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Longitudinal designs, methods and analysis in psychiatric research.

OBJECTIVE: To outline the strengths and limitations of longitudinal research designs in psychiatry, and to describe different types of longitudinal designs and methods for analyzing longitudinal data. METHOD: Key references on longitudinal methods were reviewed and examples drawn from literature in psychiatry and psychology. RESULTS: Longitudinal studies provide important information regarding the incidence and developmental trajectories of mental disorders. They allow for identification of risk factors and developmental concomitants. Recent developments in statistical methods for analyzing longitudinal data provide efficient estimates of change and predictors of change over time, identification and characteristics of distinct subgroups defined by change pattern, and improved methods for obtaining unbiased population estimates when data are incomplete. CONCLUSION: Longitudinal designs, methods and analysis can contribute to psychiatric studies on risk factors for common mental disorders, studies of early intervention and prevention and treatment outcomes.

Humans↗

Elastin in the human posterior longitudinal ligament and spinal dura. A histologic and biochemical study.

STUDY DESIGN: A histologic and biochemical study of elastin in the posterior longitudinal ligament and spinal dura was performed using autopsy cadavers. OBJECTIVE: To provide a rationale for resiliency of the PLL and the spinal dura. SUMMARY OF BACKGROUND DATA: Among the spinal ligaments, the nuchal ligament and the ligamentum flavum have a very high elastin content, and some biochemical and morphologic studies of these ligaments have been published. No reports on the elastin content in the posterior longitudinal ligament or spinal dura have been published. METHODS: Specimens of the posterior longitudinal ligament and the dura collected from three cadavers were studied histologically. For quantitative analysis of elastin and collagen, the posterior longitudinal ligament specimens were collected from 22 cadavers and the dura specimens from 20 cadavers. Elastin was extracted using the hot alkali method of Lansing et al. RESULTS: The elastic fibers in the posterior longitudinal ligament generally were arranged parallel in the cephalocaudal direction, whereas the fibers in the spinal dura had a more multidirectional arrangement. The elastin content of the posterior longitudinal ligament averaged 7.3% of the total dry weight and that of the spinal dura was 7.1% for the ventral aspect and 13.8% for the dorsal aspect. The elastin content of the spinal dura was about two times higher in all dorsal specimens than in the corresponding ventral specimens. The elastin content of the lower thoracic region was higher than that of any other region. The amino acid composition of the elastin in the posterior longitudinal ligament and spinal dura was similar to that previously determined in other spinal ligaments.

Aged↗

Long-term follow-up evaluation of surgery for ossification of the posterior longitudinal ligament.

STUDY DESIGN: We compared anterior and posterior surgery for cervical myelopathy resulting from ossification of the posterior longitudinal ligament. Surgical techniques, based on shape and distribution of ossification of the posterior longitudinal ligament, were divided into four technical phases. OBJECTIVES: Long-term follow-up data on anterior and posterior surgery were analyzed to establish guidelines for surgical treatment. SUMMARY OF BACKGROUND DATA: Comparison of anterior and posterior surgery is difficult because surgical techniques, ossification of the posterior longitudinal ligament shape classifications, and surgical criteria varied. No reports have accurately assessed spinal changes over a 10-year follow-up period. METHODS: Fifty patients received anterior surgery and 65 received posterior surgery between 1968 and 1993. Assessment after surgery was based on the recovery rate using the scoring system of the Japanese Orthopaedic Association. Spinal changes in the anterior group were assessed radiographically. RESULTS: Recovery and final results improved with phase after anterior, but not posterior, surgery. Neurologic deterioration after initial recovery was lower for the anterior group. One third of patients in the anterior group followed for more than 7 years exhibited neurologic deterioration, with most showing these changes within 10 years. Worsening was attributed to insufficient removal of lateral, superior, or inferior ossification of the posterior longitudinal ligament, reossification at the excision site, kyphotic malalignment, growth of ossification at upper cervical levels, or untreated complicated hypertrophy of the posterior longitudinal ligament. Many patients showed a good outcome after surgery. Accurate alignment and long-range fusion improved results. If the cord was compressed in a canal narrowed to under 3 mm, anterior surgery was considered "too risky." CONCLUSIONS: Complete extirpation of ossification of the posterior longitudinal ligament as confirmed by ultrasonography during surgery and long-range fusion with fibular grafts is advocated in the management of ossification of the posterior longitudinal ligament.

Follow-Up Studies↗

Mechanosensitive afferent units in the lumbar posterior longitudinal ligament.

STUDY DESIGN: The mechanosensitive afferent units in the lumbar posterior longitudinal ligament were investigated in an animal model using an electrophysiologic technique. OBJECTIVES: The objectives of this study were to identify the mechanosensitive receptive fields in the lumbar posterior longitudinal ligament and to investigate their distribution and characteristics. SUMMARY OF BACKGROUND DATA: The lumbar posterior longitudinal ligament has a nerve network originating from the sinuvertebral nerve. These fibers are thin, and most of their terminals are free nerve endings. Some immunohistochemical studies have indicated that they are immunoreactive to calcitonin gene-related peptide and/or substance P, suggesting a nociceptive function. Most of these studies investigated morphologic aspects, and there have been few studies employing electrophysiologic techniques to examine mechanosensitive units. METHODS: We used 13 adult cats. They were anesthetized and then laminectomy was performed. The L5 and L6 dorsal rootlets were draped over a recording electrode. To investigate the receptive fields in the posterior longitudinal ligament, afferent impulses were evoked by mechanical stimulation with a glass probe. When the receptive fields were located, they were stimulated electrically to obtain conduction velocity and were stimulated with a set of 17 nylon filaments to determine their mechanical thresholds. RESULTS: Thirteen units were identified in the lumbar posterior longitudinal ligament. The majority of the units were located around the intervertebral disc level of the posterior longitudinal ligament. The mean mechanical threshold was 47.04 +/- 15.25 g. According to the conduction velocities of the units, 12 units were classified into Group III (0.5-2.5 m/sec) and one unit into Group IV (2.5-20 m/sec). CONCLUSION: Mechanosensitive units classified into Group III or Group IV and with a high mechanical threshold (>7.0 g) were thought to act as nociceptive units. All units identified in this study satisfied these criteria. Our result suggests that afferent fibers from the lumbar posterior longitudinal ligament have a principally nociceptive function.

Afferent Pathways↗

Anterior decompression for myelopathy resulting from thoracic ossification of the posterior longitudinal ligament.

STUDY DESIGN: A retrospective study was conducted to investigate the anterior decompression and fusion of 12 patients with thoracic ossification of the posterior longitudinal ligament. OBJECTIVE: To evaluate the effect of myelopathy management in which the thoracic ossification of the posterior longitudinal ligament is removed. SUMMARY AND BACKGROUND DATA: Very few reports have described operative treatments for thoracic ossification of the posterior longitudinal ligament. The condition is extremely rare, even in Japan. Consequently, operative procedures for myelopathy resulting this disorder have not been established. METHODS: This study involved 12 patients with thoracic ossification of the posterior longitudinal ligament. All the patients underwent direct removal of the ossification and spinal fusion using an anterior approach. A scapula-releasing technique was used in five patients who had major ossification of the posterior longitudinal ligament at Th4. The follow-up period ranged from 2.5 to 10 years (mean, 6.5 years). The clinical effect of the decompression was evaluated with a Japanese Orthopedic Association score for cervical myelopathy. The efficacy of the decompression was determined by postoperative computed tomography scan. RESULTS: Complete removal of the ossification was achieved in eight patients. In four patients, however, residual ossification was noted. The Japanese Orthopedic Association score before the operation ranged from 4 to 7 points (mean, 5.3 +/- 0.4 points). It showed a change 3 months after the operation, ranging from 1 to 8 points (mean, 6.9 +/- 0.5 points). At 1 year after the operation, it had changed to a range of 1 to 10 points (mean, 7.2 +/- 0.6 points). At the final consultation, it had changed further to a range of 1 to 10 points (mean, 6.9 +/- 0.5 points). Patients whose ossification was not completely removed showed severe or minor postoperative deterioration. CONCLUSIONS: Total removal of the ossification might be required to manage severe myelopathy in patients with thoracic ossification of the posterior longitudinal ligament. Complete removal of the ossification gave good results in eight patients. Patients whose ossification of the posterior longitudinal ligament had not been completely removed, however, had a poor outcome.

Adult↗

Significance of bone formation markers in patients with ossification of the posterior longitudinal ligament of the spine.

STUDY DESIGN: Serum concentrations of bone formation markers were correlated with the type, location, and progression of ossification of the posterior longitudinal ligament. OBJECTIVE: To determine the relation between bone formation markers and ossification of the posterior longitudinal ligament. SUMMARY OF BACKGROUND DATA: Few reports have correlated bone formation markers with ossification of the posterior longitudinal ligament. METHODS: In this study, 43 patients with cervical ossification of the posterior longitudinal ligament and myelopathy underwent laminoplasty. The patients were observed for more than 10 years, after which plain radiographs and tomograms of the cervical region were taken. The radiographs were selectively performed to address thoracic and lumbar ossification of the posterior longitudinal ligament. Serum concentrations of bone formation markers (intact osteocalcin, osteocalcin, carboxyterminal propeptide of human type 1 procollagen, and bone-specific alkaline phosphatase) were measured and correlated with these radiographic studies. RESULTS: A positive correlation was observed between intact osteocalcin, osteocalcin, and carboxyterminal propeptide of human type 1 procollagen in patients with combinations of cervical, thoracic, or lumbar ossification of the posterior longitudinal ligament. CONCLUSIONS: Serum concentrations of intact osteocalcin, osteocalcin, and carboxyterminal propeptide of human type 1 procollagen may reflect the activity of general ectopic bone formation in patients with ossification of the posterior longitudinal ligament.

Aged↗

A flexible B-spline model for multiple longitudinal biomarkers and survival.

Often when jointly modeling longitudinal and survival data, we are interested in a multivariate longitudinal measure that may not fit well by linear models. To overcome this problem, we propose a joint longitudinal and survival model that has a nonparametric model for the longitudinal markers. We use cubic B-splines to specify the longitudinal model and a proportional hazards model to link the longitudinal measures to the hazard. To fit the model, we use a Markov chain Monte Carlo algorithm. We select the number of knots for the cubic B-spline model using the Conditional Predictive Ordinate (CPO) and the Deviance Information Criterion (DIC). The method and model selection approach are validated in a simulation. We apply this method to examine the link between viral load, CD4 count, and time to event in data from an AIDS clinical trial. The cubic B-spline model provides a good fit to the longitudinal data that could not be obtained with simple parametric models.

Acquired Immunodeficiency Syndrome↗

Gender differences in a longitudinal study of age-associated hearing loss.

Current studies are inconclusive regarding specific patterns of gender differences in age-associated hearing loss. This paper presents results from the largest and longest longitudinal study reported to date of changes in pure-tone hearing thresholds in men and women screened for otological disorders and noise-induced hearing loss. Since 1965, the Baltimore Longitudinal Study of Aging has collected hearing thresholds from 500 to 8000 Hz using a pulsed-tone tracking procedure. Mixed-effects regression models were used to estimate longitudinal patterns of change in hearing thresholds in 681 men and 416 women with no evidence of otological disease, unilateral hearing loss, or noise-induced hearing loss. The results show (1) hearing sensitivity declines more than twice as fast in men as in women at most ages and frequencies, (2) longitudinal declines in hearing sensitivity are detectable at all frequencies among men by age 30, but the age of onset of decline is later in women at most frequencies and varies by frequency in women, (3) women have more sensitive hearing than men at frequencies above 1000 Hz but men have more sensitive hearing than women at lower frequencies, (4) learning effects bias cross-sectional and short-term longitudinal studies, and (5) hearing levels and longitudinal patterns of change are highly variable, even in this highly selected group. These longitudinal findings document gender differences in hearing levels and show that age-associated hearing loss occurs even in a group with relatively low-noise occupations and with no evidence of noise-induced hearing loss.

Adult↗

Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study.

We used longitudinal data from the Massachusetts Male Aging Study, a large population-based random-sample cohort of men aged 40-70 yr at baseline, to establish normative age trends for serum level of T and related hormones in middle-aged men and to test whether general health status affected the age trends. Of 1,709 men enrolled in 1987-1989, 1,156 were followed up 7-10 yr afterward. By repeated-measures statistical analysis, we estimated simultaneously the cross-sectional age trend of each hormone between subjects within the baseline data, the cross-sectional trend between subjects within the follow-up data, and the longitudinal trend within subjects between baseline and follow-up. Total T declined cross-sectionally at 0.8%/yr of age within the follow-up data, whereas both free and albumin-bound T declined at about 2%/yr, all significantly more steeply than within the baseline data. Sex hormone-binding globulin increased cross-sectionally at 1.6%/yr in the follow-up data, similarly to baseline. The longitudinal decline within subjects between baseline and follow-up was considerably steeper than the cross-sectional trend within measurement times for total T (1.6%/yr) and bioavailable T (2-3%/yr). Dehydroepiandrosterone, dehydroepiandrosterone sulfate, cortisol, and estrone showed significant longitudinal declines, whereas dihydrotestosterone, pituitary gonadotropins, and PRL rose longitudinally. Apparent good health, defined as absence of chronic illness, prescription medication, obesity, or excessive drinking, added 10-15% to the level of several androgens and attenuated the cross-sectional trends in T and LH but did not otherwise affect longitudinal or cross-sectional trends. The paradoxical finding that longitudinal age trends were steeper than cross-sectional trends suggests that incident poor health may accelerate the age-related decline in androgen levels.

Adult↗

Longitudinal and secular trends in physical activity and sedentary behavior during adolescence.

OBJECTIVE: There is little epidemiologic research on longitudinal and secular trends in weight-related health behaviors throughout the stages of adolescence. In particular, few data are available to assess secular trends in various sedentary behaviors. The objective of this research was to investigate longitudinal and secular trends in physical activity and sedentary behavior in a large, diverse cohort of adolescents. METHODS: Project EAT-II is a 5-year longitudinal study (N = 2516) that includes 2 cohorts that allow for the observation of longitudinal changes from early to midadolescence (junior high to high school; n = 806; mean baseline age: 12.8 +/- 0.8 years) and mid- to late adolescence (high school to post-high school; n = 1710; mean baseline age: 15.8 +/- 0.8 years). EAT-II also examined secular trends in health behavior from 1999 to 2004 in midadolescence. The main outcome measures of the mixed-model regression analyses used in this research were self-reported weekly hours of moderate to vigorous physical activity, television/video viewing, and leisure-time computer use. RESULTS: Our findings indicate substantial longitudinal changes in moderate to vigorous physical activity, particularly among girls (decreasing 5.9-4.9 hours/week from early to midadolescence and 5.1-3.5 hours/week from mid- to late adolescence), and leisure-time computer use, particularly among boys (increasing 11.4-15.2 hours/week from early to midadolescence and 10.4-14.2 hours/week from mid- to late adolescence). Secular trends further indicate dramatic increases in midadolescent computer use from 1999 to 2004; girls increased from 8.8 to 11.1 hours/week, and boys increased from 10.4 to 15.2 hours/week. CONCLUSIONS: These adolescents experienced unfavorable shifts in activity patterns, such as longitudinal decreases in moderate to vigorous physical activity, coupled with longitudinal and secular increases in leisure-time computer use. Developing effective health promotion strategies that address a wide array of changing behavioral patterns will be important in promoting long-term health and active lifestyles among adolescents and young adults.

Adolescent↗

Insulin secretory response is positively associated with the extent of ossification of the posterior longitudinal ligament of the spine.

BACKGROUND: Glucose intolerance is frequently found in patients with ossification of the posterior longitudinal ligament of the spine. This study was undertaken to examine the relationship between glucose intolerance and the extent of ossification in patients with ossification of the posterior longitudinal ligament. METHODS: A total of 100 patients with ossification of the posterior longitudinal ligament (the overall study group), including fifty-two inpatients who were scheduled to have an operation (the inpatient group) and forty-eight outpatients who had undergone an operation, were analyzed. Indices of glucose metabolism-fasting plasma glucose and serum insulin levels, hemoglobin A1c level, and insulinogenic index (a ratio of the increment of the serum level of insulin to that of glucose)-as well as age and body-mass index were correlated with the extent of ossification, as determined by the number of vertebral levels affected with ossification of the posterior longitudinal ligament (extent of ossification), in the inpatient group. In addition, a similar analysis was performed in twenty-eight inpatients (the selected inpatient group) whose ages and body-mass indices were within one standard deviation of the mean values of those of the inpatient group. Association of a polymorphism in the gene of insulin receptor substrate-1, an essential substrate in insulin signaling, with the extent of ossification was evaluated with genomic DNA extracted from the overall study group. RESULTS: Multiple-regression analysis revealed direct correlations of age (p = 0.038), body-mass index (p = 0.006), and insulinogenic index (p = 0.0003) with the extent of ossification of the posterior longitudinal ligament in the inpatient group. The fasting plasma glucose level, the hemoglobin A1c level, and the stage of glucose tolerance were not associated with the extent of ossification. In the analysis of the selected inpatient group, only the insulinogenic index was correlated with the extent of ossification (p = 0.002). However, no significant association was seen between the insulin receptor substrate-1 polymorphism and the extent of ossification. CONCLUSIONS: The insulin secretory response was associated with the extent of ossification of the posterior longitudinal ligament. Since insulin receptor substrate-1 is expressed both in the spinal ligament and in the tissues regulating glucose metabolism, we speculate that some other molecules related to insulin signaling that are impaired only in the tissues regulating glucose metabolism may be responsible for the progression of ossification. We also speculate that the upregulation of insulin production due to the impairment of insulin action may stimulate osteoprogenitor cells in the ligament to induce ossification. CLINICAL RELEVANCE: The insulinogenic index may be useful as a serum marker for the prediction of progression of ossification of the posterior longitudinal ligament. This study may serve as a stimulus for evaluation of the use of various drugs that may improve the response to insulin in the tissues regulating glucose metabolism to prevent the progression of ossification.

Adult↗

[Longitudinal studies: concepts and particularities].

In this review the definition of "longitudinal study" is analysed. Most current textbooks on epidemiology do not define a longitudinal study, whereas statistical textbooks do. It is more common to talk about longitudinal data than about longitudinal studies. A longitudinal study implies the existence of repeated measurements (more than two) across follow-up. According to these ideas, a longitudinal study can be considered a subtype of cohort study that, in contrast with life-table cohort studies, allows inference to the subject level, to analyze changes in variables (exposures and outcomes) and transitions among different health states. The characteristics of this design force to paid special attention to quality control during data collection, losses during follow-up, and missing data in some measurements. The statistical analysis should take repeated measures into account, and it is what finally gives the longitudinal character to a study with repeated measurements.

Biomedical Research↗

Pax6 guides a relay of pioneer longitudinal axons in the embryonic mouse forebrain.

We have characterized a system of early neurons that establish the first two major longitudinal tracts in the embryonic mouse forebrain. Axon tracers and antibody labels were used to map the axon projections in the thalamus from embryonic days 9.0-12, revealing several distinct neuron populations that contributed to the first tracts. Each of the early axon populations first grew independently, pioneering a short segment of new tract. However, each axon population soon merged with other axons to form one of only two shared longitudinal tracts, both descending: the tract of the postoptic commissure (TPOC), and, in parallel, the stria medullaris. Thus, the forebrain longitudinal tracts are pioneered by a relay of axons, with distinct axon populations pioneering successive segments of these pathways. The extensive merging of tracts suggests that axon-axon interactions are a major guidance mechanism for longitudinal axons. Several axon populations express tyrosine hydroxylase, identifying the TPOC as a major pathway for forebrain dopaminergic projections. To start a genetic analysis of pioneer axon guidance, we have identified the transcription factor Pax6 as critical for tract formation. In Pax6 mutants, both longitudinal tracts failed to form due to errors by every population of early longitudinal axons. Taken together, these results have identified potentially important interactions between series of pioneer axons and the Pax6 gene as a general regulator of longitudinal tract formation in the forebrain.

Animals↗

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↗

Development of the longitudinal projection patterns of lumbar primary sensory afferents in the chicken embryo.

The literature on the anatomical organization of primary sensory afferents, though extensive, contains relatively little information about the longitudinal extent of the central collateral projections. Our understanding of intersegmental sensorimotor integration in the spinal cord and of the developmental mechanisms that establish its underlying circuitry could be significantly enhanced by a more complete description of these projections. To address this issue from a developmental perspective, we labeled the central projections of lumbar primary afferents in fixed preparations of the chicken embryo with the lipophilic tracer DiI. At late embryonic stages, the afferent projections had the following characteristics: Primary afferents originating from a single lumbar dorsal root ganglion bifurcated to project longitudinally in the dorsal funiculus or Lissauer's tract. Dorsal funiculus axons extended up to seven segments caudally and to at least ten segments rostrally, whereas axons in Lissauer's tract extended up to seven segments in each direction. Collaterals branched off the longitudinal axons over a range of about seven segments in each direction. Within this range, collaterals to specific terminal fields exhibited more restricted ranges. The development of these longitudinal patterns during earlier embryonic stages was followed from the time the afferents first reached the neural tube on day 4 of embryogenesis. The longitudinal axons lengthened as a single bundle up to day 10, with medial axons consistently longer than lateral axons. After day 10, the longitudinal axons were segregated into the dorsal funiculus and Lissauer's tract. Collaterals sprouted after about 2 days of longitudinal axon growth, by which time the axons had extended several segments in each direction. The segmental range over which collaterals were present reached a maximum of 20 segments at day 10. Collaterals to the different terminal areas differed in their segmental ranges already by this time. After day 10, the total segmental range of collaterals decreased to the stable level of about seven segments in each direction, which is characteristic of late-stage embryos.

Afferent Pathways↗

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↗

Cytoskeletal features in longitudinal and circular smooth muscles during development of the rat portal vein.

Immunohistochemistry of alpha-smooth muscle actin and desmin, two markers of smooth muscle cell differentiation, and electron-microscopic observation of thick filaments of myosin were performed on the media of the developing rat hepatic portal vein to gain insights into the chronology of differentiation of its longitudinal and circular smooth muscles. In accordance with the ultrastructural distribution of thin filaments, staining of alpha-smooth muscle actin is lightly positive in the myoblasts at postnatal day 1 and then extends in probably all muscle cells of the developing vessel. Desmin, which appears later than alpha-smooth muscle actin in the two muscles, is distributed throughout the longitudinal layer at day 8, whereas the first arrangements of thick filaments are detectable in most longitudinal muscle cells; at this stage, desmin and thick filaments are absent from the poorly differentiated circular muscle cells. The longitudinal muscle cells differentiate in a strikingly synchronized way from day 8 onwards, conferring a homogeneous structure to the developing and mature longitudinal layer. Several desmin-positive cells and a heterogeneous distribution of thick filaments occur in the circular muscle at day 14; the subsequent extension of these filaments in this layer results in a persisting heterogeneous distribution in the young 7-week-old adult. Many features of the mature smooth muscle cells are established within the third week in the longitudinal muscle, approximately one week before those of the circular layer. These results are consistent with the function of the longitudinal muscle as a spontaneously contractile smooth muscle unit, and emphasize the need for its fast maturation to fulfil its major role in the control of portal blood flow.

Actins↗

Changes in responsiveness of freshly isolated longitudinal muscle cells from rat uterus towards oxytocin during gestation: contractility and calcium signaling.

Changes in responsiveness of freshly isolated longitudinal muscle cells from rat uterus to oxytocin during gestation were investigated through measuring contractility as well as intracellular free calcium concentration. We have demonstrated the pregnant stage-dependent contraction of freshly isolated myometrial cells in response to an extracellular hormone, oxytocin, in Ca2+-containing medium. The oxytocin effect appeared to be through oxytocin receptor since the effect could be blocked by a specific oxytocin antagonist. The magnitude of the contraction of the isolated cells in response to extracellular oxytocin was in the order of 21 day >> 18 day > 15 day pregnant rat longitudinal muscle cells. In a concentration dependent manner, oxytocin elicited a rapid increase in [Ca2+]i of longitudinal muscle cells isolated from different stages of the pregnant rat uterus, especially at the term of pregnancy. The time (4-5 s) required to reach a maximum increase in [Ca2+]i of the isolated longitudinal muscle cells in response to oxytocin was the shortest among all previously reported studies. The results also indicated that the freshly prepared longitudinal muscle cells maintained their functional calcium signaling system. The order of the responsiveness of the isolated longitudinal muscle cells to oxytocin was 21 day >> 18 day > 15 day pregnant rats in terms of rate, affinity and magnitude. Oxytocin appears to transmit its signal mainly through stimulating a voltage-dependent and/or receptor operated nonselective calcium channel. However, the possibility that a part of the oxytocin action occurs through stimulating the release of calcium from intracellular store sites of longitudinal muscle still remains.

Animals↗