Biomedical subjects
Publications and source records attributed to H Dietz.
The immunohistochemical localization of insulin/insulin-like immunoreactivity in different regions of the human brain was reevaluated by use of monoclonal antibodies against insulin. The data obtained support our earlier findings that cerebral insulin is present in nerve cells of several brain areas.
Despite the existence of circumstantial evidence, a direct proof of an autoimmune basis for beta cell destruction in human type I diabetes has not yet been obtained. The present study was designed to test on Wistar rats whether a low-dose streptozotocin (SZ) treatment in combination with complete Freund's adjuvant (CFA) could be a useful approach to induce an autoimmune response to beta cells. Rats were weekly injected i.p. either with CFA or with SZ alone or with both CFA and SZ. Only the SZ-CFA-treated rats developed severe hyperglycemia. In these animals the pancreatic insulin content was nearly completely depleted. Only in SZ-CFA-treated rats cytotoxic autoantibodies to islet cells were found. The results show that in this new model of type I diabetes autoimmune reactions are involved in the destruction of beta cells.
Mouse monoclonal antibodies were raised against human insulin by somatic cell hybridization using the mouse myeloma line P3-X63-Ag8. Five cell lines were grown as ascites producing tumors. Insulin binding data were determined from six monoclonal antibodies by Scatchard analysis. Each anti-insulin hybridoma antibody gave a straight-line Scatchard plot confirming the homogeneity of their binding sites and their monoclonality. The equilibrium dissociation constants ranged from 2.20 X 10(-8) to 4.48 X 10(-10) mol/l. We could demonstrate positive as well as negative cooperativity of monoclonal insulin antibodies by performing insulin binding studies with defined mixtures of two different anti-insulin hybridoma antibodies.
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Thirty patients with an acute midbrain syndrome were treated by high dose barbiturate therapy. Of these patients 19 had a severe head injury. In 8 patients the symptoms of acute midbrain syndrome developed after subarachnoid haemorrhage. In three patients these symptoms were caused by postoperative swelling or ischaemia. The results of those patients, who were treated with barbiturates after head injury were much better than in 16 other patients, who had no barbiturates. The indications for high dose barbiturate therapy in neurosurgery are discussed with reference to other publications and to the pathophysiological effects of barbiturates.
A gaschromatographic method is presented for the determination of thiopental (and of its metabolite pentobarbital) in cases of severe head injuries treated by induction of therapeutic barbiturate coma. To 1 ml serum the internal standard and saturated ammonium sulphate solution are added. The mixture is extracted by chloroform and the concentrated organic phase is injected into the gaschromatograph (stationary phase: SP 2510 DA). Imprecision from day to day: Coefficient of variation 7.7%; recovery 97%. The specificity was checked by comparison with the retention time of more than 80 drugs. One determination is accomplished within 1 hour.
The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) has been used to promote monolayer formation in cultured islets isolated from fetal human or neonatal rat pancreas. Immunofluorescence with specific antiserum to insulin revealed B-cells in the outgrown monolayers. The rat islet cells were further characterized by their secretory and biosynthetic response to the action of IBMX. Both glucose-stimulated insulin release and recoverable insulin, i.e. intracellular insulin plus insulin secreted, were increased by the addition of IBMX (0.1 mmol/l) to the medium containing 10 mmol/l glucose. 3H-leucine incorporation into (pro)insulin was significantly higher following culture in 10 mmol/l glucose plus IBMX (0.1 and 1.0 mmol/l) than after cultivation with glucose alone. However, the percentage of (pro)insulin synthesized in relation to total protein synthesis was increased to a lesser extent after an acute incubation for 3 h at 1.5 mmol/l or in the absence of glucose. Moreover, the culture system employed in the present study proved to be useful for detecting islet cell antibodies bound to human as well as rat islet cells after exposure to islet cell antibody-positive sera.
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Antibodies against rat islet cells were produced by immunisation of rabbits with neonatal rat islet cells. In the presence of complement the rabbit anti-rat islet cell surface sera were strongly cytotoxic for both, neonatal rat islet cells and spleen lymphocytes as revealed by the high percentage of 51Cr release from these cells. However, after absorption with rat lymphocytes and rat liver powder the cytotoxicity of the islet cell antisera for rat lymphocytes was drastically reduced while the release of 51Cr from islet cells was only slightly influenced. These data indicate that islet cell specific antibodies were still present in the antisera after absorption. Native normal rabbit serum was also cytotoxic for neonatal rat islet cells and spleen lymphocytes. The release of 51Cr from islet cells and lymphocytes was vigorously reduced after absorption of the normal rabbit serum with lymphocytes and was paralleled by a similar decrease of insulin release from intact islets under conditions where the active insulin secretion was blocked pharmacologically. Intact islets prelabeled with 51Cr were also used as targets but this approach was less suitable for the detection of cytotoxic islet cell surface antibodies.
The present experimental study was designed to examine the correlations between brain tissue pressures, pressure gradients and cerebral blood flow distribution associated with circumscribed cerebral vasogenic oedema. Following unilateral hemispheric cryogenic injury in 42 adult cats, brain tissue pressures increased as a function of time. Interhemispheric pressure gradients became most marked one hour after the cryogenic injury (3.9 mm Hg on average), gradually decreasing thereafter. Transtentorial pressure gradients developed within the first hour after the injury, and remained above 10 mm Hg. The dye injected into one carotid system by the "single dye passage" technique was redirected towards the contralateral hemisphere and also towards the subtentorial compartment, as brain tissue pressures increased. The shift in the flow-distribution of dye and blood was more pronounced in the posterior fossa structures. When intracranial tissue pressures exceeded 60 mm Hg almost no dye entered the cranial cavity. This accompanied the marked decrease in cerebral perfusion pressure.
In spite of the severity of the injury, perforating orbito-frontal injuries have often been overlooked on account of their very scanty clinical symptoms. For this reason they are particularly dangerous. The historic, aetiological, diagnostic and clinical aspects of the lesion are discussed. Experiences from the literature are reported as well as our own observations. In nearly all of our 15 personal cases there was initially a CSF fistula and a brain injury; in all six of the late cases there had been three or more attacks of meningitis and in five the diagnosis was only made after a brain abscess had developed.
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The action of ketamine on the lysosomal of the white and gray matter was studied by estimating the ratio: free acid hydrolase beta-glucuronidase/total activity. Administration of ketamine was followed within 24 hours by stabilization of the lysosomal membrane of the white matter. Despite this protective effect on the subcellular structures of the white matter ketamine cannot, because of its excitometabolic action, be recommended as an anaesthetic agent with brain-protecting properties.
The effect of posttraumatic steroid treatment (6-methylprednisolone) on the stability of lysosomal membranes in the cat brain is studied. The share of free activity of the lysosomal enzymes beta-glucuronidase and N-acetylhexosaminidase indicates the grade of membrane stability. The results demonstrate an increased stability of lysosomal membranes in grey as well as in white matter after posttraumatic steroid treatment. This regarded as an important aspect of the protective effects of steroid treatment in posttraumatic brain edema.
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The authors describe a new approach (the Small Frontolateral Approach) for the elective microsurgical treatment of aneurysms of the rostral part of the circle of Willis, including those arising from the carotid siphon. This approach provides the advantage of permitting an easy, direct and "protective" attack to such aneurysms through a small and merely osteoplastic craniotomy.