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At least 19 recordsLinked to original sources

Reinnervation of original synaptic sites on muscle fiber basement membrane after disruption of the muscle cells.

Regenerating axons form new synapses precisely at sites of original synapses in denervated skeletal muscle. To determine what role the muscle cell plays in this phenomenon, we studied reinnervation of frog muscle at intervals after crushing the nerve and damaging the muscle fibers. Damaged muscle fibers degenerate and are phagocytized, but their basement membrane persists and acts as a scaffold for regenerating muscle cells. Specializations of the basement membrane serve to mark original synaptic sites after nerve and muscle have degenerated. Regenerating axons enter the region of damage and form functional synapses with regenerating myofibers. The new nerve terminals are found almost exclusively at the original synaptic sites, demonstrating that the integrity of the original postsynaptic cell is not necessary for topographically precise reinnervation of denervated muscle.

Animals

Cross-Platform Methylation-Based Site of Origin Classification for Squamous Cell Carcinomas.

Squamous cell carcinomas (SCCs) are one of the most common cancer types and can arise at nearly any anatomic site. Because SCCs are one of the most common metastases, do not have reliable site-specific morphologic or genomic features, and have considerable morphologic and immunohistochemical overlap with urothelial carcinomas, distinguishing between primary and metastatic squamous-appearing tumors can be challenging. This distinction can be critical to clinical management. We present Squamous cell carcinoma Methylation for Origin Site (SquaMOS), a methylation-based classifier to predict site of origin of squamous-appearing carcinomas. Trained on publicly available array-based methylation data from 1062 primary SCCs (from lung, head and neck, cervix, and esophagus) and urothelial carcinomas, SquaMOS predicted site of origin in primary tumors with 96.1% accuracy in an internal test set (n = 458) and 97.4% accuracy in an external test set from 3 institutions (n = 78). On metastatic tumors (n = 51), SquaMOS predictions were 96.1% accurate. SquaMOS was directly applicable to shallow Nanopore sequencing data (CpG probe site coverage, 0.25-2.88×) with an accuracy of 91.7% (n = 36; 100% accurate for high-confidence predictions). When tested on SCCs outside the training set types (n = 15, including 3 metastases to lung), no cases were misclassified as of lung origin, supporting accuracy of lung vs nonlung origin classification for diverse SCC types. Overall, we demonstrate highly accurate performance of the SquaMOS classifier on primary and metastatic tumors from multiple data sources, robust to suboptimal tumor purity. We illustrate transferability of our array-based classifier to low-depth Nanopore sequencing data, a potentially rapid means of site of origin determination in a clinical setting.

Humans

Reinnervation of muscle fiber basal lamina after removal of myofibers. Differentiation of regenerating axons at original synaptic sites.

Axons regenerate to reinnervate denervated skeletal muscle fibers precisely at original synaptic sites, and they differentiate into nerve terminals where they contact muscle fibers. The aim of this study was to determine the location of factors that influence the growth and differentiation of the regenerating axons. We damaged and denervated frog muscles, causing myofibers and nerve terminals to degenerate, and then irradiated the animals to prevent regeneration of myofibers. The sheath of basal lamina (BL) that surrounds each myofiber survives these treatments, and original synaptic sites on BL can be recognized by several histological criteria after nerve terminals and muscle cells have been completely removed. Axons regenerate into the region of damage within 2 wk. They contact surviving BL almost exclusively at original synaptic sites; thus, factors that guide the axon's growth are present at synaptic sites and stably maintained outside of the myofiber. Portions of axons that contact the BL acquire active zones and accumulations of synaptic vesicles; thus by morphological criteria they differentiate into nerve terminals even though their postsynaptic targets, the myofibers, are absent. Within the terminals, the synaptic organelles line up opposite periodic specializations in the myofiber's BL, demonstrating that components associated with the BL play a role in organizing the differentiation of the nerve terminal.

Animals

Acetylcholine receptors in regenerating muscle accumulate at original synaptic sites in the absence of the nerve.

We examined the role of nerve terminals in organizing acetylcholine receptors on regenerating skeletal-muscle fibers. When muscle fibers are damaged, they degenerate and are phagocytized, but their basal lamina sheaths survive. New myofibers form within the original basal lamina sheaths, and they become innervated precisely at the original synaptic sites on the sheaths. After denervating and damaging muscle, we allowed myofibers to regenerate but deliberately prevented reinnervation. The distribution of acetylcholine receptors on regenerating myofibers was determined by histological methods, using [125I] alpha-bungarotoxin or horseradish peroxidase-alpha-bungarotoxin; original synaptic sites on the basal lamina sheaths were marked by cholinesterase stain. By one month after damage to the muscle, the new myofibers have accumulations of acetylcholine receptors that are selectively localized to the original synaptic sites. The density of the receptors at these sites is the same as at normal neuromuscular junctions. Folds in the myofiber surface resembling junctional folds at normal neuromuscular junctions also occur at original synaptic sites in the absence of nerve terminals. Our results demonstrate that the biochemical and structural organization of the subsynaptic membrane in regenerating muscle is directed by structures that remain at synaptic sites after removal of the nerve.

Acetylcholine

Correlative electrophysiological and anatomical studies concerning the site of origin of escape rhythm during complete atrioventricular block in the dog.

Complete heart block was produced in eight dogs by the selective perfusion of physostigmine or neostigm into the atrioventricular (AV) node artery. A characteristic escape AV junctional rhythm emerged in each dog. After reversal of the cholinesterase paralysis with atropine, in each dog partial heart block was produced by an incision into the AV nodal region. In three of these eight dogs, a second incision placed slightly more anteriorly produced complete AV block which was followed by the emergence of an escape AV junctional rhythm similar to the one produced pharmacologically. Hearts of these three dogs were examined histologically with serial sections to determine the exact location of the incisions and their relationship to the AV node and His bundle. In each dog the incision that produced complete heart block passed directly through the junction of AV node with His bundle. In this region previous studies had demonstrated numerous P cells, which are thought to be the site of origin of normal cardiac automaticity. In each of the three hearts there were abundant P cells in continuity with the His bundle distal to the cut producing heart block. Significance of these findings is discussed relative to the locus of action of acetylcholine within the AV junction, the site of origin of AV junctional rhythm, and sme aspects of the experimental and therapeutic production of heart block.

Animals

Site of origin of the pulsatile secretion of luteinizing hormone in long-term ovariectomized rats.

If long-term ovariectomized rats are treated with the long-acting barbiturate, sodium phenobarbitone, the well-known pulsatile secretion of LH is depressed, resulting in a constant, still raised, plasma LH level. This indicates that in all probability ovariectomized rats secrete LH in both a tonic and a pulsatile way, only the latter being sensitive to phenobarbitone treatment. Constant infusions of synthetic LH-RH into phenobarbitone-treated ovariectomized rats induced a steadily increasing plasma LH concentration without pulsations, whereas pulsatile infusions of the releasing hormone, following a constant infusion, resulted in a pulsatile secretion of LH. This indicates that the pulsatile secretion of LH in ovariectomized rats is the result of a pulsatile secretion of the hypothalamic releasing hormone; the pituitary gland itself is not the site of origin of the phenomenon.

Animals

Transposition of Tn7 in Pseudomonas aeruginosa and isolation of alk::Tn7 mutations.

Conjugal crosses with Pseudomonas aeruginosa donors carrying the CAM-OCT and RP4::Tn7 plasmids result in transfer of the Tn7 trimethoprim resistance (Tp(r)) determinant independently of RP4 markers. All Tp(r) exconjugants which lack RP4 markers have CAM-OCT genes and therefore must have received CAM-OCT::Tn7 plasmids formed by transposition of Tn7 from RP4::Tn7 to CAM-OCT. Most crosses yield exconjugants carrying mutant CAM-OCT plasmids which no longer determine either camphor or alkane utilization and thus appear to carry Tn7 inserts in the cam or alk loci, respectively. Transduction and reversion experiments indicated that at least 13 alkane-negative, camphor-positive, Tp(r) CAM-OCT::Tn7 plasmids carry an alk::Tn7 mutation. Determination of linkage between the alk mutation and the Tp(r) determinant of Tn7 on these plasmids is complicated by the presence of multiple copies of the Tn7 element in the genome. Generalized transduction will remove Tn7 from a CAM-OCT alk::Tn7 plasmid to yield alk(+) cells which carry no Tp(r) determinant on the CAM-OCT plasmid (as shown by transfer of the plasmid to a second strain). But the transduction to alk(+) does not remove all Tp(r) determinants from the genome of the recipient cell because the alkane-positive transductants remain trimethoprim resistant. Thus, it appears that copies of Tn7 can accumulate in the genome of P. aeruginosa (CAM-OCT alk::Tn7) strains without leaving their original site. This result is consistent with transposition models that involve replication of the transposable element without excision from the original site.

Alkanes

Site of origin of 2,7-FAA-induced rat leukemia.

Oral administration of N,N'-2,7-fluorenylenebis-acetamide (2,7-FAA) induces mature granulocytic and erythroblastic leukemia in rats. We compared the primary site of mature granulocytic leukemia with that of erythroblastic leukemia. The nodular foci of solitary lesions and comspicuously large foci of scattered lesions were considered to be the primary site. They appeared mainly in the bone marrow of various bones. The primary site of mature granulocytic leukemia appeared more frequently in short bones than in long bones. On the contrary, that of erythroblastic leukemia appeared more frequently in long bones than in short bones. The origin of mature granulocytic leukemia seems to be concerned with bone tissue, while erythroblastic leukemia may have little relation with bone tissue.

2-Acetylaminofluorene

The fate mapping of the eleventh and twelfth day mouse otocyst: an in vitro study of the sites of origin of the embryonic inner ear sensory structures.

An experiment was undertaken to determine which sensory structures of the mouse embryo inner ear developed from what portion of the mouse otocyst. Otocysts of gestation days 10, 11, 12, and 13 were divided by surgical dissection into six anatomical groups: dorsal, ventral, anterior, posterior, medial and lateral halves. They were organ cultured separately. After a period of ten days, the explanted tissues were harvested and processed histologically for microscopic analysis. The surgical control specimens fixed at the time of explantation were composed of undifferentiated ectodermal cells for tissues of gestation days 10, 11, and 12. Otocysts of gestation days 11, and 12 showed, during the course of their subsequent growth, that the three semicircular ducts and their associated cristae developed from the dorsal and lateral halves. Only the anterior and posterior canals and cristae originated from the medial portion. The posterior half gave rise to the posterior crista and the anterior half provided for the development of the anterior and lateral cristae. The cochlear duct and its sensory epithelium developed in all the anatomical groups except the dorsal half. The utricle developed in the dorsal section of the middle third of the otocyst, while the utricular macula developed in the anterior half of the same section of the otocyst. The saccule and its macula differentiated from the ventral section of the middle third of the anterior half.

Animals

Human gastric pacesetter potential. Site of origin, spread, and response to gastric transection and proximal gastric vagotomy.

Gastric electrical activity was recorded from twenty-six patients at celiotomy. The human gastric pacemaker was localized to an area in the midcorpus along the greater curve. Pacesetter potentials were generated regularly by the pacemaker at a mean frequency of 3.2 cycles/min and were propagated circumferentially and aborally from the pacemaker, increasing in amplitude and velocity as they approach the pylorus. The pattern of pacesetter potenitals in patients with gastric ulcer, gastric cancer, and duodenal ulcer was similar to that of patients without such diseases. Complete transection of the gastric corpus isolated the distal stomach from the natural pacemaker and resulted in the appearance of a new pacemaker in the distal stomach with a slower frequency. The fact that proximal gastric vagotomy did not greatly alter the frequency of generation or the pattern of propagation of the pacesetter potential provided further evidence that both are myogenic phenomena.

Action Potentials

The site of origin of cardiac preganglionic fibers of the vagus nerve: an HRP study in the cat.

After injection of horseradish peroxidase (HRP) into the right cardiac branches of the vagus nerve in the cat, the majority of HRP-labeled neurons were located ipsilaterally in the reticular formation ventrolateral to the nucleus ambiguus. Additionally, HRP-labeled neurons were also observed within the nucleus ambiguus (Am) and the dorsal motor nucleus of the vagus nerve (DM).

Animals

Influence of site of origin of lung carcinomas on clinical presentation and central nervous system metastases.

A retrospective survey of 100 patients dying from carcinoma of the lung showed that neurological presentation and central nervous system metastases are more frequently present when the primary carcinoma is situated in the peripheral lung tissue (including lung apex). The high incidence of cases presenting neurologically and the high incidence of single secondary deposits involving the central nervous system from peripheral or apical growths suggest a difference in the mode of spread or other properties of such growths compared with the more common central carcinoma.

Adenocarcinoma

Site of origin of deep vein thrombus in the calf.

A phlebographic technique is described for demonstrating as fully as possible the stem and muscle veins of the calf. The findings in 103 examinations containing calf thrombus demonstrated by this method are presented. It is concluded that calf vein thrombosis is as likely to originate in stem veins as from the soleal muscle veins.

Clinical Trials as Topic

Possible sites of origin of human plasma ribonucleases as evidenced by isolation and partial characterization of ribonucleases from several human tissues.

The ribonucleases (RNases) present in a number of human tissues, including heart, brain, lung, and kidney, were purified, partially characterized, and compared in their properties to the previously described RNases from human liver, spleen, pancreas, and serum. The enzymes appeared to fall into two major classes: liver-spleen type RNase and plasma-type RNase. These two types of enzymes were present in varying proportions in all tissues examined. The extent to which the tissues studied possibly contribute to serum RNase levels is discussed.

Brain