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Biomedical subjects

J Kaluza

Publications and source records attributed to J Kaluza.

At least 19 recordsLinked to original sources
PubMed1999

Vascular endothelial growth factor and its receptor, KDR, in human brain tissue after ischemic stroke.

Ischemic stroke results from a reduction in cerebral blood flow to a focal region of the brain after the occlusion of an artery, causing damage to nervous tissue. There is a region of cerebral ischemic tissue (penumbra) surrounding an acute cerebral infarct that is dysfunctional but potentially viable. Restoration of perfusion in the penumbra may ameliorate the tissue damage. The identity and the role of growth factors that control the extent of tissue damage and its repair are poorly understood. Angiogenesis has been demonstrated to occur in brain tissues of patients surviving an acute ischemic stroke. In this paper we have investigated the status of a potent angiogenesis factor, vascular endothelial growth factor (VEGF), in patients after acute ischemic brain stroke. Western blotting and immunohistochemistry were used to determine protein expression, and in situ hybridization was used to quantify and localize mRNA synthesis. The expression of VEGF protein was increased in the penumbra compared with infarcted brain and contralateral hemisphere. Neurones, endothelial cells, and astrocytes in the penumbra in all patients studied had significant up-regulation of both VEGF165 and VEGF189 mRNA (p < 0.01, Wilcoxon Matched-Pairs Signed-Ranks Test) compared with infarcted tissue and the normal looking contralateral hemisphere that was used as a control. Immunohistochemistry demonstrated that kinase insert domain receptor was present in blood vessels within the infarct/penumbra and absent from the normal contralateral hemisphere. VEGF, which is important in angiogenesis, may also influence long term neuronal survival, and possibly its modulation may prove to be of therapeutic value for patients with ischemic stroke.

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PubMed1997

A putative role for platelet-derived growth factor in angiogenesis and neuroprotection after ischemic stroke in humans.

BACKGROUND AND PURPOSE: Growth factors control two important processes in infarcted tissue, ie, angiogenesis and gliosis. We recently reported that transforming growth factor-beta1 (TGF-beta1) might be involved in angiogenesis after ischemic stroke in humans; here we present data of an extensive study on platelet-derived growth factor (PDGF) and its receptors. METHODS: We studied brain samples from patients who suffered from ischemic stroke for the expression of mRNA encoding PDGF-A, PDGF-B, and PDGF receptors (PDGF-R). Proteins were examined by Western blotting and immunohistochemistry using the antibodies to PDGF-AB, PDGF-BB, PDGF-R alpha, and PDGF-R beta. RESULTS: At the mRNA level, PDGF-A and PDGF-B were expressed mainly in neurons in penumbra. PDGF-R mRNA was strongly expressed in some astrocytes but mainly in type III/IV neurons in infarct and penumbra. The least expression was seen in the contralateral hemisphere (P<.001). In contrast, both PDGF-AB and PDGF-BB immunoreactive products were present in most cell types: PDGF-R alpha and PDGF-R beta mainly on neurons, and PDGF-R beta on some endothelial cells, with less staining of all the isoforms in the contralateral hemisphere. On Western blots, PDGF-AB and -BB were expressed more within white matter than gray matter of infarct/penumbra, whereas both isoforms of receptor were expressed mainly in gray matter compared with contralateral hemisphere. There was no or very weak expression of the receptor in white matter. CONCLUSIONS: PDGF proteins are highly expressed in white matter, suggesting that PDGF may exert its function in white matter participating either in regeneration of damaged axons or in glial scar formation. PDGF-BB and its receptor expressed on microvessel endothelial cells might be involved in angiogenesis after stroke. Thus, PDGF is likely to be angiogenic and neuroprotective in stroke.

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PubMed1996

Increased expression of TGF-beta 1 in brain tissue after ischemic stroke in humans.

BACKGROUND AND PURPOSE: Occlusion in cerebral vessels results in ischemic stroke and is followed by proliferation of microvessels, ie, angiogenesis. The process is particularly marked in the border zone of the infarct, known as the ischemic penumbra. This increase in vascularization is likely to be caused by the action of angiogenic factors, such as TGF-beta 1, which is a powerful regulator of angiogenesis. METHODS: In this study we examined 10 brain samples from patients who suffered from ischemic stroke for the expression of mRNA encoding TGF-beta 1. RESULTS: The ischemic penumbra contained the highest levels of TGF-beta 1 mRNA, whereas the normal contralateral hemispheres had the least (P < .001, Mann-Whitney U test). Unlike those from normal brain, protein extracts from infarcted tissue contained active TGF-beta 1 as a 25-kD band in Western blot analysis. Extracts from the penumbra also contained a 12.5-kD isoform of TGF-beta 1. Both penumbra and infarct contained TGF-beta 1 immunoreactive products as assessed with immunohistochemistry, whereas very weak staining was observed in the contralateral hemisphere. CONCLUSIONS: These results suggest that TGF-beta 1 is important in the pathogenesis of the angiogenic response in ischemic brain tissue and its modulation may be used for therapeutic purposes.

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PubMed1996

Immunocytochemical studies of cellular reaction in human ischemic brain stroke. MAB anti-CD68 stains macrophages, astrocytes and microglial cells in infarcted area.

Studies on human brains with ischemic insult were performed with immunohistochemical methods to identify antigenic properties of cells participating in that pathology. The 10 patients of whom the brains were obtained at autopsy aged from 51 to 81 years had survived from 3 to 17 days from the onset of stroke to death. Cells involved in the process of decomposition of infarcted tissue were analysed with immunocytochemical methods and CD68, EMB11 (Dako) monoclonal antibody (MAB) was used. Three cell types were visualized e.g. macrophages, astrocytes and microglial cells. Cells identified were numerous in the boundary zone of infarcts and only rarely distributed in the surrounding tissue at a distance from the necrotic tissue. A few cells only were stained in the contralateral hemisphere and none were astrocytes. Our results provide evidence that morphologically different cell types can be marked with the same antibody, which may be in agreement with their similar function in the pathogenesis of ischemic brain stroke.

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PubMed1994

Role of angiogenesis in patients with cerebral ischemic stroke.

BACKGROUND AND PURPOSE: Stroke is one of the most common causes of mortality and morbidity in the Western world. It results from the occlusion of a cerebral artery followed by severe disturbances in blood supply through microvessels to brain tissue. Despite an extensive literature its pathophysiology is poorly understood, and this has severely impeded the logical development of therapy. METHODS: Brains were obtained from 10 patients aged 46 to 85 years with survival times of 5 to 92 days after their stroke. Infarcted areas and representative control tissues from the contralateral uninvolved brain hemisphere were collected. Microvessel density was measured microscopically. A total of 6520 microvessels were scored in 10,801 areas. The level of activation of the endothelial cells was studied by immunohistochemistry using three monoclonal antibodies, viz, E-9, raised against activated endothelial cells; IG11, recognizing vascular cell adhesion molecule-1; and anti-proliferating cell nuclear antigen. Angiogenic activity in tissue extracts was examined using an in vivo chicken chorioallantoic membrane assay. RESULTS: There was a statistically significant increase in the number of microvessels (Wilcoxon log-rank test; P < or = .01) in 9 of 10 infarcted brain tissues when compared with their contralateral normal hemisphere. In these patients the higher blood vessel counts correlated with longer survival, as ascertained by Spearman's p analysis (P < .02). The number of microvessels filled with blood cells was significantly lower in the infarcted hemispheres (P < .01). In contrast, statistically significant increased numbers of empty microvessels occurred in infarcted tissues compared with the contralateral hemisphere. Monoclonal antibody E-9 reacted weakly with normal-brain vascular endothelial cells; anti-proliferating cell nuclear antigen and IG11 were virtually negative. All three antibodies strongly stained the blood vessels of stroke tissues. The stroke tissues contained angiogenic activity, as shown by the induction of new blood vessels in a chorioallantoic membrane assay. CONCLUSIONS: We have shown that stroke causes active angiogenesis that is more developed in the penumbra. Further experiments are needed to determine if this angiogenesis has beneficial effect.

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PubMed1990

Two siblings with phenotypes mimicking peroxisomal disorders but with discordant biochemical findings.

The authors present a report on two sibling with a nearly identical phenotype mimicking peroxisomal disorder but with totally discordant biochemical findings. In an attempt to confirm the diagnosis of a peroxisomal disorder, plasma levels of very long chain fatty acids (VLCFA) and phytanic acid were determined. In addition, fibroblasts profile of VLCFA and plasmalogen levels were evaluated for Case 2. Pathomorphological examinations represented by lymph node and kidney biopsies as well as postmortem examinations of liver, adrenals and brain were performed in Case 1. The phenotypes of both siblings showed marked resemblance to those observed in children with Zellweger syndrome. The results of biochemical tests performed in Case 1, together with abundant peroxisomes in the liver and the wide spectrum of clinical abnormalities suggest pseudo-Zellweger or Zellweger-like syndromes, but no conclusive data have been found. The plasmalogen level in fibroblasts as well as the fibroblasts profile of VLCFA noted in Case 2 were within the normal range, thus excluding the possibility of a peroxisomal disorder. The striking phenotype resemblance of the siblings mimicking Zellweger, together with discordant biochemical findings, are difficult to explain on the basis of currently available tests.

Diagnosis, Differential↗
PubMed1977

Fever produced in the rat by intracerebral E. coli endotoxin.

E. coli endotoxin introduced into the brain ventricles or into various brain areas raises the body temperature of conscious rats. Endotoxin-sensitive sites were found within the anterior hypothalamus and the lower brainstem. The increase in temperature (delta T) after microinjection of endotoxin into the anterior hypothalamic nucleus was dose-dependent. Endotoxin injected into the ventricles produced monophasic hyperthermia, but microinjections into the anterior hypothalamus produced monophasic or biphasic types of hyperthermia. The second and third microinjections of endotoxin into the anterior hypothalamic nucleus subsequently caused higher responses in delta T, but not in the rate of temperature change. The effects of the fourth and furter microinjections were the same as those of the third, and no tolerance developed for 24 days. The observations of behaviour, vegetative reactions, skin temperature, and carbon dioxide production indicated that the rise in the rat body temperature induced by endotoxin represents fever and that the heat is gained, at an ambient temperature of 22 degrees C, mainly through skin vessel vasoconstriction. Aspirin abolished and reversed fever induced by endotoxin, while hydrocortisone was without effect.

Animals↗
PubMed1977

Reduction of nitro-BT by some components of the chloroform-methanol extract of the grey matter of the rat brain.

An attempt was made to extract the substance present in the nerve fibres of the cerebral cortex and basal ganglia which reduced Nitro-BT in alkaline medium pH 9-5 [4,5]. The investigations were performed on 40 white Wistar rats of both sexes and ca. 200 g of body weight. The brains taken for studies were fixed in Baker's formalin for 1,5 hr, thereafter grinded and homogenized in chloroform-methanol solution supplemented up to 100 ml of final volume after homogenisation. Thus prepared solution was left for 24 hr at 4 degrees C temperature and than centrifuged 2000 g/min. The extract was evaporated and the sediment further investigated. The following fraction were received: 1. fraction soluble in aceton, 2. fraction soluble in ethylalcohol, 3. fraction soluble in ether, 4. fraction soluble in water and 5. the sediment. Each fraction was incubated with a standard medium containing Nitro-BT. After incubation the amount of reduced Nitro-BT in each of the incubation medium was spectrophotometrically measured. The most intense reduction was found in the incubation medium with the water fraction. The spectrophotometrically determined reduction of Nitro-BT of the water fraction compared with that of the gangliosides solution were similar. The addition into the incubation media biogenic amines and N,N-diethyl-p-phenylenediamine enhances the reduction of Nitro-BT significantly. According to the results obtained an interference of gangliosides and of the investigated amines in the reduction of Nitro-BT is suggested.

Animals↗
PubMed1977

Some remarks on oxidation of aryl- and alkylamines in fibers of the central nervous system. A histochemcial study.

Experiments were performed on brains of white Wistar rats, of both sexes, weighing 180-200g and 24 cats from various sources. Frontal sections were fixed in Backer's formalin and thereafter cut in a cryostat on 10 microns thick slices, dried on air. The slices were: a) either preincubated 1 hr in room temperature in solutions of the following amines: adrenaline, noradrenaline dopamine and L-dopa, para amino-diphenylamine and its derivatives, thereafter incubated in an incubation medium which conatained nitro-BT, phenazine-methosulfate (PMS), and glycine-buffer pH 9-5 b) or simultaneously incubated with the above mentioned standard medium. It has been found that all compounds tested, enhanced the reaction significantly in the fibers of the central nervous system except L-dopa. The last compound underwents very intensive autooxidation so that its influence on the reaction could not be taken into account. The observed reaction results allow us to suggest that the oxidation-reduction reaction in the nerve fibers might be of significance in the catabolism of biogenic amines.

Animals↗
PubMed1976

Attempts at inhibition of autooxidation of catecholamines in vitro.

The authors attempted to inhibit autooxidation of catecholamines in vitro by means of sulphur-containing amino-acids, monosaccharides, and aminobutyric acids. The SH group-containing amino-acids were found to suppress autooxidation of catecholamines passing from a chloroform-methanol solution (2:1) to water or buffer solutions. A similar though less pronounced property was manifested by cysteic acid. Likewise glucose, fructose and galactose blocked the reaction. Among aminobutyric acids only gamma-aminobutyric acid inhibited autooxidation of amines. However, despite positive results obtained, these experiments cannot be utilized in studies on reduction of Nitro-BT, as no reduction of Nitro-BT occured in the solutions in which catecholamine autooxidation was brought to a stop.

Amino Acids↗