Biomedical subjects

Paul M Johnson

Publications and source records attributed to Paul M Johnson.

9 recordsLinked to original sources

PubMed2006

Increasing negative lymph node count is independently associated with improved long-term survival in stage IIIB and IIIC colon cancer.

PURPOSE: The purpose of this study was to examine the impact of the number of negative lymph nodes on survival in patients with stage III colon cancer. PATIENTS AND METHODS: Patients who underwent surgery for stage III colon cancer between January 1988 and December 1997 were identified from the Surveillance, Epidemiology and End Results cancer registry. The number of negative and positive nodes was determined for 20,702 eligible patients. Disease-specific survival was examined by substage according to the number of negative nodes identified. A proportional hazards model was constructed to determine the effect of the number of negative nodes on survival. RESULTS: For stage IIIB and IIIC patients, there was a significant decrease in disease-specific mortality as the number of negative nodes increased; cumulative 5-year cancer mortality was 27% in stage IIIB patients with 13 or more negative nodes identified versus 45% in those with three or fewer negative lymph nodes evaluated (P < .0001). In patients with stage IIIC cancer, those with 13 or more negative nodes had a 5-year mortality of 42% versus 65% in those with three or fewer negative lymph nodes evaluated (P < .0001). There was no association between the number of negative nodes identified and disease-specific survival for patients with stage IIIA disease. After controlling for the number of positive nodes, a higher number of negative nodes was found to be independently associated with improved disease-specific survival. CONCLUSION: The number of negative nodes is an important independent prognostic factor for patients with stage IIIB and IIIC colon cancer.

Aged↗

PubMed2006

Surveillance colonoscopy in individuals at risk for hereditary nonpolyposis colorectal cancer: an evidence-based review.

PURPOSE: Surveillance colonoscopy plays an important role in the management of asymptomatic patients known to carry and suspected of carrying hereditary nonpolyposis colorectal cancer gene mutations. Although the shortest interval between surveillance examinations may seem to offer the most benefit to patients, excessive use of this procedure may have unwanted consequences. This study was designed to evaluate the evidence and make recommendations regarding the optimal frequency of surveillance colonoscopy and the age at which to initiate surveillance based on the best available evidence. METHODS: MEDLINE was searched for all articles assessing surveillance colonoscopy from 1966 to 2004 by using the MESH terms "hereditary nonpolyposis colorectal cancer" and "screening." The evidence was systematically reviewed and a critical appraisal of the evidence was performed. RESULTS: There are no randomized, controlled, clinical trials examining the frequency of surveillance colonoscopy in hereditary nonpolyposis colorectal cancer. Three cohort studies were identified for review. There is one cohort study of good quality that provides evidence that surveillance colonoscopy every three years in patients with hereditary nonpolyposis colorectal cancer reduces the risk of developing colorectal cancer and the risk of death. The two remaining cohort studies provide poor evidence on which to make a recommendation. CONCLUSIONS: The best available evidence supports surveillance with complete colonoscopy to the cecum every three years in patients with hereditary nonpolyposis colorectal cancer (B recommendation). There is no evidence to support or refute more frequent screening. Further research is required to examine the potential harms and benefits of more frequent screening. However, given the potential for rapid progression from adenoma to carcinoma and missing lesions at colonoscopy, there is consensus that screening more frequently than every three years is required.

Colonoscopy↗

PubMed2006

Packaging of chemicals in the defensive secretory glands of the sea hare Aplysia californica.

Sea hares protect themselves from predatory attacks with several modes of chemical defenses. One of these is inking, which is an active release of a protective fluid upon predatory attack. In many sea hares including Aplysia californica and A. dactylomela, this fluid is a mixture of two secretions from two separate glands, usually co-released: ink, a purple fluid from the ink gland; and opaline, a white viscous secretion from the opaline gland. These two secretions are mixed in the mantle cavity and directed toward the attacking predator. Some of the chemicals in these secretions and their mechanism of action have been identified. In our study, we used western blots, immunocytochemistry, amino acid analysis, and bioassays to examine the distribution of these components: (1) an L-amino acid oxidase called escapin for A. californica and dactylomelin-P for A. dactylomela, which has antimicrobial activity but we believe its main function is in defending sea hares against predators that evoke its release; and (2) escapin's major amino acid substrates--L-lysine and L-arginine. Escapin is exclusively produced in the ink gland and is not present in any other tissues or secretions. Furthermore, escapin is only sequestered in the amber vesicles of the ink glandand not in the red-purple vesicles, which contain algal-derived chromophores that give ink its distinctive purple color. The concentration of escapin and dactylomelin-P in ink, both in the gland and after its release, is as high as 2 mg ml(-1), or 30 micromol ml(-1), which is well above its antimicrobial threshold. Lysine and arginine (and other amino acids) are packaged into vesicles in the ink and opaline glands, but arginine is present in ink and opaline at <1 mmol l(-1) and lysine is present in ink at <1 mmol l(-1) but in opaline at 65 mmol l(-1). Our previous results showed that both lysine and arginine mediate escapin's bacteriostatic effects, but only lysine mediates its bactericidal effects. Given that escapin's antimicrobial effects require concentrations of lysine and/or arginine >1 mmol l(-1), our data lead us to conclude that lysine in opaline is the primary natural substrate for escapin in ink. Furthermore, packaging of the enzyme escapin and its substrate lysine into two separate glands and their co-release and mixing at the time of predatory attack allows for the generation of bioactive defensive compounds from innocuous precursors at the precise time they are needed. Whether lysine and/or arginine are substrates for escapin's antipredatory functions remains to be determined.

Amino Acid Oxidoreductases↗

PubMed2005

Sea hares use novel antipredatory chemical defenses.

Numerous studies have demonstrated that chemical defenses protect prey from predation and have often assumed that these defenses function by repelling predators. Surprisingly, few have investigated the mechanisms whereby predators are affected by these defenses. Here, we examine mechanisms of chemical defense of sea hares (Aplysia californica), which, when attacked by spiny lobsters (Panulirus interruptus), release defensive secretions from ink and opaline glands. We show that ink-opaline facilitates the escape of sea hares by acting through a combination of novel and conventional mechanisms. Ink-opaline contains millimolar quantities of amino acids that stimulate chemoreceptor neurons in the spiny lobster's nervous system. Ink stimulates appetitive and ingestive behavior, opaline can elicit appetitive behavior but can also inhibit ingestion and evoke escape responses, and both stimulate grooming. These results suggest that these secretions function by "phagomimicry," in which ink-opaline stimulates the feeding pathway to deceive spiny lobsters into attending to a false food stimulus, and by sensory disruption, in which the sticky and potent secretions cause high-amplitude, long-lasting chemo-mechanosensory stimulation. In addition, opaline contains a chemical deterrent that opposes appetitive effects. Thus, chemical defenses may act in more complex manners than palatability assays of prey chemistry may suggest.

Amino Acids↗

PubMed2005

Pouch-vaginal fistula after ileal pouch-anal anastomosis: treatment and outcomes.

PURPOSE: Pouch-vaginal fistula is an uncommon but serious complication after ileal pouch anal anastomosis. The management of pouch-vaginal fistulas is challenging and a number of treatment options exist. The purpose of this study was to examine the outcomes after various procedures for pouch-vaginal fistula performed at our institution. METHODS: Patients who were treated for pouch-vaginal fistula at Mount Sinai Hospital were identified from a prospectively maintained database. Demographic, disease history, treatment, and outcomes data were obtained. Treatment success was defined as no recurrence of the fistula with a functioning pouch and no ileostomy. RESULTS: Since November 1982, 24 of 619 (3.9 percent) women who had primary ileal pouch-anal anastomosis performed at Mount Sinai Hospital developed a pouch-vaginal fistula. Five women had ileal pouch-anal anastomosis performed at another institution and were referred for management of their pouch-vaginal fistula. Local and/or combined abdominoperineal repairs were performed in 22 of 29 patients. Combined abdominoperineal repairs were associated with a higher success rate than that of local perineal repairs (52.9 vs. 7.9 percent, respectively, at 10 years after repair; p = 0.035). Overall, 50 percent (11/22) of patients who underwent surgical repair of a pouch-vaginal fistula had a successful result with a functioning pouch and no recurrence of the fistula, and 21 percent (6/29) of patients required pouch excision. CONCLUSIONS: The management of pouch-vaginal fistula after ileal pouch-anal anastomosis is associated with a high recurrence rate. Combined abdominoperineal repair appears to offer better results than those of local procedures.

Abdomen↗

PubMed2004

Structural changes in gill DNA reveal the effects of contaminants on Puget Sound fish.

Structural differences were identified in gill DNA from two groups of English sole collected from Puget Sound, Washington, in October 2000. One group was from the industrialized Duwamish River (DR) in Seattle and the other from relatively clean Quartermaster Harbor (QMH). Chemical markers of sediment contamination [e.g., polynuclear aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs)] established that the DR was substantially more contaminated than QMH. The levels of these chemicals in the sediments of both sites were consistent with levels of cytochrome P450 1A (CYP1A) expression in the gills of English sole from the same sites. Structural differences in gill DNA between the groups were evinced via statistical models of Fourier transform-infrared (FT-IR) spectra. Marked structural damage was found in the gill DNA of the DR fish as reflected in differences in base functional groups (e.g., C-O and NH2) and conformational properties (e.g., arising from perturbations in vertical base stacking interactions). These DNA differences were used to discriminate between the two fish groups through principal components analysis of mean FT-IR spectra. In addition, logistic regression analysis allowed for the development of a "DNA damage index" to assess the effects of contaminants on the gill. The evidence implies that environmental chemicals contribute to the DNA changes in the gill. The damaged DNA is a promising marker for identifying, through gill biopsies, contaminant effects on fish.

Animals↗

PubMed2003

Cancer-related changes in prostate DNA as men age and early identification of metastasis in primary prostate tumors.

Using statistical analyses of Fourier transform-IR spectra, we show that DNA of the histologically normal prostates of men 16-80 years old undergoes structural changes in the bases and backbone with increasing age. Of the older men (ages 55-80), 42% exhibited a DNA phenotype mimicking that of primary prostate tumors from a comparable age group. This cancer-like phenotype, which was not found in the younger men (ages 16-36), appears to arise from progressive age-related damage to DNA. The mean concentrations of 8-hydroxypurine lesions (e.g., 8-hydroxyguanine) were substantially higher for the older men than for the younger men. This finding suggests that the hydroxyl radical contributed to the structural changes that characterize the cancer-like phenotype. Strikingly, we were additionally able to discriminate between the DNA of primary prostate tumors and the DNA of primary prostate tumors from which distant metastases had been identified. Moreover, logistic regression analysis was able to predict the probability that a tumor had metastasized with approximately 90% sensitivity and specificity. Collectively, these findings are particularly promising for identifying men at risk for developing prostate cancer, as well as for the early determination of whether a primary tumor has progressed to the metastatic state. This is highly important because the prognosis of histologically similar prostate carcinomas varies, thus creating a need to predict which cancers are most likely metastatic.

Adolescent↗

PubMed2002

Antioxidant-induced changes in oxidized DNA.

N-acetylcysteine (NAC), a strong antioxidant, has antigenotoxic and anticarcinogenic properties currently being investigated in clinical trials. NAC detoxifies free radicals (e.g., the hydroxyl radical,.OH) that cause DNA changes implicated in disease (e.g., cancer). The.OH reacts with purines to form mutagenic 8-hydroxypurine (8-OH) and putatively nonmutagenic formamidopyrimidine (Fapy) lesions. Fapy lesions inhibit DNA synthesis likely modulating the mutagenic potential of the 8-OH lesions, which would suggest that the ratio of these oxidized bases is biologically important. However, little is known about how NAC modifies oxidized DNA structure or how such modifications may affect cellular processes, such as replication and transcription. By using gas chromatography-mass spectrometry and Fourier transform-infrared spectroscopy, we found that dietary NAC (5% in the diet for 14 days) affected.OH-induced structural changes in DNA of the hind leg of the BALB/c mouse. For example, mutagenic 8-hydroxyguanine (8-OH-Gua) was reduced approximately 50% (P = 0.02) in mice fed NAC compared with controls. NAC reduced the log(10) (8-OH-Gua/FapyGua) ratio from 0.58 +/- 0.15 to essentially zero, a virtually neutral redox status. DNA from control mice had a remarkably high variance compared with mice fed NAC. Moreover, the DNA from treated and control mice was distinct with respect to base structure and vertical base-stacking interactions. The findings showing that NAC lowered the concentration of 8-OH-Gua, the log ratio, and the variance (previously associated with neoplastic changes) suggest that NAC reduces the mutagenic potential of oxidized DNA. These benefits could be offset by the other structural changes found after NAC exposure, which may affect the fidelity of DNA synthesis.

Acetylcysteine↗

PubMedDate not supplied

Adequacy of nodal harvest in colorectal cancer: a consecutive cohort study.

The presence of nodal metastasis is a critical component of staging in colorectal cancer. Accurate assessment of nodal status requires sufficient node sampling, although the number of such nodes is controversial, with recommendations ranging from 6 to 17 nodes. The purpose of this study was to describe the nodal harvest in colorectal cancer and to identify factors associated with adequate lymph node harvest. Pathology reports from consecutive patients with newly diagnosed colorectal cancer undergoing resection between January 1997 and December 2000 at a tertiary care academic institution were reviewed. Identification of 12 or more lymph nodes was considered to be an adequate nodal harvest based on the current American Joint Committee on Cancer recommendations. Among the 579 consecutive specimens, the number of nodes identified was not stated for 10 (1.7%). Of the remaining 569 specimens, 4700 nodes were identified with a mean of 8.3 nodes per patient (median 7, range 0 to 60). Nodal metastases were identified in 219 patients (38.5%). Patients with one or more positive nodes had greater nodal harvest than those with negative nodes (9.5 vs. 8.2, respectively; P = 0.03). Only 22.4% of patients were found to have an adequate nodal harvest (> or =12 nodes). Right-sided resections, high surgeon volume, and gross examination of specimens by a staff pathologist were associated with higher nodal harvests, compared to left-sided resections, low surgeon volume, and gross examination of specimens by a pathology resident/technologist, respectively. There was no association with pathologist volume. In this study, nodal harvest in patients undergoing resection for colorectal cancer was highly variable. This problem appears to be multifactorial, and is related to patient, pathologic, and surgical factors.

Adult↗