[A 41-year-old patient with increasing dyspnea and pulmonary artery hypertension].
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Biomedical subjects
Publications and source records attributed to J Albrecht.
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We describe the use of flow cytofluorometry to type lymphocytes for HLA-B27 antigens. We modified the cytotoxicity test of Terasaki and McClelland [Nature (London) 1964;204:998] for use with a flow cytofluorometer. In a second assay we used a commercially available monoclonal anti-HLA-B27 antibody and indirect immunofluorescence staining of cell surfaces. Although this antibody cross reacts with B7 and Bw22 antigens, the results for HLA-B27 and the cross-reacting antigens can be separated. Comparison of our results with those by a HLA-typing laboratory for 100 patients showed total agreement of the assigned typings.
HIV-infected and noninfected H9-cell cultures were incubated with two antibodies (Biochrom, DuPont) against p24gag antigen (capsid) of HIV: the antibodies show a positive reaction against p24 antigen in the Western blot. The antibody-labeled cells were examined by fluorescence-activated cell sorting (FACS) and by microscope. The labeled infected and uninfected cells show no characteristic fluorescence pattern after previous acetone fixation. By using formalinfixation technique the monoclonal antibody (DuPont) shows a positive fluorescence pattern but also a high unspecific reactivity with uninfected H9-cells. An identification of HIV-infected living cells with this monoclonal capsid antibody seems possible, if the unspecific binding can be reduced.
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Astrocyte-enriched cultures prepared from the neonatal rat cortex were prelabelled with either [3H]myoinositol or 45Ca2+ and then exposed to various excitatory amino acids. This resulted in an increase in both the breakdown of membrane inositol phospholipids and Ca2+ flux with the following rank order of efficacy: quisqualate greater than or equal to glutamate (Glu) greater than kainate much greater than N-methyl-D-aspartate. Experiments performed with the Ca2+ ionophore A23187 and in the absence of medium Ca2+ suggested that Glu-evoked 45Ca2+ efflux was primarily the result of an increased influx of extracellular Ca2+. However, Glu-stimulated inositol lipid metabolism was found to be only partially dependent on extracellular Ca2+. The quisqualate-preferring receptor antagonist gamma-glutamylaminomethylsulphonic acid was found to be effective in reversing both Glu-evoked inositol lipid breakdown and Ca2+ flux. The results presented are suggestive of some form of interaction between Glu receptors coupled to inositol lipid turnover and Ca2+ channel opening in astrocytes.
High-dosage stosstherapy of cyclophosphamide was administered, as far as possible optimally synchronized with plasmapheresis, to 12 patients with rapidly progressive glomerulonephritis. The basis for such synchronization lies in experimental data pointing to an increased antibody production after plasmapheresis (antibody rebound). Initial large-volume plasmapheresis was followed by high-dose immunosuppression in the phase of likely maximal proliferation of antibody-producing cells. The serum creatinine level in the 12 patients was 7.7 +/- 3.3 mg/dl before treatment. Eight patients required dialysis. After a period of observation of one year, ten patients are still alive. In one patient treatment had to be discontinued because she did not tolerate it. In the other nine patients renal function stabilized on a dialysis-free level. After one year the serum creatinine level averaged 2.5 +/- 1.2 mg/dl. With one exception no maintenance immunosuppressive treatment is required after one year. These preliminary results suggest that this treatment concept further improves the prognosis of rapidly progressive glomerulonephritis.
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Rats were subjected to repeated intraperitoneal administrations of thioacetamide (TAA) in order to produce the following stages of hepatogenic encephalopathy (HE): the early stage, characterized by activation of brain metabolism (Group 1), the precomatose stage with impairment of brain metabolism (Group 2) and the stage of recovery (Group 3). A decrease of cerebral blood flow (CBF) of 50%, related to a drop of systemic arterial pressure and to increased hematocrit, were observed in groups 1 and 2 but not in group 3. However, the cerebral oxygen consumption (CMRO2), calculated from arterial venous difference in oxygen content and taking into account CBF, was markedly decreased in group 2, but remained unchanged in group 1. This reflects the state of cerebral metabolism at these stages. The results underscore the necessity of simultaneous monitoring of CBF and blood gases for distinguishing between the particular stages of HE revealed by biochemical tests.
Some patients with dissociated vertical deviation show an increasing upward drift of their squinting eye when reading small numbers at a distance of 5 m, making a special effort to shift attention to the non-squinting eye. This finding is at variance with the view that the manifestation of dissociated vertical deviation may be induced by visual inattention. The phenomenon could be explained by analogy to the occlusion test, by a binocular imbalance in visual information processing. The phenomenon may be found frequently in patients who require surgery for an especially disfiguring intermittent vertical squint. Looking for the phenomenon may be useful when deciding whether to operate for a dissociated vertical deviation: If increasing vertical deviation is observed during binocular acuity testing, surgical treatment should be considered.
Two subsequent phases of hepatogenic encephalopathy (HE), the metabolic and precomatous phase, were produced in rats by thioacetamide treatment. Plasma and brain levels of arginine and its metabolites in the arginine-glutamate pathway, and activities of 2 brain enzymes of this pathway: arginase (L-arginine amidohydrolase, EC3521) and ornithine amino-transferase (OAT, ornithine-oxo-acid aminotransferase, EC26113) were measured in these rats. Plasma arginine sharply decreased in the metabolic phase and rose above control level in the precomatous phase, whereas ornithine and glutamate increased and urea decreased in both phases. Brain amino acids levels remained unchanged throughout, confirming earlier report of their insensitivity to external manipulation. Both brain enzymes showed a similar stepwise increase in their activities up to 150% the control level. The results are indicative of increased involvement of arginine as a precursor of amino acid neurotransmitters glutamate and GABA, with possible implication for the course of HE.
In order to investigate the availability of laser-induced mass spectrometry for the determination of bacteria, ten strains of the genera Escherichia and Streptococcus were chosen. Gram-negative as well as Gram-positive lysogenic and non-lysogenic, pathogenic and non-pathogenic strains were examined. Giant pulses of a Nd: YAG laser (frequency quadrupled, wave-length 265 nm) were used to vaporize and partly ionize the bacterial material. The time-of-flight mass spectra obtained could be discriminated by using the stepwise discriminant analysis provided by BMDP software package. Two different methods relating centrifugation and washing procedures were used. With the first method a correct classification between 50.0 and 90.9 per cent (S. sanguis) by means of mass spectra of positive ions and a correct classification between 27.1 and 80.4 per cent (S. lactis-25) by means of mass spectra of negative ions was observed. Using the second method a correct classification between 40.7 and 93.3 per cent (S. lactis-25) by means of mass spectra of positive ions and a correct classification between 56.7 and 95.0 per cent by means of mass spectra of negative ions was obtained. Here S. sanguis with 93.3 and S. lactis-25 with 81.7 per cent were significantly differentiated. In this context it must be emphasized that a correct classification of 27 per cent must be considered statistically significant, if 10 different strains are used.
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The GABA level, and the glutamic acid decarboxylase (GAD) and GABA-aminotransferase (GABA-T) activities were measured in the cortex and striatum of rats in which the early stages of hepatogenic encephalopathy (HE) had been induced by few intraperitoneal administrations of thioacetamide (TAA). Besides, the GABA binding to synaptic plasma membranes (SPM) isolated from whole brain hemispheres was examined. The first part of the study revealed significant changes both in the neurotransmitter level and in the enzyme activities; no correlation was observed, however, between the accumulation of GABA and the progression of the disease. In contrast, subsequent stages of HE in the TAA model were found to be characterized by a gradual decrease of both Bmax and KD values for GABA binding, which may reflect a gradual decrease in the number of binding sites, accompanied by sensitization of the remaining receptors. The results are discussed in view of the possible involvement of this inhibitory neurotransmitter in the pathogenesis of HE.
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Lymphocyte blastogenesis induced by lectins (PHA, Con A, and PWM) was assessed in 27 drug-free patients with unipolar (n = 21) or bipolar (n = 5) depression and 13 normal controls. Fifteen patients were restudied after clinical remission. Symptomatic patients did not differ from controls nor did endogenous and nonendogenous depressions differ in their lymphocyte blastogenesis response to any of the three lectins. However, a significant reduction in lymphocyte blastogenesis with both PHA and Con A stimulation was found following somatic treatment. Cellular immune function appears to be normal in depressed patients, although the somatic therapies are associated with a reduction in this function.
Na+/K+-ATPase activity and GABA uptake were measured in the bulk isolated astrocytes and synaptosomes from rats in which an early, metabolic phase of hepatogenic encephalopathy (HE) was induced by the treatment with thioacetamide (TAA). Both the enzyme activity and the amino acid neurotransmitter uptake were increased above control in the astroglial fraction but remained unaffected in synaptosomes. The results lend support to the earlier observations that the astrocytes are the primary target cells in HE. Furthermore, they may be interpreted as indicating that the early astroglial reaction to HE comprises stimulation of the astrocytes' function, especially concerning clearance of K+ ions and neurotransmitters from the extracellular space of CNS.
The brain octopamine (OA) and phenylethanolamine (PhEA) content was determined in rats subjected to repeated intraperitoneal administrations of thioacetamide (TAA) known to produce different stages of hepatogenic encephalopathy (HE). A more than 2.5-fold increase of OA and a 2-fold increase of PhEA was observed after prolonged (3 times) administration of TAA, coinciding with impaired ammonia detoxication in brain and with the onset of pathophysiological changes typical for HE. Only insignificant changes in the content of the amines were observed in the early stages of the experiment as well as in the recovery period. The results are consistent with the "false neurotransmitter" hypothesis of Fischer and Baldessarini, assuming the participation of OA and PhEA in the pathogenesis of HE.