Chinese herbal medicine in the treatment of asthma and allergies.
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Biomedical subjects
Publications and source records attributed to C Chang.
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Whereas the human killer cell inhibitory receptors (KIRs) for HLA class I are immunoglobulin-like monomeric type I glycoproteins, the murine Ly49 receptors for H-2 are type II homodimers of the C-type lectin superfamily. Here, we demonstrate that human NK cells also express C-type lectin receptors that influence recognition of polymorphic HLA-A, HLA-B, and HLA-C molecules. These receptors are heterodimers composed of CD94 chains covalently associated with novel tyrosine-phosphorylated glycoproteins (94AP). Some NK clones recognize a common HLA-C ligand using both KIRs and CD94-94AP receptors. These findings suggest the existence of human inhibitory MHC class I receptors of the immunoglobulin and C-type lectin superfamilies and indicate overlap in ligand specificity.
The development of simultaneous resistance to structurally unrelated drugs in cancer cells is a major obstacle to effective cancer chemotherapy. This multidrug-resistance (MDR) phenomenon is largely attributed to overexpression of a 170 kD glycoprotein, which serves as a transmembrane efflux pump in extruding a variety of natural anticancer drugs such as vinblastine, doxorubicin, and taxol from cancer cells. It is desirable, therefore, to discover compounds that can block the efflux mechanism and thus reverse drug resistance. The bicinchoninic acid protein assay has been adapted for use in a microtiter plate, into an easy, indirect method for screening MDR efflux blockers in plant extracts. This spectrophotometric assay is used to determine the enhancement of adriamycin cytotoxicity against resistant cancer cells by plant extracts or pure compounds indirectly. We have shown that the optical density measured (amount of cellular protein present) correlates with the number of viable cells and that fluorescence of Adriamycin associated with the cell correlates with the concentrations of Adriamycin added to the media. In addition, the relative efficacy of MDR reversal by various alkaloids has been determined.
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Based on scientific literature and interviews with clinicians and patients, we developed a quality of life instrument for use with people with MS called the Functional Assessment of Multiple Sclerosis (FAMS). The initial item pool consisted of 88 questions: 28 from the general version of the Functional Assessment of Cancer Therapy quality of life instrument, plus 60 generated by patients, providers, and literature review. The validation samples comprised a mail survey cohort (N = 377) and a clinical cohort (N = 56). Both cohorts provides evidence for internal consistency of the derived subscales, test-retest reliability, content validity, concurrent validity, and construct validity. Principal components and Rasch measurement model analyses were applied sequentially to survey sample data, reducing test length to 44 questions, divided into six subscales: mobility, symptoms, emotional well-being (depression), general contentment, thinking/fatigue, and family/social well-being. Fifteen initially rejected questions were added back as miscellaneous (unscored) questions for their potential clinical and empirical value. The mobility subscale was strongly predictive of the Kurtzke Extended Disability Status Scale and the Scripps Neurologic Rating Scales. The other five subscales were not, indicating they measure aspects of patient quality of life not captured by the neurologic exam. The final 59-item English language instrument (FAMS version 2) is available for inclusion in clinical trials and clinical practice.
To investigate the effect of hypophyseal transection (HST) on GH secretagogue activity of the non-peptidyl GH secretagogue L-692,585 in the conscious pig, male castrated swine were randomly assigned to either a hypophyseal stalk transection group (HST; n = 3) or to a sham-operated control group (SOC; n = 3). Treatments administered were L-692,585 (100 micrograms/kg), human GH-releasing factor(1-29)NH2 (GRF; 20 micrograms/kg) or L-692,585 (100 micrograms/kg) + GRF (20 micrograms/kg) on days -7 to -3 before surgery and days +3 to +8 after surgery. To evaluate the integrity of the pituitary gland, the animals were challenged with corticotropin-releasing hormone (CRH; 150 micrograms) or GnRH (150 ng/kg) both before and after surgery. Blood was collected from -60 to +180 min post treatment and assayed for GH, cortisol and LH. Before surgery, no significant difference (P > 0.05) in peak GH response (ng/ml) was present between the two groups (SOC vs HST) in response to L-692,585 (101 +/- 12 vs 71 +/- 9) or L-692,585 + GRF (171 +/- 21 vs 174 +/- 21). Only two out of three SOC vs three out of three HST pigs responded to GRF (13 +/- 2 vs 25 +/- 3) resulting in a significant difference between groups. Following surgery, significant differences were present in peak GH response (ng/ml) between SOC and HST groups following L-692,585 (79 +/- 6 vs 13.8 +/- 1.0); however, the response to L-692,585 + GRF was similar (115 +/- 8 vs 94 +/- 7). All animals responded to GRF; however, a significant difference was present between groups due to the magnitude of the responses. Whereas the cortisol responses (ng/ml) to L-692,585 in the SOC and HST groups were similar before surgery, a significant difference was present after surgery (44.4 +/- 6.4 vs 14.6 +/- 2.1). No significant difference was noted between the HST and SOC groups in response to CRH or GnRH either before or after surgery. These results indicated that L-692,585 induced an immediate GH response in the intact animal in contrast to GRF where the GH release was variable. L-692,585 also stimulated an immediate increase in cortisol levels. Transection of the hypophyseal stalk dramatically decreased but did not ablate the GH or cortisol response to L-692,585. Co-administration of L-692,585 + GRF induced an immediate GH response of similar magnitude in the intact and HST animal. We conclude that L-692,585 has a direct but limited action at the level of the pituitary and that an intact hypophyseal stalk is required for a maximal GH and cortisol response. L-692,585 acts with GRF at the level of the pituitary to induce a maximal GH response. These findings suggest that L-692,585 stimulates GH secretion by acting in combination with GRF and interrupting the inhibitory tone of somatostatin on the somatotroph.
The effects of pyronaridine on the morphology of Plasmodium falciparum were studied in an infected owl monkey (Aotus trivirgatus) that was severely ill with a parasitemia of 28%. Thirty minutes after pyronaridine administration, distinct morphologic changes were already present in late trophozoites and schizonts. Ultrastructural observations revealed that the earliest and most distinct changes induced by pyronaridine occurred in food vacuoles. The most striking change in food vacuoles was the appearance of undigested endocytic vesicles surrounded by a single membrane in the vacuolar space. These findings suggest that vacuolar degradation is inhibited by pyronaridine, and that undigested endocytic vesicles accumulate inside parasite food vacuoles impairing hemoglobin degeneration. Thus, pyronaridine appears to interfere with the parasitic digestive system.
This paper is concerned with the time frame and the reasons why the Kangxi Emperor adopted variolation in the Qing Imperial family. The Manchus, especially the Qing Imperial family, lived in the fear of contracting smallpox. They took various strategies to protect themselves from smallpox. One of the most conspicuous methods was adopting variolation in royal family in the Kangxi reign. The purpose of this important action was to maintain the superiority of the Manchu minority and to reduce the mortality rate of smallpox in the Imperial family. In this paper, I would like to point out the time when the Kangxi Emperor intended to use variolation was earlier than we had known through the previous studies. The Emperor's decision of variolation was mainly stimulated by his personal experiences and his practical character.
In the plant Arabidopsis, ethylene signaling involves at least two putative receptors, both of which resemble the "two-component' regulators known almost exclusively in bacteria. Downstream in the pathway is a putative serine/threonine protein kinase related to the animal Raf protein kinases. This novel combination of signaling proteins has parallels with the postulated osmolarity-response pathway in yeast.
The standard treatment for ovarian cancer is cytoreductive surgery followed by platinum-based combination chemotherapy. Although high response rates of this treatment are reported, 40-60% of patients achieving a complete response may relapse. Therefore, second-line chemotherapy is required. Second-line chemotherapy of patients with recurrent ovarian cancer should be based on their sensitivity to first-line chemotherapy and the platina-free interval. Patients who respond to the platina-based chemotherapy still may be sensitive to further platina-based chemotherapy. Patients who do not respond to the platina-based chemotherapy or who have relapses shortly after first-line chemotherapy should be considered clinically resistant to further platina-based chemotherapy. For such patients the chemotherapy regimen should be changed. These regimens include paclitaxel and hexamethylmelamine. The effect of intraperitoneal chemotherapy may depend on the size of the largest residual tumor nodule and the patient's sensitivity to previous chemotherapy.
OBJECTIVE: To evaluate the value of color Doppler ultrasound examination in perinatal monitoring. METHOD: Doppler ultrasound results of 22 cases with fetal stress and 6 cases with perinatal mortality were retrospectively analyzed, and compared that of 555 normal pregnancies with same gestational age (36 to 40 weeks) using Ultramark 9 HDI color Doppler ultrasound. RESULTS: The resistance of fetal umbilical artery (FUA), fetal renal artery (FRA) and placental bed artery (PBA) in fetal stress group were significantly higher than that in normal pregnant group; there were no changes of resistance in middle cerebral artery (MCA). In perinatal mortality group, the resistance of FUA, FRA and PBA were the highest, the resistance of MCA was the lowest, and end-diastolic flow in FUA and FRA were absent or reverse. CONCLUSION: The results showed that fetal and placental flow dynamics study examined by color Doppler ultrasound is an effective method in the assessment of fetal well-being.
Expression of the human ALDH3 gene is regulated in a tissue-dependent constitutive as well as drug-inducible manner. We identified a new 5'-noncoding exon (exon 1) existing at about 3 kilobase pairs (kb) upstream from the first coding exon (exon 2) of the human ALDH3 gene. Analysis of ALDH3 mRNA revealed the existence of several isoforms with different 5' regions resulting from i) usage of multiple transcriptional initiation sites of the new exon 1, ii) usage of alternative splice acceptor sites at the 3' end of the new intron 1, and iii) alternative splicing out of exon 2. Usage of alternative splice acceptor sites was only found in tissues expressing ALDH3 constitutively, but not in Hep G2 induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Nucleotide sequence analysis and chloramphenicol acetyltransferase (CAT) expression studies showed that a strong promoter region exists at nucleotide (nt) positions -216 to +54 of the gene. Repression activities were found upstream of the -216/+54 region. Several putative drug-inducible elements exist in the regulatory region. A possible regulatory mechanism for tissue-specific constitutive and inducible expression of the human ALDH3 gene is discussed.
In the present study, the angiotensin II receptor subtype I-a (AT1a) and I-b (AT1b) mRNA levels in aortic smooth muscle (ASM), ventricular myocardium (VM) and adrenal from 12-week-old stroke-prone spontaneously hypertensive rats (SHRsp) and age-matched Wistar-Kyoto (WKY) rats with normal diet (control) and high salt-loading were examined by reverse transcriptase-polymerase chain reaction (RT-PCR). The results showed that: (1) The AT1a and AT1b mRNA levels in ASM and VM from SHRsp were lower than those from WKY rats (in ASM, 10% and 23%, while in VM, 23% and 40% lower, respectively). In contrast, both AT1a and AT1b mRNA levels in adrenal from SHRsp were higher (176% and 157%, respectively). (2) In the WKY rats with high salt-loading, the AT1a and AT1b mRNA levels in adrenal, as well as AT1b mRNA level in VM, increased significantly, as compared with the control (in adrenal, 167% and 401%, while in VM, 62%). However, the AT1a and AT1b mRNA levels in ASM, as well as AT1a mRNA level in VM, showed no obvious change. (3) In SHRsp with high salt-loading, the AT1b mRNA level in ASM, as well as AT1a and AT1b mRNA levels in VM, increased markedly (in ASM, 90%, while in VM, 590% and 200%); whereas the AT1a mRNA level in adrenal decreased significantly (58%). There was little influence on the regulation of AT1a (in ASM) and AT1b (in adrenal) receptor gene expression after high salt-loading. The results suggest that AT1a and AT1b receptors may be involved in the pathogenesis of salt-induced hypertension. The up-regulation of AT1b receptors in ASM may induce the remodeling of arterial wall, while that of AT1a and AT1b receptors in VM might contribute to ventricular hypertrophy in hypertension. Furthermore, there are certain differences between SHRsp and WKY rats with respect to the regulation of AT1a and AT1b receptor gene expression with or without external stimulation.
The key expression of the simian virus 40 (SV40) major late promoter could be repressed by the human TR4 orphan receptor via the +55 region of the SV40 major late promoter (nucleotide numbers 368-389, 5' -GTTA-AGGTTCGTAGGTCATGGA-3'). Using the coupled in vitro transcribed and translated TR4 orphan receptor with a molecular mass of 67.3 kilodaltons, electrophoretic mobility shift assay showed specific binding with a dissociation constant of 1.09 nM between the TR4 orphan receptor and the SV40 +55 oligonucleotides. In addition, chloramphenicol acetyltransferase assay demonstrated that this SV40 +55 region can function as a repressor via the TR4 orphan receptor, suppressing the transcriptional activities of both SV40 early and late promoters. Together, our data suggest that the TR4 orphan receptor may play an important role for the suppression of the SV40 gene expression.
The testicular receptor 2 (TR2) orphan receptor binds to hormone response elements (HREs) consisting of two AGGTCA half-site direct repeat consensus sequences (DR) with various spacing in the following order: DR1 > DR2 > DR5 DR4 DR6 > DR3. When binding to natural HREs, TR2 orphan receptor remains flexible with higher binding affinities to (a) cellular retinol-binding protein II promoter region (CRBPIIp) (DR1), SV40 +55 region (DR2), and retinoic acid response element beta (RARE beta) (DR5) than to (b) NGFI-B response element (NBRE) and also to (c) the palindromic thyroid hormone response element (TREpal). This wide spectrum of HRE recognition sequences suggests possible versatility of the TR2 orphan receptor in cross-talking with other signal transduction systems. Chloramphenicol acetyltransferase (CAT) assay demonstrates that the TR2 orphan receptor competes with CRBPIIp- and RARE beta-CAT gene expression activated by retinoid X receptor alpha (RXR alpha) and retinoic acid receptor alpha (RAR alpha)/RXR alpha heterodimers, respectively. In addition, this suppression may not be mediated by the formation of heterodimers between TR2 orphan receptor and either RXR alpha or RAR alpha. Instead, a minimum of 100-fold higher affinity of the TR2 orphan receptor for CRBPIIp than RXR alpha may explain why the TR2 orphan receptor dominates RXR alpha in CRBPIIp-CAT activation. Together, our data suggest that the TR2 orphan receptor may be a master regulator in modulating the activation of two key HREs, RARE beta and CRBPIIp, involved in the retinoic acid signal transduction pathway.
ERS (ethylene response sensor), a gene in the Arabidopsis thaliana ethylene hormone-response pathway, was uncovered by cross-hybridization with the Arabidopsis ETR1 gene. The deduced ERS protein has sequence similarity with the amino-terminal domain and putative histidine protein kinase domain of ETR1, but it does not have a receiver domain as found in ETR1. A missense mutation identical to the dominant etr1-4 mutation was introduced into the ERS gene. The altered ERS gene conferred dominant ethylene insensitivity to wild-type Arabidopsis. Double-mutant analysis indicates that ERS acts upstream of the CTR1 protein kinase gene in the ethylene-response pathway.
The expression of certain MHC class I allotypes by potential target cells can inhibit NK cell-mediated cytotoxicity. We recently identified the NKB1 surface Ag, expressed on T and NK cell subsets, as a putative inhibitory receptor for HLA-B class I molecules possessing the Bw4 serologic epitope. NKB1 is a 70-kDa glycoprotein that after deglycosylation migrates as a 50-kDa protein as determined by SDS-PAGE. A cDNA encoding the NKB1 receptor was cloned from a NKB1+T cell cDNA library by expression in COS-7 cells using the anti-NKB1 mAb DX9. NKB1 is a member of the lg superfamily containing three lg-like domains in the extracellular region and is related to the recently identified family (p58/NKAT) of human NK and T cell surface molecules that appear to function as inhibitory receptors for HLA class I.