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Biomedical subjects

H Min

Publications and source records attributed to H Min.

At least 19 recordsLinked to original sources

Therapeutic vaccination against metastatic carcinoma by expression-modulated and immunomodified autologous tumor cells: a first clinical phase I/II trial.

Therapeutic vaccination of tumor patients with cytokine gene-transfected tumor cells leads to tumor regression in animal models but has so far not resulted in significant clinical benefit. We and others demonstrated that tumor cells transfected to mediate overexpression of a cytokine gene activate immunologic effector cells for an improved proliferation rate and significantly higher antitumoral cytotoxic activity. Here, we performed a pilot study of therapeutic vaccination in patients with metastatic disease. Autologous tumor cells were simultaneously transfected with novel minimalistic, immunogenically defined, gene expression constructs (MIDGE) for overexpression of the two cytokines interleukin 7 (IL-7) and GM-CSF and newly designed double stem-loop immunomodulating oligodeoxyribonucleotides (d-SLIM) as a Th1-promoting and NK cell-stimulating adjuvant. Transfection was performed ex vivo by ballistomagnetic gene transfer. Patients received four subcutaneous injections of at least 1 x 10(6) of their expression-modulated and immunomodified autologous tumor cells. Ten patients have been enrolled in the study protocol. In all patients no adverse effects could be detected. IL-7 and interferon gamma levels were elevated in the serum of the patients after treatment. Interestingly, cytotoxicity of patient-derived PBLs increased significantly during treatment. All 10 patients had progressive disease when entering our protocol. One complete, one partial, and one mixed response with progression of abdominal metastases and regression of lung metastases were observed. Two patients showed a stable disease after treatment and five patients remained in progressive disease. Our observations confirm the capability of autologous expression-modified and immunomodulated tumor cell vaccines to stimulate a strong immune response in patients with metastatic cancer even in the presence of a large tumor burden.

Aged↗

Effects of butachlor on microbial populations and enzyme activities in paddy soil.

This paper reports the influences of the herbicide butachlor (n-butoxymethlchloro -2', 6'-diethylacetnilide) on microbial populations, respiration, nitrogen fixation and nitrification, and on the activities of dehydrogenase and hydrogen peroxidase in paddy soil. The results showed that the number of actinomycetes declined significantly after the application of butachlor at different concentrations ranging from 5.5 microg g(-1) to 22.0 microg g(-1) dried soil, while that of bacteria and fungi increased. Fungi were easily affected by butachlor compared to the bacteria. The growth of fungi was retarded by butachlor at higher concentrations. Butachlor however, stimulated the growth of anaerobic hydrolytic fermentative bacteria, sulfate-reducing bacteria (SRB) and denitrifying bacteria. The increased concentration of butachlor applied resulted in the higher number of SRB. Butachlor inhibited the growth of hydrogen-producing acetogenic bacteria. The effect of butachlor varied on methane-producing bacteria (MPB) at different concentrations. Butachlor at the concentration of 1.0 microg g(-1) dried soil or less than this concentration accelerated the growth of MPB, while at 22.0 microg g(-1) dried soil showed an inhibition. Butachlor enhanced the activity of dehydrogenase at increasing concentrations. The soil dehydrogenase showed the highest activity on the 16th day after application of 22.0 microg g(-1) dried soil of butachlor. The hydrogen peroxidase could be stimulated by butachlor. The soil respiration was depressed during the period from several days to more than 20 days, depending on concentrations of butachlor applied. Both the nitrogen fixation and nitrification were stimulated in the beginning but reduced greatly afterwards in paddy soil.

Acetanilides↗

[Value of regional intra-arterial induction chemotherapy for locally advanced nasopharyngeal carcinoma].

OBJECTIVE: To define the value of regional intra-arterial induction chemotherapy for locally advanced nasopharyngeal carcinoma (NPC). METHODS: 121 locally advanced NPC(stage III-IV) patients confirmed by pathology were randomly divided into two groups before radiation, and the two groups were given two different methods of chemotherapy: regional intra-arterial chemotherapy (IACT) and systemic chemotherapy (SCT). After radiation the effect of two methods was compared. RESULTS: The complete response rates were 27.9% in the IACT and 11.7% in the SCT, and 5 years survival rates were 63.9% in the IACT and 45.0% in the SCT respectively. The differences of two groups were significant. CONCLUSION: IACT is more reasonable than SCT as induction chemotherapy for these locally advanced NPC.

Adolescent↗

Osteoprotegerin reverses osteoporosis by inhibiting endosteal osteoclasts and prevents vascular calcification by blocking a process resembling osteoclastogenesis.

High systemic levels of osteoprotegerin (OPG) in OPG transgenic mice cause osteopetrosis with normal tooth eruption and bone elongation and inhibit the development and activity of endosteal, but not periosteal, osteoclasts. We demonstrate that both intravenous injection of recombinant OPG protein and transgenic overexpression of OPG in OPG(-/-) mice effectively rescue the osteoporotic bone phenotype observed in OPG-deficient mice. However, intravenous injection of recombinant OPG over a 4-wk period could not reverse the arterial calcification observed in OPG(-/-) mice. In contrast, transgenic OPG delivered from mid-gestation through adulthood does prevent the formation of arterial calcification in OPG(-/-) mice. Although OPG is normally expressed in arteries, OPG ligand (OPGL) and receptor activator of NF-kappaB (RANK) are not detected in the arterial walls of wild-type adult mice. Interestingly, OPGL and RANK transcripts are detected in the calcified arteries of OPG(-/-) mice. Furthermore, RANK transcript expression coincides with the presence of multinuclear osteoclast-like cells. These findings indicate that the OPG/OPGL/RANK signaling pathway may play an important role in both pathological and physiological calcification processes. Such findings may also explain the observed high clinical incidence of vascular calcification in the osteoporotic patient population.

Acid Phosphatase↗

A new circadian class 2 gene, opcA, whose product is important for reductant production at night in Synechococcus elongatus PCC 7942.

Gene expression in the cyanobacterium Synechococcus elongatus PCC 7942 is under the control of a circadian oscillator, such that peaks and troughs of expression recur with a periodicity of about 24 h in the absence of environmental cues. This can be monitored easily as light production from luciferase gene fusions to S. elongatus promoters. All promoters seem to exhibit circadian oscillation of expression, but the phasing of peak and trough times differs among different genes. The majority of genes are designated class 1, with expression peaks near dusk or subjective dusk (the time corresponding to dusk in the absence of a diurnal cycle). A minority, of which purF is an example, have expression peaks approximately 12 h out of phase with class 1 genes. A screen of Tn5 mutants for those in which purF phasing is altered revealed a mutant that carries an insertion in the opcA gene, previously identified as essential for glucose-6-phosphate dehydrogenase function. However, a different enzymatic reporter and in vitro luciferase assays revealed that the expression pattern of the purF promoter is not altered by opcA inactivation, but rather the reduced flavin mononucleotide substrate of luciferase is limiting at the time of the natural circadian peak. The results suggest that OpcA is involved in temporally separated reductant-generating pathways in S. elongatus and that it has a role outside of its function in activating glucose-6-phosphate dehydrogenase. The opcA gene, expected to be cotranscribed with fbp and zwf, was shown to have its own class 2 promoter, whereas the fbp promoter was determined to be in class 1. Thus, opcA expression is likely to be constitutive by virtue of the activity of two promoters in nearly opposite circadian phases.

Circadian Rhythm↗

Promotion of insecticide-treated mosquito nets in Myanmar.

A simple health promotion message administered by village midwives raised bednet usage to over 60% in trial hamlets in north Shan State, Myanmar. Treatment of the nets in the study villages produced a reduction in malaria cases. Most villagers were prepared to buy their nets at market prices and were willing to pay for the cost of re-treatment of nets, but very poor, members of the Wa ethnic group required a half-price subsidy for them to afford them. The use of insecticide treated bednets was felt to be appropriate for undeveloped and remote areas of the country where malaria control was difficult.

Adolescent↗

Differentially expressed protein Pdcd4 inhibits tumor promoter-induced neoplastic transformation.

An mRNA differential display comparison of mouse JB6 promotion-sensitive (P+) and -resistant (P-) cells identified a novel gene product that inhibits neoplastic transformation. The JB6 P+ and P- cells are genetic variants that differ in their transformation response to tumor promoters; P+ cells form anchorage-independent colonies that are tumorigenic, and P- cells do not. A differentially displayed fragment, A7-1, was preferentially expressed in P- cells at levels >/=10-fold those in P+ cells, making its mRNA a candidate inhibitor of neoplastic transformation. An A7-1 cDNA was isolated that was identical to murine Pdcd4 gene cDNAs, also known as MA-3 or TIS, and analogous to human H731 and 197/15a. Until now, the function of the Pdcd4 protein has been unknown. Paralleling the mRNA levels, Pdcd4 protein levels were greater in P- than in P+ cells. Pdcd4 mRNA was also expressed at greater levels in the less progressed keratinocytes of another mouse skin neoplastic progression series. To test the hypothesis that Pdcd4 inhibits tumor promoter-induced transformation, stable cell lines expressing antisense Pdcd4 were generated from parental P- cells. The reduction of Pdcd4 proteins in antisense lines was accompanied by acquisition of a transformation-sensitive (P+) phenotype. The antisense-transfected cells were reverted to their initial P- phenotype by overexpression of a Pdcd4 sense fragment. These observations demonstrate that the Pdcd4 protein inhibits neoplastic transformation.

Animals↗

Mapping of the KHSRP gene to a region of conserved synteny on human chromosome 19p13.3 and mouse chromosome 17.

The K homology-type splicing regulatory protein, KSRP, activates splicing through intronic splicing enhancer sequences. It is highly expressed in neural cells and is required for the neural-specific splicing of the c-src N1 exon. In this study, we mapped the gene (gene symbols KHSRP and Khsrp) to human chromosome 19 by using radiation hybrid panels and to mouse chromosome 17 by studying an interspecific backcross panel. Human KHSRP is a positional candidate gene for familial febrile convulsion and Cayman type cerebellar ataxia. Comparative analysis of the human and mouse genomes indicates that the KHSRP gene is located in regions of conserved synteny between the two species.

Alternative Splicing↗

Non-association of estrogen receptor genotypes with bone mineral density and bone turnover in Korean pre-, peri-, and postmenopausal women.

Estrogen is known to play a critical role in both skeletal maturity and the rate of bone loss. This suggests the possibility that the estrogen receptor (ER) gene is one of the candidate genes that determines peak bone density and/or bone turnover rate. We investigated two established restriction fragment length polymorphisms (RFLPs) in intron 1 at the ER gene, represented as PvuII and XbaI. In 598 healthy Korean women aged 20-74 years, we examined the association of these ER genotypes with bone mineral density (BMD) and bone turnover status. The distribution of the PvuII and XbaI RFLPs was as follows: pp 205 (34.3%), Pp 308 (51.5%), PP 85 (14.2%) and xx 384 (64.2%), Xx 180 (30.1%), XX 34 (5.7%), respectively (where capital letters signify the absence of, and lower-case letters signify the presence of, the restriction site of each RFLP). No significant genotypic differences were found in BMD and bone markers. We grouped the subjects into three categories according to their menstrual status: 104 premenopausal women with regular menstruation, 182 perimenopausal women who had amenorrhea of not less than 3 months and not more than 12 months' duration, and 312 postmenopausal women whose last menstruation was at least 12 months previously. No significant genotypic difference in either BMD or bone markers was found in any of these three groups. Furthermore we categorized women in peri- and postmenopause into a high loser group and a normal loser group according to the level of bone resorption markers. There was no difference in genotypic proportions between the high and normal loser groups. Our data suggest that these ER polymorphisms are not associated with BMD or bone turnover in Korean women.

Absorptiometry, Photon↗

[Study on the posterior vitreous detachment in patients with high myopia].

OBJECTIVE: To access the development of posterior vitreous detachment(PVD) related to age, axial length of the eye, vitreous changes as well as the myopic chorioretinal manifestation in patients with high myopia. METHODS: The vitreous status of 61 consecutive patients with high myopia(> or = -8.0 D and axial length > or = 26.0 mm) 110 eyes and 68 controls (< or = -3.0 D) 119 eyes were examined with biomicroscopic slit lamp and B-scan ultrasound. The myopic chorioretinal changes at the posterior pole were examined by indirect ophthalmoscope. The axial length of the eye was measured by A-scan ultrasound. The incidence of PVD was evaluated by Chi-square test. RESULTS: The incidence of PVD in patients with high myopia increased with age. Its overall incidence was significantly higher than that in the controls (78.2% vs 31.1%, P < 0.001). In addition, the onset of PVD in patients with high myopia occurred much earlier in age than that in the control group. Axial length was an important factor responsible for the development of PVD in patients with high myopia. The incidence of PVD and age were highly correlated (r = 0.9997, P < 0.05). Retinal detachment occurred in 5 eyes in the patients with high myopia. CONCLUSIONS: The results in the present study suggested that the incidence of PVD in patients with high myopia, increased with axial length of the eye and age. Vitreous changes are characteristic findings associated with high myopia, which was also involved in the development of PVD.

Adult↗

Fgf-10 is required for both limb and lung development and exhibits striking functional similarity to Drosophila branchless.

Fgf-10-deficient mice (Fgf-10(-/-)) were generated to determine the role(s) of Fgf-10 in vertebrate development. Limb bud initiation was abolished in Fgf-10(-/-) mice. Strikingly, Fgf-10(-/-) fetuses continued to develop until birth, despite the complete absence of both fore- and hindlimbs. Fgf-10 is necessary for apical ectodermal ridge (AER) formation and acts epistatically upstream of Fgf-8, the earliest known AER marker in mice. Fgf-10(-/-) mice exhibited perinatal lethality associated with complete absence of lungs. Although tracheal development was normal, main-stem bronchial formation, as well as all subsequent pulmonary branching morphogenesis, was completely disrupted. The pulmonary phenotype of Fgf-10(-/-) mice is strikingly similar to that of the Drosophila mutant branchless, an Fgf homolog.

Animals↗

Tumor promoter induces high mobility group HMG-Y protein expression in transformation-sensitive but not -resistant cells.

Elevated levels of high mobility group (HMG) nonhistone chromosomal proteins I and Y, alternatively spliced members of the HMG-I(Y) family of architectural transcription factors, have been linked with human cancer and with neo-plastic and metastatic phenotypes in model systems. To investigate whether HMG-I(Y) proteins may influence susceptibility to neoplastic transformation, HMG-I(Y) mRNA and protein levels were compared in the JB6 murine model of neoplastic progression. HMG-I(Y) mRNAs were expressed at very low levels in preneoplastic, transformation-resistant (P-) cell lines and were constitutively expressed at much higher levels in both transformation-sensitive (P +) and transformed (Tx) tumorigenic cell lines. HMG-I(Y) mRNAs were induced to higher levels by the tumor promoter 12-O-tetradecanoylphorbol acetate (TPA) and were sustained longer in P+ than in P- cells. Nevertheless, in both P- and P+ cells, primer extension analysis revealed that the same four major HMG-I(Y) gene transcription start sites were utilized with or without TPA treatment. RT-PCR revealed that there was always slightly more Y than I form mRNA present in all of the variant JB6 cell lines. Immunoblotting indicated that both HMG-I and -Y proteins increased in P + cells in response to TPA treatment. Remarkably, in P- cells treated with TPA, only HMG-I (and not HMG-Y) protein levels increased. This unique differential TPA-induction of the HMG-Y protein in JB6 variants suggests a role for HMG-Y in mediating tumor promoter-induced neoplastic transformation. Furthermore, these results demonstrate that HMG-I and Y protein translation and/or stability is differently regulated in JB6 P- cells and provide the first indication that I and Y proteins may have different functions.

Alternative Splicing↗

[Preliminary study on the correlation between neovasculature and metastatic nasopharyngeal carcinoma by computer image analysis].

OBJECTIVE: To investigate the significance of neoangiogenesis in metastasis of nasopharyngeal carcinoma (NPC) so as to clarify further the role of neovascularity in evaluating the prognosis of NPC and the probability of antiangiogenesis in preventing distant metastasis of NPC. METHODS: Fifty-two patients with metastatic NPC were selected and strictly matched in sex, age, T stage, and N stage with another 52 patients with non-metastatic NPC and survived a long time. The tumor tissues of all 104 patients were retrived for computer-assisted, immunohistochemical analysis of tumor vasculature. RESULTS: Counts of microvessel and relative area of all microvessels per image were significantly higher in metastatic NPCs than those of curable, non-metastatic NPCs; while average area of microvessel and average perimeter of microvessel in metastatic NPCs were smaller than those of the opposite. No significant difference in any microvessel parameter had been found among various types of metastasis. CONCLUSIONS: The alterations of microvessel parameters bore significant relationships with metastases of NPC. Evaluation of neovascularity with computer image analysis may help in estimating the prognosis of NPC and in finding out the indications for aggressive multimodal treatments. Angiogenesis inhibitors might be helpful in preventing NPC from distant metastasis.

Adult↗

[Studies on fermentation conditions of cytokinin produced by rhizobia strain 4012a].

The conditions of cytokinin fermentation of the rhizobia strain 4012a were detected by the ELISA. The results indicated that the optimal medium for cytokinin production by strain 4012a was composed of glucose 10 g/L, (NH4)2SO4 1.0, K2HPO4.3H2O 0.6, MgSO4.7H2O 0.1, CaCl2.2H2O 0.4, FeCl3.6H2O 0.04, Na2MoO4.2H2O 0.1 mg/L, calcium pantothenate 100 micrograms/L, adenine 200 mg/L. When strain 4012a was grown in 250 ml flask containing 50 ml of the medium on the rotary shaker (150 r/min) at 27 degrees C for 96 h, the yield of CTK 908 micrograms/L culture solution was obtained. It displayed bioactivity kinetin equivalents (KE) 1 mg/L medium with the radish cotyledon expansion test.

Culture Media↗

[A study on microbiological characteristics of upflow anaerobic filter].

This experiment was conducted to study the relationship between performance and bacterial population in upflow anaerobic filter by improved Hungate technique. The results obtained showed as follows: (1) There existed correlation closely between the bacterial population, COD and volatile fatty acids removal; (2) The bacterial population was affected to a small extent by the change of organic loading rate in short time and suspending performance; (3) Successful performance of the reactor depended on the microbes' composition and their coordinated metabolism.

Bacteria, Anaerobic↗