Biomedical subjects

A Dietrich

Publications and source records attributed to A Dietrich.

At least 91 records · Page 5Linked to original sources

PubMed1994

Primed lymphocytes are boosted by type II collagen of their hosts after adoptive transfer.

A central question in understanding autoimmunity is whether an endogenous self-antigen can drive an immune response initially triggered by a foreign one. This possibility is here tested by adoptive transfer, in which T and B cells from mice primed with foreign type II collagen were transferred into irradiated syngeneic hosts. Previous work with other protein antigens has established that primed cells normally respond only if boosted after transfer with antigen. In the present case, and in respect only to that portion of the antibody response able to bind to endogenous type II collagen, that requirement did not hold. This indicates that the anti-self component is indeed driven by endogenous antigen, which the transferred lymphocytes presumably obtain from their adoptive hosts. The transfers were carried out in C57BL10.A x DBA/1 mice using donors primed with either chick or bovine collagen, and the non-boosted responses, presumably driven by endogenous antigen, could be followed in a proportion of the recipients for as long as 45 days.

Animals↗

PubMed1994

Characterization of some major identity elements in plant alanine and phenylalanine transfer RNAs.

Alanine and phenylalanine tRNA sequences were amplified by PCR from Arabidopsis thaliana nuclear DNA using degenerate oligonucleotides which introduced specific mutations into the acceptor stem. The aminoacylation of T7 RNA polymerase transcripts of these sequences was investigated in vitro using partially purified bean alanyl- or phenylalanyl-tRNA synthetase. In parallel, the in vivo activity of amber suppressor derivatives of these tRNAs was investigated in transient expression assays in tobacco protoplasts using a beta-glucuronidase (GUS) reporter gene containing a premature amber stop codon. The results show that mutation of the G3:U70 base pair to G3:C70 blocks aminoacylation of plant alanine tRNA, whilst conversion of the G3:C70 pair normally found in plant tRNA(Phe) to G3:U70 enables the mutated tRNA(Phe) to be a good substrate for alanyl-tRNA synthetase and impairs its aminoacylation with phenylalanine. In addition, the amber suppressor derivative of wild-type tRNA(Phe) showed very little suppressor activity in vivo, and was poorly aminoacylated with phenylalanine in vitro, suggesting that the anticodon is a major identity determinant for tRNA(Phe) in plant cells.

Alanine-tRNA Ligase↗

PubMed1994

Suppression of arthritis by an active center analogue of Cu2Zn2-superoxide dismutase.

The anti-arthritic and anti-inflammatory efficacy of CuPu(Py)2 ([N,N'-bis(2-pyridylmethylene)-1,4-butanediamine] (N,N',N",N"))-Cu(II), a serum-stable active center analogue of Cu2Zn2-superoxide dismutase (SOD; EC 1.15.1.1), was tested in male DBA/1 x B10A (4R) mice suffering from potassium-peroxochromate-induced (PIA) or collagen type II-induced arthritis (CIA). Parameters including the arthritis index, the plasma SOD activity, and the inhibition of phagocytic responses in unseparated blood were used for the assessment of disease activity. A dose-dependent suppression of arthritis was noted in both models. The ED50 was 2.5 +/- 0.4 mumol/kg/day of CuPu(Py)2 for PIA and 4.0 +/- 1.1 mumol/kg/day for CIA. The arthritis index correlated with both the levels of reactive oxygen species (ROS) generated by phorbol ester-activated neutrophils and monocytes in unseparated blood (r = 0.892) and the SOD-like activity in plasma (r = 0.857). CuPu(Py)2 inhibited also the lipoplysaccharide-induced release of tumor necrosis factor alpha from human monocytes and neutrophils in a dose-dependent manner. Unlike SOD, which exerts successful anti-rheumatic activity mainly upon intra-articular injection, the SOD-mimic CuPu(Py)2 can be applied systemically. Non-proteinaceous low molecular weight antioxidases may well be suited to control oxidative stress-derived damage in rheumatic diseases by modulation of ROS-dependent signal transduction pathways.

Animals↗

PubMed1994

Pain after laparoscopic cholecystectomy. Intensity and localization of pain and analysis of predictors in preoperative symptoms and intraoperative events.

It is postulated that laparoscopic cholecystectomy as "patient-friendly surgery" leads to more comfort and in particular to less pain. A prospective study on pain was performed on all patients undergoing the operation over the period of 1 year (n = 382) out of a series of more than 1,000 patients who have undergone the operation in our clinic. Pain was measured by a 100-point visual analogue scale (VAS), by a five-point verbal rating scale, and by the consumption of analgesics. Pain was the most frequent symptom, both before and after the operation. The mean level of pain was 37 VAS points 5 h after the operation and declined to 16 points on the third day. In 106 patients (27.8%) the intensity of pain was higher than 50 VAS points. Analgesics were used by 282 patients (73.8%), opioids by 112 (29.3%). Pain was significantly higher in female than male patients (P < 0.05), but consumption of analgesics was similar in both groups. The most severe pain was localized to the abdominal wall wounds by 157 (41.1%) and to the right upper abdomen by 138 patients (36.1%) on the first postoperative day. Patients who needed opioids and/or had a pain level of > 50 VAS points (n = 138) had higher preoperative pain levels (P = 0.018) and preoperatively complained more frequently about nausea, vomiting, bloating, and a feeling of abdominal pressure (P = 0.003-0.031). However, predictive values of these variables were too small to be of clinical benefit.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Pain↗

PubMed1994

Highly homologous loci on the X and Y chromosomes are hot-spots for ectopic recombinations leading to XX maleness.

In 80% of XX males, maleness is due to the presence of Y-specific DNA including the SRY gene and results from an abnormal terminal X-Y interchange during paternal meiosis. Here we address the molecular basis of this ectopic recombination through the analysis of the X-Y junction in two class 3 XX males. We show that each of the rearrangements has involved X-Y highly homologous loci on the sex-specific part of these chromosomes (98.7% and 96% sequence identity over 1.2 and 1.1 kb respectively). Moreover in five out of six other XX males, the X-Y junctions are located in the same rearranged restriction fragment as in either of these patients. These fragments thus define two hot-spots of ectopic recombination which together could account for about one third of XX males. Evolution of these loci in primates is discussed.

Animals↗

PubMed1994

A YAC clone map spanning 7.5 megabases of human chromosome band Xq28.

Xq28 has been of special interest in human genetics because a large number of diseases map to this region. As a step in the molecular analysis of the as yet uncloned disease genes, and as a test for the detailed analysis of larger regions of the genome, we have constructed YAC clone contigs covering the 7.5 Mb region between IDS to the telomere on the long arm of the human X chromosome. Contigs were assembled and verified by an integrated hybridization-based strategy. Data was combined from the physical map, from YAC and cosmid mapping experiments, and from the localization of specific transcripts in the region. Two gaps in the YAC map of 250 and 100 kb were covered in part by the aid of cosmid clones, but small gaps of 50 kb each remain. The cloned region is expected to contain yet unidentified genes for at least ten genetic diseases. The construction of ordered YAC clone contigs of Xq28 represents an important step in the molecular identification of these genes, and the further analysis of one of the genetically most interesting regions of the human genome.

Chromosomes, Artificial, Yeast↗

PubMed1994

Expression of the B7/BB1 activation antigen and its ligand CD28 in T-cell-mediated skin diseases.

Interactions of CD28 (on T cells) with its recently identified ligand B7/BB1 (on antigen-presenting cells) have been shown to activate T cells via a major histocompatibility complex/Ag-independent "alternative" pathway, leading to an amplification of T-cell-mediated immune responses. The in vivo relevance of these molecules for cutaneous immunity is presently unknown. These findings prompted us to study the expression of B7/BB1 and CD28 in normal human skin and in selected T-cell-mediated inflammatory skin diseases. Biopsies were obtained from lesional skin of patients with allergic contact dermatitis, lichen planus, and, as control, from basal cell carcinoma and from healthy controls. Serial cryostat sections were stained with a panel of MoAbs directed against CD28, B7/BB1, CD3, CD1a, and KiM8 using immunohistochemistry (ABC technique). CD28 expression was observed in the majority of dermal and epidermal CD3+ T cells in contact dermatitis and lichen planus. In normal skin and basal cell carcinoma, CD28 was expressed only occasionally by perivascular T cells. In allergic contact dermatitis and lichen planus, B7/BB1-expression was found on dermal dendritic cells, on dermal macrophages, on Langerhans cells, focally on keratinocytes, and occasionally on dermal T cells. No B7/BB1 immunoreactivity was detected in normal skin and basal cell carcinoma. These findings indicate that T-cell-mediated skin diseases are accompanied by an influx of CD28+ T cells and an upregulation of B7/BB1 on cutaneous antigen-presenting cells, keratinocytes, and on some T cells. We speculate that "alternative" T cell-activation via the B7/CD28 pathway may contribute to the pathogenesis of these skin diseases.

Antibodies, Monoclonal↗

PubMed1994

Assessment of collagen type II induced arthritis in mice by whole blood chemiluminescence.

Lucigenin-enhanced chemiluminescence can be measured in 100 microliters samples of whole, unseparated mouse blood. A procedure for doing so is here described in detail, using a standard clinical luminometer. The assay measures the TPA-induced oxidative burst from granulocytes and macrophages, which is believed to depend on the overall level of inflammation in the body. It is here applied to mice suffering from type II collagen-induced arthritis, and its relation to overt disease symptoms (the arthritis score) is characterised during the course of the disease. A correlation between the assay and the arthritis score is found at the height of the disease (r = 0.42, p = .039), but not at early or very late time points, although there is a strong hint that the results of an early assay may predict the subsequent disease course. The assay provides a rapid, convenient, quantitative and economical method of assessing disease activity, which can be carried out repeatedly on the same individual. It should be applicable in other mouse models of chronic inflammatory disease. It may find application for rapid screening of novel anti-rheumatic drugs and treatments.

Acridines↗

PubMed1993

Editing corrects mispairing in the acceptor stem of bean and potato mitochondrial phenylalanine transfer RNAs.

Editing is a general event in plant mitochondrial messenger RNAs, but has never been detected in a plant mitochondrial transfer RNA (tRNA). We demonstrate here the occurrence of a tRNA editing event in higher plant mitochondria: in both bean and potato, the C encoded at position 4 in the mitochondrial tRNA(Phe)(GAA) gene is converted into a U in the mature tRNA. This nucleotide change corrects the mismatched C4-A69 base-pair which appears when folding the gene sequence into the cloverleaf structure and it is consistent with the fact that C to U transitions constitute the common editing events affecting plant mitochondrial messenger RNAs. The tRNA(Phe)(GAA) gene is located upstream of the single copy tRNA(Pro)(UGG) gene in both the potato and the bean mitochondrial DNAs. The sequences of potato and bean tRNA(Pro)(UGG) genes are colinear with the sequence of the mature bean mitochondrial tRNA(Pro)(UGG), demonstrating that this tRNA is not edited. A single copy tRNA(Ser)(GCU) gene was found upstream of the tRNA(Phe) gene in the potato mitochondrial DNA. A U6-U67 mismatched base-pair appears in the cloverleaf folding of this gene and is maintained in the mature potato mitochondrial tRNA(Ser)(GCU), which argues in favour of the hypothesis that the editing system of plant mitochondria can only perform C to U or occasionally U to C changes.

Base Sequence↗

PubMed1993

The potato mitochondrial initiator methionine tRNA gene and its flanking regions: an illustration of the diversity of mitochondrial genome rearrangements among plant species.

The initiator methionine transfer RNA (tRNA(fMet)) gene was identified on a 347 bp Eco RI-Hind III DNA fragment of the potato mitochondrial (mt) genome. The sequence of this gene shows 1 to 7 nucleotide differences with the other plant mt tRNAs(fMet) or tRNA(fMet) genes studied so far. Whereas the tRNA(fMet) gene is present as a single copy in the potato mt genome, a tRNA 'pseudogene' corresponding to 60% of a complete tRNA (from the 5' end to the variable region) and located at 105 nucleotides upstream of the tRNA(fMet) gene on the opposite strand was shown to be repeated at least three times. Furthermore, the physical environment of the tRNA(fMet) gene in the mt genome is very different among plants, which suggests that the tRNA(fMet) gene region has often been implicated in recombination events of plant mt genomes leading to important rearrangements in gene order.

Base Sequence↗

PubMed1993

Cardiac toxicity in an adolescent following chronic lithium and imipramine therapy.

A case report is presented of an adolescent male who developed hypothyroidism and cardiomyopathy 6 months after he began taking lithium and imipramine for a severe conduct disorder. After discontinuation of psychiatric medications and institution of thyroid hormone replacement therapy, he developed asymptomatic but potentially serious dysrhythmias. Evidence for potential cardiac toxicity of combined lithium and tricyclic antidepressant therapy is reviewed. Repeated assessment of cardiac function during such therapy is advised.

Adolescent↗

PubMed1993

Phorbol-12-myristate-13-acetate-treated human keratinocytes express B7-like molecules that serve a costimulatory role in T-cell activation.

In previous studies, Phorbol-12-myristate-13-acetate (PMA)-treated human keratinocytes (PMA-HNK) were shown to induce T-cell proliferation via a major histocompatibility complex (MHC)- and antigen (Ag)-independent mechanism, that was mediated in part by PMA-induced intercellular adhesion molecule (ICAM)-1 on HNK. Recently, the interaction of the B7 Ag on antigen-presenting cells with its ligand CD28 on T cells has been shown to deliver activation signals distinct from the interaction of MHC/Ag with the T-cell receptor. These findings led us to assess whether B7-dependent signals play a role in T-cell proliferation induced by PMA-HNK. We first examined B7 expression on HNK by staining with three different monoclonal antibodies (MoAbs). When analyzed by fluorescence-activated cell sorter, untreated HNK stained only faintly. By contrast, PMA induced a dose-dependent upregulation of B7 staining. This staining identifies a molecule closely related to B7 because it was blocked by purified recombinant B7 immunoglobulin. Upregulation of B7 staining was first observed 16 h after PMA treatment and persisted for at least 48 h; it was protein kinase C dependent and required de novo protein synthesis. Anti-B7 MoAbs reduced specifically the capacity of PMA-HNK to trigger proliferation of allogeneic peripheral blood mononuclear cells and T cells. The combination of anti-B7 and anti-ICAM-1 MoAbs further reduced this response. We conclude that PMA upregulates on HNK the expression of a B7-like molecule that contributes in concert with ICAM-1 to the capacity of PMA-HNK to induce proliferation of allogeneic T cells.

Animals↗

PubMed1992

Expression, characterization and purification of soluble G-protein beta gamma dimers composed of defined subunits in baculovirus-infected insect cells.

Recombinant beta 1 gamma 2 dimers of signal-transducing guanine nucleotide-binding proteins (G-proteins) carrying a mutation known to block isoprenylation of the gamma 2 subunit were expressed as a soluble protein in baculovirus-infected insect cells. The soluble beta gamma dimer was analyzed by sucrose density gradient centrifugation and purified to near homogeneity in the absence of detergents. The sedimentation velocity studies gave an S20,w value of 4.1 +/- 0.4 S. The two subunits segregated as a dimer upon sucrose density gradient centrifugation and purification by sequential ion exchange and hydroxylapatite chromatography. The results show that baculovirus-infected insect cells can be employed for high level production of pure G-protein beta gamma dimers suitable for functional and structural characterization.

Amino Acid Sequence↗

PubMed1992

Novel spirosuccinimides with incorporated isoindolone and benzisothiazole 1,1-dioxide moieties as aldose reductase inhibitors and antihyperglycemic agents.

Compounds from two novel series of spirosuccinimides were prepared. Analogs of series 2 possessed a spiro-fused isoindolone moiety while those of series 3 contained a spiro-fused benzisothiazole S,S-dioxide group. These compounds were evaluated as aldose reductase inhibitors (ARI) in vitro by their ability to inhibit glyceraldehyde reduction using a partially purified bovine lens aldose reductase preparation and in vivo as inhibitors of galactitol accumulation in the lens, sciatic nerve, and diaphragm of galactose-fed rats. Many members from the isoindolone series 2, particularly those containing an isoindolone N-methyl moiety, showed good in vitro and in vivo potency. The most potent member, the 6-chloro analog 32, was resolved, and aldose reductase activity was found to reside almost exclusively in the (+)-enantiomer. Compound 32 was approximately equipotent in the sciatic nerve of the galactose-fed rat to other cyclic imide ARI's of similar in vitro activity, namely sorbinil and ADN-138 and also to tolrestat, an acetic acid-based ARI (ED50's 4-8 mg/kg). Compounds from both series, 2 and 3, were also found to lower plasma glucose levels of genetically obese db/db and ob/ob mice with potency similar to that of ciglitazone. However, members from these series failed to lower insulin levels of the ob/ob mouse at the doses tested.

Aldehyde Reductase↗

PubMed1992

Fluorescence formation during photodynamic therapy in the nucleus of cells incubated with cationic and anionic water-soluble photosensitizers.

The variations of fluorescence during light exposure of the cationic sensitizers methylene blue (MB) and meso-tetra(4N-methylpyridyl)porphyrin (T4MPyP) as well as the anionic meso-tetra(4-sulphonatophenyl)porphyrin (TPPS4) were measured at different intracellular sites using video-intensified microscopy in combination with microspectrofluorometry. Before light exposure the sensitizers were localized in distinct parts of the cytoplasm, especially in fluorescent organelles. During irradiation a drastic fluorescence formation and increase in the cytoplasm and nucleus, which was most pronounced in the nucleoli, could be observed for the cationic sensitizers as well as TPPS4. In the case of MB the increase in fluorescence was concomitant with a spectral shift in the emission spectra. For TPPS4 and T4MPyP the formation of a second species with a Soret band shifted towards longer wavelengths was observed and correlated with the fluorescence increase in the nucleoli. Cell deformations also took place.

Animals↗

PubMed1992

Evaluation of routine upper digestive tract endoscopy before laparoscopic cholecystectomy.

Endoscopy of the upper digestive tract was performed in 376 patients with symptomatic gallstone disease before elective laparoscopic cholecystectomy. Abnormalities were found in 60 patients (16.0 per cent); these included peptic ulcer (n = 14), gastric erosions (n = 15) and oesophagitis (n = 11). Thirty patients were treated medically and two by endoscopic polypectomy. In four patients endoscopy led to cancellation of cholecystectomy; in two the complaints have persisted. Statistical analysis of 28 variables showed few significant differences in symptoms between patients with normal and those with abnormal appearances at endoscopy. It is concluded that routine endoscopy before laparoscopic cholecystectomy is neither clinically useful nor cost effective in patients with symptomatic gallstone disease. This conclusion is related exclusively to patients with typical gallstone symptoms according to the definition used in this department.

Adolescent↗

PubMed1992

In vivo import of a normal or mutagenized heterologous transfer RNA into the mitochondria of transgenic plants: towards novel ways of influencing mitochondrial gene expression?

Evidence that nuclear-encoded RNAs are present inside mitochondria has been reported from a wide variety of organisms, and is presumed to be due to import of specific cytosolic RNAs. In plants, the first examples were the mitochondrial leucine transfer RNAs of bean. In all cases, the evidence is circumstantial, based on hybridization of the mitochondrial RNAs to nuclear and not mitochondrial DNA. Here we show that transgenic potato plants carrying a leucine tRNA gene from bean nuclear DNA contain RNA transcribed from the introduced gene both in the cytosol and inside mitochondria, providing proof that the mitochondrial leucine tRNA is derived from a nuclear gene and imported into the mitochondria. The same bean gene carrying a 4 bp insertion in the anticodon loop was also expressed in transgenic potato plants and the transcript found to be present inside mitochondria, suggesting that this natural RNA import system could eventually be used to introduce foreign RNA sequences into mitochondria.

Base Sequence↗

PubMed1992

Completion of the physical map of Xq28: the location of the gene for L1CAM on the human X chromosome.

The gene for the neural cell adhesion molecule L1 (L1CAM) has been shown to be located close to the color vision pigment genes in mouse and man. This location has been confirmed by a number of different mapping strategies in both species. With pulsed field gel electrophoresis it has been proposed that L1CAM lies between the RCP, GCP, and GDX, G6PD loci. We report here a reinterpretation of the location of this gene, based on the physical linkage of L1CAM to the more proximal locus DXS15. This places L1CAM between this marker and the color vision genes (RCP, GCP), a region very dense in CpG islands, expected to contain a large fraction of the disease genes assigned to the Xq28 region. In combination with the physical mapping data on Xq28 described previously, this closes the last remaining gap in the map of the Xq27-Xq28 region. This removes the last contradiction between the maps of this region in the genomes of man and mouse, and confirms the close similarity of order and distances of markers between these organisms.

Cell Adhesion Molecules, Neuronal↗