OBJECTIVE To investigate the time and dose relation of new urine bio markers in rat model of acute kidney injury induced by genta mycin (GM)to search for more sensitive,noninvasive and specific markers than traditional approaches to monitor nephrotoxicity.METHODS SD Rats were im treated with GM5,20,80 mg·kg -1 or saline once daily.Rats were randomly divided into 20 subgroups:treated for 1 ,3,7,14 d and 14 d followed with 28 d recovery period.Ten rats per group (5 rats per sex)were scarified at 24 h after the last dosing or the end of recovery period.Blood sa mples were col-lected for blood urea nitrogen (BUN)and creatinine(CRE)analysis.Urine was collected at each nec-ropsy for urine protein by dry che mistry method,for kidney injury molecule-1 (KIM-1 )analysis by ELISA, and for β2-microglobulin (β2-MG)analysis by ELISA.Kidneys were obtained for histological exa mination after HE stains.RESULTS Positive protein(3 +)was noted for several fe male animals treated for 7 or 14 d at 80 mg·kg -1 and the tendency of recovery were noted at the end of recovery period.Co mpared with those in saline control group treated for 7 d,the seru m BUN and CRE levels for fe males and the CRE level for males were significantly increased at 80 mg·kg -1 (P <0.05),and the BUN level showed the tendency of increase for males at 80 mg·kg -1 (P >0.05).When treated for 14 d,the seru m BUN and CRE levels for fe males and males at 80 mg·kg -1 and the seru m CRE level for fe males at 20 mg·kg -1 were significantly increased when compared with those in saline control group(P <0.05). The seru m BUN and CRE recovered to base line for all animals treated for 14 d followed by a 28 d recov-ery period.Histopathological observation of kidney tissues indicated that focal tubule dilatation was noted for animals treated for 3 d at 20 and 80 mg·kg -1 ,infla mmatory cell infiltration and focal tubule dilatation were noted at 20 mg·kg -1 and focal renal tubular epithelial cell degeneration,infla mmatory cell infiltra-tion,focal casts (lightly)were noted at 80 mg·kg -1 for animals treated for 7 or 14 d.For animals treated for 14 d followed by a 28 d recovery period,only basophilic tubules and renal casts were noted at 80 mg·kg -1 .New urine bio markers determination indicated that KIM-1 level was significantly increased at 20 and 80 mg·kg -1 for animals treated for 3,7 or 14 d when compared with that in saline control group (P<0.05).For animals treated for 14 d followed by a 28 d recovery period,the KIM-1 level was still significantly higher than saline control group for males and fe males at 80 mg·kg -1 and males at 20 mg·kg -1 (P <0.05 ),but there was evidence for reversal.The β2-MG level was significantly increased at 80 mg·kg -1 for animals treated for 3 d(P<0.05),at 20 or 80 mg·kg -1 for animals treated for 7 or 14 d(P<0.05 or P<0.01 ),when compared with that in the saline control group.For animals treated for 14 d followed by a 28 d recovery period,the β2-MG level was still significantly higher than saline control group for males and fe males at 80 mg·kg -1 and fe males at 20 mg·kg -1 (P <0.05),but there was also evidence for reversal.CONCLUSION Urine KIM-1 and β2-GM are more sensitive and specific markers for early diagnosis of kidney injury induced by GM when compared with the traditional approaches to monitor nephrotoxicity.

This study was designed to prove simultaneously blocking both EGFR and COX-2-medi-ated pathways may be an efficient means of inhibiting cancer cell growth in NPC. Method: A combination of tarceva (EGFR-selectivetyrosine kinase inhibitors) with celecoxib(Cox-2 inhibitor) was studied on its effects on cell growth, cell cycle progression, apoptosis and protein expression in CNE-2 cell lines by cell growth assay, flow cy-tometric analysis assay and Western blotting. Result: ①The inhibition rate of cell growth was higher in the group treated with a combination of two agents than that the sum of rates of the two groups treated with only one agent (P<0.05). ②The combination of tarceva with celecoxib significantly induced G_1 arrest(P<0.05) ,but did not in-crease apoptosis rate(P>0.05). ③The group of combination showed less expressions of p-EGFR and COX-2 than any other group. Conclusion Simultaneously blocking EGFR and COX-2 mediated pathways would significantly in-hibit the growth of CNE-2 cell line, increase G_1 arrest and reduce the expression levels of p-EGFR and COX-2.

OBJECTIVE: To analyze the causes of misdiagnosis in patients with familial nasal bleeding and to improve the level of diagnosis and treatment. METHOD: The clinical characteristics of 7 families with nose blood were analyzed retrospectively and 2 typical cases were reported, including their treatment and misdiagnosis in consulting, out-patient and in-patient. RESULT: Typical case 1 was misdiagnosed and mistreated for 42 years, misdiagnosed as blood disease so that the patient was biopsied in bone marrow, misdiagnosed as endometriosis so that the patient was performed uterus resection. Typical case 2 was misdiagnosed and mistreated for 17 years, misdiagnosed as upper digestive tract hemorrhage so that the patient was performed endoscopic sleeve ligation, misdiagnosed as inferior turbinate hemangioma so that the patient was performed nasal endoscopic surgery. CONCLUSION Neglect of family history and the typical signs are the causes of misdiagnosis. So asking about the family history and checking for the typical signs in patients with nose blood can avoid misdiagnosis.
Diagnostic Errors ; Endoscopy ; Epistaxis ; diagnosis ; Female ; Humans ; Nasal Surgical Procedures ; Retrospective Studies ; Turbinates

OBJECTIVETo explore the expressions of HO-2 and CO in the corpus cavernosum of castrated rats in order to further study the pathogenesis of erectile dysfunction (ED).

METHODSWe randomly divided 72 male SD rats into four groups: normal control, sham operation, castration, and castration + ZnPP. We detected intracavernous pressure (ICP) and penile erection in the basic condition and after apomorphine (APO) induction, determined the expression of the HO-2 protein in the corpus cavernosum by laser scanning confocal microscopy, and measured the level of CO by spectrophotometry during different periods of penile erection.

RESULTSThe ICP in the basic condition and that after APO induction and the rate of penile erection were decreased significantly in the castration group ([11.68 ± 0.69] mmHg, [54.81 ± 3.86] mmHg, and 33.3%) and the castration + ZnPP group ([11.20 ± 0.71] mmHg, [41.17 ± 5.41] mmHg, and 22.2%) as compared with the normal control ([22.83 ± 2.66] mmHg, [66.92 ± 7.77] mm-Hg, and 100%) and the sham operation group ([23.35 ±2.22] mmHg, [70.43 ?7. 22] mmHg, and 100%) (all P <0. 01). After APO induction, ICP in the castration + ZnPP group was remarkably reduced in comparison with that in the castration group (P < 0.01), and so was the expression of the HO-2 protein before and during penile erection in the castration (445.4 ± 23.7 and 847.4 ± 35.0) and the castration + ZnPP group (390.1 ± 29.7 and 526.0 ± 52.5) compared with the normal control (512.7 ±57.4 and 1145.2 ± 89.8) and the sham operation group (583.7 ± 8.0 and 1016.3 ± 79.8), the expression of the HO-2 protein significantly decreased in the castration group (445.4 ± 23.7 and 847.4 ± 35.0) (P < 0.05 or 0.01), markedly lower in the castration + ZnPP than in the castration group during penile erection (P < 0.01) but with no significant differences among the four groups after it. Before, during and after penile erection, the levels of CO were remarkably decreased in the castration ([20.59 ± 1.01], [32.53 ± 1.26], and [18.71 ± 1.22] x 10(-7) nmol/L) and the castration +ZnPP group ([12.52 ± 1.05], [21.90 ± 1.02], and [16.56 ± 0.55] x 10(-7) nmol/L) as compared with the normal control ([26.76 ± 1.41], [48.25 ± 1.01], and [27.10 ± 1.58 ] x 10(-7) nmol/L) and the sham operation group ([25.41 ± 2.09], [ 47.90 ± 1.22], and [25.67 ± 1.20] x 10(-7) nmol/L) (P < 0.05 or 0.01), significantly lower in the castration + ZnPP than in the castration group during penile erection (P < 0.01).

CONCLUSIONDecreased expressions of HO-2 and CO may correlate with erectile dysfunction in castrated rats.

Animals ; Apomorphine ; pharmacology ; Carbon Monoxide ; metabolism ; Dopamine Agonists ; pharmacology ; Erectile Dysfunction ; etiology ; Humans ; Male ; Molecular Chaperones ; metabolism ; Orchiectomy ; Penile Erection ; drug effects ; Penis ; drug effects ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley

BACKGROUNDRetroviral vectors have been widely used to introduce foreign into various target cells in vitro, thus showing relatively high systemic delivery efficiency of various transgene products. The authors investigated the stability and efficiency of skeletal muscle-specific hybrid retroviral vectors in expression of human factor IX (FIX) in vitro and iv vivo.

METHODSFIX cDNA in LIXSN vector was replaced with a FIX minigene containing splicing donor and splicing acceptor sequence of first intron of human FIX gene. Two copies of muscle creatine kinase enhancer (MCK, Me2) were inserted in forward or reverse orientation at NheI site of 3' long terminal repeat (LTR), resulting in two hybrid vectors, which were designated as LMe2IXm2SN(F) and LMe2IXm2SN(R), respectively. The vectors were tested in vitro and in vivo for stability and muscle-specificity of factor IX expression with SCID mice.

RESULTSMuscle cells carrying vector with Me2 expressed significantly higher levels of FIX (up to 1800 ng/106.24 h) than those without Me2, thus suggesting that Me2 could specifically increase expression level of FIX in muscle cells. Myoblasts transduced with LMe2IXm2SN(R) produced much less FIX in vivo in SCID mice than LMe2IXm2SN(F). One or two copies of Me2 sequence were deleted in myoblasts transduced with LMe2IXm2SN(R) without changing the orientation of Me2.

CONCLUSIONSLTR inserted with MCK enhancers can specifically increase human FIX expression in skeletal muscle cells in vitro and in vivo, and MCK enhancer should be positioned in the same orientation as that of LTR promoter.

Animals ; Creatine Kinase ; genetics ; Creatine Kinase, MM Form ; Enhancer Elements, Genetic ; Factor IX ; analysis ; genetics ; Gene Expression ; physiology ; Genetic Techniques ; Genetic Vectors ; Hybridization, Genetic ; Isoenzymes ; genetics ; Mice ; Mice, SCID ; Retroviridae ; genetics ; Terminal Repeat Sequences

OBJECTIVE: This study was designed to prove simultaneously blocking both EGFR and COX-2-mediated pathways may be an efficient means of inhibiting cancer cell growth in NPC. METHOD: A combination of tarceva (EGFR-selective tyrosine kinase inhibitors) with celecoxib (Cox-2 inhibitor) was studied on its effects on cell growth, cell cycle progression, apoptosis and protein expression in CNE-2 cell lines by cell growth assay, flow cytometric analysis assay and Western blotting. RESULT: (1) The inhibition rate of cell growth was higher in the group treated with a combination of two agents than that the sum of rates of the two groups treated with only one agent (P < 0.05). (2) The combination of tarceva with celecoxib significantly induced G1 arrest (P < 0.05), but did not increase apoptosis rate (P > 0.05). (3) The group of combination showed less expressions of p-EGFR and COX-2 than any other group. CONCLUSION Simultaneously blocking EGFR and COX-2 mediated pathways would significantly inhibit the growth of CNE-2 cell line, increase G1 arrest and reduce the expression levels of p-EGFR and COX-2.
Apoptosis ; Celecoxib ; Cell Division ; Cyclooxygenase 2 ; metabolism ; ErbB Receptors ; metabolism ; Erlotinib Hydrochloride ; Humans ; Pyrazoles ; administration & dosage ; pharmacology ; Quinazolines ; administration & dosage ; pharmacology ; Signal Transduction ; Sulfonamides ; administration & dosage ; pharmacology ; Tumor Cells, Cultured

OBJECTIVESTo study the morphologic changes of fallopian tubal epithelium in patients with ovarian serous epithelial tumors and to explore the relationship between the tubal epithelial changes and tumorigenesis of serous ovarian carcinoma.

METHODSThe fallopian tubes in 79 cases of high-grade serous ovarian carcinoma, 12 cases of low-grade serous ovarian carcinoma, 16 cases of serous borderline ovarian tumor and 11 cases of non-ovarian benign tumors were serially examined under light microscope. Immunohistochemical study with EnVision method was used to detect the expression of p53 and bcl-2 protein in the fallopian tubal epithelium in all cases. The occurrences of secretory cell outgrowth (SCOUT), p53 signature, serous tubal intraepithelial carcinoma (STIC) and serous invasive carcinoma were analyzed.

RESULTSSCOUT in tubal epithelium was observed in 60.8% (48/79) of the high-grade serous carcinoma group, 4/12 of the low-grade serous carcinoma group, 3/16 of the serous borderline tumor group and 2/11 of the non-ovarian benign tumor group (P = 0.001). P53 signature, STIC and serous invasive carcinoma occurred only in the fallopian tubal epithelium of patients with high-grade serous ovarian carcinoma, with the positive rates being 29.1% (23/79), 15.2% (12/79) and 44.3% (35/79), respectively. Of the 23 cases with p53 signature, 17 cases had solitary lesion and 6 cases involved more than two sites. A total of 33 p53 signature positive foci were found, with 22 foci located at fimbria and 11 at ampulla. Bcl-2 expression was demonstrated in 90.9% of those foci (30/33). Of the 12 patients with STIC, 7 cases were solitary and 5 cases involved more than two sites. A total of 18 STIC foci were found, with 16 foci located at fimbria and 2 at ampulla. All of them were positive for bcl-2.

CONCLUSIONSSCOUT is found in fallopian tubal epithelium in patients with serous ovarian epithelial tumors, especially high-grade serious carcinoma. On the other hand, p53 signature, STIC and invasive serous carcinoma of tubal epithelium are observed only in patients with high-grade serous ovarian carcinoma, with a predilection of fimbrial involvement. Correlation exists between SCOUT, p53 signature, STIC and high-grade serous ovarian carcinomas. Bcl-2 and p53 immunostaining is helpful for demonstrating such lesions.

Adult ; Aged ; Cell Transformation, Neoplastic ; Cystadenocarcinoma, Serous ; metabolism ; pathology ; Epithelial Cells ; pathology ; Epithelium ; pathology ; Fallopian Tube Neoplasms ; metabolism ; pathology ; Fallopian Tubes ; pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Staging ; Ovarian Neoplasms ; metabolism ; pathology ; Precancerous Conditions ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

This study was aimed to investigate the relationship between cytogenetic evolution and disease progression in patient with MDS-RAEB. By a long term (6 years) follow-up of a patient with MDS-RAEB, peripheral blood cell count, bone marrow cell morphology and conventional cytogenetics were monitored regularly. In addition, fluorescence in situ hybridization (FISH) was applied to confirm the aberrant karyotype. The results indicated that this patient was failed with conventional chemotherapy of AML, but had response to ATRA and 6-MP in the 72 months follow-up. At initial diagnosis, the cytogenetics analysis showed normal karyotype, whereas 46, XY, 2q+[1]/46, XY[19] was found at 48 months, 46, XY, dup(1q)[3]/46, XY[7] at 56 months, and dup (1) as well as der (11) with complex karyotype at 68 months, which was accompanied by progressive decrease of platelet count. It is concluded that karyotype evolution is perhaps associated with progression of MDS.
Adult ; Chromosome Aberrations ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 11 ; Follow-Up Studies ; Humans ; Karyotyping ; Male ; Middle Aged ; Myelodysplastic Syndromes ; genetics

Adenoma, Sweat Gland ; metabolism ; Diagnosis, Differential ; Humans ; Keratin-14 ; metabolism ; Keratin-17 ; metabolism ; Keratin-18 ; metabolism ; Keratin-7 ; metabolism ; Keratins ; metabolism ; Papilloma ; metabolism ; Sebaceous Gland Neoplasms ; metabolism ; Skin Neoplasms ; metabolism ; Sweat Gland Neoplasms ; metabolism

BACKGROUNDDNA immunization is a promising novel type of immunotherapy against allergy. An estimated 79.2% patients with asthma, wheezing and/or rhinitis suffer from Dermatophagoides pteronyssinus group 2 (Der p 2) allegen. The aim of the present study was to determine whether DNA vaccine encoding Der p 2 could generate immunologic protection in recombinant Der p 2 (rDer p 2) allergen-induced allergic airway inflammation mice model and to understand the role of DNA vaccination in specific-allergen immunotherapy for asthma.

METHODSAfter DNA vaccination, BALB/c mice were sensitized by intraperitoneal injection (i.p) and challenged by intranasal instillation of rDer p 2. The lung tissues were assessed using hematoxylin and eosin. Mucus-producing goblet cells were identifed using periodic acid-Schiff (PAS)/alcian blue. The total cell number and composition of bronchoalveolar lavage samples were determined. The levels of the cytokines IL-4 and IFN-gamma, as well as IgE and IgG2a in the serum were determined by enzyme-linked immunosorbent assay. Allergen-specific IL-4 and IFN-gamma production by spleen cells were also measured by enzyme-linked immunosorbent assay. Expression of signal transducer and activator of transcription 6 (STAT6) in splenocytes were determined by Western blot.

RESULTSDNA vaccine encoding Der p 2 allergen inhibited extensive infiltration of inflammatory cells and production of mucin induced by allergen. The influx of eosinophils into the lung interstitium was significantly reduced after administration of DNA vaccine. Significant reductions of IL-4 and increase in levels of IFN-gamma in bronchoalveolar lavage fluid were observed. The allergen-specific IgE was markedly decreased in mice receiving DNA vaccination. Allergen could induce higher IFN-gamma, weaker IL-4 in cultured spleen cells from mice receiving DNA vaccine. DNA vaccination inhibited STAT6 expression of spleen cells induced by allergen.

CONCLUSIONThese results indicated that DNA vaccine encoding Der p 2 allergen generates immunologic protection in recombinant Der p 2 allergen-induced allergic airway inflammation mice model with regulating the immune response towards a Th1-type reaction.

Animals ; Antigens, Dermatophagoides ; genetics ; immunology ; Arthropod Proteins ; Asthma ; immunology ; therapy ; Eosinophilia ; prevention & control ; Humans ; Immunoglobulin E ; blood ; Immunoglobulin G ; blood ; Interferon-gamma ; biosynthesis ; Interleukin-4 ; biosynthesis ; Mice ; Mice, Inbred BALB C ; STAT6 Transcription Factor ; Th1 Cells ; immunology ; Trans-Activators ; analysis ; Vaccination ; Vaccines, DNA ; immunology