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In small micrometer volumes typical of living cells, regulatory molecules of enzymic reactions can diffuse so fast from one enzyme molecule to another that the diffusion time is much shorter than the turnover time of an enzyme. Under these conditions, a special kinetic regime of a molecular network is realized. We consider molecular networks formed by allosteric enzymes with several functional subunits, interactions between which are described by a sequential model of Koshland et al. with heterotropic or homotropic (positive and negative) cooperativities. Simple product-activated and product-inhibited reactions are investigated. We show that allosteric cross-molecular regulation and intramolecular cooperativity result in the development of coherent dynamics of enzyme molecules in such networks. Intermolecular synchronization of turnover cycles of different enzymes is accompanied by intramolecular synchronization of the dynamics of subunits belonging to the same molecules. Strong intramolecular correlations persist even at high intensity of thermal molecular fluctuations, when intermolecular synchronization is already absent.

The stereotyped pattern of veins in the Drosophila wing is generated in response to local EGF signalling. Mutations in the rhomboid (rho) gene, which encodes a sevenpass membrane protein required to enhance signalling transmitted by the EGF receptor (Egfr), inhibit vein development and disrupt the vein pattern. By contrast, net mutations produce ectopic veins in intervein regions. We have cloned the net gene and show that it encodes a basic HLH protein that probably acts as a transcriptional repressor. net and rho are expressed in mutually exclusive patterns during the development of the wing imaginal disc. Lack of net activity causes rho expression to expand, and vice versa. Furthermore, ectopic expression of net or rho results in their mutual repression and thus suppresses vein formation or generates tube-like wings composed of vein-like tissue. Egfr signalling and net exert mutually antagonising activities during the specification of vein versus intervein fate. While Egfr signalling represses net transcription, net exhibits a two-tiered control by repressing rho transcription and interfering with Egfr signalling downstream of Rho. Our results further suggest that net is required to maintain intervein development by restricting Egfr signalling, which promotes vein development, to the Net-free vein regions of the wing disc.

The stereotyped pattern of veins in the Drosophila wing is generated in response to local EGF signalling. Mutations in the rhomboid (rho) gene, which encodes a sevenpass membrane protein required to enhance signalling transmitted by the EGF receptor (Egfr), inhibit vein development and disrupt the vein pattern. By contrast, net mutations produce ectopic veins in intervein regions. We have cloned the net gene and show that it encodes a basic HLH protein that probably acts as a transcriptional repressor. net and rho are expressed in mutually exclusive patterns during the development of the wing imaginal disc. Lack of net activity causes rho expression to expand, and vice versa. Furthermore, ectopic expression of net or rho results in their mutual repression and thus suppresses vein formation or generates tube-like wings composed of vein-like tissue. Egfr signalling and net exert mutually antagonising activities during the specification of vein versus intervein fate. While Egfr signalling represses net transcription, net exhibits a two-tiered control by repressing rho transcription and interfering with Egfr signalling downstream of Rho. Our results further suggest that net is required to maintain intervein development by restricting Egfr signalling, which promotes vein development, to the Net-free vein regions of the wing disc.

Abstract: Introduction: In patients with differentiated thyroid carcinoma, elevated serum levels of thyroglobulin (hTg) may occur in spite of otherwise negative diagnostic procedures and in particular in spite of a negative iodine-131 scan. Positron emission tomography with F-18-deoxyglucose (FDG-PET) is a potentially useful method for the detection of metastatic lesions or the recurrence of thyroid cancer. We aimed to investigate whether FDG-PET is capable of detecting metastastic lesions or recurrence in patients with differentiated thyroid carcinoma, elevated serum levels of thyroglobulin, and otherwise negative diagnostic procedures, including the iodine-131 scan. Methods: From a group of 500 patients with differentiated thyroid carcinoma, a subgroup of 32 patients had elevated serum hTg-levels, negative iodine-131 scans, negative cervical and abdominal ultrasound, and negative X-ray of the chest. In 12 of these patients (hTg 77.894.3 ng/ml, range 1.5 – 277 ng/ml, median 20 ng/ml), FDG-PET was performed. All but one FDG-PET study was performed in a state of hypothyroidism (TSH 75.832.2 IU/ml, range 31 – 116 IU/ml, median 74.6 IU/ml). Results: In 6 of the 12 patients investigated, the FDG-PET was positive. In three of the patients, the diagnosis was confirmed by computed tomography or magnetic resonance imaging. In patients with a positive FDG-PET finding, the hTg level was 146.790.1 ng/ml (23 – 277 ng/ml, median 144.5 ng/ml). In contrast, in patients with a negative finding the hTg level was only 9.07.6 ng/ml (range 1.5 – 17 ng/ml, median 8.1 ng/ml), P = 0.01. Conclusion: These preliminary results show that in patients with differentiated thyroid carcinoma, elevated hTg levels, and otherwise negative “conventional” diagnostic procedures, FDG-PET is helpful in detecting metastatic lesions.

Arrhythmogenic right ventricular disease (ARVD) is a disease of unknown origin that primarily affects the right ventricle and is characterized by ventricular tachyarrhythmias which may lead to syncope and even, though rarely, sudden cardiac death. In 25 patients with ARVD, sympathetic innervation of the left ventricle was assessed by iodine-123 metaiodobenzylguanidine single photon emission tomography (1231-MIBG SPET). In addition, thallium-201 SPET was performed. The diagnosis of ARVD was made by an electrophysiological study and right and left heart catheterization including right ventricular endomyocardial biopsy. Ischaemic heart disease was excluded by coronary angiography. A group of seven patients without any evidence of heart disease served as a control group. Twenty-two of the 25 patients showed reduced uptake of 123I-MIBG. The abnormal areas were located predominantly in posterior and posteroseptal segments of the heart. No focus of increased 123I-MIBG activity could be demonstrated. No patient had signs of left ventricular involvement on left ventricular angiography. In contrast to the results of the 123I-MIBG SPET, those of 201TI SPET were normal in 16 patients. The remaining nine patients showed areas of slight hypoperfusion not correlated with the reduced 123I-MIBG uptake. 123I-MIBG scintigraphy allows detection of left ventricular adrenergic dysinnervation in ARVD patients without morphological or functional abnormalities of the left ventricle.

Methods of parametric imaging of radionuclide angiography using parameters like appearance time, peak time, transit time, height of peak, arterial slope and area of inflow were developed and evaluated regarding their diagnostic meaning in 111 patients suffering from TIA or PRIND and in 30 normal persons. The meaning of these single parameters could shown depended on the specificity of the diagnostic question. Local cerebral blood flow can be estimated most favourably by parametric images of area of inflow whereas transit time is most promising as a diagnostic tool for evaluation of total cerebral blood flow classified with reference to severity of the perfusion disturbance. Appearance time is suited very well to estimation of collateral perfusion. Blood flow in great cerebral arteries could be seen well by non parametric imaging of radioactivity inflow in the brain supplying arterial vessels in the cranial floor. Applying a combination of the parametric images, the sensitivity for detection of disturbances of cerebral blood flow amounts to 0.91. A specificity of 0.88 and accuracy of 0.90 were found. The described combination of evaluation of RNA using various parameters is considered a well suited method for detection of disturbances in local and total cerebral blood flow by means of planar imaging.

Es wird über Schmerzzustände und ihre Ursachen an den Wirbeldornfortsätzen berichtet. Diese können sowohl in den Lordosebereichen der Lendenwirbelsäule (Baastrupsches Syndrom) und der Halswirbelsäule auftreten, werden aber auch an den kyphotischen Abschnitten gefunden. Röntgenologisch kann man bei beiden Formen knöcherne Appositionen an den Dornfortsatzspitzen finden, bisweilen Nearthrosen. Die Festlegung des röntgenologischen Befundes ist jedoch nicht gleichbedeutend mit dem klinischen Krankheitsbild. Nach Beschreibung der konservativen und insbesondere der operativen Therapie werden anatomische Beobachtungen mitgeteilt und diskutiert. Wurm nimmt mit pathologisch-anatomischen Bemerkungen zu der Tatsache Stellung, daß trotz gegenteiliger Belastung der Wirbelsäule in Lordose- und Kyphosebereichen an den Dornfortsätzen fast völlig gleichartige pathologische Vorgänge ablaufen. Diese Tatsache ist nur durch funktionelle Momente erklärlich.

Zusammenfassung An Hand eigener Fälle wird die Behandlung der Knochen-Gelenktuberkulose mit TB I 698 besprochen. Bei 23 peroral behandelten Fällen (Tagesdosis 0,025 bis 0,1) war 5 mal eine günstige Beeinflussung festzustellen, die nicht zu erwarten war; 9mal schritten die Prozesse nicht fort, in 5 Fällen war der Fortschritt der Erkrankung geringer als zu erwarten war und in 2 Fällen führte ein schicksalsmäßiger Ablauf zur Verschlechterung. Als wertvolle Eigenschaft wird hervorgehoben, daß das Präparat in der Lage ist, in vielen Fällen die tuberkulöse Entzündung einzudämmen und abzustoppen und wahrscheinlich damit größere Zerstörungen zu vermeiden. Aus diesem Grunde soll man so früh wie möglich mit der Therapie beginnen. Die bisher übliche Behandlung mit exakter Ruhigstellung darf bei der Chemotherapie nicht eingesehränkt werden. Es wird weiter die lokale Behandlung von kalten Abscessen und Fisteln in 9 Fällen besprochen, bei denen es bei Überdosierung leicht zu erheblichen Einschmelzungen kommt, besonders wenn diese sekundären Weichteilherde eine starke eigene Aktivität haben. Eingehend werden grundsätzliche Fragen erörtert, die zur Beurteilung einer Chemotherapie der Knochen- und Gelenktuberkulose überhaupt von Wichtigkeit sind, um damit zu versuchen, eine Basis für weitere Untersuchungen vorzuschlagen.