bluuebunny/crossref_metadata_2025 huggingface dataset:
Macro- and Microstructure of the Superior Cervical Ganglion in Dogs, Cats and Horses during Maturation
Authors: Fioretto Emerson Ticona , de Abreu Rogério Navarro , Castro Marcelo Fernandes de Souza , Guidi Wanderley Lima , Ribeiro Antonio Augusto Coppi Maciel
Published: August 2007

The superior cervical ganglion (SCG) provides sympathetic input to the head and neck, its relation with mandible, submandibular glands, eyes (second and third order control) and pineal gland being demonstrated in laboratory animals. In addition, the SCG’s role in some neuropathies can be clearly seen in Horner’s syndrome. In spite of several studies published involving rats and mice, there is little morphological descriptive and comparative data of SCG from large mammals. Thus, we investigated the SCG’s macro- and microstructural organization in medium (dogs and cats) and large animals (horses) during a very specific period of the post-natal development, namely maturation (from young to adults). The SCG of dogs, cats and horses were spindle shaped and located deeply into the bifurcation of the common carotid artery, close to the distal vagus ganglion and more related to the internal carotid artery in dogs and horses, and to the occipital artery in cats. As to macromorphometrical data, that is ganglion length, there was a 23.6% increase from young to adult dogs, a 1.8% increase from young to adult cats and finally a 34% increase from young to adult horses. Histologically, the SCG’s microstructure was quite similar between young and adult animals and among the 3 species. The SCG was divided into distinct compartments (ganglion units) by capsular septa of connective tissue. Inside each ganglion unit the most prominent cellular elements were ganglion neurons, glial cells and small intensely fluorescent cells, comprising the ganglion’s morphological triad. Given this morphological arrangement, that is a summation of all ganglion units, SCG from dogs, cats and horses are better characterized as a ganglion complex rather than following the classical ganglion concept. During maturation (from young to adults) there was a 32.7% increase in the SCG’s connective capsule in dogs, a 25.8% increase in cats and a 33.2% increase in horses. There was an age-related increase in the neuronal profile size in the SCG from young to adult animals, that is a 1.6-fold, 1.9-fold and 1.6-fold increase in dogs, cats and horses, respectively. On the other hand, there was an age-related decrease in the nuclear profile size of SCG neurons from young to adult animals (0.9-fold, 0.7-fold and 0.8-fold in dogs, cats and horses, respectively). Ganglion connective capsule is composed of 2 or 3 layers of collagen fibres in juxtaposition and, as observed in light microscopy and independently of the animal’s age, ganglion neurons were organised in ganglionic units containing the same morphological triad seen in light microscopy.
Effects of Fibroblast Growth Factor-2 on the in vitro Culture of Caprine Preantral Follicles
Authors: Matos M.H.T. , van den Hurk R. , Lima-Verde I.B. , Luque M.C.A. , Santos K.D.B. , Martins F.S. , Báo S.N. , Lucci C.M. , Figueiredo J.R.
Published: August 2007

The aims of the present study were to evaluate the effects of fibroblast growth factor-2 (FGF-2) on survival, activation and growth of caprine early-staged (preantral) follicles using histological and ultrastructural studies. Fragments of caprine ovarian cortex were cultured for 1 or 5 days in an enriched minimum essential medium, supplemented or not with different concentrations of FGF-2 (10, 50 or 100 ng/ml). Fragments from non-cultured ovarian tissue (control) and from tissues cultured for 1 or 5 days in a specific medium were processed for transmission electron microscopy (TEM) or classical histology to evaluate the morphological quality of caprine preantral follicles and to calculate the percentages of normal follicles. Additionally, effects of FGF-2 on oocyte and follicle diameter of cultured preantral follicles were investigated. Our results showed that, although the percentages of histologically normal follicles were lower in cultured than in non-cultured ovarian tissue fragments, there were no differences in this regard among treatments, neither on day 1 nor on day 5 of culture. After 1 and 5 days of culture, a significantly higher percentage of growing follicles was observed in the medium supplemented with 50 ng/ml of FGF-2. This FGF-2 treatment furthermore resulted in an increase in diameter of both oocytes and follicles that were cultured for 5 days. TEM showed that the ultrastructural integrity of caprine preantral follicles was maintained during their 5-day culture in the presence of 50 ng/ml FGF-2. In conclusion, this study demonstrated that at a concentration of 50 ng/ml FGF-2 not only maintains the morphological integrity of caprine preantral follicles cultured for 5 days, but also stimulates the activation of primordial follicles and the growth of activated follicles.
The Herpes Simplex Virus Gene Pol Expressed in Herpes-Associated Erythema Multiforme Lesions Upregulates/Activates SP1 and Inflammatory Cytokines
Authors: Gober Michael D. , Laing Jennifer M. , Burnett Joseph W. , Aurelian Laure
Published: August 2007

Background/Aims: Herpes-simplex-virus-associated erythema multiforme (HAEM) is characterized by lesional skin expression of the viral protein Pol and localized inflammation. The objective of this study is to examine the mechanism whereby Pol induces localized inflammation. Methods: A431 cells transfected with Pol or an empty vector and lesional skin from HAEM or drug-induced erythema multiforme patients were examined for expression of the transcription factor SP1 and SP1-regulated genes by immunoblotting, immunohistochemistry and immunofluorescence. Results: SP1, TGF-β, p21waf1 and Hsp27 were upregulated in A431 cells transfected with Pol but not the empty vector. Expression was further increased by exposure to IFN-γ. Pol+ HAEM lesional skin expressed SP1, Hsp27, TGF-β and p21waf1. Normal skin and drug-induced erythema multiforme lesional skin were negative. Conclusion: The data indicate that Pol activates SP1, causing upregulation of SP1 target genes (notably TGF-β) involved in localized inflammation. Upregulation is potentiated by IFN-γ.
Fungal Thigmotropism in Onychomycosis and in a Clear Hydrogel Pad Model
Authors: Piérard G.E. , Piérard-Franchimont C. , Quatresooz P.
Published: August 2007

Background: Thigmotropism is a biological characteristic corresponding to the directional growth of cells following topographical guidance cues. This behavior has been shown experimentally with fungal hyphae of both dermatophytes and nondermatophyte molds, as well as with the mycelial phase of the dimorphic yeast Candida albicans. Objective and Methods: We presently document this phenomenon using histomycology in onychomycoses of various fungal origins. Results: This mechanism is involved in the invasive phase of the pathogen or opportunistic fungi, and it probably governs various clinical aspects of onychomycoses. We incidentally disclosed fungal invasions of hydrogel pads. Conclusion: Thigmotropism can in part explain the diversity of orientations and shapes of fungi invading nail plates. The same phenomenon was disclosed inside hydrogel pads. As this material is transparent and easy to cut for microscopic examination, fungal thigmotropism is conveniently explored by this way.
Compound Heterozygous ABCA12 Mutations Including a Novel Nonsense Mutation Underlie Harlequin Ichthyosis
Authors: Akiyama Masashi , Sakai Kaori , Sato Toshihiro , McMillan James R. , Goto Maki , Sawamura Daisuke , Shimizu Hiroshi
Published: August 2007

Recently, it has been reported that several harlequin ichthyosis (HI) patients survive the neonatal period and their condition subsequently improves. Here we describe a 2-year-old Japanese boy who exhibited typical clinical features of HI at birth. He survived beyond the neonatal period after oral retinoid treatment and, at the age of 2 years, showed moderately thick, lamellar scales and erythroderma over his whole body. The patient is a compound heterozygote for 2 ABCA12 mutations, a paternal deletion mutation c.2021_2022del (p.Lys674ArgfsX63) and a novel maternal nonsense mutation c.7444C → T (p.Arg2482X). Electron microscopic observation of a skin biopsy specimen from the perinatal period revealed epidermal ultrastructural features consistent with HI. Immunofluorescence labeling using antiserum against a C-terminal ABCA12 epitope showed loss of expression in the patient’s epidermis. The present patient demonstrates that rapid diagnosis of HI by ABCA12 expression analysis and mutation detection, and early commencement of systemic retinoid therapy are crucial to significantly improving an HI patient’s prognosis.
Dermoscopy of Eccrine Poroma
Authors: Nicolino Rachele , Zalaudek Iris , Ferrara Gerardo , Annese Pietro , Giorgio Caterina M. , Moscarella Elvira , Sgambato Anna , Argenziano Giuseppe
Published: August 2007

Eccrine poroma (EP) may clinically mimic a number of benign and malignant skin tumors. Dermoscopy improves the clinical diagnosis of many pigmented and nonpigmented skin tumors, but to date little is known about the impact of dermoscopy in the diagnosis of EP. We report 2 patients with EP and discuss the diagnostic significance of the observed dermoscopic findings.
Predictive Value of Anatomical Findings and Karyotype Analysis in the Diagnosis of Patients with Disorders of Sexual Development
Authors: Arcari A.J. , Bergadá I. , Rey R.A. , Gottlieb S.
Published: August 2007

We assessed the predictive value of anatomical findings and karyotype for establishing a diagnostic orientation in patients with disorders of sex development (DSD). We performed a retrospective chart analysis of 228 patients, grouped into 4 categories: 46,XX DSD, non-dysgenetic testicular DSD, dysgenetic testicular DSD and ovotesticular DSD. Degree of virilisation, presence of vagina, presence of palpable gonads, size of gonads and a plain karyotype was available for all cases. 46,XX DSD due to congenital adrenal hyperplasia counted for 59.2% of the cases, non-dysgenetic testicular DSD for 13.6%, dysgenetic testicular DSD for 21.5% and ovotesticular DSD for 5.7%. Excluding congenital adrenal hyperplasia (CAH), a karyotype with at least one 46,XX cell line had a high diagnostic efficiency for ovotesticular DSD. In these patients, anatomical findings were not as useful to predict the gonadal phenotype. The existence of a 45,X cell line predicted with very high efficiency dysgenetic testicular DSD. Genital palpation was only partially helpful to predict the existence of testicular tissue. Non-dysgenetic testicular DSD could be ruled out with high efficiency in patients with an abnormal karyotype. Anatomical findings were helpful in 46,XY patients: palpated masses predicted non-dysgenetic testes with high accuracy. In all cases assessment of gonadal volume was less useful.
WT1-Mediated Gene Regulation in Early Urogenital Ridge Development
Authors: Klattig J. , Sierig R. , Kruspe D. , Makki M.S. , Englert C.
Published: August 2007

The Wilms tumor protein WT1 is involved in the development of several organs, including the gonads. WT1 mutations in humans lead to syndromes associated with impaired sexual development and Wt1 knockout mice show regression of gonad anlagen. As a transcription factor, WT1 fulfills its function by regulating a set of target genes. With respect to gonad development only few in vivo WT1 targets, e.g. steroidogenic factor 1 (SF1) have been identified so far. To get a comprehensive view of WT1 targets in the gonad, we compared gene expression in urogenital ridges of wild-type and Wt1–/– embryos. We found almost 150 genes differentially expressed higher than factor three, using microarray analysis. To confirm these results we performed quantitative real-time RT-PCR for many genes and observed a high degree of concordance between microarray and real-time RT-PCR results. Employing in situ hybridization we found ‘WT1 activated genes’ to be expressed in gonads, mesonephroi and coelomic epithelium – those parts of the urogenital ridge with Wt1 expression. Interestingly, many of the differentially expressed genes are known to show sex-specific expression at later time-points. These results provide a basis for investigation of developmental pathways in the urogenital ridge downstream of WT1 and for identification of new candidate genes involved in early urogenital ridge development. For example we provide a first potential target of WT1 in the coelomic epithelium – Muc16, and a gene regulated by the WT1 target SF1 – Gata4.
Hyperplastic Polyposis following Treatment of Gastric Vascular Ectasia: A Case Report and Review of Clinical Correlates
Authors: Ghabril M. , Gross S. , Krishna M. , Raimondo M.
Published: August 2007

The etiology of gastric antral vascular ectasia (GAVE) and hyperplastic polyps (HP) is not fully understood, but there is no known overlap. We report a case of gastroduodenal HP arising in a patient treated for GAVE.
Effects of Lipid-Supplemented Total Parenteral Nutrition on Fatty Liver Disease in a Premature Neonatal Piglet Model
Authors: Hyde Matthew J. , Amusquivar Encarnación , Laws John , Corson Anne M. , Geering Richard R. , Lean Ian J. , Putet Guy , Dodds Peter F. , Herrera Emilio , Clarke Lynne
Published: August 2007

Background: Routine total parenteral nutrition (TPN) in neonatal care can result in hepatic dysfunction in 40–60% of patients, most commonly as fatty liver, but little work has been conducted on the underlying mechanisms causing hepatic dysfunction. Objective: To use a piglet model for the premature human neonate on TPN, supplemented with lipid emulsions, to investigate hepatic responses.Method:Piglets were delivered 2 days prematurely. Six control piglets were fed enterally (E), whilst twelve animals were maintained on TPN. TPN piglets received the standard TPN solution plus the lipid emulsion as either ClinOleic® (C, n = 6) or Intralipid® (I, n = 6). Hepatic lipid content and the fatty acid composition of liver triacylglyercol (TAG) as well as hepatic lipase (HL) activity were determined. Lipoprotein lipase (LPL) activity was measured in the liver, muscle and adipose tissue. The plasma concentrations of choline, bilirubin, TAG and non-esterified fatty acids (NEFA) were also measured. Results:Liver lipid was significantly increased in piglets on TPN and the tissue fatty acid profiles reflected the lipid emulsion. HL and LPL activities were reduced in liver but LPL increased in adipose tissue during TPN. Plasma concentrations of choline, bilirubin, TAG and NEFA were similar across the treatments. Conclusions:The results suggest fatty liver occurs in neonates receiving TPN and the source of the accumulated lipid appears to be the lipid emulsion used. The factors regulating lipase activity during TPN require further study. The piglet can be used as a model for neonatal TPN.
Heterogeneity in Combined Pulmonary Fibrosis and Emphysema
Authors: Jankowich Matthew D. , Polsky Michael , Klein Michael , Rounds Sharon
Published: August 2007

Background: Combined pulmonary fibrosis and emphysema (CPFE) is a unique disorder described in several case series of upper lobe emphysema associated with lower lobe fibrosis. Patients with this entity have relatively preserved lung volumes and spirometry but marked reductions in diffusing capacity on pulmonary function testing. Smoking appears to be the predominant risk factor for this disorder. Usual interstitial pneumonia has been the most common histological pattern of interstitial lung disease described on biopsy in the literature. Objectives: To characterize the clinical, imaging and pathological features of a cohort of patients with CPFE. Methods: Retrospective review of electronic medical record data, radiological imaging, and available lung biopsy specimens for a series of 10 patients with CPFE at the Providence VA Medical Center, Providence, R.I., USA. Results: We describe a series of 10 patients with CPFE. All had severe reductions in diffusing capacity out of proportion to their lung volumes and spirometry. All had predominantly upper lobe emphysema on computed tomography; 8/10 had lower lobe subpleural reticular abnormalities and honeycombing, while 2 had lower lobe ground glass changes on imaging. These 2 patients demonstrated a pattern of interstitial lung disease on biopsy characterized by intra-alveolar macrophage accumulation in association with marked alveolar septal fibrosis, consistent with a variant form of desquamative interstitial pneumonia with extensive fibrosis. Conclusions: The imaging findings and pathology in patients with CPFE are heterogeneous.
Reduced Expression of Focal Adhesion Kinase in Intrahepatic Cholangiocarcinoma Is Associated with Poor Tumor Differentiation
Authors: Ohta Ryuji , Yamashita Yo-ichi , Taketomi Akinobu , Kitagawa Dai , Kuroda Yosuke , Itoh Shinji , Aishima Shin-ichi , Maehara Yoshihiko
Published: August 2007

Objective: Focal adhesion kinase (FAK) expression has been linked to tumor cell invasion and metastasis, but its role in intrahepatic cholangiocarcinoma (ICC) has not been addressed. The goal of this study was to investigate FAK expression in ICC and to assess whether its expression is correlated with clinicopathological factors or prognosis in patients with ICC. Methods: FAK expression was examined using immunohistochemistry with sections from 56 resected ICC specimens. The correlations between FAK expression and clinical outcome were assessed. Results: The patients were divided into two groups according to the degree of FAK expression: high FAK group (n = 16) and low FAK group (n = 40). A lower expression of FAK was correlated with tumor size, poor differentiation, lymph node metastasis, vascular invasion, and intrahepatic metastasis. In the low FAK expression group, multiple recurrence and distant metastases were more prevalent than in the high FAK expression group. The overall and disease-free survival analysis indicated worse outcomes of the low FAK expression group (p < 0.01). Conclusions: A low expression of FAK in ICC is associated with a poor outcome after a surgical resection.
Amygdaloid Pathology in Alzheimer's Disease: Qualitative and Quantitative Analysis
Authors: Brady Daniel R. , Mufson Elliott J.
Published: August 2007

Pathologic evaluation of the amygdala in Alzheimer''s disease (AD) revealed, as compared to controls, a 43.7% decrease in total amygdaloid area, with areal reductions in lateral and basolateral nuclei of 52.9 and 54.3%, respectively. Thioflavin-S stained sections of the amygdala demonstrated a topographic distribution of neuritic plaques, with classic plaques located primarily in accessory basal, medial basal and cortical nuclei, whereas diffuse plaques predominated in the lateral nucleus. Neurofibrillary tangles were also topographically distributed and were up to 10 times more numerous than neuritic plaques. Tangle-bearing neurons predominated in cortical, medial, accessory basal and medial basal nuclei, whereas extracellular tangles characterized lateral and basolateral nuclei. These results are interpreted in light of known anatomical connections and suggest a predictive pattern of pathology in AD.
Distribution of Neuropeptide Y, C-Terminal Flanking Peptide of NPY and Galanin and Coexistence with Catecholamine in the Locus coeruleus of Normal Human, Alzheimer's Dementia and Parkinson's Disease Brains
Authors: Chan-Palay V. , Jentsch B. , Lang W. , Höchli M. , Asan E.
Published: August 2007

The study demonstrates the presence of neuropeptide Y (NPY)-, C-terminal flanking peptide of NPY (C-PON)-, and galanin (GA)-immunoreactive (-i) neurons and axons in the locus coeruleus in normal adult human brain and in brains of patients with senile dementia of the Alzheimer type (SDAT) and Parkinson''s disease (PD) as well as evidence for the coexistence of peptides with catecholamines in individual locus coeruleus neurons. The morphology of C-PON-i neurons is analysed in detail with a computer-assisted program. They are either multipolar neurons with round or multiangular somata, or ''bipolar'' neurons with major dendrites issuing from the two poles of fusiform cell bodies, and represent small- to medium-sized locus coeruleus neurons. In the controls, C-PON-i and NPY-i neuron numbers are highest rostrally, lower in the middle and lowest in the caudal locus coeruleus. GA-i neurons are more frequent caudally. C-PON-i neuron numbers are decreased in old normal adult brains compared to young brains. NPY-i and GA-i neuron numbers are very low in all age groups. The axonal networks are densest rostrally. C-PON-i and NPY-i axons possess larger varicosities and thicker intervaricose segments than GA-i axons. Both the peptidergic neuronal systems and the innervation pattern are detrimentally altered in SDAT and PD, more so in the latter than in the former cases. In SDAT, some C-PON-i locus coeruleus neurons display morphological alterations resembling those encountered in tyrosine hydroxylase (TH)-i neurons in the same cases, with blurred somatic outlines, misshapen cell bodies and foreshortened dendrites. However, the alterations are generally less severe than those of the TH-i neurons and many C-PON-i neurons appear to be entirely normal. Relative to the number of TH-i neurons, the numbers of peptide-i neurons are higher in SDAT than in controls, and often more neurons are located caudally. Peptide-i axonal networks are less dense, and the remaining C-PON-i and NPY-i axons are tortuous and have larger varicosities than normal. In PD, the changes of C-PON-i neuronal morphology are as severe as in the TH-i neuron population, with rounded cell bodies and loss of dendritic arbors; the peptide-i innervation is reduced. The alterations in the peptide-i systems of the locus coeruleus, especially the increase in the numbers of neurons in SDAT, may be interpreted in terms of a plasticity of the aged brain.
Adaptation in Different Types of Dementia and in Normal Elderly Subjects
Authors: Johanson A. , Gustafson L. , Smith G.J.W. , Risberg J. , Hagberg B. , Nilsson B.
Published: August 2007

Forty-two patients with organic dementia and 66 normal elderly subjects were investigated with the Meta-Contrast Technique (MCT) elucidating emotional reactions and defensive strategies. Eleven patients with Alzheimer''s disease (AD), 13 with frontotemporal degeneration (FTD), and 18 with multi-infarct dementia were studied. Defensive strategies were found to be related to the type of brain disorder and its localization. Patients with AD needed significantly longer exposure times for recognition of the emotionally loaded picture configurations in the MCT and showed more often signs of anxiety. Signs of projection and depression were typical for patients with FTD.
Monoamine Oxidase and Dementia: Treatment with an Inhibitor of MAO-B Activity
Authors: Agnoli Alessandro , Martucci Nicola , Fabbrini Giovanni , Buckley Ann E. , Fioravanti Mario
Published: August 2007

Patients suffering from Alzheimer type dementia have demonstrated an increase in MAO-B activity. Treatment of these patients with an inhibitor of the monoamine oxidase activity, such as L-Deprenyl (LD), might therefore provide a valid therapeutic intervention. The efficacy of LD was examined in a double-blind, drug versus placebo (PL) study on 20 patients diagnosed between stages 3 and 5 of primary degenerative dementia. Treatment duration was 90 days (5 mg twice a day). All patients underwent clinical, behavioral, and memory evaluations every 30 days. Subjects in the LD group demonstrated an improvement on both attention and memory measures; some of the changes were apparent after only 30 days of treatment. PL patients showed no such improvement and also evidenced a decrease in behavior efficiency during the experimental period. Two patients dropped out of the study, 1 from each treatment group. No differences were found in either the type and number of concomitant treatments or side effects between groups.
Role of the EEG in the Prediction of Dementia in Parkinson's Disease
Authors: de Weerd A.W. , Perquin W.V.M. , Jonkman E.J.
Published: August 2007

Dementia develops in 10–60% of the patients with Parkinson''s disease. Prediction of the mental condition in the years to come is important for the patient and his physician. Features of the EEG which are easily extractable from the records allow the differentiation between patients whose mental condition will deteriorate over a period of 3 years and those with normal cognitive function after that time. As the prognosis for the individual patient can be given with an accuracy of 79%, the use of the EEG in predicting the cognitive status seems justified.
Effect of Acetyl-L-Carnitine on Serum Levels of Cortisol and Adrenocorticotropic Hormone and Its Clinical Effect in Patients with Senile Dementia of Alzheimer Type
Authors: Parnetti Lucilla , Gaiti Alberto , Mecocci Patrizia , Gottfries Carl Gerhardt , Santucci Carla , Reboldi Gian Paolo , Senin Umberto
Published: August 2007

Eleven patients with senile dementia of Alzheimer type were treated with acetyl-L-carnitine (ALC) intravenously for 10 days and then orally for 50 days. Serum levels of cortisol and adrenocorticotropic hormone were measured at baseline and after the intravenous treatment. Neuropsychological assessment was also carried out at the same times and at the end of the oral treatment. The results show a trend toward a decrease of the mean cortisol levels and a significant improvement of cognitive performances. These data could support the idea of the neuronotrophic action of ALC, indicating its usefulness for the treatment of dementia disorders.
Klüver-Bucy Syndrome Preceding Ventricular Enlargement in Normal-Pressure Hydrocephalus
Authors: Bromberg Mark B. , Aldrich Michael S. , Foster Norman L. , Berent Stanley
Published: August 2007

Symptoms of normal-pressure hydrocephalus (NPH) and the complete Klüver-Bucy syndrome (KBS) developed in a previously healthy woman before the appearance of ventricular dilatation on computerized tomography. Ventricular enlargement typical of NPH occurred several months later. Following ventriculoperitoneal shunting, gait abnormalities and KBS resolved, while incontinence, memory, and intellect improved and have since remained stable. An associated sleep disturbance characterized by early onset of rapid-eye movement (REM) sleep periods and sleep spindles throughout REM sleep was also improved by treatment. NPH may impair periventricular function before ventricular dilatation becomes apparent.
Galanin Gene Expression in the Nucleus basalis of Meynert in Senile Dementia of the Alzheimer Type
Authors: Chan-Palay Victoria , Ernfors Patrik , Persson Håkan
Published: August 2007

Senile Dementia of the Alzheimer type is accompanied by a loss of cholinergic neurons, a hypertrophy of galanin-immunoreactive axonal plexuses ending on the remaining cholinergic neurons, and a doubling of the amount of galanin peptide detectable by radioimmunoassay in the nucleus basalis of Meynert. This is accompanied by the preservation of receptors labeled by 125I-galanin over rest islands of Meynert neurons detected by quantitative autoradiography. The present study shows that there is tissue-specific expression of the galanin gene demonstrated by in situ hybridization using an oligonucleotide probe complementary to porcine galanin mRNA in the Alzheimer nucleus of Meynert. These combined studies indicate a significant plastic response of galanin in the Alzheimer brain as compared to age-matched controls which may be important in the progress of the disease as well as in the development of pharmacological therapies for the disease.
Effect of Phosphatidylserine on Cerebral Glucose Metabolism in Alzheimer's Disease
Authors: Klinkhammer P. , Szelies B. , Heiss W.-D.
Published: August 2007

In a preliminary study of 8 patients with probable Alzheimer''s disease (AD), the effect of phosphatidyl-serine (PS; 500 mg daily for 3 weeks) on brain glucose metabolism was studied using positron emission tomography (PET) of fluor-18-deoxyglucose. In all cases, pretreatment PET studies showed the metabolic pattern typical for AD, with predominant decreases in the parieto-occipito-temporal and frontal association cortex and less involvement of primary cortical areas and subcortical structures. Global metabolic rate increased by 14.8% following treatment. A repeated-measures ANOVA demonstrated significant increases (p < 0.01) of glucose metabolism in defined cortical and subcortical structures ranging up to 20.3% in basal ganglia/thalamus and 19.3% in visual cortex. Metabolism was also increased in areas most involved in AD (13.5–16%). Independent from these regional differences, an inverse correlation was observed between metabolic values and changes during the treatment period. A significant change of MMS scores or daily life activity, however, could not be observed during the 3 weeks of treatment. This shown metabolic effect of PS encourages long-term clinical trials on larger patient populations in which the effect of an increment of glucose metabolism on cognitive, neuropsychological and daily life performance can be additionally evaluated.
Intrusion Errors in Patients with Degenerative or Vascular Dementia: The Cholinergic Connection?
Authors: Lorscheid Thomas , Thompson Sharon L.
Published: August 2007

Behavioral data from demented patients and scopolamine-impaired normal subjects, and morphological data from patients with Alzheimer''s disease (AD) suggest that intrusion errors may mirror the dysfunction of the cholinergic system. The Picture Recall and Recognition Task used in this study was designed to systematically measure intrusion errors (i.e. false recognition of items semantically related to target items), and false alarms (i.e. false recognition of items semantically unrelated to target items). The results taken from the baseline data of a clinical trial with geriatric patients with major depressive episode and varying degrees of cognitive impairment indicate that intrusion errors occur more often than false alarms in those patients with more severe cognitive decline. Because this pattern was only observed in patients with dementia of nonvascular origin, the results support the hypothesis that intrusion errors are a relatively specific indicator of the cholinergic deficit accompanying AD.
Psychiatric Disorders in Dementia of Alzheimer Type: Cognitive and Hemodynamic Correlates
Authors: Agniel A. , Celsis P. , Puel M. , Démonet J.F. , Rascol A. , Marc-Vergnes J.P.
Published: August 2007

Psychiatric and cognitive disorders were evaluated on an all-inclusive basis in 64 patients with dementia of Alzheimer type and related to regional cerebral blood flow (CBF) measured by SPECT. Isolated affective troubles were found in 22 patients and isolated behavioral changes in 24 cases, whereas only 5 patients presented with both type of disorders. Delirious reactions and hallucinations never occurred alone and were present in only 4 patients. The occurrence and severity of psychiatric disorders were related to the overall severity of dementia and to the magnitude of the instrumental (cortical functions) deficit for most patients, with no difference according to affective versus behavioral disorders. Later onset and higher prevalence of females characterized the group of 14 patients with preponderant psychiatric over instrumental disorders. Left parietotemporal hyperperfusion was associated with prominently decreased instrumental capacities, whereas no peculiar flow defect was associated with either type of psychiatric disorder, while in the 14 patients with preponderant psychiatric impairment, mean CBF was only slightly reduced compared to controls.
Subsets of GABA Neurons in the Human Cerebellum in Normal Controls and Senile Dementia of the Alzheimer Type Patients Detected by Glutamate Decarboxylase, GABAA/Benzodiazepine Receptor Protein, Calbindin D-28k and Parvalbumin Immunocytochemistry (Part 1 of 2)
Authors: Zetzsche Thomas , Baimbridge Kenneth G. , Möhler Hanns , Chan-Palay Victoria
Published: August 2007

The distribution of gamma-aminobutyric acid (GABA)-ergic neurons in the postmortem human cerebellar cortex and dentate nucleus was studied using antibodies against glutamate decarboxylase (GAD) and two different cytoplasmic calcium-binding proteins, parvalbumin and calbindin D-28k (CaBP), and the alpha-subunit of the GABAA/benzodiazepine receptor protein. The cerebellum of normal controls was compared to those of patients with senile dementia of the Alzheimer type (SDAT) in order to determine the involvement of these neurons in the dementing disorder. In the normal human cerebellar cortex all neuronal types except granule cells were GAD-labeled. Immunoreactivity was found predominantly in axonal structures, particularly in basket plexus around Purkinje cell somata. Antibodies against CaBP specifically stained all Purkinje cells in their entirety including axons and dendritic spines. Parvalbumin immunoreactivity was found in a subpopulation of Purkinje cells, basket and stellate cells but not in Golgi and granule cells. Parvalbumin-immunoreactive basket plexuses were found around Purkinje cell somata. The most intense labeling with the GABAA/benzodiazepine receptor antibody was found on the surface of granule cells. Purkinje, basket and stellate cells showed only a weak labeling of their surface. In the dentate nucleus only small neurons showed GAD immunoreactivity. Large neurons were densely covered with labeled axons and varicosities. No cell somata were stained with antibodies against CaBP and parvalbumin. All types of large and small dentate neurons showed immunoreactivity against GABAA/benzodiazepine receptor protein on the surface of their soma and dendrites. SDAT is accompanied by some changes in neurons belonging to the GABA subset. Fewer spines were found on the dendrites of Purkinje cells and on large dentate neurons. In the granular layer, more Purkinje axonal deformations ('torpedoes') and a hypertrophic network of Purkinje axon collaterals were found.
Depression and Senile Dementia of the Alzheimer Type: Catecholamine Changes in the Locus coeruleus – Basis for Therapy
Authors: Chan-Palay V.
Published: August 2007

This paper describes the clinical, psychometric, neuropathological, and neurotransmitter studies on 8 patients selected from the ZÜrich study on dementia. It confirms the age-related loss of norepinephrine neurons in the locus coeruleus (LC) in control patients without neurological or psychiatric disease. A relationship between the incremental loss of LC neurons in patients with senile dementia (SDAT) and presenile dementia of the Alzheimer type and the increasing severity of the clinical disease was found. The morphological characteristics of altered Alzheimer neurons with enlarged somata and distorted shortened processes are described. The norepinephrine neurons in the LC of the 3 cases with depressive disorders, depression, Parkinson's disease with depression, and SDAT with depression, had in common severe LC norepinephrine cell losses and low levels of catecholamine-synthesizing enzyme signifying reduced norepinephrine levels. The significance of these findings in relation to the possible treatments of depression in complex coexistent diseases such as depression and SDAT are discussed.
Vitamin B12 Analogues, Homocysteine, Methylmalonic Acid, and Transcobalamins in the Study of Vitamin B12 Deficiency in Primary Degenerative Dementia
Authors: Regland B. , Abrahamsson L. , Gottfries C.G. , Magnus E.
Published: August 2007

B12 analogues, homocysteine, methylmalonic acid (MMA), and unsaturated transcobalamins, all potential markers of vitamin B12 status, were analyzed in blood and cerebrospinal fluid (CSF) from 22 patients with primary degenerative dementia of Alzheimer type. The level of active vitamin B12 in serum correlated significantly with serum homocysteine, serum MMA, and CSF homocysteine. CSF B12 correlated significantly with serum homocysteine and serum MMA. The ratio of analogues and active vitamin B12 concentrations in serum (analogue/active B12 ratio) correlated significantly with serum homocysteine, serum MMA and CSF B12. This study had no control group. However, based on available reference values, high concentrations of homocysteine and MMA in serum and unsaturated transcobalamin II in plasma were interpreted as evidence of vitamin B12 depletion or deficiency. Such high concentrations were found in a significant number of patients. In 9 patients, vitamin B12 injections were administered. After treatment, serum homocysteine levels fell significantly. We conclude that vitamin B12 analogues, homocysteine, MMA, and transcobalamins may be useful as markers in studies aimed at clarifying the role of vitamin B12 deficiency in dementia disorders.
Correlation of Cognitive Skills in Nursing Home Patients with Histologic Alzheimer Changes in Specific Brain Areas
Authors: Wettstein Albert , Lang Walter
Published: August 2007

56 nursing home patients were examined psychometrically within 10 months before death. Correlation of three mnestic, three verbal and three visual-spatial skills, and six activities of daily living (ADL) with counts of senile plaques and neurofibrillary tangles in frontal, parietal, temporal, and hippocampal cortices of both hemispheres were calculated. The skill to copy a cube correlates exclusively with the severity of Alzheimer changes in the right parietal cortex, the skill to recall visually presented and named objects with right hippocampal changes. In addition, the skills of spatial orientation, calculation, and finger position imitation correlate exclusively with right hemispheric changes. The skill of temporal orientation correlates more with the left, alternating hand movements with the right hemisphere, and naming and other verbal skills equally with changes in both hemispheres. Six of the nine cognitive skills correlate best with hippocampal changes, while ADL correlate best with parietal and not significantly with hippocampal changes. Global clinical dementia ratings as well as global pathological scores are insufficient to explain the deficits in variably severe cortical changes, and they are not adequate parameters for counselling patients, their relatives, or coaching staff in nursing homes.
White Matter Gangliosides in Incomplete Infarction
Authors: Englund E. , Brun A. , Svennerholm L.
Published: August 2007

A correlative biochemical-neuropathological study was undertaken in order to analyze white matter gangliosides in the selective incomplete white matter infarctions (SIWI) frequently occurring in dementia of Alzheimer type. Cerebral white matter from cases with complete white matter infarcts and from control cases was analyzed for comparison. A reduction of gangliosides and changes in the ganglioside pattern reflected the histopathological degree of severity of SIWI. In the complete infarcts, the ganglioside loss and qualitative changes were further pronounced. The results of the study support the theory of SIWI being a subtotal infarction affecting both myelin and axons.
Alzheimer's Disease in the National Academy of Sciences Registry of Aging Twin Veterans
Authors: Breitner J.C.S. , Welsh K.A. , Magruder-Habib K.M. , Churchill C.M. , Robinette C.D. , Folstein M.F. , Murphy E.A. , Priolo C.C. , Brandt J.
Published: August 2007

The (US) National Academy of Sciences Registry of aging twin veterans contains 15,924 pairs of white male twins born between 1917 and 1927. About 8,000 pairs are living today. In preparation for a study of Alzheimer's disease (AD) in this Registry, we investigated 829 members of pairs living in North and South Carolina, Virginia, in the District of Columbia, and Maryland. A brief telephone interview for cognitive symptoms was administered to 678 (91.4%) of 742 subjects located. Cognitive dysfunction was identified initially in 124 individuals (18.3%), whose clinical histories were then obtained over the telephone. Results suggested that 108 subjects did not have AD. Ten (62.5%) of the remaining 16 subjects underwent diagnostic evaluation for dementia. One had cerebrovascular disease with coincident depression. Two others with probable AD were a monozygotic (MZ) pair. The remaining 7 subjects had possible AD or a mild but progressive cognitive disorder suggestive of early AD. Upon subsequent examination, 3 of 4 MZ co-twins showed significant symptoms that had not been detected during screening procedures. None of 3 dizygotic co-twin showed any significant abnormality. These results suggest: (1) that a combination of mailed information, telephone interviews, and clinical examination provides a feasible means of detecting AD in the Registry, (2) that about 150 pairs with presumptive AD in 1 or both subjects will be identified in a full study of the Registry; (3) that concordance for AD in MZ pairs may exceed prior estimates, but (4) that such rates of concordance are apparent only upon detailed evaluation of apparently normal co-twins as well as their impaired brothers. Longitudinal observation of pairs with apparently affected individuals will be required for definitive conclusions.
Characterization of a Partial cDNA Specific for the High Molecular Weight Microtubule-Associated Protein MAP2 That Encodes Epitopes Shared with Paired Helical Filaments of Alzheimer's Disease
Authors: Brion J.P. , Cheetham M.E. , Couck A.M. , Flament-Durand J. , Hanger D.P. , Anderton B.H.
Published: August 2007

A cDNA encoding epitopes present in paired helical filaments (PHF) in Alzheimer's disease has been characterized by DNA sequencing and by immunochemical analysis of the encoded recombinant protein fragment. The cDNA encodes 773 amino acids specific of the rat high molecular weight microtubule-associated protein MAP2. This amino acid sequence is localized in the side arm projection domain of MAP2. An antiserum raised against the expressed fusion protein encoded by this cDNA labels the high molecular weight MAP2 but not the 70 kDa MAP2c abundant in developing brain. This antiserum labels PHF in situ but only a proportion of isolated PHF. In situ hybridization on human brain sections did not demonstrate an increase in mRNA for MAP2 in tangle-bearing neurones. We suggest that the association of this MAP2 fragment with PHF in situ results from posttranslational modifications of MAP2.
Lack of Efficacy of Vinpocetine in Vascular Dementia
Authors: Robertsson B. , Wallin A. , Nyth A.L. , Gottfries C.G. , Blennow K.
Published: August 2007

Twenty-two patients suffering from mild to moderate dementia of vascular origin were treated with vinpocetine, 30 mg/day during 16 weeks, in an open pilot study. Response to treatment was assessed with the Gottfries-BrÅne-Steen geriatric rating scale and psychometric tests. Effects on concentrations of neurotransmitters in the cerebrospinal fluid (CSF) and on the blood-brain barrier function were also studied. According to the ratings and tests, the only noticeable improvement was reduced fear/panic. This improvement may very well be attributable to increased care of the patients during the study. The drug did not influence the monoamine metabolites in the CSF or the blood-brain barrier function. On the basis of these results we conclude that vinpocetine has no effect on patients suffering from mild to moderate dementia of vascular origin.
Clues to the Mechanism of Action of Acetyl-L-Carnitine in the Central Nervous System
Authors: Calvani M. , Carta A.
Published: August 2007

Acetyl-L-carnitine (ALC) shows a variety of different pharmacological properties in the aging brain. Recent findings suggest that the ultimate meaning of ALC actions may be related to its specific enhancement of energy metabolism at the mitochondrial level. ALC is an energy carrier through the mitochondrial membranes, controlling the availability of acetyl-coenzyme A. The facts that ALC acts on the electron transport chain complexes and also reduces lipid peroxidation give new insights into its mechanism of action.
Depression and Dementia in Parkinson's Disease: Catecholamine Changes in the Locus coeruleus - Basis for Therapy
Authors: Chan-Palay V.
Published: August 2007

This paper describes the clinical, psychometric, neuropathological, and neurotransmitter immunocytochemical studies on 9 patients selected from the Zürich study on dementia and Parkinson''s disease (PD). It confirms the age-related loss of norepinephrine neurons in the locus coeruleus (LC) in control patients without neurological or psychiatric disease. The loss of LC neurons in patients with PD, with coexistent depression, with nonischemic dementia or both in coexistence, increased with the severity and complexity of the diseases. The 5 cases with depressive disorders, depression, PD with depression, and PD with depression and dementia had in common severe LC norepinephrine cell losses, and neurons with low catecholamine-synthesizing enzyme and, presumably, reduced norepinephrine levels. The significance of these findings in relation to the possible treatment of depression in PD with other multiple symptoms with antidepressants such as monoamine oxidase A inhibitors, which manipulate the LC norepinephrine levels, are discussed.
Investigation of Intrathecal Synthesis of Immunoglobulin G in Primary Degenerative Dementia (Alzheimer's Disease)
Authors: Blennow Kaj , Wallin Anders , Fredman Pam , Gottfries Carl-Gerhard , Karlsson Ingvar , Svennerholm Lars
Published: August 2007

Serum and cerebrospinal fluid (CSF) from 118 patients with primary degenerative dementia (PDD; Alzheimer''s disease) and 50 healthy controls were examined in order to investigate intrathecal synthesis of immunoglobulin G (IgG), defined as an elevated IgG index (≧ 0.7) and/or the presence of oligoclonal IgG bands in CSF but not in serum. In the PDD group, 7 patients (6%) showed an intrathecal IgG synthesis. Eight patients (7%) showed oligoclonal IgG bands in serum and CSF, interpreted as a diffusion of IgG across the blood-brain barrier. In the early-onset PDD group, the mean IgG index was higher than in age-matched controls. The PDD patients with intrathecal IgG synthesis were less demented than those with normal CSF, but the intrathecal synthesis was not related to age, sex, or blood-brain barrier function. The findings suggest that immunological dysfunction could be related to PDD.
Biochemical Membrane Constituents and Activities of Alkaline and Acid Phosphatase and Cathepsin in Cortical and Subcortical Brain Areas in Dementia of the Alzheimer Type
Authors: Sofic E. , Frölich L. , Riederer P. , Jellinger K. , Heckers S. , Beckmann H. , Deinzer E. , Pantucek F. , Hebenstreit G. , Ransmayr G.
Published: August 2007

Biochemical substrates and activities of three enzymes were determined in cortical and subcortical brain areas from neuropathologically proven cases with dementia of the Alzheimer type (DAT) and age-matched control cases. Protein and total lipid content, lecithin, triglycerides, cholesterol, uric acid, alkaline and acid phosphatases and cathepsin activity were determined in homogenates from frontal, temporal, and occipital cortex, hippocampus, the amygdaloid nucleus and the putamen. Protein content was reduced in the frontal cortex only. In the hippocampus, total lipids, triglycerides, lecithin, cholesterol, and acid phosphatase activity were reduced. Cathepsin activity was reduced in the putamen, and increased in the amygdaloid body. The other brain areas appeared unaltered. Neuropathological changes were most pronounced in the hippocampus. The data indicate that only in the hippocampus, the most severely affected brain region, major alterations of membrane constituents occur. Among the neocortical brain regions, only the frontal cortex showed some signs of degradation of cell membranes. The activity of cathepsin, a lysosomal protease potentially involved in amyloidogenesis, was differentially altered. The biochemical observations do not follow the classical pattern of neuropathological degeneration in DAT.