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Biomedical subjects

J Schmidt

Publications and source records attributed to J Schmidt.

At least 271 records · Page 15Linked to original sources

Glycan vesicle formation in vitellocytes and hatching vacuoles in eggs of Echinostoma caproni and Fasciola hepatica (Digenea).

Vitelline cells, which are added to the fertilized ovum when eggs are formed in Platyhelminthes, are known to produce and secrete proteins containing vesicles for construction of the eggshell. In this study, another particular type of carbohydrate-containing vesicle is described, in the vitellocytes of Digenea. These vesicles play a role in the hatching of the miracidium from the egg. Cytochemical analysis and the binding of lectins with specificities for a variety of sugar residues revealed that the vesicles contain neutral, glycogen-like polysaccharides composed of glucosyl/mannosyl residues. The vesicles are produced at a late maturation stage of the vitellarium cells. Vitellocytes enclosed in the eggs provide nutrients for the embryo, but retain the glycan vesicles until late embryogensis. Then the vesicles merge and swell to the dimensions of the vitellocytes, and these coalesce into two vacuoles that fill the space between the embryo and the eggshell. Hatching of the miracidium is induced by exposure to light and a slight rise in temperature, i.e. conditions found in the natural environment in the morning. The eggs' internal hydrostatic pressure rises, probably due to a depolymerization of the polysaccharides that causes an osmotically driven water influx. Finally, the operculum of the egg bursts open and the miracidium escapes.

Animals↗

[Vitiligo in multiple autoimmune syndrome: a retrospective study of 11 cases and a review of the literature].

PURPOSE: The occurrence in the same patient of three or more autoimmune diseases defines multiple autoimmune disease. Multiple autoimmune disease is an unusual condition in which dermatological autoimmune diseases and especially vitiligo have an important place. METHODS: We examined retrospectively 11 cases of multiple autoimmune diseases associating vitiligo. We studied the clinical characteristics of vitiligo and those of the associated autoimmune disorders. RESULTS: Type III multiple autoimmune disease was diagnosed in all the 11 cases observed. Autoimmune vitiligo was the first autoimmune disorder observed in seven cases and was bilateral, symmetrical and acrofacial in eight cases. Autoimmune thyroid disorder was associated in ten cases. Our data confirms the important association between vitiligo and thyroid autoimmune disorders. CONCLUSION: The predominant female ratio and the acrofacial topography of skin lesions could predict association with others autoimmune disorders in patients with vitiligo.

Adolescent↗

Synthesis and radioprotective effects of adamantyl substituted 1,4-dihydropyridine derivatives.

A series of 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diesters substituted at the N-1 and/or C-4 positions of the dihydropyridine ring was synthesized. The in vitro cytotoxicity and in vitro and in vivo radioprotective efficacy of these agents were evaluated in Chinese hamster (V-79) cells and CD2F1 male mice, respectively. Compounds with at least one adamantyl substituent afforded better radioprotection than those without this substituent. Substitution of an aromatic ring at the C-4 position of the dihydropyridine ring did not enhance the radioprotectant action of the compounds.

Adamantane↗

Disseminated aseptic abscesses associated with Crohn's disease: a new entity?

Our purpose is to describe seven cases of disseminated aseptic abscesses with regard to clinical, biological, radiological, and histological information, treatment, and outcome. Data were collected on seven Caucasian patients who had proven sterile deep abscesses diagnosed in French university hospitals. The onset of the disease related to abscesses began at times from June 1988 to August 1994. Follow-up periods were 1 year, 7 months to 8 years, 2 months. The age of the patients ranged from 15 to 26 years old. At onset, all had fever and six had abdominal pain. Abscesses involved spleen and abdominal lymph nodes in six cases; liver in three; pancreas, brain, and chest in one. All had polymorphonuclear leukocytosis. Pathological examination showed granulomatous abscesses. Direct and indirect investigations failed to identify any causal microorganism. On six occasions, Crohn's disease was revealed 1 to 41 months later and in one case, it preceded the onset of abscesses. One subsequently developed Sweet's syndrome. Various antibiotic regimes were inefficient. Steroids, associated in three cases with immunosuppressive agents, resulted in a rapid improvement in six patients. In one case, splenectomy followed by 5-ASA therapy was used successfully. The dramatic effectiveness of steroids and immunosuppressive agents as well as follow-up suggest that disseminated aseptic abscesses might be an extraintestinal manifestation of Crohn's disease. Although the pathogenesis of this condition remains unknown, this entity may be related to neutrophilic dermatosis in which sterile deep abscesses have been reported.

Abdominal Abscess↗

Sequence dependent N-terminal rearrangement and degradation of peptide nucleic acid (PNA) in aqueous solution.

The stability of the PNA (peptide nucleic acid) thymine monomer ¿N-[2-(thymin-1-ylacetyl)]-N-(2-aminoaminoethyl)glycine¿ and those of various PNA oligomers (5-8-mers) have been measured at room temperature (20 degrees C) as a function of pH. The thymine monomer undergoes N-acyl transfer rearrangement with a half-life of 34 days at pH 11 as analyzed by 1H NMR; and two reactions, the N-acyl transfer and a sequential degradation, are found by HPLC analysis to occur at measurable rates for the oligomers at pH 9 or above. Dependent on the amino-terminal sequence, half-lives of 350 h to 163 days were found at pH 9. At pH 12 the half-lives ranged from 1.5 h to 21 days. The results are discussed in terms of PNA as a gene therapeutic drug as well as a possible prebiotic genetic material.

Evolution, Chemical↗

Establishment and characterization of osteoblast-like cell lines from retrovirus (RFB MuLV)-induced osteomas in mice.

Cell lines were established by a two-step method from osteomas which had been induced by infection of mice with RFB MuLV, a bone-pathogenic, replication-competent murine retrovirus. The benign tumors, consisting of mature lamellar bone and surrounded by a thin periosteum, were cultured on sponges of denatured collagen type I fibres for up to 4 weeks. At this time osteoma cells had grown into the collagenous matrix. After release and further cultivation in monolayers, the cell lines established from these cultures varied in morphology; they expressed T1, collagen type I and type III, alkaline phosphatase, osteonectin and osteopontin mRNAs at variable levels, but not osteocalcin/BGP. They also showed alkaline phosphatase activity, but lacked responsiveness to parathyroid hormone. All cell lines established from infected mice expressed retroviral and c-myc mRNA and viral protein. In contrast to cells from control mice they showed an extended life span in culture. After growth in a three-dimensional (3-D) collagen sponge culture the cells formed an extracellular matrix containing collagen type I, alkaline phosphatase and osteocalcin/BGP. These data indicate that the two-step method facilitates the establishment of osteoblast-like cell lines from osteomas and calvaria of old mice, and provides means for further analyses of retrovirus-induced skeletal pathogenesis and bone induction.

Alkaline Phosphatase↗

[External trabecular excision--alternative to filtering glaucoma operation in patients with open angle glaucoma].

BACKGROUND: Postoperative complications concerning glaucoma filtering surgery (trabeculectomy, goniotrepanation) often include hypotonia that may lead to athalamia or choroidal detachment, which are difficult to handle. Cystic non filtering blebs are due to postinflammatory reactions, and may limit the success of filtering surgery. Aim of the study was to compare the success and the complications of a new operating technique, which will be described, with those of usual glaucoma filtering surgery. PATIENTS AND METHODS: In 24 open angle glaucoma patients with mean intraocular pressure of 28.12 mm Hg (+/- 8.6) we performed external trabecular excision in 25 eyes since June 1997. Preoperative visual acuity and peak intraocular pressure were compared retrospectively in all eyes with the values of the first postoperative day, in 22 eyes after one month and in 17 eyes after 3 months. RESULTS: Intraocular pressure measured between 0 mm Hg and 16 mm Hg on the first postoperative day (7.64 mm Hg +/- 4.3), after one month between 10 mm Hg and 30 mm Hg (17.81 mm Hg +/- 5.5) and after 3 months between 9 mm Hg and 26 mm Hg (15.29 mm Hg +/- 4.2). After 1 month 10 of 22 (45%) and after 3 months 7 of 17 eyes (42%) required antiglaucomatous drugs; 3 eyes needed gonitrepanation (2 weeks, 1 month, 3 months after ETE). Concerning postoperative complications, we observed 6 choroidal detachments, once erythrocoytes in the anterior chamber, twice hyphemata, twice inflammatory reaction in the anterior chamber, two flat anterior chambers and twice a positive seidel test. CONCLUSION: Complications after ETE are similar to those after filtering surgery. Postoperative intraocular pressure dip after ETE in most eyes was not as pronounced as after goniotrepanation or trabeculectomy, and postoperative complications were all reversible. 45% of the eyes again needed antiglaucomatous drugs after one month and 42% after 3 months. A prospective long-term study has to verify the success respectively the complications of ETE.

Adult↗

The accuracy of abdominal ultrasound in the assessment of bowel disorders.

BACKGROUND: Little is known about the sensitivity, specificity, and predictive values of transabdominal ultrasonographic (US) findings in a teaching hospital setting. METHODS: We carried out a prospective study including 227 patients with symptoms suggestive of inflammatory bowel disorder. The Picker 9200 CS equipment (5-mHz curved-array probe) was used to obtain bowel images. Gastrointestinal endoscopy, enteroclysis, bowel enema, computed tomography scan, or bowel surgery was used as reference. RESULTS: Of 227 patients, 168 had pathologic findings of the bowel as final diagnosis. The overall sensitivity of US was 76%, whereas the positive predictive value was 98%. Overall specificity was 95%. The negative predictive value for bowel disorders was only 58%, since US missed pathologic findings in 48 patients. Subgroup analysis showed a sensitivity of 84% for Crohn's disease, 66% for ulcerative colitis, 46% for bowel tumors, and 60% for diverticulitis. Topographic comparisons showed that US detected inflammatory bowel-wall alterations preferentially in the terminal ileum and colon, whereas abnormalities in the duodenum, jejunum, and rectum were frequently missed (sensitivity, 10%-20%). CONCLUSIONS: Positive US findings are useful for the diagnosis of bowel processes. US is highly predictive albeit not disease-specific. Negative US examinations, however, do not exclude pathologic bowel processes. A topographic location of pathologic US findings is mostly confined to the colon.

Adult↗

Spermine deficiency in Gy mice caused by deletion of the spermine synthase gene.

Two mouse mutations gyro (Gy) and hypophosphatemia (Hyp) are mouse models for X-linked hypophosphatemic rickets and have been shown to be deleted for the 5' and 3' end of the mouse homolog of PHEX (phosphate regulating gene with homologies to endopeptidases on the X chromosome; formerly called PEX), respectively. In addition to the metabolic disorder observed in Hyp mice, male Gy mice are sterile and show circling behavior and reduced viability. The human SMS (spermine synthase) gene maps approximately 39 kb upstream of PHEX and is transcribed in the same direction. To elucidate the complex phenotype of Gy mice, we characterized the genomic region upstream of Phex. By establishing the genomic structure of mouse Sms, a 160-190 kb deletion was shown in Gy mice, which includes both Phex and Sms. There are several pseudogenes of SMS / Sms in man and mouse. Northern analysis revealed three different Sms transcripts which are absent in Gy mice. Measurement of polyamine levels revealed a marked decrease in spermine in liver and pancreas of affected male Gy mice. Analysis of brain tissue revealed no gross or histological abnormalities. Gy provides a mouse model for a defect in the polyamine pathway, which is known to play a key role in cell proliferation.

Animals↗

A T-DNA from the Agrobacterium tumefaciens limited-host-range strain AB2/73 contains a single oncogene.

Agrobacterium tumefaciens strain AB2/73 isolated from Lippia canescens has been described as a limited-host-range strain. Its tumor-inducing (Ti) plasmid has been found to lack DNA homology to known T-DNAs (L. Unger, S. F. Ziegler, G. A. Huffman, V. C. Knauf, R. Peet, L. W. Moore, M. P. Gordon, and E. W. Nester. J. Bacteriol. 164:723-730, 1985). We have isolated a T-DNA from AB2/73 by using a heterologous border sequence as a probe. The AB2/73 T-DNA sequence (3,504 bp) is flanked by canonical border sequences, has no detectable DNA homology with other T-DNAs, and contains only two genes: lsn (Lippia strain nopaline synthaselike gene) and lso (Lippia strain oncogene). The lso gene induces nondifferentiating tumors on a limited number of hosts when transferred by a Ti plasmid from a wide-host-range strain. Part of the predicted Lso protein is weakly homologous to other Agrobacterium oncoproteins encoded by rolB, rolB, orf13, gene e, gene 5, and gene 3'. A 28-kb fragment corresponding to the virA to virE region was cloned by using a heterologous vir fragment as probe. The AB2/73 vir region is homologous to most of the C58 virulence region; however, the virA gene is most related to the virA gene of the Agrobacterium vitis limited-host-range strain Ag162.

Agrobacterium tumefaciens↗

The relative safety of MRI contrast agent in acute necrotizing pancreatitis.

OBJECTIVE: To validate the safety of gadolinium-diethylenetriamine pentaacetic acid (GD-DTPA) by measuring its effect on pancreatic capillary perfusion and acinar injury in acute pancreatitis. BACKGROUND: Contrast-enhanced computed tomography (CECT) is proposed as a gold standard for early evaluation of acute necrotizing pancreatitis. However, iodinated contrast media used for CECT have been shown in these circumstances to reduce pancreatic capillary flow and increase necrosis and mortality. Recent reports suggest that post-GD MRI provides images comparable to CECT in the assessment of severe acute pancreatitis. METHODS: Necrotizing pancreatitis was induced in 14 Wistar rats by intraductal glycodeoxycholic acid (10 mM/L) and intravenous caerulein (5 microg/kg/h) over 6 hours. Intravital microscopic quantitation of pancreatic capillary blood flow was performed using fluorescein isothiocyanate-labeled erythrocytes after induction of pancreatitis and 30 and 60 minutes after an intravenous bolus of either Ringer's solution or GD-DTPA (0.2 mL/kg). RESULTS: The two study groups were comparable with regard to mean arterial pressure, heart rate, arterial blood gases, hematocrit, amylase, lipase, and trypsinogen activation peptide production throughout the experiment. GD-DTPA did not reduce capillary flow (1.93 +/- 0.05 nL/capillary/min) compared to animals infused with Ringer's solution (1.90 +/- 0.06 nL/capillary/min). CONCLUSIONS: Intravenous injection of GD-DTPA does not further impair pancreatic microcirculation or increase acinar injury in acute necrotizing pancreatitis. Because of this advantage over CT contrast medium, further development of MRI as a staging tool in acute pancreatitis seems desirable.

Animals↗

B-Cell lymphoma induction by akv murine leukemia viruses harboring one or both copies of the tandem repeat in the U3 enhancer.

Akv is an endogenous, ecotropic murine leukemia virus (MuLV) of the AKR strain. It has served as a prototype nonpathogenic or weakly pathogenic reference virus for studies of closely related potent lymphomagenic viruses such as the T-lymphomagenic SL3-3. We here report that Akv and an Akv mutant (Akv1-99) with only one copy of the 99-bp transcriptional enhancer induce malignant lymphomas with nearly 100% incidence and mean latency periods of 12 months after injection into newborn NMRI mice. Molecular analysis of tumor DNA showed that the majority of the tumors were of the B-cell type. Sequence analysis of proviral transcriptional enhancers in DNA of B-cell lymphomas revealed conservation of the enhancer sequence, as well as a lack of sequence duplications of the Akv1-99 variant, while the repeat copy number in Akv was subject to fluctuations. In support of a B-cell specificity of the Akv enhancer, a murine plasmacytoma cell line was found to sustain three- to fivefold-higher transient transcriptional activity upon the Akv and Akv1-99 enhancers than upon the enhancer of the T-lymphomagenic SL3-3 MuLV. Thus, the overall picture is that Akv MuLV possesses a B- lymphomagenic potential and that the second copy of the 99-bp sequence seems to be of minor importance for this potential. However, in one animal the lymphomas induced by Akv1-99 were of the T-cell type. Among the 24 tumors analyzed only this one harbored a clonal proviral integration in the c-myc locus. This provirus had undergone a duplication of a 113-bp sequence of the enhancer region, partly overlapping with the 99-bp repeat of Akv, as well as a few single nucleotide alterations within and outside the repeats. Taken together with previous studies, our results suggest that T- versus B-lymphomagenic specificity of the enhancer is governed by more than one nucleotide difference and that alterations in binding sites for transcription factors of the AML1 and nuclear-factor-1 families may contribute to this specificity.

3T3 Cells↗

Infectivity of a pseudorabies virus mutant lacking attachment glycoproteins C and D.

Initiation of herpesvirus infection requires attachment of virions to the host cell followed by fusion of virion envelope and cellular cytoplasmic membrane during penetration. In several alphaherpesviruses, glycoprotein C (gC) is the primary attachment protein, interacting with cell-surface heparan sulfate proteoglycans. Secondary binding is mediated by gD, which, normally, is also required for penetration. Recently, we described the isolation of a gD-negative infectious pseudorabies virus (PrV) mutant, PrV gD- Pass (J. Schmidt, B. G. Klupp, A. Karger, and T. C. Mettenleiter, J. Virol. 71:17-24, 1997). In PrV gD- Pass, attachment and penetration occur in the absence of gD. To assess the importance of specific attachment for infectivity of PrV gD- Pass, the gene encoding gC was deleted, resulting in mutant PrV gCD- Pass. Deletion of both known attachment proteins reduced specific infectivity compared to wild-type PrV by more than 10,000-fold. Surprisingly, the virus mutant still retained significant infectivity and could be propagated on normal noncomplementing cells, indicating the presence of another receptor-binding virion protein. Selection of bovine kidney (MDBK) cells resistant to infection by PrV gCD- Pass resulted in the isolation of a cell clone, designated NB, which was susceptible to infection by wild-type PrV but refractory to infection by either PrV gCD- Pass or PrV gD- Pass, a defect which could partially be overcome by polyethylene glycol (PEG)-induced membrane fusion. However, even after PEG-induced infection plaque formation of PrV gCD- Pass or PrV gD- Pass did not ensue in NB cells. Also, phenotypic gD complementation of PrV gCD- Pass or PrV gD- Pass rescued the defect in infection of NB cells but did not restore plaque formation. Glycosaminoglycan analyses of MDBK and NB cells yielded identical results, and NB cells were normally susceptible to infection by other alphaherpesviruses as well as vesicular stomatitis virus. Infectious center assays after PEG-induced infection of NB cells with PrV gD- Pass on MDBK cells indicated efficient exit of virions from infected NB cells. Together, our data suggest the presence of another receptor and receptor-binding virion protein which can mediate PrV entry and cell-to-cell spread in MDBK cells.

Animals↗

S-adenosylmethionine deficiency and TNF-alpha in lipopolysaccharide-induced hepatic injury.

S-adenosylmethionine (Adomet) is a substrate for de novo synthesis of choline. Adomet deficiency occurs in certain types of liver injury, and the injury is attenuated by exogenous Adomet. Tumor necrosis factor-alpha (TNF-alpha) is also a mediator of these models of hepatotoxicity. We investigated the role of Adomet in lipopolysaccharide (LPS)-induced liver injury in rats made deficient in both Adomet and choline. Rats were maintained on either a methionine-restricted and choline-deficient (MCD) diet or a diet containing sufficient amounts of all nutrients [methionine and choline sufficient (MCS)] and then administered either LPS or saline. MCS-LPS rats had normal liver histology and no change in serum transaminases compared with the MCS-saline control group. MCD-saline rats had hepatosteatosis but no necrosis, and a five- to sevenfold increase in transaminases vs. the MCS-saline group. MCD-LPS rats additionally had hepatonecrosis and a 30- to 50-fold increase in transaminases. Exogenous Adomet administration to MCD-LPS rats corrected the hepatic deficiency of Adomet but not of choline, prevented necrosis but not steatosis, and attenuated transaminases. Serum TNF-alpha was sixfold higher in MCD rats even without LPS challenge and 300-fold higher with LPS challenge. Exogenous Adomet attenuated increased serum TNF-alpha in MCD-LPS rats.

Alanine Transaminase↗

Redesigning nucleic acids.

A research program has applied the tools of synthetic organic chemistry to systematically modify the structure of DNA and RNA oligonucleotides to learn more about the chemical principles underlying their ability to store and transmit genetic information. Oligonucleotides (as opposed to nucleosides) have long been overlooked by synthetic organic chemists as targets for structural modification. Synthetic chemistry has now yielded oligonucleotides with 12 replicatable letters, modified backbones, and new insight into why Nature chose the oligonucleotide structures that she did.

Catalysis↗

[Intrafemoral pressure measurement in different cement removal procedures during hip prosthesis replacement operations--experimental study with cadaver femora].

During primary hip arthroplasty an increase in intramedullary pressure (IMP) of up to 1000 mm Hg can be observed. As a result of this increased intrafemoral pressure, intramedullary constituents can pass into the venous circulation creating a risk of fat embolism syndrome (FES). In the present experimental study on 9 femora obtained from human corpses, we investigated the question as to whether various methods of cement removal during total hip revision arthroplasty are also associated with increased intramedullary pressure and a risk of FES. The IMP was recorded with a standardized experimental set-up during removal of cement from the proximal and distal regions, including removal of the cement "tip" and the intramedullary plug. The methods employed for this purpose included the osteotome and mallet, a compressed air powered chisel, and a modified intracorporal lithotripter. All the methods induced fluctuations in the IMP the highest values being recorded for the conventional method using the osteotome and mallet (45 mm Hg) and the lowest values for the intracorporeal lithotripter (7.5 mm Hg). Working on the distal cement caused higher fluctuations in comparison with the proximal region. The study failed to reveal any increase in mean IMP, and all measured values were in the low pressure range (considerably below 150 mm Hg). While there seems to be no apparent risk of an FES developing during removal of cement, careless manipulation of the distal cement plug may result in higher intrafemoral pressures--above 150 mm Hg--thus increasing the risk of a fat embolism syndrome.

Bone Cements↗