Biomedical subjects

Yun Chen

Publications and source records attributed to Yun Chen.

At least 91 records · Page 5Linked to original sources

PubMed2003

Growth hormone aggravates renal abnormalities induced by neonatal enalapril treatment.

Lack of neonatal angiotensin II type-1 receptor stimulation produces irreversible abnormalities of renal function and morphology, which can be prevented by simultaneous administration of insulin-like growth factor-I (IGF-I). Given the fact that growth hormone (GH) is the strongest secretagogue for IGF-I, we wanted to explore whether GH could reproduce the effect of IGF-I. Rats were treated from 3 to 13 days of age with the angiotensin-converting enzyme inhibitor enalapril (10 mg/kg/day) and GH (4 mg/kg/day), alone or in combination. Renal gene expression of IGF-I and IGF-binding proteins (IGFBP) was determined during and after treatment. Renal function and morphology were investigated at adult age. In contrast to the beneficial effect of IGF-I, GH treatment in combination with enalapril further deteriorated both renal function and morphology as compared with enalapril treatment alone, demonstrating: reduced glomerular filtration rate, increased tubular dilation and further expansion of the outer medulla. Enalapril decreased medullary expression of IGF-I and increased renal expression of IGFBP-1, changes that were not affected by concomitant GH treatment. These findings indicate that GH and IGF-I have different roles in the renin-angiotensin system-mediated kidney development.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2003

Effects of octreotide on epidermal growth factor receptor, tissue plasminogen activator, and plasminogen activator inhibitor during intraperitoneal adhesion formation.

BACKGROUND: Intraperitoneal adhesions remain a problem after abdominal surgery. Octreotide has been proved to be able to reduce the number, strength, and extent of fibrous bands at and away from the anastomotic site in an animal model of rats with intestinal resection and reanastomosis. The aim of the present study was to investigate whether epidermal growth factor receptor (EGF-R), tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI) are involved in this process. METHODS: Laparotomy with intestinal resection and reanastomosis was performed on 60 male Wistar rats. All rats were randomly assigned to five groups: receiving no medication (control; C), normal saline (NS), octreotide solution peritoneal irrigation (Oc), octreotide intramuscular injection (IM), and Oc plus octreotide intramuscular injection (Oc + IM). The concentrations of serum EGF-R, plasma tPA, PAI-1, and PAI-2, and the strength of wound healing were measured. RESULTS: The serum EGF-R concentration showed no significant change from the preoperative level in the C and NS groups 7 and 14 days after the abdominal surgery. However, it decreased significantly on postoperative days 7 and 14 in groups Oc, IM, and Oc + IM ( P < 0.05). The plasma tPA concentrations were significantly higher than the preoperative level in all groups of rats on postoperative day 7. The levels were higher in groups Oc, IM, and Oc + IM than in group C or group NS at that time ( P < 0.05). On postoperative day 14, the plasma tPA concentrations had returned to the preoperative level in group C and group NS. However, the concentrations in groups Oc, IM, and Oc + IM still remained at a significantly higher level than the concentrations in group C and group NS. The plasma PAI-1 and PAI-2 concentrations showed no significant difference from the preoperative level in group C and group NS on days 7 and 14 after the abdominal surgery. However, the concentrations in groups Oc, IM, and Oc + IM on postoperative days 7 and 14 were markedly lower than those in groups C and NS ( P < 0.05). The wound strength was significantly greater on day 14 than on day 7 in all groups. CONCLUSIONS: In the rats with octreotide irrigation, the EGF-R level was decreased, the plasma tPA concentration was higher, and the plasma PAI-1 and PAI-2 concentrations were lower when compared with values in group C and group NS rats on days 7 and 14 after surgery. The data suggest that EGF-R, tPA, PAI-1, and PAI-2 are all involved in the mechanism of octreotide's action in reducing adhesion formation.

Animals↗

PubMed2003

Radiation-induced temporary alopecia after embolization of cerebral arteriovenous malformations.

Alopecia after endovascular embolization of cerebral arteriovenous malformations (AVMs) is uncommon. In this report, we present a 33-year-old man who developed temporary alopecia after staged embolization of a cerebral AVM. Four days after the last procedure, this patient had hair loss over his right temporoparietal and occipial areas. No scalp erythema or other sign of dermatitis was noted. The hair regrew 2 months later. The alopecia was considered to be related to repeated exposure to radiation during embolization. The experience in this case and review of the literature suggest that interventional neuroradiological procedures may cause substantial radiation exposure to the patient. Therefore, radiation use should be limited to the least amount necessary to complete the endovascular procedure to prevent radiation-induced biological changes and morbidity. Patients should be well informed of adverse effects such as alopecia.

Adult↗

PubMed2003

Perturbed medullary tubulogenesis in neonatal rat exposed to renin-angiotensin system inhibition.

BACKGROUND: Pharmacological interruption of the angiotensin II type-1 receptor (AT(1)) signalling during nephrogenesis in rats induces irreversible abnormalities in kidney morphology, comprising papillary atrophy and tubulointerstitial damage, which are characterized by tubular dilatation/atrophy and interstitial inflammation/fibrosis. This study determined the time course for development of tubular structural and inflammatory changes and possible cytokine production in the renal medulla of newborn rats exposed to angiotensin-converting enzyme (ACE) inhibition. Additionally, medullary expression of E-cadherin, a marker for tubular formation, was investigated in ACE-inhibited rats. METHODS: Newborn rats were exposed (postnatal days 0-12) to ACE inhibitor enalapril and killed at days 1, 2, 4, 9 and 13. One kidney was used for morphological evaluation and the other for immunohistochemistry, using antibodies directed against monocytes/macrophages, T cells and E-cadherin on frozen sections. In a separate experiment, rats were treated for 9 days and had their kidneys processed for western immunoblot and immunohistochemistry, where antibodies directed against monocyte chemoattractant protein-1 (MCP-1) and tumour necrosis factor-alpha (TNF-alpha) were used on paraffin sections. RESULTS: In renal medulla from enalapril-treated rats, volume fractions of tubular lumens and interstitium were increased from postnatal days 2 and 4, respectively, while that of tubular cells was decreased from 4 days of age. Concomitant loss and/or reduction in E-cadherin expression (from day 2) was observed in dilated medullary tubules of enalapril-treated rats. Furthermore, in the medulla of enalapril-treated rats, the increased number of ED2+ (resident macrophages) cells, followed by the increase in ED1+ (monocytes/macrophages) and CD4+ T cells, was observed at days 9 and 13, respectively. This was accompanied by increased medullary expression of TNF-alpha at day 9. CONCLUSIONS: Neonatal ACE inhibition perturbs medullary tubulogenesis, as indicated by tubular dilatation and a lack of E-cadherin expression in these tubules. Macrophage/monocyte-mediated immune response is a secondary event, coincidentally associated with the up-regulation of TNF-alpha.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2003

A calcium-initiated signaling pathway propagated through calcineurin and cAMP response element-binding protein activates proenkephalin gene transcription after depolarization.

Essential components of a signal-transduction pathway regulating activity-dependent neuropeptide gene transcription have been identified. Proenkephalin (PEnk) gene activation after depolarization of chromaffin cells with 40 mM KCl was blocked by the voltage-sensitive calcium-channel blocker methoxyverapamil (D600) (30 microM) and by calcineurin inhibition with 100 nM cyclosporin A or ascomycin but not by inhibiting new protein synthesis with 0.5 microg/ml cycloheximide. KCl-induced elevation of PEnk mRNA was distinct from activation of the PEnk gene by either cAMP or protein kinase C. Twenty-five micromolar forskolin- and 100 nM phorbol 12-myristate 13-acetate-induced elevations of PEnk mRNA were cycloheximide-sensitive and were not blocked by cyclosporin A or ascomycin. KCl stimulated Ser-133 phosphorylation of cAMP response element-binding protein (CREB) in chromaffin cells, and CREB phosphorylation was blocked by both ascomycin and D600. A reporter gene containing 193 bases of the PEnk gene 5' flank driving luciferase gene expression (pENK12-Luc) transfected into chromaffin cells was transcriptionally activated by KCl depolarization. Activation was blocked by both ascomycin and D600 and required an intact CREB binding site (ENKCRE2). An oligonucleotide containing the PEnk cAMP response element-2 was gel-shifted by both unstimulated and potassium-stimulated chromaffin cell nuclear extracts into a prominent complex supershifted by CREB antibodies. Finally, stimulation of transcription of the pENK12-Luc reporter by KCl in chromaffin cells was blocked by coexpression of the CREB antagonist A-CREB but not by the AP-1 antagonist A-Fos. Stimulus-transcription coupling after depolarization in chromaffin cells occurs via calcineurin-dependent activation of CREB, a pathway distinct from cAMP- or protein kinase C-initiated signaling and independent of immediate early gene regulation.

Animals↗

PubMed2003

[Comparison and analysis of expression of c-myc and p16 in cervical carcinoma].

BACKGROUND & OBJECTIVE: Activation of proto-oncogene and inactivation of tumor suppressor genes is related to the carcinogenesis of many tumors. It is still unclear whether abnormal expression of c-myc and p16 cooperate in the occurrence and progression of cervical carcinoma, and whether there exists a connection between the expression of two genes and the chemotherapy response of cervical carcinoma. This study was designed to investigate the correlation between the expression of c-myc and p16 and their roles in the genesis and development of the uterine cervical carcinoma and chemotherapy response. METHODS: Using in situ hybridization, 37 cases of cervical carcinoma (including 11 cases after chemotherapy), 21 cases of precancerous lesion and 5 cases of normal cervix were observed for c-myc and p16 mRNA with dig-labeled probes. An image analytic system was used to detect the gray degree values of the positive signals. RESULTS: The positive expression rates of p16 in normal cervix,CIN (cervical intraepithelial neoplasia) and cervical carcinoma were 100%, 71.4%, and 21.6%, respectively (P=0.0001), whereas the expression rates of c-myc were 0%, 42.9%, and 75.7% (P=0.0011), respectively. Statistically significant difference was found among the three groups for both p16 and c-myc. The expression of positive signals of c-myc increased with the increase of malignant degree, and the positive signals in CIN III were also higher than that in CIN II and CIN I. The expression rates of c-myc were decreased in cervical carcinoma after chemotherapy. There was a tendency of negative correlation between the expression of c-myc and p16(r(s)=-0.907). Expression of p16 and c-myc showed no significant difference between effectual and ineffectual chemotherapy groups. CONCLUSION: Both over expression of c-myc and descended expression of p16 may play an important role in the genesis and development of uterine cervical carcinoma. The increased expression of c-myc in different grade CIN suggests that carcinogenesis of cervix be progressive.

Female↗

PubMed2003

[Study on the production of citrinin by Monascus strains used in food industry].

In order to screen strains with less or nearly no production of citrinin, thirty-five Monascus strains used in food industry were selected to investigate the effect of cultivation condition and the medium composition on citrinin production. The results from the study indicated that all strains produced citrinin on the rice with the levels ranging from 0.28 to 2458.80 mg/kg (201.60 mg/kg for the average and 61.99 mg/kg for the median, respectively), while 30 strains (85.71%) yielded this toxin on the submerged culture with the concentration between 0.09 and 55.65 mg/kg (11.99 mg/kg for the average and 3.51 mg/kg for the median, respectively). Therefore, citrinin production in rice in this study was higher than that in the liquid. In addition, the red pigment production in rice was 3-509 (average 93) times higher than that in the liquid. One strain with the highest color value (1134 U/g) but lower citrinin production in rice was obtained. These results suggested that it is necessary to make the safety evaluation of microorganisms for the production of foods and food ingredients, to investigate the ability of citrinin production by Monascus strains preserved by either the food manufacturer or the national culture collection units and, to survey the citrinin contamination in Monascus products countrywide. It is urgent for China to establish the tolerance limit of citrinin in foods fermented by Monascus species.

Citrinin↗

PubMed2003

Primary volvulus of the ileum in a preterm infant.

Primary volvulus of the small intestine is rare in neonates. We report a case of primary volvulus of the ileum in a preterm newborn. Vomiting and abdominal distension began 10 hours after birth, followed by hypovolemia, hyponatremia, and acidosis. Plain abdominal radiograph revealed a pattern of diffuse ileus and very dilated loops at the right upper quadrant of the abdomen. Three days later, another plain film showed increased fluid accumulation and decreased air in these dilated loops. Emergency laparotomy revealed primary volvulus of the distal ileum with gangrenous change. Resection of the necrotic ileum with an end-to-end ileoileostomy was performed and the patient recovered fully. In a newborn with ileus and rapidly deteriorating hemodynamics, early surgical intervention is essential to achieve good prognosis.

Female↗

PubMed2002

Coincident elevation of cAMP and calcium influx by PACAP-27 synergistically regulates vasoactive intestinal polypeptide gene transcription through a novel PKA-independent signaling pathway.

Pituitary adenylate cyclase-activating polypeptide (PACAP) causes calcium influx, intracellular calcium release, and elevation of cAMP in chromaffin cells. Calcium influx is required for PACAP-stimulated secretion of catecholamines and neuropeptides. The role of cAMP elevation in the action of PACAP at either sympathetic or adrenomedullary synapses, however, is unknown. Here, we show that PACAP-27-induced calcium influx through voltage-sensitive calcium channels (VSCCs), together with elevation of intracellular cAMP, was sufficient to stimulate vasoactive intestinal polypeptide (VIP) biosynthesis at least 40-fold. Combined treatment of chromaffin cells with 40 mm KCl, which elevates intracellular calcium, and 25 micrometer forskolin, which elevates intracellular cAMP, caused an increase in VIP peptide and mRNA much greater than that elicited by either agent alone, and comparable to the increase caused by 10-100 nm PACAP-27. Elevation of VIP mRNA by either KCl plus forskolin, or PACAP, (1) was independent of new protein synthesis, (2) was blocked by inhibition of calcium influx through voltage-sensitive calcium channels, (3) was calcineurin dependent, and (4) was dependent on MAP kinase activation but not activation of protein kinase A. The degree of activation of two different second-messenger pathways, calcium influx and cAMP elevation, appears to determine the magnitude of transcriptional activation of the VIP gene in chromaffin cells. Maximal stimulation of VIP biosynthesis by PACAP appears to require the coincident activation of both of these pathways.

Animals↗

PubMed2002

Establishment and characterization of a rectal cancer model in mice: application to cytokine gene therapy.

BACKGROUND AND AIMS: We established an orthotopic animal model of rectal cancer in mice and applied this model to the study of the antitumor effects of cytokine-assisted tumor vaccine. MATERIALS AND METHODS: The CT-26 murine colon adenocarcinoma cells were inoculated into the submucosa of the rectum of the mice to induce the rectal tumor. The tumor growth rate and the survival time of the mice were observed. The cDNA of granulocyte-macrophage colony-stimulating factor (GM-CSF) was transduced to the CT-26 cell line via a retroviral vector, and the therapeutic effects of irradiated GM-CSF secreting tumor vaccine on the rectal tumor were investigated. RESULTS: All the mice implanted with the wild-type tumor cells had tumor growth in the rectum and died. The mean survival time of the mice was 28.9 days. Two doses of irradiated GM-CSF secreting tumor vaccine administered on days 0 and 3 after tumor cell implantation significantly prolonged the survival of the mice with rectal tumor compared with that of the control groups ( P<0.0001). In contrast, no antitumor effect was observed when the treatment with GM-CSF secreting tumor vaccine was delayed to 3 days after tumor cell implantation ( P>0.17). CONCLUSION: The results suggest that cytokine gene therapy exerts an antitumor effect on small tumors and may be considered as an adjuvant immunotherapy of rectal cancers and prevention of reimplantation of tumor cells disseminated during or following surgery. The orthotopic animal model of the rectal cancer in mice could be applied to the in vivo experimental studies of rectal cancer.

Adenocarcinoma↗

PubMed2002

[Expression of TTF-1 in thyroid tumors originating from follicular epithelium and its correlation with expression of RET, galectin-3 and mucin-1 genes].

OBJECTIVE: To explore the expression of thyroid transcription factor-1 (TTF-1) in thyroid tumors and in different parts of follicular epithelium and the correlation of expression of TTF-1 with the expression of RET, galectin-3 (Gal-3) and mucin-1 (MUC1) genes. METHODS: One hundred thirty-three samples of resected thyroid tumors were examined by streptavidin/peroxidase (S-P) immunohistochemical technique to detect the expression of TTF-1 and RET, Gal-3, and MUC1 genes. RESULTS: (1) TTF-1 was expressed in the nuclei and cytoplasm of different kinds of tumor cells and normal cells around the tumors. There was no significant difference between the expression of TTF-1 in nuclei of malignant thyroid tumor cells and that in nuclei of benign thyroid tumor cells (P > 0.05). The positive expression rate of TTF-1 was 27.40% in cytoplasm of benign tumor and was 66.10% in cytoplasm of malignant tumor was 66.10% (P < 0.05). (2) The expression rate of RET gene was 38.9% in thyroid adenoma, 88.4% in papillary carcinoma, and 87.5% in follicular carcinoma. The difference of expression rate of RET gene between adenoma and both of papillary and follicular carcinomas was statistically significant (P < 0.05). (3) The expression rate of MUC1 was 23.3% in benign tumor and 50.9% in malignant tumor. The expression rate of MUC1 was lower in benign thyroid diseases (nodular goiter and adenoma) than in thyroid papillary carcinoma and follicular carcinoma (P < 0.05). (4) The expression rate of Gal-3 gene was 38.4% in benign tumor and 88.1% in malignant tumor. (5) The expression rates of Gal-3 and MUC1 in benign lesions (nodular goiter and adenoma) were lower than those in thyroid papillary and follicular carcinomas (P < 0.05). The expression of Gal-3 and that of MUC1 in thyroid carcinomas were fundamentally parallel. However, the sensitivity of Gal-3 was higher than that of MUC1. In part of adenomas Gal-1 and MUC1 were positive locally simultaneously. The expression of TTF-1 in cytoplasm was associated with that of Gal-3 and MUC1. CONCLUSION: The expression of TTF-1 in nucleus is a phenomenon common to both normal and pathological thyroid follicles. Combined tests of RET, Gal-3 and MUC1 may act as the diagnostic markers to distinguish benign follicular tumor from malignant ones. Expression of TTF-1 in cytoplasm is probably a characteristic of malignant phenotypes of thyroid tumors.

Animals↗

PubMed2002

Ruptured cervical disc after spinal manipulation therapy: report of two cases.

STUDY DESIGN: Case reports of ruptured cervical disc after spinal manipulation therapy. OBJECTIVES: To present the rare cases of ruptured cervical disc temporally related to spinal manipulation therapy. SUMMARY OF BACKGROUND DATA: The complication of ruptured cervical disc was rare in the literature. METHODS: Two patients developed cervical myelopathy or radiculopathy after spinal manipulation therapy, and magnetic resonance imaging showed herniated cervical discs at C4-C5 and C6-C7, respectively. RESULTS: Anterior cervical discectomy was performed, and ruptured disc fragments were removed in these two patients. Both patients had good neurologic recovery after operation, and no neurologic deficits were noted after 15 and 6 months of follow-up, respectively. CONCLUSIONS: The experience of these two patients reminds us that cervical disc rupture can occur during a course of cervical spinal manipulation. Full neurologic recovery is achievable if accurate diagnosis and prompt surgical treatment are done.

Adult↗

PubMed2002

Suppression of elevated plasma interleukin-8 levels due to total ischemia and reperfusion of the small intestine by luminal perfusion with fetal bovine serum.

A previous study demonstrated that continuous enteric luminal perfusion of fetal bovine serum (FBS) protects the small intestine from total ischemia/reperfusion injury (IRI) and increases the intestinal mass. In this study, we further investigated the changes in plasma interleukin-8 (IL-8) level caused by total ischemia/reperfusion of the small intestine and the effect of FBS on plasma IL-8 levels. A 3-h total ischemia was induced in a 15-cm segment of terminal ileum and then reperfusion was instituted. Luminal perfusion of FBS was conducted via an osmotic minipump connected to the stomach through a fine polyethylene tube, starting 3 days prior to total ischemia. The rats were killed after 10 and 30 min and 1 and 3 h of total ischemia, and 1, 6, and 12 h or 1, 2, and 3 days after initiation of reperfusion. Plasma IL-8 was measured by enzyme-linked immunosorbent assay. The results were compared among the FBS-treated and untreated groups. The plasma IL-8 level was elevated from 1 h of total ischemia to 6 h after initiation of reperfusion ( P< 0.05) with a peak of 641.5 +/- 36.9 pg/ml in the untreated group and 471.6 +/- 42.2 pg/ml in the treated group. Luminal perfusion of FBS significantly suppressed plasma IL-8 levels after 1 h of total ischemia and 1 h after initiation of reperfusion ( P< 0.05). The results suggest that FBS might play a role in the treatment of total IRI of the small intestine.

Animals↗

PubMed2002

The effect on MHC class II expression and apoptosis in placenta by IFNgamma administration.

To investigate the possible mechanisms by which interferon gamma (IFNgamma) affects pregnancy, the expression of class II major histocompatibility complex (MHC) antigens and cleavage of DNA that is a hallmark of apoptosis in the placenta were examined by molecular biochemical techniques, and progesterone levels were examined by radioimmunoassay. The semi-quantitative analysis with reverse transcription-polymerase chain reaction showed that the expression of MHC class II antigen in placenta increased when rabbits were treated with high doses of IFNgamma compared with the control. However, immunohistochemical study suggested that IFNgamma did not affect MHC class II expression in trophoblasts, but had a stimulatory effect on its expression in maternal decidua and placental lymphocytes. DNA fragmentation analysis and terminal deoxynucleotidyl mediated-deoxyuridine triphosphate nick end labeling (TUNEL) assay indicated that the cleavage of DNA was detected in the placenta in both normal and IFNgamma-treated pregnancy. Quantitative analysis of apoptotic cells revealed an increase in trophoblasts treated with IFNgamma compared to those in normal pregnancy. Moreover, progesterone, which plays an important role in pregnancy, was reduced significantly in rabbits treated with IFNgamma. The results suggested that IFNgamma exerted its deleterious effect on pregnancy by inducing apoptosis in trophoblasts and by reducing the production of progesterone.

Animals↗

PubMed2002

Infertility in mice induced by the rhesus monkey chorionic gonadotropin beta-subunit glycoprotein (rmCGbeta) using DNA immunization.

The recombinant eukaryotic expression vector pCMV4-rmCGbeta, inserted full-length cDNA of the beta-subunit of rhesus monkey chorionic gonadotropin (rmCGbeta), as DNA immuno-contraceptive against CGbeta glycoprotein, has previously demonstrated the biological expression of rmCGbeta in vitro and in vivo. The plasmid DNA of pCMV4-rmCGbeta was inoculated into BALB/c mice at different doses and routes as DNA immuno-contraceptive to understand its antifertility effect. The results of immune responses indicated that the intradermal inoculation is the optimal pCMV4-rmCGbeta DNA delivery method for BALB/c mice, and the dose of 10 microg should be enough to elicit immune response. With different doses from 10-50 microg, marked reductions in the fertility of the female mice after two intramuscular inoculations of pCMV4-rmCGbeta DNA were seen, while the similar level of humoral immune responses were induced. With the dose of 20 microg of pCMV4-rmCGbeta DNA, the mice showed reduction in fertility from intraperitoneal, and intradermal to intramuscular inoculating method. The antifertility effect of antiserum from immunized mice confirmed that the antibodies elicited by pCMV4-rmCGbeta DNA could prevent pregnancy in female mice. At the same time, the full-length cDNA of beta-subunit of mouse chorionic gonadotropin (muCGbeta) was cloned from placenta and sequenced for the first time (GenBank Accession No. AF333067). Sequence analysis showed that muCGbeta shares 99.6% homology with rmCGbeta and 90.6% with hCGbeta respectively. The results indicated that the infertility of BALB/c mice induced by pCMV4-rmCGbeta contraceptive should be further studied as a CGbeta DNA contraceptive. (Mol Cell Biochem 231: 89-96, 2002)

Amino Acid Sequence↗

PubMed2002

Analysis of the PC12 cell transcriptome after differentiation with pituitary adenylate cyclase-activating polypeptide (PACAP).

Pituitary adenylate cyclase-activating polypeptide (PACAP) promotes neurite outgrowth and inhibits proliferation of rat pheochromocytoma (PC12) cells. Characterizing the PACAP-differentiated PC12 cell transcriptome should provide genetic insight into how these processes occur in these cells, and in neuronal precursors in vivo. For this purpose, RNA samples were collected from PC12 cells before or after a 6-h treatment with PACAP, from which a labeled cDNA was hybridized to a high-density cDNA array containing 15 365 genes. The genomic response to PACAP involves at least 73 genes. Among the genes differentially expressed in the presence of PACAP, 71% were up regulated, and 29% down regulated, 2-fold or more. Sixty-six percent of the messages affected by PACAP code for functionally categorized proteins, most not previously known to be regulated during PC12 cell differentiation. PACAP has been shown to induce PC12 cell neurite outgrowth through the mitogen-activated protein kinase kinase (MEK) pathway independently of protein kinase A (PKA). Therefore treatments were conducted in the absence or presence of the PKA inhibitor H89, or the MEK inhibitor U0126 in order to identify subsets of genes involved in specific aspects of PC12 cell differentiation. Co-treatment of PC12 cells with PACAP plus H89 revealed a cluster of five genes specifically regulated through the PKA pathway and co-treatment of the cells with PACAP and U0126 revealed a cluster of 13 messages specifically activated through the MEK pathway. Many of the known genes regulated by PACAP have been associated with neuritogenesis (i.e. villin 2 or annexin A2) or cell growth (i.e. growth arrest specific 1 or cyclin B2). Thus, some of the expressed sequence tags (ESTs) that exhibit the same regulation pattern (i.e. AU016391 or AW552690) may also be involved in the neuritogenic and anti-mitogenic effects of PACAP in PC12 cells. Among the 73 PACAP regulated genes, 10 are disqualified on pharmacological grounds as actors in PACAP-mediated neurite outgrowth or growth arrest, leaving 63 new PACAP-regulated genes implicated in neuronal differentiation. Thirteen of these are candidates for mediating ERK-dependent neurite outgrowth, and 47 are possibly involved in the ERK-independent growth arrest induced by PACAP.

Animals↗

PubMed2002

Effects of irradiated tumor vaccine and continuous localized infusion of granulocyte-macrophage colony-stimulating factor on neuroblastomas in mice.

BACKGROUND/PURPOSE: Immunomodulatory treatment has been proposed as a feasible strategy for neuroblastoma treatment. In this study, the antitumor effects of a continuous localized subcutaneous infusion of granulocyte-macrophage colony-stimulating factor (GM-CSF) into the injection site of irradiated tumor vaccine used as a source of tumor antigens on mouse neuroblastoma were investigated. METHODS: A/J mice were inoculated subcutaneously with wild type neuro-2a neuroblastoma cells and then treated with 5 doses of irradiated tumor vaccine or continuous localized infusion of GM-CSF (1 ng/d or 10 ng/d) via an osmotic minipump. Survival rates and survival times were compared among the groups. Tumor growth rates and animal survival times were followed and compared among different groups. Histologic and immunohistochemical analyses were performed to observe the immune response induced by various treatment strategies. RESULTS: Tumor growth rates were reduced significantly and survival times prolonged significantly by the treatment using tumor vaccine and continuous infusion of 10 ng/d of GM-CSF when compared with the control group (P <.05). One mouse treated with tumor vaccine and a 10 ng/d infusion of GM-CSF showed tumor regression and long-term survival, and no tumor growth was noted after rechallenge with wild-type neuro-2a cells. In contrast, using tumor vaccine only, or tumor vaccine combined with a 1 ng/d infusion of GM-CSF was less effective than tumor vaccine combined with a 10 ng/d infusion of GM-CSF (P <.05). Infusion of GM-CSF alone had no antitumor effects. Immunohistologic analyses showed significant CD4+ and CD8+ T cell infiltration of the tumor in the mice treated with tumor vaccine and a 10 ng/d infusion of GM-CSF. CONCLUSIONS: The results suggest that an irradiated tumor vaccine combined with continuous localized infusion of GM-CSF may induce a tumor-specific antitumor immune response that can suppress tumor growth and prolong survival. Such a treatment strategy deserves consideration as a possible adjuvant treatment for neuroblastoma.

Animals↗

PubMed2002

Multiple tuberculous brain abscesses.

Multiple tuberculous brain abscesses are rare. This report presents a female patient with a rapidly deteriorating clinical course. Computed tomographic scanning revealed multiple brain abscesses. Aspiration of one of the lesions yielded pus and positive acid-fast stained bacilli. The pathogenesis of multiple tuberculous brain abscesses is discussed.

Adult↗