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Biomedical subjects

M Wu

Publications and source records attributed to M Wu.

At least 307 records · Page 17Linked to original sources
PubMed1997

Postoperative immunotherapy for patients with hepatocarcinoma using tumor-infiltrating lymphocytes.

OBJECTIVE: To explore a more effective immunotherapy for cancer by studying tumor-infiltrating lymphocytes (TIL) of patients with hepatocarcinoma. METHODS: TIL isolated from freshly resected tumors of 12 patients with hepatocarcinomas were activated, expanded and cultured in vitro by incubation with interleukin-2, and then infused to the patients. The TIL cytotoxicity and phenotype were determined by MTT and immunohistochemical ABC methods. RESULTS: The average weight and number of cells of the tumor tissues for culture of TIL were 4.8 g and 5.8 x 10(7) respectively, and the median expansion time was 31.8 days in vitro. The maximal expansion achieved 1000 fold, and the mean amplification rate was 198.5 fold. Lymphokine-activated killer cell culture supernatant could stimulate TIL growth. Ten of 12 patients received immunotherapy of TIL. The number of cells infused reached 4 x 10(8)-1.1 x 10(10). In 3 cases of our series, TIL infusions were done through a drug pump with a catheter embedded in the hepatic artery. Eight patients whose primary hepatic carcinomas were resected completely were followed up for 16 months with only one case (12.5%) having recurrence. The recurrence rates of them at 6 and 12 months after tumor resection were remarkably lower than those of the patients who did not receive TIL infusion (19.4% and 41.6%, respectively). One patient whose tumor was not able to be removed received TIL infusion twice and local alcohol injection several times. He has been alive for 9 months. CONCLUSIONS: TIL isolated from the tumors of patients with hepatocarcinoma can be activated and expanded in vitro. It demonstrated remarkably cytotoxic activity against tumor targets. TIL infusion is an effective immunotherapy for patients with hepatocarcinoma in reducing recurrence after operation.

Adult↗
PubMed1997

[The effects of vibratory acoustic stimulation on fetal heart rate and body movement of normal fetuses at different gestational ages].

OBJECTIVE: To study the effects of vibratory acoustic stimulation (VAS) on fetal heart rate (FHR) and fetal movement (FM) of normal fetu at different gestational ages. METHOD: 435 normal second and third-trimester pregnancies were studied using real time ultrasonography. FHR baseline was recorded. Then a five-second VAS was given and FM and (or) FHR was observed. The results of vibroacoustic stimulation testing (VAS-T), sound-provoked fetal movement (SPFM) and the amplitude of FHR acceleration were evaluated. RESULTS: (1) The fetus started to response to VAS from the 24th gestational week, but most could not reach the diagnostic criteria of VAS-T. The responses of FM were normal. (2) From 28 week on, 90% of the fetu showed marked FM and acceleration of FHR after VAS. Over 98% of the term babies were reactive. (3) The detective rates of SPFM appeared significantly earlier than that of VAS-T. CONCLUSION: It suggested that the development of fetal nervous system was matured at 28 weeks, and the development of motor nerves was earlier than that of the autonomic nerves.

Acoustic Stimulation↗
PubMed1997

Identification of a novel missense mutation in Wilson's disease gene.

OBJECTIVE: To investigate the allelic heterogeneity of the ATP7B gene in Chinese patients with Wilson's disease (WD). METHODS: Exons of the ATP7B gene from 141 WD patients' DNA were amplified with polymerase chain reaction (PCR) 887-890. Mutations were then screened by single strand conformation polymorphism (SSCP) analysis and further identified by sequencing. RESULTS: The molecular structure of exon 7 of the ATP7B gene from 141 WD patients was analyzed. The same band shift in electrophoretic pattern of 4 cerebral type patients was identified with SSCP and subsequently sequenced. The results showed missense mutation at the second base of the codon as Ser 662 Cys, which is caused by a C to G transversion. CONCLUSIONS: Mutations of the ATP7B gene were investigated for the first time in China and a novel missense mutation was identified in four cases.

Adolescent↗
PubMed1996

Subpallidal outputs to the nucleus accumbens and the ventral tegmental area: anatomical and electrophysiological studies.

The goal of this study was to investigate the functional organization of the subpallidal-->accumbens direct and indirect feedback loops by both anatomical and electrophysiological methods. The results of the dextran-conjugated rhodamine injections into the subpallidal area has shown three distinct projections: (1) a substantial pathway from the subpallidal area to the ventral tegmental area, (2) a more diffuse rostral projection from the subpallidal area to the core area of the nucleus accumbens, and (3) a sparse pathway projecting rostrodorsally from the subpallidal area toward the thalamic regions. Electrical or chemical stimulation of the subpallidal region, which was studied by the axonal tracer, evoked inhibitory responses in the majority (60 and 80%, respectively) of the accumbens and ventral tegmental area neurons in a standard extracellular recording study. Less than 1/3 of the accumbens or ventral tegmental area cells showed an increase in the mean firing rate. The majority (77.5%) of all responded neurons had a latency of less than 10 ms. Furthermore, injection of glutamate into the subpallidal area not only altered the firing pattern of the accumbens neurons, but also attenuated their excitatory responses elicited by the electrical stimulation of the ventral subiculum. Our results indicate that the subpallidal area plays a predominantly inhibitory role in the ventral tegmental area-accumbens-subpallidal circuitry, presumably by its GABAergic projections, and may also modulate subicular input into the nucleus accumbens.

Animals↗
PubMed1996

Inhibition of NF-kappaB/Rel induces apoptosis of murine B cells.

Apoptosis of the WEHI 231 immature B cell lymphoma line following membrane interaction with an antibody against the surface IgM chains (anti-IgM) is preceded by dramatic changes in Nuclear Factor-kappaB (NF-kappaB)/ Rel binding activities. An early transient increase in NF-kappaB/Rel binding is followed by a significant decrease in intensity below basal levels. Here we have explored the role of these changes in Rel-related factors in B cell apoptosis. Treatment of WEH1 231 cells with N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), a protease inhibitor which prevents degradation of the inhibitor of NF-kappaB (IkappaB)-alpha, or with low doses of pyrrolidinedithiocarbamate (PDTC) selectively inhibited NF-kappaB/Rel factor binding and induced apoptosis. Bcl-XL expression protected WEHI 231 cells from apoptosis induced by these agents. Microinjection of WEHI 231 cells with either IkappaB-alpha-GST protein or a c-Rel affinity-purified antibody induced apoptosis. Ectopic c-Rel expression ablated apoptosis induced by TPCK or anti-IgM. Treatment of BALENLM 17 and A20 B lymphoma cells or normal murine splenic B lymphocytes with either TPCK or PDTC also resulted in apoptosis. These findings indicate that the drop in NF-kappaB/Rel binding following anti-IgM treatment activates apoptosis of WEHI 231 cells; furthermore, they implicate the NF-kappaB/Rel family in control of apoptosis of normal and transformed B cells.

Animals↗
PubMed1996

Tracing the auditory pathways to electrophysiologically characterized neurons with HRP and Fos double-labeling technique.

By combining HRP histochemistry with Fos immunocytochemistry, we demonstrate in this study that electrophysiologically characterized auditory neurons can be double-labeled with HRP and Fos after iontophoretic injection of HRP into the recording site. Neurons which projected fibers to the recording site were labeled with HRP and were Fos-like immunoreactive. This double-labeling technique in combination with electrophysiological recording offers the possibility to determine the fiber projections between sound-activated neurons which are identified either electrophysiologically and/or immunocytochemically.

Animals↗
PubMed1996

Solution structure of (rGCGGACGC)2 by two-dimensional NMR and the iterative relaxation matrix approach.

The three-dimensional solution structure of the RNA self-complementary duplex [sequence: see text] was derived from two-dimensional NMR and the iterative relaxation matrix approach. Each GA mismatch forms two hydrogen bonds: A-NH6 to G-O6 and A-N1 to G-NH1 (imino). This is the first three-dimensional RNA structure with imino hydrogen-bonded tandem GA mismatches. This GA structure is totally different from the sheared tandem GA structure in [sequence: see text] which also has two hydrogen bonds: A-N7 to G-NH2 and A-NH6 to G-N3 [SantaLucia, J., Jr., & Turner, D. H. (1993) Biochemistry 32, 12612-12623]. In particular, the sheared and imino GA mismatches produce a narrowing and widening of the backbone, respectively. The results show that substitutions of Watson-Crick base pairs can have dramatic effects on the three-dimensional structures of adjacent non-Watson-Crick paired regions; i.e., the structure depends on sequence context. Thus compensating substitutions in site-directed mutagenesis experiments may not always restore biological activities.

Base Sequence↗
PubMed1996

Down-regulation of the expression of the obese gene by an antidiabetic thiazolidinedione in Zucker diabetic fatty rats and db/db mice.

Obese (ob) is a recently identified gene involved in the regulation of energy balance in the mouse. We report here that AD-5075, a potent thiazolidinedione which lowered plasma glucose and triglyceride in Zucker diabetic fatty (ZDF) rats and db/db mice, decreased the expression of the ob gene in these animal models of obesity and non-insulin-dependent diabetes mellitus. The level of adipose ob mRNA in ZDF rats was 3-fold greater than that detected in the Zucker lean littermates. Chronic treatment with AD-5075 elicited a 67 and 70% reduction of ob mRNA in ZDF and control lean rats, respectively. Furthermore, the amount of adipose ob mRNA in db/db mice was 7 times higher than that detected in lean littermates. Treatment of db/db mice with AD-5075 resulted in a 78% reduction of the level of ob mRNA with parallel changes in circulating level of the ob gene product, leptin. The reduction of the ob mRNA in the Zucker lean rats was accompanied by significantly greater food intake and weight gain. However, in ZDF rats and db/db mice, there was profound increase in body weight without hyperphagia. The results demonstrate that the expression of the ob gene is up-regulated in these two rodent models of diabetes compared to their lean counterparts and that such overexpression is attenuated by treatment with an agent that improves insulin sensitivity and glucose homeostasis in vivo.

Adipose Tissue↗
PubMed1996

FLX1 codes for a carrier protein involved in maintaining a proper balance of flavin nucleotides in yeast mitochondria.

Respiratory defective mutants of Saccharomyces cerevisiae previously assigned to complementation group G178 are characterized by an abnormally low ratio of FAD/FMN in mitochondria. A nuclear gene, designated FLX1, was selected from a yeast genomic library, based on its ability to confer wild-type growth properties to a representative G178 mutant. Genetic evidence has confirmed that the flavin nucleotide imbalance of G178 mutants is caused by mutations in FLX1. The sequence of FLX1 is identical to a reading frame recently reported to be present on yeast chromosome IX (GenBank Z47047). The sequence and tripartite repeat structure of the FLX1 product (Flx1p) indicate it is a member of a protein family consisting of mitochondrial substrate and nucleotide carriers. In yeast, FAD synthetase is present in the soluble cytoplasmic protein fraction but not in mitochondria. Riboflavin kinase, the preceding enzyme in flavin biosynthesis, is present in both subcellular fractions. The absence of FAD synthetase in mitochondria implies that FAD is imported from the cytoplasm. The lower concentration of mitochondrial FAD in flx1 mutants suggests that Flx1p is involved in flavin transport, a role that is also supported by biochemical evidence indicating more efficient flux of FAD across mitochondrial membrane vesicles prepared from wild-type strains than membrane vesicles from flx1 mutants.

Alleles↗
PubMed1996

Neural tube defects and abnormal brain development in F52-deficient mice.

F52 is a myristoylated, alanine-rich substrate for protein kinase C. We have generated F52-deficient mice by the gene targeting technique. These mutant mice manifest severe neural tube defects that are not associated with other complex malformations, a phenotype reminiscent of common human neural tube defects. The neural tube defects observed include both exencephaly and spina bifida, and the phenotype exhibits partial penetrance with about 60% of homozygous embryos developing neural tube defects. Exencephaly is the prominent type of defect and leads to high prenatal lethality. Neural tube defects are observed in a smaller percentage of heterozygous embryos (about 10%). Abnormal brain development and tail formation occur in homozygous mutants and are likely to be secondary to the neural tube defects. Disruption of F52 in mice therefore identifies a gene whose mutation results in isolated neural tube defects and may provide an animal model for common human neural tube defects.

Animals↗
PubMed1996

Genetic alterations on chromosomes 3 and 9 of esophageal cancer tissues from China.

In previous studies, we had demonstrated that allelic losses in esophageal cancer (EC) tissues are frequently involved in chromosomes 3 and 9 and that EC patients and their blood relatives have low capacity to repair damaged DNA and showed genetic instability. To better define the deleted chromosomal loci and understand the genetic instability in EC tissues, we selected 12 microsatellite markers (D3S1232, D3S1238, D3S1289, D3S1480, D3S647, D3S966, D3S1317, D3S659, D9S156, D9S171, D9S176 and GSN) to examine 36 paired EC tissues for loss of heterozygosity (LOH) and microsatellite instability (MIN) on chromosomes 3 and 9. The frequent LOH was found at D9S156(9p21), D3S647(3p23) and D3S1480(3p14.2), implying the possible existence of tumor suppressor genes near the deleted loci. Higher LOH incidence at D9S156 (9/18) and D3S1480 (8/19) was observed in EC tissues from Beijing, a low EC area. More frequent LOH at D3S647 (6/14) was found in EC tissues from Yangquan, a high EC area. This geographic difference of LOH occurrence was indicative of genetic heterogeneity in the etiology of EC. 24 of 36 (66.7%) EC tissues showed MIN at one or more chromosomal loci. The putative EC suppressor genes on chromosomes 3 and 9 and the molecular basis of the genetic instability associated with EC remain to be elucidated.

Alleles↗
PubMed1996

TGF beta 1 inhibits NF-kappa B/Rel activity inducing apoptosis of B cells: transcriptional activation of I kappa B alpha.

TGF beta 1 treatment of B cell lymphomas decreases c-myc gene expression and induces apoptosis. Since we have demonstrated NF-kappa/Rel factors play a key role in transcriptional control of c-myc, we explored the effects of TGF beta1 on WEHI 231 immature B cells. A reduction in NF-kappa B/Rel activity followed TGF beta 1 treatment. In WEHI 231 and CH33 cells, we observed an increase in I kappa B alpha, a specific NF-kappa B/Rel inhibitor, due to transcriptional induction. Engagement of surface CD40 or ectopic c-Rel led to maintenance of NF-kappa B/Rel and c-Myc expression and protection of WEHI 231 cells from TGF beta 1-mediated apoptosis. Ectopic c-Myc expression overrode apoptosis induced by TGF beta 1. Thus, downmodulation of NF-kappa B/Rel reduces c-Myc expression, which leads to apoptosis in these immature B cell models of clonal deletion. The inhibition of NF-kappa B/Rel activity represents a novel TGF beta signaling mechanism.

Animals↗