Nachweis und Verteilung der Enzyme: β-d-Glucuronidase, β-d-Galaktosidase, β-d-Glucosidase und Arylsulfatase in Neurinomen

Zusammenfassung In 17 Neurinomen wurden Verteilung und Aktivität der hydrolytischen Enzyme -d-Glucuronidase, -d-Glucosidase, -d-Galaktosidase und Arylsulfatase untersucht.Die höchste Aktivität der Enzyme zeigten die verfetteten Neurinome. Es bestand eine enge Beziehung zwischen Lipidablagerung und Fermentaktivität.Daraus wurde geschlossen, daß die im Neurinom gebildeten Markscheidenlipide unter Mitwirkung der untersuchten Hydrolasen abgebaut werden.

---

Demonstration and distribution of the enzymes: -d-glucuronidase, -d-galactosidase, -d-glucosidase, and arylsulfatase in neurinomas

Summary In 17 neurinomas, distribution and activity of the hydrolytic enzymes -d-glucuronidase, -d-glucosidase, -d-galactosidase, and arylsulfatase were examined. Highest enzyme activity was seen in neurinomas stuffed with lipid material. There was close relationship between lipid deposition and enzyme activity. From these findings it was concluded that myelin lipids formed in neurinomas are degradated by means of the examined hydrolases.

     

Hydrolytic enzymes in meningiomal subtypes

Summary Estimation of activity of five hydrolytic enzymes was made in four histologically different types of human meningiomas derived from surgery. The hydrolytic enzymes examined in 13 tumors included four lysosomal enzymes: -glucuronidase, N-acetyl--d-glucosaminidase (hexosaminidase), -galactosidase, and acid phosphatase. The fifth enzyme studied was alkaline phosphatase. The one papillary-type meningioma examined appeared to contain generally greater activities of the lysosomal enzymes than the other tumor types. Alkaline phosphatase was decidedly greater in transitional type meningiomas. The correlation of histological types with alkaline phosphatase activity is discussed with regard to previous observations.     

The biochemical and morphological response of hydrolytic enzymes in the developing brain to hypocholesterolemic agents

Summary Administration of hypocholesterolemic agents to developing rats has been found to selectively induce brain hydrolases. Certain regimes also caused an appreciable increase in total brain protein content. The hypocholesterolemic agents AY-9944 and zuclomiphene were tested individually and in combination. A fourth type of treatment utilized the above drugs in combination with Triparanol. Whenever AY-9944 was used, singly or in combination with other compounds, the -glucuronidase activity of developing brain was increased. Acid phosphatase and total brain protein were increased in animals treated with AY-9944 plus zuclomiphene or AY-9944 plus zuclomiphene and Triparanol. Neither AY-9944 nor zuclomiphene alone significantly affected brain total protein or acid phosphatase. Electron microscopic examination of tissue specifically reacted for acid phosphatase demonstrated that the increased enzyme activity was localized in cells in the perivascular spaces. Alkaline phosphatase and N-acetyl--glucosaminidase, two other hydrolytic enzymes assayed, seemed to be much less influenced by the drug treatments.     

Lectin histochemistry of scrapie amyloid plaques

Summary Peroxidase-labeled lectins were used for detection of specific monosaccharide residues in amyloid plaques in brains of scrapie-infected mice. The lectins tested recognize the following residues: -d-galactosyl (Ricinus communis agglutinin 120, RCA-1), -d-galactosyl and -d-galactopyranoside (Bandeirea simplicifolia aggl., BSA), -d-mannosyl and -d-glucosyl (Concanavalin A, Con A), N-acetylglucosaminyl and sialyl (Wheat germ aggl., WGA), sialoglycoconjugates (Limulus polyphemus aggl., LPA), -l-fucosyl (Ulex europeus aggl., UEA-1 and Tetragonolobus aggl., TPA), N-acetyl-d-galactosaminyl (Helix pomatia aggl., HPA). The most intense staining reaction in amyloid plaques was observed with BSA and WGA; it was less intense with RCA-1, Con A, and HPA. This indicates that the plaque material contains glycoproteins with abundance of accessible residues of - and -galactose, N-acetyl-d-glucosamine and N-actyl-d-galactosamine, and some types of sialoglycoconjugates recognized by WGA. Such residues, like -l-flucosyl recognized by UEA-1 and TPA, were almost undectectable in the examined plaques.There were also some differences in the staining intensity between small and large plaques (WGA and HPA) and between central and peripheral areas of the plaques.In the wall of micro-blood vessels relatively strong staining reaction was observed with RCA and BSA and less intense with WGA and Con A.Support in part by grant no. 5PO1 AG 04220-03 from the National Institute of Aging, NIH     

A new form of ovine GM1-gangliosidosis

neurological signs were observed in 3 lambs at approximately 1 month of age, in a flock of 1 ram and 29 ewes with 43 lambs. Deterioration occurred such that the lambs had either died or been killed by 4 months of age. Necropsies of two of these lambs revealed a diffuse encephalopathy in which the most prominent feature was ballooned neurons. Sections of frozen brain showed PAS-positive, oil red O-negative, and weak Sudan Black-positive material in the swollen neuronal cytoplasm. The ultrastructure of the neuronal inclusions showed characteristic whorled membranes, suggesting diagnosis of a gangliosidosis. The underlying enzymic defect was investigated by assaying 11 lysosomal enzymes in extracts of kidney from an affected lamb and from normal lambs. A deficiency (90%) of acidic -d-galactosidase was found in the affected lamb. All other activities, including N-acetylneuraminidase, were normal. A specific deficiency of lysosomal -d-galactosidase was demonstrated by separating the lysosomal and cytosolic -d-galactosidase by chromatography on concanavalin A-Sepharose. Diagnosis of G_M1-gangliosidosis, analogous to the severe infantile form of the human disease, was made on the basis of the pathology and enzymology. The -d-galactosidase activity in the white blood cells of the ram and several of the ewes was consistent with their being heterozygotes. This disorder is different from a previously described lipidosis in sheep, in which there was a combined deficiency of -d-galactosidase and -neuraminidase.     

Cerebral β amyloid deposition in patients with malignant neoplasms: its prevalence with aging and effects of radiation therapy on vascular amyloid

We examined immunohistochemically 123 autopsy brains from patients aged between 30 to 59, who died as a result of malignant neoplasms. Using antiserum to amyloid protein (A), we found that cerebral A deposits began in the subjects' fifth decade; its prevalence was 0%, 9.8% and 21.5% in the fourth, fifth and sixth decades, respectively. The major form of A deposition was diffuse-type plaques, although one third of the brains with A deposition showed amyloid angiopathy. Subpial A deposition is frequently associated with amyloid angiopathy. The prevalence of cerebral A deposits was about two times higher in the patients who had received brain radiation therapy (27.8%) compared to non-radiated patients (14.8%). Amyloid angiopathy was much more prominent (P<0.05) with radiation therapy (22.2%) than without (8.0%). We found that cerebral A deposition is dependent on aging, even in patients with malignant tumors and at beginning in their forties, and that brain radiation therapy is a possible risk factor of A deposition, especially in the form of amyloid angiopathy.     

Histochemische Enzymnachweise in den neurosekretorischen Kernen der Ratte

Zusammenfassung An den Gehirnen von 36 weiblichen Ratten wurden die Enzyme Cytochromoxydase, Lactat-, Succinodehydrogenase, DPNH- und TPNH-Diaphose, sowie -Glucuronidase, -Galactosidase, -Glucosidase und Arylsulfatase in den neurosekretorischen Kernen untersucht.SDH und CyO zeigten eine niedrige Aktivität, während LDH, DPNH-Di und TPNH-Di deutlich nachweibsar waren.Die Reaktionen beim Glykosidennachweis fielen nur schwach aus, ein sicherer Nachweis der Arylsulfatase gelang nicht.

---

Histochemical demonstration of enzymes in neurosecretory nuclei of the rat

Summary The enzymes cytochromoxydase, lactic-, succino-dehydrogenase, DPNH- and TPNH-diaphorase as well as -glucuronidase, -galactoidases, -glucosidase and arylsulfatase were analysed in the paraventricular and supraoptic nucleus of the brains of 36 female rats.SDH and CyO showed a lower activity while LDH, DPNH-di and TPNH-di could be proved distinctly.On proving glycosidases the reactions were only moderate. A certain proof of arylsulfatase could not be furnished.

     

Plasma dopamine-β-hydroxylase and preschool behavior in children with conduct disorder

The preschool behavior history and a history of abuse or neglect were compared between emotionally disturbed boys with and without conduct disorder (CD), and between boys with high and low plasma dopamine--hydroxylase (DH) activities and CD. Boys with CD had the expected increase in preschool behaviors associated with attention deficit disorder (ADD) and CD as well as more reports of abuse or neglect. A higher percentage of boys with low DH were reported to have preschool behaviors associated with ADD. In contrast, more high DH subjects were reported as abused or neglected.This work was supported by grants from the National Institute of Mental Health MH38679, the Meadows Foundation, the San Antonio Area Foundation, and the Abell-Hanger Foundation.     

Lectin histochemistry of plaques and tangles in Alzheimer's disease

Summary Biotinyl derivatives of several lectins and avidin-horseradish peroxidase were used to study the localization of glycoconjugates in amyloid plaques and in neuritic tangles in brains of patients with Alzheimer's disease (AD), Downs syndrome (DS) and Gerstmann-Sträussler syndrome (GSS). The lectins tested recognize the following residues: -d-galactosyl [Ricinus communis agglutinin 120, (RCA-1) and peanut agglutinin, (PNA)]; -d-galactosyl [Griffonia simplicifolia agglutinin (GSA)]; -d-mannosyl>-d-glucosyl [concanavalin A (Con A) andLens culinaris agglutinin (LcH)];N-acetyl- andN-glycolylneuraminic acid [Limax flavus agglutinin (LFA) andLimulus polyphemus agglutinin (LPA)];N-acetyl-glucosaminyl and sialyl [wheat germ agglutinin (WGA)];N-acetyl-d-galactosaminyl [Helix pomatia agglutinin (HPA) andDolichos biflorus agglutinin (DBA)] and -l-fucosyl [Ulex europeus agglutinin (UEA-1)]. The majority of lectins listed above bind preferentially to the peripheral area of AD plaques, whereas in plaques of DS they are mainly bound to central amyloid core. In neurofibrillary tangles of AD brains only residues recognized by WGA and HPA or DBA were found, whereas in DS brains, in addition to above mentioned, -d-galactose (RCA-1) and sialic acid (LFA) were also present. In brain microblood vessels the strongest reaction in endothelia appeared with UEA-1 and RCA-1, indicating the abundance of -l-fucosyl and -d-galactosyl residues. In AD brains deposits of amyloid were noted in the wall of some blood vessels, where monosaccharide residues recognized by RCA-1, GSA, UEA and WGA but not by Con A and LFA were present. However, our studies of some organs (liver, kidney, heart and testes) of patients with generalized amyloidosis revealed a lack of these sugar residues. It indicates, that the composition of amyloid present in brains of AD is different to that in other organs in generalized amyloidosis.Supported in part by grant no. AG 04220-03 from the National Institute of Aging, NIH     

Histochemische Untersuchungen zur Verteilung und Aktivität hydrolytischer Enzyme in Gliomen

Zusammenfassung Es wird über Aktivität und Verteilung der -Glucuronidase, -Galaktosidase, -Glucosidase und Arylsulfatase in 49 Gliomen berichtet. Die höchste Aktivität in den Tumorzellen weisen die Glykosidasen auf. Mit zunehmender Malignität der Tumorart ist eine Zunahme der Glykosidasenreaktion festzustellen. Alle untersuchten Enzyme sind infolge Diffusion in zerfallenden Markscheiden und ihren Fragmenten nachweisbar.

---

Summary Activities and distribution patterns of -glucuronidase, -galactosidase, -glucosidase and arylsulfatase were demonstrated histochemically in 49 gliomas. The activities of the glycosidases were higher than that of the sulfatase, and also higher in malignant tumors than in benign ones. The enzymes tested are seen within damaged and disintegrating portions of the myelin sheath.

     

Amyloid β peptide 1–42 highly correlates with capillary cerebral amyloid angiopathy and Alzheimer disease pathology

Recent studies reported both positive [Thal et al. (2003) J Neuropathol Exp Neurol 62:1287–1301] and negative [Tian et al. (2003) Neurosci Lett 352:137–140] correlations between cerebral amyloid angiopathy (CAA) and Alzheimers disease (AD) pathology. We have recently shown high correlations between neuritic AD pathology and amyloid peptide (A) deposits in the capillary/pericapillary compartment (CapCAA) with only low correlations to general CAA (non-capillary). We have now studied the relationship between CapCAA and AD pathology with respect to the distribution of A40 and 42 in the frontal cortex of 100 human postmortem brains from both male and female, demented and non-demented patients (mean age ± SD 84.3±9.3 years). Using polyclonal antibodies to A40 and 42, capillary and plaques positivity were assessed semiquantiatively on a four-point scale. A42 deposits in capillaries correlated highly with both A42 deposits in plaques and morphological AD criteria (CERAD, Braak stages, and NIA-Reagan-Institute criteria), while only a low correlation with CAA was observed. A40 deposits in capillaries differed morphologically from A42 ones: they were limited to capillary walls, were significantly less frequent in both capillaries and plaques compared to A42 (P<0.01), and showed a low correlation with morphological AD criteria (P<0.05) and general CAA (P<0.01). By contrast, A42 deposits were seen in the glia limitans rather than in capillary walls themselves, and showed high correlation with morphological AD criteria (P<0.01). These data indicate that CapCAA is characterized by A42 deposits in pericapillary spaces or in the glia limitans. A low correlation between CAA and CapCAA, but high correlations between morphological AD criteria and CapCAA suggest different pathomechanisms for both types of CAA, and a close relation between CapCAA and AD pathology (both neuritic and plaque type). These data support the concept of a neuronal origin of A via drainage from interstitial fluid from the central nervous system along basement membranes to capillaries.List of Abbreviations AD Alzheimer disease - A beta amyloid peptide - A 40/42 CapS score of deposits of A 1–40/42 in capillaries - A 40/42 C number of A 1–40/42 positive cortical vessels - A 40/42 PS score of deposits of A 1–40/42 in plaques - A 40/42 TS total score of A 1–40/42 deposits - A 40/42 Csev severity of A 1–40/42 affection of cortical vessels - A 40/42 CS A 1–40/42 cortical score - A 40/42 L percentage of A 40/42 positive leptomeningeal vessels - A 40/42 Lsev severity of A 40/42 affection of leptomeningeal vessels - A 40/42 LS A 40/42 leptomeningeal score - ACTS A cortical total score - ALTS A leptomeningeal total score - CAA cerebral amyloid angiopathy - CAATS CAA total score - CapCAA capillary CAA - CERAD Consortium to Establish a Registry of Alzheimers Disease - NFT neurofibrillary tangle - NIA National Institute of Aging - NIA-RI National Institute of Aging and Reagan Institute - NP neuritic plaque - SP senile plaque - TS total scoreAn erratum to this article can be found at     

Regional brain kinetics of 6-fluoro-(β-11C)-L-dopa and (β-11C)-L-dopa following COMT inhibition. A study in vivo using positron emission tomography

Summary The regional brain kinetics of (-11C)-L-dopa and 6-fluoro-(-11C)-L-dopa was measured in six Rhesus monkeys using positron emission tomography (PET). Radioactivity accumulated specifically in the striatal region and the increase in L-dopa-derived radioactivity utilization with time was calculated using surrounding brain as a reference area, this being devoid of dopaminergic activity. The rate constant for selective striatal utilization i.e. grossly decarboxylation was 0.0110 ± 0.0007 (S.D) and 0.0057 ± 0.0006 min1 for (-11C)-L-dopa and 6-fluoro-(-11C)-L-dopa, respectively. After pre-treatment of the monkeys with the peripherally and centrally active catecholamine-O-methyl transferase (COMT) inhibitor Ro 40-7592 10 mg/kg, the decarboxylation rate remained unchanged (0.0112 ± 0.0015 min-1) for (11C)-L-dopa, whereas an increase in rate was measured for 6-fluoro-(-11C)L-dopa (0.0092 ± 0.0015 min–1). Differences in the distribution of radiolabelled metabolites i.e. the corresponding O-methyl-L-dopa in the reference area is most probably the reason for the difference in calculated decarboxylation rate seen between the radiotracers. The higher decarboxylation rate measured for 6-fluoro-(-11C)-L-dopa after blockade of COMT shows that the radiolabelled metabolites i.e. 6-fluoro-O-methyl-(-11C)-L-dopa significantly contributes to background radioactivity.     

Ultrastructural localization of lectin receptors on cerebral endothelium

Summary Oligosaccharide residues on the endothelial luminal plasma membrane of rat cerebral cortical vessels were localized using biotinylated lectins. In addition, the effect of pretreatment of brain slices with neuraminidase prior to the binding of cationized ferritin (CF) and certain lectins was studied.Conjugates of biotinylated lectins and avidin-d horseradish peroxidase reaction product were evenly distributed on the endothelium of arterioles, capillaries, and venules. Lectin binding sites were observed on the plasma membrane of pinocytotic vesicles open onto the vascular lumen and at the luminal end of the interendothelial space only. The following sugar residues were localized: -d-mannosyl, -d-glucosyl, -N-acetylglucosaminyl, sialyl,d-galactosyl, -l-fucosyl, and -N-acetyl-d-galactosaminyl.Following pretreatment of brain slices with neuraminidase -d-gal-(1–3)-d-galN-acetyl groups were demonstrated on endothelium. In this respect, cerebral endothelium differs from noncerebral endothelium which is reported to have peanut agglutinin binding sites without neuraminidase pretreatment.Anionic groups on cerebral endothelium were demonstrated at the same locations as the lectin binding sites. Following neuraminidase pretreatment there was reduction, but not absence, of CF binding supporting the observation that surface charge is not wholly due to sialyl groups.The role of monosaccharide residues in states of altered cerebrovascular permeability remains to be determined.Supported by Ontario Heart Foundation grant no. 2-6     

Immunohistological study of senile brains by using a monoclonal antibody recognizing β amyloid precursor protein: significance of granular deposits in relation with senile plaques

Summary Immunochemical analyses revealed that a monclonal antibody Am-3 recognized amyloid precursor protein (APP) in senile plaques extracted from Alzheimer's brain, but did not recognize amyloid protein. Immunohistochemically, however, the staining pattern of Am-3 in frozen section of Alzheimer's brain was almost the same with that of rabbit polyclonal antibody to amyloid peptide which could recognize both amyloid protein and APP. In other words, APP was present in senile plaques of various types, cerebrovascular amyloid and granular deposits. The granular deposits were 5–10 m in size and laminarily distributed in the 1st, 3rd and 4th layers of cerebral cortex. They were especially abundant in 1st and 4th layers where senile plaques were usually fewer in number. Although the distribution in the cerebral cortex was different between the senile plaques and the granular deposits, the number of the granular deposits was well correlated with that of senile plaques. The granular deposits were negative in Congo-red birefringence, but contained amyloid protein as well as APP fragment judging from positive staining by both Am-3 and polyclonal antibody to synthetic amyloid peptide. Thus, they could be regarded as pre-amyloid.     

Immunohistochemical study on the distribution of α and β subunits of S-100 protein in brain tumors

Summary The immunohistochemical distribution of and subunits of S-100 protein (S-100, S-100, respectively) in 138 cases of human brain tumors was investigated by the avidin-biotin immunoperoxidase method. Brain tumors can be divided into four groups: group 1 [S-100 (+) and/or S-100 (+)]; astrocytoma, glioblastoma, ependymoma, subependymoma, oligodendroglioma, choroid plexus papilloma, gangliocytoma, meningioma, chordoma, malignant melanoma. Group 2 [S-100 (+) and S-100 (-)]; pineoblastoma, pituitary adenoma, craniopharyngioma, rhabdomyosarcoma. Group 3 [S-100 (-) and S-100 (+)]; acoustic Schwannoma. Group 4 [S-100 (-) and S-100 (-)]; medulloblastoma, malignant lymphoma, germinoma. The S-100 immunoreactivity pattern in brain tumors was similar to those obtained using conventional anti-S-100 protein sera. In the first group of brain tumors both the number of positively stained tumor cells and the staining intensity were generally greater for S-100 than for S-100 with a few exceptions including one gemistocytic astrocytoma, one subependymoma, one malignant melanoma, and some cases of glioblastomas. As to the relationship between malignancy and S-100 protein in glioma, S-100 immunoreactivity decreased according to degree of malignancy, while that of S-100 varied, suggesting a heterogeneity of tumor cells in glioblastomas. Immunostaining for S-100 and S-100 might become a useful diagnostic procedure in brain tumors and may give us more detailed and precise data of S-100 protein in brain tumors.     

Über den Nachweis „spezifischer“ Proteine im Liquor cerebrospinalis durch die Immunoelektrophorese

Zusammenfassung Im normalen Liquor cerebrospinalis lassen sich mit der Immunoelektrophorese unter Anwendung spezieller Antiliquoreseren zwei liquor-spezifische Proteine nachweisen, die von Dencker als -CSF und -CSF bezeichnet wurden. Auch durch erschöpfende Absorption des Antiliquorserums mit menschlichem Serum lassen sich Antikörper gegen diese liquorspezifischen Proteine aus dem Antiserum nicht entfernen. Das -CSF stellt sich in der Immunoelektrophorese nach Scheidegger als lang ausgestreckte Linie in der Nähe des Antikörpergrabens dar, das -CSF verläuft geschwungener und in der Hälfte der Fälle in einem Doppelbogen ähnlich dem des Transferrins.In 90 untersuchten Seren wurden diese Linien in keinem Falle angetroffen. Von 278 teils normalen, teils pathologisch auffälligen Liquores enthielten 26 kein -CSF, und bei 7 dieser 26 Liquores fehlte auch die -CSF-Linie. Die Mehrzahl der 26 Liquores war auch sonst pathologisch verändert, ohne daß eine Beziehung zwischen Zellzahl, Gesamteiweiß und -Globulingehalt zu dem Verhalten der liquorspezifischen Proteine hergestellt werden konnte.Zugaben von Serum zum Liquorkonzentrat vor der Immunoelektrophorese löschen das -CSF leichter als das -CSF aus. Ein Fehlen der liquorspezifischen Proteine in Liquores mit erhöhtem Eiweißgehalt oder Blutbeimengung kann damit erklärt werden. Bei anderen Liquores mit fehlender Nachweisbarkeit der -CSF- oder -CSF-Linie ist eine verminderte Produktion dieser Proteine zu erwägen.

---

Summary By means of immunoelectrophoresis with specific Anti-CSF-sera, two proteins specific for the cerebrospinal fluid, named -CSF and -CSF by Dencker, can be demonstrated. Antibodies reacting with CSF-specific proteins are not abolished even after extensive absorption of the anti-CSF-serum with human serum as antigen. -CSF-proteins show up as a long smooth band close to the center groove when separated by immunoelectrophoresis according to Scheidegger. The bands of -CSF-proteins are more curved and in 50% of all cases form a double band similar to that of transferrin.These bands were not detectable in 90 serums examined. 26 out of 278 normal and pathological specimens of CSF failed to show any -CSF. The -bands were missing in 7 of these 26 specimens. The majority of these 26 specimens revealed additional pathological laboratory findings. No relation, however, appeared to exist between the presence or absence of CSF-specific proteins, cell count, total protein and -globulin.Upon the addition of serum to the concentrated specimens of CSF prior to immunoelectrophoresis, -CSF bands are eliminated more easily than the -CSF-bands. This could explain the absence of CSF-specific proteins in specimens with elevated protein or containing blood. However, a diminished production of proteins should also be considered when - and -CSF-proteins are absent.

---

---

Wir danken Frau Sigrun Bach und Fräulein Christa Wackler für ihre sorgfältige technische Mitarbeit.     

Influence of salbutamol and otherβ-agonists on hypothermia induced by clonidine,apomorphine and reserpine in mice

Summary Clonidine administered to mice induced hypothermia and this effect was antagonized by a single dose of the following-agonists: salbutamol, isoprenaline and terbutaline. The effect of these-agonists was completely antagonized by propranolol. The effect of terbutaline on reserpine-and apomorphine-induced hypothermia was also studied; it causing a slight but significant reversal of hypothermia. This effect was also blocked by propranolol.The results obtained here showed these-agonists behave in a manner similar to other antidepressant drugs. The data reinforces the view that-stimulation is of great importance in antidepressant action.     

Cerebral amyloid angiopathy in the elderly: vessel walls changes and relationship with dementia

A peptide deposits are observed in brain cortical and leptomeningeal microvessels in a few families, in patients with Alzheimer's disease and in cognitively normal elderly subjects. These deposits, which cause A amyloid angiopathy, are usually associated with other lesions induced by A peptide and tau pathologies. To investigate the consequences of cerebral amyloid angiopathy on arterial morphology and search for correlations with the degree of cognitive impairment, we carried out a prospective clinicopathological and morphometric study in 29 institutionalized elderly patients cognitively normal or affected with sporadic dementia associated with Alzheimer-type lesions, cerebral infarcts or both. We measured the external and internal diameters of arteries 40–120 m wide, containing moderate or severe A deposits, and of unaffected arteries in the temporal and frontal lobes. We found no differences in the mean external diameters. In contrast, the mean internal diameters of vessels with moderate A deposits were smaller than those of unaffected vessels. Conversely, the internal diameters of severely affected vessels were larger than those of unaffected vessels. This suggests that arterial walls become thicker during the early stages of amyloid angiopathy, and the diameter of the lumen decreases, whereas during advanced stages, the walls become thinner and the lumen becomes larger. In addition, we assessed the overall severity of amyloid angiopathy. This showed that thinner arterial walls and the severity of amyloid angiopathy were correlated to dementia. In a multivariate model that integrates the other macroscopic and microscopic lesions that may be implied in the mechanism of cognitive impairment, the severity of amyloid angiopathy per se explained 10% of the variability in the cognitive impairment.     

GSK-3β in cerebrospinal fluid of schizophrenia patients

Summary. Cerebrospinal fluid contains proteins and metabolites of brain origin and was extensively studied in psychiatry in the 1970s with few definitive results. We have recently found 40% reduced protein levels of GSK-3 in schizophrenia in postmortem prefrontal cortex, but our attempt to develop a diagnostic marker using peripheral lymphocyte GSK-3 was not successful. In this study we aimed to find whether the reduction in brain GSK-3 is reflected in CSF of schizophrenia patients. We report a significant reduction in CSF GSK-3 protein levels in six schizophrenia patients compared to seventeen healthy subjects. Our results corroborate other studies in which CSF protein levels reflect the alteration found in these proteins in schizophrenia patients postmortem brain.     

Comparative studies on the effects of β-adrenergic blockers in essential tremor

Summary To establish the criteria for the selection of a -adrenergic blocking agent (-blockers) suitable for the long-term treatment of tremor, 20 patients with essential tremor were treated with five different types of -blockers. All -blockers were effective for essential tremor, but their efficacy differed. The weaker the intrinsic sympathomimetic activity (ISA) and the more marked the membrane stabilizing activity (MSA), the more marked was the anti-tremor effect. Propranolol, which showed the strongest anti-tremor effect, had no ISA, but its long-term administration induced symptoms of heart failure, such as pretibial oedema, in most cases. In most of these cases, when propranolol was replaced by indenolol, which showed a very slight ISA, the pretibial oedema subsided and well-controlled tremor was maintained over a long period. With regard to efficacy and usefulness, it was thought that the -blockers with a very slight ISA and a marked MSA, such as indenolol, was most suitable for the long-term treatment of essential tremor.