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W Zhao

Publications and source records attributed to W Zhao.

At least 19 recordsLinked to original sources
PubMed2003

Interleukin 10 induced augmentation of delayed-type hypersensitivity (DTH) enhances Mycobacterium bovis bacillus Calmette-Guérin (BCG) mediated antitumour activity.

Intravesical BCG therapy is effective in the treatment of superficial bladder cancer. Both clinical and experimental results suggest a role for cytokines and delayed-type hypersensitivity (DTH) in BCG-induced antitumour immunity. We characterized the modulatory effects of BCG on bladder cytokine expression and determined the relationship between DTH and BCG antitumour activity. The bladders of mice were instilled with BCG through a catheter. Bladder tissue RNA and urine were collected for evaluation of cytokine expression using reverse transcriptase-polymerase chain reaction (RT-PCR) and/or ELISA. IFN-gamma and TNF-alpha, the two major cytokines associated with DTH, were efficiently induced by BCG. IL10, an important down-regulator of DTH, was also induced by BCG. Constitutive levels of IL4 and IL5 were observed, but neither IL4 nor IL5 were modulated by BCG. Similar results were observed in the kinetic analysis of urinary cytokines in patients after intravesical BCG therapy. Production of Th1 (T helper type 1) cytokines (IFN-gamma, IL2 and IL12) preceded that of the Th2 (T helper type 2) cytokine IL10. A tendency toward higher ratios of IFN-gamma versus IL10 for BCG responders also was observed. In animal studies the absence of IL10 abrogated either by antibody inhibition or the use of genetically modified, IL10 deficient (IL10-/-) mice resulted in enhanced DTH responses. Under conditions of enhanced DTH, a significant enhancement in antitumour activity was observed. These data demonstrate that DTH and its associated mononuclear infiltration and cytokine production are important to the antitumour activity of intravesical BCG therapy, and suggest that effects to diminish IL10 production may have therapeutic value.

Animals↗
PubMed2003

The successful long-term treatment of age related erectile dysfunction with hSlo cDNA in rats in vivo.

PURPOSE: We have previously reported that 1 intracorporeal injection of 100 microg hSlo/pcDNA reversed the effect of aging on erectile function in a rat model in vivo for at least 2 months. We report our further investigations of the amplitude, duration and physiological relevance of this novel gene transfer approach. MATERIALS AND METHODS: A total of 191 retired breeder Sprague-Dawley rats were given a single intracavernous injection of phosphate buffered saline, 1,000 microg pcDNA, or 10, 100 or 1,000 microg pcDNA/hSlo. The animals were studied 1 to 6 months after injection. The intracorporeal pressure (ICP) response to cavernous nerve stimulation and immunostaining as well as hematoxylin and eosin staining were done to evaluate effector nerve integrity and tissue histology, respectively. RESULTS: Gene transfer prevented an age related decrease in resting ICP and a physiologically relevant, significant effect on normalizing erection in vivo, as determined by submaximal (0.5 mA) and maximal (4.0 mA) cavernous nerve stimulation. The effects were observed 1 month after transfection and sustained for 6 months at the 100 and 1,000 microg doses of pcDNA/hSlo (p <0.026). CONCLUSIONS: The physiological manifestations of gene transfer were detected as an amelioration of the age related decrease in resting ICP, and parallel increase in the magnitude of the cavernous nerve stimulated an ICP response to a level at which visible erections were again observed in this rat model of aging in vivo.

Animals↗
PubMed2003

Long-term treatment with sterigmatocystin, a fungus toxin, enhances the development of intestinal metaplasia of gastric mucosa in Helicobacter pylori-infected Mongolian gerbils.

BACKGROUND: Helicobacter pylori is a human gastric carcinogen. Sterigmatocystin (ST), a fungus toxin, is a risk factor of gastric cancer. Cytotoxin-vacuolation toxin A (VacA) present in supernatants of H. pylori suspensions can cause gastritis and ulcer. The aim of this study was to examine the effects of H. pylori, ST and VacA in Mongolian gerbils. METHODS: Male Mongolian gerbils (n = 196) were treated with H. pylori supernatants (10 ml/1000 mg) mixed with diet or inoculated intragastrically with H. pylori alone or with ST (100 or 1000 ppb), and then killed 27 months later. Gastric tissue sections were stained with haematoxylin and eosin (H&E), periodic acid-Schiff (PAS), Alcian blue (AB, pH 2.5) and with immunostaining for PCNA and p53 expression. RESULTS: In H. pylori-infected gerbils, the normal mucosa was replaced by hyperplastic epithelium. Severe gastritis, cystic dilatation of gastric glands, hyperplastic polyps and intestinal metaplasia were observed. In H. pylori + ST (1000 ppb) gerbils, intestinal metaplasia was significantly more frequent than in H. pylori alone animals. No pathological changes were observed in the H. pylori supernatant group. Osseous metaplasia was observed in the H. pylori + ST (100 ppb) group. Serum gastrin levels of the H. pylori + ST (1000 ppb) group were significantly higher than those of the other groups. PCNA labelling index and p53 index of infected gerbils were significantly higher than those of uninfected groups. CONCLUSION: H. pylori causes gastritis, ulcer and intestinal metaplasia. ST enhances the development of intestinal metaplasia and increases gastrin levels in H. pylori-infected Mongolian gerbils.

Animals↗
PubMed2002

Seismic images of crust and upper mantle beneath Tibet: evidence for Eurasian plate subduction.

Seismic data from central Tibet have been combined to image the subsurface structure and understand the evolution of the collision of India and Eurasia. The 410- and 660-kilometer mantle discontinuities are sharply defined, implying a lack of a subducting slab beneath the plateau. The discontinuities appear slightly deeper beneath northern Tibet, implying that the average temperature of the mantle above the transition zone is about 300 degrees C hotter in the north than in the south. There is a prominent south-dipping converter in the uppermost mantle beneath northern Tibet that might represent the top of the Eurasian mantle lithosphere underthrusting the northern margin of the plateau.

Journal Article↗
PubMed2002

Potassium channels and human corporeal smooth muscle cell tone: diabetes and relaxation of human corpus cavernosum smooth muscle by adenosine triphosphate sensitive potassium channel openers.

PURPOSE: Sustained contraction of human corporeal smooth muscle depends on continuous transmembrane calcium flux through voltage gated calcium channels. K channels modulate corporeal smooth muscle membrane potential and, thus, ultimately affect transmembrane calcium flux. Therefore, we characterized relaxation responses elicited by the K channel modulators pinacidil and levcromakalim on isolated human corporeal tissue strips. We also evaluated the possibility that there may be alterations in adenosine triphosphate sensitive K channel pharmacology/function related to the presence of diabetes mellitus. MATERIALS AND METHODS: A total of 215 isolated human corporeal tissue strips obtained from 57 male patients with organic erectile dysfunction were investigated. Cumulative concentration-response curves were constructed at half log increments for steady state relaxation responses elicited by pinacidil and levcromakalim on equivalently phenylephrine pre-contracted (to approximately 75% of maximum) isolated corporeal tissue strips. Potassium currents were measured using the cell attached whole cell patch clamp technique on freshly isolated corporeal smooth muscle cells. RESULTS: A concentration dependent, glibenclamide sensitive relaxation response of phenylephrine pre-contracted corporeal tissue strips was observed for pinacidil and levcromakalim. Consistent with such observations, electrophysiological recordings on freshly isolated myocytes revealed that pinacidil (10 microM.) and levcromakalim (10 microM.) induced whole cell potassium currents that were blocked by glibenclamide (10 microM.). In addition, statistical analysis revealed that phenylephrine pre-contracted corporeal tissue strips from patients without diabetes were more sensitive to relaxation by both compounds than corporeal tissue strips excised from those with diabetes. Furthermore, relaxation responses elicited by pinacidil and levcromakalim were not affected by charybdotoxin or 4-aminopyridine but were completely reversed by KCl or tetraethylammonium chloride. CONCLUSIONS: These data indicate that the adenosine triphosphate sensitive K channel subtype is likely to have an important role in the relaxation of isolated corporeal tissue strips and, moreover, they are the molecular target for the K channel modulators/openers levcromakalim and pinacidil. Such observations are consistent with the supposition that alterations in the structure/function/activity of these potassium channels may underlie at least some aspects of observed diabetes related differences in tissue sensitivity to K channel modulators.

Adenosine Triphosphate↗
PubMed2001

Cloning, expression and characterization of a novel human REPS1 gene.

Ral is a member of the small GTPase-binding protein (G protein) family, and plays an important role in the Ras-RalGDS signal transduction pathway. A series of recent findings reveal several important downstream target proteins of Ral, such as RalBP1, Reps1, and others. Here we report another binding partner for RalBP1, which we have isolated from the human fetal brain library. The human REPS1 protein shares 83% amino acid identity with the mouse Reps1 protein. Northern blot analysis shows that the REPS1 is expressed in a variety of tissues, with the strongest expression in the heart and testis.

Adult↗
PubMed2001

The vasorelaxant effect of H(2)S as a novel endogenous gaseous K(ATP) channel opener.

Hydrogen sulfide (H(2)S) has been traditionally viewed as a toxic gas. It is also, however, endogenously generated from cysteine metabolism. We attempted to assess the physiological role of H(2)S in the regulation of vascular contractility, the modulation of H(2)S production in vascular tissues, and the underlying mechanisms. Intravenous bolus injection of H(2)S transiently decreased blood pressure of rats by 12- 30 mmHg, which was antagonized by prior blockade of K(ATP) channels. H(2)S relaxed rat aortic tissues in vitro in a K(ATP) channel-dependent manner. In isolated vascular smooth muscle cells (SMCs), H(2)S directly increased K(ATP) channel currents and hyperpolarized membrane. The expression of H(2)S-generating enzyme was identified in vascular SMCs, but not in endothelium. The endogenous production of H(2)S from different vascular tissues was also directly measured with the abundant level in the order of tail artery, aorta and mesenteric artery. Most importantly, H(2)S production from vascular tissues was enhanced by nitric oxide. Our results demonstrate that H(2)S is an important endogenous vasoactive factor and the first identified gaseous opener of K(ATP) channels in vascular SMCs.

Animals↗
PubMed2001

Neuroprotective effect of treatment with human albumin in permanent focal cerebral ischemia: histopathology and cortical perfusion studies.

In recent experimental studies, we demonstrated a highly beneficial neuroprotective effect of moderate- to high-dose human albumin treatment of transient focal cerebral ischemia, but we did not define the effect of albumin therapy in permanent focal cerebral ischemia. In this study, anesthetized Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion by retrograde insertion of an intraluminal nylon suture coated with poly-L-lysine. Albumin was administered i.v. at 2 h after onset of middle cerebral artery occlusion, in doses of either 1.25 (n=8) or 2.5 g/kg (n=6). In a separate group of animals, albumin (2.5 g/kg) was given 1 h after middle cerebral artery occlusion (n=6). Vehicle-treated rats (n=6) received 0.9% saline in equivalent volumes. Neurological status was evaluated during and 24 h after middle cerebral artery occlusion. One day after middle cerebral artery occlusion, infarct volumes and brain edema were determined. In a separate group of animals, cortical perfusion was assessed by Laser-Doppler perfusion imaging. Albumin (1.25 g/kg; n=3) or vehicle (sodium chloride 0.9%; n=3) was administered at 2 h after onset of middle cerebral artery occlusion. Higher-dose albumin therapy (2.5 g/kg) significantly improved the neurological score compared to vehicle rats at 24 h, when administered at either 1 or 2 h after middle cerebral artery occlusion. Total infarct volume was reduced by albumin (2.5 g/kg given at 2 h) by 32% compared with vehicle-treated rats. Both albumin doses (1.25 and 2.5 g/kg) significantly reduced cortical and striatal infarct areas at several coronal levels when administered at 2 h after middle cerebral artery occlusion. Brain swelling was not affected by albumin treatment. Cortical perfusion declined during middle cerebral artery occlusion in both groups. Treatment with albumin led to 48% increases in cortical perfusion (P<0.002), but saline caused no change. These results support a beneficial effect of albumin therapy in permanent focal cerebral ischemia.

Animals↗
PubMed2001

Posttranscriptional regulation of gene expression in learning by the neuronal ELAV-like mRNA-stabilizing proteins.

The view that memory is encoded by variations in the strength of synapses implies that long-term biochemical changes take place within subcellular microdomains of neurons. These changes are thought ultimately to be an effect of transcriptional regulation of specific genes. Localized changes, however, cannot be fully explained by a purely transcriptional control of gene expression. The neuron-specific ELAV-like HuB, HuC, and HuD RNA-binding proteins act posttranscriptionally by binding to adenine- and uridine-rich elements (AREs) in the 3' untranslated region of a set of target mRNAs, and by increasing mRNA cytoplasmic stability and/or rate of translation. Here we show that neuronal ELAV-like genes undergo a sustained up-regulation in hippocampal pyramidal cells only of mice and rats that have learned a spatial discrimination paradigm. This learning-specific increase of ELAV-like proteins was localized within cytoplasmic compartments of the somata and proximal dendrites and was associated with the cytoskeleton. This increase was also accompanied by enhanced expression of the GAP-43 gene, known to be regulated mainly posttranscriptionally and whose mRNA is demonstrated here to be an in vivo ELAV-like target. Antisense-mediated knockdown of HuC impaired spatial learning performance in mice and induced a concomitant down-regulation of GAP-43 expression. Neuronal ELAV-like proteins could exert learning-induced posttranscriptional control of an array of target genes uniquely suited to subserve substrates of memory storage.

Animals↗
PubMed2001

[Microvascular decompression for hemifacial spasm: experience of 215 cases].

OBJECTIVE: To investigate the relationship between pre-operational etiological diagnosis of medically intractable hemifacial spasm (HFS) and patterns of offending vessels and the curative effect of microvascular decompression (MVD). METHODS: Two hundred and fifteen patients with medically intractable HFS underwent MVD under general anesthesia. Pre-operative MRI examination was made for all cases to exclude space occupying lesion and magnetic imaging tomographic angiography (MRTA) was conducted for 145 cases of them instead of routine MRI. RESULTS: Routine MRI failed to provide information about offending vessels except for ruling out mass lesions whereas MRTA revealed the offending vessels with a positive rate of 82.8%, thus helping make correct diagnosis and operation decision. Follow-up of more than two years showed that the surgical intervention achieved a high relief rate of 91.2% without major complication, and with a low recurrence rate of only 3.5% after averaging more than two years' follow-up. CONCLUSION: Pre-operative MRTA can replace conventional MRI as a best approach for pre-operational etiological diagnosis of facial spasm. It helps perceive the offending vessels before operation. Skilled microsurgical technique along with correct recognition and mobilization of offending vessels are a must to assure MVD a high efficacious and low risk treatment of choice for HFS patients.

Adult↗
PubMed2001

Transient changes of brain-derived neurotrophic factor (BDNF) mRNA expression in hippocampus during moderate ischemia induced by chronic bilateral common carotid artery occlusions in the rat.

Chronic bilateral common carotid artery occlusion (BCCAO) induces moderate ischemia (oligemia) in the rat forebrain in the absence of overt neuronal damage. In situ hybridization for brain-derived neurotrophic factor (BDNF) mRNA was used to search for a molecular response to moderate ischemia. BDNF mRNA was significantly increased in the hippocampal granule cells at 6 h of occlusion (ANOVA, Tukey test P<0.05). At 1, 7 and 14 days BDNF mRNA levels returned to control levels. The frequency of BDNF gene expression at 6 h was 83%, which was significantly higher than the 7% incidence of histological injury in the hippocampus (Fisher's exact test, P<0.002). Cerebral blood flow was reduced to 75% of control levels in the hippocampus after 1 week of BCCAO when measured with the autoradiographic method. Measurements of tissue flow with a microprobe for laser Doppler flow excluded decreases into the ischemic range during the period when elevated gene expression was observed. Prolonged moderate ischemia (oligemia) is a sufficient stimulus for BDNF gene expression in the hippocampus. These molecular studies provide direct evidence for an involvement of the hippocampus in the BCCAO model.

Animals↗
PubMed2001

v-Ha-RaS oncogene upregulates the 92-kDa type IV collagenase (MMP-9) gene by increasing cellular superoxide production and activating NF-kappaB.

Matrix metalloproteinase 9 (MMP-9) degrades basement membrane type IV collagen and is expressed during cellular migration and invasion. Here we show that v-Ha-Ras overexpression in rat kidney epithelial cells (REC) caused upregulation of MMP-9 gene expression in part by increasing cellular oxidant levels. v-Ha-Ras mediated the production of superoxide in Ras-transfected cells, which was associated with upregulated MMP-9 gene expression. Conversely, v-Ha-Ras expression decreased steady-state levels of mRNAs from tissue inhibitor of metalloproteinase 1 (TIMP-1), an inhibitor of MMP-9; plasminogen activator inhibitor 1 (PAI-1), which indirectly activates MMP-9 by increasing plasmin levels; and collagen IV, a substrate of MMP-9 and a major component of basement membrane. Gel mobility shift assays demonstrated that Ras overexpression enhanced NF-kappaB, but not AP-1 DNA binding to motifs in the MMP-9 gene promoter. The Ras-induced increase in NF-kappaB DNA binding could be inhibited by treatment with the antioxidants N-acetyl-L-cysteine and glutathione monoester, suggesting that intracellular oxidant levels can mediate MMP-9 transcription. Our findings identify an important role for Ras in the regulation of MMP-9 expression, and suggest that increased superoxide production can upregulate MMP-9 expression and thus contribute to malignant conversion.

Animals↗
PubMed2001

Simultaneous measurement of cerebral blood flow and mRNA signals: pixel-based inter-modality correlational analysis.

The analysis of pixel-based relationships between local cerebral blood flow (LCBF) and mRNA expression can reveal important insights into brain function. Traditionally, LCBF and in situ hybridization studies for genes of interest have been analyzed in separate series. To overcome this limitation and to increase the power of statistical analysis, this study focused on developing a double-label method to measure local cerebral blood flow (LCBF) and gene expressions simultaneously by means of a dual-autoradiography procedure. A 14C-iodoantipyrine autoradiographic LCBF study was first performed. Serial brain sections (12 in this study) were obtained at multiple coronal levels and were processed in the conventional manner to yield quantitative LCBF images. Two replicate sections at each bregma level were then used for in situ hybridization. To eliminate the 14C-iodoantipyrine from these sections, a chloroform-washout procedure was first performed. The sections were then processed for in situ hybridization autoradiography for the probes of interest. This method was tested in Wistar rats subjected to 12 min of global forebrain ischemia by two-vessel occlusion plus hypotension, followed by 2 or 6 h of reperfusion (n=4-6 per group). LCBF and in situ hybridization images for heat shock protein 70 (HSP70) were generated for each rat, aligned by disparity analysis, and analyzed on a pixel-by-pixel basis. This method yielded detailed inter-modality correlation between LCBF and HSP70 mRNA expressions. The advantages of this method include reducing the number of experimental animals by one-half; and providing accurate pixel-based correlations between different modalities in the same animals, thus enabling paired statistical analyses. This method can be extended to permit correlation of LCBF with the expression of multiple genes of interest.

Algorithms↗
PubMed2001

Redox modulation of the pro-fibrogenic mediator plasminogen activator inhibitor-1 following ionizing radiation.

Fibrosis is a common form of normal tissue damage after exposure to a wide variety of insults believed to involve oxidative stress. Plasminogen activator inhibitor-1 (PAI-1) is thought to play a major role in the development of progressive fibrosis via the inhibition of extracellular matrix degradation. Because radiation causes oxidative injury, which has been shown to trigger fibrogenic responses, the present study was designed to test the hypothesis that PAI-1 expression is redox-regulated after irradiation. Irradiating rat kidney tubule epithelial cells (NRK52E) with 1-20 Gy gamma-rays led to dose-dependent increases in steady-state levels of PAI-1 mRNA and immunoreactive protein within 24 and 48 h, respectively. Enhancement of intracellular soluble thiol pools after incubation with N-acetylcysteine (2.5 mM), from 3.27 +/- 0.27 nM/mg protein to 5.34 +/- 0.52 nM/mg protein in cells incubated with N-acetylcysteine 30 min before and assessed 4 h after irradiation, abolished the radiation-induced up-regulation of PAI-1. In addition, overexpression of catalase inhibited radiation-induced increases in PAI-1 expression, suggesting a mechanistic role for hydrogen peroxide (H2O2) in regulating PAI-1 expression after oxidative insult. In support of this notion, incubating NRK52E cells with H2O2 (100 microM) also led to a nearly 3-fold increase in PAI-1 gene expression. These results demonstrate that PAI-1 is redox-regulated after exposure to ionizing radiation or H2O2 and suggest that H2O2 scavenging might represent a fundamental mechanism for modulating fibrogenic disease via inhibition of the induction of profibrogenic mediators after acute or chronic oxidative stress.

Acetylcysteine↗
PubMed2001

Inhibition of murine prostate tumor growth and activation of immunoregulatory cells with recombinant canarypox viruses.

BACKGROUND: Immunization with modified tumor cells carrying recombinant immunomodulatory genes is being explored as cancer immunotherapy. In this study, we examine whether canarypox ALVAC viruses carrying immunostimulatory cytokine genes (granulocyte-macrophage colony-stimulating factor, interleukin 2, interleukin 12, and tumor necrosis factor-alpha) can induce antitumor immunity (to rechallenge) in the RM-1 model of a highly aggressive, weakly immunogenic murine prostate cancer. METHODS: For antitumor activity studies, RM-1 murine prostate cancer cells were infected with the parental ALVAC virus or one or two recombinant ALVAC-cytokine viruses and then injected into male C57BL/6 mice. For rechallenge studies, other mice were first given an injection subcutaneously with irradiated (nonproliferating) recombinant ALVAC-infected RM-1 cells and then (10 days later) with untreated RM-1 cells. For the determination of which immune cells were required for antitumor activity, mice were immunodepleted of CD4, CD8, or natural killer (NK) NK1.1 cells with the corresponding monoclonal antibodies and were then given an injection of ALVAC-cytokine-infected RM-1 cells. For all experiments, tumor outgrowth and animal survival were monitored. RESULTS: After subcutaneous injection into mice, RM-1 cells infected with one (except ALVAC-interleukin 2) or two ALVAC-cytokine recombinants had statistically significantly greater antitumor activity than RM-1 cells infected with parental ALVAC (P<.001 for all; two-sided test). The antitumor activity of RM-1 cells infected with any two ALVAC-cytokine recombinants was greater than, but not statistically significantly different from, that of RM-1 cells infected with any one ALVAC-cytokine recombinant. NK1.1 cells were necessary for antitumor activity, but tumor-specific CD4(+) regulatory T cells were also induced that inhibited CD8(+) RM-1-specific cytotoxic T cells, resulting in the lack of immunity to a rechallenge by RM-1 cells. DISCUSSION: Canarypox viruses can transfer immunostimulatory cytokine genes into RM-1 prostate cancer cells. When such cells were injected into mice, the cytokines induced an antitumor response against this highly aggressive, weakly immunogenic tumor. This response, however, did not protect the mouse against a rechallenge with RM-1 cells because suppressor CD4(+) T cells were induced that inhibited tumor-specific CD8(+) cytotoxic T cells.

Animals↗
PubMed2001

The effect of bone morphogenetic protein-7 (BMP-7) on functional recovery, local cerebral glucose utilization and blood flow after transient focal cerebral ischemia in rats.

Bone morphogenetic protein-7 (BMP-7) has been shown to enhance dendritic growth and improve functional recovery after experimental stroke. In this study, we examined the effect of BMP-7 on functional recovery, local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCMRglu) following transient middle cerebral artery occlusion. Sprague--Dawley rats (n=29) were anesthetized with halothane/nitrous oxide and received 2-h middle cerebral artery occlusion (MCAo) by poly-L-lysine-coated intraluminal suture. Rectal and cranial temperatures were regulated at 37.0--37.5 degrees C. BMP-7 or vehicle (volume, 25 microl) was administered intracisternally in a blinded fashion at 24 h after MCAo. Neurological status was evaluated during occlusion (60 min) and daily for 2 days after MCAo. In matched animal groups, LCMRglu was measured autoradiographically with [(14)C]2-deoxyglucose (2-DG) and LCBF with [(14)C]iodoantipyrine 48 h after MCAo. Four animals groups were studied: LCMRglu series (BMP-7, n=7; vehicle, n=8); LCBF series (BMP-7, n=6; vehicle, n=8). Average three-dimensional image data sets were constructed for each group and were compared by pixel-based statistical methods. Rectal and cranial temperatures, mean blood pressure, plasma glucose and blood gases were similar among groups. BMP-7 significantly improved the total neurological score compared to vehicle at 48 h after MCAo (7.3+/-0.4 vs. 9.0+/-0.2, respectively; P<0.0003). Compared to vehicle-rats, BMP-7 enhanced glucose utilization in the basal ganglia ipsilateral to stroke and improved LCBF in ipsilateral subthalamus, but decreased LCBF and LCMRglu in contralateral cortical regions.

Animals↗
PubMed2001

NK cells are essential for effective BCG immunotherapy.

Adjuvant intravesical bacillus Calmette-Guérin (BCG) therapy is a well-established and successful adjuvant immunotherapy in the treatment of superficial bladder cancer. Although the function of natural killer (NK) cells in other immunotherapeutic regimens (e.g., lymphokine-activated killer [LAK] cell or interleukin-2 [IL-2] therapy) has been established, the contribution of NK cells to effective BCG immunotherapy is not clear. We used a human in vitro system to analyze the role of NK cells in BCG-induced cellular cytotoxicity. After stimulation of mononuclear cells with BCG for 7 days, these BCG-activated killer (BAK) cells displayed substantial cytotoxicity against bladder tumor cells. Magnetic depletion experiments and fluorescence activated cell sorting revealed that NK cells were the major effector cell population. To address NK cell function in vivo, we studied a syngeneic orthotopic murine bladder cancer model and compared BCG immunotherapy in C57BL/6 wild-type mice, NK-deficient beige mice and mice treated with anti-NK1.1 monoclonal antibody. Four weekly instillations of viable BCG significantly prolonged survival in wild-type mice compared with control mice treated with solvent alone. In contrast, BCG therapy was completely ineffective in NK-deficient beige mice and in mice treated with anti-NK1.1 monoclonal antibody. These findings suggest a key role for NK cells during BCG immunotherapy.

Animals↗