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Allergen sensitization changes as children get older. However, although research has been conducted on common allergens by age, there is scarce research on the relationship of allergen sensitization patterns and allergic diseases. In this study, we have investigated the allergen sensitization patterns and allergic diseases in different age groups.

There is a direct relationship between bodyweight and risk of diabetes. Lorcaserin, a selective serotonin 2C receptor agonist that suppresses appetite, has been shown to facilitate sustained weight loss in obese or overweight patients. We aimed to evaluate the long-term effects of lorcaserin on diabetes prevention and remission.

Oxygen partial pressure at the boundary between external oxidation layer and steel matrix was determined by characterisation of internal oxidation in Si-containing low-carbon steels oxidised under atmospheric condition. The oxygen partial pressure calculated from the rate equation of the internal oxidation matches with the equilibrium value between Fe and FeO. From the oxygen partial pressure between external oxidation layer and steel matrix, the evolution of internal oxidation zone and the diffusion profile of solute Si were numerically simulated. The calculated depth of internal oxidation and solute Si profile accords to the measured ones from the EPMA, which implies that the numerical simulation captures reasonably the evolution of the internal oxidation in the Si-containing steels.

The expression of immediate early response 3 (IER3), a protein with a short half-life, is rapidly induced by various cellular stimuli. We recently reported that IER3 induces the apoptosis of cervical cancer cells and that its expression is downregulated in patients with cervical cancer. However, the molecular mechanism involved in the rapid degradation of IER3 remains unknown. Here, we demonstrate that MDM2 is an E3 ligase that interacts with IER3 and promotes its ubiquitination, followed by proteasomal degradation. Polyubiquitination of the conserved lysine 60 of IER3 is essential for its degradation. In addition, four and a half LIM domains protein 2 (FHL2) binds to both IER3 and MDM2, allowing for efficient MDM2-mediated IER3 degradation by facilitating an association between MDM2 and IER3. Moreover, IER3 induces cell cycle arrest in cervical cancer cells and its activity is further enhanced in cells in which FHL2 or MDM2 was silenced, thereby preventing IER3 degradation. The E6 and E7 oncoproteins of human papilloma virus 18 regulated IER3 expression. FHL2 expression was significantly higher in the squamous epithelium of cervical carcinoma tissues than in non-cancerous cervical tissues, whereas cervical carcinoma expression of IER3 was downregulated in this region. Thus, we determined the molecular mechanism responsible for IER3 degradation, involving a ternary complex of IER3, MDM2 and FHL2, which may contribute to cervical tumor growth. Furthermore, we demonstrated that FHL2 serves as a scaffold for E3 ligase and its substrate during the ubiquitination reaction, a function that has not been previously reported for this protein.

An attempt is made, on the basis to published literature, to assess the amount of phosphorus that might be present in the steels without making it susceptible to grain boundary embrittlement. Embrittlement occurs when the general resistance to plastic flow is comparable to the stress required to separate crystals at their boundaries. A criterion is developed that enables a simple assessment to be made of the tendency to embrittle as a function of yield strength and the fraction of grain boundary sites that are covered by phosphorus. The latter is also sensitive to chemical composition, since some elements such as carbon segregate preferentially to phosphorus, giving rise to site competition that can permit a greater tolerance to the impurity. Other solutes affect the embrittling potency by different mechanisms, not all of which are clear.

The prospect of enhancing the hardness of low alloy steel for the manufacture of fasteners is examined using ausforming, in which the austenite is deformed rapidly at a low temperature to increase its dislocation density before quenching in order to obtain the harder martensite. Surprisingly, small deformations accomplish large gains in hardness and the dislocation density of martensite, with diminishing returns at larger deformations. The main contribution to the hardness has been identified as the extra dislocations inherited by the martensite from the deformed austenite, rather than the refinement of microstructure by the ausforming process. Clear evidence is reported for the mechanical stabilisation of the austenite due to ausforming. Tempering heat treatments tend to diminish the advantages of ausforming.

The kinetic theory for the growth of pearlite in binary and ternary steels is implemented to ensure local equilibrium at the transformation front with austenite, while accounting for both boundary and volume diffusion of solutes. Good agreement is on the whole observed with published experimental data, although the reported growth rate at the lowest of temperatures is much smaller than predicted. To investigate this, experiments were conducted to replicate the published data. It is found that the cooperation between cementite and ferrite breaks down at these temperatures, and surface relief experiments are reported to verify that the resulting transformation product is not bainite.

The surface quality of steels containing solutes that have a strong affinity for oxygen can be markedly compromised during processing at elevated temperatures. Here, we examine a class of steels that are being developed for low density applications and hence, have relatively large concentrations of aluminium and manganese. These two elements compete for what little oxygen is available in the predominantly hydrogen–nitrogen mixture used to protect the steel during heat treatment. It is found that although the general sequence of oxidation does not seem to vary as the aluminium concentration is increased, the stoichiometry of the oxides changes. Manganese rich oxide is always the first to form for all the dew points examined, but is rapidly overtaken by aluminium oxide when the dew point is kept below -30°C. In the latter case, the eventual formation of an alumina film also halts the internal oxidation of aluminium. The results obtained using a variety of high resolution microscopy and analytical techniques have been analysed by calculating phase diagrams and by creating a finite difference model to reveal aspects of the internal oxidation problem.

The anisotropy of mechanical properties in the context of steels used to fabricate large diameter pipes can be detrimental to the design and performance of the pipes. We examine here the anisotropy of strength and toughness, and with the help of detailed characterisation show that there is a complex interaction between the ability of the steel to delaminate on the rolling plane and the crystallographic texture, which promotes brittle fracture on the macroscopic fracture plane of Charpy specimens.

Some of the most modern automotive sheet steels rely on a dispersion of fine precipitates based on TiC, generated during the major phase changes that occur as the rolled material is cooled to the coiling temperature. The coils themselves cool extremely slowly, thus leading to the coarsening of the precipitates and a loss of strength. Beginning with a calculation of the interfacial energy, the precipitate coarsening kinetics are modelled as a function of the stoichiometry of titanium and carbon. The purpose was to assess the influences of interface energy and Ti/C stoichiometry which limit the rate at which the dispersion coarsens by the diffusion of solute from the small to the larger particles. It is found that Ti/C ratio plays a critical role; a titanium concentration which is slightly less than required to combine with carbon leads to a dramatic reduction in the coarsening rate.

Sr1−xBaxSi2O2N2:Eu2+phosphors were synthesized using high temperature solid state reaction. The effect of Ba incorporation on the structural and luminescence characteristics of SrSi2O2N2:Eu2+phosphors were studied. The phosphors were crystallized in triclinic crystal structure and the cell volume increases monotonically with Ba addition. The PL emission peak wavelength red shifts with Ba up to x= 0.50 beyond which no red shift is observed. The XPS analysis shows that nitrogen is being incorporated into the host lattice along with Ba addition up to x= 0.50. The as synthesized phosphors show high thermal stability. Phosphor converted light emitting diodes were realized using Sr1−xBaxSi2O2N2:Eu2+phosphors (x= 0 and x= 0.40) showing luminance efficacies of 108 and 101 lm W−1.

Steels containing sufficient concentrations of silicon tend to form a low melting temperature oxide called fayalite, which then penetrates both the steel and any other oxide to form a mechanical key. As a consequence, routine descaling operations fail to remove all traces of FeO that remain attached to the final product and oxidise to form a red oxide blemish on the surface. The formation of oxides was investigated both experimentally and by developing a new theory that permits the simultaneous formation of a variety of oxides that compete to establish the final oxide structure. The theory forms the basis for studying the evolution of oxide scales as a function of silicon concentration.

The purpose of this study was to evaluate the long-term functional and radiological outcomes of arthroscopic removal of unstable osteochondral lesions with subchondral drilling in the lateral femoral condyle. We reviewed the outcome of 23 patients (28 knees) with stage III or IV osteochondritis dissecans lesions of the lateral femoral condyle at a mean follow-up of 14 years (10 to 19). The functional clinical outcomes were assessed using the Lysholm score, which improved from a mean of 38.1 (sd3.5) pre-operatively to a mean of 87.3 (sd5.4) at the most recent review (p = 0.034), and the Tegner activity score, which improved from a pre-operative median of 2 (0 to 3) to a median of 5 (3 to 7) at final follow-up (p = 0.021). The radiological degenerative changes were evaluated according to Tapper and Hoover’s classification and when compared with the pre-operative findings, one knee had grade 1, 22 knees had grade 2 and five knees had grade 3 degenerative changes. The overall outcomes were assessed using Hughston’s rating scale, where 19 knees were rated as good, four as fair and five as poor.We found radiological evidence of degenerative changes in the third or fourth decade of life at a mean of 14 years after arthroscopic excision of the loose body and subchondral drilling for an unstable osteochondral lesion of the lateral femoral condyle. Clinical and functional results were more satisfactory.

We examine here the spot welding characteristics of transformation induced plasticity assisted steels, which contain δ-ferrite as a consequence of their aluminium concentrations of 3·5 or 5·6 wt-% and which also have high carbon contents of 0·3 or 0·4 wt-% when compared with conventional automotive steels. The resistance spot welds are tested in both shear and cross-tensile tests in order to determine the so called ductility ratio, which is a parameter associated with the fitness of such welds for automotive applications. With an increase in the δ-ferrite fraction from 0·19 to 0·5, the hardness variation across the weld and heat affected zone is decreased approximately from 400 to 150 HV. It seems that the presence of stable δ-ferrite is helpful in reducing hardness variations and in achieving a significant ductility ratio of 0·39.

ABSTRACTBackground:The goals of diabetes management have evolved over the past decade to become the attainment of near-normal glucose and cardiovascular risk factor levels. Improved metabolic control is achieved through optimized medication regimens, but costs specifically associated with such optimization have not been examined.Objective:To estimate the incremental medication cost of providing optimal therapy to reach recommended goals versus actual therapy in patients with type 2 diabetes.Methods:We randomly selected the charts of 601 type 2 diabetes patients receiving care from the outpatient clinics of Massachusetts General Hospital March 1, 1996–August 31, 1997 and abstracted clinical and medication data. We applied treatment algorithms based on 2004 clinical practice guidelines for hyperglycemia, hyperlipidemia, and hypertension to patients’ current medication therapy to determine how current medication regimens could be improved to attain recommended treatment goals. Four clinicians and three pharmacists independently applied the algorithms and reached consensus on recommended therapies. Mean incremental medication costs, the cost differences between current and recommended therapies, per patient (expressed in 2004 dollars) were calculated with 95% bootstrap confidence intervals (CIs).Results:Mean patient age was 65 years old, mean duration of diabetes was 7.7 years, 32% had ideal glucose control, 25% had ideal systolic blood pressure, and 24% had ideal low-density lipoprotein cholesterol. Care for these diabetes patients was similar to that observed in recent national studies. If treatment algorithm recommendations were applied, the average annual medication cost/patient would increase from $1525 to $2164. Annual incremental costs/patient increased by $168 (95% CI $133–$206) for antihyperglycemic medications, $75 ($57–$93) for antihypertensive medications, $392 ($354–$434) for antihyperlipidemic medications, and $3 ($3–$4) for aspirin prophylaxis. Yearly incremental cost of recommended laboratory testing ranged from $77–$189/patient.Limitations:Although baseline data come from the clinics of a single academic institution, collected in 1997, the care of these diabetes patients was remarkably similar to care recently observed nationally. In addition, the data are dependent on the medical record and may not accurately reflect patients’ actual experiences.Conclusion:Average yearly incremental cost of optimizing drug regimens to achieve recommended treatment goals for type 2 diabetes was approximately $600/patient. These results provide valuable input for assessing the cost-effectiveness of improving comprehensive diabetes care.

Polycrystalline ZrO2 and yttria-stablilized ZrO2 thin films have been deposited on Pt/Ti/SiO2/Si substrates by pulsed laser deposition methods. Pt/ZrO2/Pt and Pt/YSZ/Pt capacitor structures show giant conductivity switching behaviors which can be utilized for nonvolatile memory devices. Maximum on/off ratio of 106 and good endurance even after 105 times conductivity switching are observed in a typical Pt/ZrO2/Pt whose ZrO2 film has been deposited at 100 °C and an oxygen pressure of 50 mTorr. The Pt/ZrO2/Pt structure exhibits two ohmic behaviors in the low voltage region (V < 1.4 V) depending on the value of previously applied high voltage and Schottky-type conduction in the high voltage region (1.4 V < V < 8.9 V). It seems that conductivity switching behaviors in our Pt/ZrO2/Pt structure result from the changes in both the Schottky barrier and the bulk conductivity controlled by applied voltages. A Pt/YSZ/Pt capacitor structure has more stable reset voltage and current state than a Pt/ZrO2/Pt capacitor structure. Moreover, a Pt/YSZ/Pt capacitor structure shows higher Conductivity than a Pt/ZrO2/Pt capacitor structure, which may result from substitution of Y3+ ions for Zr4+ ions.

Modulus-tunable ultraviolet (UV) curing molds allow not only physical patterning of imprinting but also chemical patterning of microcontact printing. The mechanical properties of the mold can be tailored by the chain length of an acrylate modulator in the cross-linking reaction. This tunability can be utilized to obtain a proper balance that is needed for a given patterning technique between the rigidity requirement (tensile modulus = 320 MPa) of a mold for patterning a fine structure and the flexibility requirement (tensile modulus = 19.8 MPa) for a conformal contact. Successful low-pressure imprinting of sub-100-nm patterns and microcontact printing of submicrometer patterns verify the suitability of the mold for a wide spectrum of patterning techniques.

Posttranslational modification of proteins with farnesyl and geranylgeranyl groups is a required modification for signaling proteins that includes the small GTPases in the Ras, Rho, and Rab families, heterotrimeric G proteins, and nuclear lamin proteins. To develop antibodies capable of detecting and distinguishing prenylated proteins, we synthesized two antigens, succinylglycine-(geranylgeranyl)cysteine methyl ester (SuccG-(gg)CMe, 1) and succinylglycine-(farnesyl)cysteine methyl ester (SuccG-(f)CMe, 2). These prenylated peptides were covalently coupled to bovine serum albumin (BSA) and to keyhole limpet hemocyanin (KLH) to produce polyvalent, immunogenic bioconjugates. Immunization of rabbits with these immunogens generated polyclonal antisera that contained significant titers of anti-geranylgeranyl and anti-farnesyl antibodies. The selectivity of the polyclonal antisera was examined using ELISA and dot blotting methods. The anti-farnesyl and anti-geranylgeranyl antisera crossreacted with both antigens. Attempts to purify the polyclonal antisera by either positive or negative immunoaffinity selection protocols failed to produce selective anti-geranylgeranyl and anti-farnesyl antibodies. Moreover, both crude antisera and purified antibodies also crossreacted with myristoylated and palmitoylated BSA conjugates. Immunofluorescence staining of EYFP-CVLL or EYFP-CVIM transfected CHO-K1 cells with rabbit polyclonal antisera showed colocalized membrane fluorescence. Thus, an important caveat for the use of antibodies raised against aliphatic antigens is that extensive controls must be performed to determine selectivity.

Small-molecule oxidosqualene cyclase (OSC) inhibitors were found to be effective in assays against cloned OSC-like enzymes from human pathogens. A combinatorial library was prepared and used to identify lead compounds that inhibit the growth of Trypanosoma cruzi, Leishmania mexicana amazonensis, and Pneumocystis carinii in culture. Selectivity for the microorganisms in preference to mammalian cells was observed.

Summary: New fluorene-linked π-conjugated polyquinoxaline PFQx I and PFQx II have been synthesized and characterized. The PFQx polymers are prepared by the polycondensation of the 2,7-bis(phenyloxoacetyl)-9,9'-di-n-hexylfluorene or 2,7-bis(4-benzil)-9,9'-di-n-hexylfluorene and 3,3'-diaminobenzidine leading to the PFQx I and PFQx II . The polycondensation is usually carried out in m-Cresol. These polymers possess relatively good solubility and thermal stability. The resulting polymers exhibit a UV-visible absorption band in the range of 397–407 nm in both chloroform solution and the film state. Upon photo-excitation around the absorption maximum wavelength, their PL spectra show a maximum peaks around at 447–467 nm. Multilayered light-emitting diode with the device structure of ITO/PEDOT/PFQx I /PVK blend(2:8)/LiF/AI gives a highest EL peak in the blue region of 460 nm. J–V curve shows a turn-on voltage of 13 V.

A keratinolytic protease-producing microorganism was isolated from soybean paste waste and was identified as a strain of Bacillussp. The keratinase was purified by polyethylene glycol precipitation and two successive column chromatographies with DEAE-Toyopearl 650C and Sephacryl S-200 HR. The purified enzyme had overall 11 purification folds with an 18% yield. The results of sodium dodecyl sulfate polyacrylamide gel electrophoresis and gel filtration on Sephacryl G-200 indicated that the purified enzyme was monomeric and had a molecular weight of 134 kDa. The optimum temperature and pH were 40°C and 7.0, respectively. This enzyme was completely inhibited by EDTA and EGTA, and it was restored by the addition of Ca+2and Mg+2. These results suggested that it is a metalloprotease. The stimulated enzyme activity by reducing agents indicated that the reducing condition was important in the expression of the activity.

We present the case of a two-year and seven-month-old boy with a partially-thrombosed giant lobulated aneurysm in the supraclinoid portion of the internal carotid artery. He presented with several months of symptoms of progressive frontal headache and visual loss. CT revealed a large lobulated suprasellar mass lesion mimicking a craniopharyngioma. After the aneurysm was successfully obliterated by an endovascular procedure, regression of the giant aneurysm was confirmed on followed-up MRI. The differential diagnosis, possible etiologies, and the endovascular technique for pediatric patient will be discussed.

OBJECTIVE: Chondrocyte apoptosis has been described in studies of the pathogenesis of various arthritides. Since matrix degradation is important in the pathology of arthritis, we investigated the effect of matrix depletion on chondrocyte apoptosis. METHODS: Consecutive 1 mm sections of child's rib cartilage were cultured under 4 sets of conditions: (1) control; and treatment with (2) hyaluronidase, (3) collagenase, (4) hyaluronidase/collagenase alternately. Sections were harvested on Days 5, 8, and 11, and the proportion of apoptotic cells was measured by propidium iodide staining and flow cytometry. Changes of Fas and Fas ligand expression were verified by immunohistochemistry and Western blot. RESULTS: Collagenase treatment led to an increase of apoptosis, which began on Day 8, whereas hyaluronidase treatment had no effect on chondrocyte viability up to Day 11. Alternating hyaluronidase and collagenase treatment induced chondrocyte death earlier, but the difference in apoptotic rate was not significant on Days 8 or 11 compared to collagenase treatment alone. Immunohistochemistry showed the expression of Fas ligand in all enzymatically treated specimens. Expression of Fas receptor was ubiquitous in both control and treated specimens. CONCLUSION: The collagen framework is important in the maintenance of chondrocyte survival in human cartilage. Upregulation of Fas ligand in matrix depleted specimens suggested that the Fas pathway may have a role in apoptosis induced by matrix depletion.

Background: Cholangioscopy has been used in the treatment of bile duct stones and the diagnosis of various bile duct tumors. However, the cholangioscopic characteristics of the various types of bile duct tumors have not been clearly described. We analyzed the results of cholangioscopic examinations and classified the findings according to tumor histology. Methods: Cholangioscopic findings from 111 patients with benign or malignant bile duct tumors were reviewed. The mucosal changes, the presence of neovascularization, and the patterns of luminal narrowing were analyzed and compared with the histologic diagnosis. Results: Bile duct adenocarcinoma can be classified into 3 different types according to the cholangioscopic findings: nodular, papillary, and infiltrative. Bile duct adenoma, hepatocellular carcinoma and other types of bile duct cancer such as mucin-hypersecreting cholangiocarcinoma, biliary cystadenocarcinoma, and squamous cell carcinoma also presented unique cholangioscopic characteristics. Conclusions: Bile duct tumors exhibit characteristic cholangioscopic findings and cholangioscopy seems to be useful for differential diagnosis. (Gastrointest Endosc 2000;52:630-4.)

Gas permeation experiments of O2 and N2 were performed with conducting polyaniline (PANi) composite membranes prepared by using a porous nylon membrane as a support. PANi composite membranes were easily obtained by a novel solvent welding process. Doping, dedoping, and redoping kinetics of PANi composite membranes were studied by calculating the [Cl]/[N] content using elemental analysis. After doping and dedoping processes, the permeability of a dedoped PANi membrane decreased while selectivity slightly increased, probably because of the changes in morphology of PANi. d spacing of the PANi film decreased from 4.89 to 3.67 Å after doping, dedoping, and redoping. As redoping continued, the degree of doping increased while the d spacing decreased, resulting in a dramatic increase in selectivity of a PANi membrane. The highest O2/N2 selectivity and permeability we obtained from PANi redoped for 2 h were 28 and 0.13 barrer, respectively. O2/N2 permeation experiments with different upstream pressure and temperature were carried out to study the permeation behavior of a PANi membrane.

To provide a detailed description of the MR appearances of central neurocytoma, MR images of 13 patients with central neurocytoma were retrospectively reviewed and compared with CT examinations. The histology was confirmed by ultrastructural and immunohistochemical studies. In 12 patients the tumors were histologically benign and located in the anterior part of the lateral ventricle, 6 of which extended to the 3rd ventricle. There was one case of a histologically malignant variant involving the thalamus and lateral ventricle. The tumors were primarily solid, but contained cysts (85%, 11/13), calcifications (69%, 9/13), and signal void from tumor vessels (62%, 8/13), frequently producing heterogeneous signal intensity on both T1- and T2-weighted images. Most of the solid portion appeared isointense or slightly hyperintense relative to the cerebral cortex on all MR pulse sequences. Calcifications were iso- or hypointense on MR, making them difficult to characterize with MR alone. Intratumoral hemorrhage was seen in 2 patients on MR but not on CT. Contrast enhancement was variable in degree and pattern. Coronal and sagittal MR images were valuable in evaluating the tumor extent and origin site, and in planning the surgical approach. It is concluded that MR imaging appears to be more useful than CT in the overall evaluation of central neurocytoma, even though calcification is better characterized with CT.

The Fitzpatrick skin classification has been a useful method to categorize cutaneous sensitivity to ultraviolet radiation (UVR), although it was based originally on responses in white skin. Because the relevance of this phototype in brown skin is in question, we investigated skin phototypes of university students by a self‐reporting questionnaire and measured their MEDs in Korean, brown skin. After studying our explanation of the definition of Fitzpatrick skin types, 707 Korean university students answered the questionnaire. We then measured UVB MEDs in 156 randomly selected male students. The order of frequency of skin type was type III (55.0%), IV (29.0%), and V (12.3%) by the questionnaire, with the sun sensitive categories (types I and II) reported only for 3.7%. There was no significant difference in MEDs between types IV and V, and the mean MED of each skin type did not show a monotonic increase with increasing skin type. Subjects with MEDs of 70–90 mJ/cm2(corresponding to the MED of skin type V, as proposed by Pathak & Fitzpatrick) represented about half or more of the subjects in all categories, even types II and III. Subjects with MEDs lower than 60 mJ/cm2were more prevalent in types II and III compared with types IV and V We suggest that there is at best a weak relationship between the skin types, by the Fitzpatrick method, and MEDs in Korean, brown skin.

MR and CT features of neurocysticercosis are variable and depend fundametally on the stage in evolution of the infection, location, number and size of the worm. The authors retrospectively evaluated MR images obtained on a 2.0T superconducting unit in 22 neurocysticercosis patients and observed various MR features including some new findings. A variety of MR findings are presented with special reference to six case reports. The features include: (1) a large simple cyst containing both internal septations and a scolex; (2) suprasellar racemose cysts mimicking other cysts, (3) a fourth ventricular cyst readily depicted by aid of CSF flow-void in the sagittal plane; (4) degenerating cysts showing “white target” appearance; (5) granulomatous lesions having a “black target” appearance; and (6) a meningitic form showing Gd-DTPA enhancement of basal cisterns and of a subacute infarct.

The widely used skin phototype system first introduced by Fitzpatrick, which is based on the history of an individual tendency to burn and tan, was studied in 733 Korean men by means of a self‐assessment questionnaire. Combining two factors, individual burning and tanning tendency, less than half (43.9%) could be classified according to the skin phototype system. Furthermore, the concordant ratio between subjective skin phototypes assessed by the subjects themselves and classification by combining self‐reported burning and tanning tendencies was much lower (34.4%). In a subgroup of 156 subjects, the minimal erythema dose (MED) was determined and compared with the reported tendencies to burn and tan. The results showed that subjects with higher MEDs tended to report more tanning. We concluded that in Korean brown skin, there is a disconcordant relationship between reported burning and tanning tendencies and, though reliable for white skin, self‐assessed skin phototypes are unreliable in Korean brown skin.

Cloning of the 5 -flanking region of the rat pp120 gene has indicated that it is a housekeeping gene: it lacks a functional TATA box and contains several Sp1 binding sites and multiple transcription initiation sites at nucleotides -101, -71, -41, and -27 spread over a GC-rich area. A fragment between nucleotides -21 and -1609 exhibited promoter activity when ligated in a sense orientation into a promoterless luciferase reporter plasmid and transiently transfected into rat H4-II-E hepatoma cells. 5' progressive deletion and block substitution analyses revealed that the three proximal Sp1 boxes (boxes 3, 5, and 6) are required for basal transcription of the pp120 gene. Promoter activity was stimulated 2-3-fold in response to insulin, dexamethasone, insulin plus dexamethasone, and cAMP. Although unaltered by phorbol esters alone, promoter activity was stimulated 4-5-fold in response to phorbol esters plus cAMP. Several motifs resembling response elements for insulin (in the rat phosphoenolpyruvate carboxykinase gene), glucocorticoids, cAMP, and phorbol esters as well as a number of putative binding sites for activating proteins-1 (Jun/Fos) and -2, and liver-specific factors were detected. The role of these sites in tissue-specific expression of pp120 remains to be investigated.

Pinusolide, a labdane-type diterpene lactone isolated from Biota orientalis, was found to be a potent platelet-activating factor (PAF) receptor binding antagonist. To investigate the structure−activity relationship and find derivatives with improved pharmacological profiles, 17 pinusolide derivatives were prepared and tested for their ability to inhibit the PAF receptor binding. The results demonstrated that the carboxymethyl ester group at C-19, the integrity of the α,β-unsaturated butenolide ring, and the exocyclic olefinic function of pinusolide are all necessary for its maximum PAF receptor binding inhibitory activity. Among the derivatives, the 17-nor-8-oxo derivative 8 was found to be as potent as pinusolide. The results also suggested that several derivatives warrant further pharmaceutical and pharmacological studies due to their improved water solubility (8 and 11) and apparent lack of susceptibility to Michael-type nucleophilic addition (13 and 18).