[The cerebral circulation in xenon-CT].
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Biomedical subjects
Publications and source records attributed to H Dietz.
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The regulation of oxidative phosphorylation was studied with digitonin-treated epididymal bull spermatozoa in which mitochondria are directly accessible to low molecular compounds in the extracellular medium. Due to the high extramitochondrial ATPase activity in this cell preparation, it was possible to stimulate respiration to a small extent only by added hexokinase in the presence of glucose and adenine nucleotides. Added pyruvate kinase plus phosphoenol pyruvate, however, strongly suppressed the respiration. Under these conditions, the respiration was found to depend on the extramitochondrial [ATP]/[ADP] ratio in the range of 1-100. The contribution of the adenine nucleotide translocator to this dependence was determined by titration with the irreversible inhibitor carboxyatractyloside in the presence of ADP. Using lactate plus malate as substrate, the active state respiration was controlled to about 30% by the translocator, whereas 12 and 4% were determined in the presence of L-glycerol-3-phosphate and malate alone, respectively. In order to compare the results with those for intact cells, the adenine nucleotide patterns were determined in intact and digitonin-treated spermatozoa under conditions of controlled respiration in the presence of vanadate and carboxyatractyloside, respectively. About 21% of total cellular adenine nucleotides were found in digitonin-treated cells representing the mitochondrial compartment. While allowing for the intramitochondrial amount of adenine nucleotides, the cytosolic [ATP]/[ADP] ratio was estimated to be 6-times higher than the mitochondrial ratio in intact cells. It is concluded from the data presented that the principal mechanism by which oxidative phosphorylation in sperm mitochondria is regulated via the extramitochondrial [ATP]/[ADP] ratio is the same as that demonstrated for other isolated mitochondria.
Experimental investigations have suggested an important role of arachidonic acid metabolites in the genesis of cerebral vasospasm following subarachnoid hemorrhage. In this clinical study the cerebrospinal fluid (CSF) and serum levels of the two main arachidonic acid metabolites prostacyclin and thromboxane A2 are evaluated by measuring their stable degradation products 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TXB2) using radioimmunoassay methods during the pre- and postoperative course in patients after aneurysm rupture. Although the serum levels of both substances do not seem to be important for the clinical course of the patients, the CSF concentrations of 6-keto-PGF1 alpha and TXB2 provide important data. A close correlation between the initial TXB2 level of the individual patient and the amount of blood in the basal cisterns as detected by computed tomography scan can be demonstrated. The predictive value of this additional information for the occurrence of cerebral angiospasm is discussed. Comparing the CSF levels of both metabolites the slight preoperative elevation of 6-keto-PGF1 alpha is significantly surmounted by an extraordinary rise in TXB2 concentration. Postoperatively, after cleavage of the basal cisterns there is a decline in the CSF levels of both substances. The pre- and postoperative clinical course in comparison to the CSF levels of 6-keto-PGF1 alpha and TXB2 is demonstrated in four patients. A nearly normal course of TXB2 and 6-keto-PGF1 alpha seems to be associated with an uneventful clinical course, whereas a high TXB2 level--whether occurring preoperatively or, even more important, as a secondary postoperative rise--seems to be associated with ischemic complications and neurological deterioration. It is suggested that pre- and postoperative monitoring of CSF levels of 6-keto-PGF1 alpha and especially TXB2 may serve as a possible indicator for the detection of patients at risk of developing cerebral vasospasm.
Diagnosis and post-therapeutic follow-up of tumour patients necessitates morphological and particularly functional imaging methods. For the latter approach positron emission tomography has proven a valid tool for the measurement of perfusion, of energy consumption parameters such as oxygen extraction, glucose metabolism and amino acid uptake. However, neither perfusion nor energy consumption parameters have yielded unambiguous information on the clinical status of various tumours in respect of their malignancy and their growth status. It is shown in this paper that amino acid uptake seems to be a valid measure for the functional activity of tumour tissue for a broad range of neoplasms. The uptake of 11C-L-Methionine was measured in 33 patients having various brain tumours, and was compared with 6 patients who had an infarction, and with 8 patients suffering from arachnoidal cysts. The amino acid uptake correlated well with the histological grading of the tumours and the clinical status of the patient. The uptake was well differentiated against metabolically inactive lesions. Parallel investigations on the uptake mechanisms of amino acids in an animal model have shown that transport phenomena regulate the uptake rather than protein synthesis rates. However, protein synthesis may nevertheless exercise a control function on the transport process.
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Imbalance between the two arachidonic acid metabolites, prostacyclin (PGI2) and thromboxane A2 (TXA2), is thought to be at least in part responsible for the development of cerebral vasospasm following aneurysm rupture. In 12 patients with subarachnoid hemorrhage the pre- and postoperative serum and CSF levels of PGI2 and TXA2 were measured as a function of their stable hydrolysis products, 6-Keto-PGF1 alpha (PGI2) and thromboxane B2 (TXA2), with a highly specific radioimmunoassay. Serum levels of both metabolites were elevated in half of the patients, but no correlation to the clinical course could be found. However, TXB2 concentration in the CSF was significantly increased preoperatively with close correlation to the amount of intracisternal blood, as detected by CT scan. Furthermore, it could be demonstrated that the postoperative course of the TXB2 concentrations in the CSF reflects the clinical course in such a way that a characteristic secondary rise of TXB2, concentration postoperatively is closely related to the occurrence of cerebral vasospasm and clinical deterioration. The conclusion is drawn that measurement of arachidonic acid metabolites in the CSF may provide important information concerning the pathophysiological events following subarachnoid hemorrhage, especially with regard to incipient cerebral vasospasm.
Temporal changes in the distribution of N-isopropyl-(123I)p-iodoamphetamine (IMP) within the brain are measured with serial tomographic imaging. In the cerebellum there is a decrease in activity of 42% from the early [15-45 min postinjection (p.i.)] to the late (210-240 min p.i.) scan, while in the cortex the decrease is 18%, and in the basal ganglia there is no decrease within this time. In brain tumors there was no IMP uptake in the early as well as in the late scans, regardless of tumor type, perfusion rate, or blood-brain barrier dysfunction. In 11 of 43 patients with a cerebral infarction a real increase of 123I activity (mean +21%) was seen in the late images. This "filling in" phenomena might be useful in selecting patients for bypass surgery. In these patients the diaschisis cerebelli, seen in the early scans, disappeared in the late images. The regional distribution of IMP changes with time; spatial ratios might be blurred by temporal changes. High-flow areas such as visio-auditory centers can be delineated clearly after stimulation in fast early scans; in these areas the pharmacokinetics of 123I are different from other cortex regions. To get the full information from the IMP brain uptake, both spatial and temporal variation must be measured.
We investigated four insulin-specific hybridoma antibodies with respect to their kinetic properties as well as the binding behaviour of some combinations of them. From equilibrium binding data all but one antibodies were shown to bear homogeneous binding sites. They revealed homogeneity of binding sites also by kinetic experiments, thus with high probability being monoclonal. At 0 degree C, two of them showed discrepancies between kinetic and steady state binding data in as much as, at steady state, the measured bound-to-free ratio of tracer insulin was 3-4 times lower than calculated from kinetic data. Thus a simple bimolecular reaction mechanism could possibly not be applicable. Mixing two monoclonal insulin antibodies, neither cooperative nor additive binding to the insulin molecule could be observed but only competitive effects. Especially, no positive cooperativity between two or more antibodies could be detected, which would be able to account for the higher affinity usually observed for polyclonal vs. monoclonal antibodies.
Treatment of bull spermatozoa from epididymal cauda with 5 micrograms digitonin per microliter cells removed the permeability barrier of plasma membrane for mitochondrial substrates and effectors. Such preparations yielded a high portion of coupled mitochondria characterized by ratios of active respiration to carboxyatractyloside-inhibited respiration greater than 13 in the presence of efficient substrates. Bull sperm mitochondria oxidized pyruvate and lactate in the presence of malate as well as glycerol-3-phosphate with much higher rates than succinate or palmitoyl carnitine. For the efficient substrates the respiration coupled to ADP phosphorylation amounted to 77 to 100% of the uncoupled rate. Comparable rates of active respiration were also observed with ATP indicating the high ATPase activity present in digitonin-treated spermatozoa. Uncoupled rates of respiration corresponded to rates of intact spermatozoa, but the capacity of the phosphorylating respiration exceeded the respiration rates of intact motile spermatozoa remarkably. This indicates that the spermatozoal ATP turnover at sufficient supply of substrate is mostly controlled by ATP utilizing reactions.
The action of the antihypertensive agent Urapidil was investigated in an experimental animal model of vasogenic brain oedema. Animals with normal or raised intracranial pressure received Urapidil as a bolus injection (0.25 mg/kg body weight) followed by a continuous infusion of Urapidil (1 mg/kg body weight). The bolus injection of the drug was followed by a sharp fall in systemic blood pressure, paralleled by a rise in intracranial pressure, resulting in a shortlasting decline of cerebral perfusion pressure. During continuous infusion of Urapidil in both groups with normal or elevated ICP there was a long-lasting significant fall in the systemic blood pressure without any significant alteration of the intracranial pressure.
The author review 10 years' experience in managing brain abscess in childhood: 19 cases were treated in children from 1 to 18 years old. The etiology was rhinogenic in 5 cases, congenital heart disease in 5, hematogenous in 3, traumatic in 3, postoperative in 1, and unknown in 3 cases. Brain abscesses that developed by direct spread were located nearby the source, whereas metastatic abscesses (such as cardiogenic or hematogenous) in most cases spread via the vertebral-basilar system, usually developing in the parieto-occipital regions. Four of the 5 cases with multiple abscesses were cardiogenic and one hematogenous. The most important neurological signs were paresis (10 cases) and cranial nerve involvement (10 cases). Six abscesses were sterile and 6 grew aerobic and 6 anaerobic bacteria. In one case, aerobic as well as anaerobic bacteria were found. Fifteen patients were treated preoperatively with antibiotics. The treatment was operative in 17 cases. In two cases, gravely ill on admission, no surgical treatment was given. The etiology, localization, bacteriology, surgical methods, and results in those cases are discussed.
The presence of islet cell cytoplasmic antibodies (ICA) and islet cell surface antibodies (ICSA) at the time of diagnosis of type 1 (insulin-dependent) diabetes mellitus has been taken as evidence that autoimmune mechanisms are involved in the pathogenesis of the disease. The demonstration that ICSA in the presence of complement are preferentially lytic for beta-cells may be important in defining the role of these autoantibodies in the pathogenesis of type 1 diabetes. Because of the polyclonality of the immune response, the ICA and ICSA molecules of diabetic patient vary enormously in their binding parameters. For this reason we have generated monoclonal antibodies (MC-Ab) to islet cell antigens. In this study we investigate the effect of the two MC-Ab K28 A1 and K28 D6 resulted from the same fusion of the P3-X63-Ag8 murine myeloma cell line with the spleen cells of a Balb/c mouse immunized with rat islet cells on the hormone release of isolated rat islet in co-culture with the antibody-secreting hybridomas. The MC-Ab K28 D6 binds to both islet cell cytoplasmic and surface antigens, the K28 A1 is only reactive with cytoplasmic antigens. Surprisingly, in contrast to the monoclonal antibody K28 A1, K28 D6 enhanced the glucagon content and diminished the insulin secretion of the islets. Either the K28 D6 is directed to an epitope occurring on the beta- as well as alpha-cells or the antibody-mediated inhibition of the glucagon release results in a significantly reduced insulin secretion.
To evaluate the significance of ICSA as a prognostic marker for the development of type I diabetes we investigated 66 subjects with first degree relatives of type I (47) and type II (9) diabetes as well as subjects with anamnestical data suggestive of diabetes. Patients were studied for glucose tolerance (oGTT) and IRI-response, ICSA (indirect fluorescence of living rat islet cell suspensions), ADCC (specific 51Cr-release of serum pretreated neonatal rat islets elicited by mononuclear cells) and HLA-antigens. 23 subjects revealed normal glucose tolerance, 17 impaired glucose tolerance and 26 had a prevoius abnormality. The incidence of ICSA varied between 46 and 53 per cent, that of positive ADCC between 22 and 56 per cent, both being highest in subjects with IGT. 87 per cent of all patients revealed diabetes associated HLA-antigens. We found no correlation of ICSA with glucose tolerance, IRI-response, ADCC and HLA-antigens. In conclusion it can be said that ICSA are present in a high percentage in patients with high diabetes risk but their predictive role as a marker for the manifestation must be elucidated in follow-up studies.
11C-labelled L-methionine uptake was measured in 7 patients with brain tumours prior to surgery, and in 2 patients with infarction, using PET. The strongest uptake occurred in tumours with a high grade of malignancy (astrocytoma IV: Tumour/Non-Tumour T/NT = 2.6) while low-grade tumours accumulated less activity (astrocytoma II: T/NT = 1.4). Conventional 99mTc DTPA scans revealed a damage of blood brain barrier (BBB) in 4 patients (2 infarctions) with no or only slight 11C-methionine accumulation, while one patient with negative 99mTc-scan and negative CT accumulated methionine in the tumour region (astrocytoma II). PET, MRI, and CT are complementary with regard to extent of tumour tissue, necrotic areas and oedema. None of the brain tumours or infarcted regions took up IMP (123I amphetamine). The investigated regions showed definite uptake defects ranging from 10-50% if compared with the contralateral side. In view of the chemical pathway of methionine it is concluded that the uptake reflects metabolic activity in brain tumour tissue rather than a diffuse uptake due to BBB damage.
66 patients with gunshot wounds were treated at the Department of Neurosurgery of Hanover University up to May 1982. These included wounds inflicted by bolt guns of the type used in slaughter houses, and by bolt-setting or nail-setting tools used in building construction work. The total mortality was 50%. Seventeen patients died directly after admission or within the first 24 hours. Operation was not indicated in cases which appeared hopeless. In patients with mild neurological deficits, only the superficial skin wounds were treated to avoid additional damage to the brain. CT scans performed in approximately one-half of the patients yielded valuable information on the path of the bullet and on haematomas. Postoperatively, there were several complications, mainly pneumonia and cerebrospinal fluid fistulas; in fact, pneumonia was responsible for the death of some patients. The mortality is compared with the findings by other authors. No patients remained in need of care after rehabilitation.
Mouse monoclonal antibodies producing cell lines were generated against rat and human islet cells by somatic cell hybridization using the mouse myeloma cell line P3-X63-Ag8. Four hybrid cell lines are growing as ascites bearing tumors. All four monoclonal antibodies reacted with cytoplasmic islet cell antigens as detected by the indirect immunofluorescence technique on Bouin-fixed pancreatic sections of Wistar rats. Besides their binding to cytoplasmic antigens three of them also recognized antigens expressed at the islet cell surface. Moreover, two of these three monoclonal antibodies were capable of mediating complement dependent cytotoxicity against rat islet cells as revealed in a 51Cr-release assay.