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In vitro incubation studies using fluoride and iodoacetate as glycolytic inhibitors have been carried out on red cells of the two subjects with adenosine deaminase deficiency. For comparison, similar studies have also been carried out on red cells from a normal subject and from a child with severe combined immunodeficiency with normal adenosine deaminase activity. The adenosine formed in the adenosine deaminase deficient red cells is a measure of adenosine 5′-phosphate breakdown initiated by 5′-nucleotidase, whereas inosine 5′-phosphate, inosine and hypoxanthine formation is a measure of adenosine 5′-phosphate breakdown initiated by adenylate deaminase. With fluoride as inhibitor, nearly all of the adenosine 5′-phosphate breakdown proceeded by way of adenylate deaminase, while with iodoacetate as inhibitor, 20–30% of the adenosine 5′-phosphate breakdown was initiated by 5′-nucleotidase acting on adenosine 5′-phosphate. In addition, significant amounts of adenine were produced in adenosine deaminase deficient red cells in the presence of the glycolytic inhibitors. Possible explanations for the findings noted in this study are discussed and related to recent studies on the properties of the pertinent purine nucleotide catabolic enzymes.

Human milk was found to contain chemokinetic agents for human blood monocytes. The chemokinetic agents were whey proteins that were inactivated by heating at 56 degrees C for 20 min or treatment with trypsin. Three peaks of chemokinetic activity less than 60 kD in size were found by gel filtration chromatography. The chemokinetic activity of each peak obtained by gel filtration was partially blocked by polyclonal rabbit antibodies to recombinant human tumor necrosis factor-alpha (TNF-alpha). TNF-alpha, or a protein that immunologically cross-reacted with it, was also detected in human milk by blockage of the cytotoxicity of human milk by anti-TNF-alpha. Such proteins or others that elicit the release of TNF-alpha from the target cells may be responsible for the enhanced motility of human milk macrophages, and it is possible that they may alter the immunologic or metabolic activities of the alimentary tract of the recipient infant.

Investigations of polymorphonuclear leukocyte (PMN) function were performed in a 5-yr-old white female with delayed umbilical cord separation, impaired pus formation, and a severe defect of PMN chemotaxis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated an almost total deficiency of a high molecular weight glycoprotein(s) (GP138) in the granule and membrane fractions of the patient's cells, and NaB3H4-galactose oxidase labeling demonstrated the absence of a major glycoprotein complex on the surface of her PMNs. Monoclonal antibodies (MAb) were employed in flow cytometry experiments to demonstrate that two previously characterized glycoproteins (Mo1 and LFA1) were undetectable on the surface of the patient's PMNs and monocytes. Immunoprecipitation of 125I-labeled patient cells with subunit specific MAbs confirmed that the alpha-subunits of Mo1 (155 kD) and LFA1 (177 kD) and their common beta-subunit (94 kD) were totally deficient. Functional analyses of patient PMNs demonstrated severe impairment of adherence- and adhesion-dependent cell functions including spreading, aggregation, orientation in chemotactic gradients, antibody-dependent cellular cytotoxicity, and phagocytosis of particles (Oil-Red-0-paraffin, zymosan) selectively opsonized with C3-derived ligands. Patient PMNs demonstrated a normal capacity to rosette with IgG or C3b-coated sheep erythrocytes, but rosette formation with C3bi-coated erythrocytes was profoundly diminished. Adhesion-independent functions including shape change, N-formyl-methionyl-leucyl-3H-phenylalanine binding, and O-2 generation or secretion elicited by soluble stimuli were normal. Membrane fluidity, surface charge, and microtubule assembly were also normal. These findings provide new evidence that critical PMN surface glycoproteins are required to facilitate multiple adhesion-dependent cellular functions of the inflammatory response.

The review of adult respiratory distress syndrome (ARDS) in children by Lyrene and Truog1 summarizes their experience in 15 children ranging in age from 15 months to 14 years. We wish to emphasize that this syndrome may occur in very young infants. We have cared for a previously well 6-week-old infant who had the clinical presentation, course, and ventilatory data compatible with ARDS. The infant was found dusky and gasping in her crib and was noted at a local hospital to be tachypneic and in marked respiratory distress (Pao2 was 29 mm Hg on room air).

We have shown that a high molecular weight factor present in plasma and serum reduced the number of human T lymphocytes exhibiting the motile configuration. In contrast, B lymphocyte morphology was not affected. The activity of this factor was abolished by pepsin or trypsin, and significantly diminished by phospholipase C. Neuraminidase, phospholipase A, phospholipase D or heparin induced serum lipase activity did not change the activity of the inhibitor. Antisera to human β-lipoprotein was capable of removing most of the inhibitory activity from normal human serum. Gel filtration of serum with sephadex G-200 and Bio-Gel A-5M suggested that the molecular weight of this factor was approximately 1-2 × 106 daltons. The inhibitory material was isolated from serum by the following procedures: 1)precipitation by heparin and magnesium chloride; 2)sequetial flotation by ultracentrifugation; and 3)affinity chromaography on concanavalin A-sepharose 4B columns. The inhibitor appears to be a lipoprotein residing in the LDL2 lipoprotein fraction (density 1.030-1.073 g/dl) that is not retained on concanavalin A-sepharose 4B columns. Our studies indicated that the lipoprotein which regulates T cell morphology is distinct from those which inhibit PHA stimulation of human lymphocytes and E-rosette formation.

A 4 y/o female with delayed umbilical cord severance, granulocytosis, periodontitis & recurrent soft tissue infections demonstrated severely diminished leukocyte mobilization (Rebuck window). SDS-PAGE of patient PMN homogenates revealed deficient (

We recently studied a 27 year old woman with adenosine deaminase (ADA) deficiency. Red cell lysates exhibited less than 1 μmole/g hgb/hr conversion of either adenosine or deoxyadenosine to inosine. Lysates made from peripheral blood lymphocytes showed less than 0.5 nmoles/min/mg protein utilization of adenosine. Studies employing intact lymphocytes demonstrated conversion of [8-14C]-adenosine to [8-14C] inosine and [8-14C] hypoxanthine proceeded at 10-20% of the rate of normal lymphocytes. Mixing experiments with red cell extracts failed to demonstrate an inhibitor. She has produced 3 children, one of whom expired with ADA deficient severe combined immunodeficiency. This child's disease was somewhat atypical in that she had considerable lymphoid tissue and the gross and microscopic features of the thymus were relatively normal in appearance and cytology at autopsy. Her husband and 2 living children had approximately half normal ADA activity in their red cell lysates. Starch gel electrophoresis of these lysates indicated the presence of the ADA 1 phenotype. No consanguinity could be detected in the family. Although an absolute determination of the genetics of this disease in this family was not possible, the most likely explanation is that the mother is homozygous for a low activity ADA variant while the father is heterozygous for a more common form of ADA deficiency.

1025 CONCANAVALIN A BINDING PROTEINS OF THE HUMAN POLYMORPHONUCLEAR LEUKOCYTE PLASMA MEMBRANE

• Pustular vasculitis is a new disease concept that links cutaneous, and possibly systemic, aspects of Behcet's, bowel bypass, bowel-associated dermatosis-arthritis, and disseminated gonorrhea syndromes. The pathomechanism of pustular vasculitic lesion generation may relate to circulating immune complex (CIC)-mediated vessel damage and serum enhancement of neutrophil migration. Thalidomide, an oral pharmaceutical available on strict protocol, has therapeutic effects based on proposed modulation of CIC- and neutrophil-mediated cytotoxicity. Thalidomide therapy was started for four patients with significant morbidity from Behcet's syndrome and for one patient with bowel-associated dermatosis-arthritis syndrome. Clinical benefit was dramatic in all patients who completed sequential four-week "on" and "off" thalidomide therapeutic cycles. In three of four patients, in vivo testing for CIC after histamine injection immunopathology converted from positive (immunoreactant deposition in dermal vasculature [four hours after histamine] and CIC-mediated vasculitis [24 hours after histamine]) to negative during therapy. No effects were noted on neutrophil migration or on the LFA-1/Mac-1/p150,95 family of glycoproteins associated with neutrophil adherence as assessed qualitatively by tritium labeling of neutrophil cell surfaces. In this small patient group, thalidomide was a clinically effective, safe (with rigid monitoring) therapy whose mechanism of action may relate more to inhibitory effects on CIC-induced vasculitis than to effects on neutrophil-mediated cytotoxicity. (Arch Intern Med1986;146:878-881)

the dermal microcirculation, which are influenced by the autonomic sympathetic nervous system, s,9 Skin hyperthermia caused by a direct noxious injury or a local reflex caused by an inflammatory reaction occurring deeper in the extremity can be detected easily and imaged by thermography)'9 This localized thermographic abnormality is distinct from the pattern seen in patients with RSD, which consists of difl'use thermal alterations in the extremities in a "glove and stocking" pattern, s, 9 Relative coldness is the most common manifestation. However, for unknown reasons, an affected hand or foot may be hyperthermic) ,9 These changes have been related to sympathetic vasoconstriction and to compensatory and rebound vasodilation of skin capillaries, respectively. 6,~,9 The RSD was characterized by hypothermia in the majority of our patients, although hyperthermia was also seen. Both hypothermic and hyperthermic reactions are abnormal and may represent different stages of the disease, because there should be no significant temperature differential between normal extremities.6.8-/0 Thermography is a noninvasive technique, without known biologic hazards, that readily confirms the diagnosis of RSD by graphically documenting the subjective complaint of pain. It therefore facilitates appropriate therapy, preventing permanent disability. We have shown that results parallel therapeutic response and may be useful in evaluating and monitoring responses to various therapies. R E F E R E N C E S 1. Bernstein BH, Singsen BH, Kent JT, et al. Reflex neurovascular dystrophy in childhood. J PEDIATR 1978;93:211. 2. Fermaglich DR. Reflex sympathetic dystrophy in children. Pediatrics 1977;60:881. 3. Jaeobs JC. Pediatric rheumatology for the practitioner. New York: Springer-Verlag, 1982:165-7. 4. Kozin F, McCarty D J, Sims J~ et al. The reflex sympathetic dystrophy syndrome. I. Clinical and histologic studies: evidence for bilaterality, response to eorticosteroids and articular involvement. Am J Med 1976;60:321. 5. Kozin FF, Ryan LM, Carerra GF, et al. The reflex sympathetic dystrophy syndrome (RSDS). III. Scintigraphic studies: further evidence for the therapeutic efficacy of systemic corticosteroids, and proposed diagnostic criteria. Am J Med 1981;70:23. 6. Hendler N, Uematsu S, Long D. Thermographic validation of physical complaints in psychogenic pain patients. Psychosomatics 1982;23:283. 7. Laxer RM, Malleson RM, Morrison RT. Technetium 99m-methylene diphosphate bone scans in children with reflex neurovascular dystrophy. J PED~ATR 1985;106:437. 8. Pochaczevsky R, Wexler CE, Meyers PH, et al. Liquid crystal thermography of the spine and extremities: its value in the diagnosis of spinal root syndromes. J Neurosurg 1982; 56:386. 9. Pochaczevsky R. Thermography in skeletal and soft tissue trauma. In: Taveras JM, Ferrucei F, Norman A, eds. Radiology: diagnostic imaging and intervention, vol 5. Philadelphia: JB Lippincott, 1987:1-7. 10. Feldman F, Niekoloff EL. Normal thermographic standards for the cervical spine and upper extremities. Skeletal Radiol 1984;12:235.

A three year old white male with Class I glucose-6-phosphate dehydrogenase (G-6-PD) deficiency developed fever and lethargy. In spite of antibiotics, he developed septic shock and died twelve hours later. Blood and post-mortem liver cultures grew Chromobacterium violaceum. Molecular, kinetic and functional studies were carried out on erythrocytes (RBCs), leukocytes (PMNs) and fibroblasts of his identical twin and mother. Chemiluminescence was profoundly abnormal in the twin. G-6-PD isolated from the twin's fibroblasts demonstrated heat lability (27% of initial activity), normal G-6-P Km (56μM) and pH curve, and increased utilization of 2-d-G6P (76% of G-6-P rate); suggesting a new molecular variant (G-6-PD Beaumont). This is the first reported lethal infection in a child with neutrophil dysfunction due to PMN G-6-PD deficiency. This enzyme defect, like classic chronic granulomatous disease, may cause unique susceptibility to Chromobacterium violaceum.