A naturally occurring mutation in Fc gamma RIIA: a Q to K127 change confers unique IgG binding properties to the R131 allelic form of the receptor

Fc gamma RIIa is widely expressed on hematopoietic cells. There are two known allelic polymorphic forms of Fc gamma RIIa, Fc gamma RIIa-R131 and Fc gamma RIIa-H131, which differ in the amino acid at position 131 in the second lg-like domain. In contrast to Fc gamma RIIa-R131, Fc gamma RIIa-H131 binds hlgG2 but not mIgG1, and this differential binding has clinical implications for host defense, autoimmune disease, immunohematologic disease, and response to therapeutic monoclonal antibodies. We identified a novel Fc gamma RIIA genotype in a healthy individual homozygous for Fc gamma RIIA R/R131 in whom a C to A substitution at codon 127 changes glutamine (Q) to lysine (K) in one of the two Fc gamma RIIA genes. This individual's homozygosity for Fc gamma RIIA-R/R131 leads to the prediction that the receptors on her cells would not bind hIgG2. Monocyte and neutrophil phagocytosis of hIgG2-opsonized erythrocytes was significantly higher (P < .05) for cells from this K/Q127, R/R131 individual than for Q/Q127, R/R131 donors. Platelet aggregation stimulated by an mIgG1 anti-CD9 antibody in this individual was significantly different (P < .05) from Q/Q127, H/R131 and Q/Q127, H/H131 donors and similar to Q/Q127, R/R131. Our data show that the K127/R131 receptors have a unique phenotype, binding both hIgG2 and mIgG1. Further functionally significant mutations in human Fc gamma receptors and possible novel mechanisms for inherited differences in disease susceptibility should be sought with unbiased screening methods.     

In vitro activities of novel antifolate drug combinations against Plasmodium falciparum and human granulocyte CFUs

The potency of antimalarial dihydrofolate reductase inhibitors, alone and in synergistic combination with dihydropteroate synthetase inhibitors, against the Kenyan K39 strain of Plasmodium falciparum (pyrimethamine resistant) and against normal replicating human bone marrow cells in in vitro culture has been studied. Therapeutic indices and rank order of synergistic potency were derived. Trimethoprim, pyrimethamine, and the quinazolines WR159412 and WR158122 had the smallest therapeutic indices (1.39, 4.38, 2.56, and 90.0, respectively), while the three triazines clociguanil, WR99210, and chlorcycloguanil had the largest (3,562, 3,000, and 2,000, respectively). In rank order of decreasing activity against P. falciparum, the six most potent drug combinations were WR99210-dapsone, chlorcycloguanil-dapsone, WR158122-dapsone, WR159412-dapsone, WR159412-sulfamethoxazole, and chlorcycloguanil-sulfamethoxazole; pyrimethamine-sulfadoxine was the least potent combination. These experiments form a basis for the selection of rapidly eliminated antifolate combinations for further clinical testing.     

An Interpersonal Communication Inventory

Patterns, characteristics and styles of interpersonal communication in 316 adult men and women were investigated by use of an Interpersonal Communication Inventoy. Development of the Inventory was based upon previous research in related areas of marital communication, parent-child communication, group therapy and intragroup communication. Item analysis yielded 50 items which discriminated between good and poor communicators. Factors of good and poor communication are identified and discussed. Uses of the Inteversonul Communication Inventory in counseling, teaching and research are proposed.     

Sarcoidosis and thyrotoxicosis: A study of five patients

Regional blood flow of the gastrointestinal (GI) tract and cardiac output have been determined in male Sprague-Dawley rats weighing from 30-726 g. The cardiac output (ml/min per kg) was highest in rats weighing 80-100 g. In heavier rats the cardiac output decreased proportionally with the body weight. The gradient of blood flow to the different parts of the GI tract develops step by step. In the weaning period the blood flow (ml/min per g tissue) through the stomach was less than that through the distal parts of the GI tract. However, the blood flow through the small intestine, cecum and large intestine was uniform at this age. In rats weighing 80-100 g the blood flow through both the cecum and large intestine was less than that through the small intestine. The gradient in blood flow through the various segments of small intestine developed last.     

Wool shrinkage control and surface modification by ozone

In treating fine wool top, more ozone is needed to achieve a given level of felting shrinkage control than with coarse wool. Treatment that allows no more than about 20% top shrinkage in three successive washes is usually satisfactory for controlling fabric shrinkage. A detergent rinse after treatment markedly decreases top and fabric shrinkage. Ozonization decreases fiber strength and wet friction against glass but increases fiber-to-fiber adhesion enough to increase yarn strength. Scanning electron microscopy (SEM) of fibers before and after treatment and laundering indicates that ozone makes the fiber surface more plastic (presumably when wet) but more liable to mechanical damage and erosion, which increase with the severity of treatment and with laundering. However, treatments most effective for shrinkage control are not distinguished from less effective treatments by the degree and character of surface changes shown by SEM. Ring dyeing of fiber cross sections shows that effects of ozone are greatest near the surface. X-ray photoelectron spectroscopy (XPS) and amino acid analysis show that cystine is oxidized to cysteic acid and that carbon is also oxidized at the surface. The increased dyeability (rate and uptake) is attributed to increased wettability, changed ionic balance, and crosslink scission, which, with cuticle damage, allow greater swelling and easier penetration. As found earlier with coarse wools, acid milling (leveling) dyestuffs further decrease shrinkage of treated fine wool. The position of wool in the triboelectric series is shifted toward the negative end by ozone treatment, expressing the higher electron work function of the added sulfonic acid groups. This shift is not simply related to shrinkage. Decreased feltability is attributed to softening of the wet cuticle layer and to increased surface charge, but the mechanism needs further study.     

Further studies on the effect of aldosterone on electrical resistance of toad bladder

The fall in transepithelial electrical resistance which accompanies aldosterone stimulation of short-circuit current (Isc) in toad urinary bladder has been studied further to evaluate the possible causal role of this response in hormonal stimulation of Na+ transport. A steady-state change in tissue conductance was found to depend upon both the simultaneous stimulation of transport by the steroid and the metabolic state of the tissue. Changes in metabolic state alone did not alter resistance. A sustained increase in Na+ transport, dependent on pretreatment with aldosterone and elicited by addition of glucose, could be obtained without a sustained decrease in resistance. Amiloride, an inhibitor of Na+ uptake, produced changes in Isc that were linearly correlated with its effects on tissue conductance. On the basis of the conductance-Isc relationship with amiloride, the Isc response to aldosterone was about two-fold higher than would be predicted from its effects on conductance alone. Despite the apparent lack of a simple quantitative dependence of the change in Isc on the change in conductance when the response is fully developed, the results suggest that conductance changes may mediate the initial or early stage of the response.     

Doses to fetal and maternal organs from intravenous 59FeCl3 or 57CoCl2

Doses from intravenous intakes of 59Fe or 57Co chloride during pregnancy were estimated. Near term fetal organ doses were derived via the MIRDOSE3 newborn phantom, with mean dose/cumulated activity (S) values rescaled for compatibility with near term fetus whole body S. A detailed in vivo biodistribution database provided indications of residence times in important maternal and fetal organs. 59Fe doses to the fetus whole body from early to late pregnancy were 7-11 mGy MBq(-1) (8.5-14.3 mSv MBq(-1)), similar to that to the mother. Doses to near term fetal spleen (59 mGy MBq(-1)), liver (36), and red marrow (9) were similar or higher than to the mother. 57Co doses to fetus whole body from early to late pregnancy were 0.7-3.3 mGy MBq(-1) (2.5-8.2 mSv MBq(-1)), similar or higher than to the mother. Doses to near term fetal small intestine (34 mGy MBq(-1)). liver (4.7) and red marrow (2.7) were similar or higher than to the mother.