Demographic and clinical features as predictors of clozapine response in patients with schizophrenia spectrum disorders: A systematic review and meta-analysis.

OBJECTIVES: Clozapine (CLZ) is prescribed to (relatively) treatment-resistant patients with schizophrenia spectrum disorders. Currently, it is unknown what factors predict response to CLZ. Therefore, we performed meta-analyses to identify predictors of CLZ response, hence aiming to facilitate timely and efficient prescribing of CLZ. METHODS: A systematic search was performed in 'Pubmed' and 'Embase' until 1 January 2019. Articles were eligible if they provided data on predictors of CLZ response measured demographic and clinical factors at baseline or biochemical factors at follow-up in schizophrenia spectrum disorder patients. RESULTS: A total of 34 articles, total number of participants = 9386; N unique = 2094, were eligible. Factors significantly associated with better CLZ response were: lower age, lower PANSS negative score and paranoid schizophrenia subtype. CONCLUSION: The results of our meta-analyses suggest that three baseline demographic and clinical features are associated with better clozapine response, i.e. relatively young age, few negative symptoms and paranoid schizophrenia subtype. These variables may be taken into account by clinicians who consider treating a specific patient with CLZ.

Effects of feeding different linseed sources on omasal fatty acid flows and fatty acid profiles of plasma and milk fat in lactating dairy cows.

The aim of this experiment was to study the effects of feeding different linseed sources on omasal fatty acid (FA) flows, and plasma and milk FA profiles in dairy cows. Four ruminally cannulated lactating Holstein-Friesian cows were assigned to 4 dietary treatments in a 4×4 Latin square design. Dietary treatments consisted of supplementing crushed linseed (CL), extruded whole linseed (EL), formaldehyde-treated linseed oil (FL) and linseed oil in combination with marine algae rich in docosahexaenoic acid (DL). Each period in the Latin square design lasted 21 d, with the first 16 d for adaptation. Omasal flow was estimated by the omasal sampling technique using Cr-EDTA, Yb-acetate, and acid detergent lignin as digesta flow markers. The average DM intake was 20.6 ± 2.5 kg/d, C18:3n-3 intake was 341 ± 51 g/d, and milk yield was 32.0 ± 4.6 kg/d. Milk fat yield was lower for the DL treatment (0.96 kg/d) compared with the other linseed treatments (CL, 1.36 kg/d; EL, 1.49 kg/d; FL, 1.54 kg/d). Omasal flow of C18:3n-3 was higher and C18:3n-3 biohydrogenation was lower for the EL treatment (33.8 g/d; 90.9%) compared with the CL (21.8 g/d; 94.0%), FL (15.5 g/d; 95.4%), and DL (4.6 g/d; 98.5%) treatments, whereas whole-tract digestibility of crude fat was lower for the EL treatment (64.8%) compared with the CL (71.3%), FL (78.5%), and DL (80.4%) treatments. The proportion of C18:3n-3 (g/100 g of FA) was higher for the FL treatment compared with the other treatments in plasma triacylglycerols (FL, 3.60; CL, 1.22; EL, 1.35; DL, 1.12) and milk fat (FL, 3.19; CL, 0.87; EL, 0.83; DL, 0.46). Omasal flow and proportion of C18:0 in plasma and milk fat were lower, whereas omasal flow and proportions of biohydrogenation intermediates in plasma and milk fat were higher for the DL treatment compared with the other linseed treatments. The results demonstrate that feeding EL did not result in a higher C18:3n-3 proportion in plasma and milk fat despite the higher omasal C18:3n-3 flow. This was related to the decreased total-tract digestibility of crude fat. Feeding FL resulted in a higher C18:3n-3 proportion in plasma and milk fat, although the omasal C18:3n-3 flow was similar or lower than for the CL and EL treatment, respectively. Feeding DL inhibited biohydrogenation of trans-11,cis-15-C18:2 to C18:0, as indicated by the increased omasal flows and proportions of biohydrogenation intermediates in plasma and milk fat.

Effects of forage type, forage to concentrate ratio, and crushed linseed supplementation on milk fatty acid profile in lactating dairy cows.

The effects of an increasing proportion of crushed linseed (CL) in combination with varying forage type (grass or corn silage) and forage to concentrate ratio (F:C), and their interactions on milk fatty acid (FA) profile of high-producing dairy cows was studied using a 3-factor Box-Behnken design. Sixteen Holstein and 20 Swedish Red cows were blocked according to breed, parity, and milk yield, and randomly assigned to 4 groups. Groups were fed different treatment diets formulated from combinations of the 3 main factors each containing 3 levels. Forage type (fraction of total forage dry matter, DM) included 20, 50, and 80% grass silage, with the remainder being corn silage. The F:C (DM basis) were 35:65, 50:50, and 65:35, and CL was supplied at 1, 3, and 5% of diet DM. Starch and neutral detergent fiber content (DM basis) of the treatment diets ranged from 117 to 209 g/kg and 311 to 388 g/kg, respectively. Thirteen treatment diets were formulated according to the Box-Behnken design. During 4 experimental periods of 21 d each, all treatment diets were fed, including a repetition of the center point treatment (50% grass silage, 50:50F:C, 3% CL) during every period. Intake, production performance, and milk FA profile were measured, and response surface equations were derived for these variables. Shifting from 80% grass silage to 80% corn silage in the diet linearly increased dry matter intake (DMI), net energy for lactation (NE(L)) intake, cis-9,cis-12-C18:2 (C18:2n-6) intake, and milk yield, and linearly decreased cis-9,cis-12,cis-15-C18:3 (C18:3n-3) intake and milk fat content. Shifting from a high forage to a high concentrate diet linearly increased DMI, NE(L) intake, C18:2n-6 intake, and milk yield, and decreased milk fat content. Supplementation of CL linearly increased C18:3n-3 intake, but had no effect on DMI, NE(L) intake, milk yield, or milk fat content. Shifting from 80% grass silage to 80% corn silage linearly increased proportions of trans-10-C18:1 and C18:2n-6 in milk fat, whereas the proportions of trans-11,cis-15-C18:2 and C18:3n-3 linearly decreased. Significant interactions between CL supplementation and F:C were found for proportions of trans-10-C18:1, trans-15-C18:1, cis-15-C18:1, trans-11,cis-15-C18:2, and C18:3n-3 in milk fat, with the highest levels achieved when the diet contained 5% CL and a 35:65F:C ratio. The effect of supplementing CL on several milk FA proportions, including C18:2n-6 and C18:3n-3, depends significantly on the F:C ratio and forage type in the basal diet.

Effects of chemically or technologically treated linseed products and docosahexaenoic acid addition to linseed oil on biohydrogenation of C18:3n-3 in vitro.

Rumen biohydrogenation kinetics of C18:3n-3 from several chemically or technologically treated linseed products and docosahexaenoic acid (DHA; C22:6n-3) addition to linseed oil were evaluated in vitro. Linseed products evaluated were linseed oil, crushed linseed, formaldehyde treated crushed linseed, sodium hydroxide/formaldehyde treated crushed linseed, extruded whole linseed (2 processing variants), extruded crushed linseed (2 processing variants), micronized crushed linseed, commercially available extruded linseed, lipid encapsulated linseed oil, and DHA addition to linseed oil. Each product was incubated with rumen liquid using equal amounts of supplemented C18:3n-3 and fermentable substrate (freeze-dried total mixed ration) for 0, 0.5, 1, 2, 4, 6, 12, and 24h using a batch culture technique. Disappearance of C18:3n-3 was measured to estimate the fractional biohydrogenation rate and lag time according to an exponential model and to calculate effective biohydrogenation of C18:3n-3, assuming a fractional passage rate of 0.060/h. Treatments showed no differences in rumen fermentation parameters, including gas production rate and volatile fatty acid concentration. Technological pretreatment (crushing) followed by chemical treatment applied as formaldehyde of linseed resulted in effective protection of C18:3n-3 against biohydrogenation. Additional chemical pretreatment (sodium hydroxide) before applying formaldehyde treatment did not further improve the effectiveness of protection. Extrusion of whole linseed compared with extrusion of crushed linseed was effective in reducing C18:3n-3 biohydrogenation, whereas the processing variants were not different in C18:3n-3 biohydrogenation. Crushed linseed, micronized crushed linseed, lipid encapsulated linseed oil, and DHA addition to linseed oil did not reduce C18:3n-3 biohydrogenation. Compared with the other treatments, docosahexaenoic acid addition to linseed oil resulted in a comparable trans11,cis15-C18:2 biohydrogenation but a lesser trans10+11-C18:1 biohydrogenation. This suggests that addition of DHA in combination with linseed oil was effective only in inhibiting the last step of biohydrogenation from trans10+11-C18:1 to C18:0.

Effects of sweeteners on individual feed intake characteristics and performance in group-housed weanling pigs.

To assess the effects of 2 high intensity sodium saccharine-based sweeteners on individual feed intake characteristics and performance of group-housed weaned pigs, one hundred ninety-eight 26-d-old weanling pigs were given ad libitum access to 3 dietary treatments containing: no additional sweetener (control), 150 mg of sweetener (Sucram C-150)/kg, or 150 mg of sweetener (Sucram 3D)/kg. At weaning, piglets were allocated to 18 pens (11 pigs/pen) based on BW, sex, and ancestry, and pens were randomly assigned to 3 treatments with 6 pens per treatment. The pens were equipped with computerized feeding stations. During the first 12 d, pigs were offered pelleted prestarter diets that were replaced at once by pelleted starter diets for the last 7 d of the 19-d experimental period. The individual feed intake characteristics consisting of latency time (interval between weaning and first feed intake), initial feed intake (intake during the first 24 h following the first feed intake), the number of total visits per day, and the number of visits in which feed was consumed, together with the time and the feed intake per visit, were determined for all piglets. Performance traits and fecal consistency were determined per pen for d 0 to 5, d 5 to 12, and d 12 to 19, as well as for the total period (d 0 to 19). The initiation of feed intake was not affected by the addition of high intensity sweeteners to the diet. From 12 d postweaning, dietary sweeteners caused the piglets to focus more on feed intake and less on exploratory behavior, as shown by the increased percentage of visits with feed intake in pigs fed the Sucram 3D diet compared with those fed the control diet (P = 0.002). The overall daily feed intake increased with time but was not affected by the addition of sweeteners. Nevertheless, dietary sweeteners prevented the depression of feed intake on d 8 and 10 postweaning (d 8, P = 0.013; d 10, P = 0.014), which seemed to coincide with an improved fecal consistency score (d 5 to 12, P = 0.11; d 12 to 19, P < 0.001). However, the changes in feed intake characteristics and fecal consistency only resulted in numerical effects on postweaning pig performance (ADFI, P = 0.126; ADG, P = 0.140). The results of the present study indicate that weanling pigs need a certain period of time before clear effects of dietary sweeteners on individual feed intake characteristics and pig performance can be observed.

Iodination of newly synthesized thyroglobulin by FRTL-5 cells is selective and thyrotropin dependent.

This study shows that the Fisher rat thyroidal cell line (FRTL-5) can iodinate newly synthesized thyroglobulin. Iodinated thyroglobulin was found intra- and extracellularly. Both the synthesis of thyroglobulin and its subsequent iodination were found to be thyrotropin (TSH) dependent, with optimal activity at 10-100 microU TSH/ml. Thyroglobulin was the only protein in the culture medium, that was iodinated with high specificity and in a TSH-dependent fashion. Albumin, which was abundantly present in the culture medium, was only weakly iodinated. Various proteins, including thyroglobulin, were found to be iodinated intracellularly. Of these iodoproteins only thyroglobulin appeared in the medium suggesting selective secretion of iodinated thyroglobulin. It was shown that the other intracellular iodoproteins were no thyroglobulin breakdown products. Their function is as yet unknown.

Studies on the structures of the normal and abnormal goat thyroglobulin genes.

We have cloned the thyroglobulin (Tg) gene of normal goats and goitrous goats which have a Tg synthesis defect. At the 5'-end of the gene, we studied cosmid clones covering a region from 20 kilobases (kb) upstream from the Tg gene to 42 kb into it. Electron microscopy and restriction mapping show that this part of the gene contains 20 exons of 90-1190 bp, in total 4.9 kb of exonic information (56% of the mRNA) split by 19 introns of 150-9100 bp. The exons comprise 12% of the 5' sequences cloned. At the 3'-end, 55 kb were cloned, containing 10 kb of the gene which comprises only 3 exons of 550 bp in total. Sequence analysis of the 3'-end of the normal and abnormal Tg genes has revealed one transition mutation 3' to the reading frame in a stem-loop structure region of the last exon near the poly(A) addition site. Analysis of the promoter site and the first 5 exons has revealed only one difference between the normal and goitrous Tg genes: a Ser----Leu transition in exon 5. We also found an insertion in the fifth intron of the abnormal gene.

Normal-sized thyroglobulin messenger ribonucleic acid in Dutch goats with a thyroglobulin synthesis defect is translated into a 35,000 molecular weight N-terminal fragment.

The translation product of the thyroglobulin (Tg) mRNA in Dutch goats with a Tg synthesis defect has been characterized. The Tg mRNA has a normal size of 8.4 kilobases. Translation of goitrous polysomal Tg mRNA resulted, after immunoprecipitation with polyclonal rabbit antigoat Tg antibodies, in a single 35,000 mol wt (Mr) Tg fragment. To characterize the Tg antigens produced in vivo, thyroid hormone release by the goiter was suppressed by injecting T4 sc in newborn goitrous goats. Immunohistochemical studies showed the presence of Tg antigens almost solely in the colloidal lumen. Electrophoresis of the reduced thyroid proteins demonstrated the presence of two Tg fragments with Mr of 40,000 and 32,000, respectively; the latter is probably a breakdown product of the 40,000 Mr fragment. The difference in Mr between the in vivo and in vitro translation products (40,000 and 35,000 Mr, respectively) can be explained by the carbohydrate content (10% wt/wt) of the in vivo product, as was shown by periodic acid-Schiff-positive staining. Using monoclonal antibodies against the hormonogenic sites at the first and last parts of the Tg molecule, we demonstrated that only the first part of the Tg molecule is present. Both in vivo and in vitro 10% of the goitrous Tg mRNA molecule is translated, resulting in an N-terminal Tg fragment that easily aggregates to large S-S complexes in the colloidal lumen of goiter by H2O2 oxidation.

Autosomal recessive inheritance of goiter in Dutch goats.

The inheritance of congenital goiter due to a thyroglobulin synthesis defect in a strain of Dutch goats has been studied by Mendelian and biochemical methods. Mendelian analysis of 301 matings, resulting in 591 kids, showed an autosomal recessive mode of inheritance. A restriction fragment length polymorphism (RFLP) in the thyroglobulin gene also was used to confirm the recessive mode of inheritance of the defect. In a pedigree consisting of 27 goats, spanning four generations, the genotype determined by RFLP study was in accordance with the observed phenotype and the autosomal inheritance of the defect. Although phenotypically no differences were detected between normal and heterozygous animals, the use of RFLPs allowed the diagnosis of the three genotypes.

Biochemical analysis of desensitization of mouse mast cells.

Biochemical mechanisms of desensitization were explored by using peritoneal mouse mast cells saturated with monoclonal mouse IgE anti-DNP antibody. It was found that a 1-min incubation of the sensitized cells with 0.01 micrograms/ml DNP-HSA in the absence of Ca2+ was sufficient to desensitize the cells completely. The treated cells failed to release a detectable amount of histamine upon incubation with an optimal concentration (0.1 to 1.0 micrograms/ml) of DNP-HSA and Ca2+. Determination of the number of antigen molecules bound to mast cells revealed that only a small (less than 10%) fraction of cell-bound IgE antibody molecules reacted with desensitizing antigen, and that desensitized cells and untreated (sensitized) cells could bind comparable amounts of antigen upon incubation with rechallenging antigen. However, the binding of antigen molecules to desensitized cells failed to induce any of the early biochemical events, i.e., phospholipid methylation, cAMP rise, and 45Ca uptake, as well as histamine release. It was also found that intracellular cAMP levels in desensitized cells were comparable to those in sensitized cells. Desensitization by a suboptimal concentration of DNP-HSA was prevented by inhibitors of methyltransferases, such as 3-deaza adenosine plus L-homocysteine thiolactone. Sensitized cells pretreated with 0.01 micrograms/ml DNP-HSA in the absence of Ca2+ and in the presence of the methyltransferase inhibitors responded to an optimal concentration of antigen for histamine release when they were rechallenged in the presence of Ca2+. Inhibition of desensitization by methyltransferase inhibitors was reversed by the addition of S-adenosyl-L-methionine to the system. The results indicated that the activation of methyltransferases, induced by receptor bridging, is involved in the process of desensitization. Desensitization was inhibited by reversible inhibitors of serine proteases, such as p-aminobenzamidine, indole, and synthesized substrates of rat mast cell proteases. It was also found that diisopropylfluorophosphate (DFP), an irreversible inhibitor of serine proteases, completely blocked desensitization at the concentration of 10 to 40 nM. This concentration of DFP did not affect the antigen-induced histamine release, whereas 100- to 1000-fold higher concentrations of DFP did inhibit histamine release. The results suggest that serine proteases are involved in both the induction of histamine release and desensitization, and that the protease involved in desensitization is distinct from that involved in triggering histamine release.

Number and affinity of receptors for IgE on enriched populations of isolated rat intestinal mast cells.

Recently, particular attention has been paid to a unique subpopulation of mast cells located in the intestinal mucosa of rodents and man (Befus et al., 1982a, b; Strobel, Busuttil & Ferguson, 1983; Ruitenberg et al., 1982). These cells, presently referred to as mucosal mast cells (MMC), are morphologically, histochemically and functionally distinct from the more extensively studied connective tissue mast cells (Befus et al. 1982b; Pearce et al., 1982). Our ability to characterize the MMC more fully has been markedly enhanced by the development of techniques to enrich populations of this cell to purities of over 60% (mean 65.6 +/- 5.2%) using density centrifugation over discontinuous Percoll gradients. In this communication, we report the results of our studies to determine the number and affinity characteristics of IgG Fc (Fc epsilon) receptors on enriched MMC isolated from the intestine of rats with parasite-induced mast cell hyperplasia.

IgE-mediated triggering signals for mediator release from human mast cells and basophils.

Human basophils were developed in suspension culture of mononuclear cells of cord blood in the presence of conditioned medium of phytohemagglutinin-stimulated human T cells, from which interleukin 2 had been eliminated. Approximately 50-90% of cells recovered after 2-4 wk of culture were basophil granulocytes, which bear receptors with high affinity for human IgE. Sensitization of the cells with human IgE followed by challenge with anti-IgE resulted in the release of histamine and arachidonic acid (AA). In both the cultured basophils and human lung mast cells, bridging of cell-bound IgE with anti-IgE induced a transient increase in phospholipid methylation and intracellular cyclic AMP (cAMP), and these processes were followed by Ca2+ uptake and release of both histamine and AA. As demonstrated in rat mast cells, evidence was obtained that the activation of a proteolytic enzyme and phospholipid methylation induced by the bridging of IgE receptors are involved in the subsequent increase in AMP, and are an essential step for transduction of triggering signals for mediator release.

Suspension culture of human mast cells/basophils from umbilical cord blood mononuclear cells.

Selective growth of human mast cells/basophils was obtained in suspension cultures of mononuclear cells from umbilical cord blood. A fraction of culture supernatant of phytohemagglutinin-stimulated T cells, which lacked interleukin 2, was required for the selective growth of mast cells. When the mononuclear cells were cultured for 2-4 wk in the presence of the fraction, 50-90% of the total cells in the cultures contained metachromatic granules. Under the optimal culture conditions, the number of mast cells/basophils recovered from the cultures was 30-60% of the number of mononuclear cells plated. Cultured mast cells/basophils bear 1.2-3.83 X 10(5) IgE receptors per cell and contained 0.48-1.6 micrograms of histamine per 10(6) cells. The average forward rate constant, k1, and dissociation constant, k-1, for the binding of human IgE to IgE receptors on the cells were 1.9 X 10(5) M-1 sec-1 and 6.9 X 10(-5) sec-1, respectively (average equilibrium constant = 2.75 X 10(9) M-1). Specific binding of human IgE with high affinity indicates that the cells recovered in the suspension culture are human mast cells/basophils. Cultured cells sensitized with human IgE released a substantial amount of histamine upon exposure to anti-IgE. The results indicate that human mast cells/basophils obtained in the culture are functionally mature.

Biochemical analysis of initial triggering events of IgE-mediated histamine release from human lung mast cells.

Mast cells were isolated from human lung tissues by counter current centrifugation elutriation, followed by flotation through Percoll gradients. Purified human mast cells released histamine upon challenge with anti-IgE. An optimal concentration of anti-IgE for maximum histamine release from human lung mast cells was comparable to that required for histamine release from normal human basophil granulocytes. Human lung mast cells could be passively sensitized with mouse monoclonal IgE antibody for antigen-induced histamine release. Bridging of cell-bound IgE molecules on human mast cells by anti-IgE or its F(ab')2 fragments induced phospholipid methylation and an increase in intracellular cyclic AMP (cAMP). Incorporation of [3H]methyl groups into phospholipid reached a maximum at 30 sec after challenge with anti-IgE, whereas intracellular cAMP reached a maximum at 1 min. Both values declined to base line levels within 2 to 3 min. These biochemical events were followed by Ca2+ influx and histamine release. Ca2+ uptake and histamine release reached maximum at 2 to 3 min and 5 to 8 min, respectively. Neither phospholipid methylation nor initial rise in cAMP was inhibited by indomethacin, which indicates that these biochemical events are not the result of prostaglandin synthesis. However, inhibition of phospholipid methylation by inhibitors of S-adenosyl-L-methionine-mediated methylation, such as 3-deazaadenosine and S-isobutyryl 3-deazaadenosine, inhibited not only phospholipid methylation but also cAMP rise and subsequent Ca2+ uptake and histamine release. The results indicate that phospholipid methylation induced by bridging of IgE receptors on human mast cells is essential for Ca2+ influx and histamine release.

The human thyroglobulin gene contains two 15-17 kb introns near its 3'-end.

We have cloned overlapping segments of the human thyroglobulin gene from a genomic cosmid library. Restriction mapping and electron microscopy show that a region of 38 kb at or near the 3'-end of this gene encodes only 850 nucleotides or 10% of the messenger RNA (mRNA) sequence. The region contains five exons of 130-210 nucleotides, split by introns of 1 to 15-17 kb. This represents the lowest ratio of coding to non-coding DNA (2.2%) found thus far in any eukaryotic gene. Blot hybridization under non-stringent conditions shows the presence of only one copy of this gene in the human genome and the absence of other closely related sequences.

Biochemical analysis of glucocorticoid-induced inhibition of IgE-mediated histamine release from mouse mast cells.

Pretreatment of mouse mast cells with 10(-7) to 10(-6) M dexamethasone (DM) during overnight sensitization with mouse IgE antibody resulted in inhibition of antigen-induced histamine release and degranulation. The inhibition of both degranulation and histamine release increased linearly with the duration of the treatment; maximal inhibition was obtained after approximately 16 hr with DM. The addition of DM to sensitized mast cells immediately before antigen challenge did not affect the antigen-induced histamine release. DM interacted directly with mast cells by binding to DM-specific cytoplasmic receptors. The treatment of mast cells with DM did not affect the binding of IgE to mast cells or intracellular cAMP levels. Bridging of cell-bound IgE anti-DNP antibody on mouse mast cells either by multivalent DNP-HSA or by anti-IgE induced phospholipid methylation at the plasma membrane and Ca++ influx into the cells. Pretreatment of mast cells with DM inhibited the antigen-induced phospholipid methylation and Ca++ uptake but failed to affect histamine release by Ca++ ionophore A23187. The results suggest that DM treatment inhibits histamine release by the inhibition of the early stage of biochemical processes leading to opening Ca++ channels but does not affect the process distal to Ca++ influx or the binding of IgE molecules to IgE receptors.

Binding properties of IgE receptors on normal mouse mast cells.

Normal rat mast cells and mouse mast cells were purified, and the binding of rat IgE and mouse IgE to IgE receptors was measured. When normal rat mast cells were saturated with either rat IgE or mouse IgE, comparable numbers of IgE molecules bound to the cells. The number of the receptors on rat mast cells was approximately 3 X 10(5)/cell. The forward rate constant, K1, dissociation constant K-1, and equilibrium constant, KA, for rat IgE and mouse IgE were almost similar; KA for rat IgE and mouse IgE were 8 X 10(9) M-1 and 2.5 X 10(9) M-1, respectively. The results indicated that rat IgE and mouse IgE bind to the same IgE receptors on rat mast cells with comparable affinity. It was also found that IgE from the two species bound to mouse mast cells with high affinity. Forward rate constant, K1, for the binding of mouse IgE and rat IgE to IgE receptors on mast cells from BALB/c mice were 1.9 X 10(5) M-1 sec-1 and 1.5 X 10(5) M-1 sec-1, respectively. Mouse IgE and rat IgE dissociate from the receptors with comparable rate (approximately 10(-4) sec-1). However, mouse mast cells appear to have two distinct types of IgE receptors. One type binds both rat IgE and mouse IgE with comparable affinity, whereas the second type binds only mouse IgE. This type of receptor comprises about one-third to one-half of IgE receptors on mast cells of CBA/J mice, and about one-half to two-thirds of IgE receptors in BALB/c mice. Although the binding of rat IgE to these receptors was not detected, the presence of rat IgE along with 125I-mouse IgE interferred with the binding of the latter protein to the receptors. It was suggested that rat IgE might associate with the second type receptors with a forward rate constant comparable to those of mouse IgE, but dissociate rapidly from the receptors.

Bridging of IgE receptors activates phospholipid methylation and adenylate cyclase in mast cell plasma membranes.

Bridging of IgE receptors on normal rat mast cells by divalent anti-receptor antibodies induced phospholipid methylation and an increase in intracellular cyclic AMP within 15 sec after the receptor bridging. These biochemical events were followed by Ca2+ influx and histamine release. When IgE receptors on isolated plasma membranes were bridged by the antibody, both the increase in the incorporation of [3H]methyl into lipid fraction and the synthesis of cyclic AMP were demonstrated. The synthesis of cyclic AMP in this system was enhanced in the presence of GTP. The results indicated that the bridged IgE receptors are linked to both methyltransferases and adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] in the plasma membrane. An increase in cyclic AMP prior to receptor bridging suppressed phospholipid methylation in the plasma membrane, Ca2+ uptake, and subsequent histamine release. On the other hand, inhibition of phospholipid methylation by (S)-isobutyryl-3-deazaadenosine resulted in the suppression of cyclic AMP synthesis in the plasma membrane. These findings suggest that the activation of phospholipid methylation and the activation of adenylate cyclase are e, and subsequent histamine release. On the other hand, inhibition of phospholipid methylation by (S)-isobutyryl-3-deazadenosine resulted in the suppression of cyclic AMP synthesis in the plasma membrane. These findings suggest that the activation of phospholipid methylation and the activation of adenylate cyclase are e, and subsequent histamine release. On the other hand, inhibition of phospholipid methylation by (S)-isobutyryl-3-deazadenosine resulted in the suppression of cyclic AMP synthesis in the plasma membrane. These findings suggest that the activation of phospholipid methylation and the activation of adenylate cyclase are mutually regulated.

Ultraviolet spectrometer and polarimeter for the Solar Maximum Mission.

The detailed optical design of the Solar Maximum Mission-Ultraviolet Spectrometer and Polarimeter is discussed in conjunction with the scientific objectives that led to the design. The instrument consists of a 1.8-m effective focal length aplanatic Gregorian telescope followed by a 1-m Ebert spectrometer. The design of the Stokes polarimeter is also discussed.

Induction of calcium flux across the rat mast cell membrane by bridging IgE receptors.

Rabbit antibody against IgE receptors or its F(ab')2 fragments induced an increase of 45Ca uptake into normal mast cells, and this process was accompanied by histamine release. Evidence was obtained that a substantial portion of 45Ca uptake was due to movement of calcium across the cell membrane. Neither 45Ca uptake nor histamine release was induced by Fab' monomer fragments of the antireceptor antibody. However, bridging of receptor-bound Fab' fragments by antirabbit IgG or bridging of receptor-bound IgE by anti-IgE induced an increase in 45Ca uptake. The results collectively indicate that crosslinking IgE receptors increases the membrane permeability of the mast cells toward calcium.