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Biomedical subjects

J Bruck

Publications and source records attributed to J Bruck.

At least 19 recordsLinked to original sources

Regulatory modules that generate biphasic signal response in biological systems.

Biochemical networks might be composed of modules. It is still not clear how biochemical modules can be defined and characterised. Here we propose a functional approach to module definition, considering different classes of biphasic regulation modules, which effect optimal cell response to intermediate signal strength. Each regulation class might possess unique properties that make it especially suitable for particular biological functions.

Adaptation, Physiological↗

Scaffold proteins may biphasically affect the levels of mitogen-activated protein kinase signaling and reduce its threshold properties.

In addition to preventing crosstalk among related signaling pathways, scaffold proteins might facilitate signal transduction by preforming multimolecular complexes that can be rapidly activated by incoming signal. In many cases, such as mitogen-activated protein kinase (MAPK) cascades, scaffold proteins are necessary for full activation of a signaling pathway. To date, however, no detailed biochemical model of scaffold action has been suggested. Here we describe a quantitative computer model of MAPK cascade with a generic scaffold protein. Analysis of this model reveals that formation of scaffold-kinase complexes can be used effectively to regulate the specificity, efficiency, and amplitude of signal propagation. In particular, for any generic scaffold there exists a concentration value optimal for signal amplitude. The location of the optimum is determined by the concentrations of the kinases rather than their binding constants and in this way is scaffold independent. This effect and the alteration of threshold properties of the signal propagation at high scaffold concentrations might alter local signaling properties at different subcellular compartments. Different scaffold levels and types might then confer specialized properties to tune evolutionarily conserved signaling modules to specific cellular contexts.

Adaptor Proteins, Signal Transducing↗

[Metabolic changes in ischemic brain infarct].

Serum and cerebrospinal fluid (CSF) from 17 patients less than 3 days after brain infarction (measurement 1) and during recovery 7 +/- 2 days after infarction (measurement 2) were analysed for organic acids (energy metabolites, keto acids and amino acids). Clinical parameters improved by 32% over the period of assessment. Only serum pyruvate levels were elevated at both measurement times. Acute infarction was characterized by significant correspondence of serum and CSF concentrations for pyruvate and alpha-oxo-beta-methyl valeric acid which was lost during the recovery period. Amino acids of the L-system were roughly doubled (phenylalanine 7-fold in the CSF); increased concentrations were recorded for amino acids of the basic transport system, while amino acids of the A-system stayed unchanged (with the exception of alpha-amino butyric acid--20-fold in CSF). Except in the case of taurine, serum and CSF amino acid concentrations remained unchanged between the two measurement times. Mutual dependence of CSF and serum amino acid concentrations, existing initially for glycine, valine, leucine, tyrosine, as well as ornithine, lysine and histidine was lost in the recovery phase. This is interpreted as indication of a normalization of the blood-brain barrier.

Acids↗

[Changes in organic acids in plasma and cerebrospinal fluid in cerebral infarct].

Seventeen patients with recent cerebral infarction were included in the study. The general condition of the patients was evaluated within 3 days after the incidence (rating 1) and 7-9 days after the incidence (rating 2) using a clinical rating scale for internal, psychiatric and neurological findings. The statistical evaluation showed a clinical improvement of the score of 32%. The extent of the brain lesions was determined by cranial computed tomography. Routine analysis of the cerebrospinal fluid included determination of protein, cell count, cell type, glucose, lactic acid, and hemoglobin. In addition, spinal fluid and serum concentration of pyruvic acid, citric acid, fumaric acid, alpha-ketoglutaric acid and alpha-keto-beta-methylvaleric acid (3-MKV) were determined at the two rating times. CSF and serum values of fumaric acid, 3-MKV and pyruvic acid correlated at rating 1, while at rating 2 a correlation existed only for fumaric acid. A trend analysis infarction - postinfarction period showed the concentration of all metabolites to decrease significantly. This is interpreted as a reconstitution of the initially disturbed blood brain barrier function.

Aged↗

[Apolipoproteins A and B in cerebrovascular diseases].

The present study has proved unequivocally the value of determining apolipoproteins A and B and the APO-L A/B quotient for establishing the risk for cerebrovascular disease. The determination of apolipoproteins should be preferred to the determination of HDL, LDL and VLDL, which has been practised so far. While only 30% of a group of 88 patients suffering from cerebrovascular disease had serum cholesterol levels of more than 250 mg/dl and approx. 57% showed HDL values below 40 mg/dl, a reduced APO-L A/B relation (less than 1.75) was demonstrated in 74%. A reduced APO-L A/B quotient was also observed in more than 70% of 62 CVD patients whose cholesterol level was within the range of normal. Determination of apolipoproteins may, therefore, be regarded as further progress in risk factor diagnostic of arteriosclerotic disease.

Adult↗

[Changes in serum lipoproteins in cerebrovascular disease (author's transl)].

The determination of serum cholesterol, triglycerides and lipoprotein cholesterol (VLDL, LDL and HDL) in 96 patients suffering from cerebral vascular disease showed that some parameters were significantly different from those recorded in a control population of corresponding age HDL values below 40 mg/dl were found in 50% of cases. Pathological LDH/HDL and VLDL/HDL ratios were found in 30.9% and 37.7%, respectively, of patients with cerebrovascular disease, whose serum cholesterol level was below 250 mg/dl and triglyceride level was 175 mg/dl. Only 56% of all patients had elevated serum cholesterol and/triglyceride and triglyceride alone does not detect the risk. The difference in the VLDL/HDL ratio in patients with cerebrovascular disease and that of the control population is highly significant. The HDL values and the VLDL/HDL ratio differ significantly, also. On average, the HDL levels in women are higher than those in men, but the decrease faster with increasing age. In both sexes a decrease in HDL level occurs between the age of 40 and 80. Low HDL levels and unfavourable LDL/HDL and VLDL/HDL quotients are important risk indicators for cerebrovascular disease.

Cerebrovascular Disorders↗

Noninvasive rCBF determination by 133XE-inhalation with the gamma camera and functional imaging of wash-in and wash-out. A new combined approach for rCBE measurements in patients with cerebrovascular disease.

In 47 patients with cerebrovascular disease (CVD) a noninvasive determination of global and regional cerebral blood flow (CBF) was performed with the gamma camera. A new approach was developed for region definition and for evaluation of the "start-fit-time' as the point of minimal contamination of the recorded data by extracerebral scatter and recirculation using the region of interest (ROI)-technique in the camera field of view. In comparison with the results of probe measurement of end-tidal exhalation air no significant differences were seen and values obtained were well in the range reported by other authors. Initial slope (IS), gray matter flow (F1) and CBF-15 were used as quantitative parameters and were able to distinguish significantly (P less than 0.01) between normals, patients with mild CVD, and severe CVD. Intraexamination variation coefficient (VC) was 5%, interexamination VC was 8%. Functional, parametric images of wash-in for easier ROI-definition and judgement of isotope supply and of wash-out were generated by a computer analysis and were found to be sensitive indicators for arterial blood supply and wash-out values city. Thus it was possible to recalculate regional flow values in focal areas exactly corresponding to abnormalities seen on the functional images. So the regional information of functional images can be combined with the quantitative data in selectable areas. By tis noninvasive, easily performed method focal neurological deficits can be evaluated with high accuracy with conventional nucleus medicine equipment.

Cerebrovascular Circulation↗

[Clinical course and CSF lactate in encephalomalacia (author's transl)].

LCS level of lactate and clinical status correlate well during the initial stage of encephalomalacia (2nd-4th day) and during a period of 12 to 14 days after infarction LCS level of lactate may, therefore, be regarded as important parameter for short-term prognosis of encephalomalcia. The use of a semiquantitative clinical score also permits predictions as to the extent of remission to be expected. The reliability of this model of prognosis is limited by the comparatively small number of patients so far examined, the assumption of a linear relation between clinical alterations and changes in LCS lactate, as well as by the difficulty of determining LCS lactate in most severe cases at the specific time requested by the examination programme.

Aged↗

[Lactacidosis of the cerebrospinal fluid in apoplexy as indicator of prognosis (author's transl)].

Blood and CSF gases, as well as the level of lactate and pyruvate in blood and CSF were determined in 43 cases. of severe stroke with softening of the brain. It transpired that the CSF lactate level is the best prognostic indicator of survival. CSF values above 2,5 mMol/1 in apoplexy imply a very unfavourable prognosis. The CSF lactate level is also a very useful prognostic indicator in patients suffering from diabetes and/or uraemic metabolic disorders. As the determination of CSF lactate presents no tecnical difficulties and furnishes valuable prognostic information it would merit inclusion as a routine procedure in relevant cases.

Acidosis↗

Long-term prognosis in stroke related to cerebral blood flow.

In 180 patients, cerebral blood flow was measured between one and six weeks after acute cerebrovascular ischemia. Patients were grouped according to their clinical deficits at the time of blood flow study. Statistical analysis revealed highly significant differences among the flow values of the groups. The patients were followed up for a period of up to 6 years (mean, 34 months) after the attack, and then regrouped. In these groups, the statistical significances of differences among the flow values was even higher. Patients also were grouped according to changes in neurologic status, and again the flow values differed significantly among the groups. The results show significant relationships among flow values after cerebrovascular ischemia and neurologic deficits, change in status, and the final functional state. Cerebral blood flow measurement together with other clinical signs permits an estimation of a patient's chance for functional recovery after a stroke.

Adolescent↗