Search PubMed⌕ Search

Biomedical subjects

A Lowenthal

Publications and source records attributed to A Lowenthal.

At least 73 records · Page 4Linked to original sources

Increased GFAp levels in CSF as a marker of organicity in patients with Alzheimer's disease and other types of irreversible chronic organic brain syndrome.

Glial fibrillary acidic protein (GFAp), an astrocyte-specific protein, was determined in cerebrospinal fluid (CSF) of adults and children with global cognitive dysfunction. In children CSF-GFAp values were not closely associated with organic brain disease. However, GFAp values in CSF were increased in 65 of 121 samples of adults with dementia, independent of its cause. GFAp values were not correlated with the severity of the dementia. Increased levels in the CSF are believed to indicate reactive gliosis in most patients with dementia, whereas GFAp levels in encephalitic patients normalize after clinical recovery.

Adult↗

Anti-neurofilament antibodies in blood of patients with neurological diseases.

A method has been developed to determine quantitatively the level of the anti-neurofilament antibodies in the blood of patients affected with different neurological diseases. In 7 out of the 52 patients, taken as controls and in 33 out of the 208 patients affected with neurological diseases, the antibody levels were increased. The increases were greater in 43 patients with Parkinson dementia and amyotrophic lateral sclerosis who originated from Guam. On the other hand, the levels were very low in 10 patients affected with subacute sclerosing panencephalitis and in 11 cases with Chagas' disease. In 24 cases with dementia of Alzheimer type, the levels were normal.

Alzheimer Disease↗

Comparative study of guanidino compounds in serum and brain of mouse, rat, rabbit, and man.

The levels of 12 guanidino compounds were determined in the serum and brain of mouse, rat, rabbit, and man using cation-exchange column chromatography with the fluorescence ninhydrin detection method. A comparative study of these compounds was made in the four groups studied, for serum and brain. In rabbit and man the different guanidino compounds were also determined in various brain regions. This study provides basic analytical data that could facilitate the interpretation of further biochemical and neurochemical studies dealing with guanidino compounds that are identified as being toxins in hyperargininemia and uremia.

Animals↗

Guanidino compounds in serum and brain of audiogenically sensitive rats.

The levels of 12 guanidino compounds were determined in serum and brain of audiogenically sensitive rats with and without seizures. During audiogenic seizures the serum levels of creatine are significantly decreased, while those of guanidinoacetic acid, N-alpha-acetylarginine, creatinine, gamma-guanidinobutyric acid, arginine, guanidine and methylguanidine are significantly increased. In brain only creatinine and N-alpha-acetylarginine are markedly increased during seizure. These data demonstrate noticeable modifications of the levels of guanidino compounds in the blood during audiogenic seizure and also, in parallel, a creatinine increase in serum and brain.

Animals↗

Guanidino compounds in plasma, urine and cerebrospinal fluid of hyperargininemic patients during therapy.

The concentrations of guanidino compounds were determined in urine, plasma and cerebrospinal fluid of two patients with hyperargininemia during dietary therapy. alpha-Keto-delta-guanidinovaleric acid, N-alpha-acetylarginine, argininic acid and gamma-guanidinobutyric acid were increased in urine. In plasma, these compounds together with creatine, guanidinoacetic acid, arginine and homoarginine were also increased. In cerebrospinal fluid, only arginine, homoarginine and argininic acid were increased. Trace amounts of alpha-keto-delta-guanidinovaleric acid were found in cerebrospinal fluid of the patient treated with only a low-arginine diet. The concentrations of guanidinosuccinic acid are decreased in urine, plasma and cerebrospinal fluid. During a low-arginine diet, together with sodium benzoate therapy, the plasma and cerebrospinal fluid arginine values returned to normal. There was also a normalization of plasma guanidinoacetic acid and a marked decrease in plasma N-alpha-acetylarginine and argininic acid.

Adolescent↗

Primary cultures from defined brain areas; effects of seeding time on cell growth, astroglial content and protein synthesis.

The influence of seeding time on cell growth, astroglial content and on protein synthesis during cultivation was determined in primary cultures from 3 phylogenetically different brain areas from rat cerebral cortex, striatum and brainstem. Brainstem cultivated from 17-day-old embryos and all the cultures studied from the 3 brain areas of newborn and 7-day-old rat showed a similar increase in total and water-soluble protein during cultivation. Glial fibrillary acidic protein (GFAp, alpha-albumin) levels increased with age in all cultures studied. There was a rapid increase in GFAp (alpha-albumin) between 1 and 2 weeks in cultures from newborn and between 2 and 3 weeks in brainstem cultures from 17-day-old embryos, these increases being slower thereafter. Incorporation of [3H]valine into soluble protein was lower in 3-week-old cultures than in 1- and 2-week-old cultures derived from newborn and 7-day-old rat brain. The incorporation rates were similar in comparisons of the various cultures. Similar results were obtained from embryonic cultures, although the decrease in incorporation rate was between 3 and 4 weeks. The efficiency of incorporation (% TCA-precipitated material/total [3H]activity) was higher in 2- and 3-week-old than in 1-week-old cultures from newborn and 7-day-old rats and in 3- and 4-week-old cultures of brainstem from 17-day-old rat embryos. These findings suggest a cell differentiation during cultivation. The results show that seeding time has a variable influence on cultures from the different brain areas studied concerning cell growth, astroglial content and probably differentiation during cultivation. Embryonic cell cultures seem, in general, to develop one week later than neonatal and postnatal ones. Cultures of newborn rat cells from cerebral cortex, striatum and brainstem show many similarities in the above parameters during cultivation. This is also the case for brainstem cultures from embryonic rat.

Albumins↗

Cellular development and myelin production in primary cultures of embryonic mouse brain.

The development of cell cultures from embryonic mouse cerebral hemispheres has been followed in detail for periods up to 40 days in culture using a variety of approaches. Functionally well differentiated neurons (shown by receptor binding studies, immunocytochemistry and morphological examination) were found to be abundant early in culture and to form cell contacts with oligodendrocytes characterized both immunocytochemically and morphologically. Myelin-like membranes with the periodicity of classical myelin elaborated by oligodendrocytes were detected only after 30 days in culture when neurones were no longer present. These results are discussed with regard to possible mechanisms of initiation of myelin synthesis.

Animals↗

NMR approach of the periventricular white matter.

From a series of 117 neurological patients presenting a pathological periventricular white matter signal on NMR, the authors discuss the differential diagnosis possibilities based on the configuration of the lesions, on their localization in the brain, and on the calculated apparent T2 (T2**) values achieved with the single multi-echos technique.

Acquired Immunodeficiency Syndrome↗

Cellular composition of primary cultures from cerebral cortex, striatum, hippocampus, brainstem and cerebellum.

Primary cultures from newborn rat cerebral cortex, striatum, hippocampus, brainstem and cerebellum were grown for 14 days. There was a linear relationship between the amount of material seeded and the protein content of the respective culture. The amount of tissue material seeded was selected so that the different cultures reached confluence at 6-7 days and contained similar amounts of protein when 7 and 14 days old. The cellular content was evaluated by astroglial markers, such as the glial fibrillary acidic protein (GFAp; alpha-albumin) and the S-100 protein, and by markers for other cells expected to be in the cultures (14-3-2 protein, macrophage acidic protein (MAP), alkaline phosphatase, myelin basic protein (MBP), 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP]. Astroglial-like cells represented 60-70% of the cells present in the different cultures. Quantitation of GFAp (alpha-albumin) showed similar amounts to be present in cultures from cerebral cortex, hippocampus and striatum; however, on lower levels expressed in soluble proteins than in the corresponding brain regions of adult rats. Brainstem of adult rat contained large amounts of GFAp (alpha-albumin), while low levels were found in brainstem culture. Also, phagocytic cells (macrophages), endothelial-like cells, mesenchymal-like cells, ependymal-like cells and oligoblasts were found. Neither mature neurons, nor oligodendroglial cells were observed. It is concluded that although there might be some differences in the degree of maturation or in the cellular composition of the various cultures, they could serve as a good model system for studying the characteristics of astroglial cells from various brain regions.

Animals↗

Pergolide therapy in Parkinson's disease.

A total of 26 patients were treated with pergolide mesylate, a semi-synthetic ergot derivative with the property of direct dopamine activity. Of these patients, 18 suffered from late failure of L-dopa, while the remaining 8 had never before been treated with L-dopa. The aim of the trial was to study the activity of pergolide, either by giving it to untreated patients or by reducing as much as possible the L-dopa given in patients with parkinsonism. Adverse effects and failure rate were reduced by slowly increasing the daily dosage, by giving considerable dose flexibility whenever side-effects were manifest, and by the use of relatively low doses (mean of 3.8 mg in the L-dopa-group and 2.9 in the other group). At present, from 26 patients, 13 (50%) still remain in the study for an average treatment period of 16 months (3 weeks to 25 months for the group as a whole). All patients experienced a beneficial effect from pergolide, especially during the first months of treatment, in selfcare, rigidity, gait and automatic movements. Slight or no improvement was seen in tremor, speech and posture. The most frequent side-effects were nausea and vomiting (in the initial phase of the treatment), insomnia and psychotoxic reactions (mostly periods of confusion accompanied by visual hallucinations and paranoid illusions). The study indicated that pergolide mesylate is a useful additive for treatment of parkinsonism, but special attention should be paid to the important psychotoxic adverse effects that may appear, even at a low dose.

Aged↗

Blood-brain barrier in chronic relapsing experimental allergic encephalomyelitis: a correlative study between cerebrospinal fluid protein concentrations and tracer leakage in the central nervous system.

Blood-brain barrier (BBB) permeability in chronic relapsing experimental allergic encephalomyelitis was studied morphologically in tracer studies with horseradish peroxidase (HRP) as well as by quantitative determination of HRP, albumin, and IgG in serum and cerebrospinal fluid (CSF). BBB damage was found to be localized in demyelinating plaques and in blood vessels with vasculitis. Actively demyelinating lesions showed massive increase in BBB permeability, whereas in inactive or remyelinated lesions BBB damage was either minimal or absent. Determination of serum proteins in the CSF of animals with severe disease and a high incidence of actively demyelinating lesions showed evidence of BBB damage (reduction of Q-albumin) and an IgG-index in the normal range. In animals with only inactive lesions the Q-albumin was normal, the IgG index, however, was elevated. This finding indicates intrathecal IgG synthesis. A correlation between morphologically visualized tracer leakage in the central nervous system (CNS) with serum protein concentrations in the CSF revealed that elevated CSF albumin is a reliable indicator for BBB damage in lesions, located near the inner or outer surface of the brain and spinal cord. However, singular focal lesions with BBB damage located in the depth of the CNS parenchyma may not be accompanied by CSF protein alterations. The invariable presence of BBB damage in active inflammatory demyelinating lesions and its absence in inactive plaques or in the unaffected nervous tissue may be important in therapy, not only in experimental allergic encephalomyelitis but also in multiple sclerosis (MS).

Animals↗

A serum protein affecting the regulation of the immune system.

A thermostable alpha 2 globulin inhibiting the immunoglobulin/anti-immunoglobulin reaction was demonstrated working with subacute sclerosing panencephalitis (SSPE) and control serum IgG. This protein was isolated from SSPE and normal human blood, it inhibits the immunoglobulin/anti-immunoglobulin reaction but no other antigen/antibody reactions when applying different immunochemical methods such as nitrocellulose immunofixation, 2 site immunoradiometric assay, solid phase radioimmunoassay in coated cups. This was demonstrated, working on the one hand with measles virus strain Edmonston or SSPE virus strain D.R. and SSPE serum and on the other hand with IgG from SSPE and control serum. This alpha 2 globulin, an inhibiting protein, appears to be related to "normal immunosuppressive protein".

Alpha-Globulins↗

Hyperargininemia: the rat as a model for the human disease and the comparative response to enzyme replacement therapy with free arginase and arginase-loaded erythrocytes in vivo.

Rat erythrocytes lack arginase as do the erythrocytes of human homozygote patients with hyperargininemia due to arginase deficiency. The rat has physiological liver arginase activity and plasma arginine and ornithine levels between the homozygotes and the heterozygotes with hyperargininemia. In rats, one injection of free arginase induces a transient exogenous arginase effect which is abolished after 24 hr. One injection of isoionic arginase-loaded erythrocytes provokes an exogenous arginase effect in physiological "hyperargininemic" rats and pathological "hyperargininemic"-made rats for at least 8 and 5 days respectively. The very transient response in vivo to exogenous free arginase can be considerably prolonged by entrapment of the arginase in isoionic prepared erythrocytes.

Amino Acid Metabolism, Inborn Errors↗

Juvenile dystonic lipidosis (variant of Niemann-Pick disease type C).

In two siblings affected with dementia, epilepsy and vertical supranuclear ophthalmoplegia, foam cells and sea-blue histiocytes were found in the bone marrow. Electron microscopy of skin and neuromuscular biopsies gave presumptive evidence in favour of a storage disorder. Postmortem examination of both cases revealed an intraneuronal polymorphous lysosomal storage in the central nervous system (in the cortex and in many nuclei e.g. the substantia nigra and the reticular formation of the brain stem). In the visceral organs with the spleen most severely affected, the inclusions had a different ultrastructure, being composed of tightly apposed leaflets. The biochemical study revealed accumulation of sphingomyelin and other lipids in liver and spleen, with normal sphingomyelinase activities, which is consistent with the diagnosis of Niemann-Pick disease type C. In the brain, the most striking abnormalities involved the glycolipids. Sphingomyelinase activities were unchanged in cultivated skin fibroblasts. These data compared with those of reported cases, allowed the following conclusions to be made: (1) although the combination of clinical features appears to be unique, none of them, when considered separately, is pathognomonic for juvenile dystonic lipidosis; (2) diagnosis during life can be suggested by careful examination of nerve bundles and fibroblasts with the electron microscope, although the method of choice appears to be the study of bone marrow; but final assessment of the diagnosis, in the absence of demonstrable enzymic deficiency, requires in most cases a study of the lipid profile in a liver biopsy (or better, spleen tissue whenever available); (3) the intralysosomal storage is different, both morphologically and biochemically, in the central nervous system and in the spleen; (4) juvenile dystonic lipidosis represents a juvenile variant of Niemann-Pick disease type C, pending the discovery of the primary defect responsible for this disorder.

Adolescent↗

Identification of several forms of the glial fibrillary acidic protein, or alpha-albumin, by a specific monoclonal antibody.

A monoclonal antibody (mAb), termed UIA/NEU/I/G1 (G1), that reacted with the astroglial marker glial fibrillary acidic protein (GFAP), or alpha-albumin, is described. It was directed against a structural determinant of GFAP. The G1 mAb could be used for quantitative determination of GFAP in two-site radiometric assays and for histoimmunological demonstration of GFAP. The G1 mAb reacted with the GFAP from rat as well as from man. The presence of several different molecular weight forms of GFAP in aqueous and detergent extracts from human brain was shown with the G1 mAb. The possible meaning of these forms is discussed.

Animals↗