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Biomedical subjects

S Strauss

Publications and source records attributed to S Strauss.

At least 55 records · Page 3Linked to original sources

Inflammatory mechanisms in Alzheimer's disease.

In recent years many studies have indicated an involvement of inflammatory mechanisms in Alzheimer's disease (AD). Acute-phase proteins such as alpha 1-antichymotrypsin and c-reactive protein, elements of the complement system, and activated microglial and astroglial cells are consistently found in brains of AD patients. Most importantly, also cytokines such as interleukin-6 (IL-6) have been detected in the cortices of AD patients, indicating a local activation of components of the unspecific inflammatory system. Up to now it has remained unclear whether inflammatory mechanisms represent a primary event or only an unspecific reaction to brain tissue damage. Therefore, we investigated whether IL-6 immunoreactivity could be found in plaques prior to the onset of neuritic changes, or whether the presence of this cytokine is restricted to later stages of plaque pathology. We confirmed our previous observation that IL-6 is detectable in a significant proportion of plaques in the brains of demented patients. In AD patients IL-6 was found in diffuse plaques in a significant higher ratio as would have been expected from a random distribution of IL-6 among all plaque types. This observation suggests that IL-6 may precede neuritic changes, and that immunological mechanism may be involved both in the transformation from diffuse to neuritic plaques in AD and in the development of dementia.

Alzheimer Disease↗

Production of calibration standards for x-ray fluorescence analysis of aerosol particles precipitated on different filter materials.

Calibration results are presented for a method producing filter standards of two different materials. The first filter type is a membranous filter, the second a quartz fibre filter. Multielement solutions with predetermined elemental concentrations have been produced by an aerosol generator and preciptiated onto the respective filter materials. Additionally, the particle size-distribution in the aerosol generator, depending on the salt concentration in the nebulized solution, is presented.

Journal Article↗

The participation of interleukin-6, a stress-inducible cytokine, in the pathogenesis of Alzheimer's disease.

A loss of synapses in the cortices of demented persons appears to be the primary correlate of Alzheimer's disease (AD). However, it is still unclear how synaptic pathology is connected to other pathological findings such as neurofibrillary and neuritic degeneration or inflammatory markers in AD. Interleukin-6 (IL-6) immunoreactivity has previously been detected in plaques in the brains of AD patients. In addition, elevated IL-6 concentrations have been measured biochemically in the brains of AD patients. Since transgenic mice bearing additional copies of the IL-6 gene under the control of a brain-specific promoter develop a marked cortical pathology including severe alterations of the dendritic arborization of cortical neurons, an IL-6 related inflammatory event could well be connected to the synaptic pathology in AD. In this study, we investigated whether IL-6 immunoreactivity in plaques could already be found prior to the onset of neuritic changes, or whether the presence of this cytokine is restricted to the later stages of plaque formation. While diffuse plaques represent an early stage of plaque formation, primitive and classic plaques (displaying neuritic pathology) are thought to reflect later stages of plaque pathology. Using a silver-staining method, we classified plaque stages in serial sections of paraffin-embedded cortices of clinically diagnosed and histopathologically confirmed AD patients and of control persons with no clinical history of dementia. Adjacent sections were stained with an antibody directed against IL-6. IL-6 was detectable in a significant proportion of plaques, but only in the brains of demented patients. In the AD cases, IL-6 was found in diffuse plaques in a significantly higher ratio as would have been expected from a random distribution of IL-6 among all plaque types. This observation suggests that IL-6 expression may precede neuritic changes and that in AD an immunological mechanism may be involved both in the transformation from diffuse to primitive plaques and in the development of dementia. The reasons for the increased expression of IL-6 in the brains of AD patients are still unknown. Basal IL-6 levels were found to be slightly elevated along normal aging. Based on several studies indicating that IL-6 expression is inducible also by psychological stress, one could speculate whether long-lasting stressful experiences may contribute to the pathological process underlying Alzheimer's disease.

Aged↗

Peritoneal ventilation in rabbits: augmentation of gas exchange with cisapride.

BACKGROUND: Peritoneal ventilation has been shown to be effective in achieving extrapulmonary oxygenation and carbon dioxide elimination in an animal model of severe adult respiratory distress syndrome (ARDS). Cisapride is a "prokinetic" agent (increases gastric emptying), that may increase the splanchnic circulation and thus favourably affect gas exchange in peritoneal ventilation. METHODS: Using Doppler ultrasound the effect of cisapride on the portal venous circulation was examined in eight spontaneously breathing rabbits and the effect of cisapride on gas exchange in five rabbits spontaneously breathing room air was compared with that of a control group who did not receive cisapride. Its effect on gas exchange in five rabbits with ARDS being treated with mechanical lung and peritoneal ventilation was compared with that of a control group, and its effect on gas exchange in five rabbits with ARDS treated with conventional ventilation was also compared with that of a control group. RESULTS: Enteral administration of cisapride increased portal venous blood velocity, as measured ultrasonographically, by a mean of 188% one hour after receiving the drug. In rabbits with ARDS being treated with both peritoneal ventilation and mechanical ventilation to the lungs, those receiving cisapride had arterial oxygen tensions 1.5-3 times that of controls. Cisapride had no effect on arterial blood gas tensions in rabbits who were spontaneously breathing room air, nor in rabbits with ARDS who received only conventional mechanical lung ventilation. CONCLUSIONS: Cisapride increases arterial oxygenation in rabbits with severe ARDS treated with peritoneal ventilation, probably due to its ability to increase splanchnic circulation. It should be considered as an adjuvant medication to peritoneal ventilation.

Animals↗

Comparative audit of blood transfusion during war and peace in Sarajevo.

A comparative study was made between 146 patients receiving blood transfusion at the State Hospital, Sarajevo, in a 3-month period of peace (group 1) and 250 patients receiving transfusions in a 3-month period of war (group 2). In group 1, trauma accounted for only 7% of transfusions while it accounted for 99% in group 2. The threshold for transfusion was increased in war and the mean pretransfusion haematocrit in group 2 was 21%, compared with 27% in group 1 (P < 0.001). Less blood was also transfused per patient in war with a mean transfusion volume of 1.1 units in group 2 compared with 2.6 units in group 1 (P < 0.001). The reasons and justification for such a conservative transfusion practice in a besieged city are discussed.

Blood Transfusion↗

Interleukin-6 is present in early stages of plaque formation and is restricted to the brains of Alzheimer's disease patients.

Interleukin-6 (IL-6) immunoreactivity has previously been shown in plaques in Alzheimer's disease (AD) and elevated IL-6 concentrations have been measured biochemically in brains of AD patients. In this study, we investigated the appearance of IL-6 immunoreactivity in AD plaques according to the stage of plaque formation. Using the Bielschowsky silver-staining method, we were able to differentiate between four types of plaques described earlier: diffuse, primitive, classic and compact. While diffuse plaques represent the early stage of plaque formation, primitive and classic plaques are thought to represent later stages of plaque development. We investigated serial sections of paraffin-embedded cortices of ten clinically diagnosed and histopathologically confirmed AD patients and ten patients with no clinical history of dementia. We found plaques in the brains of both nondemented and demented persons using the silver staining method or immunohistochemistry with antibodies against the amyloid precursor protein. In the group of clinically nondemented persons, diffuse plaques were the predominant plaque type, whereas primitive plaques formed the larger portion of lesions in the group of AD brains. IL-6 could not be detected in plaques of patients without dementia. Many IL-6-positive plaques were found in six of the AD brains and to a smaller extent in the other four AD cases. In the six cases with a large number of IL-6-positive plaques, IL-6 was found in a significantly higher ratio of diffuse plaques than expected from a random distribution of IL-6 in all plaque types.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Fetal lung hyperechogenicity: prenatal ultrasonographic diagnosis, natural history and neonatal outcome.

The ultrasonographic appearance of fetal lung hyperechogenicity is most commonly associated with congenital bronchopulmonary abnormalities, such as cystic adenomatoid malformation or pulmonary lobar sequestration. Spontaneous disappearance of echogenic lung lesions has rarely been reported, mainly due to in utero resolution of cystic adenomatoid malformation. We describe four fetuses with echogenic lungs detected prenatally, none of them having been proved to have adenomatoid malformation or pulmonary sequestration of the lungs. Color Doppler sonography was used prenatally in all cases to rule out pulmonary sequestration. Three of the four fetuses showed complete resolution of the lung lesions during gestation, with normal neonatal outcome, but in one where the lesion decreased in size, intrauterine demise occurred at 28 weeks' gestation before complete resolution, and pneumonia was found at autopsy. We suggest that fetal lung hyperechogenicity may result from in utero bronchial tree obstruction with retention of mucoid fluid distal to the obstruction. With advancing gestation, in some cases the relative obstruction may be relieved, and the sonographic appearance of the lungs may return to normal. A retention of mucus in the bronchial tree should be added to the differential diagnosis of hyperechogenic lung lesions detected by antenatal ultrasound examination.

Adult↗

Increased levels of nerve growth factor (NGF) protein and mRNA and reactive gliosis following kainic acid injection into the rat striatum.

After excitotoxic lesion of the rat striatum, the time courses of local nerve growth factor (NGF) and NGF mRNA contents were investigated using a sensitive immunoassay (ELISA) and reverse transcription coupled to polymerase chain reaction (RT/PCR). To investigate a possible correlation of increased NGF expression and excitotoxin-induced reactive gliosis, striata were also analysed by immunohistochemistry with glial markers. We found elevated striatal NGF protein after lesion over the whole observation period. NGF mRNA showed a biphasic increase 10 h and 10 days after lesion, the latter co-inciding with an increased astrogliosis. These results indicate that NGF accumulation after excitotoxin-induced neurodegeneration is partly due to local reactive astrocytes.

Animals↗

Comparison of the in vitro binding characteristics of the beta-carbolines harman and norharman in rat brain and liver and in bovine adrenal medulla.

The in vitro binding of the naturally occurring beta-carbolines harman and norharman in their tritium-labelled forms to cell membranes from the rat brain and liver and from bovine adrenal medulla was investigated. Displacement of the specific [3H]harman binding in bovine adrenal medulla and rat liver by several beta-carbolines and monoamine oxidase (MAO) inhibitors revealed the pharmacological profile of a single, high-affinity binding site (KD 4.92 +/- 0.43 nmol/l, Bmax 8.47 +/- 0.17 pmol/mg protein; adrenal medulla) which corresponded to the active site of MAO type A (MAO-A). Similar characteristics have previously been found for brain tissue from rat, marmoset and pig. In order to determine the temperature dependence of the [3H]harman binding, the KD and Bmax values for rat cerebral cortex were calculated from the results of saturation experiments at 5 temperatures (range: 0 degree C-37 degrees C). Whereas the Bmax values under all conditions were approximately 4 pmol/mg protein, the KD values, with increasing temperature, ranged from approximately 3 nmol/l to 30 nmol/l. The calculated linear van't Hoff plot (-ln KD against 1/T) suggested an enthalpy-driven binding of [3H]harman to MAO-A. At least three different [3H]norharman-binding sites were detected. In the rat forebrain, approximately 85% of the specific binding (at about 2 nmol/l of [3H]norharman) can be attributed to a MAO binding site of type B: the binding is displaceable, in nmol/l concentrations by the potent and selective MAO-B inhibitors MDL 72,974 A, R(-)-deprenyl and pargyline and, in mumol/l concentrations, by S(+)-deprenyl and the potent and selective MAO-A inhibitors clorgyline, harmine, harman, harmaline, brofaromine 5-F-alpha-methyltryptamine. After suppression of the MAO binding sites with 1 mumol/l clorgyline and 1 mumol/l R(-)-deprenyl, a second binding site was found. However, the binding at this site was biphasically displaceable by harman and norharman (Hill-slopes about 0.5 and 0.6, curvilinear Rosenthal plots) suggesting the presence of negative co-operativity or of two binding sites (states). A similar clorgyline/R(-)-deprenyl resistant single (Hill-slopes of displacement by norharman, harman and 6-hydroxy-beta-carboline about unity; linear Rosenthal plots) high affinity binding sites (KD 7.5 +/- 2 nmol/l, Bmax 130+/- 30 fmol/mg protein) was found in bovine adrenal medullary cell membranes. A third quite different clorgyline/R(-)-deprenyl resistant high-affinity (KD approximately 14 nmol/l) and high-density (Bmax 10-30 pmol/mg protein) binding site was detected in the liver.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Medulla↗

Intra-operative ultrasonography as a routine screening procedure in biliary surgery.

Intra-operative cholangiography and ultrasonography were compared in screening for unsuspected common bile duct stones. In 57 consecutive patients both procedures were performed, and in 60 only ultrasonography was used. Although the study was conducted during the initial self-teaching period (regarding ultrasonography) the results show an advantage of this relatively new diagnostic technique. The false positive rate was lower and consequently the predictive value of a positive test was higher for intraoperative ultrasonography. The main benefit would thus be a lower rate of negative common bile duct explorations. Our early results suggest that the general surgeon would need only a short adaptation period to this imaging modality, which would seem to be a valuable alternative to intra-operative cholangiography.

Adult↗

Effects of perinatal hypo- and hyperthyroidism on the levels of nerve growth factor and its low-affinity receptor in cerebellum.

Deficits or excesses of thyroid hormones during critical periods of mammalian cerebellar development can lead to profound biochemical and morphological abnormalities in this system. The goal of this study was to investigate the effects of perinatal hypo- and hyperthyroidism on the ontogeny of nerve growth factor (NGF) and its low-affinity receptor (p75NGFR) in the rat cerebellum. The concentration of NGF and of p75NGFR immunoreactivity (IR) were measured, several days after birth, in cerebella of rats which had received propylthiouracil (PTU) or thyroxine. NGF concentration was markedly enhanced only on postnatal day 2 (P2) in hyperthyroid rats, whereas in hypothyroid (PTU-treated) rats NGF values were similar to age-matched controls. These observations suggest that thyroid hormone affects NGF synthesis during early periods of cerebellar development. In Purkinje cells of control animals, p75NGFR IR peaked at P10. In hypothyroid rats, the expression of p75NGFR was retarded, peaking at P15, whereas in hyperthyroid rats it was advanced, peaking at P8. The increased p75NGFR IR found in Purkinje cell bodies and the delayed disappearance of p75NGFR IR from the external granular layer of hypothyroid rats suggest different roles for thyroid hormone in the developing cerebellum. We conclude that p75NGFR and NGF are independently regulated by thyroid hormone during critical periods of cerebellar development. The effect of thyroid hormone deficiency on p75NGFR content in Purkinje cells may involve complex mechanisms such as impaired efficiency of axonal transport.

Animals↗

Renal artery stenosis secondary to neurofibromatosis in children: detection by Doppler ultrasound.

Renal artery stenosis was diagnosed in two adolescents with neurofibromatosis using Doppler ultrasound. The diagnosis was confirmed by angiography. The renal vascular lesion in neurofibromatosis usually affects the proximal segment of the artery, which is the part most optimally visualized by ultrasound. We suggest that Doppler ultrasound of the renal arteries may be a useful technique in the investigation of hypertensive children with neurofibromatosis.

Adolescent↗

Effects of interleukin-1 and interleukin-6 on metallothionein and amyloid precursor protein expression in human neuroblastoma cells. Evidence that interleukin-6 possibly acts via a receptor different from the 80-kDa interleukin-6 receptor.

Since immunohistochemical studies indicated the presence of interleukin-6 in the cortices of patients with Alzheimer's disease, we were interested in the eventual biological effects of this cytokine on neuronal cells. We found that interleukin-6 and interleukin-1 induced metallothionein expression in a human neuronal (SH-SY5Y neuroblastoma) cell line. In contrast to metallothionein, amyloid precursor protein expression was unaffected by both cytokines. When searching in the same cell line for the expression of the classical 80-kDa interleukin-6 binding protein, which is part of the dimeric interleukin-6 receptor, we were unable to detect the respective mRNA. Our findings either indicate that the interleukin-6 receptor in these cells is expressed in extremely low levels or that interleukin-6 may act upon neuronal cells via a different, yet unknown neuronal receptor.

Amyloid beta-Protein Precursor↗

Hyperoxaluria is not a cause of nephrocalcinosis in phosphate-treated patients with hereditary hypophosphatemic rickets.

The treatment of X-linked hypophosphatemia (XLH) consists of phosphate and vitamin D3 derivatives. Transient hypercalciuria and hypercalcemia are well-known signs of vitamin D intoxication. Despite urinary calcium excretion control, the danger of nephrocalcinosis in treated patients has been emphasized. It has recently been suggested that hyperoxaluria might be a causative factor of nephrocalcinosis other than calcium in phosphate-treated XLH patients. We measured urinary oxalate and phosphate excretion in 12 patients with the syndrome of hereditary hypophosphatemic rickets with hypercalciuria (HHRH) receiving only oral phosphates and in 5 XLH patients receiving both oral phosphates and vitamin D. No correlation was found between the dosage of phosphate supplements or urinary phosphate excretion and urinary oxalate excretion, in either group of patients. Nephrocalcinosis, presenting as hyperechogenicity of the medullary pyramids, was found in 2 of the 5 XLH patients and only in 2 HHRH patients who had been treated with excessive doses of vitamin D2 and calcium, prior to the true diagnosis being established. We conclude: (1) hyperoxaluria is not a cause of nephrocalcinosis in phosphate-treated patients with hereditary hypophosphatemic rickets; (2) prolonged phosphate treatment alone does not induce nephrocalcinosis in HHRH patients, and (3) we believe that in XLH patients, nephrocalcinosis is essentially due to vitamin D overdosage at some stage, or noncompliance in phosphate intake, leading to repeated undetected hypercalciuric periods.

Adolescent↗

Partial multiseptate gallbladder: sonographic appearance.

Multiseptate gallbladder, a rare congenital anomaly, is characterized by the presence of multiple thin septa dividing the gallbladder lumen into various sized chambers, often with a honeycomb appearance. In nearly all cases described previously, the entire gallbladder lumen was traversed by the septa. We describe three children, ages 3, 9, and 16 years, with sonographic features of multiseptate gallbladder, in which the septa were confined to the body and neck of the gallbladder in two, and to the fundus in one. The CT features of the anomaly also are described in one patient.

Adolescent↗