Biomedical subjects
Publications and source records attributed to J Cao.
In the paper, emission of volatile sulfur gases from paddy soil was discussed in a growth period of paddy rice by constructing a field sampling system. The result showed that COS, CS2, DMS and DMDS were mainly emitted from paddy soil. The order of emission fluxes was 81.11, 6.33 and 10.71 mg.(m2.a)-1. Sulphur emission fluxes of Chinese paddy soil was 0.013662 Tg/a, and those of world paddy soil was 0.07992 Tg/a.
OBJECTIVE: To summarize the experience in surgical treatment of patients with intracranial aneurysms. METHODS: The measures used in the treatment of 500 patients with intracranial aneurysms were retrospectively reviewed with regard to timing of surgery, induced-hypotensive anesthesia, brain protection combined with temporal occlusion of the feeding artery, dynamically monitoring of transcranial Doppler ultrasound, antivasospasm treatment, techniques of direct surgery, and endovascular embolization. RESULTS: In 465 patients undergoing surgery, intraoperative rupture was observed in 27(6.2%), postoperative death in 13 (2.7%), hemipalsy in 8(2.2%), and vegetative state in 2 (5.0%). The operative mortality was 3.8% in 210 patients before 1990, while 1.9% in 255 patients after 1990. CONCLUSION: The outcome of patients with intracranial aneurysms can be markedly improved by comprehensive measures.
OBJECTIVE: To detect the relationship of mtDNA mutation with inherited deafness and the reason for pedigree's hypersensitivity to ototoxicity of aminoglycoside antibiotics(AmAn). METHODS: Pedigree investigations were conducted. The blood samples were obtained from 12 pedigrees, and DNA was extracted from the isolated leukocytes. After that, mtDNA fragments were amplified by PCR. The 1555(G), 3243(G) and 7445(G) mutations were detected by Alw 26 I, Apa I and Xba I restriction endonuclease digestion respectively, and then sequencing of 12S rRNA, tRNA(Leu(UUR)), tRNA(Ser(UCN))and 16S rRNA gene was performed. RESULTS: Restriction endonuclease digestion and sequence analysis showed that all the pedigrees carried mtDNA mutation, among them, 10 pedigrees carried 1555(G) mutation; 2 pedigrees, 7445(G) mutation; no pedigree was found to harbor the 3243(G) mutation. Sequence analysis of 16S rRNA gene showed that the mutations are 2230(G), 2230(AG), 2243(AG), 2230(AA). CONCLUSION: The pedigrees that carried 1555(G) or 7445(G) mutation showed hereditary or congenital hearing loss. The 1555(G) or 7445(G) mutation in association with 16S rRNA gene mutation led to pedigree's hypersensitivity to AmAn ototoxicity.
OBJECTIVE: To study the structure and function of a novel serine protease gene associated with human colorectal cancer SNC19. METHODS: The cDNA sequence was determined by both manual and automatic sequencing techniques. The full length cDNA sequence was obtained by the 5'-Rapid Amplification of cDNA Ends technique and web-based analysis. Open reading frame analysis and protein function prediction were also performed. Northern blot was used to detect the expression of SNC19 in various human normal tissues and tumor cell lines. Fluorescent in situ hybridization combined with fluorescent R-banding technique was employed to map the SNC19 gene on human chromosome. RESULTS: Full length SNC19 cDNA, size 3152 bp, encodes a protein highly homologous to a mouse serine protease epithin. In normal human tissues, high SNC19 expression levels were observed in the kidney, pancreas, prostate, small intestine and colon; moderate SNC19 expression levels were observed in the placenta, lung, liver, spleen thymus, testis and peripheral blood lymphocytes; and extremely low expression levels were observed in the heart, brain, skeletal muscle and ovary. In tumor cell lines, colorectal cancer cells SW480, SW620, SW1116 and Colo205, breast cancer cell Bcap37 and gastric cancer cells MKN28 and SGC7901 showed high levels of SNC19 expression; cervical cancer cell HeLa-S3, lung cancer PAA, oral epithelial cancer cell KB and lymphoma cell Raji showed moderate levels of SNC19 expression; and tongue squamous cancer cell Tca8113, leukemia cells HL-60, K562, MOLT-4, lung cancer cell A549 and melanoma cell G361 showed very low levels of SNC19 expression. SNC19 was mapped to human chromosome 11q24-25. CONCLUSION: SNC19 encodes a novel human serine protease with 855 amino acid residues. As a novel serine protease associated with human colorectal cancer, the expression of SNC19 in various tissues and cell lines may have very important impact on their phenotypes and biological behaviors.
OBJECTIVE: To define a correlation between human papillomavirus (HPV) type 16 and telomerase activity during the carcinogenesis of oral mucosa. METHODS: HPV16 DNA and human telomerase reverse transcriptase (hTRT) mRNA were detected in 82 cases of paraffin embedded tissues including 7 cases of normal oral mucosa, 7 cases of hyperplasia lesions, 30 cases of oral dysplasia lesions and 38 cases of oral squamous cell carcinomas (OSCCs) by PCR and in situ hybridization (ISH) respectively. RESULTS: HPV16DNA was positive in 14.3% (1/7) of normal oral mucosa, 42.9% (3/7) of hyperplasia lesions, 66.6% (20/30) of dysplasia lesions and 92.1% (35/38) of OSCCs. hTRTmRNA was detectable in 30.0% (9/30) of oral dysplasia lesions and 81.6% (31/35) of OSCCs while normal oral mucosa and hyperplasia lesions were negative. Expression of HPV16DNA and hTRTmRNA were co-ordinate in 67.0% (55/82) cases. CONCLUSIONS: HPV16 infection may play an important role in carcinogenesis of oral mucosa by activation of telomerase.
OBJECTIVE: To investigate the effects of recombinant human basic fibroblast growth factor (rhbFGF) on the cell proliferation during mandibular fracture healing in rabbits. METHODS: The complex of rhbFGF and bovine type I collagen was implanted into the mandibular fracture site under periosteum of the animal. The whole mandible was harvested at 7, 14, 28, 56 and 84 days respectively after operation. The expression of proliferating cell nuclear antigen (PCNA) in callus was examined with immunohistochemical staining. RESULTS: PCNA-positive cells in callus in the rhbFGF-treated group on days 7 and 14 were more than that in the control group (P<0.01). CONCLUSIONS: It indicates that rhbFGF can stimulate cell proliferation during mandibular fracture healing in rabbits.
Biochemical property of L-arginine (L-Arg)/nitric oxide synthase (NOS)/nitric oxide (NO) system was observed in rat brain mitochondria. The results showed that there existed L-Arg transporters of high-affinity, low-transport and saturability in mitochondria membrane of normal rat brain. The maximum transport velocity (V(max)) and Michaelis constant (Km) were 5.87+/ -0.46 nmol/mg pro x min(-1) and 7.8+/- 0.56 micromol/L respectively. In normal condition, endothelium-type NOS was expressed in the mitochondria of rat brain, with its V(max) and Km being 2.7+/-0.3 nmol/mg pro x min(- 1) and 20.85+/-3.27 micromol/L, respectively. NO production was increased in a time-dependent manner and reached a maximum value at 60 min. These results suggest that the L-Arg transporters in MT membrane of normal rat brain were similar with Y(+) type amino acid transporters in cellullar membrane. Furthermore the NOS of mitochondria belongs to eNOS, whereas the L-Arg/NOS/NO system may be a source of NO.
CD81, widely expressed on the surface of various human cells including hepatocytes, is a protein involved in intracellular signal transduction pathways. Recent studies suggested that human CD81 could specifically interact with hepatitis C virus (HCV) envelope protein E2. Therefore, CD81 has been identified as a putative cellular receptor for HCV. The HCV E2-CD81 interaction was considered a molecular mechanism contributing to HCV infection and pathogenicity. MAPK/ERK is characteristically associated with cell proliferation and hypertrophy. To investigate the effect of HCV on MAPK/ERK, human HepG2 cells were used in this study. CD81 expression on HepG2 cell surface was determined by flow cytometry with method of immunofluorescence. The cells were cultured in DMEM medium without fetal calf serum for 7 h, and then treated with HCV E2 protein at different time courses. Activation of MAPK/ERK in the cells was measured by Western blot, immunohistochemical and immunofluorescent analyses. Phosphorylation of MAPK/ERK was related to the concentration of HCV E2 proteins and to the time length of stimulation. MAPK/ERK in HepG2 cells was activated by HCV E2 protein, suggesting that HCV E2-CD81 interaction might be involved in intracellular signal transduction and might play an active role in HCV pathogenicity.
There are contradictory reports on the prevalence of bone fractures associated with long-term fluoride exposure from drinking water. The prevalence of bone fracture in six rural areas of China and the exposure of fluoride in drinking water was investigated. The data including medical history and demographic information, bone fractures, fluoride content in drinking water, physical activity, cigarette smoking, alcohol consumption and dietary intakes were collected. A retrospective epidemiological study by using the same design, method, quality control and the same questionnaire was conducted. A total of 8266 male and female over 50 years of age were divided into 6 groups by the fluoride concentrations in drinking water. The subjects in each group exposed to different levels of fluoride (0.25-0.34, 0.58-0.73, 1.00-1.06, 1.45-2.19, 2.62-3.58 and 4.32-7.97 mg/L) were 1363, 1407, 1370, 1574, 1051 and 1501 respectively. It has been confirmed that drinking water was the only major source of fluoride exposure in the studied populations. The total bone fracture rates were 7.41%, 6.40%, 5.11%, 6.04%, 6.09% and 7.40% in each group. Natural bone fracture rates in each group were 3.01%, 2.21%, 1.31%, 1.65%, 1.43% and 3.66% respectively. The prevalence of bone fracture and water fluoride level appeared a U-shaped relationship. The prevalence of total bone fracture and natural bone fracture in the population with fluoride 1.00-1.06 mg/L in drinking water was the lowest, compared with the groups exposed to fluoride higher than 4.32 mg/L and lower than 0.73 mg/L. The highest prevalence of hip fracture was in the group with higher water fluoride (4.32-7.97 mg/L) exposure. In general, the prevalence of hip fracture was lower and stable up to 1.06 mg/L of fluoride in drinking water, and then it appeared to rise. Based on the data collected in this investigation, it is concluded that the long-term fluoride exposure from drinking water higher than 4.32 mg/L might increase the risk of overall fractures as well as hip fractures. The risk of overall fractures and natural fractures might be lower while the water fluoride level is at 1.00-1.06 mg/L, however, no protective benefits of fluoride for the risk of hip fracture was observed.
OBJECTIVE: To introduce the clinical characteristics of maxillofacial vascular malformation with abnormal communication between external carotid and cranial arteries. METHODS: One hundred and twenty patients with maxillofacial vascular malformations had been studied by arteriography of internal and external carotid, and vertebral arteries before embolization of tumor supplying artery. Cases found to have communications between extra- and intra-cranial arteries were analyzed. RESULTS: Fourteen patients (11.67%, 14/120) were found to have abnormal communications between external carotid and cranial arteries. Among them, 11 patients demonstrated communications between occipital and vertebral arteries, 1 patient showed ascending pharyngeal artery and vertebral artery communication, and 2 patients showed maxillary artery-ophthalmic artery communication. CONCLUSION: Embolization of tumor supplying artery is a safe and practical method for the treatment of maxillofacial vascular malformation when done under digital subtraction angiography and superselective catheterization to avoid the abnormal communicant branches.
OBJECTIVE: To collect nationwide basic data about cancer related pain. METHODS: Sixty cancer patients in each province were randomly selected to participate in this survey. The subjects represented all stages of cancer, tumor sites, and different demographic characteristics. Two self-designed structured questionnaires including reasons, types of pain and pain management were used by patients and physicians respectively. Subjects were asked to report whether he/she had experienced any type of cancer related pain and filled out the equivalent questionnaire. The severity of pain was assessed by using "visual analogue scale". Original data input and analysis were using EPI-INFO software package. RESULTS: The result showed that 61.6% (958/1555) of patients had different types of cancer related pain. Majority of pain (85.1%) were caused by advanced cancer. The major reasons (64.4%) for poor management or impedimental factors of pain care are due to patient including over-concern on opioid analgesic addiction, reluctance to report pain or refused to use opioid analgesic until at times when pain is intolerable; 26.8% belonged to physician's reasons including fear to cause addiction on opioid and lack of knowledge about cancer pain management; 16.2% are due to lack of different kinds of opioid analgesic for use and 16.1% belonged to drug regulation. CONCLUSIONS: The results showed that majority of patients (61.6%) had different types of cancer related pain. In most of patients, cancer pain was relieved when they were treated. The major reason for under-treatment or impeded factors for effective relief of cancer pain was fear of opioid addiction by both medical professionals and patients.
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Experimental studies performed prior to 1990 led to the widely held belief that matrix metalloproteinases (MMPs) produced by cancer cells are of critical importance in tumor invasion and metastasis. Based on this evidence, the pharmaceutical industry produced several well tolerated, orally active MMP inhibitors (MMPIs) which demonstrated efficacy in mouse cancer models. Phase III clinical trials initiated in 1997-98 using marimastat, prinomastat (AG3340), and BAY 12-9566 alone or in combination with standard chemotherapy in patients with advanced cancers (lung, prostate, pancreas, brain, GI tract) have recently been reported; no clinical efficacy was demonstrated. Bayer and Agouron have discontinued their ongoing Phase III drug trials of MMPIs in advanced cancer. In retrospect, the failure of MMPIs to alter disease progression in metastatic cancer might have been anticipated since MMPs appear to be important in early aspects of cancer progression (local invasion and micrometastasis) and may no longer be required once metastases have been established. Our understanding of MMP pathophysiology in cancer has expanded considerably in the past 10 years. Current views indicate that: (1) most MMPs in tumors are made by stromal cells, not carcinoma cells; (2) cancer cells induce stromal cells to synthesize MMPs using extracellular matrix metalloproteinase inducer (EMMPRIN) and cytokine stimulatory mechanisms; and (3) MMPs promote cell migration and the release of growth factors sequestered in the extracellular matrix. MMPs have a dual function in tumor angiogenesis: MMP-2 and MT1-MMP are required in breaking down basement membrane barriers in the early stage of angiogenesis, while other MMPs are involved in the generation of an angiogenic inhibitor, angiostatin. In spite of considerable recent progress in identifying multiple roles of MMPs in disease, our understanding of MMP function in cancer is far from complete (see Table 1). Based on accumulated data, it is recommended that future MMPI trials focus on: (1) patients with early stage cancer; (2) the use of MMPIs along with chemotherapy; (3) the measurement of MMPs in tumor tissue and blood as a means of identifying patients who are more likely to respond to MMPI therapy; and (4) identification of biomarkers that reflect activation or inhibition of MMPs in vivo.
The growth hormone family of cytokines transduces intracellular signals through the Jak2-Stat5 pathway to activate the transcription of target genes. Amino acids within the C termini of Stats constitute the transactivation domain but also regulate the time course of tyrosine phosphorylation and extent of DNA binding. We mutated Thr(757) in the C-terminal of Stat5a (Thr-Stat5) to Val (Val-Stat5) and Asp (Asp-Stat5) and examined the effect on nuclear translocation, DNA binding, and prolactin-induced transcriptional activation of a Stat5-responsive luciferase reporter gene. Val-Stat5 produced a 5-fold higher increase in transcriptional activity relative to Thr-Stat5; Asp-Stat5 produced a similar response to Thr-Stat5. The increased transactivation was ligand induced and was not due to differences in basal expression of Val-Stat5 or to a constitutively activated Stat5 protein. Similar rates of loss of DNA binding ability and phosphorylation of Val- and Thr-Stat5 were observed following a single pulse of prolactin, indicating that the dephosphorylation pathways were unaltered. The serine-threonine kinase inhibitor H7 inhibited the transactivation potential of Thr-, Val-, and Asp-Stat5 to a similar extent, eliminating phosphorylation of Thr(757) as a regulatory mechanism. The results suggest that Thr(757) modulates the transactivation potential of Stat5 by a mechanism(s) that is dependent on the formation of Stat5 dimers and/or their nuclear translocation.
Synthesis of polygalacturonases in alkalophilic Bacillus sp. which is sensitive to rifampin, was clearly repressed by glucose. Mutants resistant to glucose catabolic repression were selected. From spontaneous mutants, NTT33-cs52 and NTT33-cs301 produced polygalacturonase activities 57.2 to 82.4% higher than the wild type.
It has been assumed that cleavage of the N-terminal propeptide domain of membrane type-1 matrix metalloproteinase (MT1-MMP) is required for enzyme function. We recently demonstrated that the propeptide domain of MT1-MMP is not cleaved and actually is required for function of the membrane-bound enzyme in transfected COS-1 cells (Cao, J., Drews, M., Lee, H. M., Conner, C., Bahou, W. F., and Zucker, S. (1998) J. Biol. Chem. 273, 34745-34752). In this report, we have inserted the cDNA encoding the signal and propeptide sequences of MT1-MMP (MT(1-109)) and the cDNA encoding propeptide-deleted mature MT1-MMP (MT delta pro) in expression vectors that were then transfected into matrix metalloproteinase-deficient COS-1 cells. Co-expression of both the mature sequence and the prosequence of MT1-MMP as independent polypeptides (in trans) in COS-1 cells resulted in reconstitution of MT1-MMP function in terms of facilitating (125)I-labeled tissue inhibitor of metalloproteinase 2 binding to transfected cells and subsequent activation of progelatinase A. Transfection of cells with either cDNA alone resulted in non-functional cells. These results are consistent with the propeptide sequence of MT1-MMP functioning as an intramolecular chaperone involved in protein folding and trafficking to the cell surface.
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Three [3]catenanes with cavities large enough to accommodate aromatic guests have been designed and synthesized (yields = 5-20 %) by means of kinetically controlled self-assembly processes. The X-ray structural analysis of one of three [3]catenanes confirmed the presence of a rectangular cavity (dimensions = 7 x 11 A) lined by pi-electron-rich recognition sites and hydrogen-bond acceptor groups. In spite of their apparently ideal recognition features, none of these [3]catenanes bind guests incorporating a pi-electron-deficient bipyridinium unit. However, the template-directed syntheses of the [3]catenanes also produce, in yields of 2-23%, [2]catenanes incorporating a 1,5-dioxynaphtho[38]crown-10 interlocked with a bipyridinium-based tetracationic cyclophane. The X-ray structural analyses of two of these [2]catenanes revealed that a combination of [pi...pi] and [C-H...pi] interactions is responsible for the formation of supramolecular homodimers in the solid state. 1H NMR spectroscopic investigations of the four [2]catenanes demonstrated that supramolecular homodimers are also formed (Ka= 17-31M(-1), T= 185 K) in (CD3)2CO solutions. Dynamic 1H NMR spectroscopy revealed that the 1,5-dioxynaphtho[38]crown-10 and tetracationic cyclophane components in the four [2]catenanes and in the three [3]catenanes circumrotate (deltaGc(not equal to) = 9-14 kcal mol(-1)) through each other's cavity in (CD3)2CO. Similarly, the 1,5-dioxynaphthalene and the bipyridinium ring systems rotate (deltaGc(not equal to) =10-14 kcal mol(-1)) about their [O...O] and [N...N] axes, respectively, in solution.