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Biomedical subjects

J A Bellanti

Publications and source records attributed to J A Bellanti.

At least 19 recordsLinked to original sources
PubMed1999

Improvement of gene transduction efficiency in T lymphocytes using retroviral vectors.

Successful gene transfer into T lymphocytes would provide a useful therapeutic modality for the treatment of various diseases and a valuable way to study T cell functions. Currently, most protocols involving gene transfer into T lymphocytes utilize amphotropic retroviral vectors. However, transduction efficiency using these vectors is relatively low because of the high proportion of resting cells, the concentration-dependent growth manner of T lymphocytes, and the low titer of retroviral vectors. In this article we define conditions that provide high levels of transduction by using IL-2 prestimulation and LipofectAMINE for both mouse and human T lymphocytes. We compared the effects of IL-2 prestimulation on transduction efficiencies at different time points and achieved maximum transfer levels at 72 hr after the incubation. By combining the best prestimulation time and cationic lipids-LipofectAMINE at a dose of 0.8 microM, the transduction efficiencies were increased to 45-75% (62.3 +/- 4.3%) in human T lymphocytes and to 21-33% (27 +/- 1.42%) in murine T lymphocytes as determine by FDG staining and X-Gal visualization, compared with 5% with conventional methods. These results indicate that transduction efficiencies in T lymphocytes can be significantly improved by a prolonged preincubation with IL-2 and by the addition of LipofectAMINE.

Animals↗
PubMed1999

Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome.

BACKGROUND: Chronic fatigue syndrome (CFS) is a disorder of unknown etiology, consisting of prolonged, debilitating fatigue, and a multitude of symptoms including neurocognitive dysfunction, flu-like symptoms, myalgia, weakness, arthralgia, low-grade fever, sore throat, headache, sleep disturbances, and swelling and tenderness of lymph nodes. No effective treatment for CFS is known. OBJECTIVE: The purpose of the study was to evaluate the efficacy of the reduced form of nicotinamide adenine dinucleotide (NADH) i.e., ENADA the stabilized oral absorbable form, in a randomized, double-blind, placebo-controlled crossover study in patients with CFS. Nicotinamide adenine dinucleotide is known to trigger energy production through ATP generation which may form the basis of its potential effects. METHODS: Twenty-six eligible patients who fulfilled the Center for Disease Control and Prevention criteria for CFS completed the study. Medical history, physical examination, laboratory studies, and questionnaire were obtained at baseline, 4, 8, and 12 weeks. Subjects were randomly assigned to receive either 10 mg of NADH or placebo for a 4-week period. Following a 4-week washout period, subjects were crossed to the alternate regimen for a final 4-week period. RESULTS: No severe adverse effects were observed related to the study drug. Within this cohort of 26 patients, 8 of 26 (31%) responded favorably to NADH in contrast to 2 of 26 (8%) to placebo. Based upon these encouraging results we have decided to conduct an open-label study in a larger cohort of patients. CONCLUSION: Collectively, the results of this pilot study indicate that NADH may be a valuable adjunctive therapy in the management of the chronic fatigue syndrome and suggest that further clinical trials be performed to establish its efficacy in this clinically perplexing disorder.

Administration, Oral↗
PubMed1997

Recurrent respiratory tract infections in paediatric patients.

Paediatric respiratory tract infections are one of the most common reasons for physician visits and hospitalisation, and are associated with significant morbidity and mortality. The role of physicians and other healthcare professionals has expanded from merely treating disease to implementing measures aimed at health maintenance and disease prevention. Therefore, children with recurrent respiratory tract infections represent a great challenge for the paediatrician, from both therapeutic and preventive standpoints. The paediatrician must first determine whether these recurrent infections are because of host-derived factors or are the result of increased environmental exposure. Host-derived factors may be nonimmunological or related to host immunodeficiency. The leading cause of recurrent respiratory tract infections throughout the world is increased environmental exposure in children attending nursery school or daycare centres. Acute otitis media in children is of particular concern because of its high incidence, frequent recurrence, and serious long term sequelae, e.g. hearing loss. The socioeconomic impact of these recurrent infections is staggering, and there remains much scope for devising methods for their treatment and prevention. Recent approaches have included the encouragement of breastfeeding, the use of intravenous immunoglobulin and respiratory syncytical virus immune globulin, as well as methods of stimulating immunity, such as ribosomal immunotherapy.

Child Day Care Centers↗
PubMed1995

Developmental aspects of pulmonary defenses in children.

It is now generally accepted that maturational immaturity of lung defense system(s) exists in the young infant and child which, together with other maturational deficiencies of immunologic systems, contribute to their undue susceptibility to infections, many of which are associated with pulmonary infections. The alveolar macrophage (AM), of central importance to lung defense, has been studied extensively in the neonatal rabbit by our group and in the human, by others. Collectively, the results indicate small numbers of morphologically and functionally immature AMs prior to birth followed by a dramatic increase within the first 24 hr. This increase coincides with the large release from type II cells of surfactant, which not only may be involved in the functional maturation of developing AMs but also, if present in large quantities, may lead to decreased activity of these cells. There is also an age-related increase in chemotactic and microbicidal activity of AMs during maturation. Deficiencies in bone marrow pools, complement and cytokines (IFN-gamma, TNF-alpha) as well as IgG isotype switching are known to occur in the neonate which may contribute to increased susceptibility to infection and which are amenable to immune interventions.

Animals↗
PubMed1995

The role of NK cell activity in the pathogenesis of poly I:C accelerated and spontaneous diabetes in the diabetes prone BB rat.

The development of insulin dependent diabetes mellitus (IDDM) and diabetes in the diabetes prone (DP) BB rat animal model of IDDM is thought to be due to an autoimmune process. Natural killer (NK) cells have been implicated but not proven to play a pathogenetic role in BB rats due to the increased NK cell number and activity found in these animals. We have recently reported that poly I:C, an inducer of cytokines and a potent enhancer of NK cell function, accelerates the development of diabetes in DP BB rats and induces diabetes in diabetes resistant (DR) BB rats. Since we have further demonstrated that poly I:C administration to BB rats increases NK cell number and levels of inducers of NK cell activity, interferon-alpha and IL-6 which is described therein, we tested the hypothesis that NK cell activity plays an important role in poly I:C accelerated disease. The role of NK cells in poly I:C accelerated diabetes and spontaneous diabetes was examined by determining whether selective depletion of NK cells using a rat NK cell specific antibody (anti-NKR-P1 antibody) alters the development of diabetes. The treatment of BB rats with anti-NKR-P1 antibody resulted in a significantly lower mean NK cell activity of splenic mononuclear cells than that found in control animals. However, the development of diabetes and degree of insulitis was not significantly different between treatment groups. BB rats administered anti-NKR-P1 antibody with poly I:C had a lower mean splenocyte NK cell activity and lower mean NK cell number within the peripheral blood and inflamed islets than rats administered poly I:C alone. However, anti-NKR-P1 antibody administration did not alter the accelerated development of diabetes or the degree of insulitis in poly I:C treated animals. These data document that NK cells do not play a major role in the pathogenesis of poly I:C accelerated diabetes or spontaneous diabetes in the DP BB rat.

Animals↗
PubMed1994

Congenital anaemia after transplacental B19 parvovirus infection.

We report three children with congenital anaemia after intrauterine infection with B19 parvovirus. All the fetuses developed hydrops fetalis that was treated by blood transfusion. After delivery the infants had hypogammaglobulinaemia. In all three, sera lacked B19 but viral DNA was found in bone marrow. All were treated with immunoglobulin. One child died and B19 was found in various tissues. In the other two cases, virus could no longer be detected after therapy but the patients remain persistently anaemic. Persistent B19 infection should be suspected in infants with congenital red-cell aplasia.

Agammaglobulinemia↗
PubMed1994

A disturbance of interferon synthesis with the hyperproduction of unusual kinds of interferon can trigger autoimmune disease and play a pathogenetic role in AIDS: the removal of these interferons can be therapeutic.

Disturbances of interferon synthesis with the hyperproduction of unusual kinds of interferons may be the initial step which triggers autoimmune disease through a chain of pathological reactions including the disturbances of several immunological and cytokine cascades. Prolonged circulation of this interferon may be a predictive marker of an autoimmune condition; the administration of interferons to animals or humans with autoimmune disease or an underlying or latent autoimmune condition can exacerbate or trigger the disease. Healthy people do not have interferon in their blood. This fundamental disturbance of interferon synthesis can result either from a genetic predisposition or from the influence of certain viruses (or viral particles) or both factors together. AIDS has many features similar to autoimmune disease, including the hyperproduction of aberrant interferon, a type with restricted anti-HIV activity, protectively induced by HIV to allow its continued replication and survival. This interferon stimulates the production of certain cytokines and autoantibodies which help unleash the potentially self-destructive powers of the immune system, bringing immunological chaos. In other words, while usual viruses induce normal interferon, which protects the cells against viral infection, HIV induces an abnormal, defective kind of interferon which ensures virus survival. Since there is no known effective method of destroying HIV directly, removing links in this chain of reactions could indirectly destroy HIV and possibly help restore immune functioning.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1994

Cytokines and the immune response.

The recent massive growth and development of clinical immunology has been enriched by the discovery of a new family of molecules, the cytokines, which consist of various groups of polypeptide mediators involved in the communication network of the cells of the immune system. This article provides an overview of the immune system and the current status of the cytokines and their clinical application.

Antigen Presentation↗
PubMed1994

Current concepts of immune interventions in children with respiratory diseases.

In addition to their role in oxygen transport and ventilation, the lungs serve as an important defense function consisting of nonspecific and specific components. The nonspecific factors include aerodynamic filtration, mucociliary apparatus, bronchoalveolar fluid flow and lymphohematogenous drainage (anatomic systems) as well as phagocytosis and inflammation; the specific factors include B-cell immunity (IgG, A, M, D and E) and T-cell immunity (cell-mediated immunity). In the lungs, specialized lymphoid tissues in contact with epithelium (bronchus-associated lymphoid tissues; BALT) function in local antibody (secretory IgA) and cell-mediated immunity responses to foreign antigens. Based upon these considerations, a number of therapeutic interventions have been developed to enhance various components of lung defense. These include substances which enhance both nonspecific elements (leukocyte transfusion, plasma, nonspecific immunostimulants, e.g., immunoactive bacterial extracts) as well as specific elements (vaccines, intravenous gammaglobulin, plasma, interferons, cytokines). The need for further development and utilization of new immune interventions is underscored by the large number of infants and children who suffer from recurrent respiratory infections, who have either maturational immaturity (e.g. small for gestational age newborn), genetically determined (e.g. cystic fibrosis) or acquired defects (e.g. AIDS) of lung defense mechanisms. The emergence of antibiotic-resistant bacterial organisms, e.g. Streptococcus pneumoniae, poses an additional need for new immune interventions.

Adjuvants, Immunologic↗
PubMed1994

Poly I:C induction of alpha-interferon in the diabetes-prone BB and normal Wistar rats. Dose-response relationships.

Although the administration of a fixed dose of the alpha-interferon (alpha-IFN) inducer, polyinosinic polycytidilic acid (poly I:C), accelerates the development of diabetes in DP-BB rats, no reports have characterized the dose-response relationship of poly I:C with serum alpha-IFN levels and the development of diabetes. This study examines the dose-response relationships of poly I:C with the induction of serum alpha-IFN and the development of diabetes in DP-BB and normal Wistar rats. Also tested in this study is the hypothesis that the lack of development of diabetes in poly I:C-treated normal Wistar rats is attributable to a deficient alpha-IFN response. Using poly I:C doses of 0.5, 1.5, 5, and 10 micrograms/g body weight, a direct dose-response relationship was observed in DP-BB rats with the serum alpha-IFN response. Moreover, all doses of poly I:C accelerated the onset of diabetes in BB rats. Serum alpha-IFN levels inversely correlated with time of onset of diabetes (P < 0.01). Also, BB rats with higher levels of serum alpha-IFN were associated with earlier onset of diabetes (P < 0.001). Poly I:C-induced serum alpha-IFN levels were significantly lower in diabetic than in nondiabetic BB rats. In normal Wistar rats, although all doses of poly I:C significantly increased serum alpha-IFN levels, diabetes was not induced. The results of this study indicate that poly I:C administration elevates serum alpha-IFN and accelerates the development of diabetes in BB rats at even very low doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Double-blind study of cetirizine in atopic eczema in children.

An 8-week, double-blind study of the clinical efficacy of cetirizine was performed in a group of 6 to 12-year-old children suffering from atopic eczema. Patients were enrolled in the study if they presented the diagnostic criteria of atopic dermatitis established by Hanifin and Rajka. Pruritus in the cetirizine-treated group diminished significantly more rapidly than in the control group receiving only placebo. During the 8 weeks of the study, diary card scores showed a statistically significant decrease in erythema and other cutaneous symptoms, such as lichenification, in the cetirizine group. The children's parents did not observe any side effects (somnolence or decreased attention) during the study. The results of this preliminary study suggest that cetirizine can effectively control pruritus and other cutaneous symptoms in children suffering from atopic eczema without noticeable side effects.

Cetirizine↗
PubMed1994

Role of food allergy in serous otitis media.

BACKGROUND: The relationship between IgE-mediated hypersensitivity and recurrent serous otitis media has not been completely established. OBJECTIVE: The purpose of the present study was to examine the prevalence of food allergy in patients with recurrent serous otitis media. METHODS: A total of 104 unselected patients (age range 1.5 to 9 years, mean 4.6 years) with recurrent serous otitis media were evaluated for food allergy by means of skin prick testing, specific IgE tests, and food challenge. Patients who were allergic to food(s) underwent an exclusion diet of the specific offending food(s) for a period of 16 weeks. A non-double blinded food challenge was performed with the suspected offending food(s). Their middle ear effusion was monitored and assessed by tympanometry (Welch Allyn Model 23600) during the pre-elimination, elimination and challenge diet phases. RESULTS: There was a significant statistical association, by chi-square analysis, between food allergy and recurrent serous otitis media in 81/104 patients (78%). The elimination diet led to a significant amelioration of serous otitis media in 70/81 (86%) patients as assessed by clinical evaluation and tympanometry. The challenge diet with the suspected offending food(s) provoked a recurrence of serous otitis media in 66/70 patients (94%). CONCLUSIONS: The possibility of food allergy should be considered in all pediatric patients with recurrent serous otitis media and a diligent search for the putative food allergen made for proper diagnostic and therapeutic intervention.

Animals↗
PubMed1993

Genetically stable temperature-sensitive mutants of Salmonella typhi induce protection in mice.

Temperature-sensitive (ts) mutants of Salmonella typhi were isolated following treatment with nitrosoguanidine, and characterized with respect to cut-off temperature, ts phenotype and reversion frequency. Linkage of the ts mutations to selectable chromosomal markers was established by generalized transduction with bacteriophage phage Vi I, and the appropriate antibiotic resistances were transduced into the ts mutants. Multiple mutant S. typhi were then constructed by combining three independent ts mutations in one strain, utilizing linkage of three of the mutations to erythromycin-, streptomycin- and methylglyoxal-resistance. Several recombinants are genetically stable, with calculated reversion rates of less than 10(-22), and induce both protection from intraperitoneal challenge with the virulent parental wild-type S. typhi in mice and the formation of antibodies to the somatic O-9 and O-12, the flagellar H and the capsular Vi antigens.

Animals↗
PubMed1993

Studies of safety, infectivity and immunogenicity of a new temperature-sensitive (ts) 51-1 strain of Salmonella typhi as a new live oral typhoid fever vaccine candidate.

This report describes the results of a phase 1 study evaluating the safety, infectivity, and immunogenicity of a new live oral Salmonella typhi temperature-sensitive (ts) 51-1 typhoid fever vaccine in the human. Three normal male subjects aged 23-32 years received three oral doses of S. typhi ts 51-1, each dose containing 10(9) organisms. Prior to and following immunization each subject was carefully monitored by clinical and laboratory parameters over a 2 week period during which serial specimens of blood and stool were analysed for the presence of the organism. Blood specimens were also obtained for the determination of serum antibody and cell-mediated immune responses and stool filtrates were analysed for the development of coproantibody. The results of these studies indicate that: (1) the vaccine is well tolerated with no clinical or laboratory evidence of adverse reactions; (2) ts 51-1 was detected in only one stool specimen from one volunteer; the organism recovered displayed characteristics of the ts 51-1 vaccine strain; and (3) although no significant humoral or cell-mediated lymphocytotoxic immune responses were detected in the blood, coproantibody was detected in stool specimens from all of the three immunized subjects and IgA-armed ADCC activity was detected in two of three subjects. These studies indicate that S. typhi ts 51-1 may be a suitable strain for the development of an improved oral typhoid fever vaccine. Studies are in progress to determine optimal methods of vaccine delivery preparatory to large phase 2 studies of efficacy.

Administration, Oral↗