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PubMed2003

Immunology and immunotherapy of colorectal cancer.

This review critically discusses data on immunology of colorectal cancer, starting from pathology and molecular biology, and then considering the molecular characterisation of colon cancer antigens and the clinical trials of immunotherapy. A careful evaluation of histopathological studies on intra-epithelial infiltration by T cells in primary tumours, together with the analysis of HLA expression by colorectal cancer cells, suggest that anti-tumour T cell immune responses may take place in vivo in those patients, influencing prognosis and shaping the tumour immunological profile. Moreover, the molecular characterisation of tumour antigens expressed by colorectal carcinomas, together with improved understanding of mechanisms of the immune response and more sensitive methods for the in vivo detection of T cell responses, are now allowing researchers to design new and more effective vaccination protocols, with encouraging preliminary results. By drawing together the experimental evidence from different research fields, this review provides support for the concept that colorectal carcinoma is immunogenic and may reasonably be considered as a target for immunotherapy, and attempts to address critical issues and envisage future developments in this challenging research field.

Animals↗
PubMed1998

The REACH Project of the Adolescent Medicine HIV/AIDS Research Network: design, methods, and selected characteristics of participants.

PURPOSE: To describe the Reaching for Excellence in Adolescent Care and Health (REACH) Project of the Adolescent Medicine Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) Research Network, a unique collaborative effort to conceive and implement a research design intended to examine HIV pathogenesis, pubertal hormonal variation, and the effects of sexually transmitted disease comorbidity in HIV-infected youth to improve their health care. METHODS: This multidisciplinary team has drawn on basic science and clinical experience to produce a study design with relevant and feasible study aims and testable hypotheses. Particular attention has been paid to centralized training and quality control practices. Standardized measurements include direct and computer interviews, physical examination, laboratory analysis, and medical chart abstraction. The protocol has been approved by local institutional review boards. RESULTS: A highly standardized and quality control monitored protocol has been implemented at 16 sites throughout the United States collecting historical, observational, and laboratory data in a group of HIV-infected adolescents and HIV-negative controls. Preliminary data collected on subjects are consistent with published reports of the sociodemographic and clinical characteristics of the HIV epidemic in sexually active youth, thus supporting the integrity of the protocol development process. The study population is, for the most part, in older adolescence, predominantly minority and female, and with publicly financed or no health insurance. CONCLUSIONS: The REACH Project is positioned to address questions about the clinical course, immunologic profile, and viral dynamics in HIV-positive youth, and thus is able to inform drug development and management strategies for this understudied population.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Differential expression of glutathione S-transferase isoenzymes in murine small intestine and colon.

Glutathione (GSH) S-transferase (GST) isoenzymes of the small intestine and colon of female A/J mice have been purified and characterized to determine their interrelationships with other murine GSTs. Cytosolic GST activity in the small intestine was at least due to six isoenzymes with isoelectric points (pI) of 9.5, 9.3, 9.1, 8.5, 6.2 and 5.5. Small intestine isoenzymes with pI values of 9.5, 9.3, 8.5, and 6.2 were identical to the mGSTA1-1 (Alpha class), mGSTP1-1 (Pi class), mGSTM1-1 (Mu class) and mGSTA4-4 (Alpha class), respectively, of other A/J mouse tissues on the basis of their reverse-phase HPLC elution profile, immunological cross-reactivity and/or N-terminal region amino acid sequence. Even though GST9.1 of the small intestine cross-reacted with the antibodies raised against Pi class GST, reverse-phase HPLC and N-terminal amino acid sequence analyses suggested that this isoenzyme may be structurally different from mGSTP1-1 as well as mGSTP2-2. Likewise, despite immunological similarity with the Mu class GSTs, small intestine GST5.5 appeared to be different from other Mu class murine GSTs characterized previously. Cytosolic GST activity in the colon was mainly due to four isoenzymes with pI values of 9.8, 9.4, 6.6 and 5.8. While the identity of colon GST6.6 could not be established due to its low abundance, GST9.8, GST9.4 and GST5.8 were identical to mGSTP1-1, mGSTM1-1 and mGSTA4-4, respectively, of other A/J mouse tissues including the small intestine. Isoenzymes corresponding to small intestine GST9.1 and GST5.5 could not be detected in the colon. The results of the present study indicate that the small intestine of female A/J mice is better equipped for protection against toxic effects of electrophiles than colon.

Animals↗
PubMed2002

Chronic hepatitis C and autoimmune cholangitis: a case study and literature review.

We present a case of a chronic hepatitis C with damage of bile ducts resembling primary biliary cirrhosis. The immunological profile (negative antimitochondrial antibodies and positive anti-nuclear antibody) was characteristic of the autoimmune cholangitis. One year of treatment with ursodeoxycholic acid returned the liver tests to the normal range but the liver lesions remained unchanged.

Autoimmune Diseases↗
PubMed2002

Herpes simplex virus type 1 encephalitis associated with acute retinal necrosis syndrome in an immunocompetent patient.

PURPOSE: The onset of acute retinal necrosis secondary to herpes simplex encephalitis is exceptional. We report such an association in an immunocompetent patient, in whom the genome of herpes simplex virus type 1 (HSV-1) was identified successively at both sites of infection. METHODS: Polymerase chain reaction (PCR) assay of HSV-1 in cerebrospinal fluid (CSF) and aqueous humour. RESULTS: An immunocompetent patient aged 40 years presented with HSV-1 encephalitis, which was confirmed by imaging, viral serology and identification of the HSV-1 genome in the CSF. The subject's immunological profile was normal. The patient was treated with foscavir. Six weeks after clinical recovery and negative PCR, the patient presented with a unilateral acute retinal necrosis syndrome. Polymerase chain reaction of the aqueous humour was positive, while serology and PCR of the CSF remained negative. CONCLUSION: Identification of the HSV-1 genome at the two successive sites of infection stresses the possibility of brain-to-eye transmission of HSV-1.

Adult↗
PubMed2000

Assessment of peripheral blood lymphocyte subsets in idiopathic myelofibrosis.

The objective of this study was to contribute to a better characterization of the immunological profile of idiopathic myelofibrosis (IM) at presentation by analysing the blood lymphocyte subsets and their possible correlations with other disease features. Absolute blood lymphocytes and lymphocyte subsets were assessed in 31 IM patients, compared with those from 34 healthy individuals, and correlated with the patients' main clinical, hematological and bone marrow histologic features. The mean lymphocyte count of the IM patients was 1.1 (SD 0.6) x 10(9)/L, versus 1.6 (SD 0.49) x 10(9)/L in controls (p = 0.0006), with 24 of the 31 patients (77.4%) showing lymphocytopenia (< 1.5 x 10(9)/L). IM patients had significantly lower counts of CD3, CD4, CD8, and CD3 -/ CD56+ cells, and significantly higher CD3 +/CD56 + lymphocyte counts. Although no significant differences were found between patients and controls with regard to CD19+/CD5+ cell counts, increased CD5 + B-cell lymphocytes were observed in three IM patients. In one of the latter patients, Ig gene rearrangement analysis of the heavy chain gene demonstrated such a subpopulation to be clonal, but the patient did not develop features of chronic lymphoid leukemia during a 5-yr follow-up. No correlation was found between the patients' blood lymphocyte counts and other disease features. We conclude that most IM patients have absolute lymphopenia, decreased T cells and increased cytotoxic T cells at diagnosis, and 10% of them show an increased CD5 + B-cell subpopulation.

Adult↗
PubMed2001

Focal lymphocytic infiltration in aging human palatal salivary glands: a comparative study with labial salivary glands.

Investigation of age-related prevalence of various types of focal lymphocytic infiltration (FLI) and degrees of histomorphologic changes was conducted on 120 biopsies of palatal and labial salivary glands (PSG and LSG, respectively) obtained from autopsy subjects free of salivary gland tumors/diseases. Biopsies were divided into young (<30 years, n=30), adult (30-60 years, n=45) and old (>60 years, n=45) age groups. A modified Chisholm & Mason grading system was used to record grades of FLI and a modified Greenspan et al. system was used to evaluate the severity of histomorphologic changes. The prevalence of FLI in PSG increased significantly from 10% in the young group to 46.6% in the old group (P=0.0012). No significant changes were found with aging in LSG. FLI was significantly more prevalent in the adult and old age groups in PSG as compared with LSG (P=0.015 and P=0.003, respectively). Both glands demonstrated significant histomorphologic changes among age groups (p<0.0001); however, these changes were significantly less common in the old age group in PSG as compared to LSG (P=0.003). In cases showing severe histomorphologic changes, FLI was not present. Therefore, FLI should not be considered as part of the deteriorating histomorphologic changes that are usually encountered in salivary glands with aging. The immunologic profile of these infiltrates should be further clarified to understand their role, both in physiologic and pathologic conditions.

Adult↗
PubMed2002

Microbiological, immunological and genetic factors in family members with periodontitis as a manifestation of systemic disease, associated with hematological disorders.

The microflora, immunological profiles of host defence functions, and human leukocyte antigen (HLA) findings are reported for a mother, son and daughter who were diagnosed as having 'periodontitis as a manifestation of systemic diseases, associated with hematological disorders'. Examinations were made of the bacterial flora from the periodontal pocket, neutrophil chemotaxis, neutrophil phagocytosis, and the genotypes (DQB1) and serotypes (DR locus) of HLA class II antigens. Phenotypic analyses of the peripheral lymphocytes were also conducted. The subgingival microflora from the mother was dominated by Gram-negative rods, especially Porphyromonas endodontalis, Prevotella intermedia/Prevotella nigrescens and Fusobacterium nucleatum. Subgingival microflora samples from the son and daughter were dominated by Gram-positive cocci and Gram-positive rods. Through the use of polymerase chain reaction, Campylobacter rectus and Capnocytophaga gingivalis were detected in all subjects, whereas Porphyromonas gingivalis, P. intermedia, and Treponema denticola were not detected in any subjects. All three subjects showed a remarkable level of depressed neutrophil chemotaxis to N-formyl-methionyl-leucyl-phenylalanine, although their phagocyte function levels were normal, in comparison to healthy control subjects. Each subject had the same genotype, HLA-DQB1*0601, while the mother had HLA-DR2 and HLA-DR8, and the son and daughter had HLA-DR2 only. In summary, the members of this family showed a similar predisposition to periodontitis with regard to certain host defence functions. It is suggested that the depressed neutrophil chemotaxis that was identified here could be a significant risk factor for periodontitis in this family.

Adult↗
PubMed2000

Immunologic evaluation of dental patient with history of hypersensitivity reaction to sodium hypochlorite.

A 12-year-old girl, with a previous history of bronchial reaction and contact dermatitis to sodium hypochlorite, was referred for root canal treatment. Complete immunologic evaluation revealed a mild hypersensitivity condition, as it was assessed by the RAST investigation to different allergens and the DTH reactivity expressed though migration inhibition test. The absence of a serious immunologic disregulation in the patient's immunologic profile justified the term 'non-allergic hypersensitivity' to sodium hypochlorite to describe the condition.

Bronchial Hyperreactivity↗
PubMed1979

Effect of treatment on the immunological status of women with advanced breast cancer.

An immunological profile has been serially studied in 72 patients with advanced breast cancer during the course of a randomized trial of chemotherapy and hormonal manipulation. DNCB+ patients were more likely to respond to either therapy, but no other test was predictive of response. In the follow-up period all chemotherapy patients had a reduction in white-cell count which was significantly greater in those responding to treatment. None of the other tests (phytohaemagglutinin response, immunoglobulins G, A and M, or Mantoux test) demonstrated changes that could be related to treatment or response, but there was a gradual unexplained fall in IgM levels in all groups the study progressed. It is concluded that the chemotherapeutic regimen (cyclophosphamide, vincristine, adriamycin and 5-fluorouracil) is relatively non-immunosuppressive, and that hormonal therapy (oophorectomy, tamoxifen or androgens) had no detectable effect on the immune response.

Antibody Formation↗
PubMed1981

Suppressor cell activity in a proliferative disorder of T lymphocytes.

We report details of the immunological profile of a patient with the candidiasis endocrinopathy syndrome who has developed T-type chronic lymphocytic leukaemia. The patient is anergic to a panel of delayed hypersensitivity skin tests, and has poor in vitro mitogenic responses, but B cell function in vivo is not impaired. Subsequent functional studies have revealed that cells from the patient have a significant suppressive effect in coculture (P less than 0.05) on the responses of healthy donor lymphocytes (NR) to the mitogen phytohaemagglutinin (PHA). A degree of selectivity for the suppressive effect is suggested by the lack of similar effects on coculture responses to the mitogens concanavalin A (Con A) and pokeweed mitogen (PWM). Mitomycin C treatment of the patient's cells reduced their suppressive activity but significant suppression was still observed in the majority of PHA cocultures. The suppressor activity required the presence of the patient's cells in cocultures, as no suppression was observed when the patient's serum or cell culture supernatant were included instead of the patient's cells in NR cultures.

Adult↗
PubMed2003

Characterization of a mosquitocidal Bacillus thuringiensis serovar sotto strain isolated from Okinawa, Japan.

AIMS: To characterize the mosquitocidal activity of parasporal inclusions of the Bacillus thuringiensis serovar sotto strain 96-OK-85-24, for comparison with two well-characterized mosquitocidal strains. METHODS AND RESULTS: The strain 96-OK-85-24 significantly differed from the existing mosquitocidal B. thuringiensis strains in: (1) lacking the larvicidal activity against Culex pipiens molestus and haemolytic activity, and (2) SDS-PAGE profiles, immunological properties and N-terminal amino acid sequences of parasporal inclusion proteins. CONCLUSIONS: It is clear from the results that the strain 96-OK-85-24 synthesizes a novel mosquitocidal Cry protein with a unique toxicity spectrum. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of the occurrence of a mosquitocidal B. thuringiensis strain with an unusual toxicity spectrum, lacking the activity against the culicine mosquito.

Amino Acid Sequence↗
PubMed2001

Clinical significance of elevated serum interferon- inducible protein-10 levels in hepatitis C virus carriers with persistently normal serum transaminase levels.

The aim of this study was to assess the immunological profile in hepatitis C virus carriers with persistently normal serum transaminase levels. Forty-two serum HCV RNA positive patients with persistently normal serum transaminase levels (22 natural 'asymptomatic HCV carriers' and 20 biochemical responders to IFN therapy) and 23 complete responders to IFN therapy were enrolled. The HCV genotypes and serum HCV RNA levels were determined before IFN therapy in treatment responders, and at entry in the others. The serum levels of IFN-inducible protein-10 (IP-10) (a protein mainly induced by IFN-gamma), interleukin (IL)-10, and IL-4 were measured in all patients while the serum transaminase levels were normal. The serum transaminase levels and platelet counts were then monitored for the next 4 years and the changes in liver fibrosis were assessed. The serum levels of IP-10 in infected and biochemically normal patients were significantly higher than the levels in complete responders to therapy, whereas the serum levels of IL-10 and IL-4 did not vary significantly among the different groups. During the 4-year follow-up period, 10/20 (50%) biochemical responders and 12/22 (55%) asymptomatic carriers had an elevation of the serum transaminase levels. A significant (P=0.0370) increase in platelet count after 4 years and improvement in liver fibrosis were noted in treatment responders but not in infected patients. The weak but significant residual immune response as reflected by the increased serum IP-10 level may underlie the outcome of HCV carriers with persistently normal serum transaminase levels.

Alanine Transaminase↗
PubMed2001

Immunological genomics of Brugia malayi: filarial genes implicated in immune evasion and protective immunity.

Filarial nematodes are metazoan parasites with genome sizes of> 100 million base pairs, probably encoding 15 000-20 000 genes. Within this considerable gene complement, it seems likely that filariae have evolved a spectrum of immune evasion products which underpin their ability to live for many years within the human host. Moreover, no suitable vaccine currently exists for human filarial diseases, and few markers have yet been established for diagnostic use. In this review, we bring together biochemical and immunological data on prominent filarial proteins with the exciting new information provided by the Filarial Genome Project's expressed sequence tag (EST) database. In this discussion, we focus on those genes with the highest immunological profile, such as inhibitors of host enzymes, cytokine homologues and stage-specific surface proteins, as well as products associated with the mosquito-borne infective larva which offer the best opportunity for an anti-filarial vaccine. These gene products provide a fascinating glimpse of the molecular repertoire which helminth parasites have evolved to manipulate and evade the mammalian immune response.

Animals↗
PubMed2002

Relationship between reactive nitrogen intermediates and total immunoglobulin E, soluble CD21 and soluble CD23: comparison between cerebral malaria and nonsevere malaria.

To search for evidence of a protective role of the CD23/NO pathway against cerebral malaria, concentrations of reactive nitrogen intermediates (RNI) and sCD21, total immunoglobulin (Ig)E and sCD23 were compared between 17 cases of cerebral malaria and 33 controls. The geometric mean of sCD23 concentration was higher among cerebral malaria cases than among controls (optical density 2643/1495, P = 0.01). The ratio between sCD21 and sCD23 was significantly lower in cerebral malaria cases than in controls (0.67 +/- 0.02 versus 0.77 +/- 0.02, respectively, P = 0.009). Multiple linear regression analysis showed that, among cerebral malaria cases, there was a clear correlation between RNI and both IgE (P = 0.007) and sCD21 (P < 0.0001). Among controls, there was a strong negative correlation between RNI and sCD23 concentrations (r = -0.61, P < 0.0001). However, multivariate analysis unmasked the fact that, in controls, there was also a positive correlation between RNI and IgE (P = 0.045). Logistic regression showed that increased RNI concentrations were associated with a cerebral malaria adjusted odds ratio of 1.05 per unit increase [95% confidence interval (CI) 1.006-1.1, P = 0.02] and that an increased ratio between sCD21 and sCD23 was associated with protection from cerebral malaria (adjusted OR = 0.00001 per unit increase (95% CI 0-0.03, P = 0.005). These different immunological profiles suggest that, among controls, the CD23/NO pathway was chronically stimulated whereas, in cerebral malaria, its stimulation was acute, which could explain why some patients developed cerebral malaria and others did not.

Animals↗
PubMed2002

Immunomodulation by interleukin-10 therapy decreases the incidence of relapse and prolongs the relapse-free interval in Psoriasis.

The ability of interleukin-10 therapy to reduce the severity of exacerbated psoriasis has been demonstrated recently. Considering the immunobiologic properties of this cytokine we investigated the effects of long-term interleukin-10 application on the immune system and duration of psoriasis remission. We performed a placebo-controlled, double-blind, phase II trial using interleukin-10 in patients with chronic plaque psoriasis in remission. Patients received subcutaneous injections with either interleukin-10 (10 microg per kg body weight; n = 7) or placebo (n = 10) three times per week until relapse or study termination after 4 months. The treatment was well tolerated. In the placebo group almost all patients (90%) showed a relapse during the observation period. In contrast to this, only two of seven patients (28.6%) relapsed in the interleukin-10-treated group. Kaplan-Meier analysis revealed a significantly lower relapse incidence in the interleukin-10 than in the placebo group (p = 0.02). The mean relapse-free interval time was 101.6 +/- 12.6 d in the interleukin-10 group in comparison with 66.4 +/- 10.4 d in the placebo group. Immunologic activity of interleukin-10 application was indicated by an increase in soluble interleukin-2 receptor plasma levels and higher ex vivo interleukin-4 secretion capacities. Remarkably, a significant negative correlation was demonstrated between the interleukin-4 secretion capacity and Psoriasis Area and Severity Index score (r = -0.36, p < 0.01). Our data suggest that interleukin-10 therapy is immunologic effective, decreases the incidence of relapse and prolongs the disease-free interval in psoriasis. Its value should be further determined in larger trials and for the prevention of re-exacerbation of other inflammatory disorders with a similar immunologic profile.

Adult↗
PubMed2001

Systemic lupus erythematosus presenting as subacute delirium in an 82-year-old woman.

OBJECTIVES: To describe an older patient with delirium attributed to systemic lupus erythematosus (SLE) and to review the literature on neuropsychiatric manifestations of SLE in older people. DESIGN: Case report and literature review. MEDLINE search using terms systemic lupus erythematosus, neurologic, psychiatric, neuropsychiatric, autoantibodies (anti-nuclear antibody (ANA), antiphospholipid, anticardiolipin, anti-double stranded deoxyribonucleic acid (anti-dsDNA), anti-Smith), and elderly. Additional articles obtained from hand-searched references and through experts. SETTING: Hospital (case report). PARTICIPANTS: Case report and literature cases. MEASUREMENTS: None. RESULTS: SLE is increasingly diagnosed in older adults. Onset is insidious and diagnosis is delayed because of a different clinical spectrum and immunological profile than in younger adults. Autoantibodies have an important role in the pathogenesis of neuropsychiatric manifestations, while vasculitis is less common. Aggressive immunosuppressive therapy is typically indicated, although recent case reports suggest that lower doses may suffice. The American College of Rheumatology 1982 revised criteria may be inadequate to diagnose neuropsychiatric lupus in older persons. CONCLUSION: Neuropsychiatric symptoms can be prominent in older people, presenting features of SLE. This case illustrates the lowest dose of corticosteroids shown to be effective in an older patient with delirium due to SLE.

Aged↗
PubMedDate not supplied

Investigation of cytomegalovirus and human herpes viruses 6 and 7 as possible causative antigens in psoriasis.

Psoriasis is probably a T-cell-mediated autoimmune disease. Infectious models of autoimmune diseases have been proposed and in psoriasis, it has been suggested that there may be molecular mimicry between streptococcal antigens and epidermal keratins. The immunological profile of stable psoriasis plaques suggests, however, that viral antigens may be important. We investigated, using polymerase chain reaction techniques, whether DNA from either cytomegalovirus (CMV) or human herpes viruses (HHV) 6 and 7 is present in the skin of patients (n = 10) with chronic plaque psoriasis. We also investigated 29 patients for the presence of serum IgG to CMV. We found no evidence of CMV or HHV 7 DNA in psoriasis plaques although DNA for HHV 6 was detected in both involved and uninvolved skin in 1 out of 10 patients. There was no statistically significant increase in prior CMV infection, as assessed by the presence or absence of serum IgG to CMV, in psoriasis, compared to our local population. Although there is circumstantial evidence that viral antigens may be important in the pathogenesis of psoriasis we found no evidence to link infection with CMV or HHV 6 and 7 with subsequent development of chronic plaque psoriasis.

Adult↗