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Specialised sympathetic neuroeffector associations in immature rat iris arterioles.

Sympathetic nerve-mediated vasoconstriction in iris arterioles of mature rats occurs via the activation of alpha(1B)-adrenoceptors alone, while in immature rat iris arterioles, vasoconstriction occurs via activation of both alpha1- and alpha2-adrenoceptors. In mature rats the vast majority of sympathetic varicosities form close neuroeffector junctions. Serial section electron microscopy of 14 d iris arterioles has been used to determine whether restriction in physiological receptor types with age may result from the establishment of these close neuroeffector junctions. Ninety varicosities which lay within 4 microm of arteriolar smooth muscle were followed for their entire length. Varicosities rarely contained dense cored vesicles even after treatment with 5-hydroxydopamine. 47 % of varicosities formed close associations with muscle cells and 88 % formed close associations with muscle cells or melanocytes. Varicosities in bundles were as likely as single varicosities to form close associations with vascular smooth muscle cells, although the distribution of synaptic vesicles in single varicosities did not show the asymmetric accumulation towards the smooth muscle cells seen in the varicosities in bundles which were frequently clustered together. We conclude that restriction of physiological receptor types during development does not appear to correlate with the establishment of close neuroeffector junctions, although changes in presynaptic structures may contribute to the refinement of postsynaptic responses.

Animals↗

Short-term immunosuppression and surgical neoangiogenesis with host vessels maintains long-term viability of vascularized bone allografts.

Currently available methods to reconstruct large skeletal defects have limitations. These include nonunion and stress fractures in structural allografts, and inability to match the size, shape, and/or strength of most recipient sites using vascularized fibular autografts. Prosthetic diaphyseal replacements may loosen or produce periprosthetic fractures. Transplantation of living allogenic bone would enable matching donor bone to the recipient site, combined with the desirable healing and remodeling properties of living bone. We propose a novel method by which the transplantation of such tissue might be done without the risks of life-long immunosuppression, using surgical neoangiogenesis to develop a new host-derived osseous blood supply. We performed vascularized femoral allografts from 86 female Dark Agouti donor rats to male Piebald Virol Glaxo recipients across a major histocompatibility (MHC) barrier. In addition to microvascular reconstruction of the nutrient vessel, we surgically implanted a host arteriovenous (AV) bundle into the medullary canal to promote host vessel neoangiogenesis. Independent variables included patency of the implanted AV bundle, and use of 2 weeks' FK-506 immunosuppression. After 18 weeks, bone blood flow was measured, and neoangiogenic capillary density quantified. Bone blood flow and capillary density were significantly greater in transiently immunosuppressed recipients with a patent AV pedicle. We conclude that neoangiogenesis from implanted host-derived AV-bundles, combined with short-term immunosuppression maintains blood flow in vascularized bone allografts, and offers potential for clinical application.

Anastomosis, Surgical↗

Agonist-stimulated cytoskeletal reorganization and signal transduction at focal adhesions in vascular smooth muscle cells require c-Src.

Thrombin and angiotensin II (angII) have trophic properties as mediators of vascular remodeling. Focal adhesions and actin cytoskeleton are involved in cell growth, shape, and movement and may be important in vascular remodeling. To characterize mechanisms by which thrombin and angII modulate vessel structure, we studied the effects of these G protein-coupled receptor ligands on focal adhesions in vascular smooth muscle cells (VSMCs). Both thrombin and angII stimulated bundling of actin filaments to form stress fibers, assembly of focal adhesions, and protein tyrosine phosphorylation at focal adhesions, such as p130Cas, paxillin, and tensin. To test whether c-Src plays a critical role in focal adhesion rearrangement, we analyzed cells with altered c-Src activity by retroviral transduction of wild-type (WT) and kinase-inactive (KI) c-Src into rat VSMCs, and by use of VSMCs from WT (src+/+) and Src-deficient (src-/-) mice. Tyrosine phosphorylation of Cas, paxillin, and tensin were markedly decreased in VSMCs expressing KI-Src and in src-/- VSMCs. Expression of KI-Src did not inhibit stress fiber formation by thrombin. Surprisingly, actin bundling was markedly decreased in VSMCs from src-/- mice both basally and after thrombin stimulation, compared with src+/+ mice. We also studied the effect of KI-Src and WT-Src on VSMC spreading. Expression of KI-Src reduced the rate of VSMC spreading on collagen, whereas WT-Src enhanced cell spreading. In conclusion, c-Src plays a critical role in agonist-stimulated cytoskeletal reorganization and signal transduction at focal adhesions in VSMCs. c-Src kinase activity is required for the cytoskeletal turnover that occurs in cell spreading, whereas c-Src appears to regulate actin bundling via a kinase-independent mechanism.

Angiotensin II↗

Characteristics of normal prostate vascular anatomy as displayed by power Doppler.

BACKGROUND: To define the vascular anatomy of the normal prostate as depicted by power Doppler and to provide baseline data for evaluation of this modality in the diagnosis and management of prostatic disease. METHODS: The vascular anatomy of 40 subjects was studied. Power Doppler images were correlated with corresponding gray-scale images. Doppler spectral waveform measurements were obtained for the vessels identified. RESULTS: Separate branches of the capsular vessels were visualized clearly, distributed radially in the peripheral and central zones and converging toward the center of the gland. Urethral vessels were visualized in the transition zone coursing from bladder neck to verumontanum. The neurovascular bundles were identified posterolaterally along the length of the gland. No significant difference between the resistive indexes of the urethral and capsular vessels was identified (P = 0.595), although there was a significant difference between the resistive index of the neurovascular bundles and that the prostatic vessels (P < 0.001). CONCLUSIONS: The vascular anatomy of the normal prostate as displayed by power Doppler demonstrates a reproducible and symmetric flow pattern. Power Doppler is highly sensitive in depicting blood flow, the number, course, and continuity of vessels more readily than other imaging modalities, such as color Doppler. These data should allow comparison of the vascular anatomy of the normal prostate with that of the prostate with diseases such as prostate cancer and benign prostatic hyperplasia.

Adult↗

Sensory innervation of periodontal ligament of rat molars consists of unencapsulated Ruffini-like mechanoreceptors and free nerve endings.

The trigeminal ganglion (TG) of adult rats was injected with 3H-amino acids to label periodontal receptors by axonal transport; 20-24 hours after injection, samples of molar ligament were prepared for autoradiography and electron microscopy. Four types of neurites labeled from TG were found in the avascular ligament fiber regions: large, complex, Ruffini-like endings, lacking a capsule, but with finger extensions touching ligament collagen; smaller Ruffini-like endings, lacking a capsule and neural fingers; free bundles of unmyelinated axons; and free, small, myelinated axons. The vascular channels plus associated loose connective tissue that perforate the ligament contained labeled preterminal ensheathed axons, small Ruffini endings, and free unmyelinated or small myelinated axons. The incidence of labeled endings was about 5 X greater next to the lower third of the root than in the upper two-thirds or beneath the root. The TG myelinated axons (diameter range 2-15 microns) entered the ligament in sheathed nerve bundles; these branched to form numerous small preterminal axons that were surrounded by a periaxonal fluid space and a perineurial sheath. Terminal axons branched from nodes of Ranvier, left the preterminal chamber, and followed an extended branching course through the collagen fibers. Large, complex Ruffini-like endings had numerous mitochondria and were partially covered by special lamellar Schwann cells and complex basal lamina; vesicles and multivesicular bodies were found near exposed regions of the receptor. Smaller Ruffini-like endings lacked neural fingers and had a simpler structure and less elaborate Schwann cells. The structure of Ruffini-like endings was highly varied; thus a structural continuum may exist from the largest, most complex to the smallest, simplest Ruffini-like receptor. The TG unmyelinated axons entered the ligament in ensheathed bundles; they then branched into free bundles that were found in the avascular ligament or near blood vessels. No encapsulated receptors were found.

Animals↗

Asymmetric septal hypertrophy of the heart. New findings concerning the possible etiology of sudden deaths in five males.

This report describes certain interesting postmortem findings in the hearts of five subjects who died suddenly, silently, and unexpectedly, and in whom the only significant abnormality at autopsy was asymmetric septal hypertrophy (ASH) of the heart. Deep clefts, cystic faults, and dilated vascular channels were not only seen within the septal myocardium in all the hearts, but also within the left ventricular free walls of two hearts. The septal myocardium and the left ventricular free walls of two hearts and the A-V node and His bundle of one heart demonstrated mural and luminal thrombi of several dilated vascular channels. In another heart, foci of cardiocytic myofibrillar degeneration were seen, especially close to narrowed small coronary vessels. Fetal dispersion and fibrosis of the A-V node and His bundle were evident in one heart. These abnormalities in the conducting system and the ventricular myocardium suggest that the hearts of subjects with ASH are not only excellent anatomic substrates for lethal arrhythmias, but also are bound to be hemodynamically impaired. We believe that conditions such as hypoxia, increased oxygen demand by the heart or abnormal sympathetic stimulus may easily trigger fatal arrhythmias in such individuals, thereby causing sudden death.

Adolescent↗

Specialized veins in the submucosa of the equine ileocecal junction.

Spirally arranged bundles of sub-endothelial smooth muscle enfold the small to medium-sized submucosal veins in the equine ileocecal junction. The muscle bundles, accompanied by the endothelial lining, bulge into the lumen of the vessels, partly occluding the latter. Transmission electron microscopy of the muscle cells reveals features consistent with vascular smooth muscle ultrastructure. It is proposed that the throttling effect of the muscle bundles causes engorgement of the submucosal venous plexus, which then assists in the closing of the ileocecal orifice.

Animals↗

Forms of lung lymphatics: a scanning electron microscopic study of casts.

In a recent study, rats given monocrotaline underwent angiogenesis on their pleural surfaces. The rats also had novel structures in their bronchovascular bundles that were detected by scanning electron microscopy of vascular casts. These vessels could have been either new blood capillaries or dilated lymphatic capillaries. To determine if these structures were lymphatics or new blood vessels, specimens from animals that were undergoing angiogenesis were compared to those that were not. Finding similar structures in normal animals would imply that they were lymphatic. The second purpose of this work was to describe the three-dimensional anatomy of the lymphatics of the lung. Cast lymphatics were found in most lungs with edema or angiogenesis, but were rare in other conditions. The vascular structures in question were found in animals not undergoing angiogenesis and were, therefore, lymphatic. Additionally, scanning electron microscopy of casts showed several distinct forms of lymphatics in the lung. Prelymphatics are tissues planes beneath the pleura and around bronchovascular structures. They join reservoir, conduit or tubulo-saccular lymphatics. Reservoir lymphatics are broad ribbon-like structures with textured surfaces and small laterally branching pouches. They occur on the pleural surface, are closely linked with prelymphatics, and join conduit lymphatics. Conduit lymphatics are tubular structures that may contain valves, twist and go great distances without accepting tributaries. On the pleural surface, they may wind around blood vessels and vary greatly in diameter. Sacculo-tubular lymphatics surround arteries, veins and bronchioles. They have thin walls with wide saccular segments. They may be so dense that they form cylinders around the vessels or airways. Different forms of lung lymphatics suggest different function and potential.

Animals↗

Immunohistochemical distribution and biological activity of pituitary adenylate cyclase-activating polypeptide (PACAP) in the central nervous system of the frog Rana ridibunda.

The primary structure of frog pituitary adenylate cyclase-activating polypeptide (PACAP) has recently been determined and the results show that the sequence of PACAP has been highly conserved during evolution. In particular, the structure of the 1-27 fragment of PACAP is identical in frog and mammals. Using an antiserum raised against PACAP27, we have investigated the distribution of PACAP-containing neurons in the central nervous system of the frog Rana ridibunda by the immunofluorescence technique. The main populations of immunoreactive perikarya were located in the medial and ventral diencephalon, i.e., the preoptic nucleus, the ventral and dorsal infundibular nuclei, the nucleus posterocentralis thalami, and the ventral and ventrolateral areas of the thalamus. In the telencephalon, sparse cell bodies were found in the nucleus accumbens septi, the amygdala, the pallial commissure, and the bed nucleus of the pallial commissure. In the hindbrain, the torus semicircularis, the nucleus profundus and the nucleus anteroventralis tegmenti of the mesencephalon also contained populations of PACAP-immunoreactive perikarya. Beaded nerve fibers were observed throughout the brain. Occasionally they formed bundles, e.g., from the ventral infundibulum to the external vascular layer of the median eminence, from the central thalamus to the optic tectum, and rostrocaudally, from the nucleus accumbens septi to the nucleus entopeduncularis. Other areas, such as the interpeduncular nucleus, the nucleus isthmi and the roots of cranial nerves V and VIII in the medulla oblongata, were also densely innervated. The adenylate cyclase-stimulating activity of PACAP was tested by using a static incubation technique for hypothalamic slices.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Novel heparin/alginate gel combined with basic fibroblast growth factor promotes nerve regeneration in rat sciatic nerve.

We have developed an alginate gel crosslinked with covalent bonds for regeneration of dermis, nerve, and bone. Recently, a novel matrix (H/A gel) which consists of heparin and alginate covalently crosslinked with ethylenediamine, was designed. It can stabilize and release biologically active basic fibroblast growth factor (bFGF) for 1 month, which is one of the heparin-binding growth factors. In the present report, we examined the effect of this novel H/A gel on nerve regeneration in the rat sciatic nerve. In this study, regenerated axons in H/A gel with bFGF grew faster than in ordinary alginate gel with bFGF in the early stage. Myelinated fibers showed a tendency to increase in diameter toward the normal size in the later stage. Nerve bundles in the implantation exhibited minimal fibrosis and good vascularization. H/A gel with bFGF exhibited better-developed vascularization than ordinary alginate gel with bFGF. These findings suggested that H/A gel with bFGF could serve not only as an efficient cellular scaffold, but also as a stabilizing matrix for bFGF for peripheral nerve regeneration.

Alginates↗

Clinical and histological healing pattern of peri-implantitis lesions following non-surgical treatment with an Er:YAG laser.

BACKGROUND AND OBJECTIVES: The aim of the present study was to assess clinical and histo-pathological healing pattern of peri-implantitis lesions following non-surgical treatment with an Er:YAG laser (ERL). STUDY DESIGN/MATERIALS AND METHODS: Twelve patients suffering from peri-implantitis (n = 12 implants) received a single episode of non-surgical instrumentation using ERL (12.7 J/cm2). Assessment of clinical parameters (plaque index (PI), bleeding on probing (BOP), probing pocket depth, gingival recession (GR), and clinical attachment level (CAL)), surgical defect examination, and histo-pathological examination of peri-implant tissue biopsies was performed after 1, 3, 6, 9, 12, and 24 months. RESULTS: All patients exhibited improvements of all clinical parameters investigated. However, histo-pathological examination of tissue biopsies revealed a mixed chronic inflammatory cell infiltrate (macrophages, lymphocytes, and plasma cells) which seemed to be encapsulated by deposition of irregular bundles of fibrous connective tissue showing increased proliferation of vascular structures. CONCLUSION: It was concluded that a single course of non-surgical treatment of peri-implantitis using ERL may not be sufficient for the maintenance of failing implants.

Aged↗

Dopaminergic innervation of Aplysia gill muscle.

1. The fluorescence histochemical method of Hillarp and Falck was employed to investigate the distribution of dopamine in the gill of Aplysia. 2. Dopamine-containing nerve fibers and varicosities were found in close association with the lateral and medial external pinnule muscles, the circular and longitudinal muscles of the afferent vessel, and the circular muscles of the efferent vessel. 3. Other large, dopamine-containing, intensely fluorescent processes were observed lining the vascular sinuses of the gill and within the muscle bundles themselves. 4. Our findings support the hypothesis that dopamine is a neuromuscular transmitter in the gill. However, the data also suggest that dopamine may play a hormonal role as well.

Animals↗

Angiosarcoma of the head and neck with intra-oral presentation. A clinico-pathological study of four cases.

Angiosarcoma of the head and neck is a rare malignant tumour that most commonly involves the skin and subcutis, particularly of the scalp. It has been reported in intra-oral locations very rarely. This study reports on the clinico-pathological features of four such cases, in elderly patients and manifesting an aggressive course. All patients were admitted for rapidly enlarging masses involving the hard palate, alveolar crest and retromolar trigone and displaying bone destruction in three cases. Morphologically, three cases were composed by bundles of spindle cells admixed with variably sized abortive vascular channels which only showed slit-like spaces separating large clusters of epithelioid cells. In all instances, intra-cytoplasmic vacuoles containing intact or fragmented red blood cells were distinctly evident. All neoplasms showed consistent CD 31 immunoreactivity and variable degrees of CD 34 and Factor VIII related antigen positivity and were responsible for the death of the patients, for local progression or lung metastases, within 6 months from the original diagnosis. Due to their rarity, angiosarcomas with intra-oral presentation may be diagnosed with difficulty, especially on small incisional biopsies. and their differentiation from spindle cell carcinoma, malignant melanoma, anaplastic lymphoma, malignant myoepithelioma and other sarcomas that more commonly arise at this site should be based on accurate immunohistochemical characterisation.

Aged↗

Histopathological changes and expression of adhesion molecules and laminin in varicose veins.

BACKGROUND: Although varicose disease is a common pathology, etiologic factors predisposing to dilatation, elongation and tortuosity of the saphenous vein are not yet well understood. The aim of our study was to investigate morphological changes, laminin and adhesion molecules expression in the great saphenous vein. PATIENTS AND METHODS: Material obtained from 26 patients was analyzed using light microscopy, immunohistology and electron microscopy. Patients were divided into two age groups (group I, aged between 26 and 35 years and group 11, 36-45 years). RESULTS: In most patients veins were stretched out with highly varying wall thickness. The vein wall three-layered structure composed of intima, media and adventitia was changed in 78% of the cases. In most specimens endothelium was either damaged or missing. In such areas possible thrombus formation sites were observed characterized by erythrocyte accumulation. In media and adventitia smooth muscle cells were destroyed or showed altered morphology, the amount of connective tissue was increased together with irregular organization of collagen fibers and disruption of the elastic network around smooth muscle cell bundles. Laminin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression was increased in varicose veins wall, especially in the second group of patients (p<0.05). In addition, ICAM-1 and VCAM-1 expression was more pronounced in the wall of varicose veins of female than male patients (p < 0.05). CONCLUSION: We conclude that morphological alterations in varicose veins become more pronounced with advancing age, and laminin, ICAM-1 and VCAM-1 expression is related to the severity of damage and age of the patient.

Adult↗

The interspinous ligament of the lumbar spine. Magnetic resonance images and their clinical significance.

STUDY DESIGN: A preliminary study of magnetic resonance features of the interspinous ligament in degenerative lumbar spine. OBJECTIVES: To classify the magnetic resonance imaging features of the interspinous ligaments in relation to the patient's age, disc degeneration, and radiographic instability. Magnetic resonance imaging also was correlated with the histologic findings of the interspinous ligaments. SUMMARY OF BACKGROUND DATA: As reported, rupture of the interspinous ligament frequently is found in the degenerative lumbar spine. However, little information is available in the literature on imaging assessment of the interspinous ligament in degenerative lumbar disorders. METHODS: In this study, 24 interspinous ligaments at L1-L2 or L2-L3 from 15 patients with nondegenerated discs were selected to represent normal magnetic resonance features of the interspinous ligament, and 38 patients with the mean age of 49 years underwent functional radiography and magnetic resonance imaging. The magnetic resonance features of the interspinous ligament were classified into five categories according to their signal intensities: Type 1A (low intensity on T1- and T2-weighted images without hypertrophy of the spinal process); Type 1B (same signal pattern as in Type 1A with hypertrophy of spinal process); Type 2 (low intensity on T1- and high intensity on T2-weighted images); Type 3 (high intensity on T1-weighted images); and Type 4 (others). Seven patients with variable patterns of the interspinous ligament were selected to undergo histologic examinations. RESULTS: Of the interspinous ligaments considered normal, 80% were classified as Type 1A. There were 14 Type 1A, 30 Type 1B, 19 Type 2, 16 Type 3, and 20 Type 4 ligaments. The mean age and disc degeneration grade of the patients with the Type 1B ligaments was significantly higher. Instability was found to be associated with Type 2 interspinous ligaments (7 of 19), whereas instability rarely was noted in Types 1A (1 of 14) and 1B (1 of 30) ligaments. The histologic examination revealed that chondrometaplasia and necrotization of fiber bundle predominated in Type 1B, proliferation of cells and vascular invasion in Type 2, fatty degeneration in Type 3 ligaments. CONCLUSIONS: The magnetic resonance imaging characteristics may be helpful in assessing normal or pathologic changes in the interspinous ligaments.

Adolescent↗

Rerouting the plant phenylpropanoid pathway by expression of a novel bacterial enoyl-CoA hydratase/lyase enzyme function.

The gene for a bacterial enoyl-CoA hydratase (crotonase) homolog (HCHL) previously shown to convert 4-coumaroyl-CoA, caffeoyl-CoA, and feruloyl-CoA to the corresponding hydroxybenzaldehydes in vitro provided an opportunity to subvert the plant phenylpropanoid pathway and channel carbon flux through 4-hydroxybenzaldehyde and the important flavor compound 4-hydroxy-3-methoxybenzaldehyde (vanillin). Expression of the Pseudomonas fluorescens AN103 HCHL gene in two generations of tobacco plants caused the development of phenotypic abnormalities, including stunting, interveinal chlorosis and senescence, curled leaf margins, low pollen production, and male sterility. In second generation progeny, the phenotype segregated with the transgene and transgenic siblings exhibited orange/red coloration of the vascular ring, distorted cells in the xylem and phloem bundles, and lignin modification/reduction. There was depletion of the principal phenolics concomitant with massive accumulation of novel metabolites, including the glucosides and glucose esters of 4-hydroxybenzoic acid and vanillic acid and the glucosides of 4-hydroxybenzyl alcohol and vanillyl alcohol. HCHL plants exhibited increased accumulation of transcripts for phenylalanine ammonia-lyase, cinnamate-4-hydroxylase, and 4-coumarate:CoA ligase, whereas beta-1,3-glucanase was suppressed. This study, exploiting the ability of a bacterial gene to divert plant secondary metabolism, provides insight into how plants modify inappropriately accumulated metabolites and reveals the consequences of depleting the major phenolic pools.

Acyl Coenzyme A↗

Fundus findings in Leber's hereditary optic neuroretinopathy.

The acute stage of Leber's hereditary optic neuritis is characterized by dilated disc arterioles accompanied, in some cases, by superficial peripapillary hemorrhages. Decreased vision caused by centrocecal scotoma is accompanied by slow and deficient capillary filling in the papillomacular bundle and arteriovenous shunting in the upper and lower vascular arcades. These and other vascular changes disappear in the more advanced stages (optic atrophy) of the disease.

Acute Disease↗

[Successful surgical treatment of total left anomalous pulmonary venous return with intact atrial septum--a case report].

A successful repair of total left anomalous pulmonary venous return with intact atrial septum is reported. A 7-year-old girl was admitted for evaluation of cardiac murmur which was first noted at 3 months of age. She had been followed up on suspicion of ASD, without any subjective symptoms. Physical examination on admission revealed a systolic ejection murmur at left sternal border. Chest X-ray showed mild cardiomegaly and increased pulmonary vascularity. ECG showed right axis deviation and incomplete right bundle branch block. Selective pulmonary arteriography delineated anomalous return of all left pulmonary veins to RA via vertical vein, left brachiocephalic vein, and SVC, and documented the absence of an atrial septal defect. Ratio of pulmonary to systemic blood flow was 2.2. Vertical vein was anastomosed to left atrial appendage under cardiopulmonary bypass. Postoperative cardiac catheterization showed no difference of wedge pressure between bilateral PA. The patient is up and well 1 years and 6 months after operation.

Child↗