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Biomedical subjects

E Schultz

Publications and source records attributed to E Schultz.

At least 55 records · Page 3Linked to original sources

Role of satellite cells in altering myosin expression during avian skeletal muscle hypertrophy.

This study examined whether satellite cells express an embryonic isoform of myosin upon fusion with hypertrophying muscle fibers. Anterior latissimus dorsi (ALD) muscle hypertrophy was induced in adult chickens by weighting one wing. One and 7 days of wing-weighting produced significant increases in ALD muscle wet weight and in the number of mature fibers expressing ventricular-like embryonic (V-EMB) myosin. V-EMB myosin expression could be an event during regeneration of fibers injured by overload or part of the hypertrophy process itself. Although there was an increase in both the number of damaged fibers and the number of mature fibers expressing embryonic myosin after wing-weighting, results from this study suggest that these two events were not necessarily related. The apparent health of fibers expressing V-EMB myosin and the lack of correlation between the numbers of damaged and V-EMB myosin positive fibers (r = 0.20) suggest that embryonic myosin expression in mature fibers was likely a feature of the hypertrophy process itself. The appearance of V-EMB myosin in mature fibers 1 day after wing-weighting suggests that the change in myosin expression did not involve satellite cells since 24 hr is too short a time to permit more than limited satellite cell fusion. The relationship between satellite cells and embryonic myosin expression was examined more closely by labeling dividing satellite cells and their progeny with 5-bromo-2-deoxyuridine, and then colocalizing labeled myofiber nuclei and embryonic myosin in consecutive transverse sections of hypertrophied ALD muscle. One week of wing-weighting resulted in marked increases in myofiber nuclear labeling index and myofiber nuclear density compared to contralateral control. V-EMB myosin was not expressed uniformly throughout individual fibers, but rather in discrete regions of varying length. Many V-EMB myosin positive regions had a higher labeled nuclear density than V-EMB myosin negative regions indicating that V-EMB myosin expression was associated with an accumulation of satellite cell progeny in a restricted area. However, it was also clear that satellite cell progeny were not the sole source of V-EMB myosin since labeled nuclei were completely absent from 41% of the V-EMB positive regions. Furthermore, the presence of new nuclei did not result in obligatory expression of embryonic myosin because many V-EMB negative regions had a high labeled nuclear density. Thus, recently incorporated nuclei arising by satellite cell division are implicated as one, but not the sole source of embryonic myosin in hypertrophying muscle.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Inhibition of soluble catechol-O-methyltransferase and single-dose pharmacokinetics after oral and intravenous administration of entacapone.

The inhibition of soluble catechol-O-methyl-transferase (S-COMT) in red blood cells (RBCs) by entacapone, and the pharmacokinetics of entacapone after single oral (5-800 mg) and i.v. (25 mg) doses have been examined in an open study in 12 healthy young male volunteers. Oral entacapone dose-dependently decreased the activity of S-COMT in RBCs with a maximum inhibition of 82% after the highest dose (800 mg). The inhibition of S-COMT in RBCs was reversible and the activity recovered within 4-8 h. Entacapone showed linear pharmacokinetics over the dose range studied: Cmax and AUC were correlated with the dose of the drug. Oral absorption of entacapone was fast, with a tmax ranging from 0.4 to 0.9 h, depending on the dose. Systemic availability of entacapone varied between 30 and 46%. Entacapone was rapidly eliminated by metabolism with a half-life of 0.27-0.30 h after oral doses of 5 to 50 mg. After doses from 100 to 800 mg the disposition was best described by two phases with a t1/2 alpha of 0.27-0.37 h and t1/2 beta of 1.59-3.44 h. Over the dose range studied, the single oral and i.v. doses of entacapone were well tolerated. No haematological, biochemical or haemodynamic adverse effects were seen. The results show that entacapone is an orally effective and reversible COMT inhibitor in man and has simple, linear pharmacokinetics.

Administration, Oral↗

Case report 872. "Ancient" schwannoma (degenerated neurilemoma).

A case of an ancient schwannoma was presented. The rare occurrence of this tumor has resulted in only a few reported cases with descriptions of its features on imaging. Our patient's tumor, like one previously reported case, demonstrated calcification on the plain film - a finding not associated with other histologic types of schwannomas. Angiography revealed the tumor to be hypervascular. Evaluation by MRI demonstrated a lobulated, encapsulated soft tissue mass containing several cystic areas that corresponded histologically to areas of necrosis. Hypertrophied blood vessels were seen in the periphery of the tumoral mass. Too few ancient schwannomas have been reported to conclude whether or not radiographic evidence of soft tissue calcification is characteristic of this histologically distinctive subtype of schwannoma. However, since calcification is seen histologically as part of the degenerating process, its presence on plain films could be a feature of this tumor. Furthermore, the presence of cystic areas on MRI is not surprising given the pathological changes that occur in this tumor. We suggest that a diagnosis of ancient schwannoma be considered when a patient presents with a hypervascular soft tissue mass containing amorphous calcification on plain films and cystic areas on MRI. Despite the nonspecificity of these imaging findings, this point is relevant because each of these features suggests the presence of a malignant mass. Awareness of the possibility of a benign ancient schwannoma could obviate unnecessary radical surgery.

Diagnosis, Differential↗

Skeletal muscle satellite cells.

Evidence now suggests that satellite cells constitute a class of myogenic cells that differ distinctly from other embryonic myoblasts. Satellite cells arise from somites and first appear as a distinct myoblast type well before birth. Satellite cells from different muscles cannot be functionally distinguished from one another and are able to provide nuclei to all fibers without regard to phenotype. Thus, it is difficult to ascribe any significant function to establishing or stabilizing fiber type, even during regeneration. Within a muscle, satellite cells exhibit marked heterogeneity with respect to their proliferative behavior. The satellite cell population on a fiber can be partitioned into those that function as stem cells and those which are readily available for fusion. Recent studies have shown that the cells are not simply spindle shaped, but are very diverse in their morphology and have multiple branches emanating from the poles of the cells. This finding is consistent with other studies indicating that the cells have the capacity for extensive migration within, and perhaps between, muscles. Complexity of cell shape usually reflects increased cytoplasmic volume and organelles including a well developed Golgi, and is usually associated with growing postnatal muscle or muscles undergoing some form of induced adaptive change or repair. The appearance of activated satellite cells suggests some function of the cells in the adaptive process through elaboration and secretion of a product. Significant advances have been made in determining the potential secretion products that satellite cells make. The manner in which satellite cell proliferative and fusion behavior is controlled has also been studied. There seems to be little doubt that cellcell coupling is not how satellite cells and myofibers communicate. Rather satellite cell regulation is through a number of potential growth factors that arise from a number of sources. Critical to the understanding of this form of control is to determine which of the many growth factors that can alter satellite cell behavior in vitro are at work in vivo. Little work has been done to determine what controls are at work after a regeneration response has been initiated. It seems likely that, after injury, growth factors are liberated through proteolytic activity and initiate an activation process whereby cells enter into a proliferative phase. After myofibers are formed, it also seems likely that satellite cell behavior is regulated through diffusible factors arising from the fibers rather than continuous control by circulating factors.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Acute effects of hindlimb unweighting on satellite cells of growing skeletal muscle.

The proliferative behavior of satellite cells in growing rat soleus and extensor digitorum longus muscles was examined at short periods after initiation of hindlimb unweighting. Mitotic activity of satellite cells in both muscles decreased below weight-bearing control levels within 24 h of initiation of hindlimb unweighting. This satellite cell response was > or = 48 h before any atrophic morphological changes that take place in the muscles. Suppression of mitotic activity was most severe in the soleus muscle where continuous infusion of label demonstrated that virtually all mitotic activity was abolished between 3 and 5 days. The results of this study suggest that satellite cell mitotic activity is a sensitive indicator of primary atrophic changes occurring in growing myofibers and may be a predictor of future morphological changes.

Animals↗

Quantitation of satellite cell proliferation in vivo using image analysis.

A nonisotopic, double fluorescence technique was developed to study myogenic satellite cell proliferation in posthatch turkey skeletal muscle. Labeled satellite cell nuclei were identified on enzymatically isolated myofiber segments using a mouse monoclonal antibody (anti-BrdU) followed by fluorescein-5-isothiocyanate (FITC) conjugated goat anti-mouse IgG secondary antibody. Myofiber nuclei (myonuclei+satellite cell nuclei) were counterstained with propidium iodide (PI). The myofiber segment length, myofiber segment diameter, and the number of PI and FITC labeled nuclei contained in each segment was determined using a Nikon fluorescence microscope, a SIT video camera and Image-1 software. Data collected by three different operators of the image analysis system revealed 5.0 +/- 1.4 satellite cell nuclei per 1000 myofiber nuclei and 5284 +/- 462 microns3 of cytoplasm surrounding each myofiber nucleus in the pectoralis thoracicus of 9-week-old tom turkeys. BrdU immunohistochemistry coupled with the new approach of PI staining of whole myofiber mounts is an effective combination to allow the use of an efficient semi-automated image analysis protocol.

Animals↗

Satellite cell mitotic activity in posthatch turkey skeletal muscle growth.

The relationship between satellite cell mitotic activity and skeletal myofiber growth was examined in Pectoralis thoracicus and Biceps femoris muscles of Large White tom turkeys (Nicholas strain) at 3, 6, 9, 18, and 26 wk of age. Mitotically active satellite cells were labeled with 5-bromo-2'-deoxyuridine (BrdU). Labeled satellite cells were identified on enzymatically isolated myofiber segments using mouse anti-BrdU followed by fluorescein-5-isothiocyanate (FITC) conjugated goat anti-mouse IgG secondary antibodies. Myofiber nuclei (satellite cell nuclei + myonuclei) were counterstained with propidium iodide (PI). Myofiber segment diameter, myofiber segment length, and number of FITC- and PI-labeled nuclei were determined for each segment. At each age interval there was an increase in myofiber diameter, suggesting that the myofibers were growing during the entire experimental period. There was an age-related (P < .001) decrease in satellite cell mitotic activity and an age-related increase (P < .001) in the cytoplasmic volume to nucleus ratio (CNR) from 3 to 26 wk of age. An early phase of myofiber growth, between 3 and 6 wk of age, was characterized by a high level of satellite cell mitotic activity and increased CNR. Between 6 and 9 wk of age, satellite cell mitotic activity decreased, but the CNR showed no change (P > .05). During a late phase of myofiber growth, beyond 9 wk of age, satellite cell mitotic activity continued to decrease and myofiber growth occurred by an increased CNR. This study demonstrated that both Pectoralis thoracicus and Biceps femoris undergo a significant late phase of growth without appreciable production of myonuclei by satellite cell proliferation.

Age Factors↗

[Follow-up of schizoaffective psychoses in adolescence].

Of 156 adolescent inpatients with psychotic disorders (ICD-9: 295.0 to 296.9), 25 had a schizoaffective psychosis with onset before age 18. Of these, 21 were followed up an average of 6.5 years later. Six of the subjects had had only one schizoaffective episode and 15 had had a second episode an average of 14 months later. Half of the subjects had had schizoaffective episodes only. More of the patients with an initial affective episode developed schizoaffective psychosis than of those with an initial schizophrenic episode. On average there had been 0.91 episodes per year during the follow-up period. Seventy-one percent of the subjects had been unable to continue their education or work at the previous level and most had marked deficits in social adaptation. The level of social competence at the end of the first episode was of predictive value for the later social handicap. A comparison with other groups of patients of the same age showed that those with affective disorders had faired better and those with schizophrenia appeared to have the poorest outcome. The schizoaffective group tended to resemble the schizophrenic group more closely than the affective group. Patients whose schizoaffective disorder began in adulthood had fewer problems on the educational and occupational level, better social adaptation and fewer episodes per year and had spent less time in inpatient treatment than those whose disorder had begun before age 18.

Adolescent↗

Cytokine gene transcription in renal cell carcinoma.

Cytokines are powerful modulators of immune responses, the local production of which could be relevant to the interaction between tumour and immune system. This study investigated the transcription of genes encoding interleukin (IL) 2, IL-4, IL-10 and interferon (IFN) gamma in lymphocyte-infiltrated renal cell carcinoma biopsies from ten patients using the reverse polymerase chain reaction technique. Autologous peripheral blood mononuclear cells and healthy renal parenchyma tissue were tested in parallel. The beta-actin gene, used as a positive control, was transcribed in all samples. In contrast, transcription of cytokine genes was confined to tumour biopsies: IL-2 gene transcripts were detectable in five biopsies and IL-10 transcripts in seven. IL-4 and IFN-gamma gene transcripts were detectable in one biopsy each. In two patients no cytokine gene transcription could be identified. These data underline that heterogeneous patterns of cytokine gene transcription can be observed in renal cell carcinoma biopsies. Although transcription of an immunostimulatory lymphokine such as IL-2 was observed in 50 per cent of biopsies, the most frequently transcribed cytokine gene coded for an inhibitory factor, IL-10.

Aged↗

Detection of a deep lipoblastoma by MRI and ultrasound.

Lipoblastoma is a rare benign tumor of the soft tissue occurring predominantly during the first two years of life. We report here the application of MRI and ultrasound to the detection of a soft tissue lipoblastoma. By MRI and ultrasound, we precisely evaluated the extent of the tumor, the presence of atypical areas of cystic and mucoid degeneration within the tumor, and its lack of vascularity. Our patient's lipoblastoma did not demonstrate the signal characteristics of a fatty tumor on MRI.

Humans↗

Dystrophin expression improves myofiber survival in mdx muscle following intramuscular plasmid DNA injection.

Expression of Becker-like and full-length human dystrophins was stable for at least 6 months in mdx mouse muscle following intramuscular plasmid DNA injection. Intramuscular injection of a single plasmid DNA encoding both luciferase and dystrophin resulted in stable luciferase expression for at least 2 months in mdx muscle, whereas injection of plasmid DNA encoding only luciferase did not result in stable luciferase expression. These results suggest that expression of either full-length or Becker-like dystrophins protects mdx mouse myofibers from degeneration.

Animals↗

Pulmonary hypertensive response to rabbit blood components in goats: role of thromboxane.

Transfusion of small quantities of heterologous blood may cause severe pulmonary hypertensive response in certain species. To determine the responsible component in the donor blood and the main mediator, we studied the responses of goats to small quantities of rabbit blood components and observed the effects of several pharmacologic agents on these responses. In anesthetized goats, a bolus injection of 0.004 ml/kg rabbit blood caused the pulmonary arterial pressure to increase from 25.3 +/- 2.8 to 57.1 +/- 11.6 cm H2O within 45 to 90 s, and the aortic thromboxane concentration rose from 44 +/- 38 to 238 +/- 104 pg/ml. Pulmonary vascular resistance increased more than 4-fold, whereas systemic vascular resistance increased moderately (50%). The erythrocyte stroma, mainly cell membranes, caused similar responses; other blood components were all ineffective. By blocking the production of thromboxane, indomethacin and U63557A (thromboxane synthetase inhibitor) abolished nearly all of the hemodynamic responses to rabbit blood. Isoproterenol also largely attenuated the responses to rabbit blood by blocking thromboxane production without interfering with the responses to the thromboxane mimic U46619. Nitrendipine (calcium-channel blocker) equally attenuated rabbit blood and U46619-induced hemodynamic responses but did not block thromboxane production. Chlorpheniramine (H1-receptor antagonist) partially blocked the hemodynamic responses to rabbit blood without affecting thromboxane production or U46619-induced responses. We conclude that the erythrocyte membrane is the responsible component in the donor blood and thromboxane is the predominant mediator. The main action of isoproterenol is to reduce thromboxane production and histamine participates by possible interaction with cyclooxygenase products.

Animals↗

Co-transplantation of plasmid-transfected myoblasts and myotubes into rat brains enables high levels of gene expression long-term.

We have previously proposed the use of primary muscle cells as a "platform," or "vehicle" for intracerebral transgene expression. Brain grafts of minced muscle, or cultured muscle cells persisted in rat brains for at least 6 mo without any decrease in graft size, or tumor formation. Stable, but moderate levels of intracerebral transgene expression were obtained by transplanting plasmid-transfected myotubes in culture. In the present study, high and stable levels of intracerebral transgene expression were achieved by the co-transplantation of plasmid-transfected myoblasts and myotubes in culture. Approximately 5 X 10(5) myoblasts and myotubes were transfected with 10 micrograms pRSVL plasmid DNA, and 30 micrograms Lipofectin (BRL), respectively. They were mixed together (total cell number was 1 million), and stereotactically injected into the caudate nucleus of an adult rat brain. The activity of luciferase, the product of transgene expression, was stable for at least 4 mo, and much higher than the levels in myotube grafts, or co-grafts of myoblasts and minced muscle. Presumably, the myotubes served as a framework on which the myoblasts can form myotubes. The sections of brains transplanted with co-graft of myoblasts, and myotubes transfected with pRSVLac-Z were stained immunofluorescently for beta-galactosidase activity. The muscle grafts contained beta-galactosidase positive myofibers 4 mo after transplantation. Such high and stable levels of in vivo expression after postnatal gene transfer have rarely been achieved. Primary muscle cells are useful vehicle for transgene expression in brains, and potentially valuable for gene therapy of degenerative neurological disorders.

Animals↗

A simple hindlimb suspension apparatus.

This paper describes the assembly of a simple, inexpensive apparatus for application of the hindlimb suspension model to studies of the effects of unloading on mammalian physiology. Construction of a cage and suspension assembly is described using materials that can be obtained from most hardware stores. The design is kept simple for easy assembly and disassembly to facilitate cleaning and storage. The suspension assembly allows the animals full access to all portions of the floor area and provides an effective environment to study the effects of unloading.

Animals↗

Intracerebral transplants of primary muscle cells: a potential 'platform' for transgene expression in the brain.

After the transplantation of rat primary muscle cells into the caudate or cortex of recipient rats, the muscle cells were able to persist for at least 6 months. Muscle cells transfected with expression plasmids prior to transplantation were able to express reporter genes in the brains for at least 2 months. These results suggest that muscle cells might be a useful 'platform' for transgene expression in the brain.

Animals↗