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M Seiler

Publications and source records attributed to M Seiler.

33 records · Page 2Linked to original sources
PubMed1988

The activities of host and graft glial cells following retinal transplantation into the lesioned adult rat eye: developmental expression of glial markers.

We have studied the time course of the expression of glial fibrillary acidic protein (GFAP) and S-100 developmentally regulated proteins in host and graft tissue after transplantation of rat E15 retina to retinal lesion sites of adult rat hosts. Host Müller cell reactivity (GFAP staining) appeared in the peripheral retina 4.5 h after the lesion apparently in response to axotomy of the retinal ganglion cells, and then spread out in a declining wave over the whole dorsoventral extent of the retina within 1 day. From 2 days after transplantation, host glial cells appeared to migrate into the graft along the open host/graft interface, graft surfaces and blood vessels (at 8 days). Intrinsic graft glial cells (mostly Müller cells) developed approximately according to a normal time-table, but became partially reactive at 3 weeks and completely reactive at 5 weeks after transplantation. However, this reactivity seemed to have no effect on the formation of retinal laminae. Bipolar graft Müller cells were found most frequently in graft rosettes, forming an external limiting membrane around receptor inner segments, but no continuous inner limiting membrane on the vitreal surface. This was probably due to the disruption of the inner limiting membrane during transplantation, the lack or scarcity of ganglion cells or the random distribution of astrocytes in the graft.

Animals↗
PubMed1988

Retinal transplants and optic nerve bridges: possible strategies for visual recovery as a result of trauma or disease.

From the review of the current literature it is quite evident that some exciting prospects are on the horizon which will help to better explain the development and functioning of the visual system. In addition, the new technology of CNS tissue grafting coupled to other newly emerging technologies (i.e., microsurgical, microinjection, and micromanipulative techniques coupled with our knowledge of immunosuppressive methods) will allow for a realistic approach in exploring possible strategies for visual recovery as a result of trauma or disease within the near future. One specific area of research that hopefully will emerge from this new body of knowledge comes from the realization that at the present time there is no effective therapy for practically all types of hereditary retinal degenerative disorders in man. It would seem most appropriate to take advantage of the new neuronal transplantation technology mentioned in this article and the availability of hereditary retinal degeneration models in the hope of developing new methods for a therapeutic approach to this problem. Such an approach could involve replacing the abnormal, absent, and/or lost host retinal cells with tissue from healthy donors by means of a grafting technique with the goal of arresting and/or reversing the disease process. Of course, this is but one example of the many challenges in this area of research which increasingly appear to be within our grasp.

Animals↗
PubMed1988

Donor age influences on the success of retinal grafts to adult rat retina.

The rat retina can be successfully grafted within a long time period which extends into the first 2 weeks of postnatal life. Postnatal grafts taken 1-2 days (PN 1-2) after birth demonstrate no significant differences in their ability to form successful grafts. However, grafting success begins to diminish gradually starting between PN 2-4 and reaches a low point in organization and survival by PN 14. PN 21 grafts rapidly degenerate by 1 to 2 days after transplantation. Although early postnatal retinal tissue can be successfully grafted, E 15 embryonic retinas make better grafts for their ability to form consistent laminae and to integrate with host tissue in a fresh lesion paradigm.

Age Factors↗
PubMed1987

Nocodazole irreversibly reduces the capacity of rapid axoplasmic transport in vitro.

Using the frog sciatic nerve as an in vitro model system, the effects of 10(-5) M nocodazole, an antimitotic drug, on rapid axoplasmic transport were quantified and tested for reversibility. After pulse-labeling the 8th dorsal root ganglia with [3H]leucine, the nerves were incubated for 4.5 to 9 hr at 25 degrees C. Transport velocities and amounts of transported material were determined from the distribution of radioactively labeled proteins. One nerve per animal served as a control. Before ganglia labeling, the nerves were preincubated for 1 or 15 hr in 10(-5) M nocodazole, respectively. In one set of experiments, the nerves were preincubated in nocodazole for 6 hr washed for 1.5 hr and further treated in Ringer's solution to test for reversibility. We found that nocodazole did not affect the maximal transport velocity under any of the conditions tested. The amounts of rapidly transported material were reduced to 60% of controls after 1 hr of pretreatment with nocodazole, and to 30% after 6 to 15 hr of pretreatment. There was no indication for a reversibility of these effects. We conclude that 10(-5) M nocodazole shows maximal effects on rapid axoplasmic transport only if given several hours before protein synthesis, and that it reduces the capacity of rapid axoplasmic transport without affecting transport velocity. These effects are not reversible during the survival time of the in vitro preparation.

Animals↗
PubMed1987

Structural and metabolic correlates of cell injury in the hypertrophied myocardium during valve replacement.

To characterize the ultrastructural and metabolic changes occurring in the hypertrophied ventricle during cardiac operations in man, we studied 36 patients with valvular heart disease undergoing valve replacement, during which multiple doses of cold potassium cardioplegic solution were administered (Group I). Each patient had substantial ventricular hypertrophy according to measurements made of left ventricular mass, with a mean of 232.1 +/- 19.8 gm/m2 (normal: 92 +/- 16 gm/m2). Serial biopsy specimens were obtained from the left ventricular apex at the initiation of bypass, during the cross-clamp interval, and during reperfusion. Each specimen was scored from 0 to 4 according to ischemic changes in nuclear chromatin, mitochondrial swelling, myofibrillar edema, glycogen depletion, and overall cell morphology. Myocardial pH and temperature were measured continuously in the left ventricular free wall. During the cross-clamp period, ischemic injury was evidenced by changes in nuclear chromatin (0.38 +/- 0.10 to 1.25 +/- 0.21, p less than 0.0001), intracellular edema (0.43 +/- 0.06 to 0.97 +/- 0.14, p less than 0.002), overall cell morphology (0.37 +/- 0.06 to 0.97 +/- 0.14, p less than 0.001), and mitochondria (0.10 +/- 0.05 to 0.19 +/- 0.07, p less than 0.0001). During reperfusion, mitochondrial swelling increased further (0.19 +/- 0.07 to 0.35 +/- 0.08, p less than 0.0001) and glycogen stores were depleted (0.63 +/- 0.13 to 0.96 +/- 0.17, p less than 0.02), while the other structures remained unchanged. Myocardial pH declined during ischemic arrest from 6.89 +/- 0.04 to 6.40 +/- 0.04 (p less than 0.001). The changes in myocardial pH in Group I were compared to changes in myocardial pH in 10 patients (Group II) with no left ventricular hypertrophy undergoing isolated coronary bypass graft operations with the same protective techniques. In contrast to Group I, myocardial pH did not fall in Group II during ischemic arrest (6.98 +/- 0.06 to 6.94 +/- 0.05, p = not significant). Thus, with the use of current myocardial protective techniques, ultrastructural and metabolic changes indicative of ischemia are produced in the hypertrophied myocardium. The structural alterations consist of changes in nuclear chromatin and intracellular edema during the ischemic phase and by mitochondrial swelling during reperfusion.

Adult↗
PubMed1985

High yield-purification of a urinary Na+-pump inhibitor.

A Na+-pump inhibitor was purified from 140 liters of human urine to an apparent homogeneity. Tracing of the inhibitor during the different steps of purification was achieved by simultaneous determination of its capacity to inhibit the activity of Na+,K+-ATPase and ouabain binding, and to cross-react with antidigoxin antibodies. The final purification achieved a 400,000 fold. The purification steps included flash chromatography, anionic exchange chromatography, and reversed-phase HPLC on RP18, diphenyl and phenyl packings. NMR studies indicated that the final product was a non-peptidic, possibly steroidal compound. Its molecular weight as determined by mass spectrometry was 431.

Animals↗
PubMed1984

Specific retrograde transport of nerve growth factor (NGF) from neocortex to nucleus basalis in the rat.

[125I]labeled NGF injected in very small quantities into the frontal or dorsal anterior occipital cortex of adult rats, was specifically taken up and transported retrogradely to large, presumably cholinergic neurons in the nucleus basalis region (lateral preoptic nucleus, anterior lateral hypothalamic nucleus, substantia innominata, ventral globus pallidus and internal capsule), as revealed by light microscopic autoradiography. Cells projecting to the injection site in the frontal cortex were localized ipsilaterally in the more caudal parts of the nucleus basalis region, whereas cells projecting to the dorsal anterior occipital cortex could be found throughout the entire extent of the nucleus basalis and also in the vertical and horizontal limb of the nucleus of the diagonal band of Broca. Other nuclei known to project to the cortex (locus coeruleus, substantia nigra, nucleus raphe, thalamus) were consistently found to be unlabeled. In contrast to [125I]NGF, injection of [125I]cytochrome C failed to label any cell bodies in the basal forebrain nuclei by retrograde transport. This high selectivity for uptake and retrograde transport of NGF indicates the presence of membrane receptors for NGF or a closely related molecule on these cholinergic neurons of the basal forebrain innervating the cerebral cortex.

Animals↗
PubMed1983

The effect of the duodenal ulcerogen cysteamine on somatostatin and gastrin cells in the rat.

Previous studies showed a rapid decrease of somatostatin concentration in the gut and an increase in serum gastrin levels after a single dose of the duodenal ulcerogen cysteamine. An attempt was made to identify morphologic changes that would correlate with these functional changes. Rats were killed 1, 4, 8, or 24 hr after a single dose of cysteamine and sections of gastric mucosa and pancreas were processed for electron and light microscopy. Subtle ultrastructural alterations were seen in D cells of the stomach (e.g., dilation of mitochondrial cristae and endoplasmic reticulum, and apparent increase in electron density of secretory granules) after cysteamine administration. The number of somatostatin-positive cells visualized by the immunoperoxidase technique using light microscopy was decreased in 1-4 hr but returned to normal by 24 hr. The alterations observed in the G cells after cysteamine administration are consistent with release of gastrin from mature granules and increased synthesis of the hormone. The lack of major morphologic changes in the D cells suggests that cysteamine affects somatostatin without causing cell necrosis or alteration in lysosome formation. The effect of the drug may thus be mediated at the biochemical level without marked morphologic alterations.

Animals↗
PubMed1983

Time course of ischemic alterations during normothermic and hypothermic arrest and its reflection by on-line monitoring of tissue pH.

Currently there are no techniques available for the intraoperative on-line assessment of the adequacy of myocardial preservation during cardiac operation. The efficacy of a new intramyocardial pH electrode in quantitating myocardial ischemic damage and monitoring myocardial preservation was investigated by correlating changes in intramyocardial pH with the time course of metabolic, histologic, and ultrastructural alterations during global ischemia. Seventeen open-chest dogs were placed on cardiopulmonary bypass and the aorta was cross-clamped for 2 hours. In Group I (n = 8), aortic cross-clamping was performed under normothermia. Group II (n = 9) received 4 degrees C potassium cardioplegia immediately after cross-clamping and consecutively every 30 minutes thereafter. Intramyocardial carbon dioxide tension (Pco2) and intramyocardial pH were measured continuously. Serial transmural biopsies were obtained before and at 5, 15, 30, 60, 90, and 120 minutes after cross-clamping for biochemical and structural analysis. During the period of cross-clamping, mean myocardial temperature was 33 degrees C in Group I and 19 degrees C in Group II. Intramyocardial pH at the end of 2 hours of anoxic arrest reached 5.39 +/- 0.08 in Group I and 6.49 +/- 0.13 in Group II (both values p less than 0.01 compared to prebypass values). Intramyocardial Pco2 rose from 41 +/- 4 to 234 +/- 13 mm Hg in Group I (p less than 0.001) and did not change in Group II. Tissue content of adenosine triphosphate (ATP) decreased by 51% in Group I and by 14% in Group II (p less than 0.01 compared to prebypass value). Tissue creatine phosphate was depleted in Group I and decreased by 48% in Group II. The degree of ischemic damage assessed by a mean ischemic score was 2.15 +/- 0.06 in Group I and 0.75 +/- 0.19 in Group II (p less than 0.001). Irreversible structural damage assessed by electron microscopy occurred in Group I 60 to 90 minutes after cross-clamping and was associated with an intramyocardial pH below 6.2. No such damage was observed in Group II. Therefore, intramyocardial pH is shown to be a reliable indicator of the severity of ischemic damage during anoxic arrest under normothermic conditions and of the adequacy of preservation under hypothermic conditions. Measurement of intramyocardial pH may provide a potentially useful tool for the intraoperative on-line monitoring of the adequacy of myocardial preservation in patients undergoing cardiac operation.

Adenosine Triphosphate↗
PubMed1977

Developmental effects of exposing Drosophila embryos to ether vapour.

Drosophila embryos at precise developmental stages were exposed to ether vapour. The defects in the resulting embryos and adults were observed. Ether disrupted embroygenesis in specific ways, causing defects primarily at the anterior of the embryo and disorganizing the arrangement of the segments. Adults showed deficiencies and duplications of many imaginal disc and histoblast derivatives. Phenocopies of the bithorax mutation which transforms metathorax to mesothorax were observed. They were first induced at the syncytial blastoderm stage, had their peak of production at the cellular blastoderm, and were no longer observed after the anterior and posterior midgut were partially invaginated. It was observed that not only are the halter/wing transformations confined to the anterior compartment, but also leg 3 to leg 2 transformations only occurred in the anterior leg compartment.

Animals↗
PubMedDate not supplied

Ultrastructural circuitry in retinal cell transplants to rat retina.

The development of five transplants of fetal retinal tissue to adult rat eyes was examined with the electron microscope. The transplants were of 9 to 10 weeks total age after conception in four cases and 20 weeks in one case. They were at stage E15 when transplanted. Transplants developed in both the epiretinal and subretinal spaces. The transplants were heterogeneously developed with some parts showing almost normal differentiation and others little. Subretinal transplants examined in this study were more developed than epiretinal grafts. Photoreceptor cells developed both inner and outer segments. Their synaptic terminals possessed output ribbon synapses with postsynaptic processes similar to those seen in normal retinas. In regions corresponding to the inner plexiform layer, the adult complement of synapses was seen, including advanced features such as serial synapses as well as reciprocal synapses at bipolar cell dyads. Incompletely differentiated synapses of both the amacrine and bipolar cell types were often observed, especially in the rat epiretinal transplants. Ganglion cell processes could not be identified with certainty. Although transplant cells were adjacent to host photoreceptor cells and pigment epithelium, obvious specializations or interactions were not observed. The experiments suggest that embryonic rat retinal cell transplants develop most or perhaps all of the structural components and neuronal circuitry necessary to transduce light and process some visual information.

Animals↗