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J Schmidt

Publications and source records attributed to J Schmidt.

At least 487 records · Page 27Linked to original sources
PubMed1992

Elevated p53 RNA expression correlates with incomplete osteogenic differentiation of radiation-induced murine osteosarcomas.

An important role for the p53 gene in osteogenic sarcomas has been imputed by identification of somatically acquired gene alterations in human osteosarcomas and by the development of osteosarcomas in p53 transgenic mice. To study the involvement of p53 in radiation-induced osteosarcomagenesis, we have investigated gene alterations and expression of p53 in radiation-induced murine osteosarcomas and tumor-derived cell lines. Eighteen of 31 tumors and 8 of 9 cells lines showed alterations in the p53 gene region, or elevated levels of p53 RNA. Expression of the osteoblast marker gene bone gla protein was substantially reduced in tumors which simultaneously showed high steady-state levels of p53 RNA. Our data indicate that p53, in addition to its function in regulating DNA synthesis, may be involved in the control of osteogenic differentiation in osteosarcomagenesis.

Animals↗
PubMed1992

Purification and characterization of seven chloroplast ribosomal proteins: evidence that organelle ribosomal protein genes are functional and that NH2-terminal processing occurs via multiple pathways in chloroplasts.

Putative genes for 21 ribosomal proteins (RPs) have been identified in the chloroplast DNA of four plants by nucleotide sequencing and homology comparison but few of the gene products have been characterized. Here we report the purification and N-terminal sequencing of seven proteins from the spinach chloroplast ribosome. The data show them to be the homologues of Escherichia coli RPs L20, L32, L33, L36, S12, S16 and S19, and thus support the view that their genes identified in the chloroplast DNA represent functional genes. The initiating methionine residue was not detected in the mature protein in most cases but it was present in S16, indicating that only the formyl group is removed in this case. This result and the previously reported finding of N-methyl alanine at the N-terminus of chloroplast L2 indicate the existence of multiple N-terminal processing pathways in the chloroplast.

Amino Acid Sequence↗
PubMed1992

Intra-articular injections and articular cartilage metabolism. An experimental study in rabbits.

We studied the effects of repeated intra-articular injections of sterile 140 mM NaCl solution on articular cartilage in adult rabbits. After 20 injections into the knee joints over a period of 4 weeks, chondrocyte glucosaminoglycan synthesis was evenly reduced in all cartilage layers, accompanied by a significant proteoglycan depletion of the matrix which was most marked in the superficial half of the cartilage. These and other changes only partially reversed during a further 4-week period after the injections had been stopped. Our data underline the need for a clear-cut indication for intra-articular injections. The microtrauma caused by injection, in conjunction with the introduction of a carrier solution into the joint, may, at least when repeated at short intervals, lead to measurable damage to the articular cartilage.

Animals↗
PubMed1992

Response of myogenic determination factors to cessation and resumption of electrical activity in skeletal muscle: a possible role for myogenin in denervation supersensitivity.

1. We have prepared probes specific for the chicken myogenic determination genes MyoD, myogenin, myf5, and herculin and have investigated the expression of these genes in response to denervation and acute electrical stimulation in neonate chick muscle, using ribonuclease protection. 2. Upon denervation, herculin mRNA remains essentially unchanged, myf5 transcript levels approximately double, and MyoD message is up-regulated by two- to fivefold. In contrast, the message coding for myogenin, barely detectable in innervated muscle, rises dramatically (approximately 200-fold) on the second day after nerve section; in this respect it resembles acetylcholine receptor (AChR) alpha-, gamma- and delta-subunit mRNAs. Cohybridization experiments reveal that the increase in myogenin mRNA slightly precedes the rise in AChR alpha-subunit message. 3. Electrical stimulation of denervated muscle leads to an immediate decline in myogenin and AChR alpha-subunit mRNAs, with half-lives of less than an hour and approximately 4 hr, respectively; message stability measurements suggest that this is effected through a rapid shutdown of transcription. Messages coding for MyoD, myf5, and herculin decay much more slowly, as a result of slower turnover. 4. Previous experiments have indicated the involvement of a de novo induced (Tsay, H.-J., Neville, C. M., and Schmidt, J., FEBS Lett. 274:69-72, 1990) autocatalytic (Neville, C. M., Schmidt, M., and Schmidt, J., NeuroReport 2:655-657, 1991) transcription factor in the denervation-triggered up-regulation of AChR alpha-subunit expression; the denervation and electrical stimulation experiments reported here are compatible with the notion that myogenin is that factor.

Amino Acid Sequence↗
PubMed1992

Analysis of binding and activating functions of the chick muscle acetylcholine receptor gamma-subunit upstream sequence.

1. The skeletal muscle acetylcholine receptor comprises several subunits whose coordinated expression during myogenesis is probably controlled by cis elements in the individual subunit genes. We have previously analyzed promoter regions of the alpha and delta genes (Wang et al., 1988, 1990); to gain further insight into receptor regulation, we have now studied the promoter of the chick muscle gamma-subunit gene. 2. This analysis was faciliated by the close upstream proximity of the coding region of the delta-subunit gene and the consequent brevity (740 bp) of the untranslated linker connecting the two genes (Nef et al., 1984). Nuclease protection and primer extension analysis revealed that transcription of the gamma-subunit gene starts at position 56 upstream of the translational initiation site. 3. Nested deletions of the promoter region were employed to identify functionally important elements. A 360-bp sequence (-324 to +36) was found to activate transcription, in a position- and orientation-independent manner, during myotube formation. This sequence comprises 5 M-CAT (Nikovits et al., 1986) similarities and contains, at positions -52/-47 and -33/-28, two CANNTG (Lassar et al., 1989) motifs. 4. Binding experiments were performed by means of gel retardation, gel shift competition, and footprint analysis. The CANNTG motifs were found to bind MyoD and myogenin fusion proteins and to interact with proteins in nuclear extracts from cultured myotubes. 5. Point mutations in the CANNTG motifs revealed that these elements are crucial for full promoter activity in myotubes and essential in fibroblasts cotransfected with a myogenin expression vector. 6. We conclude that the activity of the gamma-subunit gene is determined largely by E boxes, which in vivo are likely to be activated by MyoD family proteins; in addition, other transactivators such as the M-CAT binding protein presumably play a role. Both CANNTG elements and M-CAT motifs are also present in the alpha- and delta-subunit enhancer and may therefore account for the coordinate expression of the three subunits during muscle differentiation.

Amino Acid Sequence↗
PubMed1992

A double surface membrane in plerocercoids of Ligula intestinalis (Cestoda: Pseudophyllidea).

The tegument of Ligula intestinalis plerocercoids is delimited by a membrane complex that in electron microscopy appears heptalaminate. We suggest that the plerocercoids are covered by two closely apposed lipid bilayers. Double membranes, which are well known in schistosomes, are thus not a unique feature of blood parasitic Digenea but could be documented for the first time in a cestode species that lives in the peritoneal cavity of its host. The surface-membrane complex of plerocercoids was lost for the most part after conventional preparation for electron microscopy but could be completely retained by improved fixation using osmium tetroxide plus potassium ferrocyanide. Furthermore, one type of vesicle in the tegumental syncytium of plerocercoids has been found to be enclosed by at least two membranes, which might indicate that these vesicles contribute to the renewal of the surface-membrane complex. Adult Ligula intestinalis removed from the gut of the final host Anas platyrhnychos or obtained by in vitro transformation exhibited a single surface membrane and lacked double membrane vesicles. The elongate electron-dense caps of the microtriches of plerocercoids were replaced by short caps in the course of worm maturation. Thus, the tegumental surface of this parasite is fundamentally altered following the change in its environment from the peritoneal cavity of the intermediate host to the intestine of the final host.

Animals↗
PubMed1992

Histopathologic correlates of serum amylase activity in acute experimental pancreatitis.

The association of serum amylase activity with the extent of pancreatic injury in acute pancreatitis is unclear. To clarify this relationship, we induced acute pancreatitis ranging from mild to lethal in 118 Sprague-Dawley rats (350-450 g). This was achieved by controlled intraductal infusion of low- or high-dose bile salt, with or without enterokinase, followed by intravenous cerulein or saline for 6 hr. Serum amylase was measured at baseline and 6 hr. Pancreatic histopathology was evaluated by two blinded pathologists employing total surface scoring (N = 118) and morphometric 20-field documentation (N = 22). Serum amylase correlated best with edema (r = 0.61) and fat necrosis (r = 0.58), less well with acinar necrosis (r = 0.53) and inflammation (r = 0.50), and poorly with hemorrhage (r = 0.33) and perivascular infiltrate (r = 0.31). Inasmuch as edema and fat necrosis are not important determinants of severity, these observations could explain the poor prognostic value of serum amylase activity in patients with acute pancreatitis.

Acute Disease↗
PubMed1992

Morphometric characteristics and homogeneity of a new model of acute pancreatitis in the rat.

Extreme maldistribution and immediate establishment of severe cellular injury are typical features of traditional bile salt models of acute pancreatitis; both factors complicate assessment and interpretation of therapeutic benefits in trials of experimental therapy. Even more important, both are indications not of the desired induction of pancreatitis but rather of local injury by barotrauma and noxious chemicals. This study contrasts the severity and regional variability of cellular injury in traditional high-dose bile salt models with that seen in a new preparation employing the combination of intravenous (iv) caerulein (CAE) and intraductal (id) low-dose glycodeoxycholic acid (GDOC). Thirty-six male Sprague-Dawley rats (350-450 g) were induced with (group A) high-dose GDOC id (34 mmol/L), low-dose GDOC id (10 mmol/L) (group B), or low-dose GDOC id combined with caerulein iv for 6 h (group C). The regional distribution of histopathologic injury within the pancreas was assessed in 20 fields/organ by two pathologists unaware of the induction technique used. High-dose GDOC id (group A) resulted in extremely heterogenous distribution of injury for all variables (edema, p = 0.001; acinar necrosis, p = 0.0001; inflammation, p = 0.0001; and hemorrhage p = 0.001). The lesions were confined to the head of the pancreas, which showed large areas of necrosis involving entire lobules, whereas adjacent areas were unaffected. Low-dose GDOC id (group B) was more homogenously distributed, but the injury was mild and regional variability (edema, p = 0.0001; acinar necrosis, p less than 0.04; inflammation, p = 0.0001; and hemorrhage p less than 0.05) was still demonstrable. In contrast, low-dose GDOC id combined with CAE iv (group C) produced moderately severe pancreatitis, which equally affected all areas of the gland. There were no geographical differences in acinar necrosis or inflammation. This feature of the new model provides a desirable prerequisite for accurate and reproducible assessment of histopathology in studies aimed at detecting effects of therapy. We suggest that it replace traditional id bile salt infusion models.

Acute Disease↗
PubMed1992

Cooperative image workstation based on explicit models of diagnostic information requirements.

A medical image workstation designed to act as a cooperative dialogue partner in diagnostic radiology has been conceived, and a prototype has been made. The system can automatically select relevant information (eg, from current and previous examinations) and generate a meaningful and appropriate image arrangement on the display screen. For a number of routinely performed tasks in radiology, the users' interaction may be as simple as switching from one patient to the next. This is shown to considerably simplify and speed up radiological image access and presentation, saving the user time and effort. The cooperative system response is based on explicit (formalized and computer-accessible) models of diagnostic information requirements. These models are context dependent and take into account that diagnostic information needs vary with radiological work procedures, workstation users, and patient cases. Initial models have been acquired from expert radiologists in two European hospitals and were integrated in a cooperative workstation prototype. For the representation of models, rule-based and object-oriented techniques were applied. The rule base was designed with a distinct modular structure, separating between rule sets for general, task-dependent, and user-dependent information requirements. The installed rule-based mechanism also offers a solution for the automatic prefetching of images to avoid transmission delays in the course of diagnostic work sessions. The first part of the report reviews the objectives for the design of cooperative workstation user interfaces and explains the benefits from the users' point of view. In the second part, the acquisition, structuring, formalization, and representation of context-dependent information requirement models is described. The rule-based model is explained using examples. A layered workstation architecture consisting of model, object, and real-time layers is presented. Difficulties in the implementation of cooperative workstations are discussed that point to future research topics and standardization efforts.

Diagnostic Imaging↗
PubMed1992

A methodological critique of the current status of eye movement desensitization (EMD).

Eye Movement Desensitization (EMD) has been recently advocated as a rapid treatment for the elimination of traumatic memories responsible for the maintenance of a number of anxiety disorders and their clinical correlates. Despite a limited conceptual framework, EMD has attracted considerable interest among clinicians and researchers. The popularity and interest generated by EMD will likely result in wide usage. We present a methodological critique of it with reference to assessment, treatment outcome, and treatment process. We also provide guidelines for judging the methodological adequacy of research on EMD and suggest intensive research to assess effectiveness, treatment components, and comparisons with other procedures.

Anxiety Disorders↗
PubMed1992

Effect of dexamethasone on proliferating osteoblasts: inhibition of prostaglandin E2 synthesis, DNA synthesis, and alterations in actin cytoskeleton.

Elevated levels of glucocorticoids caused by disease (Cushing's syndrome) or therapeutic treatment of asthma are known to cause osteoporosis. Space flight, an environmental condition, is known to cause a rise in endogenous cortisols accompanied by a significant loss of bone and calcium. Long-term space inhabitants have lost up to 18% of weight bearing bone during long-term flight. This study demonstrates that elevated concentrations of glucocorticoids lower the endogenous production of PGE2 and interfere with osteoblast proliferation. Osteoblasts grown with dexamethasone had significantly lower DNA synthesis and endogenous synthesis of PGE2. Addition of exogenous dmPGE2 to the dexamethasone growth-inhibited cells stimulated DNA synthesis over twofold. In synchronous control cultures, we found that endogenous prostaglandin synthesis increased in late G1, preceding S-phase DNA synthesis by several hours. The addition of exogenous dexamethasone to synchronous cultures resulted in a significant decrease in the prostaglandin synthesis followed by a significant decrease in DNA synthesis in parallel cultures. Further, dexamethasone caused the actin cytoskeleton to collapse and the cell morphology to become rounded and spindle shaped. Addition of exogenous PGE2 to the dexamethasone-treated osteoblasts caused recovery of the actin architecture and phenotype. These data support the hypothesis that the glucocorticoid-mediated decrease in prostaglandin synthesis may be a contributing factor in the reduced bone quality and trabecular bone formation seen in glucocorticoid-induced osteoporosis.

Actins↗
PubMed1992

Trypsinogen-activation peptides in experimental rat pancreatitis: prognostic implications and histopathologic correlates.

Intrapancreatic activation of trypsinogens is believed to occur either as a cause or a consequence of acute pancreatitis and to be associated with the more severe forms of the disease. Trypsinogen-activation peptides (TAPs) were measured in plasma, urine, and ascites of rats (n = 54) assigned to different pancreatitis-inducing regimens reproducing the entire spectrum of severity. Compared with survivors, nonsurvivors at 9 hours had significantly higher TAP levels in plasma at 3 hours (P = 0.0001), urine (peak, 1-4 hours) (P = 0.004), and ascites (P = 0.0001) after death. Stepwise discriminant analysis showed that TAP in urine and plasma were the most accurate predictors of outcome (88.2% of animals) compared with other routine laboratory parameters. Morphometric analysis showed that the best histopathologic correlates of TAP elevation were acinar necrosis and intrapancreatic hemorrhage. In a second series of experiments using a homogeneous technique of induction producing pancreatitis with a mortality of 55% at 48 hours, plasma TAP level at 3 hours (cutoff, 0.5 nmol/L) and/or urinary TAP level (peak, 1-6 hours; cutoff, 25 nmol/L) accurately predicted outcome in 85% of animals. It is concluded that the TAP assay gives an accurate early prediction of outcome in different pancreatitis models and correlates best with acinar necrosis and hemorrhage.

Acute Disease↗
PubMed1992

Chondrocalcinosis of the temporomandibular joint: an external ear canal pseudotumor.

An unusual case of calcium pyrophosphate arthropathy (pseudogout) involving the temporomandibular joint of a 53-year-old woman presented clinically as an ear canal tumor. Further evaluation and surgical exploration disclosed chondrocalcinosis of the temporomandibular joint with involvement of the bones at the left base of the skull. This case report emphasizes the importance of recognizing the lesion by frozen-section examination because excellent results can be obtained by intraoperative curettage of the calcareous deposits and local irrigation with saline solution.

Calcium Pyrophosphate↗
PubMed1992

Protein kinase C couples membrane excitation to acetylcholine receptor gene inactivation in chick skeletal muscle.

The signaling pathway connecting membrane depolarization and gene activity in skeletal muscle remains largely unknown. Using transcription elongation (run-on) analysis we have found that electrical stimulation of denervated chick skeletal muscle in vivo rapidly and selectively results in inactivation of acetylcholine receptor (AChR) subunit genes. We have studied the possible involvement of protein kinase C (PKC) in this response and have observed that electrical stimulation increases the activity of PKC in the nucleus by over two orders of magnitude within 10 min; phorbol esters, within minutes after intramuscular application, block AChR subunit genes in the absence of electrical activity; and the activity-triggered gene inactivation is blocked by the protein kinase inhibitor staurosporine or by enzyme depletion resulting from chronic pretreatment of muscle with phorbol esters. We conclude that PKC is an integral component of the pathway coupling membrane excitation and AChR gene control.

Alkaloids↗
PubMed1992

Physiologic analysis of corneal healing after epikeratophakia.

The evaluation of epithelial permeability, stromal transparency, and endothelial cell density is essential to determine the resumption of normal function in each corneal physiologic unit after refractive surgical procedures. The authors report the results of a prospective study conducted in 55 consecutive patients undergoing epikeratophakia using prelathed, lyophilized tissue lenses. Epithelial permeability was evaluated by means of fluorophotometry preoperatively and 1, 2, 4, 8, 12, 24, and 52 weeks after epikeratophakia. With few exceptions, Scheimpflug photography also was performed at the same examination times to assess stromal optical density. Endothelial cell counts were performed in each patient preoperatively and between 6 and 12 months postoperatively. The epithelial barrier function resumed normal values within 8 weeks after epikeratophakia. The optical density of both donor lenticule and recipient corneas was initially increased but returned to values comparable with those of unoperated corneas by 12 weeks postoperatively. Endothelial cell density was not affected by epikeratophakia. These results confirm the authors' preliminary observation that epikeratophakia allows a relatively quick recovery of normal corneal functions and should prompt investigators to demonstrate the safety of other refractive surgical procedures in a similar way.

Aged↗
PubMed1992

A better model of acute pancreatitis for evaluating therapy.

Existing models of acute pancreatitis have limitations to studying novel therapy. Whereas some produce mild self-limited pancreatitis, others result in sudden necrotizing injury. The authors developed an improved model providing homogeneous moderately severe injury by superimposing secretory hyperstimulation on minimal intraductal bile acid exposure. Sprague-Dawley rats (n = 231) received low-pressure intraductal glycodeoxycholic acid (GDOC) at very low (5 or 10 mmol/L) concentrations followed by intravenous cerulein. Cerulein or GDOC alone caused only very mild inflammation. However, GDOC combined with cerulein was uniformly associated with more edema (p less than 0.0005), acinar necrosis (p less than 0.01), inflammation (p less than 0.006), and hemorrhage (p less than 0.01). Pancreatic injury was further increased and death was potentiated by increasing volume and duration of intraductal low-dose GDOC infusion. There was significant morphologic progression between 6 and 24 hours. The authors conclude that (1) combining minimal intraductal bile acid exposure with intravenous hyperstimulation produces homogeneous pancreatitis of intermediate severity that can be modulated at will; (2) the injury is progressive over at least 24 hours with finite mortality rate; (3) the model provides superior opportunity to study innovative therapy.

Acute Disease↗