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PubMedDate not supplied

Mother-to-child transmission of human immunodeficiency virus (HIV) in Ireland: a prospective study.

Symptomatic HIV infection was first diagnosed in an Irish child in 1985. A prospective study was initiated to determine the vertical transmission rate (VTR) of HIV and the average age of infant seroreversion and to monitor clinical, immunologic and virologic evidence for HIV infection in seroreverters. Ninety three HIV positive infants have been prospectively identified since 1985. The predominant underlying maternal risk factor for HIV infection is intravenous drug use (IVDU) (96 per cent). Of 93 infants, median gestational age was 40 weeks and median birth weight 3125 grams. Ninety-four per cent of infants were bottle fed. Currently 72 (77 per cent) infants are uninfected, 12 (13 per cent) are infected, 4 (4.5 per cent) are indeterminate and 5 (5.5 per cent) have been lost to follow up. The intermediate estimate of vertical transmission rate (VTR) is 14.3 per cent. The median age at documented seroreversion was 12 months. There are no significant differences between infected and non-infected children in male/female ratio, gestational age, mode of delivery or birth weight. Strategies to reduce the transmission of HIV among drug users in combination with routine antenatal screening and antiretroviral prophylaxis of vertical transmission are all measures which can reduce HIV infection in our children.

AIDS Serodiagnosis↗
PubMedDate not supplied

OKT3 monitoring in the treatment of steroid-resistant acute rejection of hepatotransplant recipients.

OKT3 is a monoclonal antibody used as T-specific immunosuppressor agent in the treatment of acute rejection of hepato- or renal-transplanted patients. The immunosuppressor effect is related to the elimination and modulation of T-cells after the binding between OKT3 and the specific antigen CD3+. This drug has been used in the treatment of acute rejection. The more frequent side effects is the immunogenic reaction Human Antibody Mouse Antibody (HAMA). The aim of this study is the evaluation of the dose and the administration route of the OKT3. The results of the antibody monitoring in the plasma of the treated patients and the analysis of the clinical data were evaluated to focus a valid therapeutic protocol as well as a more rational time sampling of the circulating drug to achieve a correct monitoring. The results show a gradual increase of the hematic concentration of the drug, positively correlating the clinical data of hepatic biopsy and lymphocytic screening. These results have permitted to modify the therapeutic protocol previously performed. It has been defined the administration route choosing i.v. infusion (5 mg/die/2 h), moreover it the therapy has been shortened to 6 days. The HAMA were also evaluated and the analysis of the data showed a negative results, suggesting the possibility of the OKT3 retreatment in the cases of rescue.

Acute-Phase Reaction↗
PubMed2000

Use of major histocompatibility complex class I tetramers to monitor tumor-specific cytotoxic T lymphocyte response in melanoma patients.

There is now considerable evidence that human tumors often express antigens that render them susceptible to lysis by cytotoxic T lymphocytes (CTLs). These findings have raised hope for the development of cancer vaccines to trigger a tumor-specific immune response in cancer patients. To optimize the immunogenicity of cancer vaccines, it is important to improve the monitoring of the immune response. The use of tetrameric soluble major histocompatibility complex (MHC) class I/peptide complexes ("tetramers") to identify tumor-specific CTLs has shown that these novel reagents allow rapid and accurate analysis of human CTL responses in cancer patients. We have used fluorescence-driven cell sorting to clone tumor-specific CTLs after staining with tetrameric MHC class I/peptide complexes. Analysis of melanoma-infiltrated lymph nodes revealed that strong CTL responses often occur in vivo, and that the reactive CTLs have substantial proliferative and tumoricidal potential.

Antigens, Neoplasm↗
PubMed2006

Expression of costimulatory molecule CD80 in colonic dysplasia in ulcerative colitis: an immunosurveillance mechanism against colorectal cancer?

BACKGROUND AND AIMS: Ulcerative colitis is an established risk factor for colorectal cancer but dysplasia reports are much more frequent than invasive neoplasm diagnosis. The effective activation of T lymphocytes that provide antitumor surveillance requires the presence of costimulation molecules such as CD80 and CD86 on the surface of antigen-presenting cells. The aim of our study was to verify the presence of an in vivo immunosurveillance mechanism in the early stages of colon tumorigenesis. PATIENTS AND METHODS: Expression of CD80, CD86, and IFN-gamma in the colonic mucosa of 21 consecutive ulcerative colitis (UC) patients was quantified using reverse transcription polymerase chain reaction. After a 7-year follow-up period, we reviewed the histology of all surveillance colonoscopy specimens for colonic dysplasia. Correlation, frequency, and survival analyses were performed. RESULTS: CD80 was detectable in seven patients while expression of CD86 and IFN-gamma was evident in all patients. Histology confirmed the presence of dysplasia in eight patients. Patients who had dysplasia showed higher CD80 levels compared to those without dysplasia (p=0.02). Survival analysis demonstrated that cumulative dysplasia rates of CD80-positive patients were significantly higher than those of CD80-negative patients (p=0.04). CONCLUSION: Even if partially limited by a relatively small sample size, our study seems to show an association between CD80 expression and colonic dysplasia in UC patients that may suggest a role for CD80 in the immunosurveillance against colorectal cancer in this early stage of tumorigenesis. On the contrary, CD86 seems to be involved in the inflammatory pathogenesis of UC.

Actins↗
PubMed2002

Effect of moderate exercise on salivary immunoglobulin A and infection risk in humans.

The incidence of upper respiratory tract infections (URTI) and salivary immunoglobulin A concentrations [IgA(s)] of nine individuals were examined during 12 weeks of moderate exercise training, and compared to ten sedentary controls. Changes in maximal oxygen uptake were assessed at initial, mid-point and final evaluations (T1-3), while changes in [IgA(s)] and salivary immunoglobulin concentration-salivary albumin concentration ratio ([IgA(s)]:[Alb(s)]) were monitored at T1 and T3. During the 12 week period, symptoms of URTI were self-recorded daily. During the period of training the level of fitness significantly increased ( P<0.05) in the exercise group. The number of days recording symptoms of influenza, but not of cold, and total light URTI symptoms was significantly reduced in the exercise group during the last weeks of training. A significant increase in [IgA(s)] and in [IgA(s)]:[Alb(s)] was found in the exercise group after training. Both [IgA(s)] and [IgA(s)]:[Alb(s)] were significantly related to the number of days showing symptoms of influenza ( P<0.01) and the total number of days of sickness ( P<0.05). These data provide quantitative support for the belief that regular, moderate exercise results in an increased [IgA(s)] at rest and [IgA(s)]:[Alb(s)], which may contribute to a decreased risk of infection.

Adaptation, Physiological↗
PubMed2005

Chemopreventive agent-induced modulation of death receptors.

The goals of chemoprevention of cancer are to inhibit the initiation or suppress the promotion and progression of preneoplastic lesions to invasive cancer through the use specific natural or synthetic agents. Therefore, a more desirable and aggressive approach is to eliminate aberrant clones by inducing apoptosis rather than merely slowing down their proliferation. The increased understanding of apoptosis pathways has directed attention to components of these pathways as potential targets not only for chemotherapeutic but also for chemopreventive agents. Activation of death receptors triggers an extrinsic apoptotic pathway, which plays a critical role in tumor immunosurveillance. An increasing number of previously identified chemopreventive agents were found to induce apoptosis in a variety of premalignant and malignant cell types in vitro and in a few animal models in vivo. Some chemopreventive agents such as non-steroidal anti-inflammatory drugs, tritepenoids, and retinoids increase the expression of death receptors. Thus, understanding the modulation of death receptors by chemopreventive agents and their implications in chemoprevention may provide a rational approach for using such agents alone or in combination with other agents to enhance death receptor-mediated apoptosis as a strategy for effective chemoprevention of cancer.

Animals↗
PubMed2006

Relationship between welfare and udder health indicators in dairy ewes.

The relationships between welfare and udder health indicators were investigated in 120 midlactation Comisana ewes over a 90-day period. The welfare indicators monitored were the humoral response to chicken egg albumin (OVA), the cell-mediated immune response to phytohemagglutinin, and the plasma cortisol levels. Changes in milk components, in somatic cell count (SCC) and in bacterial count, in leukocyte populations and in anti-OVA IgG concentration were used to monitor the ewe udder health. Correlations between welfare and udder health indicators were then tested. The skinfold thickness, representative of the cell-mediated immune response, was correlated positively with the percentage of neutrophils in milk and negatively with the chloride content, the percentage of lymphocytes and anti-OVA IgG concentrations in milk. The plasma antibody titres to OVA, representative of the humoral immune response, correlated positively with the anti-OVA IgG levels in milk and negatively with the lactose content and to the percentage of neutrophils. Plasma cortisol levels correlated positively with the chloride content in milk. Our study demonstrates that information about the immune condition of animals can be successfully achieved by monitoring the immunological responses of the mammary gland. The detection of reliable indicators of animal welfare in milk can help in reducing the stress from animal handling and blood sampling from lactating animals.

Albumins↗
PubMed1985

The use of urethane sponge matrix to assess in vivo recovery of murine cellular immunity following syngeneic bone marrow transplantation.

A unique method for assessing the in vivo recovery of cellular immunity following sublethal irradiation and syngeneic bone marrow transplantation of CBA/J mice is described. This method employs the serial surgical implantation of a urethane sponge matrix followed by impregnation of the sponge matrix with alloantigen. Sponge matrices were harvested from each mouse subject at 2 weeks, 4 weeks, and 8 weeks post transplant with and without treatment with interleukin-2. Recovery of cellular immunity was assessed as a function of cytotoxic T lymphocyte activity via cell-mediated lympholysis using chromium labeled targets. Repetitive procedures of implantation and removal of the matrices from the same animal were surgically feasible and were exceptionally well tolerated by the animals with insignificant morbidity thereby permitting continuous monitoring of immunologic recovery. Although the results of treatment with interleukin-2 were inconclusive, this method provides a sensitive, technically manageable means by which to assess an antigenic response in vivo at predetermined time intervals utilizing the same mouse subject. The method additionally affords the potential of being applicable to the in vivo assessment and manipulation of other aspects of the immune response.

Animals↗
PubMed1989

Antibodies to cyclosporine A (CsA) by a novel route and their use to monitor cyclosporine levels by radioimmunoassay (RIA).

Anti-cyclosporine antibodies were generated in rabbits, using an antigen derived from CsA. CsA was linked to carrier proteins by means of a photoactive cross-linking reagent, 4-benzoylbenzoic acid (BBa), an alpha, beta-unsaturated ketone. In the presence of CsA, photolysis of BBa results in hydrogen abstraction and random insertion into the cyclosporine molecule, generating a population of CsA with carboxyl groups at various positions. Immunization with CsA-BBa-bovine serum albumin gave rise to high affinity antibodies to CsA, with Kd = 9.8 +/- 2.8 x 10(-11) M, as determined by Scatchard analysis. Specificity was determined by competition experiments in a radioimmunoassay (RIA), using a panel of six cyclosporine derivatives, substituted at different positions. The derivatives could be arranged into three groups according to their affinities. One derivative with the lowest affinity had a bulky O-t-butyl-D-serine in place of D-alanine in position 8. Serum CsA levels in 25 transplant patients were measured by RIA, and compared to levels determined with a commercially available polyclonal antibody, which is routinely used clinically. The rabbit antiserum gave values that correlated well with the results using the commercial antibody.

Animals↗
PubMed1986

Further evaluation of an immunoprecipitation assay for TSH-receptor autoantibodies in Graves' disease.

In ten patients with untreated Graves' disease, quantitative titers of TSH receptor antibodies, as measured by a recently developed immunoprecipitation assay (IPA), were correlated with results obtained in three other methods and with the severity of the hyperthyroidism, as assessed by thyroid function tests. Nine patients were positive in the IPA, six in the TBII (TSH-binding inhibitor immunoglobulins), six in the TSI (thyroid-stimulating immunoglobulins), and seven in the TGI (thyroid-growth stimulating immunoglobulins) assay. Three patients were positive in all four assays. No correlation was found between the IPA values and the results obtained in the TBII, TSI, or TGI assays. There was a modest correlation between the TBII and TSI assays (r = .74, P less than 0.02). There was a modest but significant correlation between the IPA titers of TSH receptor antibodies and serum T3 concentration, both before treatment (r = .63, P less than 0.05) and during treatment (n = 5; r = .84, P less than 0.05). No correlation between the severity of the hyperthyroidism and TBII, TSI, or TGI assays was observed. Finally, TGI did not correlate with goiter size as estimated by palpation. These results suggest that the IPA may be useful in monitoring the immunologic activity of TSH receptor antibodies in patients with Graves' disease. They suggest further that the IPA detects a number of different subpopulations of TSH receptor antibodies, including TSI, TBII, and perhaps TGI. This property may be particularly useful in screening for monoclonal TSH receptor antibodies.

Adult↗
PubMed1989

Characteristics of weekly pulmonary hypersensitivity responses elicited in the guinea pig by inhalation of ovalbumin aerosols.

We have reported the development of a guinea pig animal model for pulmonary hypersensitivity to inhaled chemicals in which respirations of animals are monitored continuously for 24 hr permitting detection of immediate- (IAR) and late-onset (LAR) airway reactions. Additionally implanted temperature transmitters allow determination of accompanying febrile responses. The current study investigated the relationship between severity of IAR and occurrence of LAR in individual animals. To quantify severity, a grading system was devised which took into account time to response, increase in breathing rate, and occurrence of airway constriction (ACR). Guinea pigs were sensitized by ip injection with 1 mg ovalbumin (OA). On Day 14, inhalation challenge with 12 mg/m3 OA resulted in severe IAR in all animals. No LAR were detected. Subsequent weekly inhalation challenges with OA resulted in less severe IARs and occasionally in absence of response. Febrile reactions were not detected. On one occasion a LAR was observed. It occurred in the animal demonstrating the most severe IARs and having the highest titer of specific homocytotropic antibody. These results are consistent with the mechanism of IAR involving release of spasmogenic mediators from mast cells as a result of antigen crosslinking of surface antibody. The mechanism of the LAR is addressed in the accompanying paper in which LARs are more consistently produced in OA-sensitized guinea pigs.

Administration, Inhalation↗
PubMed1985

Investigation of in vivo activated T cells in multiple sclerosis and inflammatory central nervous system diseases.

Monoclonal antibodies have recently been characterized which identify activated T cells at different stages of differentiation. We compared the expression of the late appearing activation antigen defined by monoclonal antibody TS2/7 with the expression of early appearing activation antigens in a group of patients with active multiple sclerosis, encephalitis, non-inflammatory other neurologic diseases, and normal controls. An increase in TS2/7 reactivity of peripheral blood T cells was found in MS patients compared to controls (P less than 0.001), however, there was no increase in the level of early activation antigens. This was in contrast to three patients with viral encephalitis, who had an increase in the early activation antigen 4F2, but minimal, if any, increase in the TS2/7 reactive antigen. This study demonstrates that in vivo, as in vitro, it is possible to identify multiple differentiation stages for activated T cells. Furthermore, the presence of activated T cells in the peripheral blood of multiple sclerosis patients suggests that there is systemic immune activation in MS, and could provide a means to monitor abnormal immunologic activity in MS when these cells are functionally characterized.

Antibodies, Monoclonal↗
PubMed1989

Use of plasma histamine levels to monitor cutaneous mast cell degranulation.

A simple, minimally invasive procedure for monitoring cutaneous mast cell degranulation in vivo in man is described. Plasma histamine levels in venous blood draining the site of intradermal histamine, morphine, and antigen challenges were determined with a modified radioenzymatic assay. Elevations in plasma histamine above baseline levels of 0 to 0.6 ng/ml were measured after intradermal histamine; levels of 1.4 to 85.2 ng/ml were obtained after a 2 microgram intradermal challenge in 16 subjects. After antigen testing, peak plasma histamine levels ranged from 1.1 to 24.4 ng/ml (n = 9), and after morphine sulfate skin testing peak plasma histamine levels ranged from 2.3 to 12.7 ng/ml (n = 4). The time to achieve peak plasma histamine levels ranged from 2 to 10 minutes after histamine, from 5 to 15 minutes after antigen, and from 1 to 8 minutes after morphine challenges. Plasma levels returned to baseline within 30 minutes after histamine and morphine challenges but took more than 60 minutes for antigen challenges. With careful choice of the skin test site in relation to venous drainage, plasma histamine increases after either histamine or antigen were reproducible and reliable. Plasma histamine levels peaked 5 to 10 minutes before maximal development of the wheal-and-flare responses after histamine, antigen, or morphine skin tests. The wheal-and-flare skin tests continued to increase in magnitude despite rapidly declining plasma histamine levels. Thus skin tests eliciting reactions ordinarily seen in an allergist's office cause measurable increases in plasma histamine levels that can be used to directly monitor mast cell degranulation in man in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗
PubMed1990

Successful small-bowel/liver transplantation.

A patient with the short-gut syndrome and antithrombin III deficiency underwent small bowel and liver grafting a year ago. Transient, mild graft-versus-host disease and intestinal rejection occurred within 2 months of grafting and were easily managed. Parenteral nutrition was discontinued 8 weeks after surgery. The patient has maintained normal nutritional indices while on an unrestricted oral diet. Small-bowel/liver grafting is feasible for patients with the short-gut syndrome and associated liver disorders. Further experience is needed to determine the specific risks, benefits, and general applicability of this procedure.

Adult↗
PubMed1988

Immunophenotype of blast cells in chronic myeloid leukemia.

The immunophenotype of peripheral blood blast cells from 14 patients in the chronic phase of chronic myeloid leukemia (CML) was studied using a panel of monoclonal antibodies (McAb) directed against megakaryocytic, granulomonocytic, erythroid and lymphoid antigenic determinants. The blast cells were enriched by a simple bovine serum albumin (BSA) density-cut separation and cooled in liquid nitrogen. The study was done using the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique on the thawed blast cells. A consistent pattern of reactivity with McAb was found in all patients, showing that blast cells were heterogeneous. A minor component of the blast cells react with platelet antibodies, most of them being labelled with anti-GPIIb-IIIa McAb. Anti-GPIb and Von Willebrand factor McAb detected 4 times fewer megakaryocytic blast cells, suggesting that these cells are located very early in the differentiation scheme. Two major blast cell compartments were labelled with early myelomonocytic (anti-CD13: MY7) and early erythroid (anti-CD36: FA6-152) McAb. The CD34 (My10) and DR antigens which are expressed by immature blast cells and myeloid progenitors of human bone marrow (BM) were present on more than 50% of the CML blast cells. Thus, the blast cells of chronic phase CML patients, showed the same cellular diversity as the increased progenitor cell compartment observed in this disease, and their differentiation stages seemed to be very closely related.

Antibodies, Monoclonal↗
PubMed1981

Effect of neonatal thymectomy and antilymphocyte globulin on non-specific mitogen stimulation in Holstein-Friesian calves.

Nine of seventeen neonatal Holstein-Friesian calves were thymectomized, treated with antilymphocyte globulin, and monitored for immunologic functional ability for 4 to 6 months. The thymus weights for 4 to 10-day-old calves and 4 to 6-month-old calves indicated a continued increase in total weight. This indicated significant thymic involution had not occurred at 4 to 6 months. Following thymectomy a wasting syndrome was not observed although an increased incidence of a lowly virulent virus infection did occur. A significant decrease in circulating lymphocytes was observed. Peripheral blood lymphocytes were stimulated in vitro by non-specific mitogens, phytohemagglutinin, bacterial lipopolysaccharide and pokeweed mitogen using the whole blood culture method. Observations included a greater response to phytohemagglutinin and pokeweed mitogen in summer months and variable age related response to all mitogens. Lipopolysaccharide stimulation results were inconclusive. It was concluded that neonatal thymectomy was not a satisfactory experimental procedure for the production of selective immunosuppression in the bovine species.

Animals↗
PubMed1991

Monitoring of rejection in renal transplantation.

With better immunosuppression, the results of kidney transplantation have improved greatly during the last 10 years. It has never been possible to completely suppress rejection, and transplant physicians and surgeons still need to maintain a constant vigilance in order that rejection does not go unrecognised in their patients. 1.1. CLINICAL FEATURES. These are often absent, although the patient may have noted a decreased urine volume and gain in weight. The kidney is sometimes tender and enlarged. 1.2. BIOCHEMICAL FEATURES. There is a rise in the plasma urea and creatinine and a reduced creatinine clearance. Unfortunately, other conditions such as cyclosporin nephrotoxicity can produce similar changes. 1.3. RADIOLOGICAL FEATURES. Isotope renography may demonstrate reduced renal perfusion and excretion but this is also seen in ATN. Ultrasound may demonstrate an increase in renal size. On Duplex renal ultrasonography changes in renal perfusion patterns can often be demonstrated. MRI has shown a loss of cortico-medullary differentiation during rejection, but this is not very specific. 1.4. CYTOLOGICAL FEATURES. The presence of lymphocytes in the urine is often indicative of rejection, as is the finding of inflammatory cells in fine needle aspirates from the transplanted kidney. 1.5. HISTOLOGICAL FEATURES. Renal biopsies are best obtained using a Biopty Gun under ultrasound control. Cellular rejection is characterised by a heavy infiltrate of lymphocytes which invade the renal tubules (tubulitis). Vascular rejection is characterised by endothelial proliferation and fibrinoid necrosis of the vessel wall. 1.6. CONCLUSION. Several of the above tests are often required to establish the presence or absence of rejection.

Graft Rejection↗