Amyotrophic lateral sclerosis with ophthalmoplegia and multisystem degeneration in patients on long-term use of respirators

Summary We describe two patients with sporadic amyotrophic lateral sclerosis (ALS), who had developed progressive external ophthalmoplegia of a predominantly supranuclear type while they survived on respirators, and displayed histopathological abnormalities both typical and atypical of ALS. Patient 1 was a 43-year-old man with ALS of 5-year duration, who had initially exhibited fulminant ALS, and remained on a respirator for 4 years. Patient 2 was a 51-year-old man with ALS of 13-year duration, who remained on a respirator for 8 years. Both patients died in a totally locked-in state. Autopsy of both patients revealed not only histopathological abnormalities consistent with ALS, but also multisystem degeneration which involved the pontine tegmentum, substantia nigra, Clarke's dorsal nuclei and spinocerebellar tracts. In addition, Patient 2 displayed intracyto-plasmic neuronal basophilic inclusion bodies which exhibited marked immunoreactivity to anti-ubiquitin antibodies. Our case reports indicate that the longer survival which is possible through the use of respirators may make one subgroup of ALS patients prone to develop atypical clinical and neuropathological features which are not observed during the natural cours of ALS.Supported by a Grant-in-Aid from the Research Committee of CNS Degenerative Diseases, the Ministry of Health and Welfare of Japan, and by a Grant from Nihon University School of Medicine, Tokyo     

Low plasma glutamine in combination with high glutamate levels indicate risk for loss of body cell mass in healthy individuals: the effect of N-acetyl-cysteine

Skeletal muscle catabolism, low plasma glutamine, and high venous glutamate levels are common among patients with cancer or human immunodeficiency virus infection. In addition, a high glycolytic activity is commonly found in muscle tissue of cachectic cancer patients, suggesting insufficient mitochondrial energy metabolism. We therefore investigated (a) whether an anaerobic physical exercise program causes similar changes in plasma amino acid levels, and (b) whether low plasma glutamine or high glutamate levels are risk factors for loss of body cell mass (BCM) in healthy human subjects, i.e., in the absence of a tumor or virus infection. Longitudinal measurements from healthy subjects over longer periods suggest that the age-related loss of BCM occur mainly during episodes with high venous glutamate levels, indicative of decreased muscular transport activity for glutamate. A significant increase in venous glutamate levels from 25 to about 40 M was seen after a program of anaerobic physical exercise. This was associated with changes in T lymphocyte numbers. Under these conditions persons with low baseline levels of plasma glutamine, arginine, and cystine levels also showed a loss of BCM. This loss of BCM was correlated not only with the amino acid levels at baseline examination, but also with an increase in plasma glutamine, arginine, and cystine levels during the observation period, suggesting that a loss of BCM in healthy individuals terminates itself by adjusting these amino acids to higher levels that stabilize BCM. To test a possible regulatory role of cysteine in this context we determined the effect of N-acetyl-cysteine on BCM in a group of subjects with relatively low glutamine levels. The placebo group of this study showed a loss of BCM and an increase in body fat, suggesting that body protein had been converted into other forms of chemical energy. The decrease in mean BCM/body fat ratios was prevented by N-acetyl-cysteine, indicating that cysteine indeed plays a regulatory role in the physiological control of BCM.Abbreviations BCM Body cell mass - HIV Human immunodeficiency virus type 1 - NAC N-Acetyl-cysteine     

A comparison of three bioelectrical impedance analyses for predicting lean body mass in a population with a large difference in muscularity

This study tested the hypothesis that, as compared to whole-body bioelectrical impedance (BI) analysis, segmental BI analysis can estimate lean body mass (LBM) more accurately in a population with a large difference in muscularity. In addition to whole-body BI, which determines impedance (Z) between the wrist and ankle, two segmental BI analyses which determine the Z value of every body segment in each of (1) the arms, legs and trunk (distal BI) and (2) the upper arms, upper legs and trunk (proximal BI) were applied to a group of 125 male athletes and 75 non-athletes. The subjects were divided into validation and cross-validation groups. Simple and multiple regression analyses were applied to (length)²/Z (BI index) values for the whole-body and each body segment, to develop the prediction equations of LBM measured using air-displacement plethysmography. In the validation group, the SE of estimation was similar in the whole-body (3.4 kg, 5.4%), distal (3.4 kg, 5.5%) and proximal BI (3.3 kg, 5.2%) analyses. However, the whole-body and distal BI analyses produced systematical errors in the estimates of LBM. Moreover, the residuals in the two methods significantly (P<0.05) correlated with the ratios of BI indices of the upper arms and upper legs to those of the arms and legs, respectively, calculated as variables approximating the relative development of lean tissues at the proximal area of limbs. On the other hand, the proximal BI analysis was validated and cross-validated. Thus, the accuracy of estimating LBM was similar in the whole-body and the two segmental BI analyses. However, the prediction equations derived from the use of the whole-body BI index and a combination of the arms, legs and trunk BI indices produced a systematical error relating to the difference between the limb segments in lean tissue development.     

Determination of total body water by multifrequency bio-electric impedance: development of several models

Multifrequency bio-electronic impedance analysis (MF BIA) measurements are taken from a heterogeneous group of patients, varying in size between obese and slim. The measuring system uses four electrodes: two current and two potential electrodes. Three new models are developed to calculate total body water (TBW) from the BIA data, and the resulting TBW values are compared with TBW determined by D₂O dilution. The results demonstrate that the most simple model provides the best TBW values. For individual patients, TBW can be determined by means of bioimpedance measurement with an accuracy of 3 litres. In the most simple model (model 1), the body is electrically represented by a cylinder, and corrections are made for the amount of fat. This is an extension of the model used by Xitron. In the more advanced models (2 and 3), the body is represented by a cylinder for the trunk, and truncated cones represent the arms and legs. In model 2, ΔTBW amounts to 3 litres. It is shown that the resistance of the trunk is proportional to the square root of the length. In model 3, it is assumed that subcutaneous fat is a poor conductor if electric current. An equation is developed that describes the partition of subcutaneous fat, and the fat layer is then removed from the cones representing arms and legs and from the cylinder that models the trunk.     

Fine structure of the carotid body of the midterm human fetus

Summary The human fetal carotid body was studied using both histochemical and electron microscopic methods. The glomus cells of a mid term fetal carotid body evidently contain catecholamines. This was demonstrated both by formaldehyder-induced fluorescence of the cells and by the presence of typical dense-cored vesicles (diameter 1430–3200 Å) in the cytoplasm of the chief cells. The glomus cells were densely innervated and the synapses found on their surface were probably cholinergic in type, containing agranular synaptic vesicles measuring 400–700 Å in diameter with a few dense-cored vesicles measuring 900 to 1300 Å. Synapses were not found in any other cell type within the glomus caroticum. The prominent feature of the glomus cell cytoplasm was the presence of the dense-cored vesicles. The density of the vesicular core varied only slightly from cell to cell. There were no perceptible differences in vesicular size between the different cells. The glomus cells were mostly surrounded by the processes of the sustentacular cells, which usually also surrounded the capillary walls. No glomus cells were ever found in direct contact with the capillary wall. The capillaries were wide and very numerous over the restricted area of the organ. They formed sinusoidal loops, probably anastomosing with each other. Finally, the features of the fine structure are discussed, correlating the present findings with our knowledge about the adult functional carotic body.     

Clonorchis sinensis: molecular cloning and localization of myosin regulatory light chain

One cDNA clone was purified from an adult Clonorchis sinensis cDNA library, and its deduced polypeptide sequence was found to be homologous with myosin regulatory light chain (MRLC) of invertebrates and vertebrates. Two amino-acid residues, Thr and Ser, were conserved at the phosphorylation sites that regulate the function of MRLCs. Recombinant C. sinensis MRLC (rCsMRLC) protein was produced and purified from Escherichia coli, and mouse anti-CsMRLC immune sera recognized a protein of molecular weight 24 kDa from a soluble protein preparation of C. sinensis. The CsMRLC protein was immunohistochemically localized to the muscle fibers of the subtegumental muscle layer and to the muscles of oral and ventral suckers. However, the rCsMRLC protein proved to be less useful antigen for the serodiagnosis of human clonorchiasis.The nucleotide sequence reported herein was submitted to GenBank and assigned accession number AY519356.     

Inhibitory interaction in the cat's lateral geniculate nucleus

Summary Spike activities of optic tract fibers and corresponding relay cells were recorded simultaneously in layers A and A₁ of the dorsal lateral geniculate nucleus of the cat. Light stimuli of various diameters were shone into the receptive field center of these unit pairs and their input/output ratios were determined. An increase of the stimulus size leads to an impairment of the input/output ratio in on-center and off-center relay cells. This suppressive effect has approximately the same latency as the excitatory response.Intracellular recordings suggest that the inhibitory effect of the surround is due to a postsynaptic process. Inhibitory postsynaptic potentials occur during and — under certain stimulus conditions —before the excitatory response. The short latency of these IPSPs suggests that they result from the activity of adjacent units with the same RF characteristics as the recorded neuron. This inhibitory input is not restricted to the RF periphery but may also be activated by stimulation within the RF center. Most neurons are also inhibited by units with antagonistic center responses.During the period of this research Ernst Pöppel held a training grant of the Stiftung Volkswagenwerk, Az. 11 1015.     

Effects of ageing on the alveolar pores of Kohn and on the cytoplasmic components of alveolar type II cells in monkey lungs

The effects of ageing on the numbers of alveolar pores of Kohn and on the cytoplasmic components of alveolar type II cells were studied in monkey lungs by scanning and transmission electron microscopy. Lung tissue from 26 female and three male pigtail macaques whose ages ranged from 1 month to 31 years (life span is 35 years) was analysed. From the age of 1 month to 10 years there was a significant increase in the number of alveolar pores (r = 0.85, p less than 0. 001); however, between the ages of 14 years to 31 years there was no significant change. In seven animals ranging in age from 1 month to 4 years (mean 2.4 years) the number of pores was 5.8 +/- 3.9 (mean +/- S.D.), whereas in 10 animals aged 16 to 31 years (mean 20.3 years) the number of pores was 32.7 +/- 17.5 (mean +/- S.D.) per alveolar profile, a significant difference (p less than 0.002). In older animals (15-20 years) there was a significant decrease, both in the number of lamellar bodies per alveolar type II cell (p less than 0.01) and in the volume density of lamellar bodies to cytoplasmic volume (p less than 0.05) compared with young animals (1 month to 4.8 years). In older animals, there was also a significant increase in the volume density of a vacuole-like dilatation of the endoplasmic reticulum in alveolar type II cells (p less than 0.05) compared with young animals. These findings suggest impaired pulmonary surfactant production with aging. Both the increased number of alveolar pores and the postulated decrease of surfactant production could play a role in the pathogenesis of pulmonary emphysema.