Aβ40 is a major form of β-amyloid in nonhuman primates

Because aged nonhuman primates show β-amyloid (Aβ) deposition in senile plaques and blood vessels similar to that seen in human aging and AD, we used C-terminal specific antibodies to Aβ₄₀ and Aβ₄₂ to investigate Aβ peptide length in the brains of 11 aged rhesus monkeys and a 59-year-old chimpanzee. In contrast to AD, where the earliest and most prominent form of Aβ in senile plaques is Aβ₄₂, in the monkey, Aβ₄₀-positive plaques predominated. The ratio of Aβ₄₎: Aβ₄₂-positive plaques averaged 2.08 in the monkey, as compared to a mean ratio of 0.37 in 68 human AD subjects (p < 0.001). Aβ₄₀ was also more prominent in the chimpanzee than in humans. Possible explanations for these findings include species differences in the cleavage of Aβ from the amyloid precursor protein or in the activity of a putative carboxy peptidase forming Aβ₄₀ from Aβ₄₂ in situ.     

Left heart function in chronic obstructive lung disease

Summary In patients with varying degrees of chronic obstructive pulmonary disease (COPD), simultaneous measurements of central hemodynamics and left ventricular radionuclide ventriculograms at rest and during exercise were made. In 21 of these patients, satisfactory echocardiograms could be performed. In seven of the patients, arterial blood pressure at rest was increased. Decreased compliance of the left ventricle was thought to be present in patients with COPD and additional arterial hypertension. The left ventricular ejection fraction (LVEF) at rest was in the high normal range in all patients. During exercise, no further increase was observed. This pattern of LVEF response seems to be typical in patients with COPD. Because the highest values were observed in the more severe COPD and right ventricular hypertrophy, it is unlikely that an impairment of left ventricular function is caused by COPD. In five of 27 patients, an abnormal decrease of LVEF and regional hypokinesis occurred during exercise, thus suggesting additional coronary heart disease. The fact that at least 30% of the patients with COPD suffered from arterial hypertension and 20% of the patients exhibited unexpected ischemia detected by regional hypokinesis in RNV during exercise, but not in the ECG, may be of practical relevance. Coronary angiography was not indicated because most of these patients were over 65 and the factor limiting the working capacity was ventilatory impairment and not angina pectoris, in all patients. For this reason, a diagnostic uncertainty remains with regard to additional coronary heart disease in the older patients with advanced chronic obstructive pulmonary disease.Lung Function Parameters VC (1) inspiratory vital capacity - FEV1 (1) forced exspiratory volume in 1 sec - Raw (cmH20/l/s) airways resistance - RV/TLC (%) residual volume/total lung capacity - paO₂ (mm Hg) O₂ partial pressure Hemodynamic Parameters CI (1/min/sqm) cardiac index - SVI (ml/sqm) stroke volume index - PAP (mm Hg) pulmonary artery mean pressure - PwP (mm Hg) pulmonary capillary wedge pressure - RRs (mm Hg) systolic arterial pressure - RRd (mm Hg) diastolic arterial pressure (at the time of catheterization) - RR(WHO) (mm Hg) mean values measured at different days (at least 3 values). Parameters Derived from Combined Radionuclide Ventriculography and Central Hemodynamics LVEF (%) left ventricular ejection fraction - LVESVI (ml/sqm) left ventricular endsystolic volume index - P/V (mm Hg/ml/sqm) peak systolic pressure/endsystolic volume index - PFR (1/sec) peak filling rate: endsystolic volume/sec Echocardiographic Parameters RV d wth (mm) right ventricular enddiastolic wall thickness - LV d wth (mm) left ventricular enddiastolic wall thickness In honor to Prof. W.E. Adam's 60th birthday     

Right ventricular function in patients with chronic obstructive pulmonary disease

Summary Simultaneous right heart catheterization and radionuclide ventriculography were performed in 27 patients with a wide range of chronic obstructive pulmonary disease. Central hemodynamics and radionuclide studies were done at rest and during exercise. In the resting state the right ventricular ejection fraction (RVEF) was in the normal range (43.3±6%). During exercise a significant (p<0.001) decrease of RVEF to 38.8±6.7% occurred. The pumonary artery mean pressures were 19.9±3.8 at rest. During exercise a significant (p<0.001) increase to 41±9.8 mm Hg occurred. There was a linear relationship between pulmonary pressures and RVEF during exercise in patients with pulmonary artery pressures not exceeding 35 mm Hg. In patients with right ventricular end-diastolic wall thickness 6 mm a curvilinear relationship between these parameters could be observed with a flattening of the curve at higher pressures (>35 mm Hg) and lower ejection fractions (<35% RVEF). Radionuclide venticulography cannot substitute for right heart catheterization. Echocardiography is useful for interpretation of right ventricular ejection fractions in advanced chronic obstructive pulmonary disease.Abbreviations CI Cardiac index (l/min/m²) - CO Cardiac output (l/min) - COPD Chronic obstructive pulmonary disease - FEV₁ Forced expiratory volume in the first second (ml) - HR Heart rate (B/min) - PAd Pulmonary artery diastolic pressure (mm Hg) - PAP Pulmonary artery mean pressure (mm Hg) - PAs Pulmonary artery peak pressure (mm Hg) - PVR Pulmonary vascular resistance (dyn·s·cm^–5) - PwP Pulmonary capillary wedge pressure (mm Hg) - RAP Right arterial pressure (mm Hg) - Raw Airway resistance (cm H₂/l/s) - RNV Radionuclide ventriculogram - RV Residual volume (l) - RVEF Right ventricular ejection fraction (%) - RVEDVI Right ventricular enddiastolic volume index (ml/m²) - RVEDVI SVI RVEF (ml/m²) - RVESVI Right ventricular endsystolic index (m²/m²) - SVI Stroke volume index (ml/m²) - TLC Total lung capacity (l) - VC Vital capacity (l)     

Immunoreactive somatostatin-28(1-12) is increased in Huntington's disease

Somatostatin-28(1-12) concentrations were measured in Huntington's disease (HD) postmortem tissue using a specific radioimmunoassay. Concentrations of immunoreactive somatostatin-28(1-12) were significantly increased in the caudate and putamen but were unchanged in cortical areas A9 and A17. Since somatostatin-28(1-12) terminates with the amino acids Arg-Glu-OH, we examined whether this dodecapeptide compound might exert a neurotoxic effect. Injections of somatostatin-28(1-12) into rat striatum showed no evidence of histologic damage.     

Absence of TREM2 polymorphisms in patients with Alzheimer's disease and Frontotemporal Lobar Degeneration

Triggering Receptor Expressed on Myeloid cells (TREM)2 deficiency originates a genetic syndrome characterized by bone cysts and presenile dementia, named Nasu-Hakola disease (NHD). Early onset dementia and marked involvement of frontal regions are features characterizing both NHD and other kinds of neurodegenerative disorders, such as Frontotemporal Lobar Degeneration (FTLD), and, in some cases, Alzheimer's disease (AD). Three Single Nucleotide Polymorphisms (SNPs) in TREM2 coding region were screened by allelic discrimination in a population of probable AD patients as well as FTLD patients as compared with age-matched controls. In addition, mutation scanning of the coding region of TREM2 gene was carried out in 7 patients with early onset AD (EOAD), 16 FTLD, and 20 controls. None of the SNPs analyzed was present, either in patients or controls. Moreover, mutation scanning of the five exons of TREM2 failed to detect the presence of novel polymorphisms. These data demonstrate that TREM2 coding region is highly conserved, implying a crucial role of this receptor. Further studies, including a functional analysis, are certainly required to clarify the role of TREM2 in neurodegenerative processes.     

Interaction between the immune and central nervous systems

Much of the understanding of tolerance has focused on the requirements for antigen-specific lymphocyte activation and function. However, there is increasing evidence for anatomic regulation of effector access to self antigens. Recently, a number of studies have provided evidence for tissue-specific “addressins” in chemokine/chemokine receptor pairs. The central nervous system (CNS) provides special anatomic barriers to the movement of cells from the vascular compartment to the parenchyma. Herein I raise the possibility that antigen, perhaps through specialized antigen-presenting cells, may play a role in regulating access of activated lymphocytes into the CNS parenchyma. The results suggest that a reexamination of the widely held dogma that all activated lymphocytes have access to the CNS parenchyma is nessary to understand the relationship between the immune and central nervous systems.     

Detection of ophthalmic arterial doppler signals with Behcet disease using multilayer perceptron neural network

Doppler ultrasound is known as a reliable technique, which demonstrates the flow characteristics and resistance of ophthalmic arteries. In this study, ophthalmic arterial Doppler signals were obtained from 106 subjects, 54 of whom suffered from ocular Behcet disease while the rest were healthy subjects. Multilayer perceptron neural network (MLPNN) employing delta-bar-delta training algorithm was used to detect the presence of ocular Behcet disease. Spectral analysis of the ophthalmic arterial Doppler signals was performed by least squares (LS) autoregressive (AR) method for determining the MLPNN inputs. The MLPNN was trained with training set, cross validated with cross validation set and tested with testing set. All these data sets were obtained from ophthalmic arteries of healthy subjects and subjects suffering from ocular Behcet disease. Performance indicators and statistical measures were used for evaluating the MLPNN. The correct classification rate was 96.43% for healthy subjects and 93.75% for unhealthy subjects suffering from ocular Behcet disease. The classification results showed that the MLPNN employing delta-bar-delta training algorithm was effective to detect the ophthalmic arterial Doppler signals with Behcet disease.     

Immunohistochemical study of neuron specific enolase and S-100 protein in Hirschsprung's disease

Summary The distribution of whole differentiated neurons in the intestines from 15 children with Hirschsprung's disease was investigated using neuron specific enolase (NSE) and the perineuronal elements were studied using S-100 protein immunostaining.In aganglionic segments, NSE immunoreactive ganglion cells and S-100 positive satellite cells were absent, but the hypertrophic nerve trunks did show a markedly positive NSE and S-100 immunoreactivity.Two different forms of aganglionic segment were present. One was the middle aganglionic segment of long segment aganglionosis which was almost completely dennervated. In the other type, there were several NSE positive nerve fibers in the muscularis propria of both the aganglionic segment of short segment aganglionosis and the distal aganglionic segment of long segment aganglionosis. These latter two aganglionic segments seemed to be innervated by extrinsic nerves.     

The consensus workshops for the detection of autoantibodies to intracellular antigens in rheumatic diseases

In 1988 and in 1989 consensus workshops were organized in order to define the interlaboratory concordance in detecting autoantibody specificities in selected sera from patients with rheumatoid disorders and to determine the possible causes of discrepancies. In total 20 sera were tested for the presence of antibodies against nRNP, Sm, Ro (SS-A), La (SS-B), Scl-70, centromeric antigens, ribosomal RNP and Jo-1. The methods used for detection by the 28 European laboratories who participated included immunofluorescence, counter-immunoelectrophoresis, immunodiffusion, immunoblotting and ELISA.

The results showed that only a combination of two or more techniques was able to detect all specificities with an adequate efficiency. Recommendations to improve the efficiency of autoantibody detection and to standardize laboratory protocols are given.     

Demonstration of Borna disease virus (BDV) in specific regions of the brain from horses positive for serum antibodies to BDV but negative for BDV RNA in the blood and internal organs

Sero- and molecular-epidemiological studies on Borna disease virus (BDV) infection show that BDV RNA is not always detected in the peripheral blood mononuclear cells (PBMCs) from serum anti-BDV antibody-positive individuals such as horses, sheep, cattle, cats, and humans. In this study we demonstrated BDV RNA signals by polymerase chain reaction only in restricted regions of the brain from horses with locomotor disease. Four of six horses examined showed apparently positive reactions for anti-BDV antibodies. Specific regions of the brain of these four horses were positive for BDV RNA but the internal organs, lymph nodes, and PBMCs were negative. Histological studies of their brains revealed no apparent histological abnormalities such as inflammatory reactions. These results suggest that BDV chronically infects certain restricted regions of brain in seropositive horses. Received: 6 January 1997