Biomedical subjects
M Molnar
Publications and source records attributed to M Molnar.
Thallium-201 uptake with negative iodine-131 scintigraphy and serum thyroglobulin in metastatic oxyphilic papillary thyroid carcinoma.
We report a case of a 48-yr-old woman who underwent surgery because of papillary oxyphilic thyroid carcinoma pT3. After total thyroidectomy, we administered 2960 MBq (131)I for ablation of the residual tissue. initial follow-up visits showed no clinical, radiological or scintigraphic evidence of residual or metastatic thyroid tissue. Serum thyroglobulin levels (Tg) and (131)I whole-body scintigraphy were negative. Three years after thyroidectomy, the patient experienced seizures, and as a consequence a brain tumor was removed. It was an undetected metastasis of the primary thyroid carcinoma. Histological examinations showed that neither the primary tumor nor the metastasis produced any Tg. With this fact in mind and the knowledge of negative (131)I whole-body scans we had to concentrate on radiological (CT and MRI scans) and nonspecific scintigraphic methods such as 201TI whole-body scintigraphy in our management of the patient. Further follow-up demonstrated multiple metastasis by 201TI whole-body scan (mediastinum, bones and soft tissue), and most of them have been removed by surgery. This case report demonstrates that, in addition to (131)I whole-body scans and measurement of serum Tg, the use of nonspecific tracers like 201TI is important to detect (131)I and/or Tg negative metastases.
A pacemaker current in dye-coupled hilar interneurons contributes to the generation of giant GABAergic potentials in developing hippocampus.
The establishment of synaptic connections and their refinement during development require neural activity. Increasing evidence suggests that spontaneous bursts of neural activity within an immature network are mediated by gamma-aminobutyric acid via a paradoxical excitatory action. Our data show that in the developing hippocampus such synchronous burst activity is generated in the hilar region by transiently coupled cells. These cells have been identified as neuronal elements because they fire action potentials and they are not positive for the glial fibrillary acidic protein staining. Oscillations in hilar cells are "paced" by a hyperpolarization-activated current, with properties of Ih. Coactivated interneurons synchronously release GABA, which via its excitatory action may serve a neurotrophic function during the refinement of hippocampal circuitry.
A critical period in the sensitivity of basal forebrain cholinergic neurones to NGF deprivation.
Cholinergic neurones of basal forebrain (BF) express receptors for nerve growth factor (NGF) and are sensitive to NGF. In many CNS structures, including the BF region, the expression of NGF and its receptors is developmentally regulated. To test whether BF neurones depend on NGF during restricted time windows of postnatal development, we antagonized endogenous NGF by implanting, in the lateral ventricle of the rat, hybridoma cells producing blocking antibodies specific for NGF. Implants were performed at postnatal day 2 (P2), P8 and P15. BF cholinergic neurones were drastically reduced in number only when endogenous NGF was antagonized during the first postnatal week. We conclude that BF cholinergic neurones are sensitive to NGF deprivation only during early postnatal development.
Evaluation of thyroid nodules with technetium-99m tetrofosmin dual-phase scintigraphy.
Technetium-99m tetrofosmin, a lipophilic cationic complex molecule, was introduced for myocardial imaging. In some biodistribution studies it has also been reported to accumulate in the thyroid gland. Our objectives were to determine which thyroid nodules retain tetrofosmin and whether preoperative evaluation of malignancy is possible. Tetrofosmin scintigraphy was performed in 57 patients with a cold thyroid nodule on previously performed pertechnetate scintigraphy. All patients had undergone ultrasonography and sonographically guided fine-needle aspiration biopsy. The tetrofosmin scintigrams were obtained 5 min (early image) and 1 h (late image) after intravenous injection of 370 MBq. Only nodules that showed clear tracer retention after 1 h in comparison with retention at 5 min were classified as TETRO positive. Nodules without late retention were classified as TETRO negative. All patients underwent surgery and the histological results were compared with the results of tetrofosmin scintigraphy. Ten out of 11 patients with thyroid carcinoma (two pT1, three pT2, five pT4) were TETRO negative. One patient with papillary carcinoma (pT2) was TETRO positive. The mean nodular to thyroid tissue (N/T) ratio for the late scan was 1.0+/-0.20. There were 21 patients with thyroid adenomas (seven follicular, seven microfollicular and seven oxyphilic); 15 of these patients were TETRO positive and six TETRO negative. The mean N/T ratio for the late images was 1.34+/-0.41. All patients with degenerative goitre (24 cases) and the one patient with Hashimoto's disease were TETRO negative after 1 h and the N/T ratio was 0.92+/-0.12 on the late scan. Our results indicate that 99mTc-tetrofosmin scanning is of little value preoperatively in distinguishing thyroid carcinoma from other thyroid nodules. Tetrofosmin tends to demonstrate thyroid adenomas but does not have a routine role in the assessment of thyroid nodules.
Scintimammography using Tc-99m tetrofosmin.
Breast cancer, the most common malignancy in women, still poses a challenge to diagnostic procedures and therapy. Despite low specificity routine mammography is the method of choice to screen women for breast cancer. In the last years other additional diagnostic procedures such as high frequency ultrasonography (US) and especially magnetic resonance imaging (MRI) have improved breast cancer diagnosis. However, all these imaging methods are lacking in specificity which makes biopsy or surgery necessary. The purpose of our study was to evaluate prospectively the sensitivity, specificity, PPV and NPV of scintimammography with a new cationic complex Tc-99m tetrofosmin in patients with suspicious mammographic lesions. One hundred and thirty seven patients in whom mammography and/or high resolution ultrasonography (10 MHz) revealed suspicious breast lesions were studied with Tc-99m tetrofosmin scintimammography. In 84 of them biopsy and/or surgery was performed for histological evaluation. After intravenous injection of 555 MBq Tc-99m tetrofosmin planar images in anterior and lateral projections (5 min.p.i.) and SPECT imaging including 3-D-reconstruction (20 min.p.i.) were performed. Scintimammography was evaluated as negative, equivocal (+), probably (+2) or definitely (+3) positive. Planar scintimammography with Tc-99m tetrofosmin was negative in 46 patients (43 true negative-f.n; 3 false negative-f.n.) and positive in 38 patients (27 true positive-t.p.; 11 false positive-t.p.). Using SPECT imaging Tc-99m scintimammography was negative in 43 cases (41 t.n.; 2f.n.) and positive in 41 cases (28 t.p.; 13 t.p). Sensitivity of Tc-99m tetrofosmin scintimammography in this prospective study was 90%, specificity 80%, PPV 71% and NPV 93% for planar imaging and 93%, 76%, 68% and 95% for SPECT, respectively. Scintimammographic results in patients with suspicious breast lesion show, that Tc-99m tetrofosmin accumulates in breast cancer as well as in some fibroadenoma with high cellularity. However, the high NPV of 93 and 95% respectively excludes breast cancer in suspicious mammographic lesions to a very high degree and therefore reduces the need of biopsy and/or surgery in most of these patients.
Multiple mitochondrial tRNA(Leu[UUR]) mutations associated with infantile myopathy.
We have identified a cluster of mitochondrial tRNA(Leu[UUR]), mutations in a severe case of infantile myopathy. There were A to G transitions found at mtDNA positions 3259, 3261, 3266 and 3268. These point mutations change the anticodon arm and the anticodon UAA, normally found in tRNA(Leu[UUR]), to UGA which is the one of the tRNAs(Ser[UCN]). This is the first anticodon alteration described in this tRNA. Another swap straight to the anticodon of tRNA(Pro) alone was recently described in a less severe case. Until now infantile myopathies have not been attributed to defined mtDNA alterations. This study reports for the first time mtDNA point mutations causing this early onset of a mitochondrial disorder. The apparent homoplasmy of these mutations and especially the location in the anticodon must be considered lethal, if the child would not have been respirated for 5 years from its birth.
Mitochondrial abnormalities and peripheral neuropathy in inflammatory myopathy, especially inclusion body myositis.
Computer retrieval in a database, comprising 7,225 muscle cases, revealed that mitochondrial myopathies do not occur more frequently in inflammatory myopathies (3.74%) than in the whole series (3.69%). A more detailed study of inclusion body myositis (IBM), however, showed that severe mitochondrial alterations were apparent in about twice as many IBM cases as expected. This confirms recent studies of others although a causal relationship has thus far not been established. Identification of mitochondrial deletions by Southern blotting corresponded to the presence of severe structural abnormalities of mitochondria. Peripheral neuropathy of variable severity was noted in all cases of IBM and mitochondrial myopathy. By contrast, the association of severe mitochondrial abnormalities with polymyositis, systemic scleroderma, and vasculitis observed in some cases of the present series may be incidental or age dependent.
Technetium-99m-tetrofosmin uptake in sarcoidosis stage I.
The uptake of 99mTc-tetrofosmin in enlarged lymph nodes, of the lung hilus, in the case of sarcoidosis Stage I (histopathologically confirmed by mediastinoscopic biopsy) is demonstrated. On a routine chest radiograph of a 78-yr-old woman, hilar lymphadenopathy was first detected. In the following mammography, disseminated micro calcifications were found in the left breast and a 99mTc-tetrofosmin study was performed for detection of breast cancer. Scintigraphy using 99mTc-tetrofosmin showed clear uptake in the hilar lymph nodes, but not in the left breast. The 99mTc-tetrofosmin uptake in the hilar lymph nodes was due to sarcoidosis confirmed by histology. Therefore, 99mTc-tetrofosmin scintigraphy may be useful in patients with suspected sarcoidosis, especially in Stage I.
Influence of human anti-mouse antibodies on thyrotropin in-vitro analysis: a comparison of 6 thyrotropin IRMA kits.
OBJECTIVE: The aim of the study was to evaluate the influence of human anti-mouse antibodies on the measurement of thyrotropin. INVESTIGATIONS: Samples from 11 patients with measureable human anti-mouse antibody titres (19 micrograms/l-3880 micrograms/l) after radioimmuno-scintigraphy were analysed with 6 different thyrotropin immuno-radiometric assay kits (IRMA). Each sample was analysed in the routine way (sample influenced by human anti-mouse antibodies), as well as after incubation with murine immunoglobulin to precipitate human anti-mouse antibodies (samples not influenced by human anti-mouse antibodies). RESULTS: Two kits showed clear deviations of measured thyrotropin levels when the human anti-mouse antibody titres were higher than 1350 micrograms/l. A third kit was influenced to a lesser extent by human anti-mouse antibodies. Three of the 6 investigated thyrotropin IRMA kits produced thyrotropin values that were unaffected by the presence of elevated human anti-mouse antibodies. In comparison with former studies after immunotherapy, the thyrotropin deviations were marginal. However, differences were found between the commercially available thyrotropin assays. According to the results of this study only three out of the six investigated kits were unaffected by human anti-mouse antibodies. CONCLUSION: Since thyrotropin is one of the key quantities for the endocrinologist dealing with the thyroid gland, every laboratory should ensure high quality thyrotropin assays by critically analysing their method for human anti-mouse antibody.
Tetrofosmin scintigraphy of thyroid disease.
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A large-scale deletion of mitochondrial DNA in a case with pure mitochondrial myopathy and neuropathy.
Here we report the findings from a male patient with myopathy and neuropathy, who has a large-scale deletion of the mitochondrial genome at nucleotides 6570-14150. In the patient's history, muscle cramps with intermittent weakness and polyneuropathy with disturbed micturition were the predominant symptoms. Morphological examination of a muscle biopsy sample revealed numerous ragged red fibers and prominent paracrystalline intramitochondrial inclusions. The sural nerve biopsy sample disclosed a chronically progressive neuropathy, predominantly axonal in type with a minor demyelinating component. In previous studies the clinical symptoms mentioned above have been related to point mutations at various positions in the mitochondrial DNA (mtDNA). The present study is the first to describe a large (8 kb) deletion of the mtDNA which had apparently caused myopathy and polyneuropathy without encephalopathy.
Sigmund Freud (1856-1939): life and work.
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Posthatching development of preproenkephalin mRNA-expressing cell populations in the pigeon telencephalon.
Enkephalin peptides are highly expressed in the vertebrate telencephalon. Our previous investigations in the pigeon and in the chicken [26] suggested that the cellular distribution of these peptides is conserved in phylogenetically 'old' telencephalic regions (e.g. the basal ganglia), while it has species-specific organizations in areas (e.g. dorsomedial forebrain and bulbus olfactorius) that are likely to play important roles in species-specific behaviors. In the present study, we investigated the posthatching development of preproenkephalin (PPE) mRNA-containing cells in the pigeon forebrain using in situ hybridization histochemistry. These cells are densely distributed in the paleostriatal complex (corresponding to the mammalian caudate-putamen) at hatching, and their density progressively decreases during the first 9 days posthatching, when it is similar to that of adult pigeons. In the dorsomedial forebrain (corresponding to the mammalian hippocampus), PPE mRNA-expressing cells are present at hatching, and their density reaches a peak around the 6th day posthatching. In the bulbus olfactorius, the first PPE mRNA-containing cells are observed after 9 days posthatching. The developmental profile of PPE mRNA expression in these areas of the pigeon telencephalon shows remarkable similarities with the development of enkephalinergic cells in corresponding brain areas of mammals. As in the mammalian caudate-putamen, the developmental expression of enkephalin peptides in the paleostriatal complex is likely to be related to neuronal withdrawal from the mitotic cycle. The developmental pattern of expression of PPE mRNA in the dorsomedial forebrain suggests that enkephalin peptides contribute to the maturation of the behavioral functions of this area.
Two novel genes involved in the sexual development of Schizosaccharomyces pombe.
We isolated two sterile mutants of Schizosaccharomyces pombe. One of them was mapped close to ste13 (8 cM). Since it turned out to be allelic with the hitherto unmapped ral2, its linkage with ste13 localizes ral2 on the right arm of chromosome II. The other mutant defines a novel class-I ste gene, ste15, closely linked to ste7 (4 cM) on chromosome I. ste15 is conjugation-specific and acts upstream of pat1 and ras1. During its genetic analysis, a phenotypic suppression of ste12-N9 was observed which was caused by mutations in the unlinked gene ssw1.
The rec8 gene of Schizosaccharomyces pombe is involved in linear element formation, chromosome pairing and sister-chromatid cohesion during meiosis.
The fission yeast Schizosaccharomyces pombe does not form tripartite synaptonemal complexes during meiotic prophase, but axial core-like structures (linear elements). To probe the relationship between meiotic recombination and the structure, pairing, and segregation of meiotic chromosomes, we genetically and cytologically characterized the rec8-110 mutant, which is partially deficient in meiotic recombination. The pattern of spore viability indicates that chromosome segregation is affected in the mutant. A detailed segregational analysis in the rec8-110 mutant revealed more spores disomic for chromosome III than in a wild-type strain. Aberrant segregations are caused by precocious segregation of sister chromatids at meiosis I, rather than by nondisjunction as a consequence of lack of crossovers. In situ hybridization further showed that the sister chromatids are separated prematurely during meiotic prophase. Moreover, the mutant forms aberrant linear elements and shows a shortened meiotic prophase. Meiotic chromosome pairing in interstitial and centromeric regions is strongly impaired in rec8-110, whereas the chromosome ends are less deficient in pairing. We propose that the rec8 gene encodes a protein required for linear element formation and that the different phenotypes of rec8-110 reflect direct and indirect consequences of the absence of regular linear elements.
Increase of mitochondria in vasa nervorum of cases with mitochondrial myopathy, Kearns-Sayre syndrome, progressive external ophthalmoplegia and MELAS.
Previous studies on patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) revealed accumulations of mitochondria in endothelial cells, smooth muscle cells of pial arterioles, and small intracerebral arteries up to 250 microns in diameter; in pericytes of capillaries, endothelial cells, and smooth muscle cells of small blood vessels in skeletal muscle; and according to preliminary results also in endothelial and smooth muscle cells of capillaries and arterioles in sural nerves. These mitochondria do not show the prominent paracrystalline inclusions which are seen in striated muscle fibres and led to the identification of this group of disorders. To corroborate our preliminary findings in peripheral nerves, additional cases have been evaluated morphometrically by electron microscopy including cases in which mitochondrial DNA (mtDNA) mutations have been identified. In fact, an increase of the mean number and an enlargement of the mean cross-sectional area of mitochondria was noted in endothelial and smooth muscle cells of endoneurial and epineurial arterioles, and in endothelial cells and in pericytes of capillaries in sural nerves of the 20 cases with mitochondrial disorders studied. This increase was statistically significant compared to the control group. However, due to heteroplasmia, which is a common feature in mitochondrial disorders, and because of the limited number of measurable blood vessels and cases, no significant differences could be detected between the various types of mitochondrial diseases which were characterized by different point mutations or deletions of mtDNA. Our findings suggest that the mitochondria play a significant role in the pathogenesis not only of myopathic and encephalopathic symptoms, but also in the pathogenesis of peripheral neuropathy which appears to be regularly associated with mitochondrial disorders.