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Biomedical subjects

W Zimmermann

Publications and source records attributed to W Zimmermann.

At least 19 recordsLinked to original sources
PubMed1995

The cea10 gene encodes a secreted member of the murine carcinoembryonic antigen family and is expressed in the placenta, gastrointestinal tract and bone marrow.

Although members of the carcinoembryonic antigen (CEA) family have been shown to convey cell adhesion in vitro, their location in some tissues contradicts such a function. As a basis for investigating their in vivo functions, we are characterizing the mouse CEA family. This paper describes the structure and expression of a new murine family member, cea10. Two full-length cDNA clones were isolated from a mouse colon library, whose deduced protein sequence comprises two immunoglobulin variable-like N-domains, directly followed by a short C-terminal domain indicating that this molecule is secreted. Although this domain organization suggests a closer relationship to the murine pregnancy-specific glycoproteins (PSG), which form a subgroup within the CEA family, sequence comparisons place Cea10 within the CEA subgroup. Overlapping cosmid clones containing the complete cea10 locus were mapped and the exons determined. No A2-like exon, characteristic for all other members of the murine CEA family, could be found. Sequences of the promoter and the first exon showed remarkably high similarity to the corresponding regions of bgp1 and bgp2, two other members of the murine CEA subgroup. Consensus sequences for two transcription factors (USF and an AP-2-like factor) that bind to the human BGP gene promoter were also present in the cea10 promoter and possibly convey expression of these genes in epithelial cells. RNase protection assays revealed transcriptional activity of cea10 in the colon and early placenta (10.5-12.5-day embryos) and to a lower extent in the small intestine, cecum, stomach, salivary glands and bone marrow. As some other CEA family members are deregulated in tumors, we quantified the expression levels of Cea10 transcripts in colonic mucosa and in adenomatous polyps of Min/+ mice. No differences in the steady-state levels of Cea10 mRNA could be found, suggesting that the Cea10 protein does not play a role in early tumor development. Taken together, Cea10 combines characteristic features of both CEA and PSG subgroup members in its structure and expression pattern.

Amino Acid Sequence↗
PubMed1995

Synthesis of heterocyclic platelet activating factor analogues.

The synthesis of heterocyclic analogues of the platelet activating factor is described. The preparation starts with acylating rac-tetrahydro-1,3-thiazine-4-carboxylic acid ethyl ester, with palmitoyl chloride to form the amide linkage. Following ester reduction, the phosphocholine part is introduced via 2-chloro-2-oxo-1,3,2-dioxaphospholane and subsequent ring opening with trimethylamine under pressure. Furthermore, the related L-thiazolidine analogue is prepared using the same procedure. In addition the sulfinyl and sulfonyl derivatives of this compound are obtained by oxidation with 3-chloro-perbencoic acid. From one sulfinyl intermediate the diastereomeres are separated and their conformations are determinated by 13C-NMR spectroscopy.

Magnetic Resonance Spectroscopy↗
PubMed1995

Borna disease virus genome transcribed and expressed in psychiatric patients.

Borna disease virus (BDV) is a neurotropic, negative and single-stranded enveloped RNA virus that persistently infects various domestic animal species. Infection causes disturbances in behaviour and cognitive functions, but can also lead to a fatal neurologic disease. Human infections seemed likely, since serum antibodies were detected in neuropsychiatric patients. Further proof came from our discovery that peripheral blood monocytes carry viral antigens. Here, we present the first data on different viral genomic transcripts in such patients' cells as well as sequence data of transcripts. Both viral markers seem to coincide with acute episodes of mood disorders, thus pointing to a new human virus infection possibly threatening mental health.

Acute Disease↗
PubMed1995

Staggering disease in cats: isolation and characterization of the feline Borna disease virus.

A Borna disease virus (BDV)-like agent was isolated from the central nervous system (CNS) of cats with a spontaneous non-suppurative encephalomyelitis ('staggering disease'). In contrast to the rabbit-adapted BDV strain V, which can be propagated in several primary and permanent cell cultures, the cat virus grew only in embryonic mink brain cells. Infection of adult Wistar rats with feline brain tissue material did not result in clinical disease during a period of 5 months, nor in growth of infectious virus in the brain. However, using the brain suspension of a newborn rat inoculated with feline brain tissue material, it was possible to induce typical Borna disease (BD) in four adult rats. This indicates a possible adaptation of the cat virus during passages in rats. By the use of an RT-PCR technique, BDV-specific RNA could be detected in a majority of brain samples from diseased cats. BDV-specific antigen was demonstrated in feline CNS samples both by immunohistochemistry and ELISA. However, the amount of BDV RNA and BDV antigen was less in the cats as compared to horses with BD, providing further support for the notion that a distinct feline BDV strain exists.

Animals↗
PubMed1995

Carcinoembryonic antigen-transgenic mice: a model for tumor immunotherapy.

The tumor marker carcinoembryonic antigen (CEA) is a 180-kD glycoprotein expressed on epithelial cells of the gastrointestinal tract and respiratory organs. It is a member of a large family belonging to the immunoglobulin superfamily. In order to develop a mouse model to study tumor immunotherapy using CEA as a target antigen, we have established mice which are transgenic for the CEA gene. The human CEA transgene maintains its spatiotemporal expression pattern in transgenic mice thus providing a suitable model in which to optimize different immunotherapy approaches, with the advantage that negative side effects due to the presence of CEA in normal tissue can be analyzed.

Animals↗
PubMed1995

[Effects of different anemia prevention forms on the blood parameters of the suckling piglet].

The results of this trials confirmed the earlier experience that suckling piglets kept indoors, without iron supplementation, develop iron deficiency after 14 days postpartum. Piglets kept outdoors did not develop iron deficiency because of the daily iron supplementation from the ground. Principally, a single dose of iron either parenteral (injection) or oral (iron paste) would supply the iron requirements of the suckling piglets. However, iron injection provided even results than that of the oral supply where some piglets treated orally, developed anemia because oral treatment runs a greater risk of misapplication. Best results were obtained by use of an iron form which can be scattered on the ground during the whole period of suckling. The piglets would receive their iron requirement freely during this period. Another form of iron-electrolyte solution can be supplied through the drinking automate. However, the results were unfavorable and the piglets developed symptoms of anemia. This could be attributed to the fact that the piglets do not require extra fluids during the suckling period, when they receive enough dam milk.

Administration, Oral↗
PubMed1994

CGM2, a member of the carcinoembryonic antigen gene family is down-regulated in colorectal carcinomas.

We have determined the precise chromosomal location, the exon structure, and the expression pattern of CGM2, a member of the carcinoembryonic antigen (CEA) gene family. CGM2 cDNA was amplified by reverse transcription-polymerase chain reaction (RT/PCR) from the colon adenocarcinoma cell line, LS174T. A defective exon is missing from this cDNA clone, leading to a novel domain organization for the human CEA family with two immunoglobulin-like domains. The derived C-terminal domain predicts that the CGM2 protein is membrane-bound through a glycosyl phosphatidylinositol anchor. RT/PCR analyses identified CGM2 transcripts in mucinous ovarian and colonic adenocarcinomas as well as in adjacent colonic tissue, but not in other tumors including leukocytes from six chronic myeloid leukemia patients. Thus, unlike several other family members, CGM2 is not expressed in granulocytes but reveals a more CEA-like expression pattern. Northern blot analyses identified a 2.5-kilobase CGM2 mRNA that is strongly down-regulated in colonic adenocarcinomas compared with adjacent colonic mucosa, suggesting a possible tumor suppressor function. In addition, a 3.2-kilobase transcript was observed in a number of colon tumors that is not detectable in normal colonic tissue. This mRNA species could represent a tumor-specific CGM2 splice variant.

Adenocarcinoma↗
PubMed1994

Synthesis of heterocyclic platelet activating factor analogues.

The synthesis of heterocyclic analogues of the platelet activating factor is described. The preparation starts with acylating rac-tetrahydro-1,3-thiazine-4-carboxylic acid ethyl ester, with palmitoyl chloride to form the amide linkage. Following ester reduction, the phosphocholine part is introduced via 2-chloro-2-oxo-1,3,2-dioxaphospholane and subsequent ring opening with trimethylamine under pressure. Furthermore, the related L-thiazolidine analogue is prepared using the same procedure. In addition the sulfinyl and sulfonyl derivatives of this compound are obtained by oxidation with 3-chloro-perbencoic acid. From one sulfinyl intermediate the diastereomeres are separated and their conformations are determinated by 13C-NMR spectroscopy.

Carbon Isotopes↗
PubMed1994

Mice transgenic for the human carcinoembryonic antigen gene maintain its spatiotemporal expression pattern.

The tumor marker carcinoembryonic antigen (CEA) is predominantly expressed in epithelial cells along the gastrointestinal tract and in a variety of adenocarcinomas. As a basis for investigating its in vivo regulation and for establishing an animal model for tumor immunotherapy, transgenic mice were generated with a 33-kilobase cosmid clone insert containing the complete human CEA gene and flanking sequences. CEA was found in the tongue, esophagus, stomach, small intestine, cecum, colon, and trachea and at low levels in the lung, testis, and uterus of adult mice of independent transgenic strains. CEA was first detected at day 10.5 of embryonic development (embryonic day 10.5) in primary trophoblast giant cells and was found in the developing gut, urethra, trachea, lung, and nucleus pulposus of the vertebral column from embryonic day 14.5 onwards. From embryonic day 16.5 CEA was also visible in the nasal mucosa and tongue. Because this spatiotemporal expression pattern correlates well with that known for humans, it follows that the transferred genomic region contains all of the regulatory elements required for the correct expression of CEA. Furthermore, although mice apparently lack an endogenous CEA gene, the entire repertoire of transcription factors necessary for correct expression of the CEA transgene is conserved between mice and humans. After tumor induction, these immunocompetent mice will serve as a model for optimizing various forms of immunotherapy, using CEA as a target antigen.

Animals↗
PubMed1994

Effects of saterinone and its enantiomers R(+)-saterinone and S(-)-saterinone on the phosphodiesterase isoenzymes from ventricular tissue of failing human hearts and porcine hearts.

Stereoisomers often exhibit differences in their pharmacological activities. Therefore, the phosphodiesterase inhibitory effects of the cardiotonic agent saterinone in form of the racemate were investigated in comparison with the inhibitory properties of its enantiomers R(+)- and S(-)-saterinone. For this purpose the phosphodiesterase isoenzymes from ventricular tissue of failing human hearts and porcine hearts were separated by DEAE-sepharose anion exchange chromatography. Four different phosphodiesterase isoenzymes were isolated from failing human myocardium and designated phosphodiesterase I-IV. Three phosphodiesterase isoenzymes could be separated from ventricular tissue of porcine hearts. A Ca2+/calmodulin stimulated phosphodiesterase I was not detectable in porcine myocardium. In failing human hearts racemic saterinone was a potent inhibitor of phosphodiesterase III (IC50 0.02 mumol/l) and IV (IC50 0.03 mumol/l) as compared to the inhibition of phosphodiesterase I (IC50 37.3 mumol/l) and II (IC50 51.4 mumol/l). In comparison with the racemate, R(+)- and S(-)-saterinone showed only slight differences in their phosphodiesterase inhibitory effects. R(+)-saterinone inhibited phosphodiesterase III slightly but significantly more potently and selectively than did S(-)-saterinone. Compared to the inhibition of phosphodiesterase I and II both enantiomers were similarly potent and selective inhibitors of phosphodiesterase III and IV. Similar results were obtained in porcine hearts. It is concluded that the racemate saterinone and its enantiomers (R(+)- and S(-)-saterinone are virtually equipotent concerning the inhibition of phosphodiesterase isoenzymes isolated from failing human hearts or porcine ventricular tissue. The enantiomers of saterinone did not exhibit distinct stereoselectivity in their phosphodiesterase inhibitory effects.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Detection of Borna disease virus RNA in naturally infected animals by a nested polymerase chain reaction.

Borna disease virus in naturally infected horses, a donkey and sheep was detected for the first time by amplification of viral RNA using PCR. In contrast to a control group of healthy horses, brain tissue was positive by this assay in all animals with neurological symptoms. The use of a second round of PCR with nested primers following Southern hybridization confirmed the specificity and increased the sensitivity of the test. Comparison with conventional methods recommends this technique for monitoring of BDV infections at a molecular level.

Animals↗
PubMed1994

A new miniature ultrasonic probe for gastrointestinal scanning: feasibility and preliminary results.

A prototype of a new miniature ultrasonic probe (Aloka) was clinically evaluated in 37 patients with a variety of gastrointestinal lesions. The probe's diameter of 2.0 mm allowed passage through the working channel of conventional endoscopes; the ultrasonic frequencies used were 15 and 20 MHz. Fourteen patients with benign and malignant gastrointestinal tumors, and thirteen patients with a variety of benign conditions, were examined, 12 of whom also underwent conventional endoscopic ultrasonography with side-viewing echoendoscopes. The image quality of the two systems was well comparable, but the ultrasonic penetration depth of the miniprobes was inferior to that of conventional endoscopic ultrasonography (EUS). All but three lesions were adequately visualized by the ultrasonic probe, whereas conventional EUS failed to completely visualize four cases. Of the two ultrasonic frequencies used, we found 15 MHz to be superior, since it provided good image quality and adequate penetration depth. In conclusion, we feel that the probe can be used for EUS indications in the gastrointestinal tract, whereas further technical improvements, such as increasing the penetration depth, are necessary before pancreatobiliary EUS can be carried out.

Adult↗
PubMed1994

The role of initial laparotomy and second-look surgery in the treatment of abdominal B-cell non-Hodgkin's lymphoma of childhood. A report of the BFM Group.

The aim of this study was to determine the role of surgery in the treatment of abdominal B-cell non-Hodgkin's lymphomas (B-NHL) in children. We analyzed the effect of surgical variables of initial laparotomy and second-look surgery on event-free survival (EFS) of 177 patients with abdominal B-NHL enrolled into the three consecutive multicenter trials NHL-BFM 81, NHL-BFM 83, and NHL-BFM 86. The therapy regimen was comparable in all 3 trials as well as the overall outcome of the patients. Patients with stage II and complete resection received 3 courses of therapy (4 in trial NHL-BFM 81), patients with stage II not resected, stage III, and stage IV received 6 courses of therapy (8 in trial NHL-BFM 81). An initial laparotomy was performed in 161 patients, in 59 of them as an urgent procedure. Complete resection of the abdominal primary was performed in 43 patients, 40 of them had a localized bowel tumor. The probability of EFS (pEFS) at 5 years is 95%, 69%, 62%, and 67% for patients with complete resection, subtotal resection (n = 36), partial resection (n = 21), or biopsy only (n = 61), respectively. Complete resection was achieved in 30 out of 40 patients with stage II, but only in 12 of 113 and 1 of 24 patients with stage III and IV, respectively. pEFS at 5 years according to stage and completeness of resection is as follows: stage II complete resected 97%; stage II not complete resected 100%; stage III/IV complete resected 92%; stage III/IV not complete resected 63%.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Neoplasms↗
PubMed1994

Physical, mental, emotional, and subjective workload components in train drivers.

This study, using 12 train drivers on a high speed track and 11 drivers on a mountain track, tried to differentiate between the physical, emotional, mental, and subjective workload components imposed on the drivers during work. With the simultaneous recording and on-line analysis of heart rate and physical activity, the emotional component in terms of the so-called additional heart rate was separated from the physical component. Mental workload was calculated by the heart rate variability and by shifts in the T-wave amplitude of the ECG. Speed of the train, mode of driving, and stress of the situation were rated by two observers who accompanied the drivers in the cabin. During speeds up to 100 km/h as compared to standstills no heart rate changes occurred, but with speeds from 100 km/h up to 200 km/h heart rate decreased indicating a monotony effect. However, heart rate variability, and T-wave amplitude indicated higher mental load during driving in most speed categories. Starting the train and coming to a halt showed greater emotional workload as compared to moving. Observer ratings of stress and subjective ratings of stress by the drivers revealed several discrepancies. Discrepancies were also seen between workload as indicated by the physiological parameters, and corresponding stress ratings by the observers or by the drivers.

Heart Rate↗
PubMed1994

Sequence conservation in field and experimental isolates of Borna disease virus.

Coding and noncoding sequences were analyzed from field and experimental isolates of Borna disease virus. For a 24-kDa protein, maximum divergence was 1.5% at the predicted amino acid level and 3.1% at the nucleotide level. For a 40-kDa protein, maximum divergence was 1.1% at the predicted amino acid level and 4.1% at the nucleotide level. The highest variability in sequence (10%) was found in a 40-nucleotide stretch of genomic RNA between coding sequences for the 40- and 24-kDa proteins. The degree of sequence conservation in these isolates, passaged in various host species in vivo and in vitro over a period of 64 years, is unusual for negative-strand RNA viruses.

Animals↗
PubMed1994

Borna disease virus: immunoelectron microscopic characterization of cell-free virus and further information about the genome.

The etiological agent of Borna disease, a persistent virus infection of the central nervous system with differently expressed symptomatology, was morphologically unknown. Here we provide the first convincing data on its phenotypic architecture. Salt-released virus comprising the biological parameters of Koch's postulates has an unsegmented single-stranded RNA. A dense band (1.22 g/cm3) in CsCl contains 90-nm particles which appear to be enveloped and a fraction of 50- to 60-nm particles. Labeling of the virions with neutralizing antisera and colloidal gold conjugates indicates that the 90-nm particles most likely represent the causative agent.

Animals↗