Biomedical subjects

L B Milligan

Publications and source records attributed to L B Milligan.

4 recordsLinked to original sources

PubMed1997

Intravenous immunoglobulin inhibits staphylococcal toxin-induced human mononuclear phagocyte tumor necrosis factor alpha production.

Intravenous gamma immunoglobulin (IVIG) is used as therapy in superantigen-mediated disease, yet its mode of action is not clear. Pooled immunoglobulin G contains high concentrations of staphylococcal exotoxin (SE)-specific antibodies which inhibit the in vitro activation of T cells. However, SE and streptococcal exotoxins are potent stimulators of monocytes as well. Monocytes exposed to SE in vitro release large amounts of tumor necrosis factor alpha (TNF-alpha). The purpose of the present study was to determine if SE-specific antibodies in IVIG can inhibit the activation of monocytes by SE. We examined the in vitro effect of IVIG on the ability of staphylococcal exotoxin A (SEA) and staphylococcal exotoxin B (SEB) to stimulate release of TNF-alpha from human mononuclear phagocytes (MO). Pretreatment of SEA with 0.1 mg of IVIG per ml resulted in a slight decrease of SEA-induced TNF-alpha secretion by MO. In contrast, pretreatment of SEB with 0.1 mg of IVIG per ml resulted in significant (greater than 50%) inhibition of SEB-induced TNF-alpha secretion at 24, 48, 72, and 96 h (P < 0.05 for TNF-alpha levels induced by SEB alone versus SEB pretreated with IVIG at all time points). Enzyme-linked immunosorbent assay and Western immunoblotting assays of the IVIG revealed high concentrations of antibodies against SEB and lower concentrations of antibodies to SEA. These data indicate that IVIG can act in a toxin-specific manner to decrease the MO TNF-alpha response to superantigens. Such inhibition may be one mechanism by which IVIG exerts an immunoregulatory role in superantigen-mediated disease.

Adjuvants, Immunologic↗

PubMed1992

Mobilization of lead in mice by administration of monoalkyl esters of meso-2,3-dimercaptosuccinic acid.

The following six monoalkyl esters of meso-2,3-dimercaptosuccinic acid (DMSA) were synthesized and evaluated for relative activities in mobilizing lead from kidneys and brains of lead-bearing mice: n-propyl (Mn-PDMS), i-propyl (Mi-PDMS), n-butyl (Mn-BDMS), i-butyl (Mi-BDMS), n-amyl (Mn-ADMS) and i-amyl meso-2,3-dimercaptosuccinate (Mi-ADMS). DMSA was used as a positive control. When each was administered intraperitoneally (i.p.) as a single dose of 2.0 mmol/kg, DMSA lowered the kidney lead concentration 52%, while the monoesters effected reductions of 54-75%. Mn-ADMS was toxic at this dose. DMSA lowered the brain lead level 20% when given as a single dose, while the monoesters conferred reductions of 64-87%. When given as 5 daily i.p. injections at 0.5 mmol/kg, DMSA reduced the kidney lead concentration 45%, while the monoesters caused reductions of 56-73%. DMSA lowered the brain lead concentration 35% on the 5-day treatment regimen, while the monoesters evoked reductions of 59-75%. Mi-ADMS was equally effective when given orally or i.p. The i.p. LD50 value of this analog in mice is 3.0 mmol/kg, a value which lies between the reported LD50 doses of DMSA (16.0 mmol/kg) and dimercaprol (1.1 mmol/kg). It is suggested that the ability of these monoesters to cross cell membranes may account for their superiority to DMSA in mobilizing brain lead in this animal model.

Animals↗

PubMed1988

Auditory brainstem response in obstructive sleep apnea.

Auditory brainstem response (ABR) has been used by several investigators to study the role of the brain stem in the pathophysiology of obstructive sleep apnea (OSA). These studies have produced conflicting results. We studied 27 preoperative OSA patients and 17 controls using click stimuli presented at a slow (11.7/second) rate and at a fast (57.7/second) rate. ABR was repeated postoperatively in 18 patients. There were no statistically significant differences in the ABRs of preoperative OSA patients when compared with the control group. However, the preoperative recordings showed statistically significant prolonged latencies for wave III (p less than 0.01) and interpeak latency (IPL) I-III (p less than 0.01) when compared to postoperative recordings. Rapid-rate testing was not helpful. Although normal sleep does not cause ABR abnormalities, the pathological sleepiness seen in OSA patients may cause brainstem dysfunction manifested by prolonged ABR latencies. These abnormalities may resolve with treatment of OSA.

Adult↗

PubMedDate not supplied

Investigation of urinary transforming growth factor alpha levels as tumor markers in patients with advanced squamous cell carcinoma of the head and neck.

The objective of this study was to determine whether transforming growth factor alpha (TGF alpha) levels could be used as nonspecific tumor markers in patients with advanced squamous cell carcinoma (SCC) of the head and neck. Fourteen patients with epidermoid carcinoma of the head and neck were followed with serial urine TGF alpha levels, and the results were compared with the extent of cancer and the course of the disease. Based on the findings of this study further research is necessary before urine TGF levels can be recommended as a routine screening test for SCC of the head and neck.

Adult↗