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Functional and phylogenetic analyses of a conserved regulatory program in the phloem of minor veins.

The minor-vein phloem of mature leaves is developmentally and physiologically distinct from the phloem in the rest of the vascular system. Phloem loading of transport sugars occurs in the minor veins, and consistent with this, galactinol synthase is expressed in the minor veins of melon (Cucumis melo) as part of the symplastic-loading mechanism that operates in this species. A galactinol synthase promoter from melon drives gene expression in the minor-vein companion cells of both transgenic tobacco (Nicotiana tabacum) and Arabidopsis. Neither of these plants use galactinol in the phloem-loading process, implying that the promoter responds to a minor-vein-specific regulatory cascade that is highly conserved across a broad range of eudicotyledons. Detailed analysis of this promoter by truncation and mutagenesis identified three closely coupled sequences that unambiguously modulate tissue specificity. These sequences cooperate in a combinatorial fashion: two promote expression throughout the vascular system of the plant, whereas the third functions to repress expression in the larger bundles. In a complementary approach, phylogenetic footprinting was used to obtain single-nucleotide resolution of conserved sites in orthologous promoters from diverse members of the Cucurbitaceae. This comparative analysis confirmed the importance of the closely coupled sites but also revealed other highly conserved sequences that may modulate promoter strength or contribute to expression patterns outside of the phloem. The conservation of this regulatory design among species that phloem load by different mechanisms supports a model for organismal development in which tissues and cell types are controlled by relatively ancient and conserved paradigms but expression of genes influencing final form and function are relatively plastic.

Arabidopsis↗

Electron microscopic observations on the pit organ of a crotaline snake Trimeresurus flavoviridis.

The pit membrane in the pit organ of a crotaline snake is about 15 micron thick. Myelinated nerve fibers from the trigeminal nerve enter the pit membrane and swell into palmate structures on demyelination. Demyelinated fibers repeat branchings and their terminals contain many mitochondria. The terminal portion is not surrounded with Schwann cell processes. There are many small vesicles (30-60 nm in diameter) in the extra-cellular space in close association with the nerve terminal membranes. The spreading of branches from each palm seemed to have a definite territory which would correspond to the unit area detected with electrophysiological methods. But no "unit structure" was revealed by electron microscopy. intraepithelial free nerve endings exist in the outer epithelial layer. The nerve bundles from the trigeminal branches contain some unmyelinated fibers which come in close contact with vascular elements in the pit membrane.

Animals↗

The aging heart.

Pathologic studies of the myocardium and valvular structures have failed to provide convincing evidence of gross or microscopic changes that can be ascribed to aging alone. Lipofuscin accumulation and basophilic degeneration in cardiac muscle cells appear to be the most consistent findings associated with aging, but they are found in other conditions. Without doubt, pathologic changes in the myocardium, valves, and coronary arteries are found more frequently in the hearts of elderly persons, but those changes are caused by disease processes associated with an aging population rather than the aging process itself. Both the sinus and atrioventricular nodes decrease in size with age owing to a loss of cellularity. These structures become infiltrated with collagen, elastic tissue, and reticular fibers. Some have found infiltration also with fat. Amyloid deposition, basophilic degeneration of cells, and lipofuscin accumulation occur but probably do not cause functional abnormalities. Similar but less dramatic changes occur in the bundle of His and individual bundle branches. Most of the data suggests that these aging changes are not due to vascular insufficiency. Age-related changes in intrinsic mechanical function have been identified as a prolongation of contraction duration, decreased inotropic responses to catecholamines and cardiac glycosides, and an increase in mechanical refractoriness. Other possible age-related changes include alterations in relaxation, which may or may not be independent of the prolongation of contraction, and changes in the viscoelastic properties of cardiac muscle. When examined in the context of the components of a model of excitation-contraction coupling, changes in action potential duration and the function of the sarcoplasmic reticulum emerge as the most likely bases for the changes. The electrical characteristics of sinus, atrioventricular, and His-Purkinje cells as well as atrial and ventricular muscle cells change with age. The sinus rate decreases, as do the escape rates of other automatic cells. The sensitivity and electrical changes produced by cardiac drugs also is affected by aging. Transmembrane electrical aging changes have been attributed to changes in the slow inward current caused by calcium and alterations in potassium conductance as well as other ionic currents. An age-related change in the function of the sarcoplasmic reticulum may be contributory. There appear to be age-related changes in both the anatomy and physiology of major arteries.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

Lung biopsy diagnosis of operative indication in secundum atrial septal defect with severe pulmonary vascular disease.

OBJECTIVE: Surgical indication was determined by lung biopsy in 91 patients with secundum atrial septal defect (ASD) and severe pulmonary hypertension > 70 mm Hg of pulmonary arterial peak pressure and/or pulmonary vascular resistance of > 8 U/m(2). METHODS AND RESULTS: Pulmonary vascular disease (PVD) in ASD was classified into four types: (1) Musculoelastosis consisting of longitudinal muscle bundles and elastic fibers; surgery is indicated no matter how severely the peripheral small pulmonary arteries are occluded. Surgery was performed in all of the 20 patients, and the postoperative course was uneventful. (2) Plexogenic pulmonary arteriopathy: surgery is indicated for a PVD index < or = 2.3. Surgery was performed in 25 of the 32 patients. The remaining seven patients for whom surgery was not indicated are under follow-up observation. No deaths have occurred among the 32 patients. (3) Thromboembolism of small pulmonary arteries: Surgery is indicated for all such cases. Surgery was indicated in all of the five patients. (4) Mixed type of plexogenic pulmonary arteriopathy and musculoelastosis: Surgery is indicated if the collateral is not observed. Surgery was performed in 15 of the 25 patients. The remaining 10 patients for whom surgery was not indicated are under follow-up observation. Nine of these 91 patients associated with primary pulmonary hypertension were eliminated from this study. CONCLUSION: No deaths due to PVD occurred among the 82 patients who underwent lung biopsy diagnosis. Lung biopsy diagnosis is concluded to be very effective.

Adult↗

Secundum atrial septal defect before and after surgery.

Twenty patients with secundum atrial septal defect, who had undergone open heart surgery were studied retrospectively. Girls were more affected than boys; the sex ratio was 1.5:1. Associated cardiac defects were diagnosed in two patients, one with moderate valvular pulmonic stenosis and the other one with small ventricular septal defect. Typical clinical findings consisted of loud first heart sound, widely fixed split second heart sound and soft ejection systolic murmur at the upper left sternal border were heard in all cases. Mid diastolic murmur due to relative tricuspid stenosis was detected in most cases (75%). Electrocardiographic findings included right axis deviation, prolonged PR-interval and right atrial enlargement were found in 50%, 15% and 60% of cases, respectively. Incomplete right bundle branch block and right ventricular enlargement were found in all cases, as was cardiomegaly with increased vascular markings were found in all cases. Paradoxical ventricular septal motion and visualization of the atrial septal defect were seen in 95% and 75% of cases, respectively. Cardiac catheterization was performed in 19 patients (95%). The pulmonary-systemic flow ratio (Qp/Qs) ranged from 1.7 to 6.3 (mean 2.9 +/- 0.67), and was correlated to the presence of mid diastolic tricuspid flow murmur and paradoxical ventricular septal motion. Simple closure of the defect was the procedure of choice, but in one patient (5%) pericardial patch was used to close the very large defect. The mortality rate was 10 per cent. Physical retardation was found in all boys and 50% of girls, before surgery. Body weight percentile increased in most cases (61.1%), while body height percentile increased in only 5.6% of cases, postoperatively. Ejection systolic murmur at the upper left sternal border was still detected in one patient (5.6%). Incomplete right bundle branch block persisted in all cases, while cardiomegaly was still found in 5.6% of cases followed-up six months to five years after surgery. There was no residual left ventricular dysfunction in all cases.

Adolescent↗

Myocardial ischemia detected by transesophageal echocardiography in a patient undergoing peripheral vascular surgery.

Prevention and early treatment of myocardial ischemia remain among the primary goals of the anesthesiologist taking care of high-risk patients, such as those undergoing vascular surgery. Guidelines have been published to assist in directing preoperative evaluation and optimization of cardiovascular status. Although perioperative monitoring allows early detection of ischemic events, all monitors have limitations that must be understood before they can be used effectively. We present a case of severe intraoperative myocardial dysfunction detected only by transesophageal echocardiography in a patient undergoing a peripheral vascular procedure. Preoperative and intraoperative management is also discussed.

Aged↗

Peptide-containing nerve fibers in human airways: distribution and coexistence pattern.

The occurrence, distribution and coexistence pattern of an array of neuropeptides and tyrosine hydroxylase in the human larynx, trachea, bronchi and lungs were studied by immunocytochemistry. A rich supply of nerve fibers containing vasoactive intestinal peptide (VIP) was seen close to blood vessels, glands and nonvascular smooth muscle. Pituitary adenylate cyclase-activating peptide (PACAP)-containing fibers were numerous among bundles of smooth muscle. Moderate numbers of helospectin-containing nerve fibers were seen in the nonvascular smooth muscle. The majority of neuropeptide Y (NPY)-containing fibers were located in the nonvascular smooth muscle; some fibers also occurred around blood vessels and glands. Substance P (SP) and calcitonin gene-related peptide (CGRP)-containing fibers were generally few and distributed beneath the epithelium, among bundles of smooth muscle, around blood vessels and glands. A conspicuous finding was the lack of SP- and CGRP-containing fibers within the respiratory epithelium. Galanin-containing nerve fibers were moderate in number among bundles of smooth muscle. Tyrosine hydroxylase-containing fibers were numerous around blood vessels and glands. The majority of the VIP-containing nerve fibers present in nonvascular smooth muscle also stored PACAP and helospectin. A subpopulation of VIP-containing fibers in both vascular and nonvascular smooth muscle and around glands stored NPY. Additionally, galanin was found to occur in many VIP-containing fibers located among bundles of smooth muscle.

Adrenergic Fibers↗

First degree atrioventricular block.

Prolongation of the PR interval is a nonspecific condition. Etiologies include normal physiologic variance, idiopathic bundle branch fibrosis, calcific valvular heart disease, ischemic heart disease, cardiomyopathies, infections resulting in myocarditis, drugs (especially type I antidysrhythmic medications), collagen vascular diseases, tumors, trauma, electrolyte imbalances, and many other miscellaneous causes. Isolated first degrees atrioventricular block is generally not associated with an increased risk of sudden death, syncope, or progression to higher degrees of atrioventricular block. Exceptions include patients with intra-atrial conduction delays prone to atrial fibrillation, acute myocardial infarction, or bundle branch disease where higher degrees of atrioventricular block may develop. Treatment consists of correction of the underlying disorder or discontinuation of the offending medication.

Diagnosis, Differential↗

Kaposi's sarcoma in AIDS: basement membrane and endothelial cell markers in late-stage lesions.

Early-stage lesions of Kaposi's sarcoma (KS) are composed of single-layered, highly flattened cells lining collagen bundles, whereas late-stage lesions contain densely packed, spindle-shaped cells. We examined the progression of KS lesions in oral mucosa and lymph nodes from patients with AIDS, using antibodies specific for blood vascular endothelial cells (Factor VIII-related antigen) and their basement membrane (Type IV collagen and laminin). In addition, the plant lectin Ulex europaeus, which selectively stains blood vessels, was also used. In early-stage KS lesions, fibronectin, laminin and Type IV collagen were co-distributed at the interface between KS cells and collagen bundles; Factor VIII-related antigen and Ulex europaeus lectin staining was present in vascular channels and in the KS cells. However, in late-stage lesions, few if any KS cells stained with antibody to Factor VIII-associated antigen, although endothelial cells lining blood vessels were positive. Strong staining for laminin and Type IV collagen was present in a pericellular pattern throughout the nodular late-stage lesions. Since lymphatic capillary endothelium does not produce basement-membrane-specific macromolecules, these results support the conclusion that KS cells are related to blood vascular endothelium but eventually lose certain endothelium-specific markers as the cells are transformed into the spindle-shaped cell type.

Acquired Immunodeficiency Syndrome↗

Vascular changes in cutaneous neurofibromas.

A variety of vascular changes has been associated with neurofibromatosis, and morphological alterations of arteries have been described previously. However, little attention has been paid to structural modifications of the microvasculature in neurofibromas themselves. Small vessels of 10 cutaneous neurofibromas, excised from patients with neurofibromatosis, were studied by using transmission electron microscopy and compared with normal skin vessels. The major alterations were: (1) increased thickness of the cytoplasm of endothelial cells which send numerous long processes to the lumen and, in some instances, obliterate it; (2) larger numbers of endothelial cell processes on the abluminal surface which are apposed to pericyte processes; (3) increased amounts of filaments and free ribosomes in the cytoplasm of endothelial cells, and (4) abundant pericytes with bundles of cytoplasmic filaments and many small subplasmalemmal densities. Mitotic figures were not seen in any of the vascular elements. These changes were interpreted to be the result of a generalized malformative process of blood vessels in neurofibromas rather than a consequence of the action of a tumor angiogenesis factor.

Adolescent↗

Human complement regulator expression by the normal female reproductive tract.

BACKGROUND: The membrane-associated proteins that regulate human complement activation are ubiquitously expressed and function cooperatively to protect cells from autologous complement damage. For classical and alternative pathways, the primary regulators at the stage of C3 proteolysis and deposition are membrane cofactor protein (MCP; CD46) and decay-accelerating factor (DAF;CD55), whereas protectin or CD59 regulates terminal component assembly. There is increasing awareness in reproductive, tumor, and transplantation immunology of the conventional and non-complement roles of these proteins. The human reproductive system may serve as a model of the non-complement functions. METHODS: We performed immunohistochemical analyses of multiple normal ovaries, fallopian tubes, cervices, and uterine corpi by using well-characterized monoclonal antibodies to provide a detailed, direct comparison of complement regulator expression. RESULTS: Membrane cofactor protein was diffusely and strongly expressed on all epithelia and vascular endothelium and was the predominant regulator on oocytes. In contrast, decay-accelerating factor had variable expression in intensity and distribution on epithelia and was notably absent on certain epithelia and oocytes. It was the only regulator present on the connective tissue between muscle bundles in the myometrium and the cervix and was found on most stroma. CD59, although staining intensity varied, was present on virtually all epithelia, vascular tissue, and stroma. CONCLUSIONS: Distinct reproducible patterns of complement regulator expression are found throughout the female reproductive tract. Differential expression on certain epithelia and oocytes may suggest non-complement activities. This comprehensive study should provide a basis for further characterization of pathological tissues and mechanisms of cellular localization.

Antigens, CD↗

Intrinsic innervation and vasculature of pre- and post-natal human thymus.

Human thyro-thymic venous connections were more numerous in pre-natal life. The thymus was vascular since the 10th week. At 11 weeks, nerves invaded the capsule and a few trabeculae. At 16 weeks, nerve bundles accompanied arteries and veins. Their branches ran close to intralobular arterioles and venules. Parenchymal nerves appeared in the cortex and medulla. Radial cortical capillaries drained into capsular venules at 20 weeks. From 28 weeks pre-natally to 3 years post-natally, nerves in the medulla ended in knobs or fine tapers. Some encircled or relayed on Hassall's corpuscles. Others were traceable to blood vessel walls. The pattern of innervation and vascularization was not altered up to 9 years. The vasculature began to be irregular at 11--13 years. Parenchymal and perivascular nerves existed up to 15 years. At 25 years, nerves were detected in the capsule and proximal parts of the trabeculae.

Adolescent↗

Intervascular smooth muscle fibers and muscular bolsters in nasal swell bodies of humans.

There is strong clinical evidence that the cavernous tissue (swell bodies) of nasal mucosa plays an important role in congestion of the nose. Still, the complex mechanisms responsible for the unique behavior of these vessels have not yet been identified, and even the morphology of these structures is still a matter of controversy. The present study was performed on nasal mucosal specimens from inferior turbinates of humans by means of histology and transmission electron microscopy. Besides the evaluation of the vascular wall structure of the nasal swell bodies, special attention was given to two morphological peculiarities: intervascular smooth muscle fibers and muscular bolsters. Intervascular smooth muscle fibers are composed of bundles of smooth muscle cells varying in diameter between 14 and 35 microns; they are attached to the muscular coat of the vessels of the cavernous tissue. Muscular bolsters are distinct protrusions of the vascular wall in nasal swell bodies; they are found not only at the transition between different vessels, but also irregularly within the course of veins of the cavernous tissue. The authors report on their understanding of the functional significance of intervascular smooth muscle fibers and muscular bolsters within the cavernous tissue for swelling mechanisms in the nose and discuss their results in light of the literature.

Connective Tissue↗

Diagnosis and management of thoracic outlet syndrome.

During the past 15 years, using plethysmography and maneuvers originally described by other researchers, we have tested 1,140 patients who had thoracic outlet symptoms. The vascular compression was recorded noninvasively, which also reflected the pressure on accompanying nerves in the brachial bundle. If the neurologic symptoms were reproduced at this time, the diagnosis of thoracic outlet syndrome was positive. Following exercise treatment (without improvement), 194 patients underwent operative exploration. By performing costoclavicular and hyperabduction maneuvers during axillary exploration, the tissue causing compression was identified and the muscle, bone, or tendon was divided or resected. Division of soft tissues in 180 patients resulted in improvement in the conditions of 173 patients (96%). Bone resection allowed relief of symptoms in six (43%) of 14 patients.

Exercise Therapy↗

Anatomy, histology, and pathology of the cardiac conduction system--Part VI.

Various pathologic conditions producing atrioventricular block are reviewed. Calcific atrioventricular block (aortic stenosis, mitral valve annular calcium), active infective endocarditis ("ring" abscess), acute and healed myocarditis, various collagen-vascular diseases, amyloidosis, and tumors are reviewed as causes of atrioventricular block. Various diseases producing bundle-branch block are also discussed.

Heart Block↗

Immunohistochemical localization of tyrosine hydroxylase in corneal nerves.

The sympathetic innervation of the mammalian cornea is thought to play an important role in the regulation of epithelial ion transport, mitogenesis, and wound healing following corneal injuries. Anatomically, the three-dimensional organization and relative density of corneal sympathetic innervation in many species remains inadequately described. In the present study, the sympathetic innervation of five different mammals (guinea pig, rat, mouse, hamster, and human) was studied in corneas sectioned parallel to the main axis of fiber orientation by labeling the fibers immunohistochemically with antiserum against tyrosine hydroxylase and an avidin-biotin-diaminobenzidine technique. The results showed that each species displayed a distinctive pattern and density of tyrosine hydroxylase immunoreactive (TH-IR) corneal innervation that was unique to that species. The overall level of TH-IR innervation was highest in the guinea pig, moderate in the human, hamster, and rat, and lowest in the mouse. In all species examined, TH-IR nerves were most numerous in the corneoscleral limbus where they either formed intimate associations with blood vessels or coursed through the connective tissue matrix apparently unrelated to vascular elements. Other TH-IR nerves entered the cornea proper in radially directed stromal nerve bundles to give rise to subepithelial plexuses of varying complexity. Occasional intraepithelial penetrations were observed in the guinea pig, human, and rat. Removal of the superior cervical ganglion resulted in the total loss of TH-IR staining from guinea pig and hamster corneas and in the substantial but incomplete loss of TH-IR staining from rat and mouse corneas, thus demonstrating their predominantly sympathetic origin. Combined sympathetic and sensory ocular denervation in the rat eliminated almost all corneal and limbal TH-IR immunostaining, thus suggesting a minor TH-IR sensory component in this species. In agreement with this conclusion, small numbers of TH-IR sensory neurons and an abundance of TH-IR fibers were observed in the trigeminal ganglia of the rat and guinea pig. Removal of the rat main ciliary ganglion resulted in the loss of additional TH-IR fibers from the chamber angle and iris, thereby confirming a partial parasympathetic contribution to the rat iridial TH-IR innervation. Following unilateral removal of the superior cervical ganglion in rats and guinea pigs, the contralateral cornea contained increased numbers of TH-IR nerves, suggesting an upregulation of tyrosine hydroxylase (TH) expression in some contralateral axons.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic Fibers↗

A focusing image probe for assessing neural activity in vivo.

We describe a compact, focusing image probe to record rapid optical changes from neural tissue. A gradient index (GRIN) lens served as a relay lens from tissue to a microscope objective which projected an image onto a CCD camera. The microscope objective and camera assembly was adjusted independently from the GRIN lens, allowing focus changes without disturbing the probe/tissue interface; firm contact minimized movement and specular reflectance. Fiber optics around the probe perimeter provided diffuse illumination from a 780 nm laser, or 660 and 560 nm light emitting diodes. To characterize depth-of-field, we imaged a black suture through increasing tissue thicknesses. Light modulation by the suture remained detectable down to 900 microm using 780 nm illumination. We acquired images from cardiorespiratory areas of the rat dorsal medulla, at different depths and illumination wavelengths. Images illuminated at 560 nm were dominated by vasculature flow patterns, while 660 nm illumination revealed different spatial patterns which preceded vascular flow by 40 ms and may represent cardiac-related neural activity. Using 780 nm light, image sequences triggered by the cardiac R-wave showed vascular perfusion changes with delayed and broader responses at deeper levels. Electrical stimulation within the vagal bundle caused fast optical changes which track the electrical response, with a different spatial distribution from hemodynamic signals.

Animals↗

Histology of the extensor retinaculum of the wrist and the ankle.

The extensor retinaculum of the wrist has been used for reconstruction of the annular pulleys of the flexor sheath. We examined the histologic structure of the extensor retinaculum and tendon sheath of the wrist and ankle in cadaveric specimens using hematoxylin-eosin and Verhoeff-van Gieson stains to detect elastin and alcian blue to detect hyaluronic acid, comparing the structure with that described previously for the annular pulleys. Three distinct layers are identified in the retinaculums of both the ankle and wrist: the inner gliding layer, with hyaluronic acid-secreting cells, shows isolated chondroid metaplasia; the thick middle layer contains collagen bundles, fibroblasts, and interspersed elastin fibers; and the outer layer consists of loose connective tissue containing vascular channels. This basic 3-layered histologic composition of the extensor retinaculum is carried in anatomic pulleys throughout the body and appears to represent an adaptive mechanism to provide both a smooth gliding surface as well as the mechanical strength to prevent tendon bowstringing. Given the same histologic structure as the annular pulleys, the extensor retinaculum is a reasonable biologic replacement for the reconstruction of deficient annular pulleys. Likewise, the extensor retinaculum of the ankle could be used to reconstruct a deficient retinaculum of the wrist.

Ankle↗