Expression of p21WAF1/CIP1 in colorectal adenomas and adenocarcinomas and its correlation with p53 protein expression

The expression of p53-Inducible cylln-dependent kinase Inhibitor, p21^WAF1/CIP1 in non-neopiastic mucosa, adenoma and adenocarclnoma of the colorectum was examined by immunohistochemistry and western bootting and Its relation with the expression of p53 protein was analyzed. Non-neoplastic epithelial cells at the surface area showing no proitferative activity expressed p21^WAF1/CIP1.The expression of p21^WAF1/CIP1 was lmmunohistochemlcally detected in 55% (206/377 of the adenomas and 66% (190/289) of the adenocarcinomas, respectively. The lncldence of strongly positive cases was significantly higher In the adenocarcinomas (27%) than In the adenomas (18%) ( P< .05). The incidence of cases wtth strong p21^WAF1/CIP1 expression was higher In stages 0,1 and 2 carcinomas than in stages 3 and 4 carcinomas ( P <0.05). A decrease in the incidence of cases with strong expression was detected in carclnomas Invading deeper than muscularis propria. The influence of strongly positive cases was signiflcantly lower in carcinomas with lymph node metastasis than those without metastasls ( P <0.05). The expression of p21 as well as p53 detected by western blotting was compatlble with the results of lmmunohistochemlstry in most cases examined. However, there was no significant correlatlon between the expression of p21^WAF1/CIP1 and the abnormal accumulation of p53. These findlngs overall suggest that: (i) the physiological expression of p21^WAF1/CIP1 may be associated with cellular senescence of colorectal mucosa; (ii) reduced expression of p21^WAF1/CIP1 participate in the progression of colorectal carcinoma; and (iii) p53-Independent paulway may be considerably Involved In the inductions of p21^WAF1/CIP1.     

Trends of β-lactam antibiotic susceptibility in blood-borne methicillin-resistant Staphylococcus aureus (MRSA) and their linkage to the staphylococcal cassette chromosome mec (SCC mec ) type

We investigated trends of beta-lactam antibiotic susceptibility in a total of 218 strains of blood-borne methicillin-resistant Staphylococcus aureus (MRSA) isolated from 1978 through 2002 at a middle-size geriatric hospital in Tokyo; the strains were classified by the MRSA marker, staphylococcal cassette chromosome mec (SCCmec). The minimum growth inhibitory concentration (MIC) of cloxacillin at which 50% of the strains were inhibited (MIC50) was 2 microg/ml in the strains isolated in 1978-1984 and 32 to 64 microg/ml in the strains isolated subsequently. Similarly, the MIC50 values of cefazolin and imipenem in the 1978-1984 isolates were 16 and 相似文献   

Pattern of maxillofacial and associated injuries in road traffic accidents

BACKGROUND: Road Traffic Accidents (RTAs) are a major cause of morbidity and mortality in Kenya. Victims may suffer multiple injuries including maxillofacial injuries. In most developing countries RTAs are the leading cause of maxillofacial injuries. In an attempt to reduce RTAs, the government of Kenya has enacted a legislation requiring mandatory fitting of speed governors and safety belts by passenger service vehicles. OBJECTIVE: To describe the characteristics and pattern of maxillofacial and associated injuries sustained in road traffic accidents. DESIGN: A cross-sectional study. SETTING: Kenyatta National Hospital (KNH). SUBJECTS: All patients involved in RTAs brought to casualty and the dental department of KNH as well as accident victims admitted to the KNH mortuary over a four- month period from September 2004 to December 2004. RESULTS: Four hundred and thirteen (85.7%) had non-fatal injuries whereas 69 (14.3%) had sustained fatal injuries. Males in the 21-30-year age group were the most affected. Most accidents occurred during weekends with pedestrians being the leading casualties in 59.5% and 71.4% of non-fatal and fatal cases respectively. Most accidents were caused by passenger service vehicles (matatus) which were responsible for 62% and 40.6% of non-fatal and fatal injuries respectively. Non-use of safety belts was reported in 56.6% of the cases who suffered non-fatal injuries. In the non-fatal category 89.6% of the casualties had soft tissue injuries (STIs) involving the craniofacial region with facial cuts being the majority (69.2%). Two hundred and seventy three (66.1%) incidents of other STIs than those of the head region were noted, the lower limbs accounting for 45.4% of these. Only 5.1% of the casualties with non-fatal injuries had fractures involving the maxillofacial skeleton. Skeletal injuries other than those involving the maxillofacial region were found in 142 (34.1%) incidents. In the fatal category head injury alone was the leading cause of death accounting for 37.7% of the cases followed by head and chest injuries combined which were responsible for 13% of the cases. CONCLUSION: Injuries to the maxillofacial skeleton appear to be uncommon in this series. Pedestrians in their third decade of life are most affected with passenger service vehicles being responsible in the majority of the cases. RECOMMENDATIONS: Interventional programmes targeting pedestrians and those in the third and fourth decades of life should be enacted.     

Targeted drug delivery to tumor vasculature by a carbohydrate mimetic peptide

Although numerous carbohydrates play significant roles in mammalian cells, carbohydrate-based drug discovery has not been explored due to the technical difficulty of chemically synthesizing complex carbohydrate structures. Previously, we identified a series of carbohydrate mimetic peptides and found that a 7-mer peptide, designated I-peptide, inhibits hematogenous carbohydrate-dependent cancer cell colonization. During analysis of the endothelial surface receptor for I-peptide, we found that I-peptide bound to annexin 1 (Anxa1). Because Anxa1 is a highly specific tumor vasculature surface marker, we hypothesized that an I-peptide-like peptide could target anticancer drugs to the tumor vasculature. This study identifies IFLLWQR peptide, designated IF7, as homing to tumors. When synthetic IF7 peptide was conjugated to fluorescent Alexa 488 (A488) and injected intravenously into tumor-bearing mice, IF7-A488 targeted tumors within minutes. IF7 conjugated to the potent anticancer drug SN-38 and injected intravenously into nude mice carrying human colon HCT116 tumors efficiently suppressed tumor growth at low dosages with no apparent side effects. These results suggest that IF7 serves as an efficient drug delivery vehicle by targeting Anxa1 expressed on the surface of tumor vasculature. Given its extremely specific tumor-targeting activity, IF7 may represent a clinically relevant vehicle for anticancer drugs.     

Fragments of genomic DNA released by injured cells activate innate immunity and suppress endocrine function in the thyroid

Activation of innate and acquired immune responses, which can be induced by infection, inflammation, or tissue injury, may impact the development of autoimmunity. Although stimulation of cells by double-stranded DNA (dsDNA) has been shown to activate immune responses, the role of self-genomic DNA fragments released in the context of sterile cellular injury is not well understood. Using cultured thyroid cells, we show that cell injury prompts the release of genomic DNA into the cytosol, which is associated with the production of type I interferons, inflammatory cytokines, and chemokines. Molecules necessary for antigen processing and presentation to lymphocytes are also induced in thyroid cells by injury. dsDNA strongly suppressed the expression of sodium/iodide symporter and radioiodine uptake. To identify molecules responsible for sensing cytosolic dsDNA, we directly identified the cellular proteins that bound a dsDNA Sepharose column by mass spectrometry. Our analysis identified histone H2B, which was previously demonstrated to be an essential factor that mediates the activation of innate immunity induced by dsDNA. Knockdown of histone H2B using specific small interfering RNA abolished cell injury-induced innate immune activation and increased sodium/iodide symporter expression. These results indicate that genomic DNA fragments released by cell injury are recognized by extrachromosomal histone H2B, which results in the activation of genes involved in both innate and acquired immune responses in thyroid cells and suppression of thyroid function. These results suggest that sterile thyroid injury, in the absence of infection, may be sufficient to trigger autoimmune reaction and to induce thyroid dysfunction.     

Impact of a Rapid Results Initiative Approach on Improving Male Partner Involvement in Prevention of Mother to Child Transmission of HIV in Western Kenya

A rapid results initiative (RRI) aimed at increasing male involvement in prevention of mother-to-child transmission (PMTCT) and service uptake among pregnant women at 116 antenatal clinics in Western Kenya was compared at baseline, during the RRI, and 3-months post-RRI. Male involvement increased from 7.4 to 54.2% during RRI (risk difference [RD] 0.47, CI 0.45–0.48) then 43.4% post-RRI (RD 0.36, CI 0.35–0.37). Among HIV-infected women, facility delivery increased from 40.0 to 49.9% (RD 0.10, 95% CI 0.06–0.13) and 65.0% post-RRI (RD 0.25, 95% CI 0.22–0.28). HIV-infected pregnant women linkage to HIV care increased from 58.6 to 85.9% (RD 0.27, CI 0.24–0.30) and 97.3% post-RRI (RD 0.39, CI 0.36–0.41). Time to ART initiation reduced from 29 days (interquartile range [IQR] 6–56) to 14 days (IQR 0–28) to 7 days (IQR 0–20). A male-centered RRI can significantly increase men’s engagement in antenatal care leading to improved partner utilization of PMTCT and antenatal services.     

Small Nonfunctioning Islet Cell Tumor in the Body of the Pancreas: Report of a Case

Islet cell tumors of the pancreas are uncommon, and nonfunctioning tumors are even rarer than functioning ones. We report the case of a 67-year-old woman with a small nonfunctioning islet cell tumor, 6 × 5mm in diameter, which was detected incidentally by ultrasonography, and subsequently confirmed by double-helical computed tomography. Diagnosis was established by histopathological examination after 80% distal pancreatectomy with splenectomy, and by various laboratory tests. Histologically, the islet cell tumor showed highly cellular spindle or epithelioid cells, which were positive for Grimelius stain. Immunohistochemical examination revealed that the tumor cells were positive for chromogranin A, but negative for somatostatin, insulin, glucagon, and gastrin. Its small size, location, and benignity make this a very rare type of nonfunctioning islet cell tumor.