Clinicopathological features of typical and nontypical hereditary non-polyposis colorectal cancer and their germline mutation of hMLH_1 and hMSH_2

Objective To study the clinicopathological features of the Chinese hereditary non-polyposis colorectal cancer and its germline mutation of hMLH1 and hMSH2. Methods Thirteen typical Chinese hereditary non-polyposis colorectal carcinoma (HNPC) C kindreds and 19 nontypical HNPCC families were registered and followed up. The germline mutation of the hMLH1 and hMSH2 of 12 index cases of 6 typical and 6 nontypical NHPCC were screened by PCR-SSCP. Samples with abnormal mobility were sequenced direcdy. Results The average age of typical HNPCC was 47, no difference existed between sexs. Location of the tumors of typical HNPCC represented 44.7% on the right half colon and non-typical HNPCC 65. 8% on the rectum. The rate of the metachronos cancer was 11.5%. The 3 - , 5 - and 10 -year survival rate was 64. 0%, 45. 3% and 31. 2% respectively. Among 12 cases, 8 showed abnormal mobility. Except for an intron polymorphinism, six exons abnormalities were found in 5 of 12 proband. Sequencing showed 4 missense,7

In vitro interference of cefotaxime at subinhibitory concentrations on biofilm formation by nontypeable Haemophilus influenzae

Objective:To investigate the in vitro interference of cefotaxime at subinhibitory concentrations [sub-minimal inhibitory concentrations(MIC)] on biofilm formation by nontypeable Haemophilus influenzae(NTHi).Methods:The interference of subinhibitory concentrations of cefotaxime on biofilm formation of the clinical strong-biofilm forming isolates of NTHi was evaluated by a microtiter plate biofilm formation assay.The effect of sub-MIC cefotaxime on bacterial cell-surface hydrophobicity was determined using a standard microbial adhesion to n-hexadecane test.Additionally,the effects on bacterial adherence to human fibronectin and expression of bacterial adhesins were also investigated.Results:Subinhibitory concentrations of cefotaxime,both at 0.1× and 0.5× MIC levels,efficiently reduced the NTHi biofilm formation,and this effect was independent of decreasing bacterial viability.Sub-MIC cefotaxime also decreased bacterial cell-surface hydrophobicity and reduced adherence to human fibronectin.Inhibition in the P2 and P6 gene expressions upon exposure to sub-MIC cefotaxime was also noted.Conclusions:Taken together,our results indicate that sub-MIC cefotaxime interferes with the formation of NTHi biofilm,and this effect is feasibly related to the interference with cell-surface hydrophobicity,fibronectin-binding activity as well as alteration of the P2 and P6 gene expression.The findings of the present study therefore provide a rationale for the use of subinhibitory concentrations of cefotaxime for treatment of NTHi-related diseases.

Synergistic and feedback signaling mechanisms in the regulation of inflammation in respiratory infections

Pneumonia, the most typical and frequent lower respiratory tract infection （LRTI）, is a leading cause of health problems in the United States. Bacteria represent the most prevailing cause of pneumonia in both children and adults. Although pneumonia with a single bacterial infection is common, a significant portion of patients with pneumonia is polymicrobial. This infection is often complexed with other physiological factors such as cytokines and growth factors. Nontypeable Haemophilus influenzae （NTHi） is the most frequently recovered Gram-negative bacterial pathogen in the respiratory system and induces strong inflammatory responses. NTHi also synergizes with other respiratory pathogens, such as Streptococcus pneumoniae and respiratory viruses and pro-inflammatory cytokines, such as tumor necrosis factor-alpha （TNF-α）. It is noteworthy that NTHi not only synergizes with growth factors such as transforming growth factor-beta （TGF-β）, but also utilizes growth factor receptors such as TGF-β receptor and epidermal growth factor receptor （EGFR）, to enhance inflammatory responses. Although appropriate inflammation is a protective response against invading pathogens, an uncontrolled inflammatory response is often detrimental to the host. Thus, inflammation must be tightly regulated. The human immune system has evolved strategies for controlling overactive inflammatory response. One such important mechanism is via regulation of negative feedback regulators for inflammation. CYLD, a multifunctional deubiquitinase, was originally reported as a tumor suppressor, but was recently identified as a negative regulator for nuclear factor-kappa B （NF-κB） signaling. It is induced by NTHi and TNF-α via a NF-κB-dependent mechanism, thereby serving as an inducible negative feedback regulator for tightly controlling inflammation in NTHi infection.