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PubMed1997

The endocrine system: alcohol alters critical hormonal balance.

Alcohol's effects on the hormonal (i.e., endocrine) system have widespread consequences for virtually the entire body. Alcohol-related hormonal disturbances can result in cardiovascular abnormalities and reproductive deficits in both males and females. Other endocrine problems stemming from excess alcohol consumption include immune dysfunction and bone disease. Researchers are exploring ways of using hormonal mechanisms to help treat alcoholics as well as to identify people predisposed to alcoholism.

Alcohol Drinking↗
PubMed2003

Correlation of clinical and laboratory surrogate markers of immunodepletion with T cell subsets (CD4 & CD8) determined flow cytometrically in HIV infected patients: a hospital based study.

CD4 count is established in HIV medicine as a marker of immune depletion. However, due to financial constraints this facility is not readily available in India. Therefore, this cross sectional study in the setting of a government hospital in Pune evaluated 72 HIV infected patients for the surrogate markers of CD4 count by correlating CD counts with clinical and easily available laboratory parameters. Using a data extraction Performa, the epidemiological and clinical data of these patients was noted. Routine hematological parameters were determined. T cell subsets were studied by 2-color flow cytometry. These included CD4 counts, CD4 percentage, CD8 counts, CD8 percentage and CD4/CD8 ratio. Status of cell-mediated immunity was determined using a Multi test CMI device and Mantoux reactivity. beta2 microglobulin levels were determined in 50 of the patients. Immunological parameters were correlated with the clinical profile and other simple laboratory markers. Statistical analysis was done using regression coefficients and paired t tests. Patients who had lesser weights had lower CD4 and CD8 counts, ALC (absolute lymphocyte counts) and CD4%. Fall in hemoglobin was associated with low CD4 count, low ALC and low CD8. ALC levels correlated well with CD4 counts below 500 cells / cmm. Patients with anergic skin response to Mantoux testing and impaired cell mediated immunity had lower CD4 counts than those who had intact cell mediated immunity. beta2 microglobulin levels did not correlate well with declining immune dysfunction. However a significant inverse correlation was established between beta2 microglobulin and CD4%.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Phenotype of peripheral blood leukocytes and survival of patients with metastatic colorectal cancer.

Immune dysfunction is prevalent in metastatic cancer. Few patients with colorectal cancer metastases are cured, and among the strategies aimed at improving the therapeutic results in patients with metastatic colorectal cancer, immunotherapy is being increasingly investigated. We evaluated retrospectively the prognostic significance of peripheral blood leukocytes in 59 patients with metastatic colorectal cancer. The relative numbers of CD3+, CD3+CD4+, CD3+CD8+, NK (CD3-CD16+CD56+), CD3+DR+, CD3+CD25+, CD3+CD69+, CD19+, CD19+CD23+, CD8+CD28+, CD8-CD28+, CD8+CD57+, CD14+DR+ and CD14+CD16+ leukocytes were analyzed by two-color flow cytometry. A three-step approach was adopted to identify predictors of prognosis using regression analysis. Based on the results of univariate survival analysis, the absolute number of white blood cells, NK/CD3+CD69+ and NK/white cell count ratios were significant indicators of prognosis. In the multivariate regression analysis a model was obtained using a single parameter, the NK/CD3+CD69+ ratio, predicting the survival with 10-15% power of regression. The present results indicate that the NK/CD3+CD69+ ratio in peripheral blood may be an independent variable in a regression model predicting the overall survival of patients with colorectal cancer metastases to be tested in prospective studies.

Antigens, CD↗
PubMed2005

Marked telomere fluctuation of leukocytes during graft-versus-host disease in allogeneic stem cell transplantation.

Immune dysfunction after allogeneic stem cell transplantation (SCT) is closely associated with cell turnover of lymphocytes and homeostasis of hematopoietic stem cells. Telomeres, repetitive sequences (TTAGGG)n on the end of linear chromosomes, reflect the mitotic history of stem cells. Using telomere fluorescence in situ hybridization (FISH) and flow cytometry (flow-FISH), we measured telomere length in lymphocytes and neutrophils at various intervals to analyze the relationship between telomere length change and clinical features in 5 patients who underwent allogeneic bone marrow transplantation. During the first year after allogeneic stem cell transplantation, a marked fluctuation of telomere length in peripheral blood leukocytes was observed in all recipients, and in 3 patients there was a reduction of telomere length during chronic graft-versus-host disease (GvHD) or during post-transplant lymphoproliferative disorder. The reduction of telomere length during GvHD was evident in lymphocytes and neutrophils, but telomere length in neutrophils tended to recover earlier than that observed in lymphocytes. The rapid reduction of telomere length in leukocytes during GvHD was too extensive to be explained by the end-replication problem, suggesting the presence of a telomerically unstable hematopoietic condition after transplant in vivo.

Bone Marrow Transplantation↗
PubMed2005

CD4+CD25+ regulatory T cells in the peripheral blood of patients with breast cancer and non-small cell lung cancer.

It is well known that immunosuppression may contribute to the progression and chemotherapy-resistance of cancer. Recent studies have demonstrated that lymphocytes with the phenotype of CD4+CD25+ regulatory T cells (T-regs) contribute to immune dysfunction in cancer patients, and a relative increase in CD4+CD25+ regulatory T cells is related to immunosuppression and tumor progression in patients with some malignancies. In the present study, we evaluated the prevalence of T-regs in the peripheral blood of patients with breast cancer and non-small cell lung cancer. The phenotype of lymphocyte CD4+CD25+ cells was analyzed in peripheral blood of patients with breast cancer (n=22) and non-small cell lung cancer (NSCLC) (n=17). The population of CD4+CD25+ cells in CD3+ and CD4+ cells was evaluated by flow cytometric analysis with triple-color staining. Patients with breast cancer did not have a higher percentage of CD4+CD25+ cells in the total CD3+ and CD4+ cells in their peripheral blood than healthy volunteers. In contrast, patients with recurrent NSCLC had significantly higher percentages of CD4+CD25+ cells in CD3+ (47.6%) and CD4+ (71.0%) than healthy volunteers (n=10) who had CD4+CD25+ cells in CD3+ (33.7%, p=0.02) and CD4+ (52.2%, p<0.03). The population of CD4+CD25+ T-regs in the peripheral blood of patients with non-small cell lung cancer was significantly higher than that in healthy volunteers but not in breast cancer patients. These findings suggest that the use of T-reg-targeted immunomodulatory therapy may be a more effective strategy for patients with non-small cell lung cancer than for those with breast cancer.

Adult↗
PubMed2005

[Natural history of human T-lymphotropic virus type 1 (HTLV-1) infection].

The natural history of human T-lymphotropic virus type-1 (HTLV-1) infection has been difficult to be clarified, because only a small proportion of HTLV-1 carriers develop adult T-cell leukemia(ATL) after a long incubation period. We have performed a long-term follow-up study of HTLV-1 carriers for 17 years. Based on the findings of this study and other studies, the natural history of HTLV-1 carriers is hypothesized as follows. The major routes of infection of this virus are from mother to child, between spouses, and through blood products. The target of HTLV-1 infection is CD4 positive peripheral blood mononuclear cells (PBMCs). The number of infected cells is supposed to be increased just after the infection, then decreased in a year. The number of infected cells does not change thereafter during more than 10 years. In 90% of newly infected people, this level is low or medium ranging from less than 0.05% to 5% of PBMCs infected; however, approximately 10% of newly infected people develop into carriers with many number of infected cells as more than 5% of PBMCs infected. Clonal expansion of infected cells is likely to be contributing to the maintenance of the HTLV-1 infection. Replication of certain clones among many infected cells may be accelerated by the expression of Tax protein and some of them develop to have a phenotype to avoid immune surveillance. Finally, some of these clones, which acquired the accumulation of genomic abnormality, develop the pre-leukemic state. The increased number of certain T-cells due to HTLV-1 infection may also cause imbalance of the immune system, resulting in immune dysfunction or inflammatory diseases like myelopathy and uveitis. Therefore, it seems to be important to find ways to prevent HTLV-1 associated diseases among the carriers especially those with many infected cells.

Adult↗
PubMed1992

Human T lymphotropic virus I, myelopathy, polymyositis and synovitis: an expanding rheumatic spectrum.

A black woman developed chronic myelopathy, polymyositis and synovitis. Although native of a nonendemic area the possibility of human T lymphotropic virus I association was considered. She tested positive and was serendipitously found to have been positive 16 years before. Risk factors were a transfusion and work as a serology technician. Sjögren's syndrome, alveolitis, gammopathy and immune dysfunction are other rheumatic manifestations of this virus.

Antibodies, Viral↗
PubMed1992

Neurosurgical infections in the compromised host.

Granulocytopenia, cellular and humoral mediated immune dysfunction are predisposing factors to the development of CNS infections in immunosuppressed patients. Brain abscess formation in the compromised host is most commonly caused by enteric bacilli, the bacterium N. asteroides, the fungus Aspergillus fumigatus, or the parasite T. gondii. Mucor and the JC virus cause invasive encephalitis in this patient population. CT and MR imaging have greatly aided in the diagnosis of intracranial lesions because of these agents. Stereotactic biopsy-aspiration for diagnosis and to relieve mass effect combined with systemic antimicrobial therapy is the treatment of choice for intracerebral abscess in the compromised host. Organ rejection and chronic immunosuppressive therapy can complicate surgical intervention in these patients. Only with a high index of suspicion, an aggressive approach to diagnosis, and rapid vigorous therapy may we hope to alter the clinical course in this difficult group of patients.

Brain Abscess↗
PubMed2005

Aspergilloma of the brain: an overview.

Fungal infections of the central nervous system (CNS) are almost always a clinical surprise. Their presentation is subtle, often without any diagnostic characteristics, and they are frequently mistaken for tuberculous meningitis, pyogenic abscess, or brain tumor. Granulocytopenia, cellular and humoral mediated immune dysfunction are predisposing factors to the development of CNS infections in immunosuppressed patients. Aspergillus fumigatus is the most common human pathogen in the genus Aspergillus. Maxillary sinusitis of dental origin or the lungs are the most common sites of primary Aspergillus infection. Infection reaches the brain directly from the nasal sinuses via vascular channels or is blood borne from the lungs and gastrointestinal tract. Single or multiple abscess formation with blood vessel invasion leading to thrombosis is a characteristic feature of Aspergillosis on neuropathologic examination. Aspergillosis should be considered in cases manifesting with acute onset of focal neurologic deficits resulting from a suspected vascular or space-occupying lesion especially in immunocompromised hosts. Aspergillosis is diagnosed on direct examinations and culture, however the diagnosis of aspergillosis of the CNS is difficult. Diagnosis of an intracranial mass lesion is best confirmed with a computed tomography or magnetic resonance imaging of the head with or without intravenous contrast. Aggressive neurosurgical intervention for surgical removal of Aspergillus abscesses, granulomas, and focally infracted brain; correction of underlying risk factors; Amphotericin B combined with flucytosine and treatment of the source of infection should form the mainstay of the management. Off late Liposomal Amphotericin B was found to be more effective and safe than conventional Amphotericin B in the management of Apergillus infections Only with a high index of suspicion, an aggressive approach to diagnosis, and rapid vigorous therapy may we hope to alter the clinical course in this group of patients.

Antifungal Agents↗
PubMed2006

Self-regulation of neutrophils during phagocytosis is modified after severe tissue injury.

Neutrophil (PMNL) function is influenced by factors released by other immune cells during the course of the immune response. We investigated the effect of neutrophil cell density and the effect of supernatant of the phagocytosis assay on the phagocytosis activity of PMNLs. The measurements were carried out with naive (control) PMNLs of healthy donors and with PMNLs obtained from patients with severe tissue injury. Phagocytosis index (FI) of PMNLs was determined at cell densities of 7.5 x 10(5)/ml and 15 x 10(5)/ml. E. coli phagocytosis of heparinized whole blood from healthy donors and patients with severe tissue injury was measured and evaluated at three different cell densities (normal, half, and double densities) by flow cytometry. Supernatants of phagocytosis assays of either control or trauma (ISS >18) patient PMNLs were added to the assay suspensions of control and trauma PMNLs. An increase in cell density of healthy donor PMNLs increased yeast phagocytic activity. In cases of tissue injury, PMNLs showed increased phagocytic activity at lower cell densities. E. coli phagocytosis was increased with the increase of cell density, and tissue injury PMNLs were more active at each cell concentration compared to naive cells. Polytrauma supernatants in most cases inhibited, while healthy supernatants mostly increased the yeast phagocytosis of healthy and trauma PMNLs. These results reinforce the idea that primed PMNLs in the presence of microbial agents produce factor(s) which inhibit some of the cell's antimicrobial functions contributing to immune-dysfunction, while unprimed PMNLs produce factor(s) which facilitate antimicrobial countermeasure. These results also demonstrate that reduced phagocytosis of tissue injury primed PMNLs is not due to cytoskeletal changes but to the humoral environment.

Adult↗
PubMed2006

Expression of Foxp3 in non-small cell lung cancer patients is significantly higher in tumor tissues than in normal tissues, especially in tumors smaller than 30 mm.

Active suppression by CD4+CD25+ T regulatory cells (T regs) plays an important role in the down-regulation of T cell responses to foreign and self-antigens. Thus far, the potential role of T regs in human tumors has been reported. T reg-mediated suppression of antitumor immune responses may partly explain the poor clinical response to vaccine-based immunotherapy for human cancer. The forkhead transcription factor Foxp3 is a critical regulator of T regs development and function. Foxp3 represents a specific marker for the T regs. In this study, we measured the Foxp3 mRNA expression in tumors and in normal tissues from 46 patients with non-small cell lung carcinoma (NSCLC), and tumor tissues showed a significantly higher expression of Foxp3 mRNA than normal tissues. The expression of Foxp3 mRNA and the tumor diameter were inversely proportional. These results suggest that T regs expressing Foxp3 selectively accumulate in tumor tissues of NSCLC and contribute to antitumor immune dysfunction, especially in the early stages.

Adult↗
PubMedDate not supplied

Cortisol response to an acute injection of IL-2 in healthy subjects and cancer patients: a first immunoneuroendocrine standardized clinical test to explore the interactions between immune and neuroendocrine systems.

Preliminary clinical studies would suggest that the immune alterations characterizing severe human illnesses, such as autoimmune diseases and cancer itself, may depend at least in part on an anomalous psychoneuroendocrine regulation of the immunity. Unfortunately, at present the psychoneuroimmune interactions may be clinically investigated only by separately analyzing the neuroendocrine and the immune systems, since there is no standardized clinical test capable of detecting the physiological response of the endocrine secretion to an immune stimulation. One of the main endocrine functions influenced by the immune activation is the hypothalamic-pituitary-adrenal axis. In fact, several cytokines have appeared to stimulate cortisol secretion by acting at a central site. On this basis, a study was planned to evaluate cortisol response to an acute IL-2 injection in healthy subjects and metastatic cancer patients, in an attempt to standardize a clinical neuroendocrinoimmune test capable of documenting possible alterations of the link between neuroendocrine and immune systems. The study included 10 healthy subjects as a control group and 10 cancer patients with metastatic disease. Control subjects were evaluated in basal conditions to determine the physiological circadian rhythm of cortisol, and after the subcutaneous (SC) injection of IL-2 (3 and 9 million IU). IL-2 at 3 million IU stimulated cortisol release in all healthy controls and in none of the cancer patients. IL-2 at 9 million IU induced a significant increase in cortisol mean levels in cancer patients, whose values, however, were still significantly lower with respect to those seen in controls in response to IL-2 at 3 million IU. No important IL-2 related side-effect occurred. This study shows that an acute SC injection of low-dose IL-2 with a following evaluation of cortisol secretion may constitute a first standardized immunoendocrine test, capable of exploring the status of the physiological link between neuroendocrine and immune systems, and of documenting the existence of important alterations in human diseases related to an immune dysfunction, such as advanced cancer, which has appeared to be characterized by a hyposensitivity of the hypothalamic-pituitary-adrenal axis to an acute cytokine administration.

Aged↗
PubMed2006

Ganoderma lucidum extract inhibits proliferation of SW 480 human colorectal cancer cells.

AIM: Ganoderma lucidum is a commonly used Chinese herb and an important ingredient in traditional Chinese medicine herbal formulations for immune dysfunction related illnesses. The effects of this medicinal mushroom on human colorectal cancer cells have not yet been evaluated. In this study, we investigated the effects of Ganoderma lucidum extract using SW 480 human colorectal cancer cell line. MATERIALS AND METHODS: Two different fractions of Ganoderma lucidum extract, i.e., a fraction containing mainly polysaccharides (GLE-1), and a triterpenoid fraction without polysaccharides (GLE-2) were analyzed. Their antiproliferative activity was evaluated by cell proliferation assay and 3H-thymidine incorporation assay. Scavenging effects of DPPH radical were assessed using ESR-spectroscopy. RESULTS: Our data showed that both GLE-1 and GLE-2 significantly inhibited the proliferation of SW 480 cells. The inhibitory effect of GLE-2 was much stronger than that of GLE-1. GLE-1 inhibited DNA synthesis in the cells and reduced the formation of DPPH radicals. CONCLUSION: Ganoderma lucidum extract inhibits proliferation of human colorectal cancer cells and possesses antioxidant properties.

Cell Division↗
PubMed2006

Interferon alpha and its contribution to autoimmunity.

It is now well accepted that interferon (IFN)alpha plays a critical role in the pathogenesis and perpetuation of specific autoimmune diseases, including systemic lupus erythematosus (SLE), autoimmune thyroid disease and type 1 diabetes. IFNalpha-based treatments are widely used for the treatment of chronic viral infections, particularly chronic hepatitis C virus infection; however, several case reports have emerged describing autoimmune conditions that have developed during IFNalpha therapy. The data support the pathogenic potential of IFNalpha in autoimmunity, although it is clear that genetic and environmental factors are also key to the development of autoimmune conditions. Several points of interaction between IFNalpha and immune effector cells have been experimentally defined, the functional consequences of many of which remain poorly understood. This review describes the most recent data in support of an important role for IFNalpha in autoimmunity, particularly SLE, and the potential mechanisms by which IFNalpha contributes to immune dysfunction. Future approaches to IFNalpha modulation as a therapeutic strategy for use in the treatment of autoimmune diseases are also discussed.

Animals↗
PubMedDate not supplied

Etrurians vs Greeks: May ACE I/D polymorphism still be considered as a marker of susceptibility to SSc?

OBJECTIVE: SSc is characterized by immune dysfunction and microvascular involvement. A different genetic background may determine a different polymorphic allele frequency between different populations, and data from literature reported conflicting results about the role of genetic components in predisposing to the disease. We carried out this study in order to compare the ACE I/D polymorphism genotype distribution and alleles frequency in two different populations from the Mediterranean area. METHODS: Forty-eight Italian and 41 Greek SSc patients compared with 112 Italian and 93 Greek controls, have been studied. The ACE I/D polymorphism has been analysed. RESULTS: The genotype distribution and allele frequency were in Hardy-Weinberg equilibrium for Italian and Greek SSc patients and controls. Among the Italian patients a significantly higher ACE D allele frequency than in the controls was found, whereas among the Greeks a higher prevalence was observed in the healthy subjects. A significant difference in ACE D allele frequency between Italian and Greek controls was observed (p = 0.04). ACE D allele was associated to the predisposition to SSc in Italians, but not in Greeks. CONCLUSION: We confirm that Italian SSc patients have a higher ACE D allele frequency that is not present in the Greek patients. Thus, the two populations living in different Mediterranean areas and resulting from the Mediterranean civilization, do not show the same ACE-gene related allele frequencies. Other populations of the Mediterranean area must be investigated by using unlinked genetic markers to verify the homogeneity of the genetic background, and to test for a "true" difference in their ethnic origin.

Amino Acid Substitution↗
PubMed2006

[Bone and joint infection].

Older adults are at risk for the immune dysfunction associated with advanced age, which contribute to their increased risk of infection. Hematogenous osteomyelitis occurs not only in children, but also in older adults. Iatrogenic septic arthritis can be occured after the intraarticular injection for the osteoarthritis in aging society. Tuberculous spondylitis occurs in older adults and the differential diagnosis with pyogenic spondylitis and vertebral metastasis is important.

Aged↗
PubMed1991

Ataxia telangiectasia presenting as an extrapyramidal movement disorder and ocular motor apraxia without overt telangiectasia.

Ataxia telangiectasia may present with few, if any, of its typical extraneurological manifestations, but the combination of an extrapyramidal movement disorder, ocular motor apraxia with head thrusting and cerebellar incoordination is characteristic. In this sporadic case there was no overt immune dysfunction, oculocutaneous telangiectasia were inconspicuous and the neurological presentation was atypical with dystonia predominating over cerebellar incoordination. The uncontrollable and disabling involuntary movements, which have not to our knowledge been described in ataxia telangiectasia before, showed a partial response to moderately large doses of benzhexol, but were refractory to all other medications. Treatment in the future is to be with increasing doses of benzhexol until the dystonia is controlled or larger doses cannot be tolerated.

Adult↗
PubMed1991

Cerebrospinal fluid interleukin-1 beta (IL-1 beta) in Alzheimer's disease and neurological disorders.

Recent studies indicate that patients with Alzheimer's disease (AD) exhibit an immune dysfunction at the central and peripheral levels. We have studied the concentration of IL-1 beta in the cerebrospinal fluid (CSF) of patients with AD, multi-infarct dementia (MID), normal pressure hydrocephalus (NPH), and multiple sclerosis (MS). CSF IL-1 beta levels were significantly higher in AD (131 +/- 17.33 pg/ml) than in MID (79.71 +/- 24.37 pg/ml, p less than 0.01), NPH (84.75 +/- 23.17 pg/ml, p less than 0.01), and MS (79.4 +/- 10.23 pg/ml, p less than 0.01). In patients with neurological disorders CSF IL-1 beta levels showed a progressive increase with age (r = +0.49, p less than 0.015). The concentration of IL-1 beta in CSF of demented patients correlated with mental deterioration (r = -0.476). According to these results we postulate that high levels of central IL-1 beta in AD might reflect a reactive neuroimmune response to: (a) abnormal epitopes exposed by lesioned neurons, (b) reactive microglia activated by exogenous and/or endogenous factors and (c) endogenous neurotrophic activation.

Aged↗