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M Ballow

Publications and source records attributed to M Ballow.

At least 19 recordsLinked to original sources
PubMed1991

Mechanisms of action of intravenous immunoglobulin therapy and potential use in autoimmune connective tissue diseases.

It has been almost 10 years since the observations on the efficacy of intravenous immunoglobulin (IVIG) in patients with autoimmune thrombocytopenic purpura. Over the next decade, IVIG was used in other types of autoimmune diseases. Much work has also been done on gaining a better understanding of the mechanism(s) by which IVIG exerts its effects in these autoimmune diseases. This review examines the proposed mechanisms of action of IVIG and establishes a rationale for the use of this type of therapy in systemic lupus erythematosus (SLE) and other autoimmune connective tissue disorders. Currently, only anecdotal reports are available on the treatment of SLE with IVIG. Nevertheless, studies thus far suggest that IVIG may be useful in selected SLE patients with cytopenias and cutaneous vasculitis and may have a steroid-sparing effect in patients with SLE and juvenile rheumatoid arthritis. In SLE patients with renal disease, it should be used cautiously because some patients have worsening of their renal function with IVIG infusions. These preliminary experiences suggest that multicenter controlled trials on the therapeutic use of IVIG in SLE and other connective tissue disorders would be important.

Animals↗
PubMed1991

The effects of retinoic acid on immunoglobulin synthesis by human cord blood mononuclear cells.

Derivatives of vitamin A have attracted considerable attention as agents which have immune potentiating properties and possibly tumor-suppressive effects. Recent investigations have shown that retinoic acid (RA) can augment immunoglobulin production of B-cell hybridomas from patients with immune deficiency. In this study we examined the ability of RA to modify the mitogen-induced polyclonal immunoglobulin synthesis of cord blood mononuclear cells (CBMC). RA in concentrations ranging from 10(-5) to 10(-7) M augmented IgM synthesis of CBMC in response to formalinized Cowans I strain Staphylococcus aureus (SAC) up to 45.6-fold which was greater at suboptimal responses to SAC. There were no changes in IgG or IgA synthesis and minimal effects on SAC-induced proliferative responses. RA did not produce similar changes in IgM synthesis of SAC-stimulated adult peripheral blood mononuclear cells (PBMC), and RA had no effect on the immunoglobulin synthesis of Epstein-Barr virus (EBV)-stimulated CBMC or adult PBMC. Time course studies showed that peak enhancement occurred when RA was added between 4 and 24 hr after culture initiation and required prior activation by SAC for augmentation of IgM synthesis. Cell separation experiments showed that prior incubation (18 hr) of an enriched T-cell fraction with RA enhanced the IgM synthesis of a T-cell-depleted B-cell fraction. These experiments and the findings that RA-induced augmentation of IgM production in response to SAC, but not to EBV suggest that the immunoregulatory effects of RA may be mediated by either T cells or T-cell products. Further studies will be necessary to understand the mechanism by which RA augments IgM synthesis of CBMC.

Adult↗
PubMed1990

Absent specific viral antibodies in patients with transient hypogammaglobulinemia of infancy.

Of 247 patients referred to the Pediatric Immunology Clinic, University of Connecticut Health Center, Farmington, Conn., for recurrent infections, 13 patients were found to have an abnormal delay in the onset of IgG synthesis and prolongation of the physiologic hypogammaglobulinemia of infancy. At first observation, their mean age was 10.6 months. All patients had abnormally low serum IgG levels (less than or equal to 2 SD for their age). The mean serum IgG level for our patient population was 270 +/- 81 mg/dl; the mean serum IgG level of the control group was 749 +/- 440 mg/dl. Clinically, these patients were first observed with recurrent otitis media, respiratory infections, bronchitis and/or asthma, and formula intolerance. Despite recurrent respiratory tract infections, specific antibodies to the respiratory viruses were absent in nine of 11 patients tested who were observed before 17 months of age. On follow-up, two of the 13 patients never developed specific antibodies to viral agents, although their serum IgG levels normalized; one patient became serology positive at the same time that the serum IgG normalized. In two patients, the serum IgG levels returned to within the normal range for age before the appearance of specific viral antibodies. In eight patients, the appearance of specific viral antibodies was detected before the serum IgG levels returned to normal. Five of these eight patients were treated for short periods (9 months) with replacement immune serum globulin (intramuscular) therapy and did clinically well. These observations suggest that replacement immune serum globulin for short periods of time does not appear to suppress the production of specific, naturally occurring antibodies and the resolution of the hypogammaglobulinemia.

Agammaglobulinemia↗
PubMed1989

Establishment and characterization of adenosine deaminase-deficient human T cell lines.

We have established long term cell lines from a patient with adenosine deaminase (ADA)-deficient severe combined immunodeficiency by stimulation of blood and bone marrow cells with PHA and IL-2 followed by transformation of the activated cells with the human retrovirus HTLV-I. Despite the absence of detectable T cells in the patients blood, cell lines grew that carried the phenotype of mature activated T cells. TJF-2, the line established from blood, was characterized in detail. The concentration of ADA in TJF-2 cells was less than 1% of normal (3.2 U vs 413.0 U). Studies with pharmacologic inhibitors of ADA suggest that the residual adenosine deaminating activity of TJF-2 is from an enzyme distinct from true ADA, a nonspecific aminohydrolyase. Growth of TJF-2 cells was hypersensitive to inhibition by 2'-deoxyadenosine compared to normal T cells (ID50, 55 microM vs greater than 1000 microM). Analysis of 2'-deoxyadenosine-challenged cells showed that TJF-2 cells accumulated significant levels of deoxyadenosine triphosphate, whereas normal T cells did not unless they were also incubated with the ADA inhibitor deoxycoformycin. Southern and Northern blot analysis of these cells revealed a grossly intact ADA gene that produced a normal size ADA mRNA. Yet, despite ADA deficiency, cells of the TJF-2 line were otherwise indistinguishable from HTLV-I-transformed T cells derived from normal donors with respect to dependence on exogenous IL-2 for growth, clonal rearrangement patterns of TCR beta-chain genes, response to PHA, and rapid restoration of cellular volume after hypotonic challenge. The TJF-2 line thus represents a unique HTLV-I-transformed human T cell line exhibiting ADA deficiency and its expected metabolic consequences.

Adenosine Deaminase↗
PubMed1989

Modulation of in vitro synthesis of immunoglobulin and the induction of suppressor activity by therapy with intravenous immune globulin.

Intravenous immune globulin has become an important modality of replacement therapy for children and adults with hypogammaglobulinemia or agammaglobulinemia. It is also evident that intravenous immune globulin is effective in patients with a variety of automimmune disorders. The present study was undertaken to evaluate the effects of intravenous immune globulin replacement therapy in patients with common variable hypogammaglobulinemia. We measured pokeweed mitogen-induced immunoglobulin synthesis of patients' peripheral blood mononuclear cells cocultured in equal numbers with normal subjects' lymphocytes to assess suppressor cell activity. The mean suppressor cell activity in coculture experiments at baseline of nine patients in the study was -16%. Suppressor activity was demonstrated in two of nine patients at baseline who received intravenous immune globulin therapy before initiation of the study. After intravenous immune globulin therapy at a low dose (100 to 200 mg/kg/mo), suppressor cell activity was demonstrated in all nine patients, which ranged from -63% to -100%. In five patients intravenous immune globulin therapy was discontinued for 4 months. There was a return to baseline levels, with suppressor activity ranging from -20% to -50%. On reinstitution of high-dose intravenous immune globulin therapy (300 to 400 mg/kg/mo), all patients except one again demonstrated increased suppressor cell activity. Cell separation and recombination cell culture experiments were performed. All patients had an intrinsic B cell defect before the initiation of therapy so that the effects of intravenous immune globulin therapy on B cell function could not be assessed. Combining normal B cells with the patient's T cell-enriched fraction showed marked suppression of pokeweed mitogen-induced immune globulin synthesis. This suppression was reversible by irradiation of the T cell fraction. Removal of CD8-positive T cells by cell sorting resulted in normal immunoglobulin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Agammaglobulinemia↗
PubMed1989

The uses of intravenous immune globulin in collagen vascular disorders.

Studies in our laboratory demonstrated that the long-term administration of intravenous immune serum globulin in patients with common variable hypogammaglobulinemia produced increased suppressor activity, which resulted in diminished in vitro B cell immunoglobulin synthesis. These studies suggested that intravenous immune globulin therapy might be a useful modality in altering immunoregulation in patients with collagen vascular autoimmune disease. In the present preliminary study, two groups of patients with collagen vascular disease were chosen: systemic lupus erythematosus and primary Sjögren's syndrome. Patients with systemic lupus erythematosus with mild clinical disease were chosen to minimize the risk of adverse effects on the disease process, particularly specific organ involvement (e.g., lupus nephritis). Each patient was used as his or her own clinical and laboratory control. Patients received 300 mg/kg of intravenous immune globulin every 4 weeks. As a whole the patient group did not experience any adverse effects from the intravenous immune globulin therapy. No clinical or laboratory changes were observed in one patient with systemic lupus erythematosus and one patient with Sjögren's syndrome. In the other patient with Sjögren's syndrome, there were subjective changes of improved well-being and increased energy levels without any objective changes in the sicca syndrome. There was a slight steroid-sparing effect (10 to 3 mg/day) but no effects on the sedimentation rate, the antinuclear antibody, or rheumatoid factor serologic studies. In a patient with steroid-dependent systemic lupus erythematosus, there was marked clinical improvement of the cutaneous vasculitis after the third infusion, with reduction in her oral steroid requirements from 25 to 7.5 mg/day.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Isolation of monocyte-depleted and monocyte-rich fractions from human mononuclear cells.

Utilizing a recently reported characteristic of monocytes to aggregate in cold, a new procedure for obtaining monocyte-rich and monocyte-depleted mononuclear fractions from human blood is described. After aggregation in cold and adherence to plastic, a fraction containing 88% monocyte (LeuM3 CD14+) is obtained. After treating the supernatant, which separates from the aggregates, with a monocyte lysosomotropic agent (L-Leucine Methyl Ester), a fraction containing 0% monocyte (LeuM3 CD14+) and 88% lymphocytes (Leu4 CD3+ and Leu 12 CD19+) is obtained. In round-bottom culture wells, this monocyte-depleted fraction produced immunoglobulins in response to pokeweed mitogen (5,826 +/- 2,356 IgM micrograms/ml), to a degree not significantly different that that produced in the presence of monocytes (7,426 +/- 3,347 IgM micrograms/ml). This suggests the presence of cells in the lymphocyte fraction, that are not monocytes but are capable of antigen presenting.

Adult↗
PubMed1987

Immunoregulatory effects of intravenous immune serum globulin therapy in common variable hypogammaglobulinemia.

Because of evidence of immunoregulatory effects of short-term administration of pooled donor gamma globulins, the effects of intravenous immune serum globulin were studied in nine adult patients with common variable hypogammaglobulinemia over a two-year period. Baseline assessment prior to immune serum globulin replacement included evaluation of B cell function, suppressor cell activity, and T cell subsets. These analyses were subsequently performed during the course of a first-year treatment period of intravenous immune serum globulin at doses of 100 to 200 mg/kg per month and a second-year trial at doses of 300 to 400 mg/kg per month. Five patients were re-evaluated following discontinuation of the intravenous immune serum globulin therapy for four months between the first and second treatment periods. During both treatment periods with intravenous immune serum globulin, suppressor cell activity increased markedly compared with baseline, and declined following discontinuation of drug therapy in the five patients. Suppressor cell activity was reversed by either irradiation of the T cell fraction or removal of the T8-positive cell fraction by flow cytometry. There was a reduction in the absolute number of total lymphocytes, the T3-positive cells (total T cells), and the T4-positive cells (helper cells) following intravenous immune serum globulin therapy; however, the percentages of the T cell subsets did not change significantly. Following immune serum globulin therapy, the number of T8-positive cells was not significantly changed but the T4:T8 ratio decreased from 2.1 at baseline to 1.5 after therapy (p greater than 0.05). These data demonstrate that long-term intravenous immune serum globulin administration modulates the immune system by increasing suppressor T cell functional activity but is not accompanied by changes in the number of T8-positive cells in the peripheral blood.

Adult↗
PubMed1987

Cyclosporine treatment of autoimmune chronic active hepatitis.

A 14-yr-old boy with a 5-yr history of autoimmune chronic active hepatitis refractory to corticosteroid therapy was given cyclosporin A (5 mg/kg X day). Before cyclosporine therapy, serum aminotransferase levels were 20 times normal and immunoglobulin G was 4 g/dl. Within 2 wk of starting cyclosporine therapy, aminotransferase levels decreased; by 2 mo they were almost normal, and at 1 yr into therapy they were normal. A decrease in cyclosporine dosage was associated with an increase in aminotransferase levels, which then again decreased as the dose was increased. Severe growth failure observed during previous corticosteroid therapy reversed during cyclosporine treatment and the patient displayed "catch-up" growth. No significant side effects were noted after 1 yr of cyclosporine therapy. Further evaluation of cyclosporine in the treatment of corticosteroid-unresponsive autoimmune chronic active hepatitis appears warranted.

Adolescent↗
PubMed1987

Tear lactoferrin levels in patients with external inflammatory ocular disease.

Lactoferrin, an iron complexing protein in normal tears, is an important component of the nonspecific host defense system of the external eye. We measured tear lactoferrin levels in patients with contact lens-induced giant papillary conjunctivitis (GPC) by an enzyme-linked immunosorbent assay (ELISA). Patients with active GPC (N = 26) had significantly reduced tear levels of lactoferrin (0.876 +/- 0.42 mg/ml) compared with normal individuals (N = 12; 1.73 +/- 0.46 mg/ml, P less than 0.0003) and the control contact lens wearers' group (N = 11; 1.57 +/- 0.92 mg/ml, P less than 0.003). Patients with vernal conjunctivitis (N = 10), an ocular disease with similar histopathology, had slightly reduced concentrations of tear lactoferrin (1.22 +/- 0.59 mg/ml). Patients with inactive GPC (N = 7) had normal tear levels of lactoferrin (1.33 +/- 0.49 mg/ml). The lactoferrin to total protein ratio in the tears was significantly reduced in patients with GPC compared to normal subjects, control contact lens wearers, and patients with inactive GPC. The decreased tear levels of lactoferrin in patients with GPC may contribute to increased coating of lenses with bacteria and their products and enhanced ocular inflammation which may play a role in the pathogenesis of GPC.

Adenoviridae Infections↗
PubMed1985

The aetiological agent of cat scratch disease.

A highly pleomorphic, gram-positive bacterium was cultured from an excised lymph node of a patient with cat scratch disease (CSD). The organism had morphological forms similar to those of the bacterium observed in Warthin-Starry stains of lymph node sections from CSD patients and may be the aetiological agent of this disease. Electron microscopic examination of lymph node sections from another patient with CSD showed organisms with morphological forms similar to those of the isolated bacterium. Biochemical and physiological analyses of this isolate suggested that it is not a commonly recognised contaminant or human pathogen and that it may be a member of the genus Rothia. This organism appears to resemble the bacterium that was identified as the aetiological agent of Parinaud's oculoglandular syndrome, a specific form of CSD, over 70 years ago.

Actinomycetaceae↗
PubMed1985

Modulation of suppressor-cell activity by cimetidine in patients with common variable hypogammaglobulinemia.

Because of evidence of a possible immunoregulatory role for cimetidine, an antagonist to histamine H2 receptors, we studied the effects of this drug in five adult patients with common variable hypogammaglobulinemia. Three patients had excessive suppressor-cell function associated with panhypogammaglobulinemia, whereas the other two had no apparent T-cell defects. The patients were given a one-month course of oral cimetidine (1200 mg daily in four divided doses). Subsequently, the three patients with excessive suppressor-cell function had a marked reduction in suppressor activity along with a decrease in the number of suppressor cells (T8+). One of these three had a marked rise in both in vitro immunoglobulin secretion and serum immunoglobulin concentrations, which was reversible after the drug was stopped for three months and reproducible when therapy with cimetidine was repeated. There was no difference in immunoglobulin secretion or suppressor-cell activity while taking cimetidine between the two patients with common variable hypogammaglobulinemia without excessive suppressor-cell activity and control patients with duodenal ulcers. The data suggest that H2-receptor antagonists may decrease excessive suppressor-cell activity and allow endogenous immunoglobulin production in some patients with common variable hypogammaglobulinemia.

Adult↗
PubMed1985

Varicella pneumonia in a bone marrow-transplanted, immune-reconstituted adenosine deaminase-deficient patient with severe combined immunodeficiency disease.

Bone marrow transplantation provides an important modality for "enzyme replacement" and the immune reconstitution of patients with adenosine deaminase (ADA) deficiency and severe combined immunodeficiency disease. We report a patient with ADA deficiency who develops severe varicella pneumonia 6 years after successful bone marrow transplantation and immune reconstitution. Marked abnormalities in T-cell mitogen responsiveness and pokeweed mitogen-induced polyclonal immunoglobulin synthesis occurred. Coculture experiments suggested the presence of increased suppressor activity. T-cell phenotyping showed decreased T3 and T4 subsets. These abnormalities slowly resolved over several months as the patient recovered from the varicella infection. ADA enzyme levels and metabolite concentrations in urine and erythrocytes remained unchanged. These findings, together with the chromosome and immune studies, suggested that the bone marrow graft remained intact. These studies indicate that immunologically reconstituted ADA-deficient patients may be at higher risk for complications related to varicella infection and suggest that the institution of preventive measures is important.

Adenosine Deaminase↗
PubMed1985

Erythroderma with spongiotic dermatitis. Association with common variable hypogammaglobulinemia.

Two middle-aged men presented with generalized erythroderma, diffuse alopecia, and hyperkeratosis of the palms and soles. Histopathologic study demonstrated spongiosis (epidermal intercellular edema) with a perivascular lymphohistiocytic infiltrate. Complete immunologic evaluation demonstrated that both patients had panhypogammaglobulinemia and markedly depressed in vitro pokeweed mitogen-induced immunoglobulin secretion. One of the patients also showed poor lymphocyte responses in vitro to T cell mitogens and antigens and had a decreased ratio of helper to suppressor cells. In both patients, the cutaneous lesions improved with systemic corticosteroids, but no significant alteration in the immunologic abnormalities was observed. This report illustrates that chronic erythroderma may be the presenting clinical manifestation of common variable hypogammaglobulinemia.

Agammaglobulinemia↗