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Proper placement of the Escherichia coli division site requires two functions that are associated with different domains of the MinE protein.

The proper placement of the Escherichia coli division septum requires the MinE protein. MinE accomplishes this by imparting topological specificity to a division inhibitor coded by the minC and minD genes. As a result, the division inhibitor prevents septation at potential division sites that exist at the cell poles but permits septation at the normal division site at midcell. In this paper, we define two functions of MinE that are required for this effect and present evidence that different domains within the 88-amino acid MinE protein are responsible for each of these two functions. The first domain, responsible for the ability of MinE to counteract the activity of the MinCD division inhibitor, is located in a small region near the N terminus of the protein. The second domain, required for the topological specificity of MinE function, is located in the more distal region of the protein and affects the site specificity of placement of the division septum even when separated from the domain responsible for suppression of the activity of the division inhibitor.

Adenosine Triphosphatases↗

Dynamic localization cycle of the cell division regulator MinE in Escherichia coli.

The MinC protein directs placement of the division septum to the middle of Escherichia coli cells by blocking assembly of the division apparatus at other sites. MinD and MinE regulate MinC activity by modulating its cellular location in a unique fashion. MinD recruits MinC to the membrane, and MinE induces MinC/MinD to oscillate rapidly between the membrane of opposite cell halves. Using fixed cells, we previously found that a MinE-green fluorescent protein fusion accumulated in an annular structure at or near the midcell, as well as along the membrane on only one side of the ring. Here we show that in living cells, MinE undergoes a rapid localization cycle that appears coupled to MinD oscillation. The results show that MinE is not a fixed marker for septal ring assembly. Rather, they support a model in which MinE stimulates the removal of MinD from the membrane in a wave-like fashion. These waves run from a midcell position towards the poles in an alternating sequence such that the time-averaged concentration of division inhibitor is lowest at midcell.

Adenosine Triphosphatases↗

The MINE regimen as intensive salvage chemotherapy for relapsed and refractory Hodgkin's disease.

BACKGROUND: Relapsed or refractory Hodgkin's disease (HD) patients were treated with an intensive salvage regimen (MINE) prior to high-dose therapy (HDT) with hematopoietic stem cell support. PATIENTS AND METHODS: One hundred HD patients who either failed to respond to a front-line chemotherapy regimen (induction failure, n = 41) or relapsed (untreated relapse, n = 54; resistant relapse, n = 5) were treated with the MINE regimen. Each course of MINE comprised mitoguazone 500 mg/m2 on days 1 and 5, ifosfamide 1500 mg/m2/d from day 1 to day 5, vinorelbine (Navelbine) 15 mg/m2 on days 1 and 5, and etoposide 150 mg/m2/d from day 1 to day 3. At least two courses were given at 4-week intervals. Then, 72 patients received HDT followed by hematopoietic stem cell support. RESULTS: After MINE salvage, 34 patients achieved a complete response (CR) and 39 a partial response, yielding an overall response rate of 75%. Patients with untreated relapse had a 92.5% response rate and those with resistant relapse or induction failure a 53% response rate. A total of 58 patients reached a CR at the end of all treatments; 12 of them relapsed. Sixty-six patients were alive with a median follow-up of 26 months, including 46 patients in CR. The 2-year survival rate for the entire group was 59%. By univariate analysis, patients with an interval between their last treatment and salvage longer than 12 months, untreated relapse, or good performance status at salvage are shown to have longer survivals. The main toxic effects were neutropenia, thrombocytopenia, and infectious episodes. Three patients died of MINE-related complications and three after HDT. CONCLUSION: Given early in the course of progressive HD, the MINE regimen reduced tumor burden in a high proportion of patients with relapsed or refractory disease. Responding patients further intensified with HDT have a better outcome than those who have not responded to salvage treatment.

Adolescent↗

Positioning of the MinE binding site on the MinD surface suggests a plausible mechanism for activation of the Escherichia coli MinD ATPase during division site selection.

Division site selection in Escherichia coli requires that the MinD protein interact with itself and with MinC and MinE. MinD is a member of the NifH-ArsA-Par-MinD subgroup of ATPases. The MinE-MinD interaction results in activation of MinD ATPase activity in the presence of membrane vesicles. The sites within MinD responsible for its interaction with MinC and MinE were studied by site-directed mutagenesis and yeast two-hybrid analysis, guided by the known three-dimensional structure of MinD proteins. This provided evidence that MinC and MinE bind to overlapping sites on the MinD surface. The results also suggested that MinE and the invariant Lys11 residue in the ATPase P-loop of MinD compete for binding to a common site within the MinD structure, thereby providing a plausible structural basis for the ability of MinE to activate the ATPase activity of MinD.

Adenosine Triphosphatases↗

MinCD-independent inhibition of cell division by a protein that fuses MalE to the topological specificity factor MinE.

We report that MinE, the topological specificity factor of cell division in Escherichia coli, inhibits septation when fused to the C terminus of the maltose-binding protein MalE. This contrasts with overexpression of MinE alone, which affects growth but has no effect on division. Inhibition by MalE-MinE was minCD independent and depended on MinE segments involved in dimerization and prevention of MinCD division inhibition. The SOS and the heat shock responses were not involved, suggesting that the inhibition comes from a direct interaction of MalE-MinE with the septation apparatus. MalE-MinE lethality was suppressed by overexpression of ftsZ, as well as by overexpression of ftsN, a suppressor of temperature-sensitive mutations in genes ftsQ, ftsA, and ftsI. We also report that high-level synthesis of MalE disturbs nucleoid partitioning.

ATP-Binding Cassette Transporters↗

Influence of the nucleoid on placement of FtsZ and MinE rings in Escherichia coli.

We previously presented evidence that replicating but unsegregated nucleoids, along with the Min system, act as topological inhibitors to restrict assembly of the FtsZ ring (Z ring) to discrete sites in the cell. To test if nonreplicating nucleoids have similar exclusion effects, we examined Z rings in dnaA (temperature sensitive) mutants. Z rings were excluded from centrally localized nucleoids and were often observed at nucleoid edges. Cells with nonreplicating nucleoids formed filaments, some of which contained large nucleoid-free areas in which Z rings were positioned at regular intervals. Because MinE may protect FtsZ from the action of the MinC inhibitor in these nucleoid-free zones, we examined the localization of a MinE-green fluorescent protein (GFP) fusion with respect to Z rings and nucleoids. Like Z rings, MinE-GFP appeared to localize independently of nucleoid position, forming rings at regular intervals in nucleoid-free regions. Unlike FtsZ, however, MinE-GFP often localized on top of nucleoids, replicating or not, suggesting that MinE is relatively insensitive to the nucleoid inhibition effect. These data suggest that both replicating and nonreplicating nucleoids are capable of topologically excluding Z rings but not MinE.

Bacterial Proteins↗

Mine blast injuries: ocular and social aspects.

BACKGROUND/AIMS: Landmines have long been used in conventional warfare. These are antipersonnel mines which continue to injure people long after a ceasefire without differentiating between friend or foe, soldier or civilian, women or children. This study focuses on Afghan non-combatants engaged in mine clearing operations in Afghanistan in the aftermath of the Russo-Afghan war. The patterns and types of injuries seen are described and experiences in their management, ways, and means to prevent them, and recommendations for the rehabilitation of the affected individuals are given. METHODS: It is a retrospective and analytical study of 84 patients aged 19-56 years who sustained mine blast injuries during mine clearing operations in Afghanistan from November 1992 to January 1996. The study was carried out at a military hospital with tertiary care facilities. The patients were divided into three groups on the basis of their injuries. Group 1 required only general surgical attention, group 2 sustained only ocular injuries, while group 3 had combined ocular and general injuries. Patients in groups 2 and 3 were treated in two phases. The first phase aimed at immediate restoration of the anatomy, while restoration of function wherever possible was done in subsequent surgical procedures in the second phase. RESULTS: It was observed that 51 out of 84 patients (60.7%) had sustained ocular trauma of a variable degree as a result of the blasts. The mean age of the victims was 29 years and they were all male. A total of 91 eyes of 51 patients (89.2%) had been damaged. Bilaterality of damage was seen in 40 (78.4%) patients. Most, 34 (37.3%), eyes became totally blind (NPL). Only a few escaped with injury mild enough not to impair vision. Foreign bodies, small and multiple, were found in the majority of eyes; most, however, were found in the anterior segment, and posterior segment injuries were proportionally less. CONCLUSIONS: The prevalence of blindness caused by mine blast injuries is quite high. The resulting psychosocial trauma to the patients and their families is tremendous and has not been adequately highlighted. These injuries are a great drain on the country's resources. Enforcement of preventive measures and the use of protective gear and sophisticated equipment by the mine clearing personnel would prove to be far more economical in terms of human life as well as medical and economic resources. There is also need for greater attention towards the establishment of support groups and rehabilitation programmes for these individuals.

Adult↗

Injuries from antipersonnel mines: the experience of the International Committee of the Red Cross.

OBJECTIVE: To describe and quantify patterns of injury from antipersonnel mines in terms of distribution of injury, drain on surgical resources, and residual disability. DESIGN: Retrospective analysis. SETTING: Two hospitals for patients injured in war. SUBJECTS: 757 patients with injuries from antipersonnel mines. MAIN OUTCOME MEASURES: Distribution and number of injuries; number of blood transfusions; number of operations; disability. RESULTS: Pattern 1 injury results from standing on a buried mine. These patients usually sustain traumatic amputation of the foot or leg; they use most surgical time and blood and invariably require surgical amputation of one or both lower limbs. Pattern 2 injury is a more random collection of penetrating injuries caused by multiple fragments from a mine triggered near the victim. The lower limb is injured but there is less chance of traumatic amputation or subsequent surgical amputation. Injuries to the head, neck, chest, or abdomen are common. Pattern 3 injury results from handling a mine: the victim sustains severe upper limb injuries with associated face injuries. Eye injuries are common in all groups. CONCLUSIONS: Patients who survive standing on a buried mine have greatest disability. Non-combatants are at risk from these weapons; in developing countries their social and economic prospects after recovery from amputation are poor.

Amputation, Traumatic↗

Antipersonnel mines: who are the victims?

The International Committee of the Red Cross (ICRC) has surgically treated 49 946 war wounded from all sides of the Afghan conflict. Two hospitals were established in Peshawar (1981) and Quetta (1983) on the Afghan border of Pakistan and inside Afghanistan in Kabul (1988). One quarter of all war wounded were injured as a result of antipersonnel mines. In 1980 a UN weapons convention adopted specific rules on the use of land mines, yet despite this, mines are still present and causing casualties long after the ceasefire. In the ICRC hospital Peshawar, 48% of all war wounded in the last year were injured as a result of mines. Non-combatants accounted for 34%, with the majority being children < 16 years old (25%); 78% of all mine injured people claimed to be returning refugees, of whom 37% had returned within three months. A significant increase in injuries occurred in children, from 14% in 1990 to 25% in 1992. For a country recovering from war, the presence of mines causes a serious environmental, social, and economic burden, and for the victims, continued tragedy not only for their families but also the whole country for many years to come.

Adolescent↗

Injuries from Antitank mines in Southern Croatia.

OBJECTIVE: Antitank mines inflict devastating injuries that are usually fatal. The objective of this retrospective study was to analyze antitank mine casualties in South Croatia during the period from 1991 to 1995. METHODS: Mechanism, degree of injury according to Abbreviated Injury Scale and Injury Severity Score, as well as surgical treatment were analyzed. FINDINGS: Of 464 mine victims, 42 (9.0%) patients sustained antitank mine injuries, and 12 of these were fatal (29%). Abbreviated Injury Scale of the antitank mine injuries was 5.3 +/- 10.6. Military personnel were injured in 29 cases, and civilians were injured in 13 cases. CONCLUSION: Although injuries from antitank mines were ravaging, and frequently fatal, a significant number of patients survived.

Abbreviated Injury Scale↗

Data mining applications in the context of casemix.

In October 1999, the Singapore Government introduced casemix-based funding to public hospitals. The casemix approach to health care funding is expected to yield significant benefits, including equity and rationality in financing health care, the use of comparative casemix data for quality improvement activities, and the provision of information that enables hospitals to understand their cost behaviour and reinforces the drive for more cost-efficient services. However, there is some concern about the "quicker and sicker" syndrome (that is, the rapid discharge of patients with little regard for the quality of outcome). As it is likely that consequences of premature discharges will be reflected in the readmission data, an analysis of possible systematic patterns in readmission data can provide useful insight into the "quicker and sicker" syndrome. This paper explores potential data mining applications in the context of casemix by using readmission data as an illustration. In particular, it illustrates how data mining can be used to better understand readmission data and to detect systematic patterns, if any. From a technical perspective, data mining (which is capable of analysing complex non-linear and interaction relationships) supplements and complements traditional statistical methods in data analysis. From an applications perspective, data mining provides the technology and methodology to analyse mass volume of data to detect hidden patterns in data. Using readmission data as an illustrative data mining application, this paper explores potential data mining applications in the general casemix context.

Cluster Analysis↗

Land mine injuries: a study of 708 victims in North Iraq and Cambodia.

OBJECTIVE: The aim of this study was to explore the effect of low-cost prehospital trauma systems on trauma outcome in land mine victims and to study prehospital risk indicators for better triage of land mine injuries. METHODS: A 5-year prospective study of the effect of in-field advanced life support provided by local paramedics was conducted in mine-infested areas in North Iraq and Cambodia. RESULTS: After implementation of a rural rescue system, there was a significant reduction in trauma mortality from 26.2% in 1997 to 11.8% in 2001 (95% confidence interval for difference, 5.1%-23.6%). The mortality rate was significantly higher in fragmentation mine victims, 25.2%, as compared with blast mine victims, 5.7% (95% confidence interval for difference, 14.4%-24.6%). The severity of associated fragment injuries in patients with traumatic amputations is a solid risk predictor (area under the curve in receiver operating characteristics plots > 0.9). CONCLUSIONS: Low-cost prehospital trauma systems improve trauma outcome in land mine victims where prehospital transit times are high. The fragment wounds represent the main challenge for trauma care providers.

Adolescent↗

[The risk of laryngeal cancer among coal miners in the light of radioactivity of mines and tobacco smoking].

Until recently the exposure associated with the short-lived radon daughters (S-LRD) was thought to apply exclusively to uranium ore mines. The last few years have brought information on the presence of this hazard in non-uranium raw materials mines, e.g. in hard coal mines. It was ascertained that the hard coal mines exposure to the S-LRD lead to increase of frequent of larynx cancer cases in this population on the Upper Silesia Region. 67 Upper Silesia hard coal mines were divided for three groups: I.--(4 number of mines), highest hazard, i.e. < 2.5 microJ/m2 (mean value of potential alpha-energy concentration of S-LRD; II degrees-28, mean hazard, i.e. > 0.4- < 2.5 microJ/m3; III.--35, lowest hazard (risk relative level-RR = 1.00), i.e. < 0.4 microJ/m3. In compare these 3 groups taking into consideration tobacco smoking standardized we have following results of the RR: for suffering natives from larynx cancer: I.--2.86 (at p < 0.05), II.--1.08, at III.--1.00, and for immigrants: I.--6.97 (at p < 0.05), II.--2.09, at III.--1.00 (it is reference level.

Case-Control Studies↗

Occupational respiratory disease in mining.

This review is based on research-based literature on occupational lung disease in the mining and related industries, focusing on conditions of public health importance arising from asbestos, coal and silica exposure. Both 'traditional' and 'new' concerns about occupational respiratory disease in miners are addressed, with the inclusion of practical evidence-based findings relevant to practitioners working in developed and developing countries. Mining is not a homogeneous industry since current miners work in formal and informal operations with numerous, and often multiple, air-borne exposures. A further occupational health challenge facing primary care practitioners are ex-miners presenting with disease only after long latency. The sequelae of silica exposure remain an occupational health priority, particularly for practitioners who serve populations with concomitant HIV and tuberculosis infection and even when exposure is apparently below the statutory occupational exposure level. Coal workers' pneumoconiosis, asbestos related diseases, lung cancer and other occupational respiratory diseases remain of considerable importance even after mining operations cease. While mining exposures contribute significantly to lung disease, smoking is a major factor in the development of lung cancer and chronic obstructive airways disease necessitating a comprehensive approach for prevention and control of mining-related occupational lung disease.

Adult↗

Respiratory symptoms and spirometry in experienced coal miners: effects of both distant and recent coal mine dust exposures.

The goal of this study was to determine whether respiratory symptoms were associated with the lower concentrations of respirable coal mine dust that were required by the U.S. Coal Mine Health and Safety Act (CMHSA) of 1969. The subjects were 1,866 male miners who had participated in the National Study of Coal Workers' Pneumoconiosis (NSCWP) and been tested at least twice, initially in either Round 1 (R1) (1969-71) or Round 2 (R2) (1972-75) and then finally in Round 4 (R4) (1985-88). Self-reported information elicited with a standardized questionnaire was used to determine the presence at the final round (i.e., R4) of chronic bronchitis, shortness of breath, and wheeze. Cumulative coal mine dust exposure was characterized for both the pre- and post-CMHSA periods. Controlling for age and other potential confounders, increased risks for the symptoms were associated with higher levels of both measurements of exposure. Moreover, the adverse effects of the lower, post-CMHSA exposure were evident for shortness of breath and wheeze especially among subjects who had little pre-CMHSA coal mining experience. These findings provide additional evidence of the limitations of the current 2.0 mg/m3 coal mine dust standard to prevent respiratory disease.

Adult↗

The accuracy of self-reported regulatory data: the case of coal mine dust.

Coal-mine owners are required to measure miner exposures to respirable dust so that compliance with Federal health regulations can be monitored. This study analyzes the problem of possible underreporting of dust exposures. Using two statistical approaches, data for three mining occupations in 54 large underground coal mines during 1976-1978 are examined for evidence of underreporting. First, regression estimates compare dust concentrations reported by coal-mine owners with those reported by government health inspectors. Then, the statistical distribution of concentrations reported by coal-mine owners are examined for the size and nature of their deviation from log-normality. Both approaches suggest widespread underreporting.

Air Pollutants, Occupational↗

Heavy metal (Pb, Zn, Cd, Fe, and Cu) contents of plant foliage near the Anvil Range lead/zinc mine, Faro, Yukon Territory.

Mining and processing of lead (Pb)/zinc (Zn) ore at the Anvil Range mine occurred near the town of Faro in the Yukon Territory, Canada, for approximately 30 years, beginning in 1968. A study was undertaken to examine whether the mining activities had left a detectable "footprint" on the environment in the way of heavy metal phytoaccumulation. Foliage of three native plant species was sampled: bog blueberry (Vaccinium uliginosum), Labrador tea (Ledum groenlandicum), and willow (Salix sp.), at approximately 0.25, 2.5, 12, 30, and 200 (control) km distant from the mill (ore-processing facility at the mine). Foliage samples were oven-dried, wet- or dry-ashed, and analyzed for metal content using ICP-AES. In addition to Pb and Zn, the primary ore constituents, copper (Cu), iron (Fe), and cadmium (Cd), were also assayed. As expected, foliar Pb and Zn concentrations were elevated in plants at the sites closest to the mill, i.e., 0.25 and 2.5 km from the mine facility. Copper and Fe, both essential nutrients for plants, were also elevated in foliage at the sites closest to the mill, but not to a level that would be of concern. Foliar Cd levels were highest in Salix relative to the other species but were not affected by proximity to the mill. Results suggest that Ledum may be the best indicator of high environmental concentrations of Pb, while Salix may be the best indicator of elevated Zn and Cd.

Environmental Exposure↗

Mercury exposure of maroon workers in the small scale gold mining in Suriname.

Suriname is experiencing a revival of small scale gold mining activities, with about 10,000 to 15,000 workers involved in 1996. The estimated production in 1995 is at least 10,000 kg crude gold. Gold is extracted with mercury and methods used are comparable with those described for gold mining in the Amazon Basin. Since no data exist on the internal mercury exposure of workers in Suriname a study was performed. A group of mercury-exposed Maroons, who are principally involved in the mining located in the tropical rainforest, is compared with nonexposed Maroons living in a non-gold mining area. Blood and urine samples of both groups were analyzed for total mercury using an atomic absorption spectrometer with an FIAS hydride system. In the study 28 exposed and 17 controls with a comparable mean age (P=0.544; exposed 27+/-7.2 years, n=26; controls 26+/-7.7 years, n=17), all males, participated. The urine levels for both groups differ statistically significantly from each other (P<0.001; exposed mean 27.5+/-21.1 microg/g creatinine; controls mean 5. 2+/-2.9 microg/g creatinine). This is, however, not the case with the blood levels (P=0.036: exposed mean 18.1+/-11.0 microg/L, n=25; controls mean 26.8+/-14.6 microg/L, n=16). In contrast with blood the urine total mercury levels in this study confirm, on a group basis, exposure to mercury as described for individuals working in the gold mining in the Amazon Basin.

Adolescent↗