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D Sorger

Publications and source records attributed to D Sorger.

At least 19 recordsLinked to original sources
PubMed2003

Triacylglycerol biosynthesis in yeast.

Triacylglycerol (TAG) is the major storage component for fatty acids, and thus for energy, in eukaryotic cells. In this mini-review, we describe recent progress that has been made with the yeast Saccharomyces cerevisiae in understanding formation of TAG and its cell biological role. Formation of TAG involves the synthesis of phosphatidic acid (PA) and diacylglycerol (DAG), two key intermediates of lipid metabolism. De novo formation of PA in yeast as in other types of cells can occur either through the glycerol-3-phosphate- or dihydroxyacetone phosphate-pathways-each named after its respective precursor. PA, formed in two steps of acylation, is converted to DAG by phosphatidate phosphatase. Acylation of DAG to yield TAG is catalyzed mainly by the two yeast proteins Dga1p and Lro1p, which utilize acyl-CoA or phosphatidylcholine, respectively, as acyl donors. In addition, minor alternative routes of DAG acylation appear to exist. Endoplasmic reticulum and lipid particles (LP), the TAG storage compartment in yeast, are the major sites of TAG synthesis. The interplay of these organelles, formation of LP, and enzymatic properties of enzymes catalyzing the synthesis of PA, DAG, and TAG in yeast are discussed in this communication.

Acylation↗
PubMed2001

Differential alteration of the nigrostriatal dopaminergic system in Wilson's disease investigated with [123I]ss-CIT and high-resolution SPET.

Wilson's disease (WD) is a copper deposition disorder which can result in a number of extrapyramidal motoric symptoms such as parkinsonism. Therefore, this study was carried out to investigate, for the first time, nigrostriatal dopaminergic function in WD in relation to different courses and severity of the disease. Using high-resolution single-photon emission tomography (SPET) after administration of 2ss-carbomethoxy-3ss-(4[123I]iodophenyl)tropane ([123I]ss-CIT), striatal dopamine transporters (DAT) were imaged in 43 WD patients and a control group of ten subjects. From the SPET images, specific [123I]ss-CIT binding ratios were obtained for the caudate heads, putamina and entire corpus striatum. In addition, to evaluate a putative dissociation between the caudate and putaminal [123I]ss-CIT binding ratios, the ratio between these binding ratios was calculated (CA/PU ratio). The SPET data were compared with clinical data on the course of the disease (CD), the severity of neurological symptoms and the degree of hepatic alteration. Whereas the specific regional [123I]ss-CIT binding ratios in patients with asymptomatic/hepatic CD did not differ from those in the control group (e.g. striatal ratios: 13.4+/-3.0 vs 11.7+/-2.8), in patients with neurological CD the ratios were significantly reduced for all striatal substructures (P=0.003 after one-factor ANOVA). For the different subgroups a tendency was detected towards a stepwise decrease in the specific [123I]ss-CIT binding ratios from pseudo-sclerosis CD (9.4+/-2.3), through pseudo-parkinsonian CD (9.1+/-2.1) to arrhythmic-hyperkinetic CD (8.5+/-1.6). However, these group differences reached significance only for the comparison with asymptomatic/hepatic CD (P=0.02). The CA/PU ratio was significantly higher in WD than in the control group (1.30+/-0.19 vs 1.11+/-0.08; P=0.003). Severity of neurological symptoms was significantly correlated with all specific regional [123I]ss-CIT binding ratios (r=-0.49 to -0.57). For degree of liver alteration, significant correlations were obtained with the putaminal binding ratio (r=-0.37) and the CA/PU ratio (r=0.44). From these results is concluded that in WD the nigrostriatal dopaminergic function is compromised to varying extents. The degree of this presynaptic alteration of dopaminergic neurotransmission depends on the clinical course and severity of this copper deposition brain disorder and also varies in the different striatal substructures.

Adult↗
PubMed2001

In vivo evidence for differential association of striatal dopamine and midbrain serotonin systems with neuropsychiatric symptoms in Parkinson's disease.

Parkinson's disease affects various neurotransmitter systems. Using SPECT, the authors measured [(123)I]beta-CIT binding ratios of the caudate, putamen, medial thalamus, and dorsal midbrain over cerebellum in 16 patients with Parkinson's disease, and examined correlations with clinical ratings. Whereas striatal binding ratios (reflecting regional dopamine transporter densities) were associated with motor symptoms, dorsal midbrain binding ratios (reflecting regional serotonin transporter densities) were significantly correlated with the mentation, behavior, and mood subscale of the Unified Parkinson's Disease Rating Scale. These findings indicate that degeneration of the nigrostriatal dopaminergic neurons and a dysfunctional serotonergic raphe system contribute differentially to motor deficits and neuropsychiatric symptoms in Parkinson's disease.

Adult↗
PubMed2000

In vivo [125I]-iodobenzovesamicol binding reflects cortical cholinergic deficiency induced by specific immunolesion of rat basal forebrain cholinergic system.

In this study, radiolabeled iodobenzovesamicol (IBVM), which is known to bind with high affinity to the vesicular acetylcholine transporter, was tested for its usefulness in imaging cortical cholinergic deficits in vivo. To induce reductions in cortical cholinergic input, the cholinergic immunotoxin 192IgG-saporin was employed. This has been shown to selectively and efficiently destroy basal forebrain cholinergic neurons in rats. The efficiency of the immunolesion was verified by histochemical acetylcholinesterase staining. [125I]-IBVM binding before and after lesioning was measured using autoradiography. Basal forebrain cholinergic cell loss resulted in a considerable reduction in [125I]-IBVM binding in the cholinoceptive target regions, but not in the striatum and cerebellum, brain regions that do not receive a cholinergic input by the basal forebrain cholinergic nuclei, suggesting that [123I]-IBVM has potential in imaging cortical cholinergic deficits in vivo, at least in animals.

Acetylcholinesterase↗
PubMed1999

Iodo-QNB cortical binding and brain perfusion: effects of a cholinergic basal forebrain lesion in the rat.

This study deals with the question of whether in vivo application of [125I]iodo-quinuclidinyl-benzilate (QNB) is able to demonstrate changes in cortical muscarinic receptor density induced by a cholinergic immunolesion of the rat basal forebrain cholinergic system, and whether the potential effects on IQNB distribution in vivo are also associated with effects on regional cerebral perfusion. Immunolesioned and control animals were injected with (R,S) [125]iodo-QNB and with [99mTc]-d,l-hexamethylpropyleneamine oxime (HMPAO). The cerebral distribution of both tracers was imaged using double tracer autoradiography. Impaired cholinergic transmission was paralleled by a 10-15% increase of [125I]iodo-QNB binding in the regions of cortex and hippocampus. The local cerebral blood flow remained unchanged after cholinergic lesion.

Acetylcholine↗
PubMed1996

Radioiodination of nicotine with specific activity high enough for mapping nicotinic acetylcholine receptors.

A novel radiochemical method is presented to synthesize 5-[123I/125I/131I]-dL-nicotine by radioiodination of 5-bromonicotine. Radioiodination of the precursor 5-dL-bromonicotine was achieved using a copper (I)-assisted nucleophilic exchange reaction in the presence of reducing agent. The reaction conditions were optimized by varying pH, concentration of Sn(II) salt, ascorbic acid, Cu(I)chloride and reaction temperature. After purification by high-performance liquid chromatography the radiochemical purity of the product exceeded 98%, with a radiochemical yield of 55% and a specific activity > or =5 GBq/micromol. Specific binding of the iodinated nicotine was demonstrated in rat brain by autoradiography. The radioactivity from the specific structures was displaced by an excess of non-radioactive nicotine (10(-3)M) with KD and Bmax of 13.1+/-7.8 nM and 22+/-2.7 fmol/mg protein and unspecific binding of about 40%. The in vivo distribution of 5-[131I]iodonicotine was determined in 20 female Wistar rats at various time intervals of 15s to 90 min post injection (p.i.) by well counting and autoradiography. Brain activity peaked within 0.5 min p.i., and then showed a biexponential washout. Initially, activity within the cerebral cortex exceeded that of the cerebellum by a factor of 1.5-2.0. It was also increased in the striatum and thalamus. However, as soon as 15 min p.i. activity was almost homogeneously distributed. In conclusion, synthesis of 5-iodo-dL-nicotine (labelled with 131I, 125I or 123I, respectively) with appropriately high specific activity for receptor studies was achieved and specific binding to nicotine receptors in rat brain was demonstrated; following intravenous injection, however, there is considerable unspecific binding, obviously due to highly flow-dependent tissue retention.

Animals↗
PubMed1995

[The prognostic value of cathepsin D in endometrial carcinoma].

The concentration of the lysosomal protease Cathepsin D was tested by means of RIA. We used the cytosols of 44 endometrial carcinoma tissue specimens and of the corresponding normal endometrial tissues (n = 42) obtained from the respective uteri after hysterectomy. All patients were in postmenopausal stage. A significant higher level of Cathepsin D expression was found in endometrial carcinoma (median value = 24.2 pmol/mg) compared to normal endometrium (median value = 11.4 pmol/mg). No difference in Cathepsin D concentration was found in relation to grade of histological differentiation (G1 vs. G2/G3), depth of myometrial invasion and tumor stage (stage IA vs. IB/IC vs. > I) as well as state of estrogen receptor (ER) and progesterone receptor (PR). After an average follow-up period of 18 months there was no significant difference in survival rate of operated patients depending on Cathepsin D concentration. However, the prognostic significance of this parameter need to be evaluated after a long-term follow-up. The overexpression of Cathepsin D seems to be important for exact biologic characterization of each endometrial carcinoma with respect to local proteolytic activity. The enhanced activity of cathepsin D may therefore serve as an additional objective malignancy criterion independent of the well-known prognostic factors.

Adenocarcinoma↗
PubMed1992

[Effects of various contraceptives on laboratory parameters in diagnosis of thyroid gland function with special reference to the free hormones FT4 and FT3].

The effect of different oral contraceptives with an estrogen content of 30-50 micrograms ethinyloestradiol on thyroid hormones and the binding protein TBG was investigated and quantified for 200 women. The sera of 220 normal persons were analysed to get normal values for T3, T4, FT4, Ft3, TBG and TSH. Under the influence of antiovulatory hormone treatment the thyroxin binding globulin increased to values above 32 mg/l in 65% of all euthyroid women. The median for T4 changed from 97 to 120 nmol/l, respectively from 2.3 to 2.8 nmol/l for T3. We think the combination of TSH, FT4 and T3 to be the best analytical tool for differential diagnosis of hyperthyreose. The FT4 level was nearly independent of variations in TBG concentration, so we can accept the normal range from 10-28 pmol/l for patients with contraceptives as well. In 16% of these euthyroid women the T3 level proved to be in the hyperthyroid range with values above 3.6 nmol/l. The FT3 determination is stronger influenced by protein changes caused by oestrogens than FT4 and should not be accepted as a favourite parameter for patients with oral contraceptives.

Adolescent↗
PubMed1991

[Cytomorphological and cytochemical studies of experimentally-induced thyroid tumors in the rat].

Carcinomas were induced to the thyroid gland of female rats, using a method originally proposed by Thomas and Bollmann (metachronous application of nitrosomethylurea and methylthiouracil), to establish cytomorphological, histomorphological, cytochemical, and flow-cytophotometric criteria for diagnosis of thyroid carcinoma. Verification was also intended of the diagnostic value of each of the methods involved for differentiation of nodular goitre. Another purpose of the study was to find out, whether chemically induced thyroid tumours in rat were comparable to thyroid neoplasms in man. This provided to the examiners genetically coherent and morphologically comparable biological material at various stages of thyroid tumour growth which included diffuse and adenomatous hyperplasias, adenomas, and, from the 18th to 42nd experimental weeks, papillary as well as follicular carcinomas in 31 to 100% of all experimental animals involved. Cytomorphological comparability of rat thyroid material (imprint specimens) with human material (fine-needle aspiration cytology) was ensured for normal as well as for hyperplastically altered thyroid glands, including adenomatous and carcinomatous changes. Hence, group typing of thyroid cytology, originally devised for human specimens, could be easily adapted to material obtained from rat. Assessment of cytological samples by microscopic criteria yielded an accuracy of 89% in malignoma diagnosis and proved to be an approach of highly informative potential also in the context of rat experiments. Use of additional cytochemical techniques (PAS, toluidine-blue, peroxidase, alkaline and acid phosphatases, gamma-glutamyl transpeptidase) as well as quantitative DNA determination by means of flow-cytophotometry was helpful in casting light at some scattered trends of change from normal for certain stages of proliferation, but it failed to enhance information in cytomorphological diagnosis of the individual case.

Adenocarcinoma↗
PubMed1990

Circannual oscillations of function compared with morphometric changes in the thyroid gland of the Wistar-rat.

To investigate biological rhythms of the thyroid gland circannual oscillations of thyroxine (T4), triiodothyronine (T3), and thyrotropin (TSH) were compared in serum samples of untreated young male Wistar-rats with the circannual changes of thyroid weights and with the relative proportion of colloid, epithelium, and interstitium of the thyroids. Animals were kept under standard environmental conditions, however, lighting conditions simulated the natural day-night changes. Thyroid weights, T4, T3, and TSH showed a statistically significant circannual rhythm with maxima in winter and spring and minima in summer and autumn. The same circannual patterns were observed in the proportion of epithelium and interstitium of the thyroids, while the colloid exhibited an inverse circannual pattern. These data were verified by biomathematical methods, like locally adjusted functional approximation, analysis of variance, and Spearman rank correlation. Our results represent an example for the concordance between functional and morphometrical changes in the course of circannual oscillations. Furthermore, these data confirm our earlier results describing higher T4-levels in the winter time (short-day) and lower serum titers in the summer time (long-day).

Animals↗
PubMed1990

[Combination of glandular and foveolar hyperplasia of the gastric mucosa--a rare mixed type].

In a 28 year-old man with epigastric pain endoscopy detected giant gastric folds and multiple superficial erosions. Histologically a mixed form of glandular and foveolar hyper plasia of the gastric mucosa was suggested (Ming's type III). Basal and pentagastrin stimulated secretion volume and acid output were moderately elevated, hypersecretion of protein was not found. Serum levels of calcium and gastrin were normal, also after secretin stimulation. The mucosa of the corpus was extensively infested with Campylobacter pylori. Therapy with cimetidine, antacids, pirenzepine and metronidazol resulted in relief of symptoms but not of histological findings. Bismuth (JatroxR) was successful in eradicating Campylobacter pylori and decreasing inflammation of the mucosa. Cause and prognosis of this mixed hyperplasia are not known.

Adult↗
PubMed1989

[Low T3 syndrome and chronic inflammatory rheumatism].

For the clarification of pathogenesis and clinical relevance of decreases of the triiodothyronine (T3) level in patients with chronic inflammatory rheumatism in a group of 63 patients with clinically, paraclinically and roentgenologically diagnosed rheumatoid arthritis (59 times) and with SLE (4 times), respectively, parallel were determined parameters of the thyroid gland function and of the rheumatic activity as well as a subtile drug anamnesis for the medication of antirheumatic drugs was established. In 33 of the 63 patients who were included into the study decreases and low normal values, respectively, for the total T3 (TT3 less than 1.5 nmol/l) were found. In comparison to the remaining 30 patients with normal TT3 a typical constellation of paraclinical parameters of the thyroid gland with distinct reduction of TT3 and free T3 (FT3), low normal total T4 (TT4), slight increase of the reverse T3 (rT3), moderate decrease of the basal and stimulated TSH and an only very small restriction of the binding capacity of the thyroid hormone (TBG) were found. A clinically relevant hypothyroidism is thus to be excluded with certainty. Antirheumatic drugs, in particular steroidal ones (glucocorticoids) may on principle also induce such paraclinical constellations, related to the thyroid gland. In our investigations a therapy with antirheumatic drugs is causally scarcely considered, since both in the group of patients with decrease of T3 and without decrease comparable quantities of antirheumatic drugs including glucocorticoids were administered and the cortisol values in the plasma do not differ. The investigations confirm our already formerly expressed supposition that also in rheumatics a "low-T3-syndrome" is existing as it is otherwise described in consumptive extrathyroidal diseases (NTI).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Changes in the blood picture in hyperthyroidism].

On the basis of a retrospective study about 276 clinically and paraclinically ascertained cases of hyperthyroidism in 34% of the patients above all mild anaemias could be proved which under thyreostatic therapy with thiamazol which after repeated incidence of an euthyroid metabolic situation vastly normalized themselves also without an anaemia-specific additional medication. Leukocytopenias (5.8%) and thrombocytopenias (3.3%) had only a low frequency in untreated hyperthyroidism. Nevertheless an unequivocal parallelity of the haematologic changes was to be observed in erythro-, granulo- and thrombopoiesis. There was a clear correlation between the activity of hyperthyroidism, measured at the T3- or T4 level, and anaemia and haemocytopenia, respectively. Lacking substance deficiency conditions and signs of haemolysis let us first of all think of a causal thyrotoxic bone-marrow damage on account of the dependence of the haematologic changes on the activity of hyperthyroidism and their immediate influencibility by aimed thyrostatic therapy. A relatively low dosed thiamazol therapy has influence on haematopoiesis and peripheral blood picture only at a very small percentage, in which cases the changes mostly are fully reversible. Thereby the initial haematologic situation before the therapy does not provide any predictability for perhaps appearing haematotoxic or allergic side-effects under thyreostatic treatment. The thiamazol therapy does not show any recognizable side-effects in the dosage administered on the investigated leukocytic functions agglomeration, adhesion and phyagocytosis. Only for the adhesion of leukocytes was proved a significant functional disturbance of leukocytes, which was, however, reversible with normalization of metabolism and with high probability was also directly thyreotoxically induced.

Adolescent↗
PubMed1988

EEG changes in untreated hyperthyroidism and under the conditions of thyreostatic treatment.

20 patients with hyperthyroidism were observed with repeated EEG measurements before and during treatment (ObsidanR; MethimazolR). 17 patients, before starting antithyroid therapy, had slight to moderate EEG abnormalities. A prevalence for moderate disturbances occurred for patients with a higher degree of hyperthyroidism. The dominant EEG frequency was higher than in euthyroid controls, but no exact correlation to T3-values could be observed. 16 patients showed abnormal reactivity to photic stimulation. One-week therapy by propranolol produced only a slight synchronizing effect in EEG's, where T3-values decreased. After 4 weeks selective therapy by MethimazolR all patients were euthyroid, but some EEG abnormalities persisted in 12 patients in a lower degree. The dominant EEG frequency decreased to control-group ranges and abnormal photic reactivity was reduced. After 6 months some EEG disturbances re-increased tentiatively, in 3 relapses excessively. These observations confirm the prognostic value of EEG measurements for the recognition of occurrence and persistence of cerebral disturbances in severe metabolic dysfunctions.

Adult↗
PubMed1986

[Modification of the diagnosis of thyroid gland function by iodine-containing roentgen contrast media].

The influence on the parameters of the thyroid gland BEI, T3-, T4- and TSH-serum level by the iodine-containing oral bile X-ray contrast remedy Falignost is demonstrated. Following a peripheral conversions inhibition from T4 to T3 by the contrast remedy the thyroid hormones in the serum are changed in different kind and duration. This influence is more expressed in patients with liver cirrhosis and continues. The risk of an iodine-induced hyperthyroidism is discussed. In the judgment of a possible disturbance of the function of the thyroid gland anamnestically is always to be asked the question about previous applications of iodine-containing drugs and it must be accordingly be taken into consideration.

Contrast Media↗
PubMed1986

[Unwanted modification of the thyroid gland by drugs with special reference to nonsteroidal antirheumatic agents].

In two retrospective clinical studies was investigated the influence of the modern non-steroidal antirheumatic drugs indometacin and diclofenac (Rewodina) on the thyroid gland and corresponding peripheral hormone parameters. Under longterm treatment with indometacin a moderate strumigenic effect could be observed, which could not clearly be proved under the diclofenac therapy. In all patients with rheumatoid arthritis, independent of the kind of pharmacotherapy, decreased T3-hormone levels were found in normal serum T4-values. The findings are discussed as "low-T3-syndrome" in rheumatoid arthritis, induced by the disease lasting for many years possibly in combination with the long-term therapy with antirheumatic drugs. In a second series of investigations in 75 out of 3,104 patients (2.4%) with a bland struma distinct references to a medicamentous evocation of the enlargement of the thyroid gland were found. Anticonvulsive drugs and the antidepressive drug lithium stood in the first place as inductors of such medicamentous struma. Of the non-steroidal antirheumatic drugs only some cases could be ascribed to phenylbutazone, whereas the more modern preparations indometacin and diclofenac in none of our patients could with certainty be made responsible for a development of struma.

Anti-Inflammatory Agents↗