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LIFE CYCLE ANALYSIS OF MAMMALIAN CELLS. I. A METHOD FOR LOCALIZING METABOLIC EVENTS WITHIN THE LIFE CYCLE, AND ITS APPLICATION TO THE ACTION OF COLCEMIDE AND SUBLETHAL DOSES OF X-IRRADIATION.

Equations are presented describing the accumulation of cells at any part of the life cycle as a result of addition of specific blocking agents. An experimental methodology using these relationships is described which makes possible analysis with relatively high resolution of the distribution of cells throughout the life cycle in normal cultures or those treated with various agents. The action of colcemide on S3 HeLa cells studied by this method revealed that colcemide has no effect on the G1, S, or G2 stages; it blocks cells quantitatively at the metaphase-anaphase region; but it accumulates mitotic figures only from the cells which have not yet entered mitosis at the time of its addition. The technique was also applied to study the efficiency of x-irradiation in delaying the entrance of G2 cells into mitosis. A definite lag was found at the lowest dose studied which was 9 rads. Only the cells confined to a central region of G2 at the time of irradiation are affected by this dose.

Animals↗

Extracorporeal life support for the treatment of viral pneumonia: collective experience from the ELSO registry. Extracorporeal Life Support Organization.

UNLABELLED: Viral pneumonia is the most common indication for pediatric extracorporeal life support (ECLS). Despite this fact, no previous studies have directly stratified patient outcome according to viral etiology. METHODS: Using the Extracorporeal Life Support Organization (ELSO) registry database, the authors reviewed the national experience of patients undergoing ECLS with culture or serologically demonstrated viral pneumonia and compared outcome parameters according to viral etiology. RESULTS: Patients differed with respect to age and weight according to the viral type. Patients with respiratory syncytial virus (RSV, median age 3 months), herpes simplex virus (HSV, 0.13 months), cytomegalovirus (CMV, 2.5 months), and adenovirus (0.6 months) were younger than those with other viruses (5.5 months). The patient groups did not significantly differ with respect to pre-ECLS Pao2 mean airway pressure (MAP), oxygenation index (OI), mode, or duration of ECLS. The overall survival of patients with viral pneumonia was 57%, although patients with RSV or CMV were found to have a 67% survival. Patients infected with HSV and adenovirus had a significantly lower survival rate (31% and 25%, respectively) when compared with those with RSV. In addition RSV pneumonia was associated with fewer cardiovascular complications than several of the other viral types. When comparison was made between survivors and nonsurvivors, a higher last pre-ECLS MAP and increased incidence of elevated creatinine and renal failure requiring dialysis were noted among nonsurvivors. CONCLUSION: ECLS remains an important modality in the treatment of neonatal and pediatric patients with respiratory failure secondary to viral pneumonia. The survival rate of these patients varies according to the type of viral infection.

Adenovirus Infections, Human↗

Social status, life changes, housing conditions, health, functional abilities and life-style as risk factors for recurrent falls among the home-dwelling elderly.

OBJECTIVE: To define the risk factors for recurrent falls in the home-dwelling elderly. DESIGN: A prospective population-based study covering two years. SETTING: Five rural municipalities around the city Oulu, northern Finland. PARTICIPANTS: All home-dwelling elderly persons (N = 1,016) aged 70 years or older living in the municipalities. OUTCOME MEASURES: The risk factors of recurrent falling by variables related to social status, life changes, housing conditions, health, functional abilities and life style, using cross-tabulations and multivariate analyses. RESULTS: The recurrent fallers (at least two falls within 365 days after the examination day) consisted of 17 men (6% of the men) and 71 women (14%). Logistic regression analyses showed female sex, urinary urgency, frequent fear of falling, dizziness, a poor pulse rate rise 30 seconds after standing up and falling during the previous year to be risk factors for recurrent falls. After the variable representing previous falls had been removed from the analysis, urinary incontinence and a change in housing conditions during the past two years emerged and urinary urgency dropped out of the model. CONCLUSIONS: Women particularly are a target group for the prevention of falls among the elderly. Urinary urgency and urinary incontinence, fear of falling, dizziness and changes in the housing conditions should be inquired about to identify the elderly at risk for falling and to take preventive interventions. In addition to testing blood pressure changes after standing up, the changes in pulse rate should be determined to identify and treat elderly people who have orthostatic conditions.

Accidental Falls↗

Loss of prohibitins, though it shortens the replicative life span of yeast cells undergoing division, does not shorten the chronological life span of G0-arrested cells.

Prohibitin proteins have been implicated in cell proliferation, ageing and the maintenance of mitochondrial integrity. The yeast prohibitins, Phb1p and Phb2p, are close in sequence to their two human counterparts, prohibitin and BAP37. Mutants of Saccharomyces cerevisiae that lack these prohibitins have a shortened replicative (budding) life span. Nevertheless, their chronological life span, measured as the survival of stationary phase (G0) cells over time, is essentially normal. Loss of prohibitins does not hypersensitise cells to their endogenous free radical production, though it does slightly increase their sensitivity to ethanol. It is unlikely, therefore, that the influences of prohibitins over replicative senescence involve free radicals, despite the evidence from many systems linking ageing to the long-term effects of oxidative stress. Yeast phb1 and phb2 mutants and also the phb1, phb2 double mutant, tend to lose respiration competence when in G0-arrest, indicating that nondividing cells lacking prohibitins have problems maintaining a functional mitochondrial electron transport chain. This may reflect an imbalance in the turnover of components of the respiratory chain in G0 cells, since the Phb1/2p complex is known to help stabilise these components. Such losses of respiratory function in G0-arrested cells are greater with the loss of Phb1p than with the loss of Phb2p, revealing the Phb1p null and Phb2p null phenotypes to be nonidentical.

Cell Division↗

Mid-life smoking and late-life dementia: the Honolulu-Asia Aging Study.

We studied the association between mid-life smoking and late-life dementia in the Honolulu Heart Program (1965-1971) and follow-up assessment for dementia (1991-1996) of 3734 Japanese-American men (80% of survivors). Neuropathologic data were available for 218 men. Adjusting for age, education and apolipoprotein E (APOE) genotype, the risk of Alzheimer's disease (AD) in smokers increased with pack-years of smoking at medium (odds ratio (OR)=2.18, 95% confidence interval (CI)=1.07-4.69) and heavy (OR=2.40; 95% CI=1.16-5.17) smoking levels. Very heavy smoking was not associated with AD (OR=1.08; 95% CI=0.43-2.63). Findings were similar when AD cases included those with cerebrovascular disease and for all dementias combined. Adjustment for cardiovascular and respiratory factors or stratification by apolipoprotein E genotype did not change these associations. In an autopsied subsample, the number of neuritic plaques increased with amount smoked. This study suggests that amount smoked is associated with an increasing risk of AD and Alzheimer-type neuropathology up to heavy smoking levels. The lack of association in very heavy smokers may be due to a hardy survivor effect.

Aged↗

European Resuscitation Council Guidelines 2000 for Adult Basic Life Support. A statement from the Basic Life Support and Automated External Defibrillation Working Group(1) and approved by the Executive Committee of the European Resuscitation Council.

The European Resuscitation Council (ERC) last issued guidelines for Basic Life Support (BLS) in 1998 [1]. These were based on the "Advisory Statements" of the International Liaison Committee on Resuscitation (ILCOR) published in 1997 [2]. Following this, the American Heart Association, together with representatives from ILCOR, undertook a series of evidence-based evaluations of the science of resuscitation [3] which culminated in the publication of "Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care" in August 2000 [4,5]. The Basic Life Support and Automated External Defibrillation Working Group (BLS&AED Group) has considered this document and has recommended changes in the ERC BLS guidelines. These are presented in this paper.

Adult↗

European Resuscitation Council Guidelines 2000 for Basic Paediatric Life Support. A statement from the Paediatric Life Support Working Group and approved by the Executive Committee of the European Resuscitation Council.

The European Resuscitation Council (ERC) last issued guidelines for Paediatric Life Support (PLS) in 1998 [1]. These were based on the "Advisory Statements" of the International Liaison Committee on Resuscitation (ILCOR) published in 1997 [2]. Following this, the American Heart Association, together with representatives from ILCOR, undertook a series of evidence-based evaluations of the science of resuscitation which culminated in the publication of "Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care" in August 2000 [3,4]. The Paediatric Life Support Working Party of the European Resuscitation Council has considered this document and the supporting scientific literature and has recommended changes to the ERC Basic PLS guidelines. These are presented in this paper. There have been few major changes to the ERC recommended guidelines as some of the changes agreed in "Guidelines 2000" had already been introduced into Europe subsequent to the 1998 ILCOR "Advisory Statements" (Fig. 1).

Adolescent↗

Vestiges of life in the oldest Greenland rocks? A review of early Archean geology in the Godthabsfjord region, and reappraisal of field evidence for > 3850 Ma life on Akilia.

The Godthåbsfjord region of West Greenland contains the most extensive, best exposed and most intensely studied early Archean rocks on Earth. A geological record has been described of numerous magmatic events between ~3.9 and 3.6 Ga, and evidence of life at >3.85 Ga and ~3.8-3.7 Ga has been proposed from two widely-separated localities. Some of these claims have recently been questioned, and the nature of the best preserved remnants of the oldest known terrestrial volcanic and sedimentary rocks in the Isua greenstone belt are being reinvestigated and substantially reinterpreted. The first part of this article reviews the evolution of geological research and interpretations, outlining the techniques by which the geological history has been determined and the ensuing controversies. The second part re-examines crucial field evidence upon which the antiquity of the oldest terrestrial life is claimed from the island of Akilia.

Biological Evolution↗

Research agenda for developing measures to examine quality of care and quality of life of patients diagnosed with life-limiting illness.

Despite the universality of dying, research has not focused on developing conceptual models and measurement tools for examining the quality of care and quality of life of dying patients and their loved ones. We present here a vision and research agenda for the development of a Tool Kit of Instruments to Measure End of Life Care (TIME). Instruments for inclusion in the eventual "Tool Kit" should be patient-focused and family-centered, clinically meaningful, administratively manageable, and psychometrically sound. Prioritizing domains to measure quality of care should be based on consumer input and synergistic with ongoing efforts to formulate guidelines and standards of care. For this vulnerable population, research is needed regarding the timing and sources of data collection. In order to achieve maximal benefit, ultimately measurement tools must be incorporated into existing measurement systems and consideration be given to generating informative reports which leads to institutional action to improve the quality of care.

Humans↗

High food supply in perinatal life appears to favour the development of insulin-treated diabetes mellitus (ITDM) in later life.

Men who were born in war and post-war periods with shortage of food supply (1943-47) showed a markedly low prevalence of insulin-treated diabetes mellitus (ITDM), but not of non-insulin-treated diabetes mellitus (NITDM) in later life. A significant increase (+54%) of ITDM prevalence was observed between 1976 and 1982 for subjects at 26-31 years of age, who were born in a post-war period (1945-50) with shortage and a peace period (1951-56) without shortage of food supply, respectively. By contrast, there was not found an increase--but even a slight decrease (-14%)--of ITDM prevalence between 1976 and 1982 for subjects at 38-43 years of age, who were born in a peace period (1933-38) without shortage and a war period (1939-44) with shortage of food supply, respectively. A similar clear dependence of diabetes prevalence on food supply in perinatal life could not be observed for NITDM. On the other hand, the prevalence of NITDM appeared to be significantly dependent--in contrast to ITDM--on food supply in adulthood.

Adult↗

A right to life for the unborn? The current debate on abortion in Germany and Norbert Hoerster's legal-philosophical justification for the right to life.

Rights to life for unborn humans and to abortion with impunity are incompatible. This observation by the German legal philosopher Norbert Hoerster contains a fundamental criticism of the state regulation on abortion in Germany. The regulation regards abortion as unlawful, but declines to prosecute if the abortion is conducted within the first three months of pregnancy and the pregnant woman received counseling at least three days prior to terminating the pregnancy. In contrast to the German legislature, Hoerster is in favor of setting the beginning of a right to life at birth. With this suggestion and the consequent demand for a general legalization of abortion, Hoerster himself has become the target of harsh criticism. The following article analyzes Hoerster's position and that of his opponents against the background of the current abortion debate in Germany. The consequences for dealing with the handicaps of Hoerster's suggested regulations will also be addressed.

Abortion, Illegal↗

Competency in end-of-life care: last hours of life.

Clinical competence, willingness to educate, and calm and empathic reassurance are critical to helping patients and families in the last hours of living. This review adapted from the Education for Physicians on End-of-Life Care (EPEC) Curriculum describes the predictable course that occurs as well as approaches to management. Management principles are the same at home or in a health care institution. However, death in an institution requires accommodations to assure privacy, cultural observances, and communication that may not be customary. In anticipation of the event, it helps to inform the family and other professionals about what to do and what to expect. Care does not end until the family has been supported with their grief reactions and those with complicated grief helped to get care. Care at the end of life is a core competency.

Clinical Competence↗

Growth patterns in euconodont crown enamel: implications for life history and mode-of-life reconstruction in the earliest vertebrates.

Euconodonts were the first vertebrates to produce a mineralized skeleton. It is concluded that the minor increments in the crown enamels of Protopanderodus varicostatus and Drepanodus robustus are probable homologues of the cross striations in hominoid enamel, although they are much more variable in thickness and represent daily to weekly growth. Major increments are superficially similar to lines of Retzuis, but represent a check in growth that is likely to have occurred at monthly intervals. Periods of above- and below-average growth are likely to have been seasonally moderated. The growth of P. varicostatus' elements are characterized by two distinct phases: the production of a triangular, asymmetrical juvenile 'proto-element' followed, in a second phase, by the development of the curved and twisted geometry of the adult element. These fundamentally different morphologies imply that juvenile and adult animals had different modes of life and/or feeding strategies. In these animals the growth of the elements was indeterminate. The growth model for euconodonts is clearly different from that of hominoid teeth as the enamel organ must have reformed repeatedly throughout life.

Animals↗

Life-threatening cardiac involvement throughout life in a case of Costello syndrome.

Costello syndrome is characterized by poor postnatal growth, mental retardation, curly hair, coarse face, loose skin of the hands and feet, and nasal papillomata. Patients with Costello syndrome have a high incidence of cardiac involvement, such as arrhythmias, hypertrophic cardiomyopathy, or congenital anomalies. The importance of cardiac involvement in Costello syndrome has not been strongly emphasized thus far, although arrhythmia and hypertrophic cardiomyopathy are both serious forms of cardiac involvement. We report the case of a Japanese girl with Costello syndrome, who experienced life-threatening cardiac involvement throughout her life.

Anus Neoplasms↗

Life history evolution in cichlids 1: revisiting the evolution of life histories in relation to parental care.

Empirical links between egg size and duration of parental care in fishes have generated a considerable amount of theory concerning life history evolution. However, to date, this link has not been investigated in relation to other important life-history traits such as clutch size and body size, or while controlling for shared ancestry between species. We provide the first phylogenetically based tests using a database with information on egg size, clutch size, body size and care duration in cichlid fishes (Cichlidae). Multiple regression analyses, based on independent contrasts on both the species and the genus level, showed that clutch size is the variable most closely related to duration of care. This pattern appeared to be driven by post-hatch care relationships. Our results show that, contrary to expectation, there is no positive link between egg size and care duration in Cichlidae. Instead, greater reproductive output through increased clutch size investment appears to have coevolved with greater care of offspring. We suggest that re-evaluation of the generality of current models of the evolution of egg size under parental care in fishes is needed.

Animals↗

'Pressure of life': ethnicity as a mediating factor in mid-life and older peoples' experience of high blood pressure.

Hypertension is a common condition which disproportionately affects African Caribbean people in England, yet this experience is rarely reported in the literature. Whilst a body of literature exists that explores chronic illness experience, little attention is paid to hypertension, nor to ethnicity as a mediating concept in chronic illness experience. This paper explores the meaning and consequences of hypertension for African Caribbean people residing in England. The study conducted was a qualitative study, informed by the ethnographic tradition. The study methods included the conduct of two focus group interviews (10 participants), 21 in-depth interviews and five vignette interviews. Thirty-six people in total participated in the study, both men and women, aged between 37 and 82 years (median age = 59.5 years) in two English cities. The sample was generated by contacting GP surgeries, community groups and associations and included economically active and retired people. The narrative accounts provided illuminate the personal biographies of the mid-life and older participants in the study, providing evidence as to how issues such as ethnicity, migration, cultural adaptation, racism and discrimination may impact upon the chronic illness experience. Participants' understandings of their self-defined condition of high blood pressure differed greatly from medical conceptualisations of the condition of hypertension. The implications of the study are that in order to provide effective health and social care for individuals of African Caribbean origin with hypertension, care-providers require insight into how migration and cultural adaptation may create major disruption to an individual's life trajectory, to which the subsequent diagnoses of chronic illness are relative in terms of the individual's response and adaptation.

Adaptation, Psychological↗

The afternoon of life: Jung's view of the tasks of the second half of life.

The second half of life is marked for some by depression and an absence of meaning. Carl Jung believed that middle and old age, like youth, have specific developmental tasks. While the developmental tasks for youth involve turning outward and engaging life, the goal for the mature individual is to consolidate an integrated personality by integrating the conscious and the unconscious parts of self. The application of Jungian principles with mature depressed clients in the clinical care setting is discussed.

Aged↗

Characteristics of the 'life spanning' phenomenon in Amoeba proteus. Independent nuclear and cytoplasmic ability to impose finite 'life span'.

Amoeba proteus given adequate food grows exponentially and clones of amoebae are normally immortal. After periods of food supply restriction to that necessary for maintenance, or food intake restriction by agitation, cells subsequently given a normal growth diet produce clones of finite life span. Reciprocal nuclear transfer between maintained and normal cells demonstrated that the nucleus and cytoplasm of maintained cells have acquired the independent ability to impose a finite life span on clones developing from cells whose other components are normal. In clones developing from maintained cells, inviable cell production is enhanced and inter-division times are prolonged. Inter-division times and clones mean doubling times do not show normal distribution.

Amoeba↗