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21.
Dietary zinc deficiency in rats induces hyperplasia in the esophagus and
increases N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumor
incidence. Previous work showed a direct relationship between epithelial
cell proliferation and esophageal tumor incidence in rats given multiple
doses of NMBA. We investigated the effects of single low doses of NMBA in
zinc-deficient rats since a single dose of 5.0 mg/kg was reported to be
non-carcinogenic in rats. Zinc-sufficient and deficient rats received a
single i.g. dose of NMBA at 0.5 or 2.0 mg/kg. At week 14, tumor incidence
was 50% with 0.8 +/- 1.0 tumors/rat, and 80% with 2.2 +/- 1.9 tumors/rat,
in deficient groups, D(0.5) and D(2.0), that received the lower and higher
dose, respectively. In addition, two small papillomas were found in one out
of eight untreated zinc-deficient rats. None of the NMBA-treated or
untreated zinc- sufficient rats had any tumors. Esophageal cell
proliferation, as determined by proliferating cell nuclear antigen (PCNA)
immunohistochemistry, showed that, irrespective of NMBA treatment,
deficient esophagi had significant increases in the number of labeled
cells, the total number of cells, and the labeling index, as compared with
zinc-sufficient ones. Mutations in Ha-ras and p53 genes in esophageal
tumors were detected by single strand conformation polymorphism (SSCP)
analysis. DNA sequencing of variant conformers revealed a point mutation
(GGA-->GAA, codon 12) in Ha-ras in 4/5 (80%) and 5/8 (63%) tumors, from
D(0.5) and D(2.0) rats, respectively. Three out of eight tumors from D(2.0)
rats exhibited SSCP mobility shifts within p53 exons 5 and 7: two tumors
(2/8, 25%) had missense mutations and the third, a silent mutation. Of the
two tumors with p53 mutations, one had a double mutation (transition at
codon 164, TCA-->TTA; transversion at codon 241, AGT-->TGT), and the
other tumor, a transition at codon 172 (AGA-->GGA), with amino acid
changes in all cases. In parallel with PCNA expression, elevated p53
expression was associated with hyperplastic and dysplastic regions, as well
as with tumors, in deficient esophagi. In short, these data indicate that
dietary zinc deficiency, with its associated sustained increased cell
proliferation in the esophagus, can drive an otherwise non-tumorigenic dose
of NMBA into a highly tumorigenic one.
相似文献
22.
Recently, the beneficial role of steroids for acute laryngotracheobronchitis has been more clearly defined for both intubated and unintubated patients. However, corticosteroids also improve the clinical signs of airway haemangiomata. Two patients are described who illustrate how this can be a source of diagnostic confusion. 相似文献
23.
Colorectal hemangioma: radiologic findings 总被引:1,自引:0,他引:1
The authors correlated radiographs with the clinical and histologic data of 12 patients with colorectal hemangioma. All patients presented with rectal bleeding, which was chronic in seven. Phleboliths were also visible in seven cases, which correlated with chronic bleeding in five. On barium studies, three masses were soft and three produced rigid narrowing. The atypical features of rigid luminal narrowing, which might mimic a carcinoma, and hypovascularity correlated with chronic bleeding or visible phleboliths, which suggest the correct diagnosis of colorectal hemangioma. 相似文献
24.
KM FOCK JY KANG HS NG TM NG KA GWEE CC LIM 《Journal of gastroenterology and hepatology》1995,10(4):379-382
Roxatidine acetate, a new H2 receptor antagonist, was compared with ranitidine in the treatment of duodenal ulcers in a double-blind multicentre study. Eighty-four patients with endoscopically proven duodenal ulcer were randomized to receive 150 mg roxatidine acetate or 300 mg ranitidine at bedtime. Repeat endoscopy was performed after 4 weeks (25–33 days) and if the ulcer had not healed, another endoscopy was performed after a further 4 weeks of treatment. Using per protocol analysis 73.6% of ulcers treated with roxatidine healed at 4 weeks compared to 72.2% of ulcers treated with ranitidine (P=NS). The healing rates at 8 weeks were 92% with roxatidine and 83.3% with ranitidine (P=NS). Using equivalence tests, the healing rate of roxatidine was found to be equivalent to that of ranitidine within a 20% region. Roxatidine users took significantly less antacids than ranitidine users (P < 0.05). There were no significant adverse effects due to roxatidine or ranitidine. Roxatidine is a safe effective drug in the treatment of duodenal ulcers with a healing rate comparable to that of ranitidine. 相似文献
25.
Antibiotic-Induced Lipopolysaccharide (LPS) Release from Salmonella typhi: Delay between Killing by Ceftazidime and Imipenem and Release of LPS 总被引:3,自引:0,他引:3 下载免费PDF全文
Petra van Langevelde Kitty M. C. Kwappenberg Paul H. P. Groeneveld Herman Mattie Jaap T. van Dissel 《Antimicrobial agents and chemotherapy》1998,42(4):739-743
It has been suggested that the antibiotic-induced release of lipopolysaccharide (LPS) is an important cause of the development of septic shock in patients treated for severe infections caused by gram-negative bacteria. β-Lactam antibiotics change the integrity of the bacterial cell envelope by binding to penicillin-binding proteins (PBP) in the membrane and thus may affect the amount of LPS that is released and the kinetics of that release. In this respect, ceftazidime at intermediate concentrations binds with a high affinity to PBP 3 and PBP 1a and thus can induce filament formation in addition to killing, whereas imipenem preferentially binds to PBP 2 and PBP 1b, leading to spheroplast formation and rapid cell lysis. We investigated the effects of these antibiotics on the killing and the release of the radioactively labelled LPS of Salmonella typhi Ty 21A. A mathematical model was developed to calculate the delay between bacterial killing and LPS release, designated the lag time. At antibiotic concentrations inducing equal killing, the amount of LPS released was the same for both antibiotics. Only after 6 h of incubation at antibiotic concentrations above 0.5 μg/ml, the amount of 3H-LPS released was slightly higher (~1.2-fold) in incubations with ceftazidime than in those with imipenem, and the maximum releases of the total label were 33.2% ± 0.89% and 27.1% ± 0.45%, respectively. Despite the clear concentration-dependent effect on the bacterial killing and subsequent LPS release, the lag time was independent of the antibiotic concentration. For ceftazidime as well as imipenem the lag time amounted to approximately 60 min. In conclusion, our findings imply that the mechanism of antibiotic-induced LPS release is independent of the PBP affinities for these β-lactam antibiotics. Furthermore, once the organism is killed by either imipenem or ceftazidime, the rate of LPS release from S. typhi does not differ according to the antibiotic with which the organism is killed, and there is little difference in the relative amount of LPS released. 相似文献
26.
27.
van der Burg SH Ressing ME Kwappenberg KM de Jong A Straathof K de Jong J Geluk A van Meijgaarden KE Franken KL Ottenhoff TH Fleuren GJ Kenter G Melief CJ Offringa R 《International journal of cancer. Journal international du cancer》2001,91(5):612-618
Tumor-specific T-helper (Th) immunity was found to play a pivotal role in the natural and vaccine-induced immune defense against tumors. Since the majority of cervical cancers express human papillomavirus type 16 (HPV16) E7 oncoprotein, it is important to investigate the Th response against this target antigen in detail. By means of PBMC cultures from HLA-typed healthy donors, we identified the central part of HPV16 E7 (E7(41-72)) as the major immunogenic region within this antigen. Furthermore, we mapped 3 distinct Th epitopes within this region (DR15/E7(50-62), DR3/E7(43-77), DQ2/E7(35-50)). In a parallel approach, employing IFN-gamma ELISPOT analysis, we detected Th immunity against HPV16 E7 in subjects with HPV16+ lesions. Several of these responses matched with the 3 Th epitopes defined in our study. A number of other HPV16+ subjects did not display any E7-specific type 1 cytokine-producing T-cell immunity, indicating failure of the immune response. Our combined data argue for more extensive as well as longitudinal analysis of HPV16-specific T-cell immunity using the ELISPOT assay described, as well as for HPV-specific vaccination of individuals with HPV+ lesions. 相似文献
28.
van der Burg SH Kwappenberg KM O'Neill T Brandt RM Melief CJ Hickling JK Offringa R 《Vaccine》2001,19(27):3652-3660
Human papillomavirus (HPV) E6 and E7 oncoproteins are attractive targets for T-cell-based immunotherapy of cervical intraepithelial neoplasia (CIN) and cancer. A newly designed vaccine, comprising the HPV16 L2, E6 and E7 as a single fusion protein (TA-CIN), was shown to elicit HPV16-specific CTL, T-helper cells and antibodies in a pre-clinical mouse model. These immune responses effectively prevented outgrowth of HPV16-positive tumour cells in a prophylactic setting as well as in a minimal residual disease setting. CTL immunity was optimally induced when TA-CIN was employed in heterologous prime-boost regimens in combination with TA-HPV, a clinical grade vaccinia-based vaccine. These data provide a scientific basis for the use of TA-CIN, alone or in combination with TA-HPV in future human trials. 相似文献
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