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Longitudinal analysis of the developmental process in chronically ill and healthy persons--empirical findings from the Bonn Longitudinal Study of Aging (BOLSA).

Chronically ill and healthy persons are compared as to social roles, dominant concerns, and in coping with stress. The comparison is based on a longitudinal analysis of data which was collected in the Bonn Longitudinal Study of Aging (BOLSA). The empirical analysis indicates that both groups show great success in mastering life situations and in coping with challenges and restrictions. This competence persists over the eight measurement points. The empirical analysis also makes clear that chronically ill patients often cope actively with stress, that they are able to accept restrictions and to look simultaneously for new possibilities in life. Social contacts have a predominant position in coping with chronic disease. Intrafamilial and extrafamilial contacts are important and helpful for chronically ill patients. As the longitudinal analysis reveals, coping with challenges and demands of life is influenced by the individual life-style. The analysis points to the aging process as a process of growth and of new potentials. This applies not only to persons who are in good health, but to chronically ill persons as well.

Activities of Daily Living

The Longitudinal Interval Follow-up Evaluation. A comprehensive method for assessing outcome in prospective longitudinal studies.

The Longitudinal Interval Follow-up Evaluation (LIFE) is an integrated system for assessing the longitudinal course of psychiatric disorders. It consists of a semistructured interview, an Instruction booklet, a coding sheet, and a set of training materials. An interviewer uses the LIFE to collect detailed psychosocial, psychopathologic, and treatment information for a six-month follow-up interval. The weekly psychopathology measures ("psychiatric status ratings") are ordinal symptom-based scales with categories defined to match the levels of symptoms used in the Research Diagnostic Criteria. The ratings provide a separate, concurrent record of the course of each disorder initially diagnosed in patients or developing during the follow-up. Any DSM-III or Research Diagnostic Criteria disorder can be rated with the LIFE, and any length or number of follow-up intervals can be accommodated. The psychosocial and treatment information is recorded so that these data can be linked temporally to the psychiatric status ratings.

Data Collection

Some comparative aspects of a longitudinal growth study in normal Spanish children and other longitudinal studies.

The differences existing among some european longitudinal growth studies make it necessary to be cautious in the use of standards constructed on different populations. The improvement of the environmental conditions during the last 20 years is probably the most important cause of the "catch-up" phenomenon of the spanish stature. It is probable that racial characteristics also play a role, even in the same country as can be appreciated on comparing two spanish longitudinal studies based on children originally from different regions. All of which indicates the need to use own standards in those countries which, like ours, have lived through a period of intense changes. Even exploratory studies of regional differences in the same country seem necessary.

Age Determination by Skeleton

[Estimation of ventricular volume derived from three transverse diameters and the longitudinal axis, compared with an area-longitudinal axis method (author's transl)].

The difficulty of automatic volume estimations of the left ventricle from cine-ventriculography lies in the accurate definition of the ventricular contour during the whole of the cardiac cycle. On the other hand, automatic determination of the long axis of the ventricle, and of three transverse diameters, is feasible. An attempt was therefore made to see whether accurate ventricular volume estimations could be obtained from these measurements. Two different geometrical models were examined: a) A complete rotational ellipsoid b) A half rotational ellipsoid. Examination of ten cine-ventriculograms (totalling 546 frames) has shown that the ventricular volume can be determined with an adequate accuracy by this method. The half ellipsoid model produced better mean results than the full ellipsoid. Its mean deviation from the area-long axis method was only minus 1.2%, that of the complete ellipsoid was minus 3.3%.

Heart Function Tests

Longitudinal characterization of impulsivity phenotypes boosts signal for genomic correlates and heritability.

Genomic correlates of impulsivity have been identified in several genome-wide association studies (GWAS) using cross-sectional designs, but no studies have investigated the molecular genetic correlates of impulsivity phenotypes using longitudinally constructed traits. In 3860 unrelated European participants in the Avon Longitudinal Study of Parents and Children (ALSPAC), we constructed longitudinal phenotypes for delay discounting and impulsive personality traits (as measured by the UPPS-P impulsive behavior scales) via assessment at ages 24, 26, and 28. We conducted GWASs of impulsivity using both cross-sectional and longitudinal phenotypes, estimated heritability and their phenotypic and genetic correlations, and evaluated their association with recently-developed polygenic risk scores (PRSs) for the impulsivity indicators themselves and also related psychiatric conditions. Latent growth curve modeling revealed a stable intercept over time for all impulsivity phenotypes. High genetic correlation of cross-sectional measures over time suggested a stable genetic component for delay discounting (rg = 0.53-0.99) and sensation seeking (rg = 0.99). Heritability estimates of the stable longitudinal phenotypes substantively improved as compared to their cross-sectional counterparts, revealing a significant SNP-heritability for delay discounting (0.22; p = 0.03) and sensation seeking (0.35; p = 0.0007). Consistent with previous reports, GWAS and gene-based analyses revealed associations between specific longitudinal impulsivity indicators and CADM2 and NCAM1 genes. The PRSs for the impulsivity indicators and disorders related to self-regulation were also significantly associated with longitudinal impulsivity traits. Finally, we validated the associations between longitudinal impulsivity phenotypes and their PRSs in an independent 13-wave longitudinal study (n = 1019) and the benefit of longitudinal phenotypes in simulation studies. In this first longitudinal genetic study of impulsivity traits, the results revealed stable genomic correlates of delay discounting and sensation seeking over time and further validated the utility of recently-developed PRSs, both in relation to the observed traits and in connecting them to psychiatric disorders. More generally, these findings support using latent intercepts as novel longitudinal phenotypes to boost signal for heritability and genomic correlates of mechanisms contributing to psychiatric disease liability.

Humans

Effects of teat cistern mural biopsy and teatoscopy stab versus longitudinal incision with or without tube implant on incisional healing in lactating dairy cattle.

Effects of teat cistern mural biopsy and full-thickness stab and longitudinal incisional healing were evaluated experimentally on clinically normal teats in 12 lactating dairy cattle. Each teat on each cow was assigned by Latin-square design to 1 of 4 surgical interventions: (I) teatoscopy only; (II) teatoscopy, stab incision, and mural biopsy; (III) longitudinal incision and mural biopsy; and (IV) longitudinal incision, mural biopsy, and tube implantation. Teatoscopy was done with a 4-mm OD arthroscope introduced through the teat canal and attached to a television camera. Teatoscopy was quicker to perform and provided a more detailed videotaped examination of the teat and gland cistern, compared with gross inspection through a longitudinal incision. In intervention-II cows, the Ferris-Smith biopsy instrument jaws introduced through a longitudinal 1-cm midteat stab incision were easy to visualize and manipulate accurately. Stab incisions closed with only 1 or 2 skin sutures healed without complications in all 12 teats. On palpation, stab incisions were significantly (P less than 0.01) less thick than longitudinal incisions at 8 weeks and were microscopically indistinguishable from the normal tissue. However, in 24 teatoscopically examined teats, 9 (38%) had microscopic evidence of teat canal injury and 12 (50%) of the quarters developed mastitis. This was attributed to trauma resulting from introduction of the arthroscope through the teat canal. Intervention III yielded satisfactory results with the least complications. All 12 longitudinal incisions healed by primary intention, and all teats remained patent. Mastitis developed in 4 (33%) quarters. Intervention IV caused considerable complications associated with the tube implant and no improvement in biopsy site healing, compared with interventions II and III. Eleven longitudinal incisions healed by primary intention. One incision dehisced, 2 (17%) tube implants dislodged, 2 (17%) became obstructed proximally, and irritations of the mucous membrane developed in 2 teats proximally and in 6 teats distally. Mastitis developed in 6 (50%) quarters. Longitudinal incisions healed with moderate submucosal fibrosis. All sutured incisions had multifocal microgranulomata in which suture material was in various stages of degradation. At 8 weeks, localized teat wall thickening could be detected at incisional and biopsy sites, but did not obstruct milk flow. Excessive granulation tissue was at the biopsy sites (72 total) at 2 weeks, and at this time, the sites were partially covered by metaplastic squamous epithelium. However, by 8 weeks, 71 (98%) of the areas were replaced by fibrous tissue with minimal protrusion into the teat cistern.

Animals

Pilot study identifying distinct circulating proteomic profiles associated with longitudinal CT-defined fibrotic and inflammatory sarcoidosis.

INTRODUCTION: Pulmonary sarcoidosis exhibits heterogeneous clinical trajectories ranging from self-limited disease resolution to chronic progressive fibrosis, yet reliable biomarkers capable of distinguishing these disease patterns remain lacking. Whether longitudinal CT-defined sarcoidosis phenotypes are associated with distinct circulating molecular signatures remains unknown. METHODS: We performed high-throughput plasma proteomics (SomaScan 11K) in participants with pulmonary sarcoidosis classified into longitudinal chest CT-defined progressive fibrosis, progressive nodular inflammatory disease, or resolving disease trajectories, along with healthy controls. CT phenotypes were assigned based on predefined longitudinal changes in reticulation, traction bronchiectasis, nodular involvement, and mediastinal lymphadenopathy across serial CT scans. One plasma sample per participant was selected from the study visit corresponding to the CT time point at which criteria for the assigned longitudinal phenotype were met. Principal component analysis, hierarchical clustering, pathway enrichment, and correlation-based analyses linking protein expression to quantitative CT features were used to evaluate whether distinct longitudinal CT phenotypes were associated with divergent proteomic signatures. RESULTS: Principal component analysis and hierarchical clustering suggested partial segregation by CT-defined phenotype. Longitudinal CT phenotypes were associated with distinct pathway-level proteomic signatures, with progressive fibrosis enriched for epithelial-mesenchymal transition signaling, and progressive nodular inflammatory disease enriched for mTORC1, MYC, oxidative phosphorylation, adipogenesis, and fatty acid metabolism pathways. Correlation analyses showed coordinated protein-expression patterns associated with fibrotic CT features and mediastinal lymph node enlargement. DISCUSSION: These findings suggest that longitudinal CT-defined fibrotic and inflammatory sarcoidosis phenotypes are associated with distinct pathway-level proteomic signatures. This pilot study provides preliminary proof-of-concept evidence that integrating longitudinal CT imaging phenotypes with plasma proteomics may serve as a framework for future mechanistic studies and biomarker discovery in pulmonary sarcoidosis.

Humans

Effects of leu-enkephalin on the mechanical activity of longitudinal and circular muscles of the small intestine of the cat.

The effects of leu-enkephalin on the spontaneous and electrically-evoked activity were studied in the longitudinal and circular strips isolated from the duodenum, jejunum and ileum of the cat. Leu-enkephalin affected the spontaneous activity of both longitudinal and circular strips, with the exception of the circular strips from the ileum, in a naloxone-dependent manner. Elimination of the neural input to the smooth muscle cells with tetrodotoxin blocked the effects of leu-enkephalin in the longitudinal and circular strips from the jejunum and in the longitudinal strips from the ileum. In the longitudinal strips from the duodenum the effect was resistant to tetrodotoxin, while in the circular strips a tetrodotoxin-sensitive component of the effect of leu-enkephalin was observed. Since leu-enkephalin evoked opposite effects in the longitudinal and circular layers of one and the same region, it is concluded that leu-enkephalin-induced modulation of the motility of the small intestine in the cat is a physiological phenomenon. Electrical stimulation, at a frequency of 5 Hz, evoked contractile responses in the longitudinal strips and relaxant, as well as low-amplitude, contractile responses in the circular strips. Rebound contractions developed after the end of stimulation in all preparations tested, with the exception of the longitudinal strips from the duodenum. Leu-enkephalin decreased the contractile components and tended to potentiate the relaxant components of the responses in a naloxone-dependent manner. Atropine inhibited the contractile components of the responses and significantly depressed the rebound contractions. Leu-enkephalin, applied after atropine, was ineffective suggesting that leu-enkephalin-induced modulation was mediated mainly through interaction with cholinergic transmission.

Animals

Noncomparability of cross-sectional and longitudinal estimates of lung growth in children.

Results from longitudinal and cross-sectional studies of pulmonary function are often compared. However, previous studies in adults suggest that results from longitudinal and cross-sectional studies are different and may not be comparable. In order to evaluate these differences further, prospectively collected data in a group of children were analyzed by both longitudinal and cross-sectional methods. Spirometry was performed longitudinally over a period of 8 years on 58 healthy children. Straight-line regressions of expiratory flow-volume parameters on height were computed by averaging the individual regression lines for each child. A cross-sectional sample from these same children was analyzed and compared to the longitudinal analysis. For all expiratory flow-volume parameters, the cross-sectional analysis resulted in a significantly greater increase in growth with increasing height than the longitudinal analysis (P less than 0.005 for slope for all parameters except PEFR, P less than 0.05 and Vmax75, P less than 0.01). These differences cannot be explained by learning or horse-racing effects, loss to follow-up, or regression to the mean; however, they could be explained by cohort changes, time trends of pulmonary function, differences in the weighted averages used in the two analyses, or incorrect modeling. These observations indicate that comparisons between cross-sectional and longitudinal investigations must be made cautiously. These data do not support many of the reasons suggested for the differences in previous reports. It is recommended that studies of pulmonary function use a control group and investigate the groups at the same time and in the same manner.

Body Height

Identification of motor neurons that contain a FMRFamidelike peptide and the effects of FMRFamide on longitudinal muscle in the medicinal leech, Hirudo medicinalis.

Excitatory motor neurons in the leech are cholinergic. By using a combination of intracellular Lucifer yellow injection and indirect immunofluorescence, we localized FMRFamidelike immunoreactivity to a number of the motor neurons innervating longitudinal and dorsoventral muscle in the leech. All excitatory motor neurons innervating longitudinal muscle (cells 3, 4, 5, 6, 8, L, 106, 107, 108) were labeled with an antiserum to FMRFamide, while the inhibitory motor neurons innervating longitudinal muscle (cells, 1, 2, 7, 9, 102) were not. The excitatory motor neuron innervating medial dorsoventral muscle (cell 117) was labeled, while the excitatory motor neuron innervating lateral dorsoventral muscle (cell 109) was not. The inhibitory motor neuron innervating dorsoventral muscle (cell 101) was also labeled. Nerve terminals along dorsoventral muscle were also labeled with the antiserum. FMRFamide was bath applied to strips of longitudinal muscle while recording tension, and the muscle's response was compared to its response to the previously identified neuromuscular transmitter ACh. Brief applications of FMRFamide caused a contraction approximately one-tenth as large as that caused by an equimolar amount of ACh. The muscle response to FMRFamide was unaffected by curare. During extended exposures, FMRFamide caused a maintained contraction in longitudinal muscle without any apparent desensitization of the FMRFamide receptors and occasionally triggered an irregular myogenic rhythm. This extended exposure to FMRFamide caused a post-exposure potentiation of the longitudinal muscle's response to ACh that shorter applications of FMRFamide did not. Thus FMRFamide may act as a transmitter or modulator in cholinergic motor neurons innervating longitudinal and dorsoventral muscles in the leech.

Acetylcholine

The glial framework of central white matter tracts: segmented rows of contiguous interfascicular oligodendrocytes and solitary astrocytes give rise to a continuous meshwork of transverse and longitudinal processes in the adult rat fimbria.

The cellular skeleton of the adult rat fimbria consists of regularly spaced interfascicular glial rows of considerable length, running in the longitudinal (axonal) axis of the tract. Each row consists of a series of repeated segments made up of a stretch of interfascicular oligodendrocytes lying in direct contact with each other, and separated from the adjacent segments by usually solitary interfascicular astrocytes. A typical segment would be around 60 microns long, and have an axial core of about eight contiguous oligodendrocytes surrounded by a shell of about 1,200 axons, 70% of which are myelinated. In the transverse plane of the tract, adjacent segments are stacked together with a core-to-core distance of around 15 microns. The interfascicular oligodendrocytes have radial stem processes (in a plane transverse to the axonal axis) which give rise to the longitudinal myelinating (internodal) processes. Both transverse and longitudinal oligodendrocytic processes are longer than the dimensions of the segment (in which their cell bodies lie) and its axonal shell. They thus cooperate in myelinating axons of adjacent segments in both planes. The interfascicular astrocytes have three distinct types of processes: radial, longitudinal, and vascular (bearing end feet). The radial astrocytic processes are thick and tapering, and the processes of individual astrocytes extend transversely (in the plane of the original embryonic radial glial processes) for a total of at least 100 microns. The considerably more numerous longitudinal astrocytic processes arise from all parts of the cell bodies and radial processes. They are up to at least 30 microns long, thin, untapering, and largely unbranched, and are interdigitated among the fimbrial axons. In the radial plane, the astrocytic radial processes spread out through a wide swathe of adjacent segments, so that the integrated meshwork of interpenetrating longitudinal processes arising from overlapping radial processes of astrocytes from many different interfascicular rows provides a continuous longitudinal substrate for the fimbrial axons.

Animals

Interaction between longitudinal and circular muscle in intestine of cat.

1. Slow waves recorded from isolated longitudinal muscle averaged 13 mV and had slow rate of rise (0.04 V/sec) whereas when recorded from intact segments the amplitude averaged 27 mV and the rate of rise was more rapid (0.09 V/sec), often with a notch between the initial peak and the plateau. Membrane potentials of longitudinal muscle were similar in isolated and intact preparations (- 66 mV). Resting potentials of circular muscle averaged - 67 mV.2. Small bundles of circular muscle tested in the double sucrose gap produced activity, either spontaneously or in response to stimulation, which fell into three categories: fast spikes (50-200 msec duration), slow spikes (1-5 sec duration), and small graded responses. The duration of fast spikes could be increased severalfold by the addition of TEA; the graded responses were converted to full-sized spikes by TEA.3. Treatment of circular muscle with Ca-free Krebs solution eliminated spikes, and in intact preparations reduced the amplitude and rate of rise of slow waves and eliminated the notch on slow waves.4. Current-voltage curves of longitudinal muscle show delayed rectification in the depolarizing quadrant; similar curves of circular muscle show anomalous rectification, i.e. a region where a very small current causes a large voltage change.5. Non-polarized electrotonic coupling between longitudinal and circular layers indicates low-resistance pathways. Apparent space constants of longitudinal muscle are greater when attached to circular muscle than when isolated.6. It is concluded that small slow potentials originate rhythmically in longitudinal muscle, that these spread passively to circular muscle where a regenerative amplification occurs which depends on Ca conductance and the amplified slow waves spread back to the longitudinal layer. In the intact intestine pacemaking is, therefore, separate from propagation and the circular muscle provides the bulk of depolarizing current for propagation.

Action Potentials

Outward currents in longitudinal colonic muscle cells contribute to spiking electrical behavior.

Electrical events in longitudinal and circular muscles of the colon are different. Longitudinal muscles generate action potentials superimposed upon small depolarizations termed myenteric potential oscillations and circular muscles generate slow wave events that persist for several seconds. Differences between circular and longitudinal muscles may be related to the potassium channels these cells express. We have studied Ca(2+)-dependent and voltage-dependent K currents of isolated longitudinal cells with the whole cell patch-clamp technique. Test depolarizations positive to -40 mV yielded a transient inward current followed by a large sustained outward current. Blockade of the inward Ca2+ current reduced the amplitude of the outward current. Outward current was also reduced by tetraethylammonium (TEA; 1 mM), suggesting that a component of the outward current is Ca2+ dependent. After blockade of the Ca(2+)-dependent outward current, a voltage- and time-dependent component of outward current remained. The activation and inactivation properties and sensitivity to TEA and 4-aminopyridine (4-AP) were characterized. The voltage-dependent outward current in longitudinal cells had different properties than the voltage-dependent K currents in circular muscle cells (i.e., more negative inactivation, less sensitivity to 4-AP). TEA (1-5 mM) increased the amplitude and frequency of action potentials in intact longitudinal muscles; 4-AP (1 mM) had little effect on electrical activity of longitudinal muscles. The data suggest that differences in electrical behavior of the 2 muscle layers may be related to the expression of different species of K channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

Differential effects of [Gln4]neurotensin on circular and longitudinal muscle of dog ileum in vitro.

We studied the effects of neurotensin analogue [Gln4]-neurotensin on isolated dog ileal longitudinal and circular muscle strips. [Gln4]neurotensin stimulated the spontaneous contractile activity of the circular muscle but inhibited that of the longitudinal muscle in a dose-dependent fashion. Hexamethonium had no effect on the spontaneous longitudinal or circular muscle contractile activity. Atropine and tetrodotoxin (TTX) both inhibited the longitudinal muscle. Atropine had no effect on the circular muscle, but TTX stimulated it. The effects of [Gln4]neurotensin on the circular muscle were reduced but not completely abolished by atropine. The inhibition of the longitudinal muscle by [Gln4]neurotensin was not reduced by any of the above antagonists but was enhanced by atropine. Electrical field stimulation (10 Hz, 100 mA) stimulated the longitudinal muscle and inhibited or stimulated the circular muscle depending on the pulse width of the stimulus. These effects were unaffected by [Gln4]neurotensin. We conclude that [Gln4]neurotensin has differential effects on isolated muscle strips of the two muscle layers in the dog ileum. It stimulates the circular muscle partially through cholinergic nerves at preganglionic sites and partially through a direct myogenic effect. [Gln4]neurotensin inhibits the spontaneous activity of the longitudinal muscle presumably by reducing the excitability of cholinergic nerves at postganglionic sites.

Animals