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Biomedical subjects

M Mittag

Publications and source records attributed to M Mittag.

25 records · Page 2Linked to original sources

[Cellular mechanisms of circadian clocks].

The mechanisms of the biological clock are today being investigated in single neurons in cell culture or in unicellular and in other microorganisms. The results show that all components of this "endogenous clock" can be found at the cellular level. The cellular circadian program is controlled by a complex system of biochemical reactions, which can contain more than one circadian pacemaker and which comprises several feed-back loops at the input and the output side. This complex temporal program is a prerequisite for specialization and survival within the chrono-ecological niches of the "temporal space" day. It enables organisms on the one hand to adaptively react to environmental changes and thereby reaching transient independence of the external, physical time course; on the other side, it ensures that the endogenous day never runs out of synchrony with the solar day of the environment.

Animals↗

Circadian expression of the luciferin-binding protein correlates with the binding of a protein to the 3' untranslated region of its mRNA.

The circadian-expressed luciferin-binding protein from the dinoflagellate Gonyaulax polyedra is regulated at the translational level. We detected a protein, apparently a dimer, that binds specifically to the 3' untranslated region of its mRNA. Its binding site was localized within a 22-nt region in the 3' untranslated region containing seven UG repeats. The binding activity of this protein cycles on a daily basis, decreasing at the beginning of the night when synthesis of luciferin-binding protein starts and increasing at the end of the night when synthesis of luciferin-binding protein stops. This suggests that it functions as a clock-controlled repressor, preventing the translation of lbp mRNA during the day.

Animals↗

Molecular cloning and genomic organization of a gene for luciferin-binding protein from the dinoflagellate Gonyaulax polyedra.

The circadian expressed luciferin-binding protein (LBP) gene from the marine bioluminescent alga Gonyaulax polyedra represents the first dinoflagellate gene that has been cloned and sequenced at both cDNA and genomic levels. Starting with a fragment from the 3'-end of the LBP cDNA that was found by immunoscreening of a cDNA library, genomic clones were obtained by the inverse polymerase chain reaction technique. Full-length cDNA clones were selected by screening a cDNA library by plaque hybridizations and by polymerase chain reaction amplifications. The LBP sequence has a 2004-nucleotide open reading frame coding for a protein of 668 amino acids (approximately 75 kDa). The reading frame and identity of the clone were confirmed by the sequence of an octapeptide obtained from a purified fragment of CNBr-treated LBP. A variant LBP cDNA was found to differ in sequence by approximately 11% at the DNA level. The untranslated regions of the mRNA are 111 nucleotides (5'-untranslated region) and 158 nucleotides (3'-untranslated region) long, respectively. The LBP gene contains no introns and exhibits certain features not typical for a eukaryotic gene. Its promoter does not include the typical TATA box within approximately 50 nucleotides upstream of the transcription start site, and the usual poly(A+) signal (AAUAAA) is not present on the end of the LBP mRNA. The copy number of the gene is very high (approximately 1000 copies/cell). However, the universal genetic code and conserved positions relevant for the translational apparatus are maintained.

Amino Acid Sequence↗

Systemic sclerosis-related Raynaud's phenomenon: effects of iloprost infusion therapy on serum cytokine, growth factor and soluble adhesion molecule levels.

Microvascular damage occurs in systemic sclerosis and is associated with increased serum levels of endothelial adhesion molecules and endothelium-associated cytokines, including vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin, endothelin-1 and vascular endothelial growth factor (VEGF). Iloprost, a prostacyclin analogue, induces clinical benefit in patients suffering from scleroderma-related Raynaud's phenomenon. This study was performed to investigate the effect of iloprost infusions on endothelium activation. Serum samples from 12 patients with systemic sclerosis were examined using specific enzyme-linked immunoassays. The serum levels of sICAM-1, sVCAM-1 and soluble E-selectin were initially elevated and significantly reduced after iloprost infusions. The serum concentrations of VEGF and endothelin-1 revealed decreased levels after therapy too. These results indicate that the well-known clinical benefit of iloprost infusions on Raynaud's phenomenon is serologically detectable by a reduction of serum levels of endothelium-associated adhesion molecules, cytokines and growth factors reflecting an improvement in endothelial function.

Adult↗

Acute hypercalcemia of the heart ("bony heart").

Cardiac abnormalities as a sign of hyperparathyroidism are common. A spectacular pitfall of peracute extended myocardiac hypercalcemia is reported. The history of a 30-year-old woman included symptoms such as insufficiency of the kidneys since childhood, secondary hyperparathyroidism, and hemodialysis for approximately 4 years. After kidney transplantation, the patient died from progressive heart failure. Three days before she died, CT showed a nearly white heart, and myocardial scintigraphy revealed a total infarction. The autopsy revealed a heart of normal size but with a weight of 590 g and with nearly bony texture. The histologic examination showed extended calcifications of the entire myocardium, thus explaining these findings. Laboratory photographs and electron microscopic images will be demonstrated. The metabolic pathogenesis of tertiary hyperparathyroidism and calciphylaxis is discussed. "Malignant" progression after kidney transplantation is stressed.

Acute Disease↗

Cutaneous breast angiosarcoma after conserving treatment of breast cancer.

Cutaneous angiosarcoma is a rare malignancy that sometimes occurs as a late sequela of breast conservation therapy. We report on a 79-year-old female who developed well-differentiated angiosarcoma in a lymphedematous left breast 5.5 years after surgery and radiotherapy for early invasive ductal breast cancer. The initial appearance was very similar to late radiation dermatitis, and histologically interpreted as scar tissue with atypical vascular lesion. The lesion progressed further, and was clinically suspicious for angiosarcoma. Thus, a second biopsy was taken which confirmed the diagnosis. A complete mastectomy removed all the tumor with clear margins. However, within a period of 16 months she presented four local recurrences which were treated by wide local excision. At present, the patient is free of locally recurrent tumour for 7 months. The few cases of breast angiosarcoma after breast conservation therapy reported so far demonstrate that these lesions are difficult to diagnose due to their rarity and their highly variable and benign appearance, which sometimes may mimic radiation-induced cutaneous changes. Since chronic lymphedema possibly contributes to the development of angiosarcoma, long-term clinical surveillance of these patients is recommended. Biopsies should be taken if new skin lesions occur.

Aged↗

[Biological age in patients with progressive scleroderma].

In 25 patients (10 male, 15 female) with systemic sclerosis aged between 28 and 79 years the biological age was determined. Alterations in the sense of "premature aging" were observed in the mean and developed stronger in male patients. They have to be counted in a greater part on the real process of disease. Compared to a healthy reference group, the expected diminishing of hand grip strength and tendon extensibility, vital capacity and partial oxygen pressure in the arteries could be confirmed. The latter correlated to an increase in rest pulse. Auditory acuity and the condition of the teeth were also reduced. Beyond that, noteworthy differences in psychological and social parameters not presumed at the beginning point to a decrease in social activities and to psychic changes. They underline the necessity of psychological counseling of the patients.

Activities of Daily Living↗