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Ultrasound biomicroscopic findings in aniridia.

PURPOSE: To describe the ultrasound biomicroscopic features of eyes with aniridia. DESIGN: Observational case series. METHODS: Nineteen eyes of 10 patients with aniridia (six males and four females) ranging in age from 3 months to 53 years (21.0 +/- 16.4, mean +/- SD), and 50 normal subjects (30 men and 20 women) ranging from 16 to 56 years (31.1 +/- 13.2) were evaluated. Ultrasound biomicroscopic findings were recorded in the 3-, 6-, 9-, and 12-o'clock directions. Adult patients (aged 16 years or older) with aniridia were compared with the age-matched controls. RESULTS: Ultrasound biomicroscopy (UBM) detected extremely tiny irises in all eyes with aniridia. The eyes with aniridia showed significantly smaller values than the controls in ciliary body length (4.49 +/- 0.63 versus 5.79 +/- 0.44 mm, P <.001, unpaired Student t test), ciliary body thickness (0.75 +/- 0.17 versus 1.24 +/- 0.22 mm, P <.001), iris root thickness (0.47 +/- 0.14 versus 0.61 +/- 0.07 mm, P <.001), scleral-ciliary process angle (31.7 +/- 3.26 versus 43.1 +/- 4.48 degree, P <.001), and anterior chamber depth (1.99 +/- 0.43 versus 2.94 +/- 0.34 mm, P <.001). In the aniridia eyes, there was a significantly positive correlation between iris thickness and ciliary body thickness (Pearson r = 0.829, P =.001). CONCLUSION: Ultrasound biomicroscopic imaging demonstrated that not only iris hypoplasia but also ciliary body hypoplasia exist in aniridia. Anterior inclination of the ciliary process was also found, which was thought to be at least partly responsible for the shallow anterior chamber.

Adolescent↗

Developmental considerations in the concept of affective illness.

A spectrum exists from change, to crisis, to turmoil, and, at times, to illness at watersheds in the life cycle. Affective experience can be a mobilizing factor and emotional catalyst in the growth experience or a devastating psychotic mood disturbance when predisposing life events and genetic disposition are operational. This paper reviews the dynamics of biologic systems, chronobiology, and time-related transitions of the developmental experience. The relationship of a developmental time clock to affective phenomenology and clinical affective disorder is discussed and presented in two case vignettes. Developmental theory and the interface between life events, stress, and affective illness are reviewed and a concept of development as a sequence of affective cycles is presented.

Adolescent↗

[Molecular dating in the genomic era].

The comparison of DNA and protein sequences of extant species might be informative for reconstructing the chronology of evolutionary events on Earth. A phylogenetic tree inferred from molecular data directly depicts the evolutionary affinities of species and indirectly allows estimating the age of their origin and diversification. Molecular dating is achieved by assuming the molecular clock hypothesis, i.e., that the rate of change of nucleotide and amino acid sequences is on average constant over geological time. If paleontological calibrations are available, then absolute divergence times of species can be estimated. However, three major difficulties potentially hamper molecular dating : (1) a limited sample of genes and organisms, (2) a limited number of fossil references, and (3) pervasive variations of molecular evolutionary rates among genomes and species. To circumvent these problems, different solutions have been recently proposed. Larger data sets are built with more genes and more species sampled through the mining of an increasing number of genomes. Moreover, independent key fossils are identified to calibrate molecular clocks, and the uncertainty on their age is integrated in subsequent analyses. Finally, models of molecular rate variations are constructed, and incorporated in the so-called relaxed molecular clock approaches. As an illustration of these improvements, we mention that the debated age of the animal (bilaterian metazoans) diversification may have occurred between 642-761 million years ago (Mya), roughly 100 Ma before the Cambrian explosion. Among mammals, the initial diversification of major placental groups may have taken place around 100 Mya, well before the Cretaceous/Tertiary boundary marking the extinction of dinosaurs.

Animals↗

Involution of the mammalian thymus, one of the leading regulators of aging.

During the past century of research on the thymus, the fact that every mammalian thymus undergoes marked morphological changes during the complex process of aging has been defined as a basic histogenetical rule. In characterizing the physiological (i.e. chronic) involution of the mammalian thymus, the term "Altersinvolution" referring to age-related involution is used. All other types of thymic involution are associated with an initial trigger and a relatively "acute" mechanism. In all of these factor-dependent cases of thymic involution, we use the term "akzidentelle Involution" (i.e. acute accidental thymic involution). Temporary thymic involution occurs during pregnancy, with a full restoration of the cellular microenvironment at the end of lactation. It is now clear that pregnancy alters the well established adaptational homeostasis between the neuroendocrine and immune axes. Such nonprogressive involution has also been observed during various seasons in various animals (i.e. seasonal involution). Changes characteristic of thymic involution begin during or soon after the first year of birth, and continue progressively throughout the entire life span. The 3% to 5% annual reduction rate of the cells of the human thymic microenvironment continues until middle age, when it slows down to less than 1% per year. According to the extrapolation of these results total loss of thymic reticuloepithelial tissue and the associated thymocytes should occur only at the age of 120 years in humans. This serious reduction of the thymic cellular microenvironment is a well controlled physiological process and is presumably under both local and global regulation by the cells of the RE meshwork and the neuroendocrine system, respectively. In humans, the age related decline in serum "facteur thymique sérique" (FTS) levels begins after 20 years of age and FTS completely disappears from the blood between the 5th and 6th decade of life. In contrast, the serum levels of thymosin-alpha 1 and thymopoietin seem to decline earlier, starting as early as 10 years of age. The influences of a variety of other hormones on the involution of the thymus have also been characterized: testosterone, estrogen and hydrocortisone treatment results in marked involution, cortisone and progesterone administration causes slight to moderate, while use of desoxycorticosterone has no effect. The experimental administration of thyroxine yielded dose dependent results: low doses resulted in thymic hypertrophy, higher doses produced slight hypertrophy and the highest employed doses caused thymic atrophy. The atrophy was of apicnotic type, very different from that detected after treatment with corticoid hormones. Thymus transplantation experiments indicate that age-related, physiological thymic involution has been genetically preprogrammed. Grafting of the thymus from one week old C3H leukemic strain mice into 6 month old hosts resulted in changes in thymic weight and an involution pattern that was synchronous in all recipients, in direct correlation with the glands in the donor, but not in the host. These data strongly suggest that the stimulus for thymus cell proliferation and differentiation is genetically determined within the organ implant. Since the thymus is the primary T-lymphopoietic organ during ontogenesis in the mammalian organism, its age-related involution with the already mentioned morphological alterations can be held responsible only for a decline in antigen-specific T lymphocyte immune functions. Thymic involution and diminished T lymphocyte proliferation can be partially restored by thymic tissue transplantation or use of thymic hormones. The leading physiological role of the thymic cellular microenvironment as a "clock" of the mammalian aging process is also discussed. "If present cells have come from pre-existing cells, then all cells can trace their ancestry back to the first formed cell in an unbroken line of descent."--Rudolf Virchow, 1858(1) "I have neve

Adaptation, Physiological↗

Age, phylogeography and population structure of the microendemic banded spring snail, Mexipyrgus churinceanus.

Recent theoretical and empirical studies of phylogeography and population structure indicate that many processes influence intraspecific evolutionary history. The present study represents the first examination of various forces influencing the spatial and temporal patterns of sequence variation in the freshwater Mexican banded spring snail, Mexipyrgus churinceanus. This snail occurs in one of the most critically endangered centres of freshwater endemism, the desert ecosystem of Cuatro Ciénegas. From cytochrome b mtDNA sequence variation, there is strong evidence of long-term isolation of three regions, suggesting that these regions represent evolutionarily distinct lineages. Molecular clock estimates of clade age indicate a time to most recent common ancestor of approximately 2.5 million years ago (Ma). The three regions differ considerably in the historical and demographic forces affecting population structure. The western populations have extremely low mtDNA diversity consistent with a severe bottleneck dating to 50,000 years before present (bp). The nearby Rio Mesquites drainage is characterized by fragmentation events, restricted gene flow with isolation by distance, and higher levels of mtDNA polymorphism. These patterns are consistent with the long-term stability of this drainage along with habitat heterogeneity and brooding contributing to population isolation and restricted gene flow. Southeastern populations show evidence of range expansion and a strong influence of genetic drift. Migration rates between drainages indicate very little gene flow between drainages except for asymmetric migration from the Rio Mesquites into both western and southeastern drainages.

Animals↗

Phylogenetic analysis and trait evolution in Australian lineages of drywood termites (Isoptera, Kalotermitidae).

A phylogenetic analysis of Australian drywood termites (Isoptera, Kalotermitidae) based on partial sequence from the cytochrome oxidase II (COII) and cytochrome b genes is presented. In addition to providing new information on the evolutionary relationships among 25 species from seven genera, we evaluate the relative likelihoods of alternative topological hypotheses, including those derived from morphology-based classifications. We also test the applicability of a molecular clock for estimating the age of the Kalotermitidae and infer the evolution of species-specific variation for habitat type and soldier caste phragmosis by mapping this information onto the independently derived phylogeny. Maximum-likelihood analysis of both nucleotide and protein sequences from a multigene data set jointly support a single topology, which is shown to be the best estimate of the true phylogeny among the alternatives tested. Our results support the monophyly of all genera but question the discrimination between Procryptotermes and Cryptotermes. A basal dichotomy among generic groups suggests two principle lines of divergence within the family. Intergeneric relationships show mixed congruence to previous proposals, resulting in one morphology-based classification being rejected. A molecular clock hypothesis is not supported due to significant among-lineage rate heterogeneity in the COII gene. Patterns revealed through trait mapping suggest that the most recently diverged taxa tend to occupy the driest habitats and that these same taxa reflect a defensive transition away from large mandibulate soldiers toward small phragmotic soldiers. The association between habitat and defensibility supports the hypothesis that these two characters have been tightly linked throughout the social diversification of termites.

Animals↗

Circadian locomotor rhythms in aged hamsters following suprachiasmatic transplant.

Circadian activity rhythms that have been eliminated by lesions of the suprachiasmatic nucleus (SCN) can be restored by fetal SCN grafts. Partial lesions of the host allow simultaneous expression of both donor and host rhythms. Because partial SCN ablation produces characteristic changes in activity rhythms that are similar to those that occur with age, including shortened period, reduced amplitude, and fragmentation, we investigated the extent to which fetal SCN grafts may be expressed by an animal whose activity rhythm exhibits these age-dependent changes. The results indicate that expression of a transplanted clock is possible in an unlesioned aged host. Grafts of fetal SCN into young hosts and cortical tissue grafts into intact aged hosts have no effect. In those aged animals that received SCN grafts, three patterns of expression emerged in the subsequent locomotor activity record: complete dominance of locomotor rhythmicity by the donor; relative coordination between donor and host rhythms; and spontaneous switching between host and donor phenotypes. The results suggest that the expression of rhythmicity by the grafted SCN may depend on the relative amplitude or strength of signals produced by the host and donor SCN.

Aging↗

Relativistic parameters of senescence.

The laws of biochemistry and biology are governed by parameters whose description in mathematical formulas is based on the three-dimensional space. It is a fact, however, that the life span of a cell and its specific functions, though limited, can be extended or diminished depending on the genetic code but also, on the natural pressure of the environment. The plasticity exhibited by a cellular system has been attributed to the change of the three-dimensional structure of the cell, with time being a simple measure of this change. The model of biological relativity proposed here, considers time as a flexible fourth dimension that corresponds directly to the inertial status of the cells. Two types of clocks are defined: the relativistic biological clock (RBC) and the mechanical clock (MC). In contrast to the MCs that show the astrological reference time, the time shown by the RBCs delay because it depends on cellular activity. The maximum and the expected life span of the cells and/or the organisms can be therefore relied on time transformation. One of the most important factors that can affect time flow is the energy that is produced during metabolic work. Based on this observation, RBCs can be constructed following series of theoretical experiments in order to assess biological time and life span changes.

Aging↗

Genetic "clocks" and "soft" events: a twin model for pubertal development and other recalled sequences of developmental milestones, transitions, or ages at onset.

We propose and explore a twin model to examine the basis for synchrony that often characterizes different facets of normal development. In so doing we also present an approach to the analysis of "soft" events; events for which available reports of dates or ages of occurrence are unreliable or inconsistent. Discrepancies among reports are accounted for by a statistical measurement model. This combines current status error reflecting uncertain definition of onset and two mechanisms for the phenomenon of "telescoping," namely, systematic compression of the time scale and heteroscedastic random measurement error. Statistically, the model can be viewed as a mixed generalized linear model with random effects within both mean and variance functions or, alternatively, as involving multiplicative random effects. We apply the model to multiple maternal reports on menarche and onset of breast development in twin daughters. Fitted to data from the Virginia Twin Study Of Adolescent and Behavioral Development by the use of penalized/predictive quasi-likelihood, the model provided much improved estimates of the true age-at-onset distribution as compared to those from a naive analysis. Results suggested that the observed variance was made up almost entirely of genetic variance and measurement error variance due to telescoping and current status errors and that the timing of breast development and menarche are largely under the control of a common set of genes. Results also indicated that maternal recollections of the onset of breast development were both more poorly defined and subject to greater recall errors than maternal recollections of menarche.

Adolescent↗

Conserved sequences of prokaryotic proteomes and their compositional age.

A full repertoire of octapeptides which are present in at least 30 bacterial proteomes of total 131 currently available is computationally derived and filtered. An original search technique is used that, in terms of computational time and memory, is similar to the Suffix tree method. The presence of a given sequence in a large number of proteomes qualifies it as a conserved sequence. The larger the number of proteomes where it is found, the higher is the conservation. The concept of compositional age of the amino acid sequences ("compositional clock") is introduced for the first time. The compositional age is calculated on the basis of the consensus temporal order of appearance of amino acids in early evolution. The correlation between the compositional age and the sequence conservation is established.

Amino Acid Sequence↗

A comparison of chronologic age and gynecologic age as indices of biologic maturity.

The clinical usefulness of gynecologic age (GA) (the difference between chronologic age [CA] and menarcheal age [MA]) is controversial. We compared CA and GA with bone age (BA) (the standard reference criterion for biologic maturity), in 107 Caucasian girls who ranged in age from 8.3 to 18.5 years. Chronologic age and GA each correlated significantly with BA. Regression analysis revealed no significant difference between the BAs of early-maturing girls and late-maturing girls of the same CA. However, the BAs of late-maturing girls were significantly greater than those of early-maturing girls of the same GA. Chronologic age may be preferable to GA in studies of adolescents that require an assessment of biologic maturity because CA is a more accurate measure of BA than is GA.

Adolescent↗

Age-related changes of the dental pulp complex and their relationship to systemic aging.

The dental pulp and its associated structures, the dentin and the cementum, are discussed. Because many of the age-related pulpal changes have components considered in several of the current theories of aging, these theories are briefly reviewed. Part 2 describes the age-related changes of the dental pulp, the dentin, and the cementum (the dental pulp complex). An attempt is made to differentiate inherent aging changes from physiologic defensive changes and pathologic irritant-induced changes. Part 3 describes the relationship of age-induced changes in the dental pulp complex to components of the current aging theories together with a unified concept of the dental pulp complex aging. Part 4 considers whether dental pulp complex aging can be used as a biomarker for generalized aging. Whether age-related changes of the dental pulp complex can be altered by interventions is discussed.

Aging↗

Progress in cytogerontology.

The finite in vitro lifetime of cultured normal cells is interpreted to be aging at the cellular level. In addition to the inverse relationship between donor age and population doubling potential (PDP), a number of biochemical and physiological increments and decrements occur prior to the cessation of cell division. The reconstruction of replicating normal human cells from the nuclei of "young" cells and the cytoplasm of "old" cells (and the reverse) suggests that the nucleus governs PDP. Several morphological changes were found to occur in late phase III cells held for up to one year in culture. Autoradiography studies show that (1) a cell population may be composed of several subpopulations, each of which is at a different stage in its life history and (2) lipid synthesis is affected much less as cells age than is DNA, RNA and protein synthesis. Changes occurring in the genetic program of individual cells seem to be the most tenable hypothesis to explain fundamental causes of aging.

Aging↗

Core body temperature in narcoleptic and normal subjects living in temporal isolation.

The aim was to detect abnormalities in the circadian temperature rhythms of narcoleptic patients, as evidence of abnormal circadian pacemaker function. Six narcoleptic patients and nine normal controls lived in a time-isolation laboratory for 18-22 days. Rectal temperature was measured every minute and modeled by mean waveforms and cosine functions, which have complementary advantages. In this study, the two types of models gave similar results: The levels, periods, amplitudes, and phases of the circadian temperature rhythms of patients and controls did not significantly differ--evidence against an abnormality of circadian pacemaker function in narcolepsy. The increases of temperature that normally follow main sleep periods were smaller in narcoleptic subjects, and narcoleptic naps, which were involuntary, were heralded and accompanied by small decreases of mean temperature.

Aged↗

Medication timing for the elderly: the impact of biorhythms on effectiveness.

The concept of chronopharmacology has significant implications for drug delivery systems. Age and illness put the elderly at greater risk for adverse drug effects, and nurses caring for the elderly have a challenging opportunity to measurably improve the quality of their care by applying chronotherapeutic concepts. Pharmacologic chronotherapy is a developing science that holds much hope for increasing the effectiveness of drug therapy and for reducing the incidence of toxic drug reactions. Nurses who are aware of the principles on which chronotherapy is based are in a unique position to improve the effectiveness of pharmacotherapy for all clients. However, appropriate timing of medications is especially important among elderly clients whose physiological processes are altered or changed by age and chronic illness. In this article, the basis of chronotherapy is discussed, and several therapeutic applications are identified.

Aged↗

Modulation of symptomatic palatal tremor by magnetic stimulation of the motor cortex.

OBJECTIVES: Magnetic stimulation of the motor cortex can be used to determine the involvement of the cortex in rhythmic movement disorders. Symptomatic palatal tremor (SPT) is thought to come from a pacemaker that is relatively resistant to internal and external stimulation. In this study, we investigated the effect of magnetic stimulation of motor cortex on SPT. METHODS: Five male patients, aged 67-79 years, with SPT after brain stem infarction or hemorrhage, all had a synchronous mouth angle twitch with the palatal movement. Electromyographic activity was recorded with a monopolar needle electrode from orbicularis oris. In experiment 1, transcranial magnetic stimulation (TMS) was delivered at 200% motor threshold (MT) to reset SPT. In experiment 2, the effect of TMS intensities was studied at 80-240% MT in two SPT patients. To determine the influence of the TMS, we used the resetting index (RI). RESULTS: TMS reset the tremor in all 5 SPT patients at 200% MT with RIs of 0.86-0.96. The latency of the tremor reappearance after TMS was longer than the pre-stimulus tremor interval, and the intervals between the subsequent tremor bursts were also prolonged. The degree of tremor resetting was closely correlated with the magnetic stimulus intensity and the latency of the tremor reappearance after TMS. CONCLUSIONS: Stimulation of the motor cortex may modulate the generator of SPT.

Aged↗