Synthesis and structure of (4,4'-H(2)bpy)[V2(HPO4)4(4,4'-bpy)2], a novel two-dimensional network compound.
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Biomedical subjects
Publications and source records attributed to L H Huang.
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Melanization constitutes an important component in various aspects of insect life, including cuticular sclerotization, egg-shell tanning, melanization of parasites and wound healing. Recently, a cDNA encoding prophenoloxidase (pro-PO), a key enzyme in the biosynthesis of melanotic material in insects, was cloned from microfilariae (mf)-inoculated mosquitoes, Armigeres subalbatus. However, results of Northern blot analyses indicated that two pro-POs might be present in Ar. subalbatus and these pro-POs might be responsible for two distinct physiological functions, egg-shell tanning and melanization of parasites. Subsequently, the second pro-PO cDNA (As-pro-PO II) was cloned from blood-fed Ar. subalbatus by rapid amplification of cDNA ends polymerase chain reaction. The 2210 bp As-pro-PO II cDNA contains a 41 bp 5'-non-coding region, a 2064 bp open reading frame and a 105 bp 3'-non-coding region. A hydrophobic signal peptide for endoplasmic reticulum targeting is not found in the N-terminal region. The deduced amino acid sequence of As-pro-PO II shares a high degree of identity (81.5%) with that of the As-pro-PO I obtained from mf-inoculated Ar. subalbatus. Both Northern blot and reverse transcription polymerase chain reaction analysis demonstrated that these two mosquito pro-POs are persistently expressed in mosquito haemocytes and not in fat body, midgut, or ovaries. The expression of As-pro-PO I and As-pro-PO II in mosquitoes is associated with melanization of mf and blood feeding, respectively.
Two new squalene synthase (SSase) inhibitors, CJ-13,981 (I) and CJ-13,982 (II), were isolated from the fermentation broth of an unidentified fungus CL 15036. They inhibited human liver microsomal SSase with IC50s of 2.8 and 1.1 microM, respectively, but showed no inhibitory activity against human brain protein farnesyltransferase (PFTase) at 100 microM. Based on FAB-MS and NMR analyses, the structures of I and II were determined to be 3-hydroxy-3,4-dicarboxy-15-hexadecenoic acid and 3-hydroxy-3,4-dicarboxyhexadecanoic acid, respectively.
A novel antibiotic, CJ-15,801 (I), was isolated from the fermentation broth of a fungus, Seimatosporium sp. CL28611. The structure was determined to be a pantothenic acid analog having an alpha,beta-unsaturated carboxylic acid moiety by spectroscopic analyses. The compound inhibits the growth of multi-drug resistant (MDR) Staphylococcus aureus strains with MIC ranging from 6.25 to 50 microg/ml.
A series of diterpenes were isolated from the fermentation broth of a fungus, Oidiodendron griseum CL37215. The diterpenes were identified as LL-Z1271alpha, LL-Z1271gamma, CJ-14,445, PR 1388, CJ-14,604 and a new diterpene, CJ-14,515. They inhibited both lipopolysaccharide-induced interleukin-1beta and tumor necrosis factor-alpha production in human whole blood with IC50s of the range from 0.049 to 100 microM.
A new squalene synthase (SSase) inhibitor, CJ-15,183 (I) was isolated from the fermentation broth of a fungus, Aspergillus aculeatus CL38916. The compound potently inhibited rat liver and Candida albicans microsomal SSases and also inhibited the human enzyme. It also showed antifungal activities against filamentous fungi and a yeast. The structure was determined to be an aliphatic tetracarboxylic acid compound consisting of an alkyl gamma-lactone, malic acid and isocitric acid moieties by spectroscopic studies.
A new antibiotic, CJ-17,665 (I) was isolated from the fermentation broth of Aspergillus ochraceus, CL41582. It inhibits growth of multi-drug resistant Staphylococcus aureus, Streptococcus pyogenes, and Enterococcus faecalis, with MICs of 12.5, 12.5 and 25 microg/ml, respectively. The structure contains a diketopiperazine and an indole N-oxide moiety that is unusual in natural products.
Two new antibiotics, CJ-16,264 (I) and CJ-16,367 (II), were isolated from the fermentation broth of an unidentified fungus CL39457. These antibiotics have a pyrrolizidinone skeleton, first discovered in fungi. Compounds I and II inhibit the growth of Gram-positive multi-drug resistant bacteria and some Gram-negative strains such as Moraxella catarrhalis and Escherichia coli with altered permeability (imp). Comparison of an antibacterial profile between the two compounds suggested that the gamma-lactone portion of I is important for the activity.
Rel transcription factors function in flies and vertebrates in immunity and development. Although Rel proteins regulate diverse processes, the control of their function is conserved. In a two-hybrid screen for additional components of the pathway using the Drosophila I-kappaB protein Cactus as a bait, we isolated a novel coiled-coil protein with N-terminal Arg-Asp (RD)- like motifs that we call Cactin. Like the other components of this pathway, Cactin is evolutionarily conserved. Over-expression of cactin in a cactus(A2) heterozygous background results in the enhancement of the cactus phenotype. Both the embryonic lethality and ventralization are strongly increased, suggesting that cactin functions in the Rel pathway controlling the formation of dorsal-ventral embryonic polarity.
In Drosophila, dorsal-ventral polarity is determined by a maternally encoded signal transduction pathway that culminates in the graded nuclear localization of the Rel protein, Dorsal. Dorsal is retained in the cytoplasm by the IkappaB protein, Cactus. Signal-dependent phosphorylation of Cactus results in the degradation of Cactus and the nuclear targeting of Dorsal. We present an in-depth study of the functional importance of Dorsal phosphorylation. We find that Dorsal is phosphorylated by the ventral signal while associated with Cactus, and that Dorsal phosphorylation is essential for its nuclear import. In vivo phospholabeling of Dorsal is limited to serine residues in both ovaries and early embryos. A protein bearing mutations in six conserved serines abolishes Dorsal activity, is constitutively cytoplasmic, and appears to eliminate Dorsal phosphorylation, but still interacts with Cactus. Two individual serine-to-alanine mutations produce unexpected results. In a wild-type signaling background, a mutation in the highly conserved PKA site (S312) produces only a weak loss-of-function; however, it completely destabilizes the protein in a cactus mutant background. Significantly, the phosphorylation of another completely conserved serine (S317) regulates the high level of nuclear import found in ventral cells. We conclude that the formation of a wild-type Dorsal nuclear gradient requires the phosphorylation of both Cactus and Dorsal. The strong conservation of the serines suggests that phosphorylation of other Rel proteins is essential for their proper nuclear targeting.
Degenerate oligonucleotide primers corresponding to the conserved regions of bacterial heat shock sigma factor RpoH (sigma 32) were used to amplify a 190-bp fragment by PCR on the X. campestris pv. campestris strain 11 chromosome. Using this fragment as a probe, plasmid pXC57 carrying a 4.7-kb insert was isolated from a genomic library of Xc11. Sequence analysis of a stretch of 2,053 bp from the pXC57 insert revealed an ORF encoding a polypeptide of 291 aa (32,854 dal) which displays 59.6% and 57.3% identity to the rpoH gene products of E. coli and P. aeruginosa, respectively. The Xc11 rpoH gene was able to complement the RpoH deficient E. coli strain A7448. Both amino acid and mRNA sequences deduced from the Xc11 rpoH gene show structural features characteristics of the corresponding sequences from those of the gamma subgroup proteobacteria. The RpoH levels in Xc11 were demonstrated to increase transiently in response to heat shock treatment by immunoblot analysis using the polyclonal antibody raised against the purified Xc11 RpoH.
Han-Dan-Gan-Le, a Chinese medicine preparation composed of Salvia miltorrhiza, Radix paeoniae, Astragalus membranaceus, Stephania tetrandra, and dried leaves of Ginkgo biloba, has been used successfully to treat human liver fibrosis and cirrhosis for years. This study was designed to examine the mechanisms of the protection. Male Wistar rats were given CCl4 (1.2 ml/kg, 2 times/week), 20% fat diet, and 30% alcohol in drinking water (every other day) for 6 weeks. Han-Dan-Gan-Le (0.5 and 1.0 g/kg, p.o., daily for 6 weeks) was administered to rats simultaneously to examine the protective effects against CCl4-induced liver fibrosis. The experimentally-induced liver fibrosis and other morphological alterations were significantly ameliorated by Han-Dan-Gan-Le. Han-Dan-Gan-Le treatments decreased CCl4-induced hepatic collagen accumulation by more than 50%, and significantly increased urinary excretion of hydroxyproline. The CCl4-induced lipid peroxidation in liver and serum was ameliorated as a result of Han-Dan-Gan-Le treatment, possibly by restoring the activity of superoxide dismutase activity in liver and erythrocytes, In conclusion, Han-Dan-Gan-Le is effective in protecting against liver fibrosis. The mechanisms of the protection appear to be due to its antioxidant properties and the modulation of hepatic collagen metabolism.
Neuronal responses of 114 cells to electrical stimulation of the optic tectum were extracellularly recorded from the contralateral nucleus rotundus (nRt) in pigeons (Columba livia), and the effects of two glutamatergic antagonists CNQX and CPP, as well as those of GABA, were examined on rotundal cells. The results show that tectal stimulation evokes excitation in neurons of the contralateral nRt and that the excitatory responses are blocked by microiontophoretically applied CNQX, CPP and GABA. It is suggested that the contralateral tectorotundal transmission is excitatory in nature and mediated by both glutamatergic AMPA and NMDA receptors and that GABA is an inhibitory transmitter within the nucleus as well. We also review our previous findings in discussing transmitters participating in the tectofugal pathway.
A novel isochroman carboxylic acid CJ-12,373 was isolated from Penicillium sp. CL22557. CJ-12,373 inhibits both DNA gyrase-mediated supercoiling and relaxation without the formation of a cleavage intermediate, suggesting that CJ-12,373 inhibits DNA gyrase at a stage distinct from the religation step. CJ-12,373 is not selective for procaryotic DNA gyrase as it also inhibits relaxation mediated by eukaryotic topoisomerase II. The antimicrobial potency of CJ-12,373, however, is largely attributed to its inhibition of DNA gyrase.
Eight novel quinolones with anti-Helicobacter pylori activity were isolated from the actinomycete Pseudonocardia sp. CL38489. The quinolones were very potent against H. pylori with MICs up to 0.1 ng/ml. The quinolones appear to be specific for H. pylori, since they did not show antimicrobial activity when tested against a panel of other microorganisms.
Hydrops fetalis is a morbid condition caused by a wide variety of diseases. Although treatment for some underlying pathologies is becoming available, the prognosis remains poor. To analyze the etiology and outcome of hydrops fetalis, we reviewed the records of 79 fetuses encountered at the National Taiwan University Hospital between January 1993 and October 1996. The mean +/- standard deviation gestational age at presentation was 24.9 +/- 6.3 weeks. One case was due to RhE incompatibility. Seventy-eight fetuses were diagnosed as having nonimmune hydrops fetalis; this was idiopathic in 20 fetuses. In the other 58, the causes and associated conditions were classified into eight groups: hematologic (25), cardiovascular (15), chromosomal (5), gastrointestinal (4), cystic hygroma (3), pulmonary (2), infection (2), and miscellaneous (3). One fetus with cystic hygroma also had a chromosomal abnormality (Turner's syndrome). The most common cause of nonimmune hydrops fetalis was homozygous alpha-thalassemia (31%). Twenty-nine fetuses were lost to follow-up after initial evaluation and 50 fetuses were delivered at our hospital. Of these, there were eight cases of antepartum death, 24 cases of intrapartum death, and 18 live births. Seventeen of the live-born infants were treated at our neonatal intensive care unit, of whom only seven survived.
The polymeric surfaces of three commercially available nylon films with mesh openings of 5 microns, 10 microns and 20 microns were treated with anhydrous ammonia gaseous plasma. Cells cultured on the plasma-treated nylon films have higher proliferation rate and assume morphology distinct from those cultured on the unmodified films. Of the three plasma-modified membranes, the one with 5 microns mesh openings supported a largest population of cell growth. The plasma-treated nylon meshes provided a stronger anchorage for the collagen matrices formed within the mesh openings. Application of this collagen/nylon meshes for cell culturing is demonstrated.
During the course of our screening for squalene synthase inhibitors and Ras farnesylation inhibitors, a novel fungal culture was discovered to produce two structurally unique compounds, CP-225,917 and CP-263,114, as well as zaragozic acid A (squalestatin I). The two compounds are characterized by a bicyclo[4.3.1]dec-1,6-diene core plus two extended alkyl chains. CP-225,917 and CP-263,114 inhibit Ras farnesyl transferase from rat brain with IC50 values of 6 microM and 20 microM, respectively. CP-225,917 inhibits squalene synthase with an IC50 value of 43 microM and CP-263,114 with an IC50 of 160 microM. The producing organism, though not fully classified, exhibits the characteristics of a sterile Phoma species.