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Biomedical subjects

Z J Wang

Publications and source records attributed to Z J Wang.

At least 37 records · Page 2Linked to original sources

Antimicrobial activity of synthetic all-D mastoparan M.

Mastoparan M, a tetradecapeptide toxin (INKAIAALAKKLL-NH2) from hornet venom and its D-form mastoparan M were synthesized chemically. All D- and L-mastoparan M forms were found to adopt 28% alpha-helical structures in a 30% trifluroethanol solution as shown by the circular dichroism spectrum. All-D mastoparan M caused 3H-thymidine release from labeled bacterial cells after incubation for 1 h and complete cell lysis by 4 h. Both L- and D-mastoparan M showed strong activity against gram-positive and gram-negative bacteria. All-D mastoparan M showed 2-fold higher antibacterial activity than L-mastoparan M. The effects of all-D mastoparan M on the surface morphology of Staphylococcus aureus (ATCC29213) and Escherichia coli (ATCC25922) were studied by scanning-beam electron microscopy. Blast-like bleb extrusions on the surface of some S. aureus and swellings on the end of E. coli were seen after culture with all-D mastoparan M. These findings indicated the all-D mastoparan M could kill bacteria by disrupting cells.

Anti-Bacterial Agents↗

Study on the dose-effect relationship of selenite with the growth of wheat.

The wheat in hydroponics culture has been chosen as a model to study the dose-effect relationship of selenite with its growth. Five different morphological end points and 12 different biological and biochemical end points during different phases of growth of wheat seedling and seed germination have been measured and analyzed. A dose-effect relationship of selenite with the growth of wheat has been obtained from data analysis. The results shows that critical threshold for beneficial effect is about 1.0 mg Se/L, and the critical threshold for adverse effect is about 5.0 mg Se/L in hydroponics culture. From the result of product of lipid peroxidation, it is assumed that the role of selenium for plant is related to the oxy-radical reaction.

Dose-Response Relationship, Drug↗

[Triterpenoid compounds of Prunella genus and their features of 13C NMR spectroscopy].

OBJECTIVE: To summarize the research advances and 13C NMR features of triterpenoid compounds in the plant of Prunella genus. METHODS: Consulting related literatures and summing up the triterpenoid compounds and their features of 13C NMR spectra. RESULT AND CONCLUSION: Up to now, 28 triterpenoid compounds were isolated from the plant of P. genus. of which 20 were in free state and 8 were triterpenoid saponins. The 13C NMR spectra of different triterpenoids showed different features in respects such as skeletons, substituent groups and positions.

Magnetic Resonance Spectroscopy↗

[Experimental research on inhibitory effect of alcohol extracts from Loranthus yadoriki Sieb. on coxsackie B3 virus].

OBJECTIVE: To investigate the antiviral effect of two components (B and C) in the alcohol extracts from Loranthus yadoriki Sieb for development of new antiviral drugs for coxsackie B3 virus(CVB3). METHOD: Using ribavirin as positive control, the plaque reduction assay was adopted for pharmadynamic detection. RESULTS: In the HEp-2 cell system, with respect to direct virucidal activity and the inhibition on CVB3 infection and multiplication, ED50s of component B were 2.32 micrograms.ml-1, 0.24 microgram.ml-1 and 1.91 micrograms.ml-1, respectively and those of component C, 1.44 micrograms.ml-1, 2.06 micrograms.ml-1 and 3.70 micrograms.ml-1 respectively. For the inhibition on multiplication of CVB3, ED50 of ribavirin was 7.55 micrograms.ml-1. CONCLUSION: Treatment indexes (TI) of the direct virucidal activity and inhibitory effects of component B on CVB3 infection and multiplication 22.6, 219 and 27.5 respectively; component C, 115, 165 and 21.6; inhibition of ribavirin on CVB3 is 38, which is comparable to those of components B and C. It is thus suggested that the anti-CVB3 action of components B and C in the alcohol extracts from Loranthus yadoriki Sieb deserves to be exploited.

Antiviral Agents↗

[The diagnostic value of combined detection of circulating antigens and antibodies in urine of patients with schistosomiasis japonica].

OBJECTIVE: To assess the value of detecting circulating antigens and antibodies in urine as a noninvasive method for the diagnosis of schistosomiasis. METHODS: A sandwich ELISA and ELISA using McAb were applied to detect circulating schistosomal antigens and specific antibodies in the urine of patients with acute and chronic schistosomiasis. RESULTS: When the urine samples from 10 cases of acute schistosomiasis and 61 cases of chronic schistosomiasis were examined, the positive rates of circulating antigens and specific antibodies were 60%, 40%, and 80%, 60.1%, respectively; when both detection was combined, the positive rates were 100% and 71.7% respectively, whereas a false positive rate of 3% of CAg or CAb was detected in the urine of 100 normal controls. CONCLUSION: The detection of circulating antigen in urine is a practicable and noninvasive method for the diagnosis of schistosomiasis.

Animals↗

[Detection of specific antibodies in saliva of patients with chronic schistosomiasis japonica].

OBJECTIVE: To investigate the feasibility of detecting specific antibodies in the saliva of schistosomiasis patients. METHODS: Specific antibodies in saliva samples of 32 schistosomiasis patients and 140 normal individuals were detected by using ELISA and the results were compared with those detected for specific antibodies in serum. RESULTS: The sensitivity and specificity of the ELISA were 90.6% and 94.4%, respectively, being slightly lower than that of the 100% sensitivity and 96.2% specificity for the serum. No significant difference between them was found (P > 0.05). CONCLUSION: Detecting specific antibodies in saliva can be used for immunodiagnosis of schistosomiasis japonica as a noninvasive method in field surveys.

Adolescent↗

Allelic imbalance at the LKB1 (STK11) locus in tumours from patients with Peutz-Jeghers' syndrome provides evidence for a hamartoma-(adenoma)-carcinoma sequence.

Patients with Peutz-Jeghers' syndrome (PJS) develop hamartomatous gastrointestinal polyps and characteristic pigmentation, as a result of germline mutations in the LKB1 gene. The hamartomas in PJS were long considered to be without malignant potential. There is, however, accumulating epidemiological evidence to suggest that PJS predisposes to cancers at several different sites (colon, pancreas, breast, ovary, testis, and cervix), although large enough patient samples are rarely available to prove this. Allelic imbalance [allele loss, loss of heterozygosity (LOH)] has previously been reported in a small number of PJS polyps, suggesting that LKB1 acts as a tumour suppressor in these tumours. This study confirms allelic loss at LKB1 in PJS polyps and shows that LOH also occurs in cancers of the colon, breast, and cervix in PJS patients. Allele loss was additionally found in a colonic adenoma from a PJS patient, strongly suggesting the existence of a hamartoma-(adenoma)-carcinoma sequence in tumourigenesis. These results provide molecular evidence that PJS patients are predisposed to cancers at several sites, as a direct result of selection for loss of the 'wild-type' LKB1 allele in tumours. Given the rare involvement of LKB1 in sporadic cancers, these data also suggest that the indirect effect on cancer risk (or 'bystander effect') proposed for hamartomas in juvenile polyposis does not apply to carcinomas in PJS.

AMP-Activated Protein Kinase Kinases↗

Magnetic resonance imaging measurement of volume magnetic susceptibility using a boundary condition.

A magnetic resonance imaging method is described for measuring the magnetic susceptibility difference between two homogeneous macroscopic compartments in contact with each other. A boundary condition is derived for the interface of the two compartments. This boundary condition predicts that across the interface there is a resonant frequency jump, which is a function of interfacial orientation relative to B0 field and the difference in susceptibility of the two sides. Based on this relationship, the magnetic susceptibility difference between two materials can be obtained from MR gradient echo imaging using signals from both sides in the vicinity of the boundary. This method is demonstrated by solution phantom experiments.

Algorithms↗

Study of the incorporation of selenium into peroxidase isozyme of wheat seedling.

The effects of selenium on the activity of peroxidase (POD) of wheat seedling and its isozyme pattern were studied using a greenhouse hydroponic experiment. The results show that the activity of POD is increased in response to higher Se concentration (approx 5.0 mg/L) in culture medium. The electrophoretic pattern of the POD isozyme was altered by growth of the wheat in a selenium medium. Se could incorporate into some POD isozymes during either seed germination or the seedling growth period. There is a dose-responsive incorporation of selenium in isozyme of POD and selenium content in the isozyme increase along with the increase of selenium concentration in the medium.

Dose-Response Relationship, Drug↗

In vivo brain myo-inositol levels in children with Down syndrome.

The Na+/myo-inositol cotransporter (SLC5A3) gene, located on the long arm of human chromosome 21, may play a key role in osmoregulation including the regulation of levels of the "idiogenic osmole," myo-inositol, in brain cells. To determine whether the levels of myo-inositol are increased in the basal ganglia of children with Down syndrome, we performed in vivo brain hydrogen 1-nuclear magnetic resonance or 1H-magnetic resonance spectroscopy and measured plasma osmolality in a cohort of children with trisomy 21. Myo-inositol is elevated in the corpus striatum of infants and children with Down syndrome, even in the absence of hypertonic stress.

Adolescent↗

Allele loss and mutation screen at the Peutz-Jeghers (LKB1) locus (19p13.3) in sporadic ovarian tumours.

Germline mutations in the LKB1 (STK11) gene (chromosome sub-band 19p13.3) cause characteristic hamartomas and pigmentation to develop in patients with Peutz-Jeghers syndrome. Peutz-Jeghers syndrome carries an overall risk of cancer that may be up to 20 times that of the general population and Peutz-Jeghers patients are at increased risk of benign and malignant ovarian tumours, particularly granulosa cell tumours. Loss of heterozygosity (allele loss, LOH) has been reported in about 50% of ovarian cancers on 19p13.3. LKB1 is therefore a candidate tumour suppressor gene for sporadic ovarian tumours. We found allele loss at the marker D19S886 (19p13.3) in 12 of 49 (24%) sporadic ovarian adenocarcinomas. Using SSCP analysis, we screened ten ovarian cancers with LOH, 35 other ovarian cancers and 12 granulosa cell tumours of the ovary for somatic mutations in LKB1. No variants were detected in any of the adenocarcinomas. Two mutations were detected in one of the granulosa cell tumours: a mis-sense mutation affecting the putative 'start' codon (ATG --> ACG, M1T); and a silent change in exon 7 (CTT --> CTA, leucine). Like BRCA1 and BRCA2, therefore, it appears that LKB1 mutations can cause ovarian tumours when present in the germline, but occur rarely in the soma. The allele loss on 19p13.3 in ovarian cancers almost certainly targets a different gene from LKB1.

AMP-Activated Protein Kinase Kinases↗

The role of humic substances in drinking water in Kashin-Beck disease in China.

We conducted in vitro and in vivo assays in a selenium-deficient system to determine if organic matter (mainly fulvic acid; FA) is involved in a free radical mechanism of action for Kashin-Beck disease. Cartilage cell culture experiments indicated that the oxy or hydroxy functional groups in FA may interfere with the cell membrane and result in enhancement of lipid peroxidation. Experiments with rats demonstrated that toxicity from FA was reduced when the hydroxy group was blocked. Induction of lipid peroxidation by FA in liver and blood of rats was similar to that exhibited by acetyl phenyl hydrazine. FA accumulated in bone and cartilage, where selenium rarely concentrates. In addition, selenium supplementation in rats' drinking water inhibited the generation of oxy-free radicals in bone. We hypothesized that FA in drinking water is an etiological factor of Kashin-Beck disease and that the mechanism of action involves the oxy and hydroxy groups in FA for the generation of free radicals. Selenium was confirmed to be a preventive factor for Kashin-Beck disease.

Animals↗

Germline mutations of the LKB1 (STK11) gene in Peutz-Jeghers patients.

Germline mutations of the LKB1 (STK11) serine/threonine kinase gene (chromosome 19p13.3) cause Peutz-Jeghers syndrome, which is characterised by hamartomas of the gastrointestinal tract and typical pigmentation. Peutz-Jeghers syndrome carries an overall risk of cancer that may be up to 20 times that of the general population. Here, we report the results of a screen for germline LKB1 mutations by DNA sequencing in 12 Peutz-Jeghers patients (three sporadic and nine familial cases). Mutations were found in seven (58%) cases, in exons 1, 2, 4, 6, and 9. Five of these mutations, two of which are identical, are predicted to lead to a truncated protein (three frameshifts, two nonsense changes). A further mutation is an in frame deletion of 6 bp, resulting in a deletion of lysine and asparagine; the second of these amino acids is conserved between species. The seventh mutation is a missense change in exon 2, converting lysine to arginine, affecting non-conserved amino acids and of uncertain functional significance. Despite the fact that Peutz-Jeghers syndrome is usually an early onset disease with characteristic clinical features, predictive and diagnostic testing for LKB1 mutations will be useful for selected patients in both familial and non-familial contexts.

AMP-Activated Protein Kinase Kinases↗

Three-dimensional multivoxel proton MR spectroscopy of the brain in children with neurofibromatosis type 1.

BACKGROUND AND PURPOSE: Neurofibromatosis type 1 (NF1), the most common autosomal dominant genetic disorder, frequently manifests as focal areas of signal intensity (FASI) on T2-weighted MR images. The purpose of our study was to investigate whether tumor(s), focal areas of signal intensity (FASI), and normal brain can be differentiated by using 3D multivoxel localized proton MR spectroscopy in children with neurofibromatosis type 1 (NF1) disorder. METHODS: Five children with NF1 and two healthy control subjects, all in the 3- to 11-year-old age group, were studied with a new 3D proton MR spectroscopy technique: a hybrid of 1D fourth-order transverse Hadamard spectroscopic imaging and 2D chemical shift imaging. A 3D volume-of-interest (VOI) was image-guided onto the site of the abnormality and identified on three orthogonal images. Proton MR spectroscopy partitioned the VOI into 6 x 6 x 4 (or 8 x 8 x 4) voxels, 1.5 (or 1.0) cm3 each. RESULTS: Simultaneous coverage of the entire VOI yielded good spectral signal-to-noise ratio from 136 (or 256) voxels in 27 minutes. Proton MR spectroscopy indicated that FASI a) are characterized by significantly elevated choline (Cho), reduced creatine (Cr), 2>Cho: Cr>1.3, and near normal N-acetylaspartate (NAA) levels; b) are different from tumors that exhibit Cho:Cr>2 and no NAA; c) have no intrinsic lipid or lactate signal(s); and d) correlate in spatial extent but are more extensive than indicated by MR imaging. CONCLUSION: Three-dimensional multivoxel proton MR spectroscopy reveals distinct metabolic features that differentiate normal, FASI, and tumor regions in the pediatric brain.

Aspartic Acid↗

Pharmacokinetics, tissue distribution and photodynamic therapy efficacy of liposomal-delivered hypocrellin A, a potential photosensitizer for tumor therapy.

Hypocrellin A, from Hypocrella bambusae, is a novel photosensitizer of high singlet oxygen quantum yield for photodynamic therapy (PDT). Tissue distributions were studied in tumor-bearing mice as a function of time following administration. The tumor model was S-180 sarcoma transplanted into one hind leg of male Kunming mice; hypocrellin A (HA) was delivered to the mice by intravenous injection of 5 mg/kg of body weight as a suspension either as a unilamellar liposome or in dimethyl sulfoxide (DMSO)-solubilized saline. The HA was isolated from several tissues and organs, as well as tumors and peritumoral muscles and skin. Quantitation was performed by a high-performance liquid chromatographic technique with detection that utilizes the native fluorescence of HA. Independent of the delivery system, the dye was retained in tumors at higher concentrations than in normal tissues, except for kidney, liver, lung and spleen. The dye retention in tumors was high and was vehicle dependent. For the liposomal system, the maximal accumulation in tumor and maximal ratios of dye in tumor versus peritumoral muscle and skin occurred 12 h postinjection; for the DMSO saline system, the maximal ratio occurred earlier, 6 h postadministration. Liposomal delivery improved the selective accumulation of the dye in tumor with higher maximal levels in tumor and higher ratios of tumor-to-muscle and tumor-to-skin. Levels of dye were very low or not detectable in the brain. The PDT efficacy of HA in the liposome and DMSO saline systems was determined by evaluating the tumor volume regression percent. The PDT efficacy of HA in liposomes was highest when light treatment was performed at 12 h postinjection, consistent with the highest retention of HA in tumors. Similarly, the maximal PDT efficacy in DMSO saline was attained at 6 h postinjection, the highest HA retention point in tumor. Moreover, the peak PDT efficacy of HA in liposomes was much higher than that of HA in DMSO saline and even hematoporphyrin monomethylether.

Animals↗

Stress-induced secretion of growth inhibitors: a novel tumor suppressor function of p53.

p53 tumor suppressor gene controls cell response to a variety of stresses inducing growth arrest or apoptosis in damaged cells. It largely determines the sensitivity of tumor and normal cells to radiation and chemotherapy, and, therefore, defines both the efficacy and limitations of anti-cancer treatment. To determine molecular mechanisms of p53-dependent stress response in normal tissues we identified and compared the spectra of radiation-responsive genes in cells of different origin and p53 status using a cDNA array hybridization technique. The majority of genes identified were p53-dependent and cell type specific. Several of the new p53 responders encode known secreted growth inhibitory factors. This suggests that p53, in addition to its intrinsic antiproliferation activity, can cause 'bystander effect' by inducing export of growth suppressive stimuli from damaged cells to neighboring cells. Consistently, a p53-dependent accumulation of factors, which causes growth inhibitory effects in a variety of cell lines, was found after gamma irradiation in the media from established and primary cell cultures and in the urine of irradiated mice. Moreover, p53-dependent factors released by normal human fibroblasts potentiated the cytotoxic effect of a chemotherapeutic drug on co-cultivated tumor cells. This suggests a previously unknown role for normal cells in chemo- and radiation therapy of cancer.

3T3 Cells↗

Prognostic value of proton MR spectroscopy of cerebral hemisphere tumors in children.

We studied 14 young people with newly diagnosed hemisphere tumors, aged from 3 to 20 years (average 10 years). All underwent surgery following MR imaging (MRI) and spectroscopy (MRS). The tumors studied were three glioblastomas, one each of ganglio-glioblastoma, primitive neuroectodermal tumor (PNET), rhabdoid teratoid tumor, pilocytic astrocytoma, ependymoma, anaplastic ependymoma, and gliomatosis cerebri, and four gangliogliomas. Four patients died; ten patients are alive (five with stable residual tumor, five with no evident tumor). Images and spectra were acquired on a 1.5-T imager. Proton MRS was performed before gadolinium injection in all but one case. Single-voxel techniques were utilized in all cases, using a spin-echo or STEAM sequence with a long echo time (135 or 270 ms). Peak areas of N-acetyl aspartate (NAA), choline (Cho), and creatine and phosphocreatine (Cr) were assessed. The NAA/Cho peak-area ratio was very low in the patients who died (mean +/- s.d. 0.20 +/- 0.14), and higher in the patients who are alive (0.74 +/- 0.47; P = 0.007 by two-tailed t-test). The Cr/Cho peak-area ratio also followed a similar trend for the two groups (mean +/- s.d. 0.17 +/- 0.07 and 0.49 +/- 0.30, respectively; P = 0.01 by two-tailed t-test).

Brain↗