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Biomedical subjects

B J Ank

Publications and source records attributed to B J Ank.

26 records · Page 2Linked to original sources

Enhanced interferon production and lymphokine-activated cytotoxicity of human placental cells.

The immunologic competence of human placental mononuclear cells was compared to that of adult and cord blood mononuclear cells. Mononuclear cells were isolated from fresh placentas by digestion with collagenase and DNase, followed by Ficoll-Hypaque and discontinuous Percoll separation. Placental cells incubated with phytohemagglutinin (PHA) synthesized significantly more interferon-gamma (IFN-gamma) at 2 days (29 +/- 5.5 IU/ml) and 5 days (46 +/- 8.5 IU/ml) than PHA-activated cord cells (3.6 +/- 0.6 IU/ml at 2 days and 2.7 +/- 0.7 IU/ml at 5 days) but less than PHA-activated adult cells (81 +/- 20 IU/ml at 2 days and 270 +/- 161 IU/ml at 5 days). Placental and adult cells, but not cord cells, also synthesized significant quantities of IFN-gamma following incubation with interleukin-2 (IL-2). There was synergism between IL-2 and PHA activation for IFN-gamma production for some cord samples. After a 5- to 7-day incubation with IL-2, the lymphocyte-activated killer (LAK cell) cytotoxicity of placental cells (measured in a 3-hr chromium-release assay at an E:T ratio of 40:1) was enhanced 13-fold against K562 target cells (6 +/- 2% to 77 +/- 4%) compared to a 4-fold increase in cord cells (16 +/- 4% to 68 +/- 3%) and a 2-fold increase in normal adult cells (35 +/- 4% to 65 +/- 3%. Against the natural killer (NK)-resistant Raji target, placental cells increased their LAK cytotoxic activity (3 +/- 1% to 59 +/- 7%) compared to a 7-fold increase with cord cells (6 +/- 1% to 43 +/- 3%) and a 3-fold increase with adult cells (11 +/- 2% to 38 +/- 4%). A notable degree of cytotoxic activity in the absence of IL-2 against Molt targets was noted in 11 of 14 (79%) placental cell samples at 5 days. Only 10 of 24 (42%) adult and 17 of 37 (40%) cord samples showed spontaneous cytotoxic activity equal to or greater than 10%. Some placental samples actually showed an increase in cytotoxic activity when incubated without IL-2. The ability of placental cells to produce significant levels of IFN-gamma, to develop considerable LAK activity, and to maintain or develop cytotoxic activity in the absence of IL-2 suggests a vigorous, active immune system of the placenta compared to the relatively dormant immune system of the neonate. These observations suggest that placental cells may have a primary role in fetal defense.

Adult↗

Cytotoxic studies in human newborns: lessened allogeneic cell-induced (augmented) cytotoxicity but strong lymphokine-activated cytotoxicity of cord mononuclear cells.

Nonspecific cytotoxic responses such as natural killer activity can be increased in vitro by incubating effector cells with soluble factors or allogeneic cells. We sought to determine if newborn cells, known to be deficient in most cytotoxic responses, including resting NK activity, could develop enhanced cytotoxic responses following incubation with allogeneic cells (augmented cytotoxicity) or with lymphokines (lymphokine-activated cytotoxicity). Cord whole mononuclear cells (WMC) incubated with irradiated Raji cells for 5 days develop lower levels of cytotoxicity toward K562 targets at both a 20:1 effector:target (E:T) ratio (39 +/- 2.7% vs 49 +/- 3.6%) and a 10:1 E:T ratio (29 +/- 2.6% vs 40 +/- 3.6%) than do adult cells. Lessened specific cytotoxicity of cord cells developed toward the sensitizing Raji cells was also observed at both E:T ratios. Attempts to enhance the induced cytotoxicity by incubation with interferon or isoprinosine were unsuccessful. In contrast, lymphokine (i.e., interleukin 2)-activated killer (LAK) cytotoxicity is not deficient in cord WMC. Indeed, the level of LAK cytotoxicity is equivalent to that observed with similarly treated adult cells despite a lower baseline level of cytotoxicity toward the target cells. In the presence of purified IL-2 for 5 days, cord WMC cytotoxicity against K562 cells increased from 12 +/- 2.6 to 71 +/- 4.2% and against Raji cells increased from 9.6 +/- 2.5 to 48 +/- 6.7%. Similarly treated adult cells increased their killing against K562 from 23 +/- 4.2 to 61 +/- 4.5% and against Raji from 12 +/- 3.0 to 36 +/- 5.3%. This substantial lymphokine-activated cytotoxicity of newborn cells suggests the possibility of therapeutic intervention with purified lymphokines in neonatal infections or neoplasms.

Cytotoxicity, Immunologic↗

Immune function in pure iron deficiency.

Immunologic studies were performed in ten iron-deficient children, aged 12 to 30 months, before and after iron replacement. Chronic infection, malnutrition, and vitamin deficiency were excluded. Mean hemoglobin levels went from 8.2 +/- 0.2 (SEM) to 12.3 +/- 0.3 g/dL after iron replacement. Mean T-cell percentage increased from 50% +/- 3.0% to 58% +/- 3.7%. Absolute numbers of T cells were unchanged. Three children converted negative in vitro proliferative responses to Candida or tetanus antigen. Mean stimulation indexes increased for Candida (6.8 +/- 1.7 to 17.9 +/- 6.7) and tetanus (19.5 +/- 6.0 to 31.7 +/- 8.5). Nine of 16 delayed hypersensitivity skin tests were positive before and ten of ten were positive after iron therapy. The IgG and IgA levels did not change significantly, but IgM levels decreased from 181 +/- 13 to 128 +/- 5 mg/dL. We conclude that T-cell immunity is slightly impaired in pure iron deficiency and that these subtle defects can be corrected with oral iron replacement.

Anemia, Hypochromic↗

Bactericidal activity and chemotaxis in pemphigus vulgaris and bullous pemphigoid.

Host defense mechanisms were studied in six patients with pemphigus vulgaris (PV) and six patients with bullous pemphigoid (BP). Polymorphonuclear (PMN) leukocyte killing of Staphylococcus organisms was evaluated, and chemotaxis of PMN and mononuclear (MN) leukocytes in patients was compared with that in twenty age- and sex-matched controls. All patients had extensive widespread disease with the clinical diagnosis confirmed by immunopathologic studies. No statistically significant differences were observed in the PMN leukocyte bactericidal activity between PV patients and controls. In BP patients, PMN leukocyte bactericidal activity was very slightly reduced when normal cells and patient serum were used, but activity was normal when patient cells and patient serum were used. PMN leukocyte chemotaxis was normal in PV and BP patients. MN leukocyte chemotaxis was normal in PV patients and increased in BP patients when compared with that in controls. This study indicated that in spite of very severe and extensive disease, patients with PV and BP have intact neutrophil and monocyte functions. Drugs that compromise the patient's ability to fight infections should be used cautiously and judiciously.

Blood Bactericidal Activity↗

Survival of oral human immune serum globulin in the gastrointestinal tract of low birth weight infants.

Six immature infants were given oral feedings of 10% preservative-free human immune serum globulin ranging from 1 to 8 ml/kg/day. A seventh infant served as a control. Undigested and partially digested IgG was detected in the stools in significant quantities in all but the control infant. This coproantibody retained significant opsonic activity for type III group B streptococci as determined by a chemiluminescence assay, but lost most of its tetanus antibody activity. The newborn infants' enzymatic immaturity or rapid transit time permits the passage of intact IgG or partially digested IgG to pass throughout the gastrointestinal tract.

Digestion↗

Decreased bactericidal activity of leukocytes of stressed newborn infants.

Previous studies have established that leukocyte phagocytosis and intracellular killing are normal in term and low-birthweight newborns who are well. To determine the effect of stress or illness on newborn leukocyte function, the phagocytic and bactericidal activity of leukocytes from 40 sick newborns was compared with that of leukocytes from 12 newborns and 23 normal adults. To eliminate abnormal phagocytosis resulting from serum opsonic defects in newborn sera, pooled adult sera were used in all assays. Twenty-five of the 40 stressed newborns (63%) had decreased in vitro activity against either Staphylococcus aureus 502A or Escherichia coli, or both, compared with decreased activity in two of 12 well infants (17%) and in four of 23 adult controls (17%). The mean bactericidal activity (percentage of organisms killed after two hours) of leukocytes from stressed newborns against S. aureus (83% +/- 2 [SEM]) and E. coli. (87% +/- 4 [SEM]) was significantly less than in the combined well infant and adult control group (94% +/- 1 for S. aureus and 97% +/- .5 for E. coli). Although the more severely ill infants had an increased incidence of impaired antibacterial activity, the degree of impairment was not related to the severity of illness. No consistent relationship of decreased activity to birthweight, gestational age, age when studied, or specific diagnosis was seen. The leukocyte abnormality in stressed infants against S. aureus was principally a killing defect, while against E. coli both phagocytosis and killing were abnormal. This study indicates that a wide variety of neonatal disorders may affect one or more of the steps required for normal bacterial killing. The lability of leukocytic antibacterial function under stress is an additional mechanism for the newborn's increased susceptibility to infection.

Blood Bactericidal Activity↗