The effect of hyperbaric oxygen on reperfusion of ischemic axial skin flaps: a laser Doppler analysis.

This study evaluates the microvascular reperfusion of ischemic skin flaps with and without acute hyperbaric oxygen (HBO) treatment. Thirty-two axial pattern epigastric skin flaps (3 x 6 cm) in male Wistar rats were subjected to 8 hours of global ischemia by pedicle clamp occlusion. The rats were divided into the following control and two experimental groups: Control (n = 12) with ischemia, no HBO; Group 1 (n = 11) with HBO treatment (three 1.75-hour dives, 2.5 absolute atm, 100% O2) during ischemia; and Group 2 (n = 9) with HBO treatment (two 1.75-hour dives) immediately after ischemia. Laser Doppler flows were recorded in two distal standardized flap locations at 0.5, 2, 4, and 18 hours after reperfusion in control rats and Group 1 rats and at 18 hours only in Group 2 rats, using a Med-Pacific 6000 laser Doppler unit. Mean distal flap laser Doppler flows (mV) were Control: 0.5 hours = 23.2 +/- 11.9, 2 hours = 52.8 +/- 27.3, 4 hours = 53.6 +/- 32.1, 18 hours = 40.2 +/- 36.2; Group 1: 0.5 hours = 71.8 +/- 30.9 (p less than 0.05 vs. control), 2 hours = 74.3 +/- 27.3, 4 hours = 67.4 +/- 20.6, 18 hours = 79.1 +/- 40.3 (p less than 0.05 vs. control); and Group 2: 18 hours = 90.3 +/- 47.9 (p less than 0.05 vs. control). It is concluded that acute HBO treatment of ischemic rat skin flaps improves distal microvascular perfusion as measured by laser Doppler flowmetry. This effect is observed for HBO treatment given either during or immediately after prolonged global ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

乳腺管状小叶癌

乳腺管状小叶癌（Tubulolobular carcinoma，TLC）最初是被作为小叶癌的管状变型。作者总结了27例TLC的组织学、免疫表型和临床特征，并与纯小管癌和经典型小叶癌进行了比较。此组患者年龄43-79岁（中位年龄60岁）。1例双侧乳腺受累，5例病变为多灶性。肿瘤直径0．5-2．5cm，色灰褐，质硬。组织学观察：TLC的肿瘤细胞形成管状和条索状两种结构模式并相互混杂，且两者比例相当（统称为管状小叶模式）。     

Germline mutations of the CDKN2 gene in UK melanoma families

Germline mutations in CDKN2 on chromosome 9p21, which codes for the cyclin D kinase inhibitor p16, and more rarely, mutations in the gene coding for CDK4, the protein to which p16 binds, underlie susceptibility in some melanoma families. We have sequenced all exons of CDKN2 and analysed the CDK4 gene for mutations in 27 UK families showing evidence of predisposition to melanoma. Five different germline mutations in CDKN2 were found in six families. Three of the mutations (Met53Ile, Arg24Pro and 23ins24) have been reported previously. We have identified two novel CDKN2 mutations (88delG and Ala118Thr) which are likely to be associated with the development of melanoma, because of their co-segregation with the disease and their likely functional effect on the CDKN2 protein. In binding assays the protein expressed from the previously described mutation, Met53Ile, did not bind to CDK4/CDK6, confirming its role as a causal mutation in the development of melanoma. Ala118Thr appeared to be functional in this assay. Arg24Pro appeared to bind to CDK6, but not to CDK4. No mutations were detected in exon 2 of CDK4, suggesting that causal mutations in this gene are uncommon. The penetrance of these mutant CDKN2 genes is not yet established, nor is the risk of non-melanoma cancer to gene carriers.      

The impact of health insurance on an African-American population with colorectal cancer.

This study evaluates the impact of health insurance as a substitute for social class on tumor location, presentation, stage, grade, and age-adjusted survival in an African-American population. Patients were stratified by insurance into two groups: group 1 (private insurance and Medicare parts A & B) and group 2 (Medicaid, Medical Charity, self-pay, uninsured, or unemployed). A total of 212 patients were evaluated. Of these, 210 patients were insured or had Medical Charity, and two were uninsured. The type of health insurance did not significantly affect age-adjusted survival. However, age and stage at presentation were positive predictors of age-adjusted survival. Higher socioeconomic status was associated with group 1 health insurance.     

Multigenic control of skin tumor susceptibility in SENCARA/Pt mice

Skin tumors induced in mice by initiation-promotion (2 microg DMBA-2 microg TPA) protocols were found to be under multigenic control. Eighty- one N2 mice from the cross (BALB/cAnPt x SENCARA/Pt)F1 x SENCARA/Pt that were either solidly resistant (no papillomas) or highly susceptible (> or = 7 papillomas/mouse) were subjected to a 'genome scan' using 89 microsatellite markers to check for associations with susceptible and resistant phenotypes. A locus on Chr 5 (Skts4) was found to control the susceptibility of SENCARA/Pt mice and the resistance of BALB/cAnPt mice to papilloma formation. In addition, higher than expected linkage scores were seen for the markers D9Mit271, D11Mit268 and D12Mit56. Further work is required to establish whether genes determining papilloma formation are located in these regions of the genome. In general, no evidence was seen for loss of heterozygosity in microsatellite markers on Chrs 5, 9 and 11 in 17 microdissected papillomas from (BALB/c x SENCARA)F1 hybrid mice.      

Clinicopathological Features of Colon Polyps from African-Americans

Background and Aims  

Among the ethnic groups, the age-standardized incidence rate of colorectal cancer (CRC) is highest among African-Americans. The majority of CRC arise from preexisting adenoma. It is shown that 30% of the US adult population has adenomas. The potential risk of malignant transformation in adenomas differs by specific pathologic and clinical characteristics that we aimed to study in AAs.     

Simian virus 40 large tumor antigen-immortalized normal human liver epithelial cells express hepatocyte characteristics and metabolize chemical carcinogens.

Normal human liver tissue and cultured human hepatocytes are valuable models to study xenobiotic metabolism and toxicity, but they only have a limited in vitro life-span and are not readily available. This report describes the establishment of replicative cultures of human adult liver epithelial cells in serum-free medium. The longevity of three of these cultures, derived from different donors, was extended by introduction of the simian virus 40 large T antigen gene. Two cell lines, THLE-2 and -3, established with a recombinant simian virus 40 large T antigen virus have undergone > 100 population doublings, are nontumorigenic when injected into athymic nude mice, have near-diploid karyotypes, and do not express alpha-fetoprotein. The cells express cytokeratin 18 and albumin in early passage, whereas higher-passage cells in logarithmic-phase growth also express cytokeratin 19. THLE-2 and -3 cells metabolize benzo[a]pyrene, N-nitrosodimethylamine, and aflatoxin B1 to their ultimate carcinogenic metabolites that adduct DNA, which indicates functional cytochrome P450 pathways. Other enzymes involved in metabolism of chemical carcinogens, such as epoxide hydrolase, NADPH cytochrome P450 reductase, superoxide dismutase, catalase, glutathione S-transferases, and glutathione peroxidase are also retained by THLE cells. Thus, these immortalized human liver cells constitute an in vitro model for pharmacotoxicological studies and for the investigation of etiology and pathogenesis of human hepatocellular carcinoma.     

Helicobacter pylori Protection Against Reflux Esophagitis

Background and Aim

Negative association has been reported between presence of Helicobacter pylori and developing gastroesophageal reflux disease (GERD) and its complications. The aim of this study was to determine whether H. pylori (HP) can be protective against GERD in an African American (AA) population.

Methods

From 2004 to 2007, we studied 2,020 cases; esophagitis (58), gastritis (1,558), both esophagitis and gastritis (363) and a normal control group (41). We collected their pathology and endoscopy unit reports. HP status was determined based on staining of gastric biopsy.

Results

HP data was available for 79 % (1,611) of the cases. The frequency of HP positivity in gastritis patients was 40 % (506), in esophagitis patients 4 % and in normal controls 34 % (11), while HP was positive in 34 % of the patients with both esophagitis and gastritis. After adjusting for effects of age and sex, odds ratio of HP was 0.06 (95 % CI 0.01–0.59; P value = 0.01) for the esophagitis group versus the normal group.

Conclusions

Our results show H. pylori has a significant negative association with esophagitis in AAs which may point to a protective role of H. pylori in the pathogenesis of esophagitis. In addition, H. pylori may be the reason for the low GERD complications in AAs.