Myoneural junctions and toxic agents

Denz, F. A.

doi:10.1002/path.1700630206

Cited by 7 publications

(1 citation statement)

References 27 publications

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“…Toxicants that were shown to exert their disruptive effects at the intercellular junctions in target organs, including cells and tissues, such as at the neuromuscular interface, between embryonic mesenchymal cells during development possibly to perturb intercellular communication, were first reported in the 1950s and 1980s [ 1 , 2 , 3 , 4 ]. Interestingly, toxicants that exert their disruptive effects at the cell-cell interface, most notably in cell junctions (or cell adhesion sites) in testicular cells, such as Sertoli cells, germ cells, and Leydig cells, which in turn lead to defects in spermatogenesis and male reproductive dysfunction, were not found in the literature until the 1980s and 1990s [ 5 , 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Cell-Cell Interaction-Mediated Signaling in the Testis Induces Reproductive Dysfunction—Lesson from the Toxicant/Pharmaceutical Models

Wang

et al. 2022

Cells

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Emerging evidence has shown that cell-cell interactions between testicular cells, in particular at the Sertoli cell-cell and Sertoli-germ cell interface, are crucial to support spermatogenesis. The unique ultrastructures that support cell-cell interactions in the testis are the basal ES (ectoplasmic specialization) and the apical ES. The basal ES is found between adjacent Sertoli cells near the basement membrane that also constitute the blood-testis barrier (BTB). The apical ES is restrictively expressed at the Sertoli-spermatid contact site in the apical (adluminal) compartment of the seminiferous epithelium. These ultrastructures are present in both rodent and human testes, but the majority of studies found in the literature were done in rodent testes. As such, our discussion herein, unless otherwise specified, is focused on studies in testes of adult rats. Studies have shown that the testicular cell-cell interactions crucial to support spermatogenesis are mediated through distinctive signaling proteins and pathways, most notably involving FAK, Akt1/2 and Cdc42 GTPase. Thus, manipulation of some of these signaling proteins, such as FAK, through the use of phosphomimetic mutants for overexpression in Sertoli cell epithelium in vitro or in the testis in vivo, making FAK either constitutively active or inactive, we can modify the outcome of spermatogenesis. For instance, using the toxicant-induced Sertoli cell or testis injury in rats as study models, we can either block or rescue toxicant-induced infertility through overexpression of p-FAK-Y397 or p-FAK-Y407 (and their mutants), including the use of specific activator(s) of the involved signaling proteins against pAkt1/2. These findings thus illustrate that a potential therapeutic approach can be developed to manage toxicant-induced male reproductive dysfunction. In this review, we critically evaluate these recent findings, highlighting the direction for future investigations by bringing the laboratory-based research through a translation path to clinical investigations.

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Section: Introductionmentioning

confidence: 99%

Cell-Cell Interaction-Mediated Signaling in the Testis Induces Reproductive Dysfunction—Lesson from the Toxicant/Pharmaceutical Models

Wang

et al. 2022

Cells

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Lymphocytes of Patients With Myasthenia Gravis

Namba¹

1969

Arch Neurol

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ERUM globulin, particularly the IgG fraction, of patients with myasthenia gravis reacts with skeletal muscle, cardiac muscle and thymic epithelial cells, as well as nuclei of various tissues.1-7 These findings indicate a possible role of the serum globulin in the pathogenesis of myasthenia gravis. However, there is no evidence that the serum globulin is directly responsible for the neuromuscular block in myasthenic patients; in fact, after administration of serum from patients with high titers of muscle antibody to other myasthenic patients, neuromuscular transmission improved, suggesting that the globulin may exert a protective effect.8,9There have been only a few studies on lymphocytes in myasthenia gravis. Tissue culture of lymphocytes of myasthenic patients responded normally in deoxyribonucleic acid synthesis and blast transformation to stimulation by phytohemagglutinin,10 responses considered to be indicative of the immunological competence of lymphocytes. Delayed hypersensitivity induced by 1-chloro-2, 4-dinitrobenzene, which is mediated by lymphocytes, has been reported to be either reduced11 or normal12 in patients with myas¬ thenia gravis.We have found that lymphocytes of myas¬ thénie patients caused a more severe system¬ ic graft-versus-host reaction in mice than normal human lymphocytes.13 In the pres¬ ent study, the local effect of lymphocytes of patients with myasthenia gravis on rats has been evaluated. Materials and MethodsCirculating lymphocytes were isolated by ster¬ ile procedures from the blood of myasthénie patients, normal humans, and rabbits, according to the method of Coulson and Chalmers.14 Isolated lymphocytes with a purity of 96% to 99% were resuspended to a final concentration of 15,000 cells per cubic millimeter in medium 199, a culture medium with known chemical composition. Suspensions of erythrocytes from myasthénie patients and from normal humans were prepared during the isolation of lympho¬ cytes, and the erythrocyte concentration in medium 199 was adjusted to the concentration of the lymphocyte suspension. Serum was sepa¬ rated from coagulated blood by centrifugation.The patients studied in this investigation are described in Table 1. Prior to obtaining blood, medication was withheld for at least 12 hours, and, when necessary, respiration was supported mechanically. Normal human blood was ob¬ tained from one woman and four men, age 22 to 43 years. Blood was also obtained from five normal rabbits and four rabbits that had been immunized with a saline extract of rat skeletal muscle. The extract was the supernatant ob¬ tained by centrifugation for 15 minutes at 13,-000 X g of a homogenate of a mixture of one part by weight of rat skeletal muscle and five parts by volume of physiologic saline. Equal volumes of the extract and Freund's complete adjuvant were mixed, and 0.2 ml of the mixture was injected into the footpads of rabbits once every two weeks for 12 weeks. An additional intravenously administered booster injection of 0.5 ml of extract was given one week before obtaining blo...

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Some morphological features of the myoneural junctions in certain normal muscles of the rat

1974

Anat. Rec.

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In frozen sections and whole mount preparations of the normal soleus, diaphragm, or intercostal muscles of the rat, myoneural junctions of different AChE and silver staining intensities were regularly observed. Muscle fibers of different diameters showed end-plates of varying staining intensities. No correlation was found between a certain staining intensity and diameter of the end-plates or between muscle fiber diameters and the ratio of pale to strongly stained end-plates. There was, however, a tendency for the smaller muscle fibers to have end-plates of smaller mean diameter than those in the larger muscle fibers.

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Myoneural junctions and toxic agents

Cited by 7 publications

References 27 publications

Cell-Cell Interaction-Mediated Signaling in the Testis Induces Reproductive Dysfunction—Lesson from the Toxicant/Pharmaceutical Models

Cell-Cell Interaction-Mediated Signaling in the Testis Induces Reproductive Dysfunction—Lesson from the Toxicant/Pharmaceutical Models

Lymphocytes of Patients With Myasthenia Gravis

Some morphological features of the myoneural junctions in certain normal muscles of the rat

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