 (46%) were initially misdiagnosed. The addition of immunohistochemical stains can assist in preventing such misdiagnoses and should be included in all atypical lymphoma/carcinoma cases. Only one of the patients (3%) with primary EML did not progress to ANLL in the absence of chemotherapy. In contrast, 66% of patients who received chemotherapy for the primary EML never developed ANLL. The prognostic significance of EML at presentation and medullary relapse of ANLL is uncertain. Isolated extramedullary recurrence of ANLL always heralds bone marrow relapse and should be treated with reinduction chemotherapy. Close clinical follow-up observation is necessary to insure resolution of EML. Radiation therapy is an effective local treatment for resistant or symptomatic EML. CONCLUSION: Many advances in diagnoses and treatment of EML have been made. Future investigations are needed to define the clinical significance of EML in patients with ANLL treated with modern chemotherapy or bone marrow transplantation.

Age Factors↗
PubMed2003

Osteoclast apoptosis: the role of Fas in vivo and in vitro.

Both the number and the activity of osteoclasts are critical for maintaining normal bone turnover. The number is determined by rates of cell differentiation and death. Fas-mediated apoptosis is a dominant mechanism for apoptosis. Here, we show the presence of the Fas receptor on mouse, human, avian, and cultured RAW264.7 (murine) derived osteoclasts and the up-regulation of its expression during mouse osteoclast differentiation. Additionally, Fas is a fully functional death receptor in osteoclasts, and its signaling pathway is consistent with classical Fas signaling in other cell systems, involving mitochondrial release of cytochrome c and activation of caspases 3 and 9. This demonstration of Fas-mediated apoptosis in mature osteoclasts provides a new and potent mechanism for the regulation of osteoclast life span. The in vivo significance of Fas-mediated apoptosis in bone (osteoclasts) was demonstrated in aged Lpr and Gld mice, which have a dysfunctional immune system. Lpr mice, which have a defect in the Fas gene, have decreased bone mineral density, bone volume, trabecular thickness, and increased osteoclast number. Gld mice, which have a Fas ligand mutation, have a slight yet insignificant decrease in bone mineral density, but a highly significant increase in osteoclast number. Taken together, these data demonstrate that the Fas/Fas ligand system is important in the regulation of bone turnover and may represent a critical link between the immune system and bone remodeling in development and in various diseases.

Animals↗
PubMed2004

Congenital leptin deficiency due to homozygosity for the Delta133G mutation: report of another case and evaluation of response to four years of leptin therapy.

Congenital leptin deficiency is a rare, but treatable, cause of severe early-onset obesity. To date, two United Kingdom families of Pakistani origin carrying a frameshift/premature stop mutation, c.398delG (Delta133G), and one Turkish family carrying a missense mutation, c.313C>T (Arg(105)Trp), have been described. Affected subjects are homozygotes and manifest severe obesity and hyperphagia accompanied by metabolic, neuroendocrine, and immune dysfunction. The effects of recombinant leptin therapy have been reported in three children with the Delta133G mutation, and in all cases this has led to a dramatic resolution of clinical and biochemical abnormalities. We now report a Canadian child, of Pakistani origin but unrelated to the previously reported subjects, presenting with severe hyperphagia and obesity, who was found to be homozygous for the Delta133G mutation. In this child, 4 yr of therapy with sc injections of recombinant leptin provided additional evidence for the sustained beneficial effects of leptin replacement on fat mass, hyperinsulinemia, and hyperlipidemia. In addition, leptin administration corrected abnormal thyroid biochemistry and allowed the withdrawal of T(4) treatment, providing additional support for the role of leptin in the regulation of the human hypothalamic-pituitary-thyroid axis.

Body Composition↗
PubMed2004

Is there still a place for dopamine in the modern intensive care unit?

For many years, dopamine was considered an essential drug in the intensive care unit (ICU) for its cardiovascular effects and, even more, for its supposedly protective effects on renal function and splanchnic mucosal perfusion. There is now ample scientific evidence that low dose dopamine is ineffective for prevention and treatment of acute renal failure and for protection of the gut. Until recently, low-dose dopamine was considered to be relatively free of side effects. However, it is now clear that low-dose dopamine, besides not achieving the preset goal of organ protection, may also be deleterious because it can induce renal failure in normo- and hypovolemic patients. Furthermore, dopamine may cause harm by impairing mucosal blood flow and by aggravating reduced gastric motility. Dopamine also suppresses the secretion and function of anterior pituitary hormones, thereby aggravating catabolism and cellular immune dysfunction and inducing central hypothyroidism. In addition, dopamine blunts the ventilatory drive, increasing the risk of respiratory failure in patients who are being weaned from mechanical ventilation. We conclude that there is no longer a place for low-dose dopamine in the ICU and that, in view of its side effects, its extended use as a vasopressor may also be questioned.

Animals↗
PubMed2003

The refeeding syndrome and hypophosphatemia.

The refeeding syndrome is an underappreciated entity characterized by acute electrolyte derangements--notably hypophosphatemia--that occur during nutritional repletion of patients with significant suboptimal caloric intake. Adverse effects of hypophosphatemia include cardiac failure, muscle weakness, immune dysfunction, and death. Hypokalemia and hypomagnesemia commonly complicate refeeding syndrome as well; however, this report briefly reviews the clinical manifestations of refeeding-induced hypophosphatemia.

Aged↗
PubMed2001

Pulmonary infectious mortality among patients with end-stage renal disease.

BACKGROUND: Infection is the second-leading cause of death among patients with end-stage renal disease (ESRD). This is due in part to advanced age, comorbid conditions, and immune dysfunction observed in uremic states. Although one may hypothesize that pulmonary infectious mortality is higher among patients with ESRD compared with the general population (GP), no such data are currently available. METHODS: We compared annual pulmonary infectious mortality rates among patients with ESRD to those in the GP. The data were abstracted from the United States Renal Data System and the National Center for Health Statistics, respectively, and were stratified by age, gender, race, and presence or absence of diabetes mellitus (DM). In the GP, primary and multiple cause-of-death analyses were performed to account for potential limitations of the data sources. RESULTS: Overall, pulmonary infectious mortality rate was 14-fold to 16-fold higher in dialysis patients and approximately twofold higher in renal transplant recipients compared with the GP. After stratification for age, differences between groups decreased but retained their magnitude. CONCLUSION: Patients with ESRD treated with dialysis have higher pulmonary infectious mortality rates compared with the GP, even after stratification for age, race, and DM. Consequently, this patient population must be considered at high risk for the development of lethal pulmonary infections.

Adult↗
PubMed1991

HIV and periodontal health. A study of military personnel with HIV.

In 230 military personnel who were seropositive for the human immunodeficiency virus, the prevalence of viral and fungal infections in the mouth was clearly related to the degree of immune dysfunction as measured by T4-lymphocyte counts. The relation between periodontal health and T4 counts was less clear. Tobacco use was related to the increased occurrence of both mucosal lesions and periodontal diseases.

Adolescent↗
PubMed1999

Association between reduced human leukocyte antigen (HLA)-DR expression on blood monocytes and increased plasma level of interleukin-10 in patients with severe burns.

Severe thermal injury causes an immune dysfunction which includes a decrease of monocyte human leukocyte antigen DR (HLA-DR) expression. Interleukin-10 exerts a negative influence on this parameter in vitro. In this study we determined the prognostic value of reduced monocyte HLA-DR expression with regard to infectious complications, and the in vivo association between monocyte HLA-DR and plasma interleukin-10 concentration. Both quantities were measured serially in 19 patients with severe burns. HLA-DR expression was determined by direct immunofluorescence on a flow cytometer, and interleukin-10 was measured by ELISA. After burn trauma the percentage of HLA-DR expressing monocytes fell markedly (median: 53% at day 2, 36% at day 4, 31% at day 7, 28% at day 9, 35% at day 12, and 42% at day 14; compared to 93% for healthy volunteers). Moreover, patients who became septic showed lower monocyte HLA-DR expression than non-septic patients; the differences were significant at day 2 (p < 0.01) and day 7 (p < 0.05). Plasma concentrations of interleukin-10 increased after thermal injury (median: 40 ng/l at day 2, 43 ng/l at day 4, 77 ng/l at day 7, 120 ng/l at day 9, 63 ng/l at day 12, and 82 ng/l at day 14). Individual HLA-DR expression and interleukin-10 concentration were negatively correlated, the association reaching statistical significance at day 4 (p=0.006) and day 7 (p=0.031). Thus, after severe burn injury monocyte HLA-DR expression has prognostic value and is negatively associated with interleukin-10 plasma concentration.

Adolescent↗
PubMed1999

Leucocyte activation markers in clinical practice.

The response against tissue injury and infection begins with the early activation of molecular and cellular elements of the inflammatory and immune response. Severe tissue injury, necrosis, and infection induce imbalanced inflammation associated with leukocyte over-stimulation and excessive or dysregulated release of cellular mediators. Clinical and experimental studies have shown that these mediators are directly related to progressive post-injury complications. Persistent increased levels of pro-inflammatory mediators produce tissue injury. Excessive production and activity of anti-inflammatory mediators cause anergy and/or immune dysfunction with increased susceptibility to infection. Leukocyte activation is assessed by cell surface phenotype expression, cellular mediators determination, or by measuring functional responses using isolated cells. Potential routine clinical uses are: evaluation of severity and prognosis in critically ill patients, immunomonitoring of sepsis, and detection of tissue injury, necrosis, and infection. In practice, the determination of cellular activation markers is restricted by a limited number of automated methods and by the cost of reagents. The availability of flow cytometry and immunoassay automated systems can contribute to a wider use in practice. Here we review the immunopathophysiology of polymorphonuclear neutrophil, monocyte, macrophage, and lymphocyte activation in response to tissue injury and infection. In addition, laboratory methods for their determination, and clinical applications in practice, are discussed.

Animals↗
PubMed2001

Development of agents for the treatment of systemic sclerosis.

Systemic sclerosis (SSc) is a multisystem connective tissue disease characterised clinically by fibrosis and ischaemic atrophy. Internal organ involvement can be life-threatening. Although there are effective treatments for some of the organ-based manifestations of SSc, for example proton-pump inhibitors for upper gastrointestinal disease, no drug has so far been proven to modify the underlying disease process. Our increased understanding of the pathogenesis of SSc, which involves a complex interplay between excessive collagen production, vascular abnormalities and immune dysfunction, is directing development of drugs which hold promise as 'disease-modifying' agents. Some of the drugs under investigation for the treatment of SSc have already been used in other conditions which 'overlap' with SSc, for example primary pulmonary hypertension. Conversely, it is to be hoped that in the future, drugs shown to be effective in SSc might prove beneficial for other fibrotic diseases.

Humans↗
PubMed2005

Emerging therapies in multiple sclerosis.

Multiple sclerosis (MS) is the most common neurological cause of disability in young people. The disease-modifying treatments, IFN-beta and glatiramer acetate, have been widely available over the last decade and have shown a beneficial effect on relapse rate and magnetic resonance imaging parameters of disease activity; however, their effect on disease progression and disability is modest. Therefore, the search for alternative treatment strategies continues. As understanding of the heterogeneous pathophysiology of MS has increased, emphasis has shifted to more selective therapy that targets components of the inflammatory cascade and the promotion of remyelination and neuroprotection. These agents target the blood-brain barrier, systemic immune dysfunction, local inflammation and neurodegeneration. Combination therapies are being investigated for patients who fail first-line treatments. Many new drugs are being developed and tested that address these issues with the aim of finding a more effective and convenient therapy. These include humanized monoclonal antibodies such as daclizumab (IL-2 antagonist), oral immunomodulators such as sirolimus and statins and neuroprotective agents such as NMDA antagonists and Na+-channel blockers. Many of the treatments discussed in this review are still at early stages of development, but provide exciting potential treatment options; others have proved disappointing in larger extended-phase studies.

Animals↗