New oxidation pathway of 3,5-di-tert-butyl-4-hydroxytoluene: An ionspray tandem mass spectrometric and gas chromatographic/mass spectrometric study

The autoxidation of 3,5-di-tert-butyl-4-hydroxytoluene (BHT, 1) in bar soap was investigated with ionspray tandem mass spectrometric and on-line gas chromatographic/mass spectrometric methods. The oxidation products of BHT were extracted from the bar soap surface, concentrated, and fractionated with open-column chromatography to remove the impurities. New oxidation products of BHT (BHT phenol-type dimer 7 and others) were identified with the two mass spectrometric methods. The results suggested that oxidation of BHT in bar soap occurred in a way different from that in the previous studies. In the new pathway, oxidation of BHT first generates an excited state of phenol-type dimer 4, and then this species decomposes, due to its high energy, to form dimer 7. The mechanism of oxidation is discussed.     

Early and late events in Fc epsilon RI signal transduction in human cultured mast cells

Protein tyrosine phosphorylation and other biochemical events have been shown to occur after cross-linking of Fc epsilonRI in rodent mast cells. To investigate the mechanism of Fc epsilonRI signal transduction in human mast cells, we used human cultured mast cells (HCMC) generated from cord blood cells in the presence of recombinant human stem cell factor and IL-6. We found that on cross-linking of Fc epsilonRI: 1) HCMC released histamine; 2) rapid tyrosine phosphorylation of multiple cellular substrates, including Syk, HS1, c-Cbl, ERK-1, and ERK-2, was observed; 3) intracellular Ca2+ and inositol phosphate production were increased within the first minute after Fc epsilonRI cross-linking; and 4) genistein, a tyrosine kinase inhibitor, inhibited both protein tyrosine phosphorylation and histamine release in a dose-dependent manner. These results were consistent with previous studies in rodent mast cells. In contrast, no tyrosine phosphorylation of phospholipase C gamma1 and Btk (Bruton's tyrosine kinase) were observed in our experimental conditions. These results suggest that the greater part of the early and late signaling events in HCMC is similar to those obtained with rodent mast cells and indicated that the requirement of tyrosine phosphorylation in the activation process of each of the signaling molecules might be different in HCMC and rodent mast cells. Our finding indicates that HCMC may be useful for analysis of Fc epsilonRI-mediated signal transduction in human mast cells.     

Assessment of oxacillin salt agar for detection of MRSA identified by presence of the mecA gene

Progressive growth of immunogenic murine tumors elicits a tumor-specific but functionally deficient T-cell immune response in the draining lymph nodes. These T cells, referred to as "pre-effector" cells could be induced in vitro to differentiate into mature immune effector cells, capable of mediating the regression of established metastases. Initially, tumor cells were used to stimulate the in vitro maturation of pre-effector cells. Alternatively, we found that pre-effector cells could be activated by sequential stimulation with anti-CD3 and interleukin-2 in the absence of tumor cells. In adoptive immunotherapy, these activated cells mediated therapeutic effects that were exquisitely specific to the tumor that triggered the pre-effector cell response in vivo. Since the anti-CD3 interaction with T cells is polyclonal, the activated lymph node cell population must also contain a significant number of T cells that do not have tumor specificity. In an attempt to selectively activate tumor-sensitized pre-effector cells, we recently utilized superantigenic bacterial toxins as T-cell stimuli for effector cell generation. Superantigens combine with major histocompatibility class II molecules to form the ligands that stimulate T cells bearing distinct T-cell receptor V beta elements. Lymph node cells draining the MCA 205 sarcoma stimulated with staphylococcal enterotoxins A (SEA), B (SEB), or C2 (SEC2) resulted in selective expansions of V beta 3 and 11, V beta 3 and 8, or V beta 8.2 T cells, respectively. Adoptive immunotherapy experiments revealed that SEB- and SEC2-, but not SEA- stimulated cells, mediated tumor-specific eradication of pulmonary metastases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical study on azithromycin in 10% fine granules and 100mg capsules in the field of pediatrics

Azithromycin (AZM), a new oral macrolide antibiotic, in 10% fine granules or 100 mg capsules was given to pediatric patients to treat various infections. The following results were obtained in our studies of AZM for its antibacterial activities against clinical isolates, its pharmacokinetics, its efficacy, and its safety. 1. MICs of AZM, erythromycin (EM) and clarithromycin (CAM) were determined against a total of 57 strains all at 10(6) cfu/ml. Among Gram-positive cocci, MICs of AZM ranged from 0.78 to > 100 micrograms/ml against Staphylococcus aureus (20 strains), from 0.05 to 0.1 microgram/ml against Streptococcus pyogenes (11 strains), and from 0.0125 to 3.13 micrograms/ml against Streptococcus pneumoniae (10 strains). These MICs were similar to those of the other macrolides. Among Gram-negative bacilli, MICs of AZM were 0.05 micrograms/ml against Moraxella subgenus Branhamella catarrhalis (1 strain), from 0.78 to 3.13 micrograms/ml against Haemophilus influenzae (9 strains), 0.78 micrograms/ml against Haemophilus parainfluenzae (1 strain) and 6.25 micrograms/ml against salmonella sp. (1 strain). These values were similar to or lower than those of the other macrolides. Against Mycoplasma pneumoniae, MICs of AZM were < or = 0.0008 micrograms/ml in three strains. One strain of M. pneumoniae showed tolerance to AZM at MIC 25 micrograms/ml. The other agents exhibited higher MIC than AZM against this organism. 2. Plasma samples were collected from five patients receiving fine granules and four patients receiving capsules for drug level determination. The patients received AZM at 10.0 approximately 16.3 mg/kg body weight once daily for 3 days. Drug concentrations in plasma at two hours after Day 3 dosing were in a range between 0.02 and 0.19 micrograms/ml for fine granules and were in a range between 0.11 and 0.42 micrograms/ml for capsules. 3. Urine samples were collected from four patients receiving fine granules and four patients receiving capsules. Drug levels were determined to be 3 micrograms/ml at post-treatment 48 hours for fine granules and post-treatment 72 hours for capsules. Urinary excretion rates of AZM in three patients on capsules lied in a range between 4.69 and 10.17%. 4. Effectiveness of AZM in fine granules was evaluated in 128 patients having a total of 19 different infections. AZM was rated "excellent" in 51 patients, "good" in 63, "fair" in 8, "poor" in 6, resulting in an efficacy rate of 89.1%. Effectiveness of AZM in capsular form was evaluated in 23 patients with five different infections. AZM was found "excellent" in 13 patients and "good" in 10, resulting in an efficacy rate of 100%. 5. AZM in fine granules eradicated 45 strains of 54 in 8 different bacteria. AZM in capsules eradicated 9 strains of 10 strains in 6 different bacteria. 6. As for adverse reactions, one patient complained of eruption, one vomiting, one loose stool, five diarrhea, when administered with fine granular form of AZM. One patient on AZM capsules experienced urticaria and vomiting. 7. As for abnormal laboratory changes, three patients were found with decreased WBC, seven with increased eosinophil, two with increased GOT and GPT, one with increased GPT. They were all on fine granular form of AZM. As far as abnormalities found in patients administered with AZM in capsular form, two showed decreased WBC, one decreased WBC along with increased eosinophil, and three increased eosinophil.     

The Adoption of Electronic Innovations with Indirect Network Externalities that Compete with Standalone Physical Products

The authors consider how a change in product form impacts the adoption decision for an innovative product based on digital technology. Examples of changes in product form often arise in products that feature indirect network externalities, such as MP3 players, PDAs and e‐readers. Existing research suggests that, for innovations with indirect network externalities, the consumer's hardware adoption decision is influenced by the availability of complementary products. However, these studies of complementary products tend to focus on products that exist only as complementary products, such as DVDs, CDs, and video games. This research focuses on the case of an innovative hardware product that uses digital complementary products that compete with standalone versions of the same products. The authors argue that high levels of experience with a standalone product that competes with an innovative hardware/software bundle should increase the consumer's appreciation of (1) the utilitarian benefits of the hardware/software bundle and (2) the hedonic benefits of the standalone product, some of which may not be transferable to the electronic hardware. An analysis of data collected from 549 potential adopters of e‐readers in Japan support these hypotheses. The findings have important implications for the design and marketing of digital innovations that involve a change in product form.     

Gas permeabilities of cellulose nitrate/poly(ethylene glycol) blend membranes

The permeability (P) of cellulose nitrate (CN)/poly(ethylene glycol) (PEG) blend membranes for N₂, O₂, and CO₂ has been measured as a function of film composition. The system CN/PEG-300 showed excellent miscibility, and films of the composition from 100/0 to 50/50 could be used for permeability measurements. P for each gas has been found to be almost constant or rather slightly lowered up to ca. 20 wt % PEG-300 content and then increased appreciably with increasing fraction of PEG. The increment of permeability was most remarkable for CO₂, and hence the permselectivity for CO₂ was considerably enhanced. Such a behavior of P has been found to be attributable to the plasticizing effect of PEG molecule lowering the glass transition temperature of the blend polymers. The effect of the molecular weight of PEG and that of closed voids generated in glassy blend membranes fabricated from acetone cast on gas permeabilities have been also discussed.     

Monohexosylceramides of larval and adult forms of the tapeworm,spirometra erinacei

The occurrence of glycosphingolipids with unique carbohydrate structures in different species of cestode, Platyhelminth, which had been shown, previously, prompted us to study the molecular species of the monohexosylceramides (cerebrosides) in the pseudophyllidean cestode,Spirometra erinacei. The purpose of the study was to obtain a basis for future investigations of the physiological role of glycolipids in parasitism. Cerebrosides were isolated froms. erinacei at two growth stages, i.e., from the larval form (plerocercoid) and from the adult tapeworms (intestinal form). The cerebrosides were separated into four subfractions by silica gel column chromatography, and their constituents were analyzed by gasliquid chromatography, gas chromatography/mass spectrometry, and high-performance liquid chromatography/mass spectrometry. The hexoses of the cerebrosides consisted primarily of galactose in both growth stages, while only a small amount of glucose was detected. The ceramides were composed of sphinganine (d18∶0) and phytosphingosine (t18∶0) as sphingoid bases, and of nonhydroxy fatty acids ranging from C₁₆ to C₃₀ and hydroxy stearic acid (18h∶0). The cerebrosides of adult tapeworms contained more 18h∶0 than those of plerocercoids. The combination of hexoses and ceramides in the cerebroside molecules was slightly different in the two growth stages: the glucocerebrosides of plerocercoids contained only d18∶0-nonhydroxy fatty acids in their ceramide moieties, whereas those of adult tapeworms contained varying ceramide moieties. Our data indicate that the molecular species of glycolipids present were essentially homeostatic throughout growth in spite of the entirely different environmental conditions, although there were slight differences in the hexose distribution in the two growth stages.