Impaired thymus-derived lymphocyte function in patients with malignant brain tumour

Cell-mediated immunity was evaluated in 28 patients with malignant glioma, using in vivo and in vitro tests of lymphocyte function. The results were compared to those found in patients with carcinomatosis (11 subjects), benign brain tumours (9), other neurological disorders (20) and normal, healthy controls (21). Significant impairments of delayed hypersensitivity responses to common antigens was found in patients with malignant glioma and in those with generalised malignancy. A less significant depression of lymphocyte responses was also detected in patients with meningioma. The impairment in cell-mediated immunity was shown not be due to a serum blocking factor. Our data indicate that there is defective T cell function in patients with glioma, similar to that reported in cases with malignancies outside the central nervous system. This impaired immunity may have clinical significance.     

Mouse Inoculation Studies Reveal No Transmissible Agent in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) resembles the spongiform encephalopathies in its dual pattern of inherited and sporadic cases, its uniform prevalence in different populations, its late onset (suggestive of a long incubation period) and its pathological picture of neuronal degeneration without inflammation. There is a well-established protocol for primary transmission of scrapie and related diseases to mice. Using this, we inoculated four long-lived, inbred, mouse strains with cord material fresh-frozen within three hours of death, from a case of ALS or a control case. No motor neuron loss, gliosis or tract demyelination was found in the experimental group. Fifty per cent of each group were observed for more than 600 days. Two types of lesions were found in these animals at death: widespread foci of white matter vacuolation and bilateral thalamic mineral deposits. They were present in the control group at the same incidence and severity as in the experimental group and were thus considered to represent an age-related change. Attention is drawn to them because they have been claimed as significant when found in a transgenic model of spongiform encephalopathy. The results of our carefully-controlled experiment suggest that it is unlikely that ALS is caused by a scrapie-like agent capable of transmission to mice.     

Determination of brucella immunoglobulin G agglutinating antibody titer with dithiothreitol.

The routine brucella agglutination test measures both immunoglobulin M (IgM) and IgG brucella antibody titers; however, only an elevated IgG titer is significant for differentiating active from inactive disease in patients with symptoms lasting 3 or more weeks. The IgG antibody titer can be determined by treating the serum wih 2-mercaptoethanol to inactivate the IgM brucella antibodies while leaving the IgG brucella antibodies intact. Dithiothreitol, which also inactivates IgM, was compared with 2-mercaptoethanol for the determination of IgG brucella agglutination titers. The dithiothreitol and 2-mercaptoethanol test results agreed within +/- 1 dilution step in 103 of 105 serum specimens tested, for a 98.1% rate of agreement. The results indicate that dithiothreitol can be used in place of 2-mercaptoethanol for determining IgG brucella agglutination titers. Dithiothreitol does not have the offensive odor or the irritant properties of 2-mercaptoethanol.     

Ultrastructural study of large efferent neurons in the superior colliculus of the cat after retrograde labeling with horseradish peroxidase

The ultrastructure of large neurons in the stratum griseum intermedium of the cat superior colliculus was examined following injections of horseradish peroxidase (HRP) into the dorsal tegmental decussation. Four HRP-labeled cells were selected, and the synaptology of their cell bodies and selected regions of proximal and distal dendrites was examined. The four neurons represent four morphologically distinct cell types: multipolar radiating, tufted, large vertical, and medium-sized trapezoid radiating. These four neurons correspond with cell types X1, X2, X3, and T1 respectively, according to the recent classification of neurons in the superior colliculus of the cat by Moschovakis and Karabelas (J. Comp Neurol. 239:276-308, '85). The three X type neurons are similar in having 83% of their somata and over 74% of their proximal dendrites contacted by synaptic profiles. Distal dendrites of the X type neurons, however, receive fewer synaptic contacts. In contrast, in the T1 cell, only 69% of the soma membrane is contacted by synaptic profiles, and the synaptic coverage on proximal and distal dendrites does not vary much from this. Of the eight types of synaptic terminals described in the stratum griseum intermedium of the cat superior colliculus by Norita (J. Comp. Neurol. 190:29-48, '80), only five are found in contact with the X and T type efferent neurons described here. There are some regional differences in terminal distribution, although each terminal is represented on each cell. Type III terminals (small, contain mostly pleomorphic vesicles, and make symmetrical contacts) are the most abundant on cell bodies and dendrites of all four cell types. Terminal types II (medium-sized, containing round and flattened vesicles, and making asymmetrical contacts), and IV (medium to large in size, containing flattened vesicles, and making symmetrical contacts) are well represented. In general, terminal types I (small, containing densely packed round vesicles, and making asymmetrical contacts) and VI (small and irregular in shape, containing flattened vesicles and making symmetrical contacts) are found infrequently. The identity of different types of synaptic terminal is discussed.     

The stability of betamethasone-17-valerate in semi-solid bases

The stability of betamethasone-17-valerate in semi-solid bases has been investigated. Emphasis has been placed on the stability problems which could arise upon dilution of proprietary preparations by the use of model systems. Betamethasone-17-valerate has been shown to decompose to betamethasone-21-valerate and betamethasone alcohol. Quantitation of the decomposition was by direct densitometry on thin layer chromatographic plates. The decomposition was found to be an apparent first order process and to depend on the diluent used and its concentration. Attempts were also made to relate the rate of decomposition to the pH of the base used, and to stabilize the products.