A brief introduction to the research achievement on the strategy and technical measures for interrupting the transmission of lymphatic filariasis in China.
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China↗
Biomedical subjects
J Chang
Publications and source records attributed to J Chang.
[The structures and characteristic infrared spectra of beta-DDB and its derivatives].
The characteristic infrared bands of the 3, 4-methylenedioxy-5-methoxybenzoate, 6-Br-3, 4-methylenedioxy-5-methoxybenzoate, beta-DDB (6, 6'-dimethoxy-4, 5, 4', 5'-dimethylenedioxy-2, 2'-dimethoxycarbonylbiphenyl) and its five derivatives were assigned. The effects of the substituents of these compounds on their IR data were discussed. The results indicated the varying of ester alkyl mainly influences the C=O double band stretching mode, but has little effects on the C=C double band stretching mode of the phenyl. When the H atom was substituted by other substituents, the absorptions of the C=O and C=C both changed.
Biphenyl Compounds↗
A stabilized molten globule protein.
A predominant conformational isomer of non-native alpha-lactalbumin (alpha-LA) has been purified by thermal denaturation of the native alpha-LA using the technique of disulfide scrambling. This unique isomer retains a substantial content of alpha-helical structure. It is stabilized by two native disulfide bonds within the alpha-helical domain and two scrambled non-native disulfide bonds at the beta-sheet domain. This denatured isomer of alpha-LA exhibits structural characteristics that are consistent with the well-documented molten globule state. The ability to prepare a stabilized and structurally defined molten globule provides a useful model for studying the folding and unfolding pathways of proteins.
Circular Dichroism↗
Apoptosis and proliferation as predictors of chemotherapy response in patients with breast carcinoma.
BACKGROUND: Laboratory evidence suggests that many anticancer agents exert their effect by altering the ratio between apoptosis and cellular proliferation. The objective of this clinical study was to examine in vivo changes in apoptotic index (AI), Bcl-2 expression, proliferation (Ki-67 and S-phase fraction [SPF]), and ploidy as potential indicators of chemoresponsiveness. METHODS: Twenty-eight women with primary operable breast carcinoma received 2M (mitoxantrone 11 mg/m2, methotrexate 35 mg/m2 every 3 weeks) for 4 cycles before surgery/radiotherapy, and an additional 2 cycles were given after surgery. Clinical response was assessed after four cycles of treatment according to World Health Organization criteria. Changes in molecular markers were assessed from biopsies obtained by fine-needle aspiration performed before treatment, repeated after 24 and/or 72 hours (T1), and on Days 7 and 21 after the first cycle of chemotherapy. Flow cytometric analysis was used to assess SPF, ploidy, and AI (in situ DNA nick end labeling assay) whereas Ki-67 and Bcl-2 were evaluated by immunocytochemical analysis. RESULTS: The overall response rate was 61% (17 of 28 patients), with a 14% (4 of 28 patients) complete response rate. Patients with diploid carcinomas (P = 0.04) with high Ki-67 (P = 0.0001) and SPF (P = 0.09) were more likely to respond to treatment. Median AI increased by 3.4% with interquartile (IQ) range of 3.2 in responders, compared with only -0.1% (IQ range, 2.2) in nonresponders at T1 (P = 0.03). Median Ki-67 decreased by -12.0% (IQ range, 22.9) in responders and increased by 18.5% (IQ range, 15.1) in nonresponders on Day 21 (P = 0.003). Median Bcl-2 scores increased by 1.0 (IQ range, 4.0) in responders and were unchanged at 0.0 (IQ range, 0.5) in nonresponders (P = 0.08). Changes in SPF or ploidy were not significantly predictive of response. CONCLUSIONS: The results of this preliminary study support evidence that chemotherapy may increase apoptosis, decrease Ki-67, and increase Bcl-2 expression in primary breast carcinomas that subsequently respond to therapy. Methodology allowing morphological confirmation of apoptosis would be advantageous.
Antineoplastic Combined Chemotherapy Protocols↗
The CNS midline cells coordinate proper cell cycle progression and identity determination of the Drosophila ventral neuroectoderm.
The CNS midline cells, specified by the single-minded (sim) gene, are required for the proper patterning of the ventral CNS and epidermis, which are derived from the Drosophila ventral neuroectoderm. Defects in the sim mutant are characterized by the loss of the gene expression, which is required for the proper formation of the ventral neurons and epidermis, and by a decrease in the spacing of longitudinal and commissural axon tracks. Molecular and cellular mechanisms for these defects were analyzed to elucidate the precise role of the CNS midline cells in proper patterning of the ventral neuroectoderm during embryonic neurogenesis. These analyses showed that the ventral neuroectoderm in the sim mutant fails to carry out its proper formation and characteristic cell division cycle. This resulted in the loss of the dividing neuroectodermal cells that are located ventral to the CNS midline. The CNS midline cells are also required for the cell cycle-independent expression of the neural and epidermal markers. This indicates that the CNS midline cells are essential for the establishment and maintenance of the ventral epidermal and neuronal cell lineage by cell-cell interaction. On the other hand, the CNS midline cells do not cause extensive cell death in the ventral neuroectoderm. This study indicates that the CNS midline cells play important roles in the coordination of the proper cell cycle progression and the correct identity determination of the adjacent ventral neuroectoderm along the dorsoventral axis.
Animals↗
Health care policy. U.S. priorities-HIV prevention.
One of the scientific anomalies of the AIDS epidemic is the large difference in infection rates across populations. Given limited resources and segregated epidemics, prevention funding should be directed to population segments with high HIV prevalence and incidence. However, recent surveys of U.S. populations indicate that the allocation of prevention dollars is not consistent with the distribution of HIV in the population.
Disease Outbreaks↗
Gene expression monitoring for gene discovery in models of peripheral and central nervous system differentiation, regeneration, and trauma.
Gene expression monitoring using gene expression microarrays represents an extremely powerful technology for gene discovery in a variety of systems. We describe the results of seven experiments using Incyte GEM technology to compile a proprietary portfolio of data concerning differential gene expression in six different models of neuronal differentiation and regeneration, and recovery from injury or disease. Our first two experiments cataloged genes significantly up- or down-regulated during two phases of the retinoic acid-induced differentiation of the embryonal carcinoma line Ntera-2. To identify genes involved in neuronal regeneration we performed three GEM experiments, which included changes in gene expression in rat dorsal root ganglia during the healing of experimentally injured sciatic nerve, in regenerating neonatal opossum spinal cord, and during lipopolysaccharide stimulation of primary cultures of rat Schwann cells. Finally we have monitored genes involved in the recovery phase of the inflammatory disease of the rat spinal cord, experimental allergic encephalomyelitis, as well as those responsible for protection from oxidative stress in a glutamate-resistant rat hippocampal cell line. Analysis of the results of the approximately 70,000 data points collected is presented.
Animals↗
The Finland-United States investigation of non-insulin-dependent diabetes mellitus genetics (FUSION) study. I. An autosomal genome scan for genes that predispose to type 2 diabetes.
We performed a genome scan at an average resolution of 8 cM in 719 Finnish sib pairs with type 2 diabetes. Our strongest results are for chromosome 20, where we observe a weighted maximum LOD score (MLS) of 2.15 at map position 69.5 cM from pter and secondary weighted LOD-score peaks of 2.04 at 56.5 cM and 1.99 at 17.5 cM. Our next largest MLS is for chromosome 11 (MLS = 1.75 at 84.0 cM), followed by chromosomes 2 (MLS = 0.87 at 5.5 cM), 10 (MLS = 0.77 at 75.0 cM), and 6 (MLS = 0.61 at 112.5 cM), all under an additive model. When we condition on chromosome 2 at 8.5 cM, the MLS for chromosome 20 increases to 5.50 at 69.0 cM (P=.0014). An ordered-subsets analysis based on families with high or low diabetes-related quantitative traits yielded results that support the possible existence of disease-predisposing genes on chromosomes 6 and 10. Genomewide linkage-disequilibrium analysis using microsatellite marker data revealed strong evidence of association for D22S423 (P=.00007). Further analyses are being carried out to confirm and to refine the location of these putative diabetes-predisposing genes.
Aged↗
The Finland-United States investigation of non-insulin-dependent diabetes mellitus genetics (FUSION) study. II. An autosomal genome scan for diabetes-related quantitative-trait loci.
Type 2 diabetes mellitus is a complex disorder encompassing multiple metabolic defects. We report results from an autosomal genome scan for type 2 diabetes-related quantitative traits in 580 Finnish families ascertained for an affected sibling pair and analyzed by the variance components-based quantitative-trait locus (QTL) linkage approach. We analyzed diabetic and nondiabetic subjects separately, because of the possible impact of disease on the traits of interest. In diabetic individuals, our strongest results were observed on chromosomes 3 (fasting C-peptide/glucose: maximum LOD score [MLS] = 3.13 at 53.0 cM) and 13 (body-mass index: MLS = 3.28 at 5.0 cM). In nondiabetic individuals, the strongest results were observed on chromosomes 10 (acute insulin response: MLS = 3.11 at 21.0 cM), 13 (2-h insulin: MLS = 2.86 at 65.5 cM), and 17 (fasting insulin/glucose ratio: MLS = 3.20 at 9.0 cM). In several cases, there was evidence for overlapping signals between diabetic and nondiabetic individuals; therefore we performed joint analyses. In these joint analyses, we observed strong signals for chromosomes 3 (body-mass index: MLS = 3.43 at 59.5 cM), 17 (empirical insulin-resistance index: MLS = 3.61 at 0.0 cM), and 19 (empirical insulin-resistance index: MLS = 2.80 at 74.5 cM). Integrating genome-scan results from the companion article by Ghosh et al., we identify several regions that may harbor susceptibility genes for type 2 diabetes in the Finnish population.
Age Factors↗
Local structural elements in the mostly unstructured transcriptional activation domain of human p53.
DNA transcription is initiated by a small regulatory region of transactivators known as the transactivation domain. In contrast to the rapid progress made on the functional aspect of this promiscuous domain, its structural feature is still poorly characterized. Here, our multidimensional NMR study reveals that an unbound full-length p53 transactivation domain, although similar to the recently discovered group of loosely folded proteins in that it does not have tertiary structure, is nevertheless populated by an amphipathic helix and two nascent turns. The helix is formed by residues Thr(18)-Leu(26) (Thr-Phe-Ser-Asp-Leu-Trp-Lys-Leu-Leu), whereas the two turns are formed by residues Met(40)-Met(44) and Asp(48)-Trp(53), respectively. It is remarkable that these local secondary structures are selectively formed by functionally critical and positionally conserved hydrophobic residues present in several acidic transactivation domains. This observation suggests that such local structures are general features of acidic transactivation domains and may represent "specificity determinants" (Ptashne, M., and Gann, A. A. F. (1997), Nature 386, 569-577) that are important for transcriptional activity.
Amino Acid Sequence↗
Decrease of hindpaw withdrawal latency by cocaine- and amphetamine-regulated transcript peptide to the mouse spinal cord.
Immunohistochemical studies with the use of an antiserum against the cocaine- and amphetamine-regulated transcript (CART) peptide-(55-102) showed an abundance of CART-immunoreactive fibers in the mouse dorsal horn laminae I and II. A few CART-positive somata were scattered in the dorsal horn and around the central canal. Intrathecal injection of the CART peptide-(55-102) at doses 3, 10 and 100 ng caused a dose-dependent and significant decrease of paw withdrawal latency; whereas, saline injection was without significant effect. Our results provide the first evidence that CART-immunoreactive fibers are present in the dorsal horn and that the peptide administered intrathecally produces hyperalgesia, as assessed by paw withdrawal latency in mice.
Animals↗
Rebound from nitric oxide inhibition triggers enhanced monocyte activation and chemotaxis.
Exposure of human peripheral blood monocytes to the NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP) resulted in a rapid shift in cellular conformation of spontaneously activated cells from ameboid to round. The population of activated cells, approximately 7. 1 +/- 1.2%, was reduced 7-fold to 1.1 +/- 0.4% following 0.5 h exposure to SNAP. Observation of monocytes for 6 h demonstrated a gradual release from NO inhibition initiating at 2.5 h following SNAP treatment and a period of hyperactivity that was maximal at approximately 5 h following SNAP exposure. During the rebound from the NO inhibition phase, there was a significant increase in the population of activated monocytes and an increased responsiveness to chemotactic agents such as IL-1, IL-8, and fMLP relative to that of cells treated with the chemotactic agents alone. Conformational changes induced by SNAP were associated with a reduction in F-actin and loss of filopodial extension. The loss and recovery of F-actin staining paralleled changes in cell activity, suggesting that NO may alter cellular activity by modulation of cytoskeletal actin. These data taken together suggest that inhibition of monocyte activity by NO results in an excitatory phase observed subsequent to release from NO inhibition and increased sensitivity to chemotactic agents. We propose that this rebound from NO inhibition may provide increased immunosurveillance to rectify immunological problems that have been encountered during the period of inhibition.
Cell Migration Inhibition↗
The structure of denatured bovine pancreatic trypsin inhibitor (BPTI).
In the presence of denaturant and thiol initiator, the native bovine pancreatic trypsin inhibitor (BPTI) denatures by shuffling its native disulfide bonds and converts to a mixture of scrambled isomers. The extent of denaturation is evaluated by the relative yields of the scrambled and native species of BPTI. BPTI is an exceedingly stable molecule and can be effectively denatured only by guanidine thiocyanate (GdmSCN) at concentrations higher than 3-4 M. The denatured BPTI consists of at least eight fractions of scrambled isomers. Their composition varies under increasing concentrations of GdmSCN. In the presence of 6 M GdmSCN, the most predominant fraction of scrambled BPTI accounts for 56% of the total structure of denatured BPTI. Structural analysis reveals that this predominant fraction contains the bead-form isomer of scrambled BPTI, bridged by three pairs of neighboring cysteines, Cys5-Cys14, Cys30-Cys38 and Cys51-Cys55. The extreme conformational stability of BPTI has important implications in its distinctive folding pathway.
Animals↗
Absence of proximal duct apoptosis in the ventral prostate of transgenic mice carrying the C3(1)-TGF-beta type II dominant negative receptor.
BACKGROUND: Prostatic epithelial cells are sensitive to the inhibitory effects of TGF-beta. However, TGF-beta signaling in the prostate is dependent on androgenic status. Under the in vivo conditions, it is difficult to dissociate the effect of TGF-beta from that of androgen on the prostate. METHODS: The objective of the present study was to create and verify a transgenic mouse system in which epithelial cells of the ventral prostate are insensitive to the actions of TGF-beta. By using a modified prostate-specific promoter, C3(1), the TGF-beta dominant negative receptor is only expressed in the epithelial cells of the ventral prostate, and these cells are resistant to TGF-beta. Morphology of transgenic animal prostates was compared to wild-type animal prostates by immunohistochemistry and microscopy. RESULTS: The prostate of transgenic mice exhibited an abnormal morphology with multiple layers of epithelial cells lining the proximal ducts, in contrast to the simple cuboidal monolayer of cells seen in the normal prostate. This observation was accompanied by a loss of apoptosis in this region, as seen by TUNEL assay. There was no significant difference in serum levels of testosterone between the wild-type and transgenic animals. CONCLUSIONS: These results demonstrated that a loss of sensitivity to TGF-beta results in the accumulation of multiple layers of epithelial cells in the proximal region of the ventral prostate. This abnormal growth illustrates that TGF-beta plays an important role in regulating prostate growth. The current transgenic system can be used as an experimental model to study the functional role of TGF-beta in prostatic growth and function.
Activin Receptors, Type I↗
Distribution, chemical coding and origin of nitric oxide synthase-containing nerve fibres in the guinea pig nasal mucosa.
The distribution, chemical coding and origin of nitric oxide synthase (NOS)-containing nerve fibres in the respiratory mucosa of the nasal septum of the guinea pig were examined using nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry and immunohistochemistry. A rich supply of NADPH-d-positive nerve fibres was observed around blood vessels and in nasal glands where nerve fibres frequently penetrated into the epithelia of acini and intralobular ducts. NADPH-d reactivity was also found in the nerve fibres located under or within the respiratory epithelium. Combined immunofluorescence and histochemical staining of the same preparation demonstrated virtually complete overlapping of NOS immunoreactivity and NADPH-d reactivity in nerve fibres, indicating that NADPH-d can be used as a marker for NOS-containing neurons. Double-labelling using antibodies to vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), and calcitonin gene-related peptide (CGRP) revealed that NADPH-d-positive nerve fibres frequently contained VIP or NPY, but not CGRP. Pterygopalatine ganglionectomy significantly reduced the number of NADPH-d-positive nerve fibres innervating the respiratory epithelium as well as blood vessels and nasal glands. Neither superior cervical ganglionectomy nor sensory denervation by capsaicin treatment affected the distribution of NADPH-d-positive fibres. These results indicate that NOS-containing nerve fibres innervating the respiratory epithelium as well as blood vessels and nasal glands in the guinea pig originate mainly from the pterygopalatine ganglion, and suggest that NO may play a significant role as a neurotransmitter and/or neuromodulator in the control of the respiratory epithelium as well as vasculature and nasal glands.
Animals↗
Cocaine- and amphetamine-regulated transcript-immunoreactivity in the rat sympatho-adrenal axis.
Distribution of cocaine- and amphetamine-regulated transcript-like immunoreactivity (CART-LI) was studied in the rat spinal cord, sympathetic ganglia and adrenal glands by immunohistochemical methods, utilizing a polyclonal antiserum raised against the CART peptide fragment 55-102. CART-LI was detected in nerve fibers and in basket-like terminals surrounding many postganglionic neurons of the superior cervical ganglion (SCG), stellate, paravertebral and prevertebral ganglia. Postganglionic neurons exhibited low or non-detectable levels of CART-LI. Surgical sectioning of the cervical sympathetic trunk for 6-7 days resulted in a nearly complete loss of CART-LI fibers and terminals in the SCG. In the adrenal gland, CART-LI nerve fibers formed a plexus underneath the capsule, some of which bifurcated and made a sharp turn toward the adrenal medulla, where clusters of chromaffin cells were intensely labeled. The detection of CART-LI in sympathetic ganglia and adrenal glands extends the previous observation of the presence of CART-LI in sympathetic preganglionic neurons and further supports the notion that CART peptide(s) may function as a signaling molecule in the sympatho-adrenal axis.
Amphetamine↗
Relative profile and dose verification of intensity-modulated radiation therapy.
PURPOSE: To develop a quality assurance (QA) procedure to assess the intensity profile and dosimetry for intensity-modulated (IM) treatment fields using electronic portal imaging devices (EPIDs). METHODS AND MATERIALS: A series of rapidly acquired (approximately 1/sec) portal images are summed and converted to dose. For relative intensity QA, the intended profile is subtracted point-by-point from the measured profile forming a series of error values. The standard deviation, sigma, of the errors, a measure of the goodness of the match, is minimized by applying a normalization and uniform scatter subtraction from the measured profile. For dose verification (dose to isocenter), an empirically determined phantom-correction factor is added to incorporate the effect of patient presence on EPID readings. Seventy prostate treatment fields were used in a phantom study to verify these approaches. Sensitivity was studied by creating artificial mismatches. RESULTS: The average sigma for relative profile verification is 3.3% (percentage of average intended intensity) whereas artificial mismatches resulted in sigma values from 5% to 27%. The average isocentric dose calculated from EPID readings is 1.001 relative to the planned dose with a standard deviation of 0.018. CONCLUSIONS: An EPID can be used for profile verification and absolute isocentric dose measurement for IM fields.
Algorithms↗
Expression of the RNA-binding protein TIAR is increased in neurons after ischemic cerebral injury.
T-cell restricted intracellular antigen-related protein (TIAR) is an RNA recognition motif-type RNA-binding protein that has been implicated in the apoptotic death of T-lymphocytes and retinal pigment epithelial cells. Western blots prepared with a monoclonal antibody against TIAR showed expression in normal rat hippocampus, and induction by 15 min of global cerebral ischemia. This increased expression was evident at 8 hr after ischemia and maximal at 24 hr, whereas expression at 72 hr was reduced below basal levels. Expression of TIAR protein was also increased in parietal cortex 6 and 24 hr after 90 min of focal cerebral ischemia induced by middle cerebral artery (MCA) occlusion, as well as in cultured cortical neurons and astroglia after exposure to hypoxia in vitro. Immunocytochemistry showed that increased expression of TIAR occurred mainly in the CA1 sector of hippocampus 24 hr after global ischemia, and in cortical and striatal neurons 24 hr after 20 or 90 min of focal ischemia. Double-labeling studies showed that TIAR protein expression was co-localized with DNA damage in neuronal cells. The findings suggest that TIAR may be involved in neuronal cell death after cerebral ischemic injury.
Animals↗