Proteomic profiling in microdissected hepatocellular carcinoma tissue using ProteinChip technology

At present, the molecular mechanisms of hepatocellular carcinogenesis are not well understood. It is known, however, that cancer development and progression are accompanied by profound changes at the cellular and subcellular level, involving RNA/DNA and protein structure and function. Therefore, high-throughput, proteomic techniques targeting these biological molecules may provide novel insights into HCC genesis and prognosis. We characterized tissue protein profiles from 10 HCC patients using ProteinChip technology (SELDI) which is able to detect minute amounts of proteins and moreover to analyze complex protein pattern. Therefore, after histopathological examination, proteins from kryostat sections of non-tumorous hepatic tissue as well as from central and peripheral tumor areas were isolated from complete histological sections or from selected and microdissected tissue areas. Analysis on the SAX and WCX ProteinChip Arrays revealed 14-26, and 25-29 differentially expressed peaks respectively, which characterized non-tumorous and tumor tissue (p< or =0.05). One feature which allows differentiation between central tumor and peripheral tumor regions could only be detected in microdissected tissue. Using ProteinChip technology in combination with tissue microdissection it is possible to investigate complex changes at the protein level in hepatocellular cancer associated with tumor development and progression.     

Methylation of multiple genes in prostate cancer and the relationship with clinicopathological features of disease

Promoter methylation plays an important role in the inactivation of tumor suppressor genes during tumorigenesis. We examined the methylation status of glutathione s-transferase Pi1 (GSTP1), retinoic acid receptor beta (RARB), CD44, E-cadherin (ECAD), RAS association domain family protein 1A (RASSF1A) and endothelin B receptor (EDNRB) genes in 81 prostate cancer and 42 benign prostatic hyperpasia specimens. Genomic DNA was isolated from archived formaldehyde-fixed and paraffin-embedded tissue blocks. Methylation-specific PCR (MSP) was carried out after bisulfite treatment of genomic DNA. Methylation frequencies in prostate cancer and benign prostatic hyperplasia were 72% and 5% for GSTP1, 40% and 0% for RARB, 72% and 38% for CD44, 61% and 14% for ECAD, 49% and 19% for RASSF1A and 72% and 62% for EDNRB, respectively. Methylation of GSTP1, RARB, CD44, ECAD and RASSF1A, but not of EDNRB was detected at a statistically higher frequency in prostate cancer than in the benign prostatic hypertrophy specimens. Methylation of RARB occurred more frequently in early onset (age <55 years) as compared to late onset disease (age >70 years) (odds ratio, 8.6; 95% CI, 1.4-51.4; P=0.02). Methylation of RARB also occurred more frequently in stage III as compared to stage II disease (odds ratio, 3.2; 95% CI, 1.1-8.8; P=0.03). A methylation index (MI) was calculated as the total number of genes methylated, excluding EDNRB. A trend toward higher MI was noted in stage III as compared to stage II disease, and in Gleason score 7 as compared to Gleason score 6 tumors. Our results suggest that the methylation of selected genes in prostate cancers correlates with clinicopathological features of poor prognosis.     

Formula with reduced content of improved,partially hydrolyzed protein and probiotics: infant growth and health

Objective

This study determined growth and stool characteristics of infants fed a formula with reduced content of a partially hydrolyzed protein of improved quality and assessed the effect of the addition of a probiotic on infant growth and health.

Design, methods

The double-blind study involved three formulas: a reduced protein (1.90 g/100 kcal) formula (formula RP), the same formula with Bifidobacterium lactis (formula RP+P), and a higher-protein (2.39 g/100 kcal) control formula (C). Protein of the formulas consisted of partially hydrolyzed modified whey proteins. Normal term infants were randomly assigned to one of the formulas, which were fed from soon after birth to 4 months of age; 88 infants completed the study. Growth was measured and formula tolerance, stool characteristics, and illness incidence were recorded.

Results

All three formulas supported growth equally well. Plasma concentrations of urea and of threonine and proline were markedly (significantly) lower with RP and RP+P than with C. No differences in feeding-related behaviors were noted, but stools were softer with formula C than with the other formulas. Infants fed RP+P had significantly fewer episodes of diarrhea (0.21 episodes) than infants fed RP (0.41 episodes) or C (0.91 episodes).

Conclusion

A reduced-protein formula with and without added probiotics (B. lactis) supports normal growth of infants during the first 4 months. In addition, it leads to lower plasma levels of urea, threonine, and proline. Supplementation of the formula with Bifidobacterium lactis offers protection against diarrheal illness.

     

Is there evidence for a latent class called 'hypomanic temperament'?

BACKGROUND: Affective disorders belong to the most common psychiatric disorders. Several risk factors have been postulated and empirically investigated. Researchers like Akiskal [Interpersonal Factors in the Origin and Course of Affective Disorders, Gaskell, London, 1996] have pointed out the associations between sub-affective temperaments and affective disorders. However, no study has dealt with the issue whether there is a latent class of such sub-affective temperaments or if such temperaments are best conceptualized as fully dimensional. We investigated whether the Hypomanic Personality Scale [J. Abnorm. Psychol. 121 (1986) 214-222] as an indicator of hyperthymia is taxonic in structure. METHODS: We chose two different samples to address this issue: A sample of young adults (n = 1,966) and another sample of adolescents (n = 4,045). We ran MAXCOV-HITMAX analyses based on identical subsets of items in both samples. RESULTS: Neither in the sample of young adults nor in the sample of adolescents there was evidence for a latent class called 'hypomanic temperament'. LIMITATION: Only one indicator for vulnerability and one procedure to test for latent classes was used. Furthermore, we do not know how many of our sample had a life-time history or current affective disorders. CONCLUSIONS: The hypomanic-hyperthymic temperament is best conceptualized as a dimension in the general population. However, before drawing final conclusions about the taxonicity of the risk for affective disorders, more research is needed using different measures, samples and methods to resolve this question of the dimensionality of vulnerability. Additionally, the question remains open how to conceptualize mania itself.     

Fast breath-hold T2-weighted MR imaging reduces interobserver variability in the diagnosis of adenomyosis

OBJECTIVE: We compared two rapid MR imaging T2-weighted pulse sequences with high-resolution turbo spin-echo for the diagnosis of adenomyosis, and we evaluated interobserver variability. SUBJECTS AND METHODS: Fifty-six consecutive patients referred for hysterectomy prospectively underwent MR imaging. Two fast pulse sequences using a breath-hold technique-true fast imaging with steady-state free precession (FISP) and turbo inversion recovery-and turbo spin-echo T2-weighted images of the pelvis were obtained in each patient. The images were analyzed in a blinded manner and independently by three reviewers with different levels of experience for the accuracy of adenomyosis diagnosis, image quality, anatomic visualization, and image artifacts. The accuracy for the diagnosis of adenomyosis on turbo spin-echo T2-weighted imaging combined with one or two fast pulse sequences was evaluated for each reviewer. RESULTS: Twenty-four patients (42.9%) had a histologic diagnosis of adenomyosis. The accuracy for the diagnosis of adenomyosis for reviewers 1, 2, and 3 using turbo spin-echo T2-weighted, true FISP, and turbo inversion recovery sequences was 83.9%, 67.8%, 75%; 83.9%, 67.8, 78.5%; and 87.5%, 73.2%, and 75%, respectively. A difference in the accuracy rate was found among the observers for the three sequences (p < 0.001). Whatever the pulse sequence, the accuracy rate was higher for the reviewer with more experience in gynecologic imaging. The combination of turbo spin-echo T2-weighted imaging with at least one rapid sequence increased the accuracy of observers with little experience in gynecology. With turbo inversion recovery sequences, the image quality score was low for the three reviewers compared with turbo spin-echo T2-weighted and true FISP sequences. The combination of turbo spin-echo T2-weighted and true FISP sequences gave the highest image quality scores. CONCLUSION: Breath-hold T2-weighted sequences optimize the accuracy of MR imaging for the diagnosis of adenomyosis and reduce interobserver variability.     

Chronic lithium nephropathy: MR imaging for diagnosis

PURPOSE: To evaluate the appearance of lithium nephropathy at magnetic resonance (MR) imaging. MATERIALS AND METHODS: Sixteen patients with renal insufficiency and clinical and laboratory evidence of nephropathy secondary to therapy with lithium salts were examined with a 1.5-T MR imaging unit with T1-weighted, T2-weighted fast imaging with steady-state precession (true FISP), rapid acquisition with relaxation enhancement, half-Fourier turbo spin-echo, and gadolinium-enhanced (FISP three-dimensional MR angiographic) sequences. Renal size and the presence, number, location and size of parenchymal cysts were analyzed. The cysts in each kidney were defined as rare (fewer than 10 cysts), sparse (between 10 and 30 cysts), abundant (30-60 cysts), or very abundant (more than 60 cysts). RESULTS: The mean length of both kidneys was 104 mm +/- 9 in seven cases, and one or both kidneys were less than 90 mm in length in nine cases. Renal microcysts measuring from 1 to 2 mm were detected in all patients. They were either very abundant (n = 12), abundant (n = 2), or sparse (n = 2). The cysts were located with equal abundance in both the cortex and the medulla in 11 cases and were predominantly located in the renal cortex in five cases. No renal artery stenosis was present. CONCLUSION: Microcysts secondary to long-term lithium therapy can be detected with MR imaging.     

Revascularization in multivessel disease: comparison between two-year outcomes of coronary bypass surgery and stenting

OBJECTIVE: The recent appreciation that stenting has improved the short- and long-term outcomes of patients treated with coronary angioplasty has made it imperative to reconsider the comparison between surgery and percutaneous interventions in patients with multivessel disease. METHODS: One thousand two hundred five patients were randomly assigned to undergo bypass surgery or angioplasty with stent implantation when there was consensus between the cardiac surgeon and interventional cardiologist as to equivalent treatability. The primary clinical end point was freedom from major adverse cardiac and cerebrovascular events at 1 year. Major adverse cardiac and cerebrovascular events at 2 years constituted a secondary end point. RESULTS: At 2 years, 89.6% of the surgical group and 89.2% of the stent group were free from death, stroke, and myocardial infarction (log-rank test P =.65). Among patients who survived without stroke or myocardial infarction, 19.7% in the stent group underwent a second revascularization, as compared with 4.8% in the surgical group (P <.001). At 2 years, 84.8% of the surgical group and 69.5% of the stent group were event-free survivors (log-rank test P <.001), and 87.2% in the surgical cohort and 79.6 % in the stent group were angina-free survivors (P =.001). In the diabetes subgroup, 82.3% of the surgical group and 56.3% of the stent group were free from any events after 2 years (log-rank test P <.001). CONCLUSION: The difference in outcome between surgery and stenting observed at 1 year in patients with multivessel disease remained essentially unchanged at 2 years. Stenting was associated with a greater need for repeat revascularization. In view of the relatively greater difference in outcome in patients with diabetes, surgery clearly seems to be the preferable form of treatment for these patients.