A Geometric Clustering Tool (AGCT) to robustly unravel the inner cluster structures of time-series gene expressions.

Systems biology aims at holistically understanding the complexity of biological systems. In particular, nowadays with the broad availability of gene expression measurements, systems biology challenges the deciphering of the genetic cell machinery from them. In order to help researchers, reverse engineer the genetic cell machinery from these noisy datasets, interactive exploratory clustering methods, pipelines and gene clustering tools have to be specifically developed. Prior methods/tools for time series data, however, do not have the following four major ingredients in analytic and methodological view point: (i) principled time-series feature extraction methods, (ii) variety of manifold learning methods for capturing high-level view of the dataset, (iii) high-end automatic structure extraction, and (iv) friendliness to the biological user community. With a view to meet the requirements, we present AGCT (A Geometric Clustering Tool), a software package used to unravel the complex architecture of large-scale, non-necessarily synchronized time-series gene expression data. AGCT capture signals on exhaustive wavelet expansions of the data, which are then embedded on a low-dimensional non-linear map using manifold learning algorithms, where geometric proximity captures potential interactions. Post-processing techniques, including hard and soft information geometric clustering algorithms, facilitate the summarizing of the complete map as a smaller number of principal factors which can then be formally identified using embedded statistical inference techniques. Three-dimension interactive visualization and scenario recording over the processing helps to reproduce data analysis results without additional time. Analysis of the whole-cell Yeast Metabolic Cycle (YMC) moreover, Yeast Cell Cycle (YCC) datasets demonstrate AGCT's ability to accurately dissect all stages of metabolism and the cell cycle progression, independently of the time course and the number of patterns related to the signal. Analysis of Pentachlorophenol iduced dataset demonstrat how AGCT dissects data to identify two networks: Interferon signaling and NRF2-signaling networks.

Occupational exposure to pentachlorophenol causing lymphoma and hematopoietic malignancy for two generations.

OBJECTIVE: Pentachlorophenol (PCP) is characterized as likely carcinogen of lymphoma and hematopoietic neoplasm. But the carcinogenicity to human was uncertain based on population studies. A systematic review was conducted to explore two kinds of associations, one was between the workers exposed to PCP with lymphoma and hematopoietic neoplasm, the other was between childhood lymphoma and leukemia with their parents exposed to PCP. METHODS: Systematic search for epidemiologic studies was carried out and the data were collected from MEDLINE database and from the reference lists of relevant studies. Data were extracted from 20 included studies published between 1986 and 2012. RESULTS: The meta-analysis suggested a significant association between lymphoma and workers' occupational exposing to PCP, for the pooled odds ratio = 2.57 (95% confidence interval (CI) = 1.52-4.35). The subgroup analysis indicated significant association for non-Hodgkin's lymphoma, but not for Hodgkin's disease. The cohort studies also showed comparatively higher relative risk (RR) and standardized mortality ratio (SMR). Two of the cohort studies found increased RR as the cumulative exposure time added. Another cohort study discovered that the white males had significantly elevated non-Hodgkin's lymphoma mortality (SMR = 1.98, 95% CI = 1.15-3.17), and males of other races had increased leukemia mortality (SMR = 4.57, 95% CI = 1.25-11.7). For the relationship of childhood leukemia and parental exposure to PCP, three published studies suggested an increased risk of childhood leukemia because of their parental exposure to PCP at the preconception period. CONCLUSION: Our review provided the evidence that occupational exposure of workers to PCP might increase the risk of lymphoma and hematopoietic neoplasm in themselves and in their children.

Morbidity in former sawmill workers exposed to pentachlorophenol (PCP): a cross-sectional study in New Zealand.

BACKGROUND: From 1950 to 1990 pentachlorophenol (PCP) was used widely in the New Zealand sawmill industry, and persistent claims of long-term health effects have been made. METHODS: We surveyed surviving members of a cohort enumerated to study mortality in sawmill workers employed from 1970 to 1990. Estimates of historical exposure were based on job titles held, using the results of a PCP biomonitoring survey conducted in the 1980s. The survey involved interviews and clinical examinations, with interviewers and examiners blinded to exposure status. RESULTS: Of the 293 participants 177 had not been exposed, and of the 116 exposed all but 10% had low or short-term PCP exposure. Nevertheless, a number of significant associations between PCP exposure and the prevalence of various symptoms were observed including associations between: (i) exposure levels and self-reported tuberculosis, pleurisy or pneumonia (P < 0.01) and a deficit in cranial nerve function (P = 0.04); (ii) duration of employment and thyroid disorders (P = 0.04), and neuropsychological symptoms including often going back to check things (P = 0.04), low libido (P = 0.02) and heart palpitations (P = 0.02), and a strong dose-response trend for frequent mood changes without cause (P < 0.01); and (iii) cumulative exposure and frequent mood changes without cause (P = 0.02), low libido (P = 0.04), and in the overall number of neuropsychological symptoms reported (P = 0.03). CONCLUSIONS: PCP exposure was associated with a number of physical and neuropsychological health effects that persisted long after exposure had ceased.

Accident insurance, sickness, and science: New Zealand's no-fault system.

This article explores the process of seeking compensation for occupational illness under a no-fault accident insurance scheme. The author uses two case studies--firefighters who attended a fire at a chemical storage depot and timbermill workers who worked with pentachlorophenol--to illustrate how science can be used to deny compensation to sick and dying workers. The results of the studies suggest that a no-fault accident compensation scheme, considered to be a victory for workers, offers no guarantee of just outcomes for working people. And science can be co-opted and used to support business and state interests against workers; this ideological support is increasingly hidden behind the development of "objective" systems of assessing compensation claims.

Assessment of pentachlorophenol-exposed timber workers using a test-of-poisoning model.

Sixty-two former New Zealand timber workers who were exposed to pentachlorophenol (PCP) at work were interviewed, examined, and assessed both by laboratory investigations and psychometrically for clinical syndromes that could be related to PCP exposure. Three such syndromes were identified: an acute complex of fever, headaches, upper and lower respiratory tract and eye irritation, skin disease, and foul smelling and discolored sweat; a chronic fatigue syndrome, beginning while still at work and frequently persisting; and a delayed encephalopathy. Neither of the sustained syndromes was considered characteristic of PCP poisoning, and many confounders were identified. An exposure index and a test-of-poisoning score had a statistically insignificant correlation.

[Pentachlorophenol poisoning. Report of 4 cases and review of the literature]. / Intoxicación por pentaclorofenol. Descripción de cuatro casos y revisión de la literatura.

Pentachlorophenol (PCP) was, and still is, one of the most frequently used fungicides and pesticides. The use of PCP has been more restricted during the last few years. PCP's most important industrial application is as a wood preservative. The pentachlorophenol can be absorbed into the body by all the routes of occupational exposure. Some epidemiological observations suggest that exposure to PCP solutions may result in an increased risk for certain diseases in humans, e.g., immunodeficiency, blood disorders, malignancies, congenital anomalies. Chronic poisoning is difficult to detect since symptoms are often vague. Acute poisoning is due to interference with oxidative phosphorylation and can present itself as an unexpected case of sudden death. Four cases of PCP poisoning, including one fatalitie, occurred in two small wood preservative plants. All cases presented with increased serum creatinine phosphokinasa. The clinical finding are reported, and treatment modalities commented. At present there is no antidote for PCP. The basis for treatment is intensive supportive care to maintain vital bodily function. In one patient plasmapheresis was used and rapid recover was obtained. It is suggested that such therapy may be lifesaving in such intoxications.

Human pentachlorophenol poisoning.

Pentachlorophenol (PCP) was, and still is, one of the most frequently used fungicides and pesticides. Its toxicity is due to interference with oxidative phosphorylation. Acute and chronic poisoning may occur by dermal absorption, inhalation or ingestion. Chronic poisoning occurs mainly in sawmill workers or people living in log homes treated with PCP-containing wood protecting formulations. Quantitative determination of PCP in urine and serum is useful to detect occupational or subclinical exposure. The clinical features of acute and chronic PCP poisoning can be classified systematically into effects on the skin, metabolism (fever), the haematopoietic tissue, the respiratory system, the central and peripheral nervous system, the kidney and the gastrointestinal tract. Although PCP is not classified as a human carcinogen, some epidemiological observations suggest that exposure to chlorophenols in general and PCP solutions in particular may result in an increased risk for certain malignant disorders such as nasal carcinoma and soft tissue sarcoma. There is concern that contamination of PCP-solutions with products such as chlorodibenzo-p-dioxins is the real cause of this suspected carcinogenicity. No specific antidote exists for the treatment of (acute) PCP poisoning. The basis of the treatment of acute poisoning is intensive supportive care with prevention of dangerous rise in temperature. Use of PCP-based products as indoor wood preservatives poses an unacceptable risk to human health.

Dioxin intoxication from chronic exposure of horses to pentachlorophenol-contaminated wood shavings.

Investigations into the cause of health problems on a horse-breeding farm led to the discovery of high concentrations (630 to 9,810 mg/kg of bedding) of pentachlorophenol in wood shavings used as bedding for horses over a period of 2 to 4 years. Toxicologic signs in the horses were characteristic of toxic effects associated with exposure of polychlorinated dibenzo-p-dioxins and dibenzofurans. Tissue residue analysis confirmed presence of toxic polychlorinated dibenzo-p-dioxin and dibenzofuran isomers known to be in pentachlorophenol, substantiating the bioavailability of polychlorinated dibenzo-p-dioxins and dibenzofurans in the wood shavings. The findings provide evidence that residue concentrations in the range of 2 ng/g of toxic polychlorinated dibenzo-p-dioxin isomers in liver or fat correlate with toxicologic effects in horses.

Aplastic anaemia associated with organochlorine pesticide: case reports and review of evidence.

Three patients with aplastic anaemia had a history of substantial previous exposure to organochlorine pesticides. The temporal association between chemical exposure and the onset of first symptoms of anaemia was strongly supportive. Organochlorines have the property of lipid affinity and accumulation in adipose tissue. Objective evidence of clinically important concentrations of tissue pesticide residues may be a useful confirmation of previous exposure. In the patients studied the presence of Lindane (gamma hexachlorocyclohexane) was shown using gas chromatography/mass spectrometry with selective ion monitoring of fragments obtained from one heavily exposed patient, with concentrations about five times greater than a matched control. The presence of clinically important tissue concentrations of pentachlorophenol was also confirmed in a second patient exposed to this agent. The long term safety of organochlorine pesticides remains doubtful as they were introduced before adequate toxicological screening tests had been developed. The central registration of possible haematological adverse reactions, however, forms an important epidemiological method in the study of environmental chemical hazards and should be complied with whenever possible.

[Toxic environmental factors in sudden infant death (SIDS)]. / Zur Problematik schädigender Umwelteinflüsse beim plötzlichen Kindstod (SIDS).

The increasing number of discussions on the influence of toxic environmental factors, including SIDS, prompted systematic postmortem chemical-toxicological investigations to be carried out on 54 SIDS cases and 2 control cases of the same age group. Tissue levels of arsenic, lead, cadmium, mercury, and pentachlorphenol, as well as other organic noxious agents, were measured in several organs. In addition, the COHb concentrations were determined. In spite of the widely scattered values, the extreme levels measured and the arithmetic means and median averages of As, Pb, Cd, Hg, PCP, and COHb had no more range in concentrations than can be expected for toxic effects - according to present knowledge anyway. It was observed that infants from an urban environment showed no greater concentration of noxious agents than did infants from rural regions. There were also no differences between SIDS cases and the controls, nor was there a correlation between infections of the respiratory system that are often morphologically detected - including laryngitis - and higher concentrations of these agents in the organs of SIDS cases.

Pentachlorophenol intoxication: report of a fatal case, with comments on the clinical course and pathologic anatomy.

A case of a 33-yr-old man who died following occupational exposure to pentachlorophenol is presented. Postmortem examination revealed cerebral edema and fatty degeneration of the viscera. Review of the literature indicates that the clinical syndrome of poisoning with the compound results from mitochondrial toxicity with derangement of aerobic metabolism.

Pentachlorophenol poisoning.

Pentachlorophenol (PCP) is a pesticide commonly used as a wood preservative. Although exposure has been well controlled in large chemical manufacturing plants, over-exposures have recently becomes a concern at smaller facilities. Five cases of PCP poisoning, including two fatalities, occurred in two small wood preservative plants. All cases presented with fever, including severe hyperpyrexia in two; an increased anion gap and renal insufficiency were noted in two others. PCP may uncouple oxidative phosphorylation, resulting in a poisoning syndrome characterized by hyperpyrexia, diaphoresis, tachycardia, tachypnea, abdominal pain, nausea, and even death.