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PubMed1986

Niche expansion in bacteria: can infectious gene exchange affect the rate of evolution?

Recombination occurs by infectious gene transfer in bacteria, at rates much lower than recombination by sexual reproduction in other organisms. Thus, recombination may accelerate evolution in bacteria only under restricted conditions, such as occur when mutations at several loci are required for the evolution of an expanded ecological niche. Mathematical ("chemostat") models of several such cases--evolution of independence from three limiting essential or "interactive-essential" resources; evolution of the ability to use three new substitutable resources; and evolution of resistance to three growth inhibitors--were analyzed by computer simulation. All combinations of three mutation rates (U) and four values for the "infectious gene transfer rate parameter" (chi) were considered. Recombination accelerated evolution most when U was low and chi was high, but was unlikely to have large effects when chi was low enough to be realistic for natural populations of Escherichia coli. Recombination had the largest effects when resources were substitutable, and in that case could have substantially reduced the chance of random loss of the favored "triple mutant" while it was still rare. The simulations also revealed some interesting features of selection for an expanded niche. Evolution of independence from essential resources occurred more rapidly when the resources were weakly complementary than when they did not interact. Selection for the ability to use all substitutable resources was weak after all intermediate types that used only one or two of the resources had arisen.

Anti-Bacterial Agents↗
PubMed1988

Dietary fat in relation to prognostic indicators in breast cancer.

The relation of diet, especially fat intake, to recognized prognostic indicators for breast cancer was investigated in 666 women with a newly diagnosed infiltrating breast carcinoma. Diet during the year preceding diagnosis was assessed by interview using a food frequency questionnaire covering the intake of 114 food items. Prognostic indicators included axillary node involvement at diagnosis, estrogen receptor status, and selected histologic features of the primary tumor such as nuclear grade, histologic grade, tubule formation, mitotic activity, and nuclear size of tumor cells. After adjustment for total energy intake, age, body weight, and tumor size at diagnosis, an increase in saturated fat intake was related to an increased frequency of node involvement at diagnosis among postmenopausal patients. In contrast, an elevation in polyunsaturated fat intake was related to a reduction of the percentage of patients with positive nodes at diagnosis. This relation was observed among both premenopausal and postmenopausal patients. Dietary fat was not related to the estrogen receptor status of tumors. No association was found between dietary habits and histologic features of the primary tumor. These data suggest that dietary fat may have an effect on the growth or spread of breast cancer during the preclinical phase of the disease and that this effect may vary according to the type of fat considered.

Aged↗
PubMed1988

Prediction of in-vivo modification sites of proteins from their primary structures.

In order to make better use of the information contained in rapidly expanding amino acid sequence data, a new method to predict various modification sites of proteins from their primary structures is presented. It is also applicable to the prediction of other functional sites in proteins. Here we show the examples of N-glycosylation and serine/threonine phosphorylation sites. The method is essentially an elaboration of consensus sequence pattern matching based on stepwise discriminant analysis. The occurring amino acids near a potential modification site are represented by six numerical values which reflect various properties of amino acids. Longer-range effects around these sites are also considered. The stepwise procedure enabled us to automatically select effective features for discrimination. A computer program with our method first identifies potential modification sites by a sequence pattern, NX(S/T) for N-glycosylation or (S/T) for phosphorylation, and then decides by discriminant analysis whether a potential site is likely to be a true modification site. The prediction accuracy in the second step of discrimination was about 60% for glycosylation sites and about 80% for phosphorylation sites.

Amino Acid Sequence↗
PubMed1992

Sleep deprivation in the rat: XVI. Effects in a light-dark cycle.

To avoid a possible confound between the effects of sleep loss and disturbed circadian rhythms in previous studies of total sleep deprivation (TSD) by the disk-over-water method, TSD rats and their yoked control (TSC) rats had been maintained in constant light both before and during the experiment. With circadian rhythms of both groups flattened by constant light, group differences in outcome measures could be attributed to sleep loss. However, the constant light control entailed the possibility that the sleep loss effects might obtain only in constant light. To evaluate this possibility, three TSD-TSC rat pairs maintained on a 12 hour light: 12 hour dark (LD) schedule were studied. TSC rats showed only minor changes during the deprivation period. As in previous studies, TSD rats showed increased food intake; decreased weight; increased energy expenditure; debilitated appearance; lesions on the tail and paws; an initial increase followed by a large decrease in body temperature; impending death; and recovery sleep, which featured large, selective, sustained rebounds of paradoxical sleep and a reversal of all observed TSD-induced changes. Thus, TSD produced the same changes during an LD schedule as during constant light. The amplitude of the diurnal body temperature rhythm declined over the course of TSD and then almost completely recovered during the first day of recovery sleep. The decline was interpreted as the result of deprivation-induced thermoregulatory changes.

Animals↗
PubMed1993

Survival with colorectal cancer in ulcerative colitis. A study of 102 cases.

OBJECTIVE: This study was undertaken to correlate postoperative survival of patients with ulcerative colitis-associated colorectal cancer with the stage, configuration, size, and mucin content of the tumor. SUMMARY BACKGROUND DATA: The factors influencing prognosis in colorectal cancer in the general population are well accepted, but less is known about their influence in cases of colorectal cancer associated with ulcerative colitis. METHODS: The authors reviewed the records of 102 patients with ulcerative colitis-associated colorectal cancer admitted to The Mount Sinai Hospital between 1959 and 1988. Tumors were classified on independent pathologic review according to histologic stage, configuration, size, and mucin content. Comparisons among survival curves were tested by the generalized Wilcoxon test. Cox regression models were used to examine the joint effects of selected clinicopathologic features on postoperative survival rates. RESULTS: Complete follow-up was obtained for 93 patients (92%). Overall 5-year actuarial survival was 52%. When factors were analyzed one at a time, survival was significantly poorer among patients with advanced cancer stage, larger tumor size, infiltrating and ulcerating configuration, and high mucin concentration. On multivariate analysis by the Cox regression model, however, only cancer stage emerged as a factor independently predicting survival. CONCLUSIONS: For colitis-associated colorectal cancers, as for noncolitic cancers, histologic stage is the most important variable determining postoperative survival. The distribution of stages in our series and the survival rates within each stage did not differ appreciably from the distributions and survival rates reported for noncolitic colorectal cancers.

Adult↗
PubMed1999

Surgical treatment of inflammatory bowel disease.

Although laparotomy with resection remains the treatment of choice for most patients who require surgery for intestinal Crohn's disease, mounting evidence supports the safety and efficacy of less traditional approaches and procedures (ie, laparoscopy, stricture-plasty). In contrast to the approach to intestinal disease, many centers are advocating a more aggressive operative approach to perianal Crohn's disease. Over the past few years, restorative proctocolectomy with ileal pouch-anal anastomosis has emerged as the operation of choice for most patients requiring surgery for ulcerative colitis. As experience with the operation grows, patient selection, technical features, and management of postoperative complications are being more clearly defined and optimized.

Journal Article↗
PubMed2000

Attending to and remembering tactile stimuli: a review of brain imaging data and single-neuron responses.

Clinical and neuroimaging observations of the cortical network implicated in tactile attention have identified foci in parietal somatosensory, posterior parietal, and superior frontal locations. Tasks involving intentional hand-arm movements activate similar or nearby parietal and frontal foci. Visual spatial attention tasks and deliberate visuomotor behavior also activate overlapping posterior parietal and frontal foci. Studies in the visual and somatosensory systems thus support a proposal that attention to the spatial location of an object engages cortical regions responsible for the same coordinate referents used for guiding purposeful motor behavior. Tactile attention also biases processing in the somatosensory cortex through amplification of responses to relevant features of selected stimuli. Psychophysical studies demonstrate retention gradients for tactile stimuli like those reported for visual and auditory stimuli, and suggest analogous neural mechanisms for working memory across modalities. Neuroimaging studies in humans using memory tasks, and anatomic studies in monkeys support the idea that tactile information relayed from the somatosensory cortex is directed ventrally through the insula to the frontal cortex for short-term retention and to structures of the medial temporal lobe for long-term encoding. At the level of single neurons, tactile (such as visual and auditory) short-term memory appears as a persistent response during delay intervals between sampled stimuli.

Animals↗
PubMed2002

Role of endoscopic ultrasound (EUS) and EUS-guided fine needle aspiration in the diagnosis and treatment of cystic lesions of the pancreas.

INTRODUCTION AND AIMS: Cystic neoplasms of the pancreas may be inadvertently treated as benign pseudocysts in clinical practice, often without the use of cytology, cyst tumor markers, or histopathology. We assessed the utility of EUS-guided fine-needle aspiration (EUS-FNA) to assist in the diagnosis and management of pancreatic cysts. METHODOLOGY: All patients who had pancreatic cysts detected by EUS over a 24-month period were analyzed. Preoperative diagnosis was derived from an algorithm combining clinical history and endosonographic features. In selected cases, EUS-FNA was performed and cyst fluid aspirates were analyzed. Surgical specimens served as diagnostic standard. RESULTS: A total of 43 patients with pancreatic cysts underwent 45 EUS examinations. Surgical specimens were obtained from 9 patients (mucinous cystadenocarcinoma, 3; adenocarcinoma, 3; pancreatic endocrine tumor, 2; and benign cyst, 1); diagnostic EUS correctly predicted malignant cysts in 8/9 (88.9%). One case inaccurately interpreted by EUS as cystic neoplasm turned out to be a benign cyst on resection. Twenty-one patients underwent EUS-FNA. The cytologic interpretation was adenocarcinoma in 9.5% (2/21); suspicious for malignancy or atypical cells in 19.0% (4/21); benign in 66.6% (14/21); and insufficient cells in 4.8% (1/21). CONCLUSION: The information gathered from clinical history and EUS, complemented by fluid analysis after EUS-guided FNA, predicts neoplastic pancreatic cysts and assists in decision-making for medical or surgical approach.

Algorithms↗
PubMedDate not supplied

Pelvic inflammatory disease associated with Neisseria gonorrhoeae and Chlamydia trachomatis: clinical correlates.

The purpose of this study was to determine whether selected clinical features can distinguish salpingitis associated with endocervical Neisseria gonorrhoeae from that caused by Chlamydia trachomatis in black, inner-city adolescents. We reviewed retrospectively the charts of teenagers presenting to a university hospital outpatient department between January 1982 and January 1984 who were diagnosed as having salpingitis. We included all teenagers who presented with a history of low abdominal pain plus (1) either cervical motion tenderness (n = 15), adnexal tenderness (n = 13), or both (n = 57); and (2) either cervical cultures positive for N. gonorrhoeae and negative for C. trachomatis (n = 31) or cervical cultures negative for N. gonorrhoeae and positive for C. trachomatis (n = 54). Discriminant analysis indicated that the presence of breakthrough vaginal bleeding (standard regression coefficient [SRC] = 0.301; P = 0.023), current usage of oral contraception (SRC = 0.408; P = 0.009), and an elevated erythrocyte sedimentation rate (SRC = 0.522; P = 0.0002) were significantly more often related to the presence of endocervical C. trachomatis. However, we found no significant differences between the two groups for other variables that have been described as distinguishing features (i.e., duration of pain, fever, and leukocyte count).

Adolescent↗
PubMed2005

New drug delivery for corneal neovascularization using polyion complex micelles.

PURPOSE: To introduce photodynamic therapy (PDT) for corneal neovascularization (NV) by polyion complex (PIC) micelles, a novel drug delivery system. METHODS AND RESULTS: Development of specific drug delivery systems to corneal NV sites is an important part of next-generation photodynamic therapy. Nanocarriers consisting of PIC micelles bound by polyethylene glycol (PEG) shell exhibit good stability, high drug-loading capacity, and excellent potential for controlled drug release. Encapsulation of the photosensitizer dendrimer porphyrin (DP) into PIC micelles (DP-micelles) conveys adequate stability and increased photocytotoxicity without compromising photophysical properties of DP stability. We assessed the accumulation of DP-micelles and observed that the DP-micelles were incorporated into the corneal NV area. CONCLUSIONS: PIC micelles possess attractive features of selective accumulation at the corneal NV site. PDT using DP-micelles appears to be effective and safe for the treatment of corneal NV.

Animals↗
PubMed2004

Nodal involvement in bladder cancer cases treated with radical cystectomy: incidence and prognosis.

PURPOSE: We studied the factors that promote the incidence of nodal metastasis and characterized survival predictions in cases treated with radical cystectomy. MATERIALS AND METHODS: We retrospectively studied 418 bladder cancer cases treated with radical cystectomy and bilateral endopelvic lymphadenectomy. The incidence of nodal involvement was correlated with several patient and tumor characteristics. The number of involved nodes was also correlated with the number of retrieved nodes. Finally, survival in node positive cases was correlated with some select pathological features. RESULTS: Of the 418 cases nodal involvement was reported in 110 (26.3%). The mean number of harvested nodes per patient +/- SE was 17.9 +/- 6.7. The mean number of positive nodes per involved case was 4.1 +/- 5.4. A weak correlation between the number of retrieved nodes and number of positive nodes was noted (r = 0.4). Tumor pT stage and grade, and lymphovascular invasion were independent factors promoting the incidence of nodal involvement. Three-year disease-free survival in node positive cases was 37.8% +/- 4.8%. Two factors had an independent impact on survival in node positive cases, namely pT stage and the number of positive nodes. CONCLUSIONS: Tumor pT stage and grade, and lymphovascular invasion independently influence the incidence of lymph node involvement. There was a weak correlation between the number of retrieved nodes and number of positive nodes. The survival probability in pT N+ cases depended on pT stage and the number of involved nodes. A prospective study with anatomical mapping of retrieved nodes is necessary to define the optimal extent of lymphadenectomy with cystectomy.

Adult↗
PubMed2002

Invasive papillary carcinomas of the extrahepatic bile ducts: a clinicopathologic and immunohistochemical study of 13 cases.

Carcinomas of the extrahepatic bile ducts are uncommon neoplasms that are morphologically heterogeneous and associated with a poor prognosis. We have previously shown that the noninvasive and minimally invasive papillary carcinomas of the extrahepatic bile ducts behave as in situ carcinomas and are associated with a better prognosis. We reviewed the clinical records of 13 patients with invasive papillary carcinomas of the extrahepatic bile ducts and analyzed the microscopic features and selected immunohistochemical reactivity (p53, Mib-1, and Dpc4) that might correlate with patient survival. In addition, we present the updated SEER (Surveillance, Epidemiology, and End Results) data of the National Cancer Institute for the invasive extrahepatic bile duct carcinomas compiled from 1975 to 1998. The 13 patients with papillary carcinoma had a male to female ratio of 1:1, and their ages ranged from 33 to 89 years. Painless jaundice and abdominal pain were the most common complaints. Five tumors were located in the distal portion, one in the mid portion, and six in the proximal portion of the common bile duct. One papillary carcinoma arose in the right hepatic duct. The Whipple procedure was performed in six patients, common bile duct resection in six, and right hepatic lobectomy in one. The cell phenotype of the papillary carcinomas was biliary in nine and intestinal in three. One tumor had both biliary and intestinal phenotypes. Four tumors dedifferentiated (two to undifferentiated small cell carcinomas, one to small [oat] cell carcinoma, and one to giant cell carcinoma). Two papillary carcinomas extended into the pancreas and three into the liver. Only one patient had lymph node metastases at presentation. Follow-up was available in 10 patients. Six patients died of disease from 2 weeks to 2 years and 1 month after surgery. Four patients are alive with no evidence of disease from 4 months to 8 years and 8 months after surgery. Of 174 invasive papillary carcinomas compiled by the SEER program, 71 were confined to the ductal wall, and 61 had regional lymph node metastases. Papillary carcinomas confined to the ductal wall have better 10-year relative survival rates than adenocarcinomas limited to the wall (21% versus 12%). Likewise papillary carcinomas with lymph node metastasis have better prognosis than adenocarcinoma with nodal metastases (10-y survival rate of 12% versus 5%). Currently, the histologic type and the stage of the disease are the most important prognostic factors in these papillary carcinomas. Separation of invasive and noninvasive or minimally invasive papillary carcinoma is critical in estimating the patient outcome. Our findings suggest that there is no correlation between p53, Ki-67, and Dpc4 expression in these tumors and survival of the patients.

Adult↗
PubMed2004

Incomplete cytoreduction in 174 patients with peritoneal carcinomatosis from appendiceal malignancy.

OBJECTIVE: The aim of this study was to analyze the survival of patients with peritoneal dissemination of appendiceal malignancy having incomplete cytoreductive surgery. SUMMARY BACKGROUND DATA: Cytoreductive surgery plus perioperative intraperitoneal chemotherapy has emerged as a new and potentially curative treatment option for patients with peritoneal dissemination of appendiceal mucinous tumors. The goal of surgery is to remove all visible disease. Nevertheless, in some patients, complete cytoreduction is not possible. METHODS: Over a 30-year period, 645 patients with epithelial peritoneal surface malignancy of appendiceal origin were treated with cytoreductive surgery and intraperitoneal chemotherapy by a single surgeon. One hundred seventy-four (27.1%) of these patients had an incomplete cytoreduction. A critical statistical analysis of the impact of selected clinical features on survival was performed from a prospective database. RESULTS: Mortality and morbidity rates were 0% and 33.3%, respectively. Median survival of these 174 patients was 20.5 months and their 1-year, 3-year, and 5-year survival rates were 71%, 34%, and 15%, respectively. By multivariate analysis, the presence of signet ring cells and lymph node involvement were independent prognostic indicators of poor survival (P = 0.047 and P < 0.001, respectively). Patients who underwent more than 1 cytoreduction or repeat intraperitoneal chemohyperthermia showed significant improvement in survival (P = 0.018 and P < 0.001, respectively) CONCLUSION: Incomplete cytoreduction plus perioperative intraperitoneal chemotherapy of peritoneal dissemination from appendiceal malignancy results in limited long-term survival. Patients with signet ring histology or lymph node involvement have an especially poor outcome. Repeat cytoreduction and intraperitoneal chemohyperthermia may improve outcome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Complex patterns of abnormal heartbeats.

Individuals having frequent abnormal heartbeats interspersed with normal heartbeats may be at an increased risk of sudden cardiac death. However, mechanistic understanding of such cardiac arrhythmias is limited. We present a visual and qualitative method to display statistical properties of abnormal heartbeats. We introduce dynamical "heartprints" which reveal characteristic patterns in long clinical records encompassing approximately 10(5) heartbeats and may provide information about underlying mechanisms. We test if these dynamics can be reproduced by model simulations in which abnormal heartbeats are generated (i) randomly, (ii) at a fixed time interval following a preceding normal heartbeat, or (iii) by an independent oscillator that may or may not interact with the normal heartbeat. We compare the results of these three models and test their limitations to comprehensively simulate the statistical features of selected clinical records. This work introduces methods that can be used to test mathematical models of arrhythmogenesis and to develop a new understanding of underlying electrophysiologic mechanisms of cardiac arrhythmia.

Arrhythmias, Cardiac↗
PubMed2004

Rich example of geometrically induced nonlinearity: from rotobreathers and kinks to moving localized modes and resonant energy transfer.

We present an experimentally realizable, simple mechanical system with linear interactions whose geometric nature leads to nontrivial, nonlinear dynamical equations. The equations of motion are derived and their ground state structures are analyzed. Selective "static" features of the model are examined in the context of nonlinear waves including rotobreathers and kinklike solitary waves. We also explore "dynamic" features of the model concerning the resonant transfer of energy and the role of moving intrinsic localized modes in the process.

Journal Article↗
PubMed2006

Iterated maps for annealed Boolean networks.

Boolean networks are used to study the large-scale properties of nonlinear systems and are mainly applied to model genetic regulatory networks. A statistical method called the annealed approximation is commonly used to examine the dynamical properties of randomly generated Boolean networks that are created with selected statistical features. However, in the literature there are several variations of the annealed approximation. These approximations cannot be interchangeably used in all cases due to different background assumptions. In this paper, we present the so-called four-state model, derive the different approximations from this model, and make the differences and connections between these approximations explicit. As an application of the presented results, we study the properties of the Boolean networks that are constructed with random functions, canalizing functions, and regulatory functions found in the biological literature.

Journal Article↗
PubMed1991

Peripheral vision lipreading aid.

Lipreading provides a limited amount of information about speech signals to profoundly deaf people. Visual displays using peripheral vision as an alternative sensory modality can provide supplementary speech information. The utility of a cosmetically acceptable peripheral vision display was explored. A pair of eyeglasses with a commercially available two-dimensional red LED array (5 x 7), and its associated electronics was developed. The display is visible only to the wearer, and is located in the temporal field and the horizontal meridian of the right eye. Selected speech features were encoded as visual patterns for presentation to the lipreader. These features of the speech signal (the fundamental frequency of the speech, high-frequency energy, and low-passed speech signal or total energy envelope) were presented with the objective of providing information about voicing and plosion/frication. Experiments demonstrate the capability of the peripheral display in conveying speech information. Presenting vowel-consonant-vowel syllables, the performance was in excess of 76% with aided lipreading as compared to 41% by lipreading only.

Communication Devices for People with Disabilities↗